HEFIYA 40 mg Injectable Solution

Зміст інструкції

1. Hefiya 20 mg injectable solution in pre-filled syringe
   1. What is Hefiya and what is it used for
   2. What you need to know before your child uses Hefiya
   3. How to use Hefiya
   4. Possible side effects
   5. How to store Hefiya
   6. Contents of the pack and other information
   7. Instructions for Use
   8. Choice of injection site:
   9. Cleaning the injection site:
   10. Administration of the injection:
   11. Disposal of used syringes:
2. Hefiya 20 mg injectable solution in pre-filled syringe
   1. What is Hefiya and what is it used for
   2. What you need to know before your child uses Hefiya
   3. How to use Hefiya
   4. Possible side effects
   5. How to store Hefiya
   6. Package contents and other information
   7. Instructions for Use
   8. Choice of injection site:
   9. Injection site cleaning:
   10. Administration of the injection:
   11. Disposal of used pre-filled syringes:
3. Hefiya 40 mg injectable solution in pre-filled syringe
   1. Cos’è Hefiya e a cosa serve
   2. What you need to know before using Hefiya
   3. How to use Hefiya
   4. Possible side effects
   5. How to store Hefiya
   6. Contents of the pack and other information
   7. Instructions for Use
   8. Choice of injection site:
   9. Cleaning the injection site:
   10. Administration of the injection:
   11. Disposal of used syringes:
4. Hefiya 40 mg injectable solution in pre-filled pen
   1. What is Hefiya and what is it used for?
   2. What you need to know before using Hefiya
   3. How to use Hefiya
   4. Possible side effects
   5. How to store Hefiya
   6. Contents of the pack and other information
   7. Instructions for Use
   8. Choice of injection site:
   9. Cleaning the injection site:
   10. Removing the pen cap:
   11. How to hold the pen:
   12. Start of injection:
   13. Completion of the injection:
   14. Disposal of used pens:
5. Hefiya 40 mg injectable solution in pre-filled syringe
   1. What is Hefiya and what is it used for
   2. What you need to know before using Hefiya
   3. How to use Hefiya
   4. Possible side effects
   5. How to store Hefiya
   6. Package contents and other information
   7. Instructions for Use
   8. Choice of injection site:
   9. Injection site cleaning:
   10. Administration of the injection:
   11. Disposal of used syringes:
6. Hefiya 40 mg injectable solution in pre-filled pen
   1. What is Hefiya and what is it used for
   2. What you need to know before using Hefiya
   3. How to use Hefiya
   4. Possible side effects
   5. How to store Hefiya
   6. Contents of the pack and other information
   7. Instructions for Use
   8. Choice of injection site:
   9. Injection site cleaning:
   10. Removing the cap from your pen:
   11. How to hold the pen:
   12. Start of the injection:
   13. Completion of the injection:
   14. Check that the green indicator
   15. Disposal of used pens:
7. Hefiya 80 mg injectable solution in pre-filled syringe
   1. What is Hefiya and what is it used for
   2. What you need to know before using Hefiya
   3. How to use Hefiya
   4. Possible side effects
   5. How to store Hefiya
   6. Package contents and other information
   7. Instructions for Use
   8. Choice of injection site:
   9. Cleaning the injection site:
   10. Administration of the injection:
   11. Disposal of used syringes:
8. Hefiya 80 mg injectable solution in pre-filled pen
   1. What is Hefiya and what is it used for
   2. What you need to know before using Hefiya
   3. How to use Hefiya
   4. Possible side effects
   5. How to store Hefiya
   6. Contents of the pack and other information
   7. Instructions for Use
   8. Choice of injection site:
   9. Injection site cleaning:
   10. Removing the pen cap:
   11. How to hold the pen:
   12. Start of the injection:
   13. Completion of the injection:
   14. Check that the green indicator
   15. Disposal of used pens:

Hefiya 20 mg injectable solution in pre-filled syringe

adalimumab

20 mg/0.4 mL
Read this leaflet carefully before your child uses this medicine as it contains
important information.

• Keep this leaflet. You may need to read it again.
• Your doctor will give you a Patient Reminder Card, which contains important safety information that you need to know before your child starts using Hefiya and during treatment with Hefiya. Keep this Patient Reminder Cardwith you or your child during treatment and for 4 months after the last Hefiya injection given to your child.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed only for your child. Do not give it to other people, even if they have the same symptoms as your child, as it could be dangerous.
• If your child experiences any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Hefiya is and what it is used for
• 2. What you need to know before your child uses Hefiya
• 3. How to use Hefiya
• 4. Possible side effects
• 5. How to store Hefiya
• 6. Contents of the pack and other information
• 7. Instructions for use

1. What is Hefiya and what is it used for

Hefiya contains the active ingredient adalimumab, a medicine that acts on the body's immune system (defense).
Hefiya is indicated for the treatment of the inflammatory diseases listed below:

• polyarticular juvenile idiopathic arthritis,
• arthritis associated with enthesitis,
• pediatric plaque psoriasis,
• pediatric Crohn’s disease,
• pediatric non-infectious uveitis.

The active ingredient contained in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumor necrosis factor (TNFα), which is
involved in the immune system (defense) and is present at higher concentrations in the
inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and decreases the
inflammatory process in these diseases.
Polyarticular juvenile idiopathic arthritis and arthritis associated with enthesitis
Polyarticular juvenile idiopathic arthritis and arthritis associated with enthesitis are inflammatory
diseases of the joints, which typically first appear during childhood.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged
2 to 17 years and arthritis associated with enthesitis in children and adolescents aged 6-17 years.
Other disease-modifying drugs, such as methotrexate, may be administered at diagnosis.
If these drugs do not work satisfactorily, Hefiya will be administered to patients for the
treatment of polyarticular juvenile idiopathic arthritis or arthritis associated with enthesitis.
Pediatric plaque psoriasis
Plaque psoriasis is an inflammatory skin condition that causes red, scaly, and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the
nails, causing them to break, thicken, and lift from the nail bed, which can be
painful. Psoriasis is thought to be caused by a problem with the body's immune system that
leads to increased production of skin cells.
Hefiya is used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years in
whom topical medications and UV light therapy have not worked optimally or are not indicated.
Pediatric Crohn’s disease
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat moderate to severe Crohn’s disease in children and adolescents aged
6 to 17 years.
Your child may first be given other medications. If these drugs do not work in
a satisfactory manner, Hefiya will be administered to your child to reduce the typical symptoms
of their disease.
Pediatric non-infectious uveitis
Non-infectious uveitis is an inflammatory disease that affects certain parts of the eye.
Inflammation leads to decreased vision and/or the presence of mobile bodies in the eye
(black dots or thin lines that move across the visual field). Hefiya works by reducing this
inflammation.
Hefiya is used for the treatment of children aged 2 years and older with chronic non-infectious uveitis with
inflammation affecting the front of the eye.
Your child may first be given other medications. If these drugs do not work in
a satisfactory manner, Hefiya will be administered to your child to reduce the typical symptoms
of their disease.

2. What you need to know before your child uses Hefiya

Do not use Hefiya

• If your child is allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If there is a severe infection present, including tuberculosis, sepsis (blood poisoning) or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell your doctor if your child has signs or symptoms of infection, such as for example fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).
• If there is moderate or severe heart failure. It is important to tell your doctor if there has been or is a serious heart condition (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya
Allergic reaction

• If you experience allergic reactions with symptoms such as a feeling of tightness in the chest, wheezing, dizziness, swelling or skin rash, do not administer Hefiya again and contact your doctor immediately as, in rare cases, these reactions can be life-threatening.

Infection

• If an infection occurs, including long-term or localized infections (for example, leg ulcers), consult your doctor before starting treatment with Hefiya. If you have doubts, contact your doctor.
• You may be more likely to get infections during treatment with Hefiya. This risk may increase if your child’s lung function is reduced. These infections can be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning).
• In rare cases, these infections can be life-threatening to the patient. It is important to tell your doctor about the presence of symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may advise you to temporarily suspend Hefiya.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will need to check if your child has signs or symptoms typical of tuberculosis before starting therapy with Hefiya. This will involve collecting a detailed medical assessment including your child’s medical history and clinical examinations (e.g. a chest X-ray and a tuberculin test). The performance and results of these tests must be recorded on your child’s Patient Reminder Card. It is very important to tell your doctor if your child has ever had tuberculosis, or if they have had close contact with people with tuberculosis. Tuberculosis can develop during therapy even if your child has received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, fatigue, moderate fever) or other infections appear during or after therapy.

Travel/recurrent infection

• Tell your doctor if your child has lived in or travelled to regions where fungal infections, such as histoplasmosis, coccidioidomycosis or blastomycosis, are common.
• Tell your doctor if your child has had recurrent infections or if they have conditions that increase the risk of infection.

Hepatitis B virus

• Tell your doctor if your child is a carrier of the hepatitis B virus (HBV), if they have an active infection with the hepatitis B virus or if they think they may be at risk of contracting the hepatitis B virus. Your doctor should test your child for hepatitis B virus infection. Taking adalimumab can reactivate hepatitis B virus infection in subjects who are carriers of this virus. In some rare cases, especially if your child is taking other medications that suppress the immune system, reactivation of hepatitis B virus infection can be life-threatening.

Surgery or dental procedures

• Before surgery or dental procedures, tell your doctor that your child is taking Hefiya. Your doctor may advise you to temporarily suspend Hefiya.

Demyelinating disease

• If your child suffers from or develops demyelinating diseases (diseases that affect the insulating layer around nerves), such as multiple sclerosis, your doctor will decide whether it is appropriate to start or continue treatment with Hefiya. Tell your doctor immediately if your child develops symptoms such as changes in vision, weakness of arms or legs, or numbness or tingling that affects any part of the body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause diseases and should not be given during treatment with Hefiya if they cause infections. Consult your doctor before vaccinating your child. In children, it is recommended, if possible, to administer the vaccinations recommended for their age before starting therapy with Hefiya.
• If your daughter is taking Hefiya during pregnancy, the baby may have an increased risk of contracting an infection up to about 5 months after the last dose she took during pregnancy. It is important that you tell your daughter’s pediatrician or other healthcare provider about her use of Hefiya during pregnancy, so that they can decide when the baby should receive any type of vaccination.

Heart failure

• It is important to inform your doctor about any heart problems, both past and present. If mild heart failure is present and concomitant treatment with Hefiya, your doctor should carefully assess and monitor your heart condition. If new symptoms of heart failure appear or existing symptoms worsen (for example, shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If your child has a persistent fever, bruising or easy bleeding, or paleness, see your doctor immediately. The latter may decide to interrupt the therapy.

Tumor

• In children and adults treated with Hefiya or other anti-TNFα drugs, very rare cases of certain types of tumors have occurred. Patients with severe, long-standing rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukemia (cancers affecting blood cells and bone marrow). If your child is taking Hefiya, the risk of developing lymphomas, leukemia or other tumors may increase. In rare circumstances, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also taking azathioprine or mercaptopurine. Tell your doctor if your child is taking azathioprine or mercaptopurine with Hefiya.
• Cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If damaged areas of skin appear during or after treatment, or if the appearance of existing damaged areas changes, report it to your doctor.
• There have been cases of neoplasms, in addition to lymphoma, in patients with a specific type of

lung disease called chronic obstructive pulmonary disease (COPD) treated with another
anti-TNFα. If your child suffers from COPD or smokes heavily, they should discuss with their doctor whether
treatment with an anti-TNFα is appropriate.
Autoimmune diseases

• Rarely, treatment with Hefiya can lead to the manifestation of a syndrome like lupus. Tell your doctor if you develop symptoms such as a persistent unexplained skin rash, fever, joint pain or fatigue.

Children and adolescents

• Do not give Hefiya to children with polyarticular juvenile idiopathic arthritis under the age of 2 years.
• Do not give Hefiya to children with pediatric plaque psoriasis or pediatric ulcerative colitis under the age of 4 years.
• Do not give Hefiya to children with pediatric Crohn’s disease under the age of 6 years.
• Do not use the pre-filled syringe of 40 mg if doses less than 40 mg are recommended.

Other medicines and Hefiya
Tell your doctor or pharmacist if your child is taking, has recently taken or might
take any other medicines.
Hefiya can be taken both with methotrexate and with other disease-modifying antirheumatic drugs
(sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts), corticosteroids
or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken at the same time as medicines containing the active ingredients anakinra or
abatacept due to the increased risk of serious infections. The combination of adalimumab and other
anti-TNF and anakinra or abatacept is not recommended due to the possible increased risk of
infections, including serious infections and other possible drug interactions. If you have doubts, consult
your doctor.

Pregnancy and breastfeeding

• Your daughter should consider using adequate contraceptive measures to prevent pregnancy and continue them for at least 5 months after the last therapy with Hefiya
• If a pregnancy is in progress, if your daughter suspects or is planning a pregnancy, ask her doctor for advice on taking this medicine.
• Hefiya should only be used during pregnancy if necessary.
• According to a pregnancy study, no increased risk of birth defects was found when the mother had received adalimumab during pregnancy, compared to mothers who had the same condition but had not received adalimumab.
• Hefiya can be used during breastfeeding.
• If your daughter takes Hefiya during pregnancy, the baby may have an increased risk of contracting an infection.
• It is important that you tell your daughter’s pediatrician or other healthcare provider about her use of Hefiya during pregnancy, before the baby receives any type of vaccination (for more information on vaccines, see “Warnings and precautions”).

Driving and using machines
Hefiya may affect, albeit only to a modest extent, the ability to drive, ride a bicycle or
operate machinery. After taking Hefiya, you may experience visual disturbances and a
sensation that the environment around you is spinning (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.4 mL of dose, which is essentially
‘sodium-free’.

3. How to use Hefiya

Use this medicine following the instructions of your doctor or pharmacist exactly. If you have
any doubts, consult your doctor or pharmacist.
Hefiya is available in 40 mg pens and prefilled syringes of 20 mg and 40 mg for the
administration to patients of a full dose of 20 mg or 40 mg.

How and route of administration
Hefiya is administered by injection under the skin (for subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for Use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist
explaining that your child has received more medicine than they should have. Always keep the box of the
medicine, even if empty.

If you forget to use Hefiya
If you forget to give your child an injection, you should inject the next dose of Hefiya as soon
as you remember. Then resume your child's dose regularly according to the prescribed dosage
schedule.

If you stop using Hefiya
The decision to stop using Hefiya should be discussed with your child's doctor. Symptoms may return after treatment is stopped.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Most side effects are mild to moderate in form. However, some may be serious and require treatment. Side effects may occur
up to 4 months or more after the last injection of Hefiya.

Seek urgent medical attentionif you notice any of the following signs of an allergic reaction or
heart failure

• severe skin rash, hives;
• swelling of the face, hands, feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during exertion or when lying down, or swollen feet.

Inform your doctor as soon as possibleif you notice any of the following reactions

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning when urinating, fatigue or weakness, or cough;
• symptoms of nerve problems, such as tingling, numbness, double vision, or weakness of the arms or legs;
• signs of skin cancer such as swelling or an open sore that does not heal;
• signs and symptoms suggesting the onset of blood system disorders, such as persistent fever, bruising, bleeding, paleness.

The following side effects have been observed with Hefiya:

Very common(may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis and pneumonia);
• headache;
• abdominal pain (stomach ache);
• nausea and vomiting;
• skin rash;
• muscle pain.

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including tooth infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• infections affecting the joints;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergies);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, stabbing sensations or numbness;
• migraine;
• symptoms of nerve root compression (including back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (feeling of spinning);
• feeling of a fast heartbeat;
• high blood pressure;
• hot flashes;
• hematoma (solid swelling with coagulated blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux;
• dry syndrome (including dry eyes and dry mouth);
• itching;
• itchy skin rash;
• bruising;
• skin inflammation (such as eczema);
• nail breakage of fingers and toes;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (fluid accumulation in the body, causing swelling of the affected tissue);
• fever;
• reduced platelets in the blood, which increases the risk of bleeding or bruising;
• difficulty healing.

Uncommon(may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when immune defenses are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that can affect lungs, skin and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• neuropathy (nerve damage);
• stroke;
• hearing loss, tinnitus;
• feeling of irregular heartbeat such as palpitations;
• heart problems that can cause shortness of breath or swelling at the ankles;
• acute myocardial infarction;
• formation of a sac in the wall of a major artery, inflammation and a blood clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal accumulation of fluid in the pleural space);
• inflammation of the pancreas causing severe pain in the abdomen and back;
• difficulty swallowing;
• facial edema (swelling);
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle catabolism;
• systemic lupus erythematosus (immune system disorder, including inflammation of the skin, heart, lungs, joints and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare(may affect up to 1 in 1,000 people)

• leukemia (a cancer that affects the blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as inflammation of the optic nerve in the eye and Guillain-Barré syndrome, a condition that can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lung);
• intestinal perforation (hole in the wall of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (inflammation of the liver caused by your own immune system);
• cutaneous vasculitis (inflammation of the blood vessels in the skin);
• Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and skin rash with blisters);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy reddish-purple rash).

Not known(frequency cannot be estimated based on available data)

• T-cell hepato-splenic lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer associated with human herpes virus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which manifests as a skin rash accompanied by muscle weakness);
• weight gain (weight gain has been low for most patients).

Some of the side effects observed with adalimumab may be asymptomatic and can
only be detected through blood tests. These include:

Very common(may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased lipids in the blood;
• increased liver enzymes.

Common(may affect up to 1 in 10 people)

• increased white blood cell count;
• decreased platelet count;
• increased uric acid in the blood;
• alteration of sodium in the blood;
• decreased calcium in the blood;
• decreased phosphorus in the blood;
• increased sugar in the blood;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• decreased potassium in the blood.

Uncommon(may affect up to 1 in 100 people)

• high levels of bilirubin in the blood (liver blood test).

Rare(may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell and platelet counts.

Reporting of side effects
If your child experiences any side effects, including those not listed in this
leaflet, please tell your doctor or pharmacist. You can also report side effects directly
through the national reporting system listed in Annex V. By reporting side effects
you can help provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label/blister/box after the
writing Exp.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.
Alternative storage conditions:
When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 21 days – ensure the medicine is
protected from light. Once it has been removed from the refrigerator to be stored at room temperature, the
pre-filled syringe must be used within 21 days or discarded, even if it is subsequently
placed back in the refrigerator. You must record the date on which the pre-filled syringe is removed from
the refrigerator for the first time and the date after which the syringe must be discarded.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled syringe contains 20 mg of adalimumab in 0.4 mL of solution.
• The excipients are adipic acid, citric acid monohydrate, sodium chloride, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2 “Hefiya contains sodium”).

Description of the appearance of Hefiya and contents of the pack
Hefiya 20 mg solution for injection in pre-filled syringe for paediatric use is supplied in 0.4 mL of
solution from clear to slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use glass type I transparent syringe with a 29 gauge stainless
steel needle and a needle safety device with finger grip, rubber needle cap (thermoplastic elastomer) and plastic plunger, containing 0.4 mL of solution.
The pack contains 2 pre-filled syringes of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Sandoz nv/sa
Tél/Tel: +32 2 722 97 97

Lietuva
Sandoz Pharmaceuticals d.d filialas
Tel: +370 5 2636 037

Luxembourg/Luxemburg
Sandoz nv/sa
Tél/Tel.: +32 2 722 97 97

Česká republika
Sandoz s.r.o.
Tel: +420 225 775 111

България
Сандоз България КЧТ
Тел.: +359 2 970 47 47

Magyarország
Sandoz Hungária Kft.
Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige
Sandoz A/S
Tlf: +45 63 95 10 00

Malta
Sandoz Pharmaceuticals d.d.
Tel: +356 99644126

Deutschland
Hexal AG
Tel: +49 8024 908 0

Nederland
Sandoz B.V.
Tel: +31 36 52 41 600

Eesti
Sandoz d.d. Eesti filiaal
Tel: +372 665 2400

Österreich
Sandoz GmbH
Tel: +43 5338 2000

Ελλάδα
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε.
Τηλ: +30 216 600 5000

Polska
Sandoz Polska Sp. z o.o.
Tel.: +48 22 209 70 00

España
Sandoz Farmacéutica, S.A.
Tel: +34 900 456 856

Portugal
Sandoz Farmacêutica Lda.
Tel: +351 21 000 86 00

France
Sandoz SAS
Tél: +33 1 49 64 48 00

România
Terapia S.A.
Tel: +40 264 50 15 00

Hrvatska
Sandoz d.o.o.
Tel: +385 1 23 53 111

Slovenija
Sandoz farmacevtska družba d.d.
Tel: +386 1 580 29 02

Ireland
Rowex Ltd.
Tel: + 353 27 50077

Slovenská republika
Sandoz d.d. - organizačná zložka
Tel: +421 2 50 70 6111

Italia
Sandoz S.p.A.
Tel: +39 02 96541

Suomi/Finland
Sandoz A/S
Puh/Tel: +358 10 6133 400

Κύπρος
Sandoz Pharmaceuticals d.d.
Τηλ: +357 22 69 0690

United Kingdom (Northern Ireland)
Sandoz GmbH
Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu.

7. Instructions for Use

To avoid possible infections and to ensure you use the medicine correctly, it is important that
you follow these instructions.
Make sure you read, understand and follow these Instructions for Use before injecting Hefiya.
The healthcare professional must show you how to prepare and inject Hefiya correctly using the
pre-filled syringe before you use the medicine for the first time. If you have any doubts, contact
your healthcare professional.

Hefiya single-use pre-filled syringe with safety device for the needle and additional finger grip

Figure A: Hefiya pre-filled syringe with needle safety device and grip

additional for fingers

It is important that you:

• do not openthe outer box until you are ready to use the syringe;
• do not usethe syringe if the blister seals are broken, as use may not be safe;
• never leavethe syringe unattended where it could be tampered with by others;
• if you drop the syringe, do not useit if it appears damaged or if it fell after you removed the needle cap;
• do not removethe needle cap until the time of injection;
• be careful not to touchthe wings of the needle safety device before use. If you do, the needle safety device may be activated too early. Do not removethe finger grip before the injection;
• inject Hefiya 15-30 minutes after removing it from the refrigerator, for a more comfortable injection;
• dispose of the used syringe immediately after use. Do not reuse the syringe.See “4. Disposalof used syringes”at the end of these Instructions for Use.

How should you store Hefiya?

• Store the outer packaging of the syringes in a refrigerator, at a temperature between 2° and 8°C.
• When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 21 days - make sure to protect the medicine from light. Once it is removed from the refrigerator to be stored at room temperature, the pre-filled syringe must be used within 21 days or discarded, even if it is subsequently placed back in the refrigerator. You must record the date on which the pre-filled syringe is removed from the refrigerator for the first time and the date after which it must be discarded.
• Store the syringes in the original packaging until you are ready to use them, to protect the medicine from light.
• Do not store the syringes at extremely hot or cold temperatures.
• Do not freeze the syringes.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The packaging contains:

• Syringe/s pre-filled with Hefiya (see Figure A). Each syringe contains 20 mg/0.4 mL of Hefiya.

The packaging does not contain (see Figure B):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container.

Figure B: items not included in the packaging
See “4. Disposal of used syringes”at the end of these Instructions for Use.

Before the injection

Figure C: the needle safety device is not

activated – the syringe is ready for use

Figure D: the needle safety device is

activated – do not use
In this configuration, the
needle safety device is ACTIVATED.
DO NOT USEthe syringe (see

Figure D).

Preparing the syringe

• For a more comfortable injection, remove the blister containing the syringe from the refrigerator and leave it closed on the work surface for about 15-30 minutes to reach room temperature.
• Remove the syringe from the blister.
• Look through the window. The solution should be colourless or slightly yellowish and from clear to slightly opalescent. Do not use the syringe if you notice particles and/or changes in colour. If you have any doubts about the appearance of the solution, contact your pharmacist for assistance.
• Do not use the syringe if it is broken or if the needle safety device is activated. Return the syringe and packaging to the pharmacy. In this configuration, the needle safety device is NOT ACTIVATED. The syringe is ready for use (see Figure C).
• Check the expiry date (Exp.) of the syringe. Do not use the syringe if the expiry date has been exceeded.

Contact your pharmacist if the syringe does not pass any of the checks above.

1. Choice of injection site:

• The recommended injection site is the front of the thighs. You can also use the lower abdomen, but not the area within 5 cm around the navel (see Figure E).
• Choose a different site each time you give an injection.
• Do not inject the medicine into areas where the skin is painful, bruised, red, flaky, or hardened. Avoid areas with scars or stretch marks. If you have psoriasis, DO NOT inject the medicine directly into areas with psoriasis plaques.

Figure E: how to choose the injection

site

2. Cleaning the injection site:

• Wash your hands thoroughly with water and soap.
• Using a circular motion, clean the injection site with a swab soaked in alcohol. Allow to dry before administering the injection (see Figure F).
• Do not touch the cleaned area before the injection.

Figure F: how to clean the

injection site

3. Administration of the injection:

• Carefully pull off the needle cap to remove it from the syringe (see Figure G).
• Discard the needle cap.
• You may see a drop of liquid at the end of the needle. This is normal.

Figure G: how to pull off the cap

of the needle

• Gently create a skin fold at the injection site (see Figure H).
• Insert the needle into the skin as shown.
• Push the entire needle into the skin to ensure that all of the medicine is administered.

Figure H: how to insert the needle

• Hold the syringe as shown (see Figure I).
• Slowly press the plunger all the way down so that the plunger head is completely between the fins of the needle safety device.
• While holding the syringe in position, keep the plunger pressed down completely for 5 seconds.

Figure I: how to hold the syringe

• Keep the plunger fully depressedwhile carefully withdrawing the needle from the injection site, then release the skin (see Figure J).

Figure J: how to withdraw the needle

• Slowly release the plunger and allow the needle safety device to automatically cover the exposed needle (see Figure K).
• You may notice a small amount of blood at the injection site. You can press a cotton ball or gauze on the injection site and hold for 10 seconds. Do not rub the injection site. If necessary, you can cover the injection site with a small adhesive bandage.

Figure K: how to slowly release

the plunger

4. Disposal of used syringes:

• Dispose of the used syringe in a sharps disposal container (reclosable, puncture-resistant container). For your safety and health and that of others, used needles and syringes must never be reused.
• Do not dispose of any medicine down the drain or in household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Unused medicine and waste derived from that medicine must be disposed of in accordance with local regulations.

If you have any doubts, consult a doctor, pharmacist or nurse who is familiar with
Hefiya.

Hefiya 20 mg injectable solution in pre-filled syringe

adalimumab

20 mg/0.2 mL
Read this leaflet carefully before your child uses this medicine as it contains
important information.

• Keep this leaflet. You may need to read it again.
• Your doctor will give you a Patient Reminder Card, which contains important safety information that you need to know before your child starts using Hefiya and during treatment with Hefiya. Keep this Patient Reminder Cardwith you or your child during treatment and for 4 months after the last Hefiya injection given to your child.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed only for your child. Do not give it to other people, even if they have the same symptoms as your child, as it could be dangerous.
• If your child experiences any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Hefiya is and what it is used for
• 2. What you need to know before your child uses Hefiya
• 3. How to use Hefiya
• 4. Possible side effects
• 5. How to store Hefiya
• 6. Contents of the pack and other information
• 7. Instructions for use

1. What is Hefiya and what is it used for

Hefiya contains the active ingredient adalimumab, a medicine that acts on the body's immune system (defense system).
Hefiya is indicated for the treatment of the inflammatory diseases listed below:

• polyarticular juvenile idiopathic arthritis,
• arthritis associated with enthesitis,
• pediatric plaque psoriasis,
• pediatric Crohn’s disease,
• pediatric non-infectious uveitis.

The active ingredient contained in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumor necrosis factor (TNFα), which is
involved in the immune system (defense) and is present in higher concentrations in the
inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and reduces the
inflammatory process in these diseases.
Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged
from 2 to 17 years. Other disease-modifying drugs, such as methotrexate, may be given at diagnosis.
If these drugs do not work satisfactorily, patients will be given Hefiya for the treatment of polyarticular
juvenile idiopathic arthritis.
Arthritis associated with enthesitis
Arthritis associated with enthesitis is an inflammatory disease of the joints and the areas where the
tendons attach to the bones.
Hefiya is used to treat arthritis associated with enthesitis in children and adolescents aged
from 6 to 17 years.
Initially, other disease-modifying medications, such as methotrexate, may be given to patients. If these
medications do not work well enough, patients will be given Hefiya to treat arthritis associated with
enthesitis.
Pediatric plaque psoriasis
Plaque psoriasis is an inflammatory skin condition that causes red, scaly, and hardened patches of skin
covered with silvery scales. Plaque psoriasis can also affect the nails, causing them to break, thicken, and
lift from the nail bed, which can be painful. Psoriasis is thought to be caused by a problem with the body's
immune system that leads to increased production of skin cells.
Hefiya is used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years who
have not responded optimally to topical medications and UV therapy or are not indicated.
Pediatric Crohn’s disease
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat moderate to severe Crohn’s disease in children and adolescents aged
from 6 to 17 years.
Your child may first be given other medications. If these medications do not work satisfactorily, your
child will be given Hefiya to reduce the typical symptoms of their disease.
Pediatric non-infectious uveitis
Non-infectious uveitis is an inflammatory disease that affects certain parts of the eye.
Inflammation leads to decreased vision and/or the presence of mobile bodies in the eye
(black dots or thin lines that move across the field of vision). Hefiya works by reducing this
inflammation.
Hefiya is used for the treatment of children from 2 years of age with chronic non-infectious uveitis with
inflammation affecting the front of the eye.
Your child may first be given other medications. If these medications do not work satisfactorily, your
child will be given Hefiya to reduce the typical symptoms of their disease.

2. What you need to know before your child uses Hefiya

Do not use Hefiya

• If your child is allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If there is a severe infection, including tuberculosis, sepsis (blood poisoning) or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell your doctor if your child has signs or symptoms of infection, such as, for example, fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).
• If there is moderate or severe heart failure. It is important to tell your doctor if there has been or is a serious heart condition (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya
Allergic reaction

• If you experience allergic reactions with symptoms such as a feeling of tightness in the chest, wheezing, dizziness, swelling or skin rash, do not give Hefiya again and contact your doctor immediately, as in rare cases, these reactions can be life-threatening.

Infections

• If your child has an infection, including long-term or localized infections (for example, leg ulcers), consult your doctor before starting treatment with Hefiya. If you have any doubts, contact your doctor.
• You may be more likely to get infections during treatment with Hefiya. This risk may increase if your child's lung function is reduced. These infections can be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning).
• In rare cases, these infections can be life-threatening to the patient. It is important to tell your doctor about the presence of symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may advise you to temporarily stop Hefiya.

Tuberculosis (TB)

• Because cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will need to check if your child has signs or symptoms typical of tuberculosis before starting therapy with Hefiya. This will involve collecting a detailed medical assessment including your child's medical history and clinical tests (e.g., a chest X-ray and a tuberculin test). The performance and results of these tests must be recorded in your child’s Patient Reminder Card. It is very important to tell your doctor if your child has ever had tuberculosis, or if they have had close contact with people with tuberculosis. Tuberculosis may develop during therapy even if your child has received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, moderate fever) or other infections appear during or after therapy.

Travel/recurring infection

• Tell your doctor if your child has lived in or traveled to regions where fungal infections, such as histoplasmosis, coccidioidomycosis or blastomycosis, are very common.
• Tell your doctor if your child has had recurrent infections or has conditions that increase the risk of infection.

Hepatitis B virus

• Tell your doctor if your child is a carrier of the hepatitis B virus (HBV), has an active infection with the hepatitis B virus, or thinks they may be at risk of contracting the hepatitis B virus. Your doctor should test your child for hepatitis B virus infection. Taking adalimumab can reactivate hepatitis B virus infection in subjects who are carriers of this virus. In some rare cases, especially if your child is undergoing therapy with other drugs that suppress the immune system, reactivation of hepatitis B virus infection can be life-threatening to the patient.

Surgery or dental procedures

• Before surgery or dental procedures, tell your doctor that your child is taking Hefiya. Your doctor may advise you to temporarily stop Hefiya.

Demyelinating disease

• If your child has or develops demyelinating diseases (diseases that affect the insulating layer around nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Tell your doctor immediately if your child develops symptoms such as changes in vision, weakness of arms or legs, or numbness or tingling that affects any part of the body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause diseases and should not be given during treatment with Hefiya if they cause infections. Consult your doctor before vaccinating your child. In children, it is recommended, if possible, to administer the vaccinations scheduled for their age before starting therapy with Hefiya.
• If your daughter takes Hefiya during pregnancy, the baby may have a higher risk of contracting an infection up to about 5 months after the last dose she took during pregnancy. It is important that you inform your daughter's pediatrician or other healthcare provider about your daughter's use of Hefiya during pregnancy, so that they can decide when the baby should receive any type of vaccination.

Heart failure

• It is important to inform your doctor about any heart problems, both past and present. If your child has mild heart failure and is receiving concomitant treatment with Hefiya, your doctor will need to carefully assess and monitor your heart condition. If new symptoms of heart failure or worsening of existing symptoms (e.g., shortness of breath or swelling of the feet) appear, contact your doctor immediately.

Fever, bruising, bleeding or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If your child has a persistent fever, bruising or easy bleeding, or paleness, see your doctor immediately. The doctor may decide to stop therapy.

Tumor

• Very rarely, some types of tumors have occurred in children and adults treated with Hefiya or other anti-TNFα drugs. Patients with severe, long-standing rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukemia (cancers that affect blood cells and bone marrow). If your child takes Hefiya, the risk of developing lymphomas, leukemia or other tumors may increase. In rare circumstances, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also taking azathioprine or mercaptopurine. Tell your doctor if your child is taking azathioprine or mercaptopurine with Hefiya.
• Cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If damaged areas of skin appear during or after treatment, or if the appearance of damaged signs or areas changes, report it to your doctor.
• There have been cases of neoplasms, in addition to lymphoma, in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα. If your child suffers from COPD, or smokes heavily, they should discuss with their doctor whether treatment with an anti-TNFα is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya can lead to the manifestation of a syndrome like lupus. Tell your doctor if symptoms such as a persistent unexplained skin rash, fever, joint pain or fatigue develop.

Children and adolescents

• Do not give Hefiya to children with juvenile idiopathic polyarticular arthritis under the age of 2 years.
• Do not give Hefiya to children with pediatric plaque psoriasis or pediatric ulcerative colitis under the age of 4 years.
• Do not give Hefiya to children with pediatric Crohn's disease under the age of 6 years.
• Do not use the pre-filled syringe of 40 mg if doses less than 40 mg are recommended.

Other medicines and Hefiya
Tell your doctor or pharmacist if your child is taking, has recently taken or might
take any other medicine.
Hefiya can be taken both with methotrexate and with other disease-modifying antirheumatic drugs
(sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts), corticosteroids
or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya should not be taken at the same time as medicines containing the active ingredients anakinra or
abatacept due to the increased risk of serious infections. The combination of adalimumab and other
anti-TNF and anakinra or abatacept is not recommended due to the possible increased risk of
infections, including serious infections and other possible drug interactions. If you have any doubts, ask
your doctor.

Pregnancy and breastfeeding

• Your daughter should consider using adequate contraceptive measures to prevent pregnancy and continue using them for at least 5 months after the last therapy with Hefiya
• If a pregnancy is in progress, if your daughter suspects or is planning a pregnancy, ask

for advice from her doctor about taking this medicine.

• Hefiya should only be used during pregnancy if necessary.
• According to a pregnancy study, no increased risk of birth defects was found when the mother received adalimumab during pregnancy, compared to mothers who had the same condition but had not received adalimumab.
• Hefiya can be used during breastfeeding.
• If your daughter takes Hefiya during pregnancy, the baby may have a higher risk of contracting an infection.
• It is important that you inform your daughter's pediatrician or other healthcare provider about her use of Hefiya during pregnancy, before the baby receives any type of vaccination (for more information about vaccines, see “Warnings and precautions”).

Driving and using machines
Hefiya may affect, albeit only to a modest extent, the ability to drive, ride a bicycle or
operate machinery. After taking Hefiya, you may experience vision disturbances and a
feeling that the environment around you is rotating (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.2 mL of dose, which is essentially
‘sodium-free’.

3. How to use Hefiya

Use this medicine following the doctor’s or pharmacist’s instructions exactly. If you have
any doubts, ask your doctor or pharmacist.
The recommended doses of Hefiya in each approved indication are listed in the following
table. The doctor may prescribe a different concentration of Hefiya if the child needs a
different dose.

How and route of administration
Hefiya is administered by injection under the skin (subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist
explaining that your child has received more medicine than they should have. Always keep the box of the
medicine, even if it is empty.

If you forget to use Hefiya
If you forget to give your child an injection, you should inject the next dose of Hefiya as soon
as you remember. Then resume your child’s dose regularly according to the established dosage
schedule.

If you stop the treatment with Hefiya
The decision to stop using Hefiya should be discussed with your child’s doctor. Symptoms may return after treatment is stopped.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Most side effects are mild to moderate in form. However, some can be serious and require treatment. Side effects may occur
up to 4 months or more after the last injection of Hefiya.

Seek urgent medical attentionif you notice any of the following signs of an allergic reaction or
heart failure

• severe skin rash, hives;
• swelling of the face, hands, feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during physical activity or when lying down, or swollen feet.

Inform your doctor as soon as possibleif you notice any of the following reactions

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning when urinating, fatigue or weakness, or cough;
• symptoms of nerve problems, such as tingling, numbness, double vision or weakness of the arms or legs;
• signs of skin cancer such as swelling or an open sore that does not heal;
• signs and symptoms suggesting the onset of blood system disorders, such as persistent fever, bruising, bleeding, paleness.

The following side effects have been observed with Hefiya:

Very common(may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis and pneumonia);
• headache;
• abdominal pain (stomach ache);
• nausea and vomiting;
• skin rash;
• muscle pain.

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including tooth infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• infections affecting the joints;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergy);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, pricking or numbness;
• migraine;
• symptoms of nerve root compression (including back pain and leg pain);
• visual disturbances;
• eye inflammation;
• inflammation of the eyelids and swelling of the eyes;
• dizziness (feeling of spinning);
• feeling of a fast heartbeat;
• high blood pressure;
• hot flushes;
• hematoma (solid swelling with coagulated blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux;
• dry syndrome (including dry eyes and dry mouth);
• itching;
• itchy skin rash;
• bruising;
• skin inflammation (such as eczema);
• breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (fluid retention in the body, causing swelling of the affected tissue);
• fever;
• reduced platelets in the blood, which increases the risk of bleeding or bruising;
• difficulty healing.

Uncommon(may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when immune defenses are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that can affect lungs, skin and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• feeling of irregular heartbeat such as palpitations;
• heart problems that can cause shortness of breath or swelling in the ankles;
• acute myocardial infarction (heart attack);
• formation of a sac in the wall of a major artery, inflammation and blood clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal collection of fluid in the pleural space);
• inflammation of the pancreas causing severe pain in the abdomen and back;
• difficulty swallowing;
• facial edema (swelling);
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle catabolism;
• systemic lupus erythematosus (an autoimmune disorder, including inflammation of the skin, heart, lungs, joints and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare(may affect up to 1 in 1,000 people)

• leukemia (a cancer that affects the blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as inflammation of the optic nerve in the eye and Guillain-Barré syndrome, a condition that can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lungs);
• intestinal perforation (hole in the wall of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (inflammation of the liver caused by your own immune system);
• cutaneous vasculitis (inflammation of the blood vessels of the skin);
• Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and skin rash with blisters);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy, reddish-purple skin rash).

Not known(frequency cannot be estimated from available data)

• T-cell hepatosplenic lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer associated with human herpesvirus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which manifests as a skin rash accompanied by muscle weakness);
• weight gain (weight gain has been low for most patients).

Some of the side effects observed with adalimumab may be asymptomatic and can
only be detected through blood tests. These include:

Very common(may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased lipids in the blood;
• increased liver enzymes.

Common(may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in the blood;
• alteration of sodium in the blood;
• reduced calcium in the blood;
• reduced phosphorus in the blood;
• increased sugar in the blood;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• reduced potassium in the blood.

Uncommon(may affect up to 1 in 100 people)

• high levels of bilirubin in the blood (liver blood test).

Rare(may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell and platelet count.

Reporting of side effects
If your child experiences any side effects, including those not listed in this
leaflet, please inform your doctor or pharmacist. You can also report side effects directly
through the national reporting system reported in Annex V. By reporting side
effects you can contribute to providing more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label/blister/box after the
writing Exp.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.
Alternative storage conditions:
When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 42 days – ensure to protect the medicine
from light. Once it has been removed from the refrigerator to be stored at room temperature, the
pre-filled syringe must be used within 42 days or discarded, even if it is subsequently
placed back in the refrigerator. You must record the date on which the pre-filled syringe is removed from
the refrigerator for the first time and the date after which the syringe must be discarded.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled syringe contains 20 mg of adalimumab in 0.2 mL of solution.
• The excipients are adipic acid, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections.

Description of Hefiya and package contents
Hefiya 20 mg injectable solution in a pre-filled syringe for paediatric use is supplied in 0.2 mL of
solution ranging from clear to slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use glass type I transparent syringe with a 29 gauge stainless
steel needle with a finger grip, rubber needle cap (thermoplastic elastomer) and
plastic plunger, containing 0.2 mL of solution.
The multi-pack contains 2 (2 packs of 1) pre-filled syringes of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Sandoz nv/sa
Tél/Tel: +32 2 722 97 97

Lietuva
Sandoz Pharmaceuticals d.d filialas
Tel: +370 5 2636 037

Luxembourg/Luxemburg
Sandoz nv/sa
Tél/Tel.: +32 2 722 97 97

Česká republika
Sandoz s.r.o.
Tel: +420 225 775 111

България
Сандоз България КЧТ
Тел.: +359 2 970 47 47

Magyarország
Sandoz Hungária Kft.
Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige
Sandoz A/S
Tlf: +45 63 95 10 00

Malta
Sandoz Pharmaceuticals d.d.
Tel: +356 99644126

Deutschland
Hexal AG
Tel: +49 8024 908 0

Nederland
Sandoz B.V.
Tel: +31 36 52 41 600

Eesti
Sandoz d.d. Eesti filiaal
Tel: +372 665 2400

Österreich
Sandoz GmbH
Tel: +43 5338 2000

Ελλάδα
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε.
Τηλ: +30 216 600 5000

Polska
Sandoz Polska Sp. z o.o.
Tel.: +48 22 209 70 00

España
Sandoz Farmacéutica, S.A.
Tel: +34 900 456 856

Portugal
Sandoz Farmacêutica Lda.
Tel: +351 21 000 86 00

France
Sandoz SAS
Tél: +33 1 49 64 48 00

România
Sandoz Pharmaceuticals SRL
Tel: +40 21 407 51 60

Hrvatska
Sandoz d.o.o.
Tel: +385 1 23 53 111

Slovenija
Sandoz farmacevtska družba d.d.
Tel: +386 1 580 29 02

Ireland
Rowex Ltd.
Tel: + 353 27 50077

Slovenská republika
Sandoz d.d. - organizačná zložka
Tel: +421 2 50 70 6111

Italia
Sandoz S.p.A.
Tel: +39 02 96541

Suomi/Finland
Sandoz A/S
Puh/Tel: +358 10 6133 400

Κύπρος
Sandoz Pharmaceuticals d.d.
Τηλ: +357 22 69 0690

United Kingdom (Northern Ireland)
Sandoz GmbH
Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu .

7. Instructions for Use

To avoid possible infections and to ensure you use the medicine correctly, it is important that you
follow these instructions.
Make sure to read, understand and follow these Instructions for Use before injecting Hefiya.
The healthcare professional must show you how to prepare and inject Hefiya correctly using the
single-dose pre-filled syringe before you use the medicine for the first time. If you have any doubts, please contact
your healthcare professional.

Hefiya Single-Use Pre-filled Syringe

Figure A:Hefiya pre-filled syringe

It is important that you:

• do not usethe pre-filled syringe if the seal of the outer packaging is broken, because use may not be safe;
• do notopen the inner packaging until you are ready to use the Hefiya pre-filled syringe;
• never leavethe pre-filled syringe unattended where it could be tampered with by others;
• if you drop the syringe, do not useit if it appears damaged or if it was dropped after you removed the needle cap;
• do not removethe needle cap until the time of injection;
• inject Hefiya15-30 minutes after removing it from the refrigerator, for a more comfortable injection;
• dispose of the used syringe immediately after use. Do not reuse the syringe.See “4. Disposal of used syringes”at the end of these Instructions for Use;
• consult your doctor or nurse for advice on the appropriate injection site and technique if you are underweight or if you are injecting a child.

How should you store the Hefiya single-dose pre-filled syringe?

• Store the single-dose Hefiyasyringe in the original packaging to protect the medicine from light.
• Store the outer packaging of the pre-filled syringes in a refrigerator, at a temperature between 2° and 8°C.
• If necessary (for example if you are travelling), you can store the pre-filled syringe at room temperature up to 25°C for a maximum of 42 days.
• After 42 days, discard the pre-filled syringe stored at room temperature.
• You must record the date the pre-filled syringe is removed from the refrigerator for the first time and the date after which it must be discarded.
• Do notstore the pre-filled syringe at extremely hot or cold temperatures.
• Do notfreeze the pre-filled syringe.
• Do notuse the pre-filled syringe after the expiry date stated on the outer packaging or on the syringe label. If the expiry date has passed, return the entire package to the pharmacy.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean flat surface.
The syringe packaging contains:

• Hefiya pre-filled syringe (see Figure A). Each pre-filled syringe contains 20 mg/0.2 mL of adalimumab.

The Hefiya pre-filled syringe packaging does not contain (see Figure B):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container. See “4. Disposal of used syringes”at the end of these Instructions for Use.
• Adhesive bandage.

Figure B:items not included in the packaging

Preparing the pre-filled syringe

• For a more comfortable injection, remove the package containing the pre-filled syringe from the refrigerator and leave it closedon the work surface for about 15-30 minutes to reach room temperature.
• Remove the pre-filled syringe from the box and inspect it. The solution should be colourless to slightly yellowish and from clear to slightly opalescent. Do not usethe syringe if you notice particles and/or changes in colour. If you have any doubts about the appearance of the solution, contact your pharmacist for assistance.
• Do notuse the pre-filled syringe if it is broken. Return the entire product package to the pharmacy.
• Check the expiry date (Exp.) of the pre-filled syringe. Do not use the pre-filled syringe if the expiry date has passed.

Contact your pharmacist if the pre-filled syringe fails any of the checks listed
above.

1. Choice of injection site:

The injection site is the point on the body where you will administer
the injection with the prefilled syringe of Hefiya.

• The recommended injection site is the front of the thighs. You can also use the lower abdomen, but not the area within 5 cm around the navel (see Figure C).
• Choose a different site each time you administer an injection.
• Do notinject the medicine into areas where the skin is painful, bruised, reddened, flaky or hardened. Avoid areas with scars or stretch marks. If you suffer from psoriasis, do notinject the medicine directly into areas with psoriasis plaques.

Figure C:how to choose the injection
site

2. Injection site cleaning:

• When you are ready to use the pre-filled syringe, wash your hands thoroughly with water and soap.
• Using a circular motion, clean the injection site with a swab soaked in alcohol. Allow to dry before administering the injection (see Figure D).
• Do nottouch this area again before administering the injection. Allow the skin to dry before the injection. Do not fan or blow air onto the cleaned area.

Figure D:how to clean the injection
site

3. Administration of the injection:

• Carefully pull off the needle cap to remove it from the syringe (see Figure E).
• Dispose of (eliminate) the needle cap.
• You may see a drop of liquid at the end of the needle. This is normal.

Figure E:how to pull off the needle cap

• Gently create a skin fold at the injection site (see Figure F).
• Insert the needle into the skin at a 45° angle, as shown (see Figure F).

Figure F:how to insert the needle

• Hold the prefilled single-dose syringe as shown (see Figure G).
• Press the plunger slowlyuntil it stops.
• While holding the syringe in place, keep the plunger pressed down completely for 5 seconds.
• Carefully withdraw the needle from the injection site, then release the skin. You may notice a small amount of blood at the injection site. You can press a cotton ball or gauze on the injection site and hold it for 10 seconds. Do notrub the injection site. If necessary, you can cover the injection site with a small adhesive bandage.

Figure G:how to press the plunger

4. Disposal of used pre-filled syringes:

• Dispose of the used syringe in a sharps disposal container (a resealable, puncture-resistant container). For your safety and health, and that of others, used needles and syringes must never be reused.
• Do not dispose of any medicine down the drain or in household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Unused medicine and waste from that medicine must be disposed of in accordance with local regulations.

Figure H:how to dispose of the used
pre-filled syringe

If you have any doubts, consult a doctor, pharmacist or nurse who is familiar with
Hefiya.

Hefiya 40 mg injectable solution in pre-filled syringe

adalimumab

40 mg/0.8 mL
Read this leaflet carefully before using this medicine as it contains important
information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will give you a Patient Reminder Card, which contains important safety information that you need to know before administering Hefiya and during treatment with Hefiya. Keep this Patient Reminder Cardwith you during treatment and for 4 months after the last injection (or the last injection given to your son/daughter) of Hefiya.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed only for you. Do not give it to other people, even if their symptoms are the same as yours, as it could be dangerous.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Hefiya is and what it is used for
• 2. What you need to know before you use Hefiya
• 3. How to use Hefiya
• 4. Possible side effects
• 5. How to store Hefiya
• 6. Contents of the pack and other information
• 7. Instructions for use

1. Cos’è Hefiya e a cosa serve

Hefiya contains the active ingredient adalimumab, a medication that acts on the body's immune system (defense system).
Hefiya is indicated for the treatment of the inflammatory diseases listed below:

• rheumatoid arthritis,
• polyarticular juvenile idiopathic arthritis,
• arthritis associated with enthesitis,
• ankylosing spondylitis,
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis,
• psoriatic arthritis,
• psoriasis,
• hidradenitis suppurativa,
• Crohn’s disease,
• ulcerative colitis and
• non-infectious uveitis

The active ingredient contained in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumor necrosis factor (TNFα), which is
involved in the immune system (defense system) and is present at higher concentrations in the
inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and decreases the
inflammatory process in these diseases.
Rheumatoid Arthritis
Rheumatoid arthritis is an inflammatory disease of the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, other disease-modifying drugs, such as
methotrexate, may be initially administered. If these drugs do not work satisfactorily, you will be given Hefiya to treat
rheumatoid arthritis.
Hefiya can also be used for the treatment of severe, active and progressive rheumatoid arthritis
without prior treatment with methotrexate.
Hefiya may slow the progression of cartilage and bone damage in the joints,
caused by the disease, and improve physical function.
Generally Hefiya is used with methotrexate. If your doctor believes that treatment with
methotrexate is not appropriate, Hefiya may be administered alone.
Polyarticular Juvenile Idiopathic Arthritis and Arthritis Associated with Enthesitis
Polyarticular juvenile idiopathic arthritis and arthritis associated with enthesitis are inflammatory diseases
of the joints, which typically manifest for the first time during childhood.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents of
ages 2 to 17 years and arthritis associated with enthesitis in children and adolescents aged 6-17 years.
Other disease-modifying drugs, such as methotrexate, may be administered at diagnosis.
If these drugs do not work satisfactorily, patients will be given Hefiya for
treatment of polyarticular juvenile idiopathic arthritis or arthritis associated with enthesitis.
Ankylosing Spondylitis and Axial Spondyloarthritis without Radiographic Evidence of Ankylosing Spondylitis
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of spondylitis
are inflammations of the spine.
Hefiya is used in adults to treat these conditions. If you have ankylosing spondylitis or
axial spondyloarthritis without radiographic evidence of ankylosing spondylitis, you will first take other
medications. If these medications do not work satisfactorily, you will take Hefiya to reduce the signs and
symptoms of the disease.
Plaque Psoriasis in Adults and Children
Plaque psoriasis is an inflammatory skin condition that causes reddish, scaly, and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the
nails, causing them to break, thicken, and lift from the nail bed, which can be
painful. Psoriasis is believed to be caused by a problem with the body's immune system that
leads to increased production of skin cells.
Hefiya is used to treat moderate to severe plaque psoriasis in adults. Hefiya is
also used to treat severe plaque psoriasis in children and adolescents from 4 to 17 years of age in
whom topical medications and UV light therapy have not worked optimally or are not indicated.
Psoriatic Arthritis
Psoriatic arthritis is an inflammatory disease of the joints associated with psoriasis.
Hefiya is used to treat psoriatic arthritis in adults. Hefiya may slow the damage to cartilage
and bone in the joints, caused by the disease, and improve physical function.
Hidradenitis Suppurativa in Adults and Adolescents
Hidradenitis Suppurativa (sometimes called inverse acne) is a long-term inflammatory disease of the skin and is often painful. Symptoms may include painful nodules and abscesses (cysts)
that may drain pus.
It most frequently affects specific areas of the skin, such as the submammary region, armpits,
inner thighs, groin, and buttocks. Scars can also form in the affected areas.
Hefiya is used to treat Hidradenitis Suppurativa in adults and adolescents aged 12 years and over. Hefiya may reduce the number of nodules and abscesses you have and the pain that is often associated with
this disease. Initially, you may receive other medications. If these medications do not work in
a satisfactory manner, you will receive Hefiya.
Crohn’s Disease in Adults and Children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat Crohn’s disease in adults and children aged 6 to 17 years. If
you suffer from Crohn’s disease, you will first be given other medications. If you do not
respond adequately to these medications, you will be given Hefiya to
reduce the typical symptoms of Crohn’s disease.
Ulcerative Colitis in Adults and Children
Ulcerative colitis is an inflammation of the large intestine.
Hefiya is used to treat moderate to severe ulcerative colitis in adults and children aged 6
to 17 years. If you have ulcerative colitis, you may first take other medications. If these medications do not
work satisfactorily, you will take Hefiya to reduce the signs and symptoms of the disease.
Non-Infectious Uveitis in Adults and Children
Non-infectious uveitis is an inflammatory disease that affects certain parts of the eye.
Inflammation leads to decreased vision and/or the presence of mobile bodies in the eye
(black dots or thin lines that move across the field of vision). Hefiya works by reducing this
inflammation.
Hefiya is used for the treatment of:

• Adults with non-infectious uveitis with inflammation affecting the back of the eye
• Children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front of the eye

2. What you need to know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or any of the other ingredients of this medicine (listed in section 6).
• If you have a severe infection, including tuberculosis, sepsis (blood poisoning) or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell your doctor if you have signs or symptoms of infection, such as e.g. fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).
• If you have moderate or severe heart failure. It is important to tell your doctor if you have had or have a serious heart condition (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya
Allergic reaction

• If you experience allergic reactions with symptoms such as a feeling of tightness in the chest, wheezing, dizziness, swelling or skin rash, do not administer Hefiya again and contact your doctor immediately as, in rare cases, these reactions can be life-threatening.

Infection

• If you have an infection, including long-term or localized infections (for example, leg ulcers), consult your doctor before starting treatment with Hefiya. If you have doubts, contact your doctor.
• You may be more likely to contract infections during treatment with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning).
• In rare cases, these infections can be life-threatening. It is important to tell your doctor about the presence of symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may advise you to temporarily stop Hefiya.

Tuberculosis (TB)

• Because cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will need to check if you have signs or symptoms typical of tuberculosis before starting therapy with Hefiya. This will involve collecting a detailed medical assessment including your medical history and clinical examinations (e.g. a chest X-ray and a tuberculin test). The performance and results of these tests must be recorded on the Patient Reminder Card. It is very important to tell your doctor if you have ever had tuberculosis, or if you have had close contact with people with tuberculosis. Tuberculosis can develop during therapy even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, fatigue, moderate fever) or other infections appear during or after therapy.

Travel/recurring infection

• Tell your doctor if you have lived in or traveled to regions where fungal infections, such as histoplasmosis, coccidioidomycosis or blastomycosis, are common.
• Tell your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.

Hepatitis B virus

• Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active infection with the hepatitis B virus or if you think you may be at risk of contracting the hepatitis virus
• B. Your doctor should test you for hepatitis B virus infection. Taking adalimumab can reactivate hepatitis B virus infection in subjects who are carriers of this virus. In some rare cases, especially if the patient is undergoing therapy with other drugs that suppress the immune system, reactivation of hepatitis B virus infection can endanger the patient's life.

Age over 65 years

• If you are over 65 years of age, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection while you are being treated with Hefiya. It is important to inform your doctor if symptoms of infections such as fever, wounds, feeling tired or dental problems appear.

Surgery or dental procedures

• Before surgery or dental procedures, tell your doctor that you are taking Hefiya. Your doctor may advise you to temporarily stop Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases that affect the insulating layer around nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Tell your doctor immediately if you experience symptoms such as changes in vision, weakness of arms or legs or numbness or tingling that affects any part of the body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause diseases and should not be administered during treatment with Hefiya if they cause infections. Consult your doctor before getting vaccinated. In children, it is recommended to administer the vaccinations appropriate for their age before starting therapy with Hefiya, if possible. If you take Hefiya during pregnancy, the baby may have a higher risk of contracting an infection up to about 5 months after the last dose you took during pregnancy. It is important that you inform your pediatrician or other healthcare provider of your use of Hefiya during pregnancy, so that they can decide when the baby should receive any type of vaccination.

Heart failure

• It is important to inform your doctor about any heart problems, both past and present. If you have mild heart failure and are receiving concomitant treatment with Hefiya, your doctor will need to carefully assess and monitor your heart condition. If new symptoms of heart failure appear or if existing symptoms worsen (e.g. shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising or easy bleeding or paleness, see your doctor immediately. The latter may decide to stop therapy.

Cancer

• Very rarely, some types of cancer have occurred in children and adults treated with Hefiya or other anti-TNFα drugs. Patients with severe, long-standing rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukemia (cancers that affect blood cells and bone marrow). If you take Hefiya, the risk of developing lymphomas, leukemia or other cancers may increase. In rare circumstances, a specific and serious type of lymphoma has been observed in patients undergoing therapy with adalimumab. Some of these patients were also taking azathioprine or

mercaptopurine. Tell your doctor if you are taking azathioprine or mercaptopurine with Hefiya.

• Cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If damaged areas of skin appear during or after treatment, or if the appearance of damaged areas or lesions changes, report it to your doctor.
• There have been cases of neoplasms, in addition to lymphoma, in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα. If you suffer from COPD, or smoke heavily, you should discuss with your doctor whether treatment with an anti-TNFα is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya can lead to the manifestation of a syndrome like lupus. Tell your doctor if you experience symptoms such as persistent unexplained skin rash, fever, joint pain or fatigue.

Children and adolescents

• Do not give Hefiya to children with polyarticular juvenile idiopathic arthritis under the age of 2 years.
• Do not give Hefiya to children with pediatric plaque psoriasis or pediatric ulcerative colitis under the age of 4 years.
• Do not give Hefiya to children with pediatric Crohn's disease under the age of 6 years.
• Do not use the pre-filled syringe of 40 mg if doses less than 40 mg are recommended.

Other medicines and Hefiya
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
Hefiya can be taken both with methotrexate and with other disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts), corticosteroids
or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken in conjunction with medicines containing the active ingredients anakinra or
abatacept due to the increased risk of having serious infections. The combination of adalimumab and other anti-TNF and anakinra or abatacept is not recommended due to the possible increase in the risk of
infections, including serious infections and other possible drug interactions. If you have doubts, consult
your doctor.

Pregnancy and breastfeeding

• You should consider using adequate contraceptive measures to prevent pregnancy and continue using them for at least 5 months after the last therapy with Hefiya
• If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor for advice on taking this medicine.
• Hefiya should only be used during pregnancy if necessary.
• According to a pregnancy study, no increased risk of birth defects was found when the mother received adalimumab during pregnancy, compared to mothers with the same condition who did not receive adalimumab.
• Hefiya can be used during breastfeeding.
• If you take Hefiya during pregnancy, the baby may have a higher risk of contracting an infection.
• It is important that you inform your pediatrician or other healthcare provider of your use of Hefiya during pregnancy, before the baby receives any type of vaccination (for more information on vaccines see “Warnings and precautions”).

Driving and using machines
Hefiya may affect, albeit only to a modest extent, your ability to drive, ride a bicycle or use machinery. After taking Hefiya, you may experience vision disturbances and a feeling that the environment around you is rotating (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 mL of dose, i.e. essentially
‘sodium-free’.

3. How to use Hefiya

Use this medicine following the instructions of your doctor or pharmacist exactly. If you have
doubts, consult your doctor or pharmacist.
Hefiya is available in pens of 40 mg and prefilled syringes of 20 mg and 40 mg for the
administration to patients of a full dose of 20 mg or 40 mg.

How and route of administration
Hefiya is administered by injection under the skin (subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for Use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist
explaining that you have taken more medicine than you should. Always keep the medicine box,
even if empty.

If you forget to use Hefiya
If you forget to give an injection, you should inject the next dose of Hefiya as soon as you
remember. Then resume the dose regularly according to the established dosage schedule.

If you stop treatment with Hefiya
The decision to stop using Hefiya must be discussed with your doctor. Symptoms may
return after stopping treatment.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most side effects are mild to moderate. However, some can be serious and require treatment. Side effects may occur
up to 4 months or more after the last injection of Hefiya.

Seek urgent medical attentionif you notice any of the following signs of an allergic reaction or
heart failure

• severe skin rash, hives;
• swelling of the face, hands, feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath on exertion or when lying down, or swollen feet.

Tell your doctor as soon as possibleif you notice any of the following reactions

• signs and symptoms of infection such as fever, feeling unwell, sores, dental problems, burning when urinating, fatigue or weakness, or cough;
• symptoms of nerve problems, such as tingling, numbness, double vision, or weakness of the arms or legs;
• signs of skin cancer such as a swelling or open sore that does not heal;
• signs and symptoms suggesting the development of blood disorders, such as persistent fever, bruising, bleeding, paleness.

The following side effects have been observed with Hefiya:

Very common(may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness or itching);
• respiratory tract infections (including common cold, runny nose, sinusitis and pneumonia);
• headache;
• abdominal pain (stomach ache);
• nausea and vomiting;
• skin rash;
• muscle pain.

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including tooth infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• infections of the joints;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergy);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, pricking or numbness;
• migraine;
• symptoms of nerve root compression (including back pain and leg pain);
• visual disturbances;
• eye inflammation;
• inflammation of the eyelids and swelling of the eyes;
• dizziness (feeling of spinning);
• feeling of a fast heartbeat;
• high blood pressure;
• hot flushes;
• bruise (solid swelling with clotted blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux;
• dry eye syndrome (including dry eyes and dry mouth);
• itching;
• itchy rash;
• contusion;
• skin inflammation (such as eczema);
• nail breakage of the fingers and toes;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (fluid retention in the body, causing swelling of the affected tissue);
• fever;
• reduced platelets in the blood, which increases the risk of bleeding or bruising;
• difficulty healing.

Uncommon(may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when immune defenses are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that can affect lungs, skin and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• feeling of irregular heartbeat such as palpitations;
• heart problems that can cause shortness of breath or swelling of the ankles;
• acute myocardial infarction (heart attack);
• formation of a sac in the wall of a major artery, inflammation and a blood clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal accumulation of fluid in the pleural space);
• inflammation of the pancreas causing severe abdominal and back pain;
• difficulty swallowing;
• facial edema (swelling);
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (an immune system disorder, including inflammation of the skin, heart, lungs, joints and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare(may affect up to 1 in 1,000 people)

• leukemia (a cancer that affects the blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as inflammation of the optic nerve in the eye and Guillain-Barré syndrome, a condition that can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lungs);
• intestinal perforation (hole in the wall of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (inflammation of the liver caused by your own immune system);
• cutaneous vasculitis (inflammation of the blood vessels in the skin);
• Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and skin rash with blisters);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy, reddish-purple skin rash).

Not known(frequency cannot be estimated from the available data)

• T-cell hepatosplenic lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer associated with human herpes virus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which manifests as a skin rash accompanied by muscle weakness);
• weight gain (weight gain has been modest for most patients).

Some of the side effects observed with adalimumab may be asymptomatic and can
only be detected through blood tests. These include:

Very common(may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased blood lipids;
• increased liver enzymes.

Common(may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in the blood;
• alteration of sodium in the blood;
• reduced calcium in the blood;
• reduced phosphorus in the blood;
• increased blood sugar;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• reduced potassium in the blood.

Uncommon(may affect up to 1 in 100 people)

• high levels of bilirubin in the blood (liver blood test).

Rare(may affect up to 1 in 1,000 people)

• low white blood cells, red blood cells and platelets.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the national
reporting system listed in Annex V. By reporting side effects you can help
provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label/blister/box after the
writing Exp.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.
Alternative storage conditions:
When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 21 days – make sure to protect the medicine
from light. Once it is removed from the refrigerator to be stored at room temperature, the
pre-filled syringe must be used within 21 days or discarded, even if it is subsequently
placed back in the refrigerator. You must record the date on which the pre-filled syringe is removed from
the refrigerator for the first time and the date after which the syringe must be discarded.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled syringe contains 40 mg of adalimumab in 0.8 mL of solution.
• The excipients are adipic acid, citric acid monohydrate, sodium chloride, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2 “Hefiya contains sodium”).

Description of Hefiya and contents of the pack
Hefiya 40 mg solution for injection in a pre-filled syringe is presented in 0.8 mL of solution which is from clear to slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use glass type I transparent syringe with a 29 gauge stainless steel needle and a needle safety device with finger grip, rubber needle cap (thermoplastic elastomer) and plastic plunger, containing 0.8 mL of solution.
The packs contain 1 and 2 pre-filled syringes of Hefiya.
Multipacks contain 6 (3 packs of 2) pre-filled syringes of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and in pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria
For further information on this medicinal product, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Sandoz nv/sa
Tél/Tel: +32 2 722 97 97

Lietuva
Sandoz Pharmaceuticals d.d filialas
Tel: +370 5 2636 037

България
Сандоз България КЧТ
Тел.: +359 2 970 47 47

Luxembourg/Luxemburg
Sandoz nv/sa
Tél/Tel.: +32 2 722 97 97

Česká republika
Sandoz s.r.o.
Tel: +420 225 775 111

Magyarország
Sandoz Hungária Kft.
Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige
Sandoz A/S
Tlf: +45 63 95 10 00

Malta
Sandoz Pharmaceuticals d.d.
Tel: +356 99644126

Deutschland
Hexal AG
Tel: +49 8024 908 0

Nederland
Sandoz B.V.
Tel: +31 36 52 41 600

Eesti
Sandoz d.d. Eesti filiaal
Tel: +372 665 2400

Österreich
Sandoz GmbH
Tel: +43 5338 2000

Ελλάδα
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε.
Τηλ: +30 216 600 5000

Polska
Sandoz Polska Sp. z o.o.
Tel.: +48 22 209 70 00

España
Sandoz Farmacéutica, S.A.
Tel: +34 900 456 856

Portugal
Sandoz Farmacêutica Lda.
Tel: +351 21 000 86 00

France
Sandoz SAS
Tél: +33 1 49 64 48 00

România
Terapia S.A.
Tel: +40 264 50 15 00

Hrvatska
Sandoz d.o.o.
Tel: +385 1 23 53 111

Slovenija
Sandoz farmacevtska družba d.d.
Tel: +386 1 580 29 02

Ireland
Rowex Ltd.
Tel: + 353 27 50077

Slovenská republika
Sandoz d.d. - organizačná zložka
Tel: +421 2 50 70 6111

Italia
Sandoz S.p.A.
Tel: +39 02 96541

Suomi/Finland
Sandoz A/S
Puh/Tel: +358 10 6133 400

Κύπρος
Sandoz Pharmaceuticals d.d.
Τηλ: +357 22 69 0690

United Kingdom (Northern Ireland)
Sandoz GmbH
Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

7. Instructions for Use

To avoid possible infections and to ensure you use the medicine correctly, it is important that
you follow these instructions.
Make sure you read, understand and follow these Instructions for Use before injecting Hefiya.
The healthcare professional must show you how to prepare and inject Hefiya correctly using the
prefilled syringe before you use the medicine for the first time. If you have any doubts, please contact
your healthcare professional.

Hefiya single-use prefilled syringe with safety device for the needle and additional finger grip

Figure A: Hefiya prefilled syringe with needle safety device and grip

additional for fingers

It is important that you:

• do not openthe outer box until you are ready to use the syringe;
• do not usethe syringe if the blister seals are broken, as use may not be safe;
• never leavethe syringe unattended where it could be tampered with by others;
• if you drop the syringe, do not useit if it appears damaged or if it fell after you removed the needle cap;
• do not removethe needle cap until the time of injection;
• be careful not to touchthe wings of the needle safety device before use. If you do, the needle safety device may be activated too early. Do not removethe finger grip before the injection;
• inject Hefiya 15-30 minutes after removing it from the refrigerator, for a more comfortable injection;
• dispose of the used syringe immediately after use. Do not reuse the syringe.See “4. Disposalof used syringes”at the end of these Instructions for Use.

How should you store Hefiya?

• Store the outer package of syringes in a refrigerator, at a temperature between 2° and 8°C.
• When necessary (for example when traveling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 21 days - make sure to protect the medicine from light. Once it is removed from the refrigerator to be stored at room temperature, the prefilled syringe must be used within 21 days or discarded, even if it is subsequently placed back in the refrigerator. You must record the date on which the prefilled syringe is removed from the refrigerator for the first time and the date after which it must be discarded.
• Store the syringes in the original packaging until you are ready to use them, to protect the medicine from light.
• Do not store the syringes at extremely hot or cold temperatures.
• Do not freeze the syringes.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean flat surface.
The package contains:

• Hefiya prefilled syringe/s (see Figure A). Each syringe contains 40 mg/0.8 mL of Hefiya.

The package does not contain (see Figure B):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps container.

Figure B: items not included in the package
See “4. Disposal of used syringes”at the end of these Instructions for Use.

Before the injection

Figure C: the needle safety device is not

activated – the syringe is ready for use

Figure D: the needle safety device

is activated – do not use
In this configuration, the
needle safety device
is ACTIVATED.
DO NOT USEthe syringe (see

Figure D).

Preparing the syringe

• For a more comfortable injection, remove the blister containing the syringe from the refrigerator and leave it closed on the work surface for about 15-30 minutes to reach room temperature.
• Remove the syringe from the blister. In this configuration, the needle safety device is NOT ACTIVATED. The syringe is ready for use (see Figure C).
• Look through the window. The solution should be colorless or slightly yellowish and from clear to slightly opalescent. Do not use the syringe if you notice particles and/or color changes. If you have any doubts about the appearance of the solution, contact your pharmacist for assistance.
• Do not use the syringe if it is broken or if the needle safety device is activated. Return the syringe and package to the pharmacy.
• Check the expiry date (Exp.) of the syringe. Do not use the syringe if the expiry date has been exceeded.

Contact your pharmacist if the syringe does not pass any of the checks above.

1. Choice of injection site:

• The recommended injection site is the front of the thighs. You can also use the lower abdomen, but not the area within 5 cm around the navel (see Figure E).
• Choose a different site each time you administer an injection.
• Do not inject the medicine into areas where the skin is painful, bruised, red, flaky, or hardened. Avoid areas with scars or stretch marks. If you suffer from psoriasis, DO NOT inject the medicine directly into areas with psoriasis plaques.

Figure E: how to choose the injection

site

2. Cleaning the injection site:

• Wash your hands thoroughly with water and soap.
• Using a circular motion, clean the injection site with a swab soaked in alcohol. Allow to dry before administering the injection (see Figure F).
• Do not touch the cleaned area before the injection.

Figure F: how to clean the

injection site

3. Administration of the injection:

• Carefully pull off the needle cap to remove it from the syringe (see Figure G).
• Discard the needle cap.
• You may see a drop of liquid at the end of the needle. This is normal.

Figure G: how to pull off the cap

of the needle

• Gently create a skin fold at the injection site (see Figure H).
• Insert the needle into the skin as shown.
• Push the entire needle into the skin to ensure that all of the medicine is administered.

Figure H: how to insert the needle

• Hold the syringe as shown (see Figure I).
• Slowly press the plunger all the way down so that the plunger head is completely between the fins of the needle safety device.
• While holding the syringe in position, keep the plunger pressed down completely for 5 seconds.

Figure I: how to hold the syringe

• Keep the plunger fully depressedwhile carefully withdrawing the needle from the injection site, then release the skin (see Figure J).

Figure J: how to withdraw the needle

• Slowly release the plunger and allow the needle safety device to automatically cover the exposed needle (see Figure K).
• You may notice a small amount of blood at the injection site. You can press a cotton ball or gauze on the injection site and hold it for 10 seconds. Do not rub the injection site. If necessary, you can cover the injection site with a small adhesive bandage.

Figure K: how to release slowly

the plunger

4. Disposal of used syringes:

• Dispose of the used syringe in a sharps disposal container (a resealable, puncture-resistant container). For your safety and health, and that of others, used needles and syringes must never be reused.
• Do not dispose of any medicine in wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Unused medicine and waste derived from that medicine must be disposed of in accordance with local regulations.

If you have any doubts, consult a doctor, pharmacist or nurse who is familiar with
Hefiya.

Hefiya 40 mg injectable solution in pre-filled pen

adalimumab

40 mg/0.8 mL
Read this leaflet carefully before you use this medicine as it contains important
information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will give you a Patient Reminder Card, which contains important safety information that you need to know before administering Hefiya and during treatment with Hefiya. Keep this Patient Reminder Cardwith you during treatment and for 4 months after the last injection (or the last injection given to your son/daughter) of Hefiya.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, as it could be dangerous.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Hefiya is and what it is used for
• 2. What you need to know before you use Hefiya
• 3. How to use Hefiya
• 4. Possible side effects
• 5. How to store Hefiya
• 6. Contents of the pack and other information
• 7. Instructions for use

1. What is Hefiya and what is it used for?

Hefiya contains the active ingredient adalimumab, a medicine that acts on the body's immune system (defense system).
Hefiya is indicated for the treatment of the inflammatory diseases listed below:

• rheumatoid arthritis,
• polyarticular juvenile idiopathic arthritis,
• arthritis associated with enthesitis,
• ankylosing spondylitis,
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis,
• psoriatic arthritis,
• psoriasis,
• hidradenitis suppurativa,
• Crohn’s disease,
• ulcerative colitis and
• non-infectious uveitis.

The active ingredient contained in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumor necrosis factor (TNFα), which is
involved in the immune system (defense system) and is present at higher concentrations in the
inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and decreases the
inflammatory process in these diseases.
Rheumatoid Arthritis
Rheumatoid arthritis is an inflammatory condition of the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, other disease-modifying drugs, such as
methotrexate, may be initially given. If these drugs do not work adequately, you will be given Hefiya to treat
rheumatoid arthritis.
Hefiya can also be used for the treatment of severe, active and progressive rheumatoid arthritis
without prior treatment with methotrexate.
Hefiya may slow the progression of damage to the cartilage and bones of the joints, caused
by the disease, and improve physical function.
Generally Hefiya is used with methotrexate. If your doctor believes that treatment with
methotrexate is not appropriate, Hefiya may be administered alone.
Polyarticular Juvenile Idiopathic Arthritis and Arthritis Associated with Enthesitis
Polyarticular juvenile idiopathic arthritis and arthritis associated with enthesitis are inflammatory diseases
of the joints, which typically manifest for the first time during childhood.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents of
ages 2 to 17 years and arthritis associated with enthesitis in children and adolescents of 6-17 years of age.
Other disease-modifying drugs, such as methotrexate, may be given at diagnosis.
If these drugs do not work adequately, patients will be given Hefiya for the
treatment of polyarticular juvenile idiopathic arthritis or arthritis associated with enthesitis.
Ankylosing Spondylitis and Axial Spondyloarthritis without Radiographic Evidence of Ankylosing Spondylitis
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of spondylitis
are inflammations of the spine.
Hefiya is used in adults to treat these conditions. If you have ankylosing spondylitis or axial spondyloarthritis without radiographic evidence of ankylosing spondylitis, you will first take other
drugs. If these drugs do not work adequately, you will take Hefiya to reduce the signs and
symptoms of the disease.
Plaque Psoriasis in Adults and Children
Plaque psoriasis is an inflammatory skin condition that causes red, scaly and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the
nails, causing them to break, thicken and lift from the nail bed, which can be
painful. Psoriasis is thought to be caused by a problem with the body's immune system that
leads to an increase in skin cell production.
Hefiya is used to treat moderate to severe plaque psoriasis in adults. Hefiya is
also used to treat severe plaque psoriasis in children and adolescents from 4 to 17 years of age in
whom topical medications and light therapy have not worked optimally or are not indicated.
Psoriatic Arthritis
Psoriatic arthritis is an inflammatory disease of the joints associated with psoriasis.
Hefiya is used to treat psoriatic arthritis in adults. Hefiya may slow the damage to the cartilage
and bones of the joints, caused by the disease, and improve physical function.
Hidradenitis Suppurativa in Adults and Adolescents
Hidradenitis Suppurativa (sometimes called inverse acne) is a long-term inflammatory disease of the skin and is often painful. Symptoms may include painful nodules and abscesses (cysts)
that may drain pus. It most frequently affects specific areas of the skin, such as the
submammary region, armpits, inner thighs, groin and buttocks. Scars may also form in the affected areas.
Hefiya is used to treat Hidradenitis Suppurativa in adults and adolescents from 12 years of
age. Hefiya may reduce the number of nodules and abscesses you have and the pain that is often associated with
this disease. Initially, you may receive other medications. If these medications do not work in
adequately, you will receive Hefiya.
Crohn’s Disease in Adults and Children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat Crohn’s disease in adults and children aged 6 to 17 years. If
you suffer from Crohn’s disease, you will first be given other medications. If you do not
respond adequately to these medications, you will be given Hefiya to
reduce the typical symptoms of Crohn’s disease.
Ulcerative Colitis in Adults and Children
Ulcerative colitis is an inflammation of the large intestine.
Hefiya is used to treat moderate to severe ulcerative colitis in adults and children aged 6
to 17 years. If you have ulcerative colitis, you may first take other medications. If these medications do not
work adequately, you will take Hefiya to reduce the signs and symptoms of the disease.
Non-Infectious Uveitis in Adults and Children
Non-infectious uveitis is an inflammatory disease that affects certain parts of the eye.
Inflammation leads to a decrease in vision and/or the presence of floaters in the eye
(black dots or thin lines that move across the field of vision). Hefiya works by reducing this
inflammation.
Hefiya is used for the treatment of:

• Adults with non-infectious uveitis with inflammation affecting the back of the eye
• Children from 2 years of age with chronic non-infectious uveitis with inflammation affecting the front of the eye

2. What you need to know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a severe infection, including tuberculosis, sepsis (blood poisoning) or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell your doctor if you have signs or symptoms of infection, such as, for example, fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).
• If you have moderate or severe heart failure. It is important to tell your doctor if you have had or have a serious heart condition (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.
Allergic reaction

• If you experience allergic reactions with symptoms such as a feeling of tightness in the chest, wheezing, dizziness, swelling or skin rash, do not administer Hefiya again and contact your doctor immediately as, in rare cases, these reactions can be life-threatening.

Infection

• If you have an infection, including long-term or localized infections (for example, leg ulcers), consult your doctor before starting treatment with Hefiya. If you have doubts, contact your doctor.
• You may be more likely to get infections during treatment with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning).
• In rare cases, these infections can be life-threatening. It is important to tell your doctor about the presence of symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may advise you to temporarily stop Hefiya.

Tuberculosis (TB)

• Because cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will need to check if you have signs or symptoms typical of tuberculosis before starting therapy with Hefiya. This will involve collecting a detailed medical assessment including your medical history and clinical examinations (e.g. a chest X-ray and a tuberculin test). The performance and results of these tests must be recorded on the Patient Reminder Card. It is very important to tell your doctor if you have ever had tuberculosis, or if you have had close contact with people with tuberculosis. Tuberculosis can develop during therapy even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, fatigue, moderate fever) or other infections appear during or after therapy.

Travel/recurring infection

• Tell your doctor if you have lived in or travelled to regions where fungal infections, such as histoplasmosis, coccidioidomycosis or blastomycosis, are common.
• Tell your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.

Hepatitis B virus

• Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active infection with the hepatitis B virus or if you think you may be at risk of contracting the hepatitis virus

• B. Your doctor should test you for hepatitis B virus infection. Taking adalimumab can reactivate hepatitis B virus infection in subjects who are carriers of this virus. In some rare cases, especially if the patient is undergoing therapy with other drugs that suppress the immune system, reactivation of hepatitis B virus infection can be life-threatening.

Age over 65 years

• If you are over 65 years of age, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection while you are being treated with Hefiya. It is important to tell your doctor if symptoms of infections such as fever, wounds, feeling tired or dental problems appear.

Surgery or dental procedures

• Before surgery or dental procedures, tell your doctor that you are taking Hefiya. Your doctor may advise you to temporarily stop Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases that affect the insulating layer around the nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Tell your doctor immediately if you experience symptoms such as changes in vision, weakness of arms or legs, or numbness or tingling that affects any part of the body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause diseases and should not be administered during treatment with Hefiya if they cause infections. Consult your doctor before getting vaccinated. In children, it is recommended, if possible, to administer the vaccinations scheduled for their age before starting therapy with Hefiya. If you have taken Hefiya during pregnancy, the child may have a higher risk of contracting this infection up to about 5 months after the last dose you took during pregnancy. It is important that you inform your pediatrician or other healthcare provider of your use of Hefiya during pregnancy, so that they can decide when the child should receive any type of vaccination.

Heart failure

• It is important to tell your doctor about any heart problems, whether past or present. If you have mild heart failure and are receiving concomitant treatment with Hefiya, your doctor will need to carefully assess and monitor your heart condition. If new symptoms of heart failure appear or existing symptoms worsen (e.g. shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising or easy bleeding or paleness, see your doctor immediately. The latter may decide to interrupt the therapy.

Cancer

• Very rarely, some types of cancer have occurred in children and adults treated with adalimumab or other TNF-alpha inhibitors. Patients with severe, long-standing rheumatoid arthritis may have a higher than average risk of developing a

lymphoma and leukemia (cancers that affect blood cells and bone marrow). If you
take Hefiya, the risk of developing lymphomas, leukemia or other cancers may increase. In rare
circumstances, a specific and serious type of lymphoma has been observed in patients treated with adalimumab.
Some of these patients were also taking azathioprine or mercaptopurine. Tell your doctor if you are taking azathioprine or mercaptopurine with Hefiya.

• In addition, cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If damaged areas of skin appear during or after treatment or if the appearance of existing damaged areas changes, report it to your doctor.
• There have been cases of neoplasms, in addition to lymphoma, in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another TNF-alpha inhibitor. If you suffer from COPD, or smoke heavily, you should discuss with your doctor whether treatment with a TNF-alpha inhibitor is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the manifestation of a syndrome like lupus. Tell your doctor if you experience symptoms such as persistent unexplained skin rash, fever, joint pain or fatigue.

Children and adolescents

• Do not give Hefiya to children with polyarticular juvenile idiopathic arthritis under the age of 2 years.
• Do not give Hefiya to children with pediatric plaque psoriasis or pediatric ulcerative colitis under the age of 4 years.
• Do not give Hefiya to children with pediatric Crohn’s disease under the age of 6 years.
• Do not use the pre-filled pen of 40 mg if doses less than 40 mg are recommended.

Other medicines and Hefiya
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
Hefiya can be taken both with methotrexate and with other disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts), corticosteroids
or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken at the same time as medicines containing the active ingredients anakinra or
abatacept due to the increased risk of serious infections. The combination of adalimumab and other anti-TNF and anakinra or abatacept is not recommended due to the possible increase in the risk of
infections, including serious infections and other possible drug interactions. If you have doubts, consult
your doctor.

Pregnancy and breastfeeding

• You should consider using appropriate contraceptive measures to prevent pregnancy and continue using them for at least 5 months after the last therapy with Hefiya.
• If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor for advice on taking this medicine.
• Hefiya should only be used during pregnancy if necessary.
• According to a pregnancy study, no increased risk of birth defects was found when the mother received adalimumab during pregnancy, compared to mothers with the same condition who had not received adalimumab.
• Hefiya can be used during breastfeeding.
• If you take Hefiya during pregnancy, the child may have a higher risk of contracting an infection.
• It is important that you inform your pediatrician or other healthcare provider of your use of Hefiya during pregnancy, before the child receives any type of vaccination (for more information on vaccines, see “Warnings and precautions”).

Driving and using machines
Hefiya may affect, albeit to a modest extent, your ability to drive, ride a bicycle or use machinery. After taking Hefiya, you may experience visual disturbances and a feeling that the environment around you is rotating (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 mL dose, i.e. essentially
‘sodium-free’.

3. How to use Hefiya

Use this medicine following exactly the instructions of your doctor or pharmacist. If you have
doubts, consult your doctor or pharmacist.
Hefiya is available in pens of 40 mg and prefilled syringes of 20 mg and 40 mg for the
administration to patients of a full dose of 20 mg or 40 mg.

How and route of administration
Hefiya is administered by injection under the skin (for subcutaneous injection).
Detailed instructions on how to inject Hefiya are reported in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist
explaining that you have taken more medicine than you should. Always keep the medicine box,
even if empty.

If you forget to use Hefiya
If you forget to make an injection, you must inject the next dose of Hefiya as soon as you
remember. Then resume the dose regularly according to the established dosage schedule.

If you stop the treatment with Hefiya
The decision to stop using Hefiya must be discussed with your doctor. Symptoms may
return after stopping treatment.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Most side effects are mild to moderate. However, some can be serious and require treatment. Side effects may occur
up to 4 months or more after the last injection of Hefiya.

Seek medical attention urgentlyif you notice any of the following signs of an allergic reaction or
heart failure

• severe skin rash, hives;
• swelling of the face, hands, feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath on exertion or when lying down, or swollen feet.

Inform your doctor as soon as possibleif you notice any of the following reactions

• signs and symptoms of infection such as fever, feeling unwell, sores, dental problems, burning when urinating; fatigue or weakness or cough;
• symptoms of nerve problems, such as tingling, numbness, double vision or weakness of the arms or legs;
• signs of skin cancer such as swelling or an open sore that does not heal;
• signs and symptoms suggesting the onset of blood system disorders, such as persistent fever, bruising, bleeding, paleness.

The following side effects have been observed with Hefiya

Very common(may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis and pneumonia);
• headache;
• abdominal pain (stomach ache);
• nausea and vomiting;
• skin rash;
• muscle pain.

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including tooth infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• infections affecting the joints;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergy);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, pricking sensations or numbness;
• migraine;
• symptoms of nerve root compression (including back pain and leg pain);
• visual disturbances;
• eye inflammation;
• inflammation of the eyelids and swelling of the eyes;
• dizziness (feeling of spinning);
• feeling of a fast heartbeat;
• high blood pressure;
• hot flushes;
• bruise (solid swelling with coagulated blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux;
• dry eye syndrome (including dry eyes and dry mouth);
• itching;
• itchy skin rash;
• contusion;
• skin inflammation (such as eczema);
• breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (fluid retention in the body, causing swelling of the affected tissue);
• fever;
• reduced platelets in the blood, which increases the risk of bleeding or bruising;
• difficulty healing.

Uncommon(may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when defenses are lowered;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that can affect lungs, skin and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor;
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• feeling of irregular heartbeat such as palpitations;
• heart problems that can cause shortness of breath or swelling of the ankles;
• acute myocardial infarction (heart attack);
• formation of a sac in the wall of a major artery, inflammation and blood clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal collection of fluid in the pleural space);
• inflammation of the pancreas causing severe abdominal and back pain;
• difficulty swallowing;
• facial edema (swelling);
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle catabolism;
• systemic lupus erythematosus (immune system disorder, including inflammation of the skin, heart, lungs, joints and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare(may affect up to 1 in 1,000 people)

• leukemia (a cancer that affects the blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as inflammation of the optic nerve in the eye and Guillain-Barré syndrome, a condition that can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lungs);
• intestinal perforation (hole in the wall of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (inflammation of the liver caused by your own immune system);
• cutaneous vasculitis (inflammation of the blood vessels in the skin);
• Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and skin rash with blisters);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy, reddish-purple skin rash).

Frequency not known(the frequency cannot be estimated from the available data)

• T-cell hepatosplenic lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer associated with human herpes virus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which manifests as a skin rash accompanied by muscle weakness);
• weight gain (weight gain has been low for most patients).

Some of the side effects observed with adalimumab may be asymptomatic and can
only be detected through blood tests. These include:

Very common(may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased lipids in the blood;
• increased liver enzymes.

Common(may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in the blood;
• alteration of sodium in the blood;
• reduced calcium in the blood;
• reduced phosphorus in the blood;
• increased sugar in the blood;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• reduced potassium in the blood.

Uncommon(may affect up to 1 in 100 people)

• high levels of bilirubin in the blood (liver blood test).

Rare(may affect up to 1 in 1,000 people)

• low white blood cell count, red blood cell count and platelet count.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the national
reporting system listed in Annex V. By reporting side effects you can help
provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label/blister/box after the
word Exp.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled pen in the outer packaging to protect the medicine from light.
Alternative storage conditions:
When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 21 days – ensure the medicine is
protected from light. Once removed from the refrigerator for storage at room temperature, the
pre-filled pen must be used within 21 days or discarded, even if it is subsequently
placed back in the refrigerator. You must record the date on which the pre-filled pen is removed from
the refrigerator for the first time and the date after which the pen must be discarded.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled pen contains 40 mg of adalimumab in 0.8 mL of solution.
• The excipients are adipic acid, citric acid monohydrate, sodium chloride, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections (see section 2 “Hefiya contains sodium”).

Description of Hefiya’s appearance and contents of the pack
Hefiya 40 mg solution for injection in a pre-filled pen is supplied as 0.8 mL of solution from clear
to slightly opalescent, from colourless to slightly yellowish.
Hefiya is supplied in a single-use pre-filled syringe assembled in a triangular-shaped pen with
a transparent window and label. The syringe inside the pen is type I glass with a 29 gauge needle
made of stainless steel, an internal rubber needle cap (thermoplastic elastomer)
and a rubber stopper, containing 0.8 mL of solution.
Packs contain 1 and 2 pre-filled pens of Hefiya.
Multipacks contain 6 (3 packs of 2) pre-filled pens of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in a pre-filled syringe and in a pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Sandoz nv/sa
Tél/Tel: +32 2 722 97 97

Lietuva
Sandoz Pharmaceuticals d.d filialas
Tel: +370 5 2636 037

Luxembourg/Luxemburg
Sandoz nv/sa
Tél/Tel.: +32 2 722 97 97

Česká republika
Sandoz s.r.o.
Tel: +420 225 775 111

България
Сандоз България КЧТ
Тел.: +359 2 970 47 47

Magyarország
Sandoz Hungária Kft.
Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige
Sandoz A/S
Tlf: +45 63 95 10 00

Malta
Sandoz Pharmaceuticals d.d.
Tel: +356 99644126

Deutschland
Hexal AG
Tel: +49 8024 908 0

Nederland
Sandoz B.V.
Tel: +31 36 52 41 600

Eesti
Sandoz d.d. Eesti filiaal
Tel: +372 665 2400

Österreich
Sandoz GmbH
Tel: +43 5338 2000

Ελλάδα
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε.
Τηλ: +30 216 600 5000

Polska
Sandoz Polska Sp. z o.o.
Tel.: +48 22 209 70 00

España
Sandoz Farmacéutica, S.A.
Tel: +34 900 456 856

Portugal
Sandoz Farmacêutica Lda.
Tel: +351 21 000 86 00

France
Sandoz SAS
Tél: +33 1 49 64 48 00

România
Terapia S.A.
Tel: +40 264 50 15 00

Hrvatska
Sandoz d.o.o.
Tel: +385 1 23 53 111

Slovenija
Sandoz farmacevtska družba d.d.
Tel: +386 1 580 29 02

Ireland
Rowex Ltd.
Tel: + 353 27 50077

Slovenská republika
Sandoz d.d. - organizačná zložka
Tel: +421 2 50 70 6111

Italia
Sandoz S.p.A.
Tel: +39 02 96541

Suomi/Finland
Sandoz A/S
Puh/Tel: +358 10 6133 400

Κύπρος
Sandoz Pharmaceuticals d.d.
Τηλ: +357 22 69 0690

United Kingdom (Northern Ireland)
Sandoz GmbH
Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu.

7. Instructions for Use

To avoid possible infections and to ensure you use the medicine correctly, it is important that
you follow these instructions.
Make sure you read, understand and follow these Instructions for Use before injecting Hefiya.
The healthcare professional must show you how to prepare and inject Hefiya correctly using the
pre-filled pen before you use the medicine for the first time. If you have any doubts, contact
your healthcare professional.

Single-use pre-filled pen of Hefiya

Figure A: parts of the Hefiya pen
In Figure A, the pen is shown without the cap. Do notremove the cap until you are ready to administer
the injection.

It is important that you:

• do not openthe outer box until you are ready to use the pen;
• do not usethe pen if the outer packaging seal or the pen safety seal is broken;
• never leavethe pen unattended where it could be tampered with by others;
• if you drop the pen, do not useit if it appears damaged or if it was dropped after you removed the cap;
• inject Hefiya 15-30 minutes after removing it from the refrigerator, for a more comfortable injection;
• dispose of the used pen immediately after use. Do not reuse the pen.See “4. Disposalof used pens”at the end of these Instructions for Use.

How should you store the pen?

• Store the pen in its packaging in a refrigerator, at a temperature between 2° and 8°C.
• When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 21 days - make sure to protect the medicine from light. Once it is removed from the refrigerator to be stored at room temperature, the pre-filled pen must be used within 21 days or discarded, even if it is subsequently placed back in the refrigerator. You must record the date on which the pre-filled pen is removed from the refrigerator for the first time and the date after which it must be discarded.
• Store the pen in its original packaging until you are ready to use it, to protect the medicine from light.
• Do not store the pen at extremely hot or cold temperatures.
• Do not freeze the pen.

Keep Hefiya and all medicines out of the reach of children.
What do you need for the injection?
Place the following items on a clean, flat surface.
The packaging contains:

• Pen/s pre-filled with Hefiya (see Figure A). Each pen contains 40 mg/0.8 mL of Hefiya. The packaging does not contain (see Figure B):
• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container.

Figure B: items not included in the packaging
See “4. Disposal of used pens”at the end of these Instructions for Use.

Before the injection
Preparing the pen

• For a more comfortable injection, remove the pen from the refrigerator approximately 15-30 minutes before the injection to allow it to reach room temperature.
• Look through the window. The solution should be colourless to slightly yellowish and from clear to slightly opalescent. Do not usethe pen if you notice particles and/or colour changes. If you have any doubts about the appearance of the solution, contact your pharmacist for assistance.

Figure C: safety checks before

the injection

• Check the expiry date (Exp.) of the pen. Do not use the pen if the expiry date has passed.
• Do not use the pen if the safety seal is broken.

Contact your pharmacist if the pen fails any of the checks above.

1. Choice of injection site:

• The recommended injection site is the front of the thighs. You can also use the lower part of the abdomen, but not the area within 5 cm around the navel (see Figure D).
• Choose a different site each time you administer an injection.
• Do not inject the medicine into areas where the skin is painful, bruised, reddened, flaky or hardened. Avoid areas with scars or stretch marks. If you suffer from psoriasis, DO NOT inject the medicine directly into areas with psoriasis plaques.

Figure D: how to choose the injection

site

2. Cleaning the injection site:

• Wash your hands thoroughly with water and soap.
• Using a circular motion, clean the injection site with a swab soaked in alcohol. Allow to dry before administering the injection (see Figure E).
• Do not touch the cleaned area before the injection.

Figure E: how to clean the

injection site

3. Removing the pen cap:

• Remove the cap only when you are ready to use the pen.
• Rotate the cap in the direction of the arrows (see Figure F).
• Once the cap is removed, discard it. Never try toreplace the cap.
• Use the pen within 5 minutes of removing the cap.
• You may notice some drops of liquid coming out of the needle. This is normal.

Figure F: how to remove the cap

4. How to hold the pen:

• Hold the pen at 90 degrees to the clean injection site (see Figure G).

CorrectIncorrect

Figure G: how to hold the pen

Injection
Read before performing the injection
During the injection you will feel 2 clicks:
o The first clickindicates that the injection has started.
o A moment later, a second clickindicates that the injection is almostfinished.
You must keep the pen pressed firmly against the skin until you see a green
indicatorfill the window and stop moving.

5. Start of injection:

• Press the pen firmly against the skin to start the injection (see Figure H).
• The first clickindicates that the injection has started.
• Keep pressingthe pen firmly against the skin.
• The green indicatorshows the progress of the injection.

Figure H: how to start the injection

6. Completion of the injection:

• Pay attention to the second clickwhich indicates that the injection is almostcomplete.
• Check that the green indicatorfills the window and has stopped moving (see Figure I).
• Now you can remove the pen.

Figure I: how to complete

the injection

After the injection

• 7.Check that the green indicator fills the window(see Figure J) :
• This means that the medicine has been administered. Contact your doctor if the green indicator is not visible.
• You may notice a small amount of blood at the injection site. You can press a cotton ball or gauze onto the injection site and hold it for 10 seconds. Do not rub the injection site. If necessary, you can cover the injection site with a small adhesive bandage.

Figure J: how to check

the green indicator

8. Disposal of used pens:

• Dispose of the used pen in a sharps disposal container (a resealable, puncture-resistant container). For your safety and the safety of others, used pens should never be reused.
• Do not dispose of any medicine down the drain or in household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Unused medicine and waste from that medicine must be disposed of in accordance with local regulations.

If you have any doubts, consult a doctor, pharmacist or nurse who is familiar with
Hefiya.

Hefiya 40 mg injectable solution in pre-filled syringe

adalimumab

40 mg/0.4 mL
Read this leaflet carefully before using this medicine as it contains important
information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will give you a Patient Information Card, which contains important safety information that you need to know before administering Hefiya and during treatment with Hefiya. Keep this Patient Information Card with you during treatment and for 4 months after the last injection (or the last injection given to your child) of Hefiya.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Hefiya is and what it is used for
• 2. What you need to know before you use Hefiya
• 3. How to use Hefiya
• 4. Possible side effects
• 5. How to store Hefiya
• 6. Contents of the pack and other information
• 7. Instructions for use

1. What is Hefiya and what is it used for

Hefiya contains the active ingredient adalimumab, a medicine that acts on the body's immune system (defense system).
Hefiya is indicated for the treatment of the inflammatory diseases listed below:

• rheumatoid arthritis,
• polyarticular juvenile idiopathic arthritis,
• arthritis associated with enthesitis,
• ankylosing spondylitis,
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis,
• psoriatic arthritis,
• plaque psoriasis,
• hidradenitis suppurativa,
• Crohn’s disease,
• ulcerative colitis,
• non-infectious uveitis

The active ingredient contained in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumor necrosis factor (TNFα), which is
involved in the immune system (defense system) and is present at higher concentrations in the
inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and decreases the
inflammatory process in these diseases.
Rheumatoid Arthritis
Rheumatoid arthritis is an inflammatory condition of the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, other disease-modifying drugs, such as
methotrexate, may be initially taken. If these drugs do not work satisfactorily, you will be given Hefiya to treat
rheumatoid arthritis.
Hefiya can also be used for the treatment of severe, active and progressive rheumatoid arthritis
without prior treatment with methotrexate.
Hefiya may slow the progression of damage to the cartilage and bones of the joints,
caused by the disease, and improve physical function.
Generally Hefiya is used with methotrexate. If your doctor believes that treatment with
methotrexate is not appropriate, Hefiya may be administered alone.
Polyarticular Juvenile Idiopathic Arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged
from 2 to 17 years. Other disease-modifying drugs, such as methotrexate, may be given at diagnosis. If these drugs do not work satisfactorily, patients will be
administered Hefiya.
Arthritis Associated with Enthesitis
Arthritis associated with enthesitis is an inflammatory disease of the joints and the areas where the
tendons attach to the bones. Hefiya is used to treat arthritis associated with enthesitis in patients aged
6 years or older.
Other disease-modifying drugs, such as methotrexate, may initially be taken. If
these medicines do not work well enough, patients will be given Hefiya.
Ankylosing Spondylitis and Axial Spondyloarthritis without Radiographic Evidence of Ankylosing Spondylitis
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of ankylosing
spondylitis are inflammations of the spine.
Hefiya is used in adults to treat these conditions. If you have ankylosing spondylitis or axial spondyloarthritis without radiographic evidence of ankylosing spondylitis, you will first take other
medicines. If these drugs do not work satisfactorily, you will take Hefiya to reduce the signs and
symptoms of the disease.
Plaque Psoriasis in Adults and Children
Plaque psoriasis is an inflammatory skin condition that causes red, scaly, and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the
nails, causing them to break, thicken, and lift from the nail bed, which can be
painful. Psoriasis is believed to be caused by a problem with the body's immune system that
leads to increased production of skin cells.
Hefiya is used to treat moderate to severe plaque psoriasis in adults. Hefiya is
also used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years in
whom topical medications and UV light therapy have not worked optimally or are not indicated.
Psoriatic Arthritis
Psoriatic arthritis is an inflammatory disease of the joints associated with psoriasis.
Hefiya is used to treat psoriatic arthritis in adults. Hefiya may slow the damage to the cartilage
and bones of the joints, caused by the disease, and improve physical function.
Hidradenitis Suppurativa in Adults and Adolescents
Hidradenitis Suppurativa (sometimes called inverse acne) is a long-term inflammatory disease of the skin and is often painful. Symptoms may include painful nodules and abscesses (cysts)
that can drain pus.
It most frequently affects specific areas of the skin, such as the submammary region, armpits,
inner thighs, groin, and buttocks. Scars can also form in the affected areas.
Hefiya is used to treat

• moderate to severe Hidradenitis Suppurativa in adults and
• moderate to severe Hidradenitis Suppurativa in adolescents aged 12 to 17 years.

Hefiya may reduce the number of nodules and abscesses you have and the pain that is often associated with this
disease. Initially, you may receive other medications. If these drugs do not work satisfactorily, you will receive Hefiya.
Crohn’s Disease in Adults and Children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat

• moderate to severe Crohn’s disease in adults and
• moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.

If you suffer from Crohn’s disease, you will first be given other medications. In the event that you do not
respond adequately to these drugs, you will be given Hefiya to
reduce the typical symptoms of Crohn’s disease.
Ulcerative Colitis in Adults and Children
Ulcerative colitis is an inflammation of the large intestine.
Hefiya is used to treat

• moderate to severe ulcerative colitis in adults and
• moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

If you have ulcerative colitis, you may first take other medications. If these drugs do not work
satisfactorily, you will take Hefiya to reduce the signs and symptoms of ulcerative colitis.
Non-Infectious Uveitis in Adults and Children
Non-infectious uveitis is an inflammatory disease that affects certain parts of the eye.
Inflammation leads to decreased vision and/or the presence of floaters in the eye
(small dark spots or thin lines that move across the field of vision). Hefiya works by reducing this
inflammation.
Hefiya is used for the treatment of:

• Adults with non-infectious uveitis with inflammation affecting the back of the eye
• Children aged 2 years and older with chronic non-infectious uveitis with inflammation affecting the front of the eye. Other medications may initially be taken. If the response to these medications is not adequate, you will be given Hefiya.

2. What you need to know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a severe infection, including tuberculosis, sepsis (blood poisoning) or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell your doctor if you have signs or symptoms of infection, such as e.g. fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).
• If you have moderate or severe heart failure. It is important to tell your doctor if you have had or have a serious heart condition (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya
Allergic reaction

• If you experience allergic reactions with symptoms such as a feeling of tightness in the chest, wheezing, dizziness, swelling or skin rash, do not administer Hefiya again and contact your doctor immediately as, in rare cases, these reactions can be life-threatening.

Infections

• If you have an infection, including long-term or localized infections (for example, leg ulcers), consult your doctor before starting treatment with Hefiya. If you have doubts, contact your doctor.
• You may be more likely to get infections during treatment with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning).
• In rare cases, these infections can be life-threatening. It is important to tell your doctor about the presence of symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may advise you to temporarily stop Hefiya.

Tuberculosis (TB)

• Because cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will need to check if you have signs or symptoms typical of tuberculosis

before starting therapy with Hefiya. This will involve collecting a detailed medical assessment including your medical history and clinical tests (e.g. a chest X-ray and the tuberculin test). The performance and results of these tests must be recorded in the

Patient Reminder Card. It is very important to tell your doctor if you have ever had tuberculosis, or if you have had close contact with people with tuberculosis. Tuberculosis can develop during therapy even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, moderate fever) or other infections appear during or after therapy.
Travel/recurrent infection

• Tell your doctor if you have lived in or travelled to regions where fungal infections, such as histoplasmosis, coccidioidomycosis or blastomycosis, are common.
• Tell your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.

Hepatitis B virus

• Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active infection with the hepatitis B virus or if you think you may be at risk of contracting the hepatitis
• B virus. Your doctor should test you for hepatitis B virus infection. Taking adalimumab can reactivate hepatitis B virus infection in people who are carriers of this virus. In some rare cases, especially if the patient is undergoing therapy with other drugs that suppress the immune system, reactivation of hepatitis B virus infection can be life-threatening.

Age over 65 years

• If you are over 65 years of age, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection while you are being treated with Hefiya. It is important to tell your doctor if symptoms of infections such as fever, wounds, feeling tired or dental problems appear.

Surgery or dental procedures

• Before surgery or dental procedures, tell your doctor that you are taking Hefiya. Your doctor may advise you to temporarily stop Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases that affect the insulating layer around the nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Tell your doctor immediately if you experience symptoms such as changes in vision, weakness of arms or legs or numbness or tingling that affects any part of the body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause diseases and should not be administered during treatment with Hefiya in case they cause infections. Consult your doctor before getting vaccinated. In children, it is recommended, if possible, to administer the vaccinations recommended for their age before starting therapy with Hefiya. If you take Hefiya during pregnancy, the child may have a higher risk of contracting an infection up to about 5 months after the last dose you took during pregnancy. It is important that you tell the pediatrician or other healthcare provider of

your use of Hefiya during pregnancy, so that they can decide when the child should receive any type of vaccination.
Heart failure

• It is important to tell your doctor about any heart problems, both past and present. If you have mild heart failure and are receiving concomitant treatment with Hefiya, your doctor should carefully assess and monitor your heart condition. If new symptoms of heart failure or worsening of existing symptoms (e.g. shortness of breath or swelling of the feet) appear, contact your doctor immediately.

Fever, bruising, bleeding or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising or easy bleeding or paleness, see your doctor immediately. The latter may decide to stop the therapy.

Tumor

• In children and adults treated with Hefiya or other anti-TNFα drugs, very rare cases of certain types of tumors have occurred. Patients with severe, long-standing rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukemia (cancers that affect blood cells and bone marrow). If you are taking Hefiya, the risk of developing lymphomas, leukemia or other tumors may increase. In rare circumstances, a specific and serious type of lymphoma has been observed in patients undergoing therapy with adalimumab. Some of these patients were also taking azathioprine or mercaptopurine. Tell your doctor if you are taking azathioprine or mercaptopurine with Hefiya.
• Cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If damaged areas of skin appear during or after treatment or if the appearance of damaged areas changes, report it to your doctor.
• Cases of neoplasms, other than lymphoma, have been reported in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα. If you suffer from COPD, or smoke heavily, you should discuss with your doctor whether treatment with an anti-TNFα is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the manifestation of a syndrome like lupus. Tell your doctor if you experience symptoms such as persistent unexplained skin rash, fever, joint pain or fatigue.

Children and adolescents

• Do not give Hefiya to children with polyarticular juvenile idiopathic arthritis under the age of 2 years.
• Do not give Hefiya to children with pediatric plaque psoriasis or pediatric ulcerative colitis under the age of 4 years.
• Do not give Hefiya to children with pediatric Crohn's disease under the age of 6 years.
• Do not use the pre-filled syringe of 40 mg if doses less than 40 mg are recommended.

Other medicines and Hefiya
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
Hefiya can be taken both with methotrexate and with other disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts), corticosteroids
or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya should not be taken at the same time as medicines containing the active ingredients anakinra or
abatacept due to the increased risk of having serious infections. The combination of adalimumab and other anti-TNF and anakinra or abatacept is not recommended due to the possible increased risk of
infections, including serious infections and other possible drug interactions. If you have doubts, consult
your doctor.

Pregnancy and breastfeeding

• You should consider using adequate contraceptive measures to prevent pregnancy and continue using them for at least 5 months after the last therapy with Hefiya
• If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor for advice on taking this medicine.
• Hefiya should only be used during pregnancy if necessary.
• According to a pregnancy study, no increased risk of birth defects was found when the mother received adalimumab during pregnancy, compared to mothers with the same condition who did not receive adalimumab.
• Hefiya can be used during breastfeeding.
• If you take Hefiya during pregnancy, the child may have a higher risk of contracting an infection.
• It is important that you tell the pediatrician or other healthcare provider of your use of Hefiya during pregnancy, before the child receives any type of vaccination (for more information on vaccines see “Warnings and precautions”).

Driving and using machines
Hefiya may affect, albeit only to a modest extent, your ability to drive, ride a bicycle or operate
machinery. After taking Hefiya, you may experience visual disturbances and a sensation that the
environment around you is spinning (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.4 mL of dose, i.e. essentially
‘sodium-free’.

3. How to use Hefiya

Use this medicine following the instructions of your doctor or pharmacist exactly. If you have
doubts, consult your doctor or pharmacist.
The recommended doses of Hefiya in each approved indication are listed in the following
table. The doctor may prescribe a different concentration of Hefiya if you need a different
dose.

How and route of administration
Hefiya is administered by injection under the skin (subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist
explaining that you have taken more medicine than you should. Always keep the medicine box,
even if empty.

If you forget to use Hefiya
If you forget to give an injection, you should inject the next dose of Hefiya as soon as you
remember. Then resume the dose regularly according to the established dosage schedule.

If you stop using Hefiya
The decision to stop using Hefiya should be discussed with your doctor. Symptoms may
return after stopping treatment.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Most side effects are mild to moderate in form. However, some may be serious and require treatment. Side effects may occur
up to 4 months or more after the last injection of Hefiya.

Seek urgent medical attentionif you notice any of the following signs of an allergic reaction or
heart failure

• severe skin rash, hives;
• swelling of the face, hands, feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath on exertion or when lying down or swollen feet.

Inform your doctor as soon as possibleif you notice any of the following reactions

• signs and symptoms of infection such as fever, feeling unwell, wounds, dental problems, burning when urinating, fatigue or weakness or cough;
• symptoms of nerve problems, such as tingling, numbness, double vision or weakness of the arms or legs;
• signs of skin cancer such as swelling or an open sore that does not heal;
• signs and symptoms suggesting the onset of blood system disorders, such as persistent fever, bruising, bleeding, pallor.

The following side effects have been observed with adalimumab:

Very common(may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis and pneumonia);
• headache;
• abdominal pain (stomach ache);
• nausea and vomiting;
• skin rash;
• muscle pain.

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including tooth infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• infections affecting the joints;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergy);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, pricking or numbness;
• migraine;
• symptoms of nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• inflammation of the eyelids and swelling of the eyes;
• dizziness (feeling of spinning);
• feeling of a fast heartbeat;
• high blood pressure;
• hot flashes;
• hematoma (solid swelling with coagulated blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux;
• dry eye syndrome (including dry eyes and dry mouth);
• itching;
• itchy skin rash;
• bruising;
• skin inflammation (such as eczema);
• breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (fluid retention in the body, causing swelling of the affected tissue);
• fever;
• reduced platelets in the blood, which increases the risk of bleeding or bruising;
• difficulty healing.

Uncommon(may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when defenses are lowered;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that can affect the lungs, skin and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• feeling of irregular heartbeat such as palpitations;
• heart problems that can cause shortness of breath or swelling of the ankles;
• acute myocardial infarction (heart attack);
• formation of a sac in the wall of a major artery, inflammation and blood clot in a vein, blockage of a blood vessel;
• lung disease that causes shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal collection of fluid in the pleural space);
• inflammation of the pancreas that causes severe pain in the abdomen and back;
• difficulty swallowing;
• facial edema (swelling);
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle catabolism;
• systemic lupus erythematosus (immune system disorder, including inflammation of the skin, heart, lungs, joints and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare(may affect up to 1 in 1,000 people)

• leukemia (a cancer that affects the blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as inflammation of the optic nerve in the eye and Guillain-Barré syndrome, a condition that can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lung);
• intestinal perforation (hole in the wall of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (inflammation of the liver caused by your own immune system);
• cutaneous vasculitis (inflammation of the blood vessels in the skin);
• Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and skin rash with blisters);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy, reddish-purple skin rash).

Not known(frequency cannot be estimated from available data)

• T-cell hepato-splenic lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer associated with human herpes virus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which manifests as a skin rash accompanied by muscle weakness);
• weight gain (weight gain has been low for most patients).

Some of the side effects observed with adalimumab may be asymptomatic and can
only be detected through blood tests. These include:

Very common(may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased lipids in the blood;
• increased liver enzymes.

Common(may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in the blood;
• alteration of sodium in the blood;
• reduced calcium in the blood;
• reduced phosphorus in the blood;
• increased sugar in the blood;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• reduced potassium in the blood.

Uncommon(may affect up to 1 in 100 people)

• high levels of bilirubin in the blood (liver blood test).

Rare(may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell and platelet count.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the national reporting system detailed in
Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label/blister/box after the
word Exp.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.
Alternative storage conditions:
When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 42 days – ensure that the medicine is
protected from light. Once it has been removed from the refrigerator to be stored at room temperature, the
pre-filled syringe must be used within 42 days or discarded, even if it is subsequently
placed back in the refrigerator. You must record the date on which the pre-filled syringe is removed from
the refrigerator for the first time and the date after which the syringe must be discarded.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active ingredient is adalimumab. Each pre-filled syringe contains 40 mg of adalimumab in 0.4 mL of solution.
• The excipients are adipic acid, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections.

Description of Hefiya and package contents
Hefiya 40 mg solution for injection in a pre-filled syringe is supplied in 0.4 mL of solution from clear to
slightly opalescent, colorless or slightly yellowish.
Hefiya is supplied in a single-use glass type I transparent syringe with a 29 gauge stainless steel needle
and a needle safety device with a finger grip, rubber needle cap (thermoplastic elastomer) and plastic plunger, containing 0.4 mL of solution.
The packs contain 1 and 2 pre-filled syringes of Hefiya.
Multipacks contain 6 (3 packs of 2) pre-filled syringes of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen.

Marketing authorisation holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Sandoz nv/sa
Tél/Tel: +32 2 722 97 97

Lietuva
Sandoz Pharmaceuticals d.d filialas
Tel: +370 5 2636 037

Luxembourg/Luxemburg
Sandoz nv/sa
Tél/Tel.: +32 2 722 97 97

Česká republika
Sandoz s.r.o.
Tel: +420 225 775 111

България
Сандоз България КЧТ
Тел.: +359 2 970 47 47

Magyarország
Sandoz Hungária Kft.
Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige
Sandoz A/S
Tlf: +45 63 95 10 00

Malta
Sandoz Pharmaceuticals d.d.
Tel: +356 99644126

Deutschland
Hexal AG
Tel: +49 8024 908 0

Nederland
Sandoz B.V.
Tel: +31 36 52 41 600

Eesti
Sandoz d.d. Eesti filiaal
Tel: +372 665 2400

Österreich
Sandoz GmbH
Tel: +43 5338 2000

Ελλάδα
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε.
Τηλ: +30 216 600 5000

Polska
Sandoz Polska Sp. z o.o.
Tel.: +48 22 209 70 00

España
Sandoz Farmacéutica, S.A.
Tel: +34 900 456 856

Portugal
Sandoz Farmacêutica Lda.
Tel: +351 21 000 86 00

France
Sandoz SAS
Tél: +33 1 49 64 48 00

România
Sandoz Pharmaceuticals SRL
Tel: +40 21 407 51 60

Hrvatska
Sandoz d.o.o.
Tel: +385 1 23 53 111

Slovenija
Sandoz farmacevtska družba d.d.
Tel: +386 1 580 29 02

Ireland
Rowex Ltd.
Tel: + 353 27 50077

Slovenská republika
Sandoz d.d. - organizačná zložka
Tel: +421 2 50 70 6111

Italia
Sandoz S.p.A.
Tel: +39 02 96541

Suomi/Finland
Sandoz A/S
Puh/Tel: +358 10 6133 400

Κύπρος
Sandoz Pharmaceuticals d.d.
Τηλ: +357 22 69 0690

United Kingdom (Northern Ireland)
Sandoz GmbH
Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines
Agency: http://www.ema.europa.eu .

7. Instructions for Use

To avoid possible infections and to ensure you use the medicine correctly, it is important that
you follow these instructions.
Make sure you read, understand and follow these Instructions for Use before injecting Hefiya.
The healthcare professional must show you how to prepare and inject Hefiya correctly using the
pre-filled single-dose syringe before you use the medicine for the first time. If you have any doubts, please contact
your healthcare professional.

Hefiya single-use pre-filled syringe with safety device for the needle and additional finger grip

Figure A:Hefiya pre-filled syringe with needle safety device and finger grip

It is important that you:

• do not usethe pre-filled syringe if the blister seals are broken, because use may not be safe;
• do not openthe outer carton until you are ready to use the pre-filled syringe;
• never leavethe pre-filled syringe unattended where it could be tampered with by others;
• if you drop the syringe, do not use itif it appears damaged or if it was dropped after you removed the needle cap;
• do not removethe needle cap until the time of injection;
• be careful not to touch the wings of the needle safety devicebefore use. If you do, the needle safety device may be activated too early.
• do not removethe finger grip before the injection;
• injectHefiya 15-30 minutes after removing it from the refrigerator, for a more comfortable injection;
• dispose of the used syringe immediately after use. Do not reuse the pre-filled syringe.See “4. Disposal of used pre-filled syringes”at the end of these Instructions for Use.

How should you store the Hefiya single-dose pre-filled syringe?

• Store the outer packaging of the pre-filled syringes in a refrigerator, at a temperature between 2° and 8°C.
• When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 42 days - make sure to protect the medicine from light. Once it is removed from the refrigerator to be stored at room temperature, the pre-filled syringe must be used within 42 days or discarded, even if it is subsequently placed back in the refrigerator. You must record the date on which the pre-filled syringe is removed from the refrigerator for the first time and the date after which it must be discarded.
• Store the pre-filled syringes in the original packaging until you are ready to use them, to protect the medicine from light.
• Do not store the pre-filled syringes at extremely hot or cold temperatures.
• Do not freeze the pre-filled syringes.

Keep Hefiya and all medicines out of the reach of children.
What do you need for the injection?
Place the following items on a clean, flat surface.
The syringe packaging contains:

• Syringe/s pre-filled with Hefiya ( seeFigure A). Each pre-filled syringe contains 40 mg/0.4 mL of adalimumab.

The Hefiya pre-filled syringe packaging does not contain ( seeFigure B):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container. See “4. Disposal of used syringes” at the end of these Instructions for Use.
• Adhesive bandage.

Figure B:items notincluded in the packaging

Before the injection

Figure D:the needle safety device is
activated – do not use

Figure C:the needle safety device is not
activated – the syringe is ready for use
or In this configuration, the needle safety
device is NOT ACTIVATED.
or The syringe is ready for use (see

Figure C).
or In this configuration, the needle safety
device is ACTIVATED.
or DO NOT USEthe syringe (see

Figure D).

Preparing the syringe

• For a more comfortable injection, remove the carton containing the pre-filled syringe from the refrigerator and leave it closedon the work surface for about 15-30 minutes to reach room temperature.
• Remove the pre-filled syringe from the blister.
• Look through the window. The solution should be colourless or slightly yellowish and from clear to slightly opalescent. Do not use the syringe if you notice particles and/or changes in colour. If you have any doubts about the appearance of the solution, ask your pharmacist for assistance.
• Do not usethe pre-filled syringe if it is broken or if the needle safety device is activated. Return the pre-filled syringe and packaging to the pharmacy.
• Check the expiry date (Exp.) of the pre-filled syringe. Do not use the pre-filled syringe if the expiry date has passed

Ask your pharmacistif the syringe does not pass any of the checks above.

1. Choice of injection site:

• The recommended injection site is the front of the thighs. You can also use the lower abdomen, but not the area within 5 cm around the navel (see Figure E).
• Choose a different site each time you administer an injection.
• Do notinject the medicine into areas where the skin is painful, bruised, reddened, flaky or hardened. Avoid areas with scars or stretch marks. If you suffer from psoriasis, DO NOT inject the medicine directly into areas with psoriasis plaques.

Figure E:how to choose the injection site

2. Injection site cleaning:

• Wash your hands thoroughly with water and soap.
• Using a circular motion, clean the injection site with a swab soaked in alcohol. Allow to dry before administering the injection (see Figure F).
• Do nottouch the cleaned area before the injection.

Figure F:how to clean the injection site

3. Administration of the injection:

• Carefully pull off the needle cap to remove it from the prefilled syringe (see Figure G).
• Dispose of the needle cap.
• You may see a drop of liquid at the end of the needle. This is normal.

Figure G:how to pull off the needle cap

• Gently create a skin fold at the injection site (see Figure H).
• Insert the needle into the skin as shown.
• Push the entire needle into the skin to ensure that all of the medicine is delivered.
• Use the syringe within 5 minutes of removing the cap.

FigureH:how to insert the needle

• Hold the prefilled syringe as shown (see Figure I).
• Slowly press the plunger all the way in so that the plunger head is completely between the fins of the needle safety device.
• While holding the syringe in position, keep the plunger pressed in completely for 5 seconds.

Figure I:how to hold the syringe

• Keep the plunger fullypressedwhile carefully withdrawing the needle from the injection site, then release the skin (see Figure J) .

Figure J:how to withdraw the needle

• Slowly release the plunger and let the needle safety device automatically cover the exposed needle (see Figure K).
• You may notice a small amount of blood at the injection site. You can press a cotton ball or gauze on the injection site and hold for 10 seconds. Do not rub the injection site. If necessary, you can cover the injection site with a small adhesive bandage. Figure K:how to slowly release the plunger

4. Disposal of used syringes:

• Dispose of the used syringe in a sharps disposal container (reclosable, puncture-resistant container, see Figure L). For your safety and health and that of others, used needles and syringes must never be reused.
• Do not dispose of any medicine down the drain or in household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Unused medicine and waste from that medicine must be disposed of in accordance with local regulations.

Figure L:how to dispose of the used
prefilled syringe

If you have any doubts, consult a doctor, pharmacist or nurse familiar with
Hefiya.

Hefiya 40 mg injectable solution in pre-filled pen

adalimumab

40 mg/0.4 mL
Read this leaflet carefully before using this medicine as it contains important
information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will give you a Patient Reminder Card, which contains important safety information that you need to know before administering Hefiya and during treatment with Hefiya. Keep this Patient Reminder Cardwith you during treatment and for 4 months after the last injection (or the last injection given to your son/daughter) of Hefiya.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, as it could be dangerous.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Hefiya is and what it is used for
• 2. What you need to know before you use Hefiya
• 3. How to use Hefiya
• 4. Possible side effects
• 5. How to store Hefiya
• 6. Contents of the pack and other information
• 7. Instructions for use

1. What is Hefiya and what is it used for

Hefiya contains the active ingredient adalimumab, a medicine that acts on the body's immune system (defense system).
Hefiya is indicated for the treatment of the inflammatory diseases listed below:

• rheumatoid arthritis,
• polyarticular juvenile idiopathic arthritis,
• arthritis associated with enthesitis,
• ankylosing spondylitis,
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis,
• psoriatic arthritis,
• plaque psoriasis,
• hidradenitis suppurativa,
• Crohn’s disease,
• ulcerative colitis,
• non-infectious uveitis.

The active ingredient contained in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumor necrosis factor (TNFα), which is
involved in the immune system (defense system) and is present in higher concentrations in the
inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and decreases the
inflammatory process in these diseases.
Rheumatoid Arthritis
Rheumatoid arthritis is an inflammatory disease of the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, other disease-modifying drugs, such as
methotrexate, may be initially administered. If these drugs do not work satisfactorily, you will be given Hefiya to treat
rheumatoid arthritis.
Hefiya can also be used for the treatment of severe, active and progressive rheumatoid arthritis
without prior treatment with methotrexate.
Hefiya may slow the progression of cartilage and bone damage in the joints caused
by the disease, and improve physical function.
Generally, Hefiya is used with methotrexate. If your doctor believes that treatment with
methotrexate is not appropriate, Hefiya may be administered alone.
Polyarticular Juvenile Idiopathic Arthritis
Polyarticular juvenile idiopathic arthritis is an inflammatory disease of the joints, which in
generally manifests for the first time during childhood.
Hefiya is used to treat polyarticular juvenile idiopathic arthritis in children and adolescents aged
from 2 to 17 years. Other disease-modifying drugs, such as methotrexate, may be administered at diagnosis.
If these drugs do not work satisfactorily, patients will be
administered Hefiya.
Arthritis Associated with Enthesitis
Arthritis associated with enthesitis is an inflammatory disease of the joints and the areas where the
tendons attach to the bones. Hefiya is used to treat arthritis associated with enthesitis in patients aged
6 years or older.
Other disease-modifying drugs, such as methotrexate, may be initially administered. If
these medicines do not work well enough, patients will be administered Hefiya.
Ankylosing Spondylitis and Axial Spondyloarthritis without Radiographic Evidence of Ankylosing Spondylitis
Ankylosing spondylitis and axial spondyloarthritis without radiographic evidence of spondylitis
ankylosing are inflammations of the spine.
Hefiya is used in adults to treat these conditions. If you have ankylosing spondylitis or axial spondyloarthritis without radiographic evidence of ankylosing spondylitis, you will first take other
drugs. If these drugs do not work satisfactorily, you will take Hefiya to reduce the signs and
symptoms of the disease.
Plaque Psoriasis in Adults and Children
Plaque psoriasis is an inflammatory skin condition that causes red, scaly, and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the
nails, causing them to break, thicken, and lift from the nail bed, which can be
painful. Psoriasis is thought to be caused by a problem with the body's immune system that
leads to increased production of skin cells.
Hefiya is used to treat moderate to severe plaque psoriasis in adults. Hefiya is
also used to treat severe plaque psoriasis in children and adolescents aged 4 to 17 years in
whom topical medications and UV therapy have not worked optimally or are not indicated.
Psoriatic Arthritis
Psoriatic arthritis is an inflammatory disease of the joints associated with psoriasis.
Hefiya is used to treat psoriatic arthritis in adults. Hefiya may slow the damage to cartilage
and bone in the joints caused by the disease, and improve physical function.
Hidradenitis Suppurativa in Adults and Adolescents
Hidradenitis Suppurativa (sometimes called inverse acne) is a long-term inflammatory disease of the skin and is often painful. Symptoms may include painful nodules and abscesses (cysts)
that can drain pus. It most often affects specific areas of the skin, such as the underarm region, armpits, inner thighs, groin, and buttocks. Scars can also form in the affected areas.
Hefiya is used to treat

• moderate to severe Hidradenitis Suppurativa in adults and
• moderate to severe Hidradenitis Suppurativa in adolescents aged 12 to 17 years.

Hefiya may reduce the number of nodules and abscesses you have and the pain that is often associated with this
disease. Initially, you may receive other medications. If these medications do not work in a
satisfactory manner, you will receive Hefiya.
Crohn’s Disease in Adults and Children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat

• moderate to severe Crohn’s disease in adults and
• moderate to severe Crohn’s disease in children and adolescents aged 6 to 17 years.

If you suffer from Crohn’s disease, you will first be administered other medications. In the event that you do not
respond adequately to these medications, you will be administered Hefiya to
reduce the typical symptoms of Crohn’s disease.
Ulcerative Colitis in Adults and Children
Ulcerative colitis is an inflammation of the large intestine.
Hefiya is used to treat

• moderate to severe ulcerative colitis in adults and
• moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

If you have ulcerative colitis you may initially take other medications. If these medications do not work
satisfactorily, you will take Hefiya to reduce the signs and symptoms of ulcerative colitis.
Non-Infectious Uveitis in Adults and Children
Non-infectious uveitis is an inflammatory disease that affects some parts of the eye.
Inflammation leads to decreased vision and/or the presence of floaters in the eye
(black dots or thin lines that move across the field of vision). Hefiya works by reducing this
inflammation.
Hefiya is used for the treatment of:

• Adults with non-infectious uveitis with inflammation affecting the back of the eye.
• Children aged 2 years and older with chronic non-infectious uveitis with inflammation affecting the front of the eye.

Initially, other medications may be administered. If the response to these medications is not
adequate, you will be given Hefiya.

2. What you need to know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a severe infection, including tuberculosis, sepsis (blood poisoning) or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell your doctor if you have signs or symptoms of infection, such as, for example, fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).
• If you have moderate or severe heart failure. It is important to tell your doctor if you have had or have a serious heart condition (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.
Allergic reaction

• If you experience allergic reactions with symptoms such as a feeling of tightness in the chest, wheezing, dizziness, swelling or skin rash, do not administer Hefiya again and contact your doctor immediately, as in rare cases, these reactions can be life-threatening.

Infections

• If you have an infection, including long-term or localized infections (for example, leg ulcers), consult your doctor before starting treatment with Hefiya. If you have doubts, contact your doctor.
• You may be more likely to contract infections during treatment with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning).
• In rare cases, these infections can be life-threatening. It is important to tell your doctor about the presence of symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may advise you to temporarily suspend Hefiya.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will need to check if you have signs or symptoms typical of tuberculosis before starting therapy with Hefiya. This will involve collecting a detailed medical assessment including your medical history and clinical examinations (e.g. a chest X-ray and a tuberculin test). The performance and results of these tests must be recorded on the Patient Reminder Card. It is very important to tell your doctor if you have ever had tuberculosis, or if you have had close contact with people with tuberculosis. Tuberculosis may develop during therapy even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, moderate fever) or other infections appear during or after therapy.

Travel/recurring infection

• Tell your doctor if you have resided or traveled to regions where fungal infections, such as histoplasmosis, coccidioidomycosis or blastomycosis, are very common.
• Tell your doctor if you have had recurrent infections or if you have conditions that increase the risk of infection.

Hepatitis B virus

• Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active infection with the hepatitis B virus or if you think you may be at risk of contracting the hepatitis virus
• B. Your doctor should test you for hepatitis B virus infection. Taking adalimumab can reactivate hepatitis B virus infection in subjects who are carriers of this virus. In some rare cases, especially if the patient is undergoing therapy with other drugs that suppress the immune system, reactivation of hepatitis B virus infection can endanger the patient's life.

Age over 65 years

• If you are over 65 years of age, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection while you are being treated with Hefiya. It is important to inform your doctor if symptoms of infections such as fever, wounds, feeling tired or dental problems appear.

Surgery or dental procedures

• Before surgery or dental procedures, tell your doctor that you are taking Hefiya. Your doctor may advise you to temporarily suspend Hefiya.

Demyelinating disease

• If you suffer from or develop demyelinating diseases (diseases that affect the insulating layer around nerves), such as multiple sclerosis, your doctor will decide whether or not to start or continue receiving treatment with Hefiya. Tell your doctor immediately if you experience symptoms such as changes in vision, weakness of arms or legs, or numbness or tingling that affects any part of the body.

Vaccination

• Certain vaccines contain live but attenuated forms of bacteria or viruses that cause diseases and should not be administered during treatment with Hefiya if they cause infections. Consult your doctor before getting vaccinated. In children, it is recommended, if possible, to administer the vaccinations scheduled for their

age before starting therapy with Hefiya. If you have taken Hefiya during pregnancy, the child may have a higher risk
of contracting such an infection up to about 5 months after the last dose you took
during pregnancy. It is important that you inform the pediatrician or other healthcare professional of
your use of Hefiya during pregnancy, so that they can decide when the child should
receive any type of vaccination.
Heart failure

• It is important to inform your doctor about any heart problems, both past and present. If you have mild heart failure and are receiving concomitant treatment with Hefiya, your doctor must carefully assess and monitor your heart condition. If new symptoms of heart failure appear or existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding or paleness

• In some patients, the body may not be able to produce a sufficient amount of blood cells to fight infections or stop bleeding. If you have persistent fever, bruising or easy bleeding or paleness, see your doctor immediately. The latter may decide to interrupt therapy.

Tumor

• In children and adults treated with adalimumab or other anti-TNFα drugs, some types of tumors have very rarely occurred. Patients with severe, long-standing rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukemia (cancers affecting blood cells and bone marrow). If you are taking Hefiya, the risk of developing lymphomas, leukemia or other tumors may increase. In rare circumstances, a specific and serious type of lymphoma has been observed in patients undergoing therapy with adalimumab. Some of these patients were also taking azathioprine or mercaptopurine. Tell your doctor if you are taking azathioprine or mercaptopurine with Hefiya.
• In addition, cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If damaged skin areas appear during or after treatment or if the appearance of damaged signs or areas changes, report it to your doctor.
• There have been cases of neoplasms, other than lymphoma, in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα. If you suffer from COPD, or smoke heavily, you should discuss with your doctor whether treatment with an anti-TNFα is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the manifestation of a syndrome like lupus. Tell your doctor if you experience symptoms such as a persistent unexplained skin rash, fever, joint pain or fatigue.

Children and adolescents

• Do not give Hefiya to children with polyarticular juvenile idiopathic arthritis under the age of 2 years.
• Do not give Hefiya to children with pediatric plaque psoriasis or pediatric ulcerative colitis under the age of 4 years.
• Do not give Hefiya to children with pediatric Crohn's disease under the age of 6 years.
• Do not use the pre-filled pen 40 mg if doses less than 40 mg are recommended.

Other medicines and Hefiya
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
Hefiya can be taken both with methotrexate and with other disease-modifying antirheumatic drugs (sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts), corticosteroids
or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya should not be taken in combination with medicines containing the active ingredients anakinra or
abatacept due to the increased risk of having serious infections. The combination of adalimumab and other anti-TNF and anakinra or abatacept is not recommended due to the possible increased risk of
infections, including serious infections and other possible drug interactions. If you have doubts, consult
your doctor.

Pregnancy and breastfeeding

• You should consider using adequate contraceptive measures to prevent pregnancy and continue them for at least 5 months after the last therapy with Hefiya.
• If you are pregnant, suspect you are pregnant or are planning a pregnancy, ask your doctor for advice on taking this medicine.
• Hefiya should only be used during pregnancy if necessary.
• According to a pregnancy study, no increased risk of birth defects was found when the mother received adalimumab during pregnancy, compared to mothers who had the same condition but had not received adalimumab.
• Hefiya can be used during breastfeeding.
• If you take Hefiya during pregnancy, the child may have a higher risk of contracting an infection.
• It is important that you inform the pediatrician or other healthcare professional of your use of Hefiya during pregnancy, before the child receives any type of vaccination (for more information on vaccines, see “Warnings and precautions”).

Driving and using machines
Hefiya may affect, albeit only to a modest extent, your ability to drive, ride a bicycle or use machines. After taking Hefiya, you may experience vision disturbances and a feeling that the environment around you is rotating (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.4 mL of dose, i.e. essentially
‘sodium-free’.

3. How to use Hefiya

Use this medicine following the instructions of your doctor or pharmacist exactly. If you have
doubts, consult your doctor or pharmacist.
The recommended doses of Hefiya in each approved indication are listed in the following
table. Your doctor may prescribe a different concentration of Hefiya if you need a different
dose.

How and route of administration
Hefiya is administered by subcutaneous injection (subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist
explaining that you have taken more medicine than you should. Always keep the medicine box,
even if empty.

If you forget to use Hefiya
If you forget to give an injection, you should inject the next dose of Hefiya as soon as you
remember. Then resume the dose regularly according to the prescribed dosage schedule.

If you stop treatment with Hefiya
The decision to stop using Hefiya must be discussed with your doctor. Symptoms may
return after stopping treatment.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Most side effects are mild to moderate. However, some can be serious and require treatment. Side effects may occur
up to 4 months or more after the last injection of Hefiya.

Seek medical attention urgentlyif you notice any of the following signs of an allergic reaction or
heart failure

• severe skin rash, hives;
• swelling of the face, hands, feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath on exertion or when lying down or swollen feet.

Inform your doctor as soon as possibleif you notice any of the following reactions

• signs and symptoms of infection such as fever, feeling unwell, sores, dental problems, burning when urinating; fatigue or weakness or cough;
• symptoms of nerve problems, such as tingling, numbness, double vision or weakness of the arms or legs;
• signs of skin cancer such as swelling or an open sore that does not heal;
• signs and symptoms suggesting the onset of blood system disorders, such as persistent fever, bruising, bleeding, paleness.

The following side effects have been observed with Hefiya

Very common(may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis and pneumonia);
• headache;
• abdominal pain (stomach ache);
• nausea and vomiting;
• skin rash;
• muscle pain.

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including tooth infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• joint infections;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergy);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, prickling or numbness;
• migraine;
• symptoms of nerve root compression (including back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (feeling of spinning);
• feeling of a fast heartbeat;
• high blood pressure;
• hot flushes;
• hematoma (solid swelling with clotted blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux;
• dry eye syndrome (including dry eyes and mouth);
• itching;
• itchy skin rash;
• bruising;
• skin inflammation (such as eczema);
• nail breakage of the fingers and toes;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in the urine;
• kidney problems;
• chest pain;
• edema (fluid retention in the body, causing swelling of the affected tissue);
• fever;
• reduced platelets in the blood, which increases the risk of bleeding or bruising;
• difficulty healing.

Uncommon(may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when defenses are lowered;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that can affect lungs, skin and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• feeling of irregular heartbeat such as palpitations;
• heart problems that can cause shortness of breath or swelling of the ankles;
• acute myocardial infarction (heart attack);
• formation of a sac in the wall of a major artery, inflammation and blood clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal collection of fluid in the pleural space);
• pancreatitis (inflammation of the pancreas causing severe abdominal and back pain);
• difficulty swallowing;
• facial edema (swelling);
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle catabolism;
• systemic lupus erythematosus (immune system disorder, including skin, heart, lung, joint and other organ inflammation);
• interrupted sleep;
• impotence;
• inflammations.

Rare(may affect up to 1 in 1,000 people)

• leukemia (a cancer that affects the blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic nerve inflammation in the eye and Guillain-Barré syndrome, a condition that can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lung);
• intestinal perforation (hole in the wall of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (inflammation of the liver caused by your own immune system);
• cutaneous vasculitis (inflammation of the skin blood vessels);
• Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and skin rash with blisters);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy reddish-purple skin rash).

Not known(frequency cannot be estimated based on available data)

• T-cell hepato-splenic lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer related to human herpes virus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which manifests as a skin rash accompanied by muscle weakness);
• weight gain (for most patients the weight gain has been low).

Some of the side effects observed with adalimumab may be asymptomatic and can
only be detected through blood tests. These include:

Very common(may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased lipids in the blood;
• increased liver enzymes.

Common(may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in the blood;
• alteration of sodium in the blood;
• reduced calcium in the blood;
• reduced phosphorus in the blood;
• increased sugar in the blood;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• reduced potassium in the blood.

Uncommon(may affect up to 1 in 100 people)

• high levels of bilirubin in the blood (liver blood test).

Rare(may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell and platelet counts.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the national
reporting system listed in Annex V. By reporting side effects you can help provide
more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label/blister/box after the
word Exp.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled pen in the outer packaging to protect the medicine from light.
Alternative storage conditions:
When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 42 days – ensure to protect the medicine
from light. Once removed from the refrigerator for storage at room temperature, the
pre-filled pen must be used within 42 days or discarded, even if subsequently
placed back in the refrigerator. You must record the date on which the pre-filled pen is removed from
the refrigerator for the first time and the date after which the pen must be discarded.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled pen contains 40 mg of adalimumab in 0.4 mL of solution.
• The excipients are adipic acid, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections.

Description of the appearance of Hefiya and contents of the pack
Hefiya 40 mg solution for injection in a pre-filled pen is supplied as 0.4 mL of solution from clear
to slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use pre-filled syringe assembled in a triangular-shaped pen with
a transparent window and label. The syringe inside the pen is type I glass with a calibre 29 needle in stainless steel, an internal rubber needle cap (thermoplastic elastomer)
and a rubber stopper, containing 0.4 mL of solution.
The packs contain 1, 2 and 4 pre-filled pens of Hefiya.
Multiple packs contain 6 (3 packs of 2) pre-filled pens of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in a pre-filled syringe and in a pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Sandoz nv/sa
Tél/Tel: +32 2 722 97 97

Lietuva
Sandoz Pharmaceuticals d.d filialas
Tel: +370 5 2636 037

Luxembourg/Luxemburg
Sandoz nv/sa
Tél/Tel.: +32 2 722 97 97

Česká republika
Sandoz s.r.o.
Tel: +420 225 775 111

България
Сандоз България КЧТ
Тел.: +359 2 970 47 47

Magyarország
Sandoz Hungária Kft.
Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige
Sandoz A/S
Tlf: +45 63 95 10 00

Malta
Sandoz Pharmaceuticals d.d.
Tel: +356 99644126

Deutschland
Hexal AG
Tel: +49 8024 908 0

Nederland
Sandoz B.V.
Tel: +31 36 52 41 600

Eesti
Sandoz d.d. Eesti filiaal
Tel: +372 665 2400

Österreich
Sandoz GmbH
Tel: +43 5338 2000

Ελλάδα
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε.
Τηλ: +30 216 600 5000

Polska
Sandoz Polska Sp. z o.o.
Tel.: +48 22 209 70 00

España
Sandoz Farmacéutica, S.A.
Tel: +34 900 456 856

Portugal
Sandoz Farmacêutica Lda.
Tel: +351 21 000 86 00

France
Sandoz SAS
Tél: +33 1 49 64 48 00

România
Sandoz Pharmaceuticals SRL
Tel: +40 21 407 51 60

Hrvatska
Sandoz d.o.o.
Tel: +385 1 23 53 111

Slovenija
Sandoz farmacevtska družba d.d.
Tel: +386 1 580 29 02

Ireland
Rowex Ltd.
Tel: + 353 27 50077

Slovenská republika
Sandoz d.d. - organizačná zložka
Tel: +421 2 50 70 6111

Italia
Sandoz S.p.A.
Tel: +39 02 96541

Suomi/Finland
Sandoz A/S
Puh/Tel: +358 10 6133 400

Κύπρος
Sandoz Pharmaceuticals d.d.
Τηλ: +357 22 69 0690

United Kingdom (Northern Ireland)
Sandoz GmbH
Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu.

7. Instructions for Use

To avoid possible infections and to ensure you use Hefiya correctly, it is important that you
follow these instructions.
Make sure you read, understand and follow these Instructions for Use before injecting Hefiya.
The healthcare professional must show you how to prepare and inject Hefiya correctly using the
Hefiya single-dose pre-filled pen before you use the medicine for the first time. If you have any doubts,
ask your healthcare professional.

Hefiya Single-Use Pre-filled Pen

Figure A:parts of the Hefiya pen
In Figure A, the pen is shown without the cap. Do not removethe cap until you are ready to administer
the injection.

It is important that you:

• do not usethe pen if the outer package seal or the pen safety seal is broken;
• keep the pen in the sealed outer packaging until you are ready to use it;
• never leavethe pen unattended where it could be tampered with by others;
• do not usethe pen if it has been dropped, appears damaged or has been dropped after you have removed the cap;
• injectHefiya 15-30 minutes after removing it from the refrigerator, for a more comfortable injection;
• dispose of the used pen immediately after use. Do not reuse the pen.See “4. Disposal of used pens”at the end of these Instructions for Use.

How should you store the pen?

• Store the pen packaging in a refrigerator, at a temperature between 2° and 8°C.
• When necessary, for example when travelling, Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 42 days - make sure to protect the medicine from light. Once it is removed from the refrigerator to be stored at room temperature, the pre-filled pen must be used within 42 days or discarded, even if it is subsequently placed back in the refrigerator.
• You must record the date the pre-filled pen is removed from the refrigerator for the first time and the date after which it must be discarded.
• Store the pen in its original packaging until you are ready to use it, to protect the medicine from light.
• Do not store the pen at extremely high or low temperatures.
• Do not freeze the pen.

Keep Hefiya and all medicines out of the reach of children.
What do you need for the injection?
Place the following items on a clean, flat surface.
The package contains:

• Hefiya pre-filled pen/s (see Figure A). Each pen contains 40 mg/0.4 mL of adalimumab.

The pen package does not contain (see Figure B):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container. See “8. Disposal of used pens”at the end of these Instructions for Use.
• Adhesive bandage.

Figure B:items not included in the package

Preparing the pen
Before the injection

• For a more comfortable injection, remove the pen from the refrigerator approximately 15-30 minutes before the injection to allow it to reach room temperature.
• Look through the window. The solution should be colourless or slightly yellowish and from clear to slightly opalescent. Do not usethe pen if you notice particles and/or colour changes. You may notice some air bubbles. This is normal. If you have any doubts about the appearance of the solution, ask your pharmacist for assistance.
• Check the expiry date (Exp.) of the pen (see Figure C). Do not use the pen if the expiry date has been passed.
• Do not use the pen if the safety seal is broken.

Figure C:safety checks before
the injection

Ask your pharmacist if the pen does not pass
any of the checks listed above.

1. Choice of injection site:

• The recommended injection site is the front of the thighs. You can also use the lower abdomen, but not the area within 5 cm around the navel (see Figure D).
• Choose a different site each time you administer an injection.
• Do notinject the medicine into areas where the skin is painful, bruised, reddened, flaky or hardened. Avoid areas with scars or stretch marks. If you suffer from psoriasis, DO NOTinject the medicine directly into areas with psoriasis plaques.

Figure D:how to choose the injection site

2. Injection site cleaning:

• Wash your hands thoroughly with water and soap.
• Using a circular motion, clean the injection site with a swab soaked in alcohol. Allow to dry before administering the injection (see Figure E).
• Do nottouch the cleaned area before the injection.

Figure E:how to clean the injection site

3. Removing the cap from your pen:

• Remove the cap only when you are ready to use the pen.
• Rotate the cap in the direction of the arrows (see Figure F).
• Once the cap is removed, discard it. Do notattempt to replace the cap.
• Use the pen within 5 minutes of removing the cap.
• You may notice a few drops of liquid coming out of the needle. This is normal.

Figure F:how to remove the cap

4. How to hold the pen:

• Hold the pen at 90 degrees to the clean injection site (see Figure G).

CorrectIncorrect
Figure G:how to hold the pen

Injection
Read before performing the injection
During the injection you will feel 2 clicks:
o The first clickindicates that the injection has started.
o A few moments later, a second clickindicates that the injection is almostcomplete.
You must keep the pen pressed firmly against the skin until you see a green
indicatorfill the window and stop moving.

5. Start of the injection:

• Press the pen firmly against the skin to start the injection (see Figure H).
• The first click indicates that the injection has started.
• Keep pressingthe pen firmly against the skin.
• The green indicator shows the injection progress. Figure H:how to start the injection

6. Completion of the injection:

• Pay attention to the second click which indicates that the injection is almost complete.
• Check that the green indicator fills the window and has stopped moving (see Figure I).
• You can now remove the pen.

Figure I:how to complete the injection

After the injection

7. Check that the green indicator

fills the window(see Figure J) :

• This means that the medicine has been administered. Contact your doctor if the green indicator is not visible.
• You may notice a small amount of blood at the injection site. You can press a cotton ball or gauze on the injection site and hold it for 10 seconds. Do not rub the injection site. If necessary, you can cover the injection site with a small adhesive bandage.

Figure J:how to check the green indicator

8. Disposal of used pens:

• Dispose of the used pen in a sharps disposal container (resealable, puncture-resistant container, see Figure K). For your safety and the safety of others, used pens must never be reused.
• Do not dispose of any medicine down the drain or in household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Unused medicine and waste from that medicine must be disposed of in accordance with local regulations.

Figure K:how to dispose of the used pen

If you have any doubts, consult a doctor, pharmacist or nurse familiar with
Hefiya.

Hefiya 80 mg injectable solution in pre-filled syringe

adalimumab

Read this leaflet carefully before using this medicine as it contains important information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will give you a Patient Reminder Card, which contains important safety information that you need to know before administering Hefiya and during treatment with Hefiya. Keep this Patient Reminder Cardwith you during treatment and for 4 months after the last injection (or the last injection given to your child) of Hefiya.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed only for you. Do not give it to other people, even if their symptoms are the same as yours, as it could be dangerous.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Hefiya is and what it is used for
• 2. What you need to know before using Hefiya
• 3. How to use Hefiya
• 4. Possible side effects
• 5. How to store Hefiya
• 6. Contents of the pack and other information
• 7. Instructions for use

1. What is Hefiya and what is it used for

Hefiya contains the active ingredient adalimumab, a medication that acts on the body's immune system (defense system).
Hefiya is indicated for the treatment of the inflammatory diseases listed below:

• rheumatoid arthritis,
• plaque psoriasis,
• hidradenitis suppurativa,
• Crohn’s disease,
• ulcerative colitis,
• non-infectious uveitis

The active ingredient contained in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumor necrosis factor (TNFα), which is
involved in the immune system (defense system) and is present in higher concentrations in the
inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and decreases the
inflammatory process in these diseases.
Rheumatoid Arthritis
Rheumatoid arthritis is an inflammatory condition of the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have moderate to severe rheumatoid arthritis, other disease-modifying drugs, such as
methotrexate, may be initially administered. If these medications do not work satisfactorily, you will be given Hefiya to treat
rheumatoid arthritis.
Hefiya can also be used for the treatment of severe, active and progressive rheumatoid arthritis
without prior treatment with methotrexate.
Hefiya may slow the progression of damage to the cartilage and bones of the joints,
caused by the disease, and improve physical function.
Generally, Hefiya is used with methotrexate. If your doctor believes that treatment with
methotrexate is not appropriate, Hefiya may be administered alone.
Plaque Psoriasis
Plaque psoriasis is an inflammatory skin condition that causes reddish,
scaly and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the
nails, causing them to break, thicken and lift from the nail bed, which can be
painful. Psoriasis is believed to be caused by a problem with the body's immune system that
leads to an increase in skin cell production.
Hefiya is used to treat moderate to severe plaque psoriasis in adults.
Hidradenitis Suppurativa in adults and adolescents
Hidradenitis Suppurativa (sometimes called inverse acne) is a long-term inflammatory disease of the skin and is often painful. Symptoms may include painful nodules and abscesses (cysts)
that may drain pus.
It most frequently affects specific areas of the skin, such as the submammary region, the armpits,
the inner thighs, the groin, and the buttocks. Scars may also form in the affected areas.
Hefiya is used to treat

• moderate to severe hidradenitis suppurativa in adults and
• moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.

Hefiya may reduce the number of nodules and abscesses you have and the pain that is often associated with this
disease. Initially, you may receive other medications. If these medications do not work adequately, you will receive Hefiya.
Crohn’s Disease in adults and children
Crohn’s disease is an inflammation of the intestine.
Hefiya is used to treat

• moderate to severe Crohn’s disease in adults and
• Crohn’s disease in children and adolescents aged 6 to 17 years.

If you suffer from Crohn’s disease, you will first be given other medications. If you do not
respond adequately to these medications, you will be given Hefiya to
reduce the typical symptoms of Crohn’s disease.
Ulcerative Colitis in adults and children
Ulcerative colitis is an inflammation of the large intestine.
Hefiya is used to treat

• moderate to severe ulcerative colitis in adults and
• moderate to severe ulcerative colitis in children aged 6 to 17 years.

If you have ulcerative colitis, you may first take other medications. If these medications do not work
satisfactorily, you will take Hefiya to reduce the signs and symptoms of ulcerative colitis.
Non-infectious Uveitis in adults and children
Non-infectious uveitis is an inflammatory disease that affects certain parts of the eye.
Inflammation leads to a decrease in vision and/or the presence of floaters in the eye
(small dark spots or thin lines that move across the field of vision). Hefiya works by reducing this
inflammation.
Hefiya is used for the treatment of:

• Adults with non-infectious uveitis with inflammation affecting the back of the eye.
• Children aged 2 years and older with chronic non-infectious uveitis with inflammation affecting the front of the eye.

You may first be given other medications. If you do not respond satisfactorily to
these medications, you will be given Hefiya.

2. What you need to know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or any of the other ingredients of this medicine (listed in section 6).
• If you have a severe infection, including tuberculosis, sepsis (blood poisoning) or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell your doctor if you have signs or symptoms of infection, such as, for example, fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).
• If you have moderate or severe heart failure. It is important to tell your doctor if you have had or have a serious heart condition (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.
Allergic reaction

• If you experience allergic reactions with symptoms such as a feeling of tightness in the chest, wheezing, dizziness, swelling or skin rash, do not administer Hefiya again and contact your doctor immediately as, in rare cases, these reactions can be life-threatening.

Infections

• If you have an infection, including long-term or localized infections (for example, leg ulcers), consult your doctor before starting treatment with Hefiya. If you have doubts, contact your doctor.
• You may be more likely to contract infections during treatment with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning).
• In rare cases, these infections can be life-threatening. It is important to tell your doctor about the presence of symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may advise you to temporarily stop Hefiya.

Tuberculosis (TB)

• Because cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will need to check if you have signs or symptoms typical of tuberculosis before starting therapy with Hefiya. This will involve collecting a detailed medical assessment including your medical history and clinical examinations (e.g. a chest X-ray and a tuberculin test). The performance and results of these tests must be recorded on the Patient Reminder Card. It is very important to tell your doctor if you have ever had tuberculosis, or if you have had close contact with people with tuberculosis. Tuberculosis can develop during therapy even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, mild fever) or other infections appear during or after therapy.

Travel/recurring infection

• Tell your doctor if you have lived in or travelled to regions where fungal infections, such as histoplasmosis, coccidioidomycosis or blastomycosis, are very common.
• Tell your doctor if you have had recurrent infections or if you have conditions that increase the risk of infection.

Hepatitis B virus

• Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active infection with the hepatitis B virus, or if you think you may be at risk of contracting the hepatitis virus.
• Your doctor should test you for hepatitis B virus infection. Taking adalimumab can reactivate hepatitis B virus infection in subjects who are carriers of this virus. In some rare cases, especially if the patient is undergoing therapy with other drugs that suppress the immune system, reactivation of hepatitis B virus infection can be life-threatening.

Age over 65 years

• If you are over 65 years of age, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection while you are being treated with Hefiya. It is important to inform your doctor if symptoms of infections such as fever, wounds, feeling tired or dental problems appear.

Surgery or dental procedures

• Before surgery or dental procedures, tell your doctor that you are taking Hefiya. Your doctor may advise you to temporarily stop Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases that affect the insulating layer around nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Tell your doctor immediately if you experience symptoms such as changes in vision, weakness of arms or legs, or numbness or tingling that affects any part of the body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause diseases and should not be administered during treatment with Hefiya if they cause infections. Consult your doctor before getting vaccinated. In children, it is recommended, if possible, to administer the vaccinations recommended for their age before starting therapy with Hefiya. If you take Hefiya during pregnancy, the baby may have a higher risk of contracting an infection up to about 5 months after the last dose you took during pregnancy. It is important that you inform the pediatrician or other healthcare provider of your use of Hefiya during pregnancy, so that they can decide when the baby should receive any type of vaccination.

Heart failure

• It is important to inform your doctor about any heart problems, both past and present. If you have mild heart failure and are concomitantly treated with Hefiya, your doctor must carefully assess and monitor your heart condition. If new symptoms of heart failure appear or existing symptoms worsen (e.g., shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising or easy bleeding, or paleness, see your doctor immediately. The latter may decide to interrupt the therapy.

Cancer

• In children and adults treated with Hefiya or other anti-TNFα drugs, some types of cancer have occurred very rarely. Patients with severe, long-standing rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukemia (cancers that affect blood cells and bone marrow). If you take Hefiya, the risk of developing lymphomas, leukemia or other cancers may increase. In rare circumstances, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also taking azathioprine or mercaptopurine. Tell your doctor if you are taking azathioprine or mercaptopurine with Hefiya.
• Cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If damaged areas of skin appear during or after treatment, or if the appearance of existing damaged areas changes, report it to your doctor.
• Cases of neoplasms, other than lymphoma, have been reported in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα. If you suffer from COPD, or smoke heavily, you should discuss with your doctor whether treatment with an anti-TNFα is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the manifestation of a syndrome such as lupus. Tell your doctor if you experience symptoms such as a persistent unexplained skin rash, fever, joint pain or fatigue.

Children and adolescents

• Do not give Hefiya to children with polyarticular juvenile idiopathic arthritis under the age of 2 years.
• Do not give Hefiya to children with pediatric plaque psoriasis or pediatric ulcerative colitis under the age of 4 years.
• Do not give Hefiya to children with pediatric Crohn's disease under the age of 6 years.
• Do not use the prefilled syringe of 80 mg if doses other than 80 mg are recommended.

Other medicines and Hefiya
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
Hefiya can be taken both with methotrexate and with other disease-modifying antirheumatic drugs
(sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts), corticosteroids
or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya must not be taken in conjunction with medicines containing the active ingredients anakinra or
abatacept due to the increased risk of having serious infections. The association of adalimumab and other
anti-TNF and anakinra or abatacept is not recommended due to the possible increase in the risk of
infections, including serious infections and other possible drug interactions. If you have any doubts, ask
your doctor.

Pregnancy and breastfeeding

• You should consider using appropriate contraceptive measures to prevent pregnancy and continue them for at least 5 months after the last therapy with Hefiya
• If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor for advice on taking this medicine.
• Hefiya should only be used during pregnancy if necessary.
• According to a pregnancy study, no increased risk of birth defects was found when the mother received adalimumab during pregnancy, compared to mothers who had the same condition but had not received adalimumab.
• Hefiya can be used during breastfeeding.
• If you take Hefiya during pregnancy, the baby may have a higher risk of contracting an infection.
• It is important that you inform the pediatrician or other healthcare provider of your use of Hefiya during pregnancy, before the baby receives any type of vaccination (for more information on vaccines, see “Warnings and precautions”).

Driving and using machines
Hefiya may affect, albeit to a modest extent, your ability to drive, ride a bicycle or operate
machinery. After taking Hefiya, you may experience vision disturbances and a feeling that the
environment around you is rotating (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 mL of dose, i.e. essentially
‘sodium-free’.

3. How to use Hefiya

Use this medicine following the instructions of your doctor or pharmacist exactly as given. If you have
any doubts, ask your doctor or pharmacist.
The recommended doses of Hefiya in each approved indication are listed in the following
table. Your doctor may prescribe a different concentration of Hefiya if your child needs a
different dose.

How and route of administration
Hefiya is administered by injection under the skin (subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist
explaining that you have taken more medicine than you should. Always keep the medicine packaging,
even if it is empty.

If you forget to use Hefiya
If you forget to give an injection, you should inject the next dose of Hefiya as soon as you
remember. Then resume the dose regularly according to the prescribed schedule.

If you stop using Hefiya
The decision to stop using Hefiya should be discussed with your doctor. Symptoms may
return after stopping treatment.
If you have any doubts about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Most side effects are mild to moderate. However, some can be serious and require treatment. Side effects may occur
up to 4 months or more after the last injection of Hefiya.

Seek urgent medical attentionif you notice any of the following signs of allergic reaction or
heart failure

• severe skin rash, hives;
• swelling of the face, hands, feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during activity or when lying down or swollen feet.

Tell your doctor as soon as possibleif you notice any of the following reactions

• signs and symptoms of infection such as fever, feeling unwell, sores, dental problems, burning when urinating, fatigue or weakness or cough;
• symptoms of nerve problems, such as tingling, numbness, double vision or weakness of the arms or legs;
• signs of skin cancer such as swelling or an open sore that does not heal;
• signs and symptoms suggesting the onset of blood system disorders, such as persistent fever, bruising, bleeding, paleness.

The following side effects have been observed with Hefiya:

Very common(may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis and pneumonia);
• headache;
• abdominal pain (stomach ache);
• nausea and vomiting;
• skin rash;
• muscle pain.

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including tooth infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• infections affecting the joints;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergy);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, prickling or numbness;
• migraine;
• symptoms of nerve root compression (including lower back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (feeling of spinning);
• feeling of a fast heartbeat;
• high blood pressure;
• hot flushes;
• bruise (solid swelling with clotted blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux;
• dry syndrome (including dry eyes and dry mouth);
• itching;
• itchy skin rash;
• contusion;
• skin inflammation (such as eczema);
• breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in urine;
• kidney problems;
• chest pain;
• edema (fluid buildup in the body, causing swelling of the affected tissue);
• fever;
• decreased platelets in the blood, which increases the risk of bleeding or bruising;
• difficulty healing.

Uncommon(may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when immune defenses are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that can affect lungs, skin and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing;
• feeling of irregular heartbeat such as palpitations;
• heart problems that can cause shortness of breath or swelling in the ankles;
• acute myocardial infarction (heart attack);
• formation of a sac in the wall of a major artery, inflammation and blood clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal accumulation of fluid in the pleural space);
• inflammation of the pancreas causing severe pain in the abdomen and back;
• difficulty swallowing;
• facial edema (swelling);
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle breakdown;
• systemic lupus erythematosus (immune system disorder, including inflammation of the skin, heart, lungs, joints and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare(may affect up to 1 in 1,000 people)

• leukemia (a cancer that affects the blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as inflammation of the optic nerve in the eye and Guillain-Barré syndrome, a condition that can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lung);
• intestinal perforation (hole in the wall of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (inflammation of the liver caused by your own immune system);
• cutaneous vasculitis (inflammation of the blood vessels in the skin);
• Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and skin rash with blisters);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy, reddish-purple skin rash).

Not known(frequency cannot be estimated from available data)

• T-cell hepatic-splenic lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer associated with human herpes virus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which manifests as a skin rash accompanied by muscle weakness);

and weight gain (weight gain has been small for most patients).

Some of the side effects observed with adalimumab may be asymptomatic and can
only be detected through blood tests. These include:

Very common(may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased blood lipids;
• increased liver enzymes.

Common(may affect up to 1 in 10 people)

• increased white blood cell count;
• decreased platelet count;
• increased uric acid in the blood;
• alteration of sodium in the blood;
• decreased calcium in the blood;
• decreased phosphorus in the blood;
• increased sugar in the blood;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• decreased potassium in the blood.

Uncommon(may affect up to 1 in 100 people)

• high levels of bilirubin in the blood (liver blood test).

Rare(may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell and platelet counts.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the national
reporting system listed in Annex V. By reporting side effects you can help provide
more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label/blister/box after the
word Exp.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.
Alternative storage conditions:
When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 42 days – ensure that the medicine is
protected from light. Once removed from the refrigerator to be stored at room temperature, the
pre-filled syringe must be used within 42 days or discarded, even if it is subsequently
placed back in the refrigerator. You must record the date on which the pre-filled syringe is removed from
the refrigerator for the first time and the date after which the syringe must be discarded.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Hefiya contains

• The active ingredient is adalimumab. Each pre-filled syringe contains 80 mg of adalimumab in 0.8 mL of solution.
• The excipients are adipic acid, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections.

Description of Hefiya and package contents
Hefiya 80 mg injectable solution in a pre-filled syringe is supplied in 0.8 mL of solution from clear to
slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use glass type I transparent syringe with a 29 gauge stainless
steel needle and a needle safety device with a finger grip, rubber needle cap (thermoplastic elastomer) and plastic plunger, containing 0.8 mL of solution.
The packs contain 1 and 2 pre-filled syringes of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in pre-filled syringe and pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Sandoz nv/sa
Tél/Tel: +32 2 722 97 97

Lietuva
Sandoz Pharmaceuticals d.d filialas
Tel: +370 5 2636 037

Luxembourg/Luxemburg
Sandoz nv/sa
Tél/Tel.: +32 2 722 97 97

Česká republika
Sandoz s.r.o.
Tel: +420 225 775 111

България
Сандоз България КЧТ
Тел.: +359 2 970 47 47

Magyarország
Sandoz Hungária Kft.
Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige
Sandoz A/S
Tlf: +45 63 95 10 00

Malta
Sandoz Pharmaceuticals d.d.
Tel: +356 99644126

Deutschland
Hexal AG
Tel: +49 8024 908 0

Nederland
Sandoz B.V.
Tel: +31 36 52 41 600

Eesti
Sandoz d.d. Eesti filiaal
Tel: +372 665 2400

Österreich
Sandoz GmbH
Tel: +43 5338 2000

Ελλάδα
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε.
Τηλ: +30 216 600 5000

Polska
Sandoz Polska Sp. z o.o.
Tel.: +48 22 209 70 00

España
Sandoz Farmacéutica, S.A.
Tel: +34 900 456 856

Portugal
Sandoz Farmacêutica Lda.
Tel: +351 21 000 86 00

France
Sandoz SAS
Tél: +33 1 49 64 48 00

România
Sandoz Pharmaceuticals SRL
Tel: +40 21 407 51 60

Hrvatska
Sandoz d.o.o.
Tel: +385 1 23 53 111

Slovenija
Sandoz farmacevtska družba d.d.
Tel: +386 1 580 29 02

Ireland
Rowex Ltd.
Tel: + 353 27 50077

Slovenská republika
Sandoz d.d. - organizačná zložka
Tel: +421 2 50 70 6111

Italia
Sandoz S.p.A.
Tel: +39 02 96541

Suomi/Finland
Sandoz A/S
Puh/Tel: +358 10 6133 400

Κύπρος
Sandoz Pharmaceuticals d.d.
Τηλ: +357 22 69 0690

United Kingdom (Northern Ireland)
Sandoz GmbH
Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu .

7. Instructions for Use

To avoid possible infections and to ensure you use the medicine correctly, it is important that
you follow these instructions.
Make sure you read, understand and follow these Instructions for Use before injecting Hefiya.
The healthcare professional must show you how to prepare and inject Hefiya correctly using the
single-use prefilled syringe before you use the medicine for the first time. If you have any doubts, please contact
your healthcare professional.

Hefiya single-use prefilled syringe with safety device for the needle and additional finger grip

Figure A:Hefiya prefilled syringe with needle safety device and finger grip

It is important that you:

• do not usethe syringe if the prefilled seals are broken, because use may not be safe;
• do not openthe outer carton until you are ready to use the prefilled syringe;
• never leavethe prefilled syringe unattended where it could be tampered with by others;
• if you drop the syringe, do not use itif it appears damaged or if it fell after you removed the needle cap;
• do not removethe needle cap until the time of injection;
• be careful not to touch the wings of the needle safety devicebefore use. If you do, the needle safety device may be activated too early.
• do not removethe finger grip before the injection;
• injectHefiya 15-30 minutes after removing it from the refrigerator, for a more comfortable injection;
• dispose of the used syringe immediately after use. Do not reuse the prefilled syringe.See “4.Disposal of used prefilled syringes”at the end of these Instructions for Use.

How should you store the Hefiya single-dose prefilled syringe?

• Store the outer packaging of the prefilled syringes in a refrigerator, at a temperature between 2° and 8°C.
• When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 42 days - make sure to protect the medicine from light. Once it is removed from the refrigerator to be stored at room temperature, the prefilled syringe must be used within 42 days or discarded, even if it is subsequently placed back in the refrigerator. You must record the date on which the prefilled syringe is removed from the refrigerator for the first time and the date after which it must be discarded.
• Store the prefilled syringes in the original packaging until you are ready to use them, to protect the medicine from light.
• Do not store the prefilled syringes at extremely hot or cold temperatures.
• Do not freeze the prefilled syringes.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The syringe prefilled package contains:

• Syringe/s prefilled with Hefiya (see Figure A). Each prefilled syringe contains 80 mg/0.8 mL of adalimumab.

The Hefiya prefilled syringe package does not contain (see Figure B):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps disposal container. See “4. Disposal of used syringes”at the end of these Instructions for Use.
• Adhesive bandage.

Figure B:items notincluded in the package

Before the injection

Figure C:the needle safety device is not
activated – the single-dose prefilled syringe is
ready for use

Figure D:the needle safety device is
activated – do not use
In this configuration, the syringe prefilled needle safety device is activated.
or do not usethe syringe (see Figure D).
or In this configuration, the needle safety device is not activated.
or The syringe is ready for use (see

Figure C).

Preparing the syringe

• For a more comfortable injection, remove the package containing the prefilled syringe from the refrigerator and leave it closedon the work surface for about 15-30 minutes to reach room temperature.
• Remove the prefilled syringe from the blister.
• Look through the window. The solution should be colourless or slightly yellowish and from clear to slightly opalescent. Do not use the syringe if you notice particles and/or colour changes. If you have any doubts about the appearance of the solution, contact your pharmacist for assistance.
• Do not usethe prefilled syringe if it is broken or if the needle safety device is activated. Return the prefilled syringe and the package to the pharmacy.
• Check the expiry date (Exp.) of the prefilled syringe. Do not use the prefilled syringe if the expiry date has passed.

Contact your pharmacist if the syringe does not pass any of the checks above.

1. Choice of injection site:

• The recommended injection site is the front of the thighs. You can also use the lower abdomen, but not the area within 5 cm around the navel (see Figure E).
• Choose a different site each time you administer an injection.
• Do notinject the medicine into areas where the skin is painful, bruised, reddened, flaky or hardened. Avoid areas with scars or stretch marks. If you suffer from psoriasis, DO NOT inject the medicine directly into areas with psoriasis plaques.

Figure E:how to choose the injection site
of injection

2. Cleaning the injection site:

• Wash your hands thoroughly with water and soap.
• Using a circular motion, clean the injection site with a swab soaked in alcohol. Allow to dry before administering the injection (see Figure F).
• Do nottouch the cleaned area before the injection.

Figure F:how to clean the injection
site

3. Administration of the injection:

• Carefully pull off the needle cap to remove it from the pre-filled syringe (see Figure G).
• Discard the needle cap.
• You may see a drop of liquid at the end of the needle. This is normal.

Figure G:how to pull off the cap
of the needle

• Gently create a skin fold at the injection site (see Figure H).
• Insert the needle into the skin as shown.
• Push the entire needle into the skin to ensure that all of the medicine is delivered.
• Use the syringe within 5 minutes of removing the cap.

Figure H:how to insert the needle

• Hold the pre-filled syringe as shown (see Figure I).
• Slowly press the plunger all the way down so that the plunger head is completely between the fins of the needle safety device.
• While holding the syringe in position, keep the plunger pressed down completely for 5 seconds.

Figure I:how to hold the syringe

• Keep the plunger fully depressedwhile carefully withdrawing the needle from the injection site, then release the skin (see Figure J) .

Figure J:how to withdraw the needle

• Slowly release the plunger and let the needle safety device automatically cover the exposed needle (see Figure K).
• You may notice a small amount of blood at the injection site. You can press a cotton ball or gauze on the injection site and hold for 10 seconds. Do not rub the injection site. If necessary, you can cover the injection site with a small adhesive bandage. Figure K:how to slowly release the plunger

4. Disposal of used syringes:

• Dispose of the used syringe in a sharps disposal container (a resealable, puncture-resistant container, see Figure L). For your safety and health and that of others, used needles and syringes must never be reused.
• Do not dispose of any medicine down the drain or in household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Unused medicine and waste derived from that medicine must be disposed of in accordance with local regulations.

Figure L:how to dispose of the used
prefilled syringe

If you have any doubts, consult a doctor, pharmacist, or nurse who is familiar with
Hefiya.

Hefiya 80 mg injectable solution in pre-filled pen

adalimumab

Read this leaflet carefully before using this medicine as it contains important
information for you

• Keep this leaflet. You may need to read it again.
• Your doctor will give you a Patient Reminder Card, which contains important safety information that you need to know before administering Hefiya and during treatment with Hefiya. Keep this Patient Reminder Cardwith you during treatment and for 4 months after the last injection (or the last injection given to your child) of Hefiya.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be dangerous.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Hefiya is and what it is used for
• 2. What you need to know before using Hefiya
• 3. How to use Hefiya
• 4. Possible side effects
• 5. How to store Hefiya
• 6. Contents of the pack and other information
• 7. Instructions for use

1. What is Hefiya and what is it used for

Hefiya contains the active ingredient adalimumab, a medicine that works on the body's immune system (defense system).
Hefiya is indicated for the treatment of the inflammatory diseases listed below:

• rheumatoid arthritis,
• plaque psoriasis,
• hidradenitis suppurativa,
• Crohn's disease,
• ulcerative colitis,
• non-infectious uveitis.

The active ingredient contained in Hefiya, adalimumab, is a human monoclonal antibody. Monoclonal antibodies are proteins that bind to a specific target.
The target of adalimumab is a protein called tumor necrosis factor (TNFα), which is
involved in the immune system (defense system) and is present at higher concentrations in the
inflammatory diseases listed above. By binding to TNFα, Hefiya blocks its action and reduces the
inflammatory process in these diseases.
Rheumatoid Arthritis
Rheumatoid arthritis is an inflammatory disease of the joints.
Hefiya is used to treat rheumatoid arthritis in adults. If you have rheumatoid arthritis of moderate to severe degree, other disease-modifying drugs, such as
methotrexate, may initially be administered. If these drugs do not work satisfactorily, you will be given Hefiya to treat
rheumatoid arthritis.
Hefiya can also be used for the treatment of severe, active and progressive rheumatoid arthritis
without prior treatment with methotrexate.
Hefiya may slow the progression of cartilage and bone damage in the joints, caused
by the disease, and improve physical function.
Generally, Hefiya is used with methotrexate. If your doctor believes that treatment with
methotrexate is not appropriate, Hefiya may be administered alone.
Plaque Psoriasis
Plaque psoriasis is an inflammatory skin condition that causes reddish,
scaly and hardened patches of skin covered with silvery scales. Plaque psoriasis can also affect the
nails, causing them to break, thicken and lift from the nail bed, which can be
painful. Psoriasis is believed to be caused by a problem with the body's immune system that
leads to increased production of skin cells.
Hefiya is used to treat moderate to severe plaque psoriasis in adults.
Hidradenitis Suppurativa in adults and adolescents
Hidradenitis Suppurativa (sometimes called inverse acne) is a long-term inflammatory disease of the skin and is often painful. Symptoms may include painful nodules and abscesses (cysts)
that may drain pus.
It most frequently affects specific areas of the skin, such as the submammary region, the armpits,
the inner thighs, the groin and the buttocks. Scars may also form in the affected areas.
Hefiya is used to treat

• moderate to severe hidradenitis suppurativa in adults and
• moderate to severe hidradenitis suppurativa in adolescents aged 12 to 17 years.

Hefiya may reduce the number of nodules and abscesses you have and the pain that is often associated with this
disease. Initially, you may receive other medications. If these medications do not work adequately, you will receive Hefiya.
Crohn's Disease in adults and children
Crohn's disease is an inflammation of the intestine.
Hefiya is used to treat
moderate to severe Crohn's disease in adults and
moderate to severe Crohn's disease in children and adolescents aged 6 to 17 years.
If you suffer from Crohn's disease, you will first be given other medications. If you do not
respond adequately to these medications, you will be given Hefiya to
reduce the typical symptoms of Crohn's disease.
Ulcerative Colitis in adults and children
Ulcerative colitis is an inflammation of the large intestine.
Hefiya is used to treat

• moderate to severe ulcerative colitis in adults and
• moderate to severe ulcerative colitis in children and adolescents aged 6 to 17 years.

If you have ulcerative colitis, you may first take other medications. If these medications do not work
satisfactorily, you will take Hefiya to reduce the signs and symptoms of the disease.
Non-infectious Uveitis in adults and children
Non-infectious uveitis is an inflammatory disease that affects certain parts of the eye.
Inflammation leads to a decrease in vision and/or the presence of floaters in the eye
(black dots or thin lines that move across the field of vision). Hefiya works by reducing this
inflammation.
Hefiya is used for the treatment of:

• Adults with non-infectious uveitis with inflammation affecting the back of the eye
• Children aged 2 years and older with chronic non-infectious uveitis with inflammation affecting the front of the eye

You may first be given other medications. If you do not respond satisfactorily to
these medications, you will be given Hefiya.

2. What you need to know before using Hefiya

Do not use Hefiya

• If you are allergic to adalimumab or to any of the other ingredients of this medicine (listed in section 6).
• If you have a severe infection, including tuberculosis, sepsis (blood poisoning) or other opportunistic infections (unusual infections associated with a weakened immune system). It is important to tell your doctor if you have signs or symptoms of infection, such as e.g. fever, wounds, feeling tired, dental problems (see “Warnings and precautions”).
• If you have moderate or severe heart failure. It is important to tell your doctor if you have had or have a serious heart condition (see “Warnings and precautions”).

Warnings and precautions
Talk to your doctor or pharmacist before using Hefiya.
Allergic reaction

• If you experience allergic reactions with symptoms such as a feeling of tightness in the chest, wheezing, dizziness, swelling or skin rash, do not administer Hefiya again and contact your doctor immediately as, in rare cases, these reactions can be life-threatening.

Infections

• If you have an infection, including long-term or localized infections (for example, leg ulcers), consult your doctor before starting treatment with Hefiya. If you have doubts, contact your doctor.
• You may be more likely to contract infections during treatment with Hefiya. This risk may increase if your lung function is reduced. These infections can be serious and include tuberculosis, infections caused by viruses, fungi, parasites or bacteria, or other unusual infectious organisms and sepsis (blood poisoning).
• In rare cases, these infections can be life-threatening. It is important to tell your doctor about the presence of symptoms such as fever, wounds, feeling tired or dental problems. Your doctor may advise you to temporarily stop Hefiya.

Tuberculosis (TB)

• Since cases of tuberculosis have occurred in patients treated with adalimumab, your doctor will need to check if you have signs or symptoms typical of tuberculosis before starting therapy with Hefiya. This will involve collecting a detailed medical assessment including your medical history and clinical examinations (e.g. a chest X-ray and a tuberculin test). The performance and results of these tests must be recorded in the Patient Reminder Card. It is very important to tell your doctor if you have ever had tuberculosis, or if you have had close contact with people with tuberculosis. Tuberculosis can develop during therapy even if you have received preventive treatment for tuberculosis. Contact your doctor immediately if symptoms of tuberculosis (persistent cough, weight loss, lack of energy, moderate fever) or other infections appear during or after therapy.

Travel/recurring infection

• Tell your doctor if you have lived in or travelled to regions where fungal infections, such as histoplasmosis, coccidioidomycosis or blastomycosis, are very common.
• Tell your doctor if you have had recurrent infections or if you have conditions that increase your risk of infection.

Hepatitis B virus

• Tell your doctor if you are a carrier of the hepatitis B virus (HBV), if you have an active infection with the hepatitis B virus or if you think you may be at risk of contracting the hepatitis
• B virus. Your doctor should test you for hepatitis B virus infection. Taking adalimumab can reactivate hepatitis B virus infection in subjects who are carriers of this virus. In some rare cases, especially if the patient is undergoing therapy with other drugs that suppress the immune system, reactivation of hepatitis B virus infection can be life-threatening.

Age over 65 years

• If you are over 65 years of age, you may be more susceptible to infections while taking Hefiya. You and your doctor should pay particular attention to signs of infection while you are being treated with Hefiya. It is important to tell your doctor if symptoms of infections such as fever, wounds, feeling tired or dental problems appear.

Surgery or dental procedures

• Before surgery or dental procedures, tell your doctor that you are taking Hefiya. Your doctor may advise you to temporarily stop Hefiya.

Demyelinating disease

• If you have or develop demyelinating diseases (diseases that affect the insulating layer around nerves), such as multiple sclerosis, your doctor will decide whether to start or continue treatment with Hefiya. Tell your doctor immediately if you experience symptoms such as changes in vision, weakness of arms or legs, or numbness or tingling that affects any part of the body.

Vaccination

• Certain vaccines contain live but weakened forms of bacteria or viruses that cause diseases and should not be administered during treatment with Hefiya if they cause infections. Consult your doctor before getting vaccinated. In children, it is recommended, if possible, to administer the vaccinations recommended for their age before starting therapy with Hefiya. If you have taken Hefiya during pregnancy, the child may have a greater risk of contracting this infection. It is important that you tell the pediatrician or other healthcare provider about your use of Hefiya during pregnancy, so that they can decide when the child should receive any type of vaccination.

Heart failure

• It is important to tell your doctor about any heart problems, both past and present. If you have mild heart failure and are receiving concomitant treatment with Hefiya, your doctor must carefully assess and monitor your heart condition. If new symptoms of heart failure appear or existing symptoms worsen (e.g. shortness of breath or swelling of the feet), contact your doctor immediately.

Fever, bruising, bleeding or paleness

• In some patients, the body may not be able to produce enough blood cells to fight infections or stop bleeding. If you have persistent fever, bruising or easy bleeding or paleness, see your doctor immediately. The latter may decide to interrupt the therapy.

Tumor

• In children and adults treated with adalimumab or other anti-TNFα drugs, very rare cases of certain types of tumors have occurred. Patients with severe, long-standing rheumatoid arthritis may have a higher than average risk of developing lymphoma and leukemia (cancers that affect blood cells and bone marrow). If you take Hefiya, your risk of developing lymphomas, leukemia or other tumors may increase. In rare circumstances, a specific and serious type of lymphoma has been observed in patients treated with adalimumab. Some of these patients were also taking azathioprine or mercaptopurine. Tell your doctor if you are taking azathioprine or mercaptopurine with Hefiya.
• In addition, cases of non-melanoma skin cancer have been observed in patients taking adalimumab. If damaged areas of skin appear during or after treatment, or if the appearance of damaged areas changes, report it to your doctor.
• There have been cases of neoplasms, in addition to lymphoma, in patients with a specific type of lung disease called chronic obstructive pulmonary disease (COPD) treated with another anti-TNFα. If you suffer from COPD, or smoke heavily, you should discuss with your doctor whether treatment with an anti-TNFα is appropriate.

Autoimmune diseases

• Rarely, treatment with Hefiya may lead to the manifestation of a syndrome such as lupus. Tell your doctor if you experience symptoms such as a persistent unexplained skin rash, fever, joint pain or fatigue.

Children and adolescents

• Do not give Hefiya to children with polyarticular juvenile idiopathic arthritis under the age of 2 years.
• Do not give Hefiya to children with pediatric plaque psoriasis or pediatric ulcerative colitis under the age of 4 years.
• Do not give Hefiya to children with pediatric Crohn's disease under the age of 6 years.
• Do not use the pre-filled pen of 80 mg if doses other than 80 mg are recommended.

Other medicines and Hefiya
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
Hefiya can be taken both with methotrexate and with other disease-modifying antirheumatic drugs
(sulfasalazine, hydroxychloroquine, leflunomide and parenteral gold salts), corticosteroids
or analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs).
Hefiya should not be taken at the same time as medicines containing the active ingredients anakinra or
abatacept due to the increased risk of having serious infections. The combination of adalimumab and other
anti-TNF and anakinra or abatacept is not recommended due to the possible increased risk of
infections, including serious infections and other possible drug interactions. If you have any doubts, consult
your doctor.

Pregnancy and breastfeeding

• You should consider using adequate contraceptive measures to prevent pregnancy and continue using them for at least 5 months after the last therapy with Hefiya.
• If you are pregnant, suspect you are pregnant or are planning a pregnancy, ask your doctor for advice on taking this medicine.
• Hefiya should only be used during pregnancy if necessary.
• According to a pregnancy study, no increased risk of birth defects was found when the mother had received adalimumab during pregnancy, compared to mothers who had the same condition but had not received adalimumab.
• Hefiya can be used during breastfeeding.
• If you take Hefiya during pregnancy, the child may have a greater risk of contracting an infection.
• It is important that you tell the pediatrician or other healthcare provider about your use of Hefiya during pregnancy, before the child receives any type of vaccination (for more information on vaccines, see “Warnings and precautions”).

Driving and using machines
Hefiya may affect, albeit only to a modest extent, your ability to drive, ride a bicycle or operate
machinery. After taking Hefiya, you may experience visual disturbances and a feeling that the environment
around you is spinning (dizziness).

Hefiya contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 0.8 mL dose, i.e. essentially
‘sodium-free’.

3. How to use Hefiya

Use this medicine following exactly the instructions of your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended doses of Hefiya in each approved indication are listed in the following
table. The doctor may prescribe a different concentration of Hefiya if the child needs a
different dose.

How and route of administration
Hefiya is administered by injection under the skin (subcutaneous injection).
Detailed instructions on how to inject Hefiya are provided in section 7, “Instructions for use”.

If you use more Hefiya than you should
If you accidentally inject Hefiya more frequently than you should, contact your doctor or pharmacist
explaining that you have taken more medicine than you should. Always keep the medicine box,
even if empty.

If you forget to use Hefiya
If you forget to give an injection, you should inject the next dose of Hefiya as soon as you
remember. Then resume the dose regularly according to the established dosage schedule.

If you stop using Hefiya
The decision to stop using Hefiya must be discussed with your doctor. Symptoms may
return after stopping treatment.
If you have any doubts about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Most side effects are mild to moderate. However, some may be serious and require treatment. Side effects may occur
up to 4 months or more after the last injection of Hefiya.

Seek medical attention urgentlyif you notice any of the following signs of an allergic reaction or
heart failure

• severe skin rash, hives;
• swelling of the face, hands, feet;
• difficulty breathing, difficulty swallowing;
• shortness of breath during activity or when lying down, or swollen feet.

Inform your doctor as soon as possibleif you notice any of the following reactions

• signs and symptoms of infection such as fever, feeling unwell, sores, dental problems, burning when urinating; fatigue or weakness or cough;
• symptoms of nerve problems, such as tingling, numbness, double vision or weakness of the arms or legs;
• signs of skin cancer such as swelling or an open sore that does not heal;
• signs and symptoms suggesting the onset of blood disorders, such as persistent fever, bruising, bleeding, paleness.

The following side effects have been observed with Hefiya

Very common(may affect more than 1 in 10 people)

• reactions at the injection site (including pain, swelling, redness or itching);
• respiratory tract infections (including cold, runny nose, sinusitis and pneumonia);
• headache;
• abdominal pain (stomach ache);
• nausea and vomiting;
• skin rash;
• muscle pain.

Common(may affect up to 1 in 10 people)

• serious infections (including sepsis and influenza);
• intestinal infections (including gastroenteritis);
• skin infections (including cellulitis and herpes zoster infection);
• ear infections;
• mouth infections (including tooth infections and herpes simplex);
• reproductive system infections;
• urinary tract infections;
• fungal infections;
• infections affecting the joints;
• benign tumors;
• skin cancer;
• allergic reactions (including seasonal allergy);
• dehydration;
• mood changes (including depression);
• anxiety;
• sleep disorders;
• sensory disturbances such as tingling, pricking or numbness;
• migraine;
• symptoms of nerve root compression (including back pain and leg pain);
• visual disturbances;
• eye inflammation;
• eyelid inflammation and eye swelling;
• dizziness (feeling of spinning);
• feeling of a fast heartbeat;
• high blood pressure;
• hot flashes;
• hematoma (solid swelling with clotted blood);
• cough;
• asthma;
• shortness of breath;
• gastrointestinal bleeding;
• dyspepsia (indigestion, bloating, heartburn);
• acid reflux;
• dry syndrome (including dry eyes and dry mouth);
• itching;
• itchy skin rash;
• bruising;
• skin inflammation (such as eczema);
• breaking of fingernails and toenails;
• increased sweating;
• hair loss;
• onset or worsening of psoriasis;
• muscle spasms;
• blood in the urine;
• kidney problems;
• chest pain;
• edema (fluid retention in the body, causing swelling of the affected tissue);
• fever;
• reduced platelets in the blood, which increases the risk of bleeding or bruising;
• difficulty healing.

Uncommon(may affect up to 1 in 100 people)

• unusual infections (including tuberculosis and other infections) that occur when immune defenses are reduced;
• neurological infections (including viral meningitis);
• eye infections;
• bacterial infections;
• diverticulitis (inflammation and infection of the large intestine);
• tumors, including tumors of the lymphatic system (lymphoma) and melanoma (a type of skin cancer);
• immune system disorders that can affect lungs, skin and lymph nodes (most commonly a condition called sarcoidosis);
• vasculitis (inflammation of blood vessels);
• tremor (shaking);
• neuropathy (nerve damage);
• stroke;
• hearing loss, ringing in the ears;
• feeling of irregular heartbeat such as palpitations;
• heart problems that can cause shortness of breath or swelling in the ankles;
• acute myocardial infarction (heart attack);
• formation of a sac in the wall of a major artery, inflammation and a blood clot in a vein, blockage of a blood vessel;
• lung disease causing shortness of breath (including inflammation);
• pulmonary embolism (blockage of a pulmonary artery);
• pleural effusion (abnormal collection of fluid in the pleural space);
• inflammation of the pancreas causing severe pain in the abdomen and back;
• difficulty swallowing;
• facial edema (swelling);
• inflammation of the gallbladder, gallstones;
• fatty liver (accumulation of fat in liver cells);
• night sweats;
• scarring;
• abnormal muscle catabolism;
• systemic lupus erythematosus (immune system disorder, including inflammation of the skin, heart, lungs, joints and other organs);
• interrupted sleep;
• impotence;
• inflammations.

Rare(may affect up to 1 in 1,000 people)

• leukemia (a cancer that affects the blood and bone marrow);
• severe allergic reaction with shock;
• multiple sclerosis;
• neurological disorders (such as optic nerve inflammation in the eye and Guillain-Barré syndrome, a condition that can cause muscle weakness, abnormal sensations, tingling in the arms and upper body);
• cardiac arrest;
• pulmonary fibrosis (scarring of the lung);
• intestinal perforation (hole in the wall of the intestine);
• hepatitis (inflammation of the liver);
• reactivation of hepatitis B infection;
• autoimmune hepatitis (inflammation of the liver caused by your own immune system);
• cutaneous vasculitis (inflammation of the blood vessels in the skin);
• Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and skin rash with blisters);
• facial edema (swelling) associated with allergic reactions;
• erythema multiforme (inflammatory skin rash);
• lupus-like syndrome;
• angioedema (localized swelling of the skin);
• lichenoid skin reaction (itchy reddish-purple skin rash).

Not known(frequency cannot be estimated based on available data)

• T-cell hepato-splenic lymphoma (a rare blood cancer that is often fatal);
• Merkel cell carcinoma (a type of skin cancer);
• Kaposi's sarcoma, a rare cancer associated with human herpes virus 8 infection. Kaposi's sarcoma most commonly manifests with purple lesions on the skin;
• liver failure;
• worsening of a condition called dermatomyositis (which manifests as a skin rash accompanied by muscle weakness);
• weight gain (weight gain has been low for most patients).

Some of the side effects observed with adalimumab may be asymptomatic and can
only be detected through blood tests. These include:

Very common(may affect more than 1 in 10 people)

• low white blood cell count;
• low red blood cell count;
• increased lipids in the blood;
• increased liver enzymes.

Common(may affect up to 1 in 10 people)

• increased white blood cell count;
• reduced platelet count;
• increased uric acid in the blood;
• altered sodium in the blood;
• reduced calcium in the blood;
• reduced phosphorus in the blood;
• increased sugar in the blood;
• increased lactate dehydrogenase in the blood;
• presence of autoantibodies in the blood;
• reduced potassium in the blood.

Uncommon(may affect up to 1 in 100 people)

• high levels of bilirubin in the blood (liver blood test).

Rare(may affect up to 1 in 1,000 people)

• low white blood cell, red blood cell and platelet counts.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, please tell your
doctor or pharmacist. You can also report side effects directly through the national
reporting system listed in Annex V. By reporting side effects you can help provide
more information on the safety of this medicine.

5. How to store Hefiya

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label/blister/box after the
word Exp.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the pre-filled pen in the outer packaging to protect the medicine from light.
Alternative storage conditions:
When necessary (for example when travelling), Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 42 days – ensure to protect the medicine
from light. Once removed from the refrigerator for storage at room temperature, the
pre-filled pen must be used within 42 days or discarded, even if subsequently
returned to the refrigerator. You must record the date on which the pre-filled pen is removed from
the refrigerator for the first time and the date after which the pen must be discarded.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Hefiya contains

• The active substance is adalimumab. Each pre-filled pen contains 80 mg of adalimumab in 0.8 mL of solution.
• The excipients are adipic acid, mannitol (E 421), polysorbate 80 (E 433), hydrochloric acid (E 507), sodium hydroxide (E 524) and water for injections.

Description of the appearance of Hefiya and contents of the pack
Hefiya 80 mg solution for injection in a pre-filled pen is supplied as 0.8 mL of solution from clear
to slightly opalescent, colourless or slightly yellowish.
Hefiya is supplied in a single-use pre-filled syringe assembled in a triangular-shaped pen with
a transparent window and label. The syringe inside the pen is type I glass with a 29 gauge needle
made of stainless steel, an internal rubber needle cap (thermoplastic elastomer)
and a rubber stopper, containing 0.8 mL of solution.
The packs contain 1, 2 and 3 pre-filled pens of Hefiya.
Not all pack sizes may be marketed.
Hefiya is available in a pre-filled syringe and in a pre-filled pen.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH Schaftenau
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Sandoz nv/sa
Tél/Tel: +32 2 722 97 97

Lietuva
Sandoz Pharmaceuticals d.d filialas
Tel: +370 5 2636 037

Luxembourg/Luxemburg
Sandoz nv/sa
Tél/Tel.: +32 2 722 97 97

Česká republika
Sandoz s.r.o.
Tel: +420 225 775 111

България
Сандоз България КЧТ
Тел.: +359 2 970 47 47

Magyarország
Sandoz Hungária Kft.
Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige
Sandoz A/S
Tlf: +45 63 95 10 00

Malta
Sandoz Pharmaceuticals d.d.
Tel: +356 99644126

Deutschland
Hexal AG
Tel: +49 8024 908 0

Nederland
Sandoz B.V.
Tel: +31 36 52 41 600

Eesti
Sandoz d.d. Eesti filiaal
Tel: +372 665 2400

Österreich
Sandoz GmbH
Tel: +43 5338 2000

Ελλάδα
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε.
Τηλ: +30 216 600 5000

Polska
Sandoz Polska Sp. z o.o.
Tel.: +48 22 209 70 00

España
Sandoz Farmacéutica, S.A.
Tel: +34 900 456 856

Portugal
Sandoz Farmacêutica Lda.
Tel: +351 21 000 86 00

France
Sandoz SAS
Tél: +33 1 49 64 48 00

România
Sandoz Pharmaceuticals SRL
Tel: +40 21 407 51 60

Hrvatska
Sandoz d.o.o.
Tel: +385 1 23 53 111

Slovenija
Sandoz farmacevtska družba d.d.
Tel: +386 1 580 29 02

Ireland
Rowex Ltd.
Tel: + 353 27 50077

Slovenská republika
Sandoz d.d. - organizačná zložka
Tel: +421 2 50 70 6111

Italia
Sandoz S.p.A.
Tel: +39 02 96541

Suomi/Finland
Sandoz A/S
Puh/Tel: +358 10 6133 400

Κύπρος
Sandoz Pharmaceuticals d.d.
Τηλ: +357 22 69 0690

United Kingdom (Northern Ireland)
Sandoz GmbH
Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines
Agency: http://www.ema.europa.eu.

7. Instructions for Use

To avoid possible infections and to ensure you use Hefiya correctly, it is important that you
follow these instructions.
Make sure you read, understand and follow these Instructions for Use before injecting Hefiya.
The healthcare professional must show you how to prepare and inject Hefiya correctly using the
Hefiya single-dose pre-filled pen before you use the medicine for the first time. If you have any doubts,
ask your healthcare professional.

Hefiya Single-Use Pre-filled Pen

Figure A:parts of the Hefiya pen
In Figure A, the pen is shown without the cap. Do not removethe cap until you are ready to administer
the injection.

It is important that you:

• do not usethe pen if the outer package seal or the pen safety seal is broken;
• keep the pen in the sealed outer packaging until you are ready to use it;
• never leavethe pen unattended where it could be tampered with by others;
• do not usethe pen if it has been dropped, appears damaged, or if it has been dropped after you removed the cap;
• injectHefiya 15-30 minutes after taking it out of the refrigerator, for a more comfortable injection;
• dispose of the used pen immediately after use. Do not reuse the pen.See “4. Disposal of used pens”at the end of these Instructions for Use.

How should you store the pen?

• Store the pen in the packaging in a refrigerator, at a temperature between 2° and 8°C.
• When necessary, for example when travelling, Hefiya can be stored at room temperature (up to 25°C) for a maximum period of 42 days - make sure to protect the medicine from light. Once it has been removed from the refrigerator for storage at room temperature, the pre-filled pen must be used within 42 days or discarded, even if it is subsequently placed back in the refrigerator.
• You must record the date on which the pre-filled pen is removed from the refrigerator for the first time and the date after which it must be discarded.
• Store the pen in the original packaging until you are ready to use it, to protect the medicine from light.
• Do not store the pen at extremely high or low temperatures.
• Do not freeze the pen.

Keep Hefiya and all medicines out of the reach of children.
What is needed for the injection?
Place the following items on a clean, flat surface.
The package contains:

• Hefiya pre-filled pen(s) (see Figure A). Each pen contains 80 mg/0.8 mL of adalimumab.

The pen package does not contain (see Figure B):

• Alcohol swab.
• Cotton ball or gauze.
• Sharps container. See “8. Disposal of used pens”at the end of these Instructions for Use.
• Adhesive bandage.

Figure B:items not included in the package

Before the injection
Preparing the pen

• For a more comfortable injection, remove the pen from the refrigerator about 15-30 minutes before the injection to allow it to reach room temperature.
• Look through the window. The solution should be colourless or slightly yellowish and from clear to slightly opalescent. Do not usethe pen if you notice particles and/or colour changes. You may notice some air bubbles. This is normal. If you have any doubts about the appearance of the solution, ask your pharmacist for assistance.
• Check the expiry date (Exp.) on the pen (see Figure C). Do not use the pen if the expiry date has passed.
• Do not use the pen if the safety seal is broken.

Ask your pharmacist if the pen does not pass
any of the checks above.

Figure C:safety checks before
the injection

1. Choice of injection site:

• The recommended injection site is the front of the thighs. You can also use the lower part of the abdomen, but not the area within 5 cm around the navel (see Figure D).
• Choose a different site each time you administer an injection.
• Do not inject the medicine into areas where the skin is painful, bruised, reddened, flaky or hardened. Avoid areas with scars or stretch marks. If you suffer from psoriasis, DO NOTinject the medicine directly into areas with psoriasis plaques.

Figure D:how to choose the injection site

2. Injection site cleaning:

• Wash your hands thoroughly with water and soap.
• Using a circular motion, clean the injection site with a swab soaked in alcohol. Allow to dry before administering the injection (see Figure E).
• Do not touch the cleaned area before the injection.

Figure E:how to clean the injection site

3. Removing the pen cap:

• Remove the cap only when you are ready to use the pen.
• Rotate the cap in the direction of the arrows (see Figure F).
• Once the cap is removed, discard it. Nevertry to put the cap back on.
• Use the pen within 5 minutes of removing the cap.
• You may notice a few drops of liquid coming out of the needle. This is normal.

Figure F:how to remove the cap

4. How to hold the pen:

• Hold the pen at 90 degrees to the clean injection site (see Figure G).

CorrectIncorrect
Figure G:how to hold the pen

Injection
Read before performing the injection
During the injection you will feel 2 clicks:
o The first clickindicates that the injection has started.
o A moment later, a second clickindicates that the injection is almostfinished.
You must keep the pen pressed firmly against the skin until you see a green
indicatorfill the window and stop moving.

5. Start of the injection:

• Press the pen firmly against the skin to start the injection (see Figure H).
• The first clickindicates that the injection has started.
• Keep pressingthe pen firmly against the skin.
• The green indicatorshows the progress of the injection.

Figure H:how to start the injection

6. Completion of the injection:

• Pay attention to the second clickwhich indicates that the injection is almostcomplete.
• Check that the green indicatorfills the window and has stopped moving (see Figure I).
• You can now remove the pen.

Figure I:how to complete the injection

After the injection

7. Check that the green indicator

fills the window(see Figure J) :

• This means that the medicine has been administered. Contact your doctor if the green indicator is not visible.
• You may notice a small amount of blood at the injection site. You can press a cotton ball or gauze on the injection site and hold it for 10 seconds. Do not rub the injection site. If necessary, you can cover the injection site with a small adhesive bandage.

Figure J:how to check the green indicator

8. Disposal of used pens:

• Dispose of the used pen in a sharps container (a closable, puncture-resistant container, see Figure K). For your safety and the safety of others, used pens must never be reused.
• Do not dispose of any medicine down the drain or in household waste. Ask your doctor or pharmacist how to dispose of medicines you no longer use. This will help protect the environment. The unused medicine and waste derived from that medicine must be disposed of in accordance with local regulations. Figure K:how to dispose of the used pen

If you have any doubts, please contact a doctor, pharmacist, or nurse familiar with
Hefiya.