AVTOZMA 20 mg /Ml Concentrate For Infusion Solution

Зміст інструкції

1. Avtozma 20 mg/mL concentrate for solution for infusion
   1. What is Avtozma and what is it used for
   2. What you need to know before you are given Avtozma
   3. How Avtozma is administered
   4. Possible side effects
   5. How to store Avtozma
   6. Contents of the pack and other information
2. Avtozma 162 mg injectable solution in pre-filled syringe
   1. What is Avtozma and what is it used for
   2. What you need to know before you use Avtozma
   3. How to use Avtozma
   4. Possible side effects
   5. How to store Avtozma
   6. Package contents and other information
   7. Instructions for Use
   8. Obtain everything necessary for the injection.
   9. Inspect the package
   10. Inspect the pre-filled syringe.
   11. Wait 30 minutes.
   12. Inspect the medicine.
   13. Wash your hands.
   14. Choose an appropriate injection site (see
   15. Clean the injection site.
   16. Remove the cap.
   17. Insert the prefilled syringe into the
   18. Perform the injection.
   19. Remove the pre-filled syringe from the site of
   20. Injection site care.
   21. Disposal of the pre-filled syringe.
   22. Injection Recording.
3. Avtozma 162 mg injectable solution in a pre-filled pen
   1. What is Avtozma and what is it used for
   2. What you need to know before you use Avtozma
   3. How to use Avtozma
   4. Possible side effects
   5. How to store Avtozma
   6. Contents of the pack and other information
   7. Instructions for Use
   8. Obtain everything necessary for the injection.
   9. Inspect the package
   10. Inspect the prefilled pen.
   11. Wait 45 minutes.
   12. Inspect the medicine.
   13. Wash your hands.
   14. Choose an appropriate injection site (see
   15. Clean the injection site.
   16. Remove the cap.
   17. Insert the prefilled pen into the injection site.
   18. Perform the injection.
   19. Remove the prefilled pen from the site of
   20. Injection site care.
   21. Disposal of Avtozma.
   22. Injection Recording.

Avtozma 20 mg/mL concentrate for solution for infusion

tocilizumab

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before this medicine is given to you as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you only.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

contains important safety information that you must know before you are
given Avtozma and during treatment with Avtozma.

Contents of this leaflet:

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

1. What is Avtozma and what is it used for

Avtozma contains the active substance tocilizumab, a protein produced by specific immune cells (monoclonal antibody), which blocks the action of a specific protein (cytokine) called interleukin-6. This protein is involved in the body's inflammatory processes and blocking it can reduce inflammation in your body. Avtozma helps to reduce symptoms such as pain and swelling of the joints and can also improve your performance in daily activities. Avtozma has been shown to slow down damage to the cartilage and bone of the joints caused by the disease and to improve your ability to perform normal daily activities.

• Avtozma is used to treat adultswith moderate to severe active rheumatoid arthritis (RA), an autoimmune disease, if previous therapies have not worked well enough. Avtozma is usually used in combination with methotrexate. Avtozma can also be used alone if your doctor believes that methotrexate is inappropriate.
• Avtozma can also be used to treat adult patients who have not previously been treated with methotrexate if they suffer from severe, active and progressive rheumatoid arthritis.
• Avtozma is used to treat children with systemic JIA. Avtozma is used for children aged 2 years and older who have active systemic juvenile idiopathic arthritis (SJIA), an inflammatory disease that causes pain and swelling of one or more joints, accompanied by fever and rash. Avtozma is used to improve the symptoms of SJIA and can be given in combination with methotrexate or alone.
• Avtozma is used in children with polyarticular JIA.Avtozma is used for children aged 2 years and older with active polyarticular juvenile idiopathic arthritis (pJIA), an inflammatory disease that causes pain and swelling of one or more joints. Avtozma is used to improve the symptoms of pJIA and can be given in combination with methotrexate or alone.
• Avtozma is used to treat adults and childrenaged 2 years and older with severe or potentially life-threatening cytokine release syndrome (CRS), an adverse effect that affects patients undergoing CAR-T (chimeric antigen receptor T-cell) cell-based therapies used to treat certain malignant tumors.
• Avtozma is used to treat adultswith 2019 coronavirus disease (COVID-19) undergoing systemic corticosteroid therapy and who require supplemental oxygen or mechanical ventilation.

2. What you need to know before you are given Avtozma

You will not be given Avtozma

• if you are allergicto tocilizumab or any of the excipients of this medicine (listed in section 6) (see special warnings at the end of this paragraph under the heading “Avtozma contains polysorbate”)
• if you have a serious active infection. If any of these apply to you, tell your doctor or the nursing staff administering the infusion.

Warnings and precautions
Tell your doctor or nurse before you are given Avtozma.

• If you experience allergic reactions, such as chest tightness, wheezing, severe dizziness, a feeling of faintness, swelling of the lips or skin rash during or immediately after the infusion, tell your doctor immediately.
• If you have an infectionof any kind, whether short-term or long-term, or if you get infections frequently. Tell your doctor immediatelyif you feel unwell. Avtozma can reduce the body's ability to fight infections and may worsen an existing infection or increase your chances of getting a new infection.
• If you have had tuberculosis,tell your doctor. The doctor will check for signs and symptoms of tuberculosis before starting treatment with Avtozma. If symptoms of tuberculosis (persistent cough, weight loss, fatigue, low-grade fever), or any other infection appear during or after treatment, tell your doctor immediately.
• If you have a history of intestinal ulcersor diverticulitis, tell your doctor. Symptoms may include abdominal pain and unexplained changes in your usual bowel habits accompanied by fever.
• If you have a liver disease, tell your doctor. Your doctor may want to do a blood test to check your liver function before using Avtozma.
• If a patient has been recently vaccinated(whether an adult or a child), or plans to be vaccinated, tell your doctor. All patients, especially children, should be up to date on all vaccinations before starting treatment with Avtozma, unless it is necessary to start urgently. Some types of vaccines should not be used during treatment with Avtozma.
• If you have a cancer, tell your doctor. The doctor will need to decide if you can still receive Avtozma.
• If you have cardiovascular risk factorssuch as high blood pressure or high cholesterol levels, tell your doctor. These factors should be monitored while you take Avtozma.
• If you have moderate to severe kidney problems, your doctor will monitor you.
• If you have persistent headaches.

Your doctor will perform blood tests before giving you Avtozma and during treatment,
to determine if you have a low number of white blood cells or platelets, or an elevated
level of liver enzymes.

Children and adolescents
The use of Avtozma is not recommended in children under 2 years of age.
If a child has a history of macrophage activation syndrome(uncontrolled activation and proliferation
of specific blood cells), tell your doctor. They will need to decide if the patient
can still receive Avtozma.

Other medicines and Avtozma
Tell your doctor if you are taking any other medicines (or your child is, if they are
the patient) or if you have recently taken any, including medicines available without a prescription.
Avtozma can affect how some medicines work and the dose of these medicines may
need to be adjusted. Tell your doctorif you are using medicines that contain the following
active ingredients:

• methylprednisolone, dexamethasone used to reduce inflammation
• simvastatin or atorvastatin, used to reduce cholesterol levels
• calcium channel blockers (e.g. amlodipine), used to treat high blood pressure
• theophylline, used to treat asthma
• warfarin or phenprocoumon, anticoagulants used to thin the blood
• phenytoin, used to treat convulsions
• cyclosporine, used to suppress the immune systemduring organ transplantation
• benzodiazepines (e.g. temazepam), used to treat anxiety.

Due to the lack of clinical experience, tocilizumab is not indicated for use with other biological drugs
for the treatment of RA, systemic juvenile idiopathic arthritis or polyarticular juvenile idiopathic arthritis.

Pregnancy, breastfeeding and fertility
Avtozma should not be used during pregnancyunless absolutely necessary.
Tell your doctor if you are pregnant, if you might become pregnant or if you are planning a pregnancy.

Women of childbearing potentialmust use effective contraception during and for up to 3 months after
treatment.

Stop breastfeeding if you are about to be given Avtozmaand tell your doctor.
At least 3 months must pass after the last dose of Avtozma before breastfeeding is started.
It is not known whether Avtozma passes into breast milk
Available data currently do not indicate an effect on fertility from this treatment.

Driving and using machines
This medicine can cause dizziness. If you feel dizzy, do not drive or use machines.

Avtozma contains polysorbate
This medicine contains 0.5 mg of polysorbate 80 per mL. Polysorbates can cause
allergic reactions. Tell your doctor if you have known allergies.

3. How Avtozma is administered

This medicine is subject to limited medical prescription by the doctor.
Avtozma will be administered drop by drop into a vein by a doctor or nurse.They will dilute
a solution, prepare the intravenous infusion and monitor it during and after
administration.

Adult patients with AR
The usual dose of Avtozma is 8 mg per kg of body weight. Depending on your response, the doctor
may reduce the dose to 4 mg/kg and return it to 8 mg/kg when appropriate.
Adult patients will receive Avtozma every 4 weeks through a drop-by-drop injection into a
vein (intravenous infusion) for one hour.

Children with AIGs (aged 2 years or older)
The usual dose of Avtozma depends on body weight.

• If the body weight is less than 30 kg: the dose is 12 mg for each kilogram of bodyweight.
• If the body weight is 30 kg or more: the dose is 8 mg for each kilogram of body weight. The dose is calculated based on body weight with each administration.

Children with AIGs will receive Avtozma every 2 weeks through an injection
drop by drop into a vein (intravenous infusion) for one hour.

Children with AIGp (aged 2 years or older)
The usual dose of Avtozma depends on body weight.

• If the body weight is less than 30 kg: the dose is 10 mg for each kilogram of weightbody.
• If the body weight is 30 kg or more: the dose is 8 mg for each kilogram of body weightThe dose is calculated based on body weight with each administration

Children with AIGp will receive Avtozma every 4 weeks through a drop-by-drop injection into a
vein (intravenous infusion) for one hour.

Patients with CRS
In patients weighing 30 kg or more, the usual dose of Avtozma is 8 mg for each
kilogram of body weight.

In patients weighing less than 30 kg, the dose is 12 mg for each kilogram of weight
body.
Avtozma can be given alone or in combination with corticosteroids.

Patients with COVID-19
The indicated dose of Avtozma is 8 mg for each kilogram of body weight. A second dose may
be necessary.

If you are given too much Avtozma
Since Avtozma will be administered by a doctor or nurse, it is unlikely that
you will be given too much. However, if you have any concerns, contact your doctor.

If you do not receive a dose of Avtozma
Since Avtozma will be administered by a doctor or nurse, it is unlikely that
you will miss a dose. However, if you have any concerns, contact your doctor or nurse.

If you stop treatment with Avtozma
You should not stop treatment with Avtozma without first talking to your doctor.
If you have any doubts about the use of this medicine, contact your doctor or nurse.

4. Possible side effects

Like all medicines, Avtozma can cause side effects, although not everybody gets them.
Side effects can occur up to 3 months after the last dose of Avtozma.

Possible serious common side effects:report to your doctor immediately.

These are common: they may affect up to 1 in 10 people

Allergic reactionsduring or after the infusion:

• difficulty breathing, chest tightness or dizziness
• skin rash, itching, hives, swelling of the lips, tongue or face If you notice any of these symptoms, tell your doctor immediately.

Signs of serious infections

• fever and chills
• blisters in the mouth or on the skin
• stomach pain

Signs and symptoms of liver toxicity

These may affect up to 1 in 1000 people

• fatigue
• abdominal pain
• jaundice (yellowing of the skin and the white of the eyes)

If you notice any of these symptoms, tell your doctor as soon as possible.
Very common side effects

These may affect more than 1 in 10 people

• upper respiratory tract infections with typical symptoms such as cough, stuffy nose, runny nose, sore throat and headache
• high levels of fats in the blood (cholesterol).

Common side effects

These may affect up to 1 in 10 people

• lung infection (pneumonia)
• shingles (herpes zoster)
• cold sores (oral herpes simplex), blister formation
• skin infections (cellulitis) sometimes associated with fever and chills
• skin rash and itching, hives
• allergic reactions (hypersensitivity)
• eye infection (conjunctivitis)
• headache, dizziness, high blood pressure
• mouth ulcers, stomach pain
• fluid retention (edema) in the lower legs, weight gain
• cough, shortness of breath
• low number of white blood cells (neutropenia, leukopenia) detected through blood tests
• abnormalities in liver function tests (increased transaminases)
• increased bilirubin as shown in blood tests
• low levels of fibrinogen in the blood (a protein involved in blood clotting).

Uncommon side effects

These may affect up to 1 in 100 people

• diverticulitis (fever, nausea, diarrhea, constipation, stomach pain)
• red and swollen areas in the mouth
• high levels of fats in the blood (triglycerides)
• gastric ulcer
• kidney stones
• hypothyroidism

Rare side effects

These may affect up to 1 in 1000 people

• Stevens-Johnson syndrome (skin rash, which may involve severe blistering and peeling of the skin)
• life-threatening allergic reactions (anaphylaxis [fatal])
• inflammation of the liver (hepatitis), jaundice

Very rare side effects

These may affect up to 1 in 10,000 people

• low number of white blood cells, red blood cells and platelets in blood tests
• liver failure

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. 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.

Children with AIGs
In general, side effects of a similar type to those in adult patients with AR have been observed in patients with AIGs. Some side effects have been observed more frequently: inflammation of the nose and throat, diarrhea, low white blood cells and increased liver transaminases.

Children with AIGp
In general, the side effects in AIGp patients were similar to those observed in adult patients with AR. Some side effects were observed more frequently: inflammation of the nose and throat, headache, feeling unwell (nausea) and low white blood cells.

5. How to store Avtozma

Keep Avtozma out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
If necessary, the infusion solution diluted with sodium chloride 0.9% injectable solution or
with sodium chloride 0.45% injectable solution may be stored in a refrigerator for a maximum
of 1 month or at room temperature not exceeding 30 °C for a maximum of 48 hours.
Do not dispose of any medicine in waste water 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 Avtozma contains

• The active substance is tocilizumab. Each 4 mL vial contains 80 mg of tocilizumab (20 mg/mL). Each 10 mL vial contains 200 mg of tocilizumab (20 mg/mL). Each 20 mL vial contains 400 mg of tocilizumab (20 mg/mL).
• The excipients are L-histidine, L-threonine, L-methionine, polysorbate 80 and water for injections.

Description of Avtozma and contents of the pack
Avtozma is a concentrate for solution for infusion. The concentrate is a liquid of appearance from
clear to slightly opalescent, from colourless to light yellow.
Avtozma is supplied in vials containing 4 mL, 10 mL and 20 mL of concentrate for solution for
infusion. Packs of 1 and 4 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B torony
Hungary

Manufacturer
Nuvisan France SARL
2400, Route des Colles,
06410, Biot,
France
Midas Pharma GmbH
Rheinstr. 49,
55218 Ingelheim,
Germany
KYMOS S.L.
Ronda Can Fatjó, 7B.
08290 Cerdanyola del Vallès,
Barcelona,
Spain
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Celltrion Healthcare Belgium BVBA
Tél/Tel: +32 2 643 71 81
[email protected]

Lietuva
Celltrion Healthcare Hungary Kft.
Tel.: +36 1 231 0493

Luxembourg/Luxemburg
Celltrion Healthcare Belgium BVBA
Tél/Tel: +32 2 643 71 81
[email protected]

Česká republika
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

България
Celltrion Healthcare Hungary Kft.
Teл.: +36 1 231 0493

Magyarország
Celltrion Healthcare Hungary Kft.
Tel:. +36 1 231 0493

Danmark
Celltrion Healthcare Hungary Kft.
Tlf: +36 1 231 0493

Malta
Mint Health Ltd.
Tel: +356 2093 9800

Deutschland
Celltrion Healthcare Deutschland GmbH
Tel: +49(0)30 346494150
[email protected]

Nederland
Celltrion Healthcare Netherlands B.V.
Tel: + 31 20 888 7300
[email protected]

Eesti
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Norge
Celltrion Healthcare Hungary Kft.
Tlf: +36 1 231 0493

España
CELLTRION FARMACEUTICA (ESPAÑA)
S.L.
Tel: +34 919 94 23 90

Österreich
Astro-Pharma GmbH
Tel: +43 1 97 99 860

Ελλάδα
ΒΙΑΝΕΞ Α.Ε.
Τηλ: +30 210 8009111

Polska
Celltrion Healthcare Hungary Kft.
Tel.: +36 1 231 0493

France
Celltrion Healthcare France SAS
Tél.: +33 (0)1 71 25 27 00

Portugal
CELLTRION PORTUGAL, UNIPESSOAL
LDA.
Tel: +351 21 936 8542

Hrvatska
Oktal Pharma d.o.o.
Tel: +385 1 6595 777

România
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Ireland
Celltrion Healthcare Ireland Limited
Tel: +353 1 223 4026

Slovenija
OPH Oktal Pharma d.o.o.
Tel.: +386 1 519 29 22

Ísland
Celltrion Healthcare Hungary Kft.
Sími: +36 1 231 0493

Slovenská republika
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Italia
Celltrion Healthcare Italy S.r.l.
Tel: +39 02 47927040

Suomi/Finland
Celltrion Healthcare Finland Oy.
Puh/Tel: +358 29 170 7755

Κύπρος
C.A. Papaellinas Ltd
Τηλ: +357 22741741

Sverige
Celltrion Sweden AB
[email protected]

Latvija
Celltrion Healthcare Hungary Kft.
Tālr.: +36 1 231 0493

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

The following information is intended exclusively for healthcare professionals:
Instructions for dilution before administration
Medicinal products to be administered parenterally must be visually inspected before
administration to exclude the presence of particulate matter or signs of colour change. Only solutions
appearing from clear to slightly opalescent, from colourless to light yellow, and free from visible
particles should be diluted. Use a sterile needle and syringe to prepare Avtozma.
For polyvinyl chloride (PVC) infusion bags, bags free of di-2-ethylhexyl phthalate (DEHP-free) must be used.

Adult patients with AR, COVID-19 and CRS (≥ 30 kg)
Under aseptic conditions, draw a volume of sterile, non-pyrogenic sodium chloride solution 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) from a 100 mL infusion bag equal to the volume of Avtozma concentrate necessary for the patient’s dose. The required amount of Avtozma
concentrate (0.4 mL/kg) must be drawn from the vial and introduced into the 100 mL infusion bag. The final volume must be 100 mL. To mix the solution, gently invert
the infusion bag to avoid foam formation.

Use in the paediatric population
Patients with AIGs, AIGp and CRS weighing ≥ 30 kg
Under aseptic conditions, draw a volume of sterile, non-pyrogenic sodium chloride solution 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) from a 100 mL infusion bag equal to the volume of Avtozma concentrate necessary for the patient’s dose. The required amount of Avtozma
concentrate ( 0.4 mL/kg) must be drawn from the vial and introduced into the 100 mL infusion bag. The final volume must be 100 mL. To mix the solution, gently invert
the infusion bag to avoid foam formation.

Patients with AIGs and CRS weighing < 30 kg
Under aseptic conditions, draw a volume of sterile, non-pyrogenic sodium chloride solution 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) from a 50 mL infusion bag equal to the volume of
Avtozma concentrate necessary for the patient’s dose. The required amount of Avtozma concentrate
( 0.6 mL/kg) must be drawn from the vial and introduced into the 50 mL infusion bag. The
final volume must be 50 mL. To mix the solution, gently invert the infusion bag
to avoid foam formation.

Patients with AIGp weighing < 30 kg
Under aseptic conditions, draw a volume of sterile, non-pyrogenic sodium chloride solution 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) from a 50 mL infusion bag equal to the volume of
Avtozma concentrate necessary for the patient’s dosage. The required amount of Avtozma
concentrate (0.5 mL/kg) must be drawn from the vial and introduced into the 50 mL infusion bag. The final volume must be 50 mL. To mix the solution, gently invert
the infusion bag to avoid foam formation.
Avtozma is for single use.
Unused medicinal product and waste materials derived from such medicinal product should be disposed of in accordance with
local regulations.

Avtozma 162 mg injectable solution in pre-filled syringe

tocilizumab

Medicinal product subject to additional monitoring. This will allow the rapid identification of new safety information. You can contribute by reporting any adverse effects encountered during the use of this medicine. See the end of section 4 for information on how to report adverse effects.

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• 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 may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4

contains important safety information that you must know before you are administered Avtozma and during treatment with Avtozma.

Contents of this leaflet:

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

1. What is Avtozma and what is it used for

Avtozma contains the active substance tocilizumab, a protein produced by specific immune cells
(monoclonal antibody) that blocks the action of a specific protein (cytokine) called
interleukin-6. This protein is involved in the body's inflammatory processes and blocking it
can reduce inflammation in your body. Avtozma is used to treat:

• adults with active moderate to severe rheumatoid arthritis (RA), an autoimmune disease, if previous therapies have not worked well enough.
• adults with severe, active and progressive rheumatoid arthritis (RA), who have not previously been treated with methotrexate.

Avtozma helps to reduce the symptoms of RA, such as pain and swelling of the joints, and
can also improve your ability to perform daily activities. Avtozma has been shown
to slow down damage to the cartilage and bone of the joints caused by the disease and to
improve your ability to perform normal daily activities. Avtozma is usually used in combination with another medicine for RA called
methotrexate. Avtozma can still be used alone if the doctor decides that
treatment with methotrexate is inappropriate.

• adults with an artery disease called giant cell arteritis (GCA), caused by inflammation of the larger arteries in the body, especially those that carry blood to the head and neck. Symptoms include headache, fatigue, and pain in the jaw/jawbone. Effects can include stroke and blindness.

Avtozma can reduce the pain and swelling of arteries and veins in the head, neck, and
arms.
GCA is often treated with medicines called steroids, which are generally effective, but
can cause unwanted effects if used at high doses for prolonged periods. In addition, the
reduction of the steroid dose can cause a flare-up of GCA. Adding
Avtozma to the treatment means being able to use steroids for a shorter period, while still keeping
GCA under control.

• children and adolescents, 1 year of age and older, with active systemic juvenile idiopathic arthritis (SJIA), an inflammatory disease that causes pain and swelling in one or more joints, as well as fever and rash.

Avtozma is used to determine an improvement in the symptoms of SJIA. It can be
administered in combination with methotrexate or alone.

• children and adolescents, 2 years of age and older, with active polyarticular juvenile idiopathic arthritis (pJIA), an inflammatory disease that causes pain and swelling in one or more joints.

Avtozma is used to determine an improvement in the symptoms of pJIA. It can be
administered in combination with methotrexate or alone.

2. What you need to know before you use Avtozma

Do not use Avtozma

• if you or a pediatric patient under your care are allergic to tocilizumab or any of the excipients of this medicine (listed in section 6) (see the special warnings at the end of this paragraph under the heading “Avtozma contains polysorbate”).
• if you or a pediatric patient under your care has a severe active infection.

If any of these conditions apply to you, tell your doctor. Do not use Avtozma.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you use Avtozma.

• If you experience allergic reactions, such as chest tightness, wheezing, severe dizziness or a feeling of faintness, swelling of the lips, tongue, skin itching or facial itching, hives or rash during the injection or immediately afterwards, tell your doctor immediately.
• If you experience any symptoms indicative of an allergic reaction after receiving Avtozma, do not take the next dose until you have informed your doctor AND they have told you to take it.
• If you have an infectionof any type, short-term or long-term, or if you have frequent infections. Tell your doctor immediatelyif you feel unwell. Avtozma may reduce the body's ability to respond to infections and could worsen an existing infection or increase the chances of developing a new infection.
• If you have had tuberculosis, tell your doctor. The doctor will look for signs and symptoms of tuberculosis before starting therapy with Avtozma. If symptoms of tuberculosis (persistent cough, weight loss, fatigue, low-grade fever) or any other infection appear during or after therapy, tell your doctor immediately.
• If you have had intestinal ulcersor diverticulitis, tell your doctor. Symptoms may include abdominal pain and unexplained changes in bowel habits accompanied by fever.
• If you have a liver disease, tell your doctor. Your doctor may want to do a blood test to check your liver function before you use Avtozma.
• If a patient has been recently vaccinated or plans to be vaccinated, tell your doctor. All patients should be up to date with all vaccinations before starting treatment with Avtozma. Some types of vaccines should not be given during therapy with Avtozma.
• If you have cancer, tell your doctor. The doctor will need to decide if you can still receive Avtozma.
• If you have cardiovascular risk factorssuch as high blood pressure or high cholesterol levels, tell your doctor. These factors should be monitored while you take Avtozma.
• If you have moderate to severe kidney problems, your doctor will monitor you.
• If you have persistent headache.

Your doctor will perform a blood test before giving you Avtozma, to determine if
you have a low number of white blood cells or platelets, or a high level of liver
enzymes.

Children and adolescents
The use of Avtozma in the subcutaneous injectable solution is not recommended in children under
1 year of age. Avtozma should not be given to children with JIA weighing
less than 10 kg.
If a child has a history of macrophage activation syndrome(uncontrolled activation and
proliferation of specific blood cells), tell your doctor. They will need to decide
whether the patient can still be treated with Avtozma.

Other medicines and Avtozma
Tell your doctor if you are taking any other medicines or if you have recently taken any.
Avtozma may affect the way some medicines work and the dose of these may need to
be adjusted. Tell your doctorif you are using medicines that contain the following active ingredients:

• methylprednisolone, dexamethasone used to reduce inflammation
• simvastatin or atorvastatin, used to reduce cholesterol levels
• calcium channel blockers (e.g. amlodipine), used to treat high blood pressure
• theophylline, used to treat asthma
• warfarin or phenprocoumon, anticoagulants used to thin the blood
• phenytoin, used to treat seizures
• cyclosporine, used to suppress the immune system during organ transplantation
• benzodiazepines (e.g. temazepam), used to treat anxiety

Due to the lack of clinical experience, tocilizumab is not indicated for use with other biological drugs
for the treatment of RA, JIA, systemic JIA or giant cell arteritis.

Pregnancy, breastfeeding and fertility
Avtozma should not be used during pregnancyunless strictly necessary. Tell your doctor if you are
pregnant, might become pregnant or are planning a pregnancy.

Women of childbearing potential mustuse effective contraception during and up to 3 months after
treatment.

Stop breastfeeding if you are about to be given Avtozmaand tell your doctor. At least 3 months must
pass after the last dose of Avtozma before breastfeeding is started. It is not known if
Avtozma passes into breast milk

Driving and using machines
This medicine can cause dizziness. If you feel dizzy, do not drive or use machines.

Avtozma contains polysorbate
This medicine contains 0.2 mg of polysorbate 80 per pre-filled syringe. Polysorbates
can cause allergic reactions. Tell your doctor if you have known allergies.

3. How to use Avtozma

Always use this medicine exactly as your doctor, pharmacist or
nurse has instructed. If you are unsure, ask your doctor, pharmacist or nurse.
Treatment will be prescribed and initiated by healthcare professionals experienced in the diagnosis and treatment
of AR, AIGs, AIGp or ACG.

Recommended dose
The dose for adults with AR and ACG is 162 mg (the contents of 1 pre-filled syringe)
administered once a week.

Children and adolescents with AIGs (aged 1 year or older)
The usual dose of Avtozma depends on the patient's weight.

• If the patient weighs less than 30 kg: the dose is 162 mg (the contents of 1 pre-filled syringe) once every 2 weeks.
• If the patient weighs 30 kg or more: the dose is 162 mg (the contents of 1 pre-filled syringe) once a week.

Children and adolescents with AIGp (aged 2 years or older)
The usual dose of Avtozma depends on the patient's weight.

• If the patient weighs less than 30 kg: the dose is 162 mg (the contents of 1 pre-filled syringe) once every 3 weeks.
• If the patient weighs 30 kg or more: the dose is 162 mg (the contents of 1 pre-filled syringe) once every 2 weeks.

Avtozma is administered by injection under the skin ( subcutaneous). Initially, Avtozma may be
administered by your doctor or nurse. However, your doctor may decide that you are able to inject Avtozma yourself. In this case, you will be instructed on how to self-inject Avtozma. Parents and caregivers will be instructed on how to inject Avtozma into
patients who are unable to self-inject the medicine, such as children.
Talk to your doctor if you have any questions about self-administering an injection or about child
administration”.

If you use more Avtozma than you should
Since Avtozma will be administered using a pre-filled syringe, it is unlikely
that you will be given too much. However, if you have any concerns, contact your doctor, pharmacist or nurse.

If an adult with AR or ACG or a child or adolescent with AIGs misses or forgets
a dose
It is very important to use Avtozma exactly as prescribed by your doctor. Keep track of your
next dose.

• If you have forgotten the weekly dose and less than 7 days have passed since the missed dose, administer the dose on the next scheduled day.
• If you have forgotten the dose every other week and less than 7 days have passed since the missed dose, inject the dose as soon as you remember and administer the next dose regularly on the scheduled day and time.
• If you have forgotten the dose and more than 7 days have passed since the missed dose, or if you are unsure when to inject Avtozma, contact your doctor or pharmacist.

If a child or adolescent with AIGp misses or forgets a dose
It is very important to use Avtozma exactly as prescribed by your doctor. Keep track of the
next dose.

• If a dose has been forgotten and less than 7 days have passed since the missed dose, inject the dose as soon as you remember and administer the next dose regularly on the scheduled day and time.
• If a dose has been forgotten and more than 7 days have passed since the missed dose, or if you are unsure when to inject Avtozma, contact your doctor or pharmacist.

If you stop using Avtozma
Do not stop using Avtozma without first talking to your doctor.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or
nurse

4. Possible side effects

Like all medicines, Avtozma can cause side effects, although not everybody gets them.
Side effects may occur up to 3 months or more after stopping Avtozma.

Possible serious common side effects: tell your doctor immediately.

These are common: may affect up to 1 in 10 people

Allergic reactionsduring or after the injection:

• difficulty breathing, chest tightness or dizziness;
• skin rash, itching, hives, swelling of the lips, tongue or face.

If you notice any of these symptoms, tell your doctor immediately.

Signs of serious infections:

• fever and chills
• blisters in the mouth or on the skin
• stomach pain

Signs and symptoms of liver toxicity

These can affect up to 1 in 1000 people

• fatigue
• abdominal pain
• jaundice (yellowing of the skin and the white of the eyes)

If you notice any of these symptoms, tell your doctor as soon as possible.

Very common side effects:

May affect 1 in 10 or more patients

• upper respiratory tract infections with typical symptoms such as cough, stuffy nose, runny nose, sore throat and headache
• high levels of fats in the blood (cholesterol)
• reactions at the injection site.

Common side effects:

May affect up to 1 in 10 patients

• lung infection (pneumonia)
• shingles (herpes zoster)
• cold sores (oral herpes simplex), blister formation
• skin infections (cellulitis) sometimes associated with fever and chills
• skin rash and itching, hives
• allergic reactions (hypersensitivity)
• eye infection (conjunctivitis)
• headache, dizziness, high blood pressure
• mouth ulcers, stomach pain
• fluid retention (edema) in the lower legs, weight gain
• cough, shortness of breath
• low number of white blood cells as shown by blood tests (neutropenia, leucopenia)
• abnormalities in liver function tests (increased transaminases)
• increased bilirubin as shown by blood tests.
• low levels of fibrinogen in the blood (a protein involved in blood clotting).

Uncommon side effects:

May affect up to 1 in 100 patients

• diverticulitis (fever, nausea, diarrhea, constipation, stomach pain)
• red and swollen areas in the mouth
• high levels of fats in the blood (triglycerides)
• gastric ulcer
• kidney stones
• hypothyroidism.

Rare side effects:

These can affect up to 1 in 1000 users

• Stevens-Johnson syndrome (skin rash, which may involve severe blistering and peeling of the skin)
• life-threatening allergic reactions (anaphylaxis [fatal])
• inflammation of the liver (hepatitis), jaundice.

Very rare side effects:

May affect up to 1 in 10,000 patients

• low number of white blood cells, red blood cells and platelets in blood tests
• liver failure.

Side effects in children and adolescents with AIGs or AIGp
Side effects observed in children and adolescents with AIGs or AIGp are generally
similar to those recorded in adults. Some side effects are found more often in
children and adolescents: inflammation of the nose and throat, headache, feeling unwell
(nausea) and low white blood cell counts.
If you experience any of these side effects, tell your doctor, pharmacist or nurse. This

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

5. How to store Avtozma

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 carton and on the label of the
pre-filled syringe (Exp.). The expiry date refers to the last day of the month.
Store in a refrigerator (2°C – 8°C). Do not freeze. Once removed from the refrigerator, the pre-filled syringe
can be stored for a maximum of 3 weeks at a temperature equal to or below
30°C.
Keep the pre-filled syringes in the outer packaging to protect them from light and moisture.
The medicine should not be used if the solution is cloudy or contains particles, if it is not transparent
or has a colour different from yellow, or if any part of the pre-filled syringe appears
damaged.
The syringe should not be shaken. After removing the cap, the injection must be started
within 5 minutes to prevent the medicine from drying out and blocking the needle. If the pre-filled syringe
is not used within 5 minutes of removing the cap, it must be disposed of in a puncture-resistant container
and a new pre-filled syringe used.
If, after inserting the needle, it is not possible to push the plunger, the pre-filled syringe must be discarded
in a puncture-resistant container and a new pre-filled syringe used.

6. Package contents and other information

What Avtozma contains

• The active substance is tocilizumab. Each pre-filled syringe of 0.9 mL contains 162 mg of tocilizumab.
• The other excipients are L-histidine, L-threonine, L-methionine, polysorbate 80 and water for injections.

Description of Avtozma and package contents
Avtozma is an injectable solution. The solution is from transparent to yellow.
Avtozma is supplied in a pre-filled 0.9 mL syringe containing 162 mg of tocilizumab solution
for injection.
The pre-filled syringe of Avtozma for patient use is available in packs
containing:

• 1 pre-filled syringe
• 4 pre-filled syringes
• 12 (3 packs of 4) pre-filled syringes (multiple packs)

Not all pack sizes may be marketed.
Marketing Authorisation Holder
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B tower
Hungary

Manufacturer
Nuvisan France SARL
2400, Route des Colles,
06410, Biot,
France
Midas Pharma GmbH
Rheinstr. 49,
55218 Ingelheim,
Germany
KYMOS S.L.
Ronda Can Fatjó, 7B.
08290 Cerdanyola del Vallès,
Barcelona,
Spain
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Celltrion Healthcare Belgium BVBA
Tél/Tel: +32 2 643 71 81
[email protected]

Lietuva
Celltrion Healthcare Hungary Kft.
Tel.: +36 1 231 0493

България
Celltrion Healthcare Hungary Kft.
Teл.: +36 1 231 0493

Luxembourg/Luxemburg
Celltrion Healthcare Belgium BVBA
Tél/Tel: +32 2 643 71 81
[email protected]

Česká republika
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Magyarország
Celltrion Healthcare Hungary Kft.
Tel:. +36 1 231 0493

Danmark
Celltrion Healthcare Hungary Kft.
Tlf: +36 1 231 0493

Malta
Mint Health Ltd.
Tel: +356 2093 9800

Deutschland
Celltrion Healthcare Deutschland GmbH
Tel: +49 (0)30 346494150
[email protected]

Nederland
Celltrion Healthcare Netherlands B.V.
Tel: + 31 20 888 7300
[email protected]

Eesti
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Norge
Celltrion Healthcare Hungary Kft.
Tlf: +36 1 231 0493

España
CELLTRION FARMACEUTICA (ESPAÑA)
S.L.
Tel: +34 919 94 23 90

Österreich
Astro-Pharma GmbH
Tel: +43 1 97 99 860

Ελλάδα
ΒΙΑΝΕΞ Α.Ε.
Τηλ: +30 210 8009111

Polska
Celltrion Healthcare Hungary Kft.
Tel.: +36 1 231 0493

France
Celltrion Healthcare France SAS
Tél.: +33 (0)1 71 25 27 00

Portugal
CELLTRION PORTUGAL, UNIPESSOAL
LDA.
Tel: +351 21 936 8542

Hrvatska
Oktal Pharma d.o.o.
Tel: +385 1 6595 777

România
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Ireland
Celltrion Healthcare Ireland Limited
Tel: +353 1 223 4026

Slovenija
OPH Oktal Pharma d.o.o.
Tel.: +386 1 519 29 22

Ísland
Celltrion Healthcare Hungary Kft.
Sími: +36 1 231 0493

Slovenská republika
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Italia
Celltrion Healthcare Italy S.r.l.
Tel: +39 02 47927040

Suomi/Finland
Celltrion Healthcare Finland Oy.
Puh/Tel: +358 29 170 7755

Κύπρος
C.A. Papaellinas Ltd
Τηλ: +357 22741741

Sverige
Celltrion Sweden AB
[email protected]

Latvija
Celltrion Healthcare Hungary Kft.
Tālr.: +36 1 231 0493

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

7. Instructions for Use

Read and follow the instructions for use included with your prefilled syringe of Avtozma before starting to use it each time you receive a refill. There may be new information. Before using Avtozma for the first time, a healthcare professional will show you how to do it correctly.

Important Information

• Do notremove the syringe cap until you are ready to inject Avtozma.
• Never attempt to disassemble the prefilled syringe.
• Do notreuse the same syringe.
• Do notshake the prefilled syringe.
• Do notuse the prefilled syringe if it has been dropped or appears damaged.
• Instructions for patients regarding hypersensitivity reactions (or anaphylaxis):If you develop any symptoms during or following an injection, such as, but not limited to, rash, itching, chills, swelling of the face, lips, tongue or throat, chest pain, wheezing, difficulty breathing or swallowing, dizziness or fainting, you should immediately go to the emergency room while not in the clinic.

Storage of Avtozma

• Store unused prefilled syringes in the original packaging and in a refrigerator at a temperature between 2 °C and 8 °C. Do notfreeze.
• Once removed from the refrigerator, Avtozma can be stored for a maximum of 3 weeks at a temperature of 30 °C or below. If not used within 3 weeks, Avtozma must be discarded.
• Keep the prefilled syringe away from direct sunlight.
• Do notremove the prefilled syringe from the original packaging during storage.
• Do notleave the prefilled syringe unattended.
• Keep the prefilled syringe out of the reach of children. Contains small parts.

Parts of the prefilled syringe (see Figure A).

Before useAfter use
Plunger
orange
Grip
white
Observation
window
MedicineNeedle
Needle
shield
Cap
Figure A
Preparing the injection

1. Obtain everything necessary for the injection.

• a.Prepare a clean, flat surface, such as a table or counter, in a well-lit area.
• b.Remove the package containing the prefilled syringe from the refrigerator.
• c.Make sure you have the following items available (see Figure B):
• Package containing the prefilled syringe of Avtozma

Not included in the package:

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

Package
containing the
prefilled
syringe
Cotton ball
or gauze
and alcohol
swab
Bandage
Container
for sharp
objects

Figure B

2. Inspect the package

• a.Examine the package and make sure you have the correct medicine (Avtozma) and dosage.
• b.Check the expiration date printed on the package to ensure it has not passed.

• Do notuse the prefilled syringe if the expiration date has already passed.
• Do notuse the prefilled syringe if you are opening the package for the first time and it seems to have already been opened or is damaged, and check that it is properly sealed.

Figure C

3. Inspect the pre-filled syringe.

• a.Open the package and remove 1 single-dose pre-filled syringe. Return any remaining Avtozma pre-filled syringes in the package to the refrigerator.
• b.Check the expiration date printed on the Avtozma pre-filled syringe ( see Figure D).
• Do notuse the pre-filled syringe if the expiration date has passed. If the expiration date has passed, discard the pre-filled syringe in a sharps container and take a new one.
• c.Check the pre-filled syringe to make sure it is not damaged and there are no signs of liquid leakage.
• Do notuse the pre-filled syringe if it has been dropped, is damaged, or has liquid leakage.

Figure D

4. Wait 30 minutes.

• a.Leave the pre-filled syringe out of its packaging at room temperature (between 20 °C and 25 °C) for 30 minutes to allow it to warm up (see Figure E).
• Do notheat the pre-filled syringe using heat sources such as hot water or a microwave.
• Do notexpose the pre-filled syringe to direct sunlight.
• Do notremove the cap while the pre-filled syringe reaches room temperature.
• If the pre-filled syringe does not reach room temperature, you may experience discomfort and have difficulty pressing the plunger.

30
minutes
Figure E

5. Inspect the medicine.

• a.Hold Avtozma with the cap pointing downwards.
• b.Observe the medicine and make sure the liquid is clear and from colorless to light yellow and that it does not contain particles or flakes (see Figure F).
• Do notuse the prefilled syringe if the liquid is cloudy, discolored, or if it contains particles or flakes. Dispose of the prefilled syringe in a sharps container and use a new one.
• The presence of air bubbles is normal.

Figure F

6. Wash your hands.

• a.Wash your hands thoroughly with water and soap and dry them (see Figure G).

Figure G

7. Choose an appropriate injection site (see

Figure H).

• a.The sites where you can administer the injection are:
• the front of the thighs;
• the abdomen, except for the area within 5 cm around the navel;
• the outer area of the upper arms (only if the injection is administered by the person assisting you or the healthcare professional).
• Do notself-administer the injection in the outer area of the upper arms.
• Each time you administer an injection, a different site must be used, at least 2.5 cm away from the area used for the previous injection.
• Do notadminister the injection over moles, scars, bruises, or in areas where the skin appears sore, red, or hardened.
• Do notadminister the injection through clothing.

Figure H

8. Clean the injection site.

• a.Disinfect the injection site using a swab soaked in alcohol and let it dry for about 10 seconds (see Figure I). This will reduce the risk of infection.
• Make sure you do nottouch this area before performing the injection.
• Do notblow on or fan the disinfected area.

Figure I
Injection administration

9. Remove the cap.

• a.Hold the pre-filled syringe in one hand by grasping the body. With the other hand, gently remove the cap by pulling it horizontally (see Figure J). Note: if you are unable to remove the cap, ask the person providing you with assistance or contact your healthcare professional.

• Do nothold the plunger while removing the cap.
• You may notice a drop of liquid on the tip of the needle. This is normal.
• If not used within 5 minutes of removing the needle cap, the pre-filled syringe must be disposed of in a puncture-resistant container or a sharps container, and a new pre-filled syringe must be used.
• b.Immediately dispose of the cap in a sharps container (see step 14“Disposal of the pre-filled syringe” and Figure N) Figure J
• Do notreinsert the cap onto the pre-filled syringe.
• Do nottouch the safety sleeve for the needle located on the tip of the pre-filled syringe to avoid accidental needle stick injury.

10. Insert the prefilled syringe into the

injection site.

• a.With one hand, gently pinch a fold of skin at the injection site.

90°
45°
OK

Note: this operation is important to ensure
that the injection occurs under the skin (in the
adipose tissue) and not at a greater depth (in the
muscle).

O

• Do notpull back the plunger.
• b.Insert the needle to its full length into the skin fold at an angle of inclination between 45° and 90°, making a quick and decisive movement (see Figure K). 90°45°OKNote: choosing the correct angle of inclination is important as it ensures that the medicine is released under the skin (in the adipose tissue); otherwise the injection may be painful and the medicine ineffective. Figure K
• Do nottouch the plunger while inserting the needle into the skin.

11. Perform the injection.

• a.After inserting the needle, release the skin fold.
• b.Slowly press the plunger all the way down, until the entire dose of medication has been administered and the syringe is empty (see Figure L).

• If you are unable to press the plunger down, you must discard the prefilled syringe and use a new prefilled syringe.
• Do notchange the position of the prefilled syringe after starting to inject the medication.
• If the plunger is not pressed completely, the needle shield will not extend to cover the needle when it is withdrawn.
• If the needle is not covered, proceed with caution and dispose of the syringe (see step 14“Disposal of the prefilled syringe”). Figure L

12. Remove the pre-filled syringe from the site of

injection.

• a.When the pre-filled syringe is empty, remove the needle from the injection site and release the plunger until the needle is completely covered by the shield (see Figure M).
• Bleeding events may occur (see phase 13 “Injection site care”).
• If the medicine comes into contact with the skin, wash the area with water.
• Do notreuse the pre-filled syringe.

Figure M
After the injection

13. Injection site care.

• a.If you notice any drops of blood, you can treat the injection site by gently pressing, without rubbing, a cotton ball or gauze onto the site and apply a bandage, if necessary.
• Do notrub the injection site.

14. Disposal of the pre-filled syringe.

• a.Replace the pre-filled syringe into the sharps container immediately after use (see Figure N).

Note: if the injection is administered by another person, that person must be careful when removing the pre-filled syringe and disposing of it to avoid accidental needle stick injury and transmission of infection.

• Do notreuse the pre-filled syringe.
• Do notreplace the cap on the pre-filled syringe.
• Do notdiscard the sharps container in household waste.
• Do notrecycle the sharps container.
• Keep the Avtozma pre-filled syringe and the sharps container out of the reach of children.

Dispose of the full container following the instructions received from your healthcare professional or pharmacist. If you do not have a sharps container, you can use a resealable, puncture-resistant household waste container. Unused medicine and waste from that medicine must be disposed of in accordance with local regulations.

15. Injection Recording.

• a.Note the date, time, and specific body part where you administered the injection. Figure N

Avtozma 162 mg injectable solution in a pre-filled pen

tocilizumab

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• 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 you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

contains important safety information that you must know before you are
given Avtozma and during treatment with Avtozma.

Contents of this leaflet:

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

1. What is Avtozma and what is it used for

Avtozma contains the active ingredient tocilizumab, a protein produced by specific immune cells
(monoclonal antibody) that blocks the action of a specific protein (cytokine) called
interleukin-6. This protein is involved in the body's inflammatory processes and blocking it
can reduce inflammation in your body. Avtozma is used to treat:

• adults with active moderate to severe rheumatoid arthritis (RA), an autoimmune disease, if previous therapies have not worked well enough.
• adults with severe, active and progressive rheumatoid arthritis (RA), who have not previously been treated with methotrexate.

Avtozma helps to reduce the symptoms of RA, such as pain and swelling of the joints, and
can also improve your ability to perform daily activities. Avtozma has been shown
to slow down damage to the cartilage and bone of the joints caused by the disease and to
improve your ability to carry out normal daily activities.
Avtozma is usually used in combination with another medicine for RA called
methotrexate. Avtozma can still be used alone if your doctor decides that
treatment with methotrexate is inappropriate.

• adults with an artery disease called giant cell arteritis (GCA), caused by inflammation of the large arteries in the body, especially those that carry blood to the head and neck. Symptoms include headache, fatigue and pain in the jaw/mandible. Effects can include stroke and blindness.

Avtozma can reduce the pain and swelling of arteries and veins in the head, neck and arms.
GCA is often treated with medicines called steroids, which are generally effective, but
can cause unwanted effects if used at high doses for prolonged periods. In addition, the
reduction of the steroid dose can cause a flare-up of GCA. Adding
Avtozma to the treatment means that steroids can be used for a shorter period, while
keeping GCA under control.

• children and adolescents, 12 years of age and older, with activesystemic juvenile idiopathic arthritis(SJIA), an inflammatory disease that causes pain and swelling in one or more joints, as well as fever and rash.

Avtozma is used to determine an improvement in the symptoms of SJIA. It can be
administered in combination with methotrexate or alone.

• children and adolescents, 12 years of age and older, with activepolyarticular juvenile idiopathic arthritis(pJIA), an inflammatory disease that causes pain and swelling in one or more joints.

Avtozma is used to determine an improvement in the symptoms of pJIA. It can be
administered in combination with methotrexate or alone.

2. What you need to know before you use Avtozma

Do not use Avtozma

• if you or a pediatric patient under your care are allergic to tocilizumab or to any of the other ingredients of this medicine (listed in section 6) (see special warnings at the end of this paragraph under the heading “Avtozma contains polysorbate”).
• if you or a pediatric patient under your care has a severe active infection.

If any of these conditions apply to you, tell your doctor. Do not use Avtozma.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you use Avtozma.

• If you experience allergic reactions, such as chest tightness, wheezing, severe dizziness or a feeling of lightheadedness, swelling of the lips, tongue, skin itching or facial itching, hives or skin rash during the injection or immediately afterwards, tell your doctor immediately.
• If you experience any symptoms indicative of an allergic reaction after receiving Avtozma, do not take the next dose until you have informed your doctor AND they have told you to take it.
• If you have an infectionof any kind, whether short-term or long-term, or if you have frequent infections. Tell your doctor immediatelyif you feel unwell. Avtozma may reduce the body's ability to respond to infections and may worsen an existing infection or increase the chances of developing a new infection.
• If you have had tuberculosis, tell your doctor. The doctor will look for signs and symptoms of tuberculosis before starting therapy with Avtozma. If symptoms of tuberculosis (persistent cough, weight loss, fatigue, mild fever) or any other infection appear during or after therapy, tell your doctor immediately.
• If you have had intestinal ulcersor diverticulitis, tell your doctor. Symptoms may include abdominal pain and unexplained changes in bowel habits associated with fever.
• If you have a liver disease, tell your doctor. Your doctor may want to do a blood test to check your liver function before you use Avtozma.
• If a patient has been recently vaccinatedor plans to be vaccinated, they must inform the doctor. All patients should be up to date on all vaccinations before starting treatment with Avtozma. Some types of vaccines should not be given during therapy with Avtozma.
• If you have a tumor, tell your doctor. The doctor will need to decide whether you can still receive Avtozma.
• If you have cardiovascular risk factorssuch as high blood pressure or high cholesterol levels, tell your doctor. These factors should be monitored while you take Avtozma.
• If you have moderate to severe kidney problems, your doctor will monitor you.
• If you have persistent headache.

The doctor will perform blood tests before giving you Avtozma, to determine if you have
a low number of white blood cells or platelets, or a high level of liver enzymes.

Children and adolescents
The use of Avtozma in a pre-filled pen is not recommended in children under 12 years of age.
Avtozma should not be given to children with AIGs who weigh less than 10 kg.
If a child has a history of macrophage activation syndrome(uncontrolled activation and
proliferation of specific blood cells), tell your doctor. The doctor will
decide whether the patient can still be treated with Avtozma.

Other medicines and Avtozma
Tell your doctor if you are taking or have recently taken any other medicines. Avtozma
can affect the way some medicines work and the dose of these may need to be
adjusted. Tell your doctorif you are using medicines that contain the following active ingredients:

• methylprednisolone, dexamethasone used to reduce inflammation
• simvastatin or atorvastatin, used to lower cholesterol levels
• calcium channel blockers (e.g. amlodipine), used to treat high blood pressure
• theophylline, used to treat asthma
• warfarin or phenprocoumon, anticoagulants used to thin the blood
• phenytoin, used to treat seizures
• cyclosporine, used to suppress the immune system during organ transplantation
• benzodiazepines (e.g. temazepam), used to treat anxiety.

Due to the lack of clinical experience, tocilizumab is not indicated for use with other biological drugs
for the treatment of RA, AIGs, AIGp or ACG.

Pregnancy, breastfeeding and fertility
Avtozma should not be used during pregnancyunless strictly necessary. Tell your doctor if you are
pregnant, if you might become pregnant or if you are planning a pregnancy.

Women of childbearing potential mustuse effective contraception during and up to 3 months after
treatment.

Stop breastfeeding if you are about to be given Avtozmaand tell your doctor. At least 3 months must pass
after the last dose of Avtozma before breastfeeding is started. It is not known whether
Avtozma passes into breast milk.

Driving and using machines
This medicine can cause dizziness. If you feel dizzy, do not drive or use machines.

Avtozma contains polysorbate
This medicine contains 0.2 mg of polysorbate 80 per pre-filled syringe. Polysorbates
can cause allergic reactions. Tell your doctor if you have known allergies.

3. How to use Avtozma

Use this medicine following the instructions of your doctor, pharmacist or
nurse exactly. If you have any doubts, ask your doctor, pharmacist or nurse.
Treatment will be prescribed and initiated by healthcare professionals experienced in the diagnosis and treatment
of AR, AIGs, AIGp or ACG.

Recommended dose
The dose for all adults with AR or ACG is 162 mg (the content of 1 pre-filled pen)
administered once a week.

Adolescents with AIGs (aged 12 years or older)
The usual dose of Avtozma depends on the patient's weight.

• If the patient weighs less than 30 kg: the dose is 162 mg (the content of 1 pre-filled pen) once every 2 weeks.
• If the patient weighs 30 kg or more: the dose is 162 mg (the content of 1 pre-filled pen) once a week.

The pre-filled pen should not be used to treat children under 12 years of age.

Adolescents with AIGp (aged 12 years or older) The usual dose of Avtozma depends
on the patient's weight.

• If the patient weighs less than 30 kg: the dose is 162 mg (the content of 1 pre-filled pen)
• once every 3 weeks.
• If the patient weighs 30 kg or more: the dose is 162 mg (the content of 1 pre-filled pen) once every 2 weeks.

The pre-filled pen should not be used to treat children under 12 years of age.
Avtozma is administered by injection under the skin (subcutaneously). Initially, Avtozma may be
administered by your doctor or nurse. However, your doctor may decide that you are able to inject Avtozma yourself. In this case, you will be instructed on how to self-inject Avtozma. Parents and caregivers of patients will be instructed on how to inject Avtozma into
patients who are unable to self-inject the medicine.
Talk to your doctor if you have any questions about self-administering an injection or
administering an injection in a teenage patient you are caring for. At the end of this

If you use more Avtozma than you should
Since Avtozma will be administered to you using a pre-filled pen, it is unlikely that
you will be given too much. However, if you have any concerns, contact your doctor, pharmacist or
nurse.

If an adult with AR or ACG or an adolescent with AIGs misses or forgets a dose
It is very important that you use Avtozma exactly as prescribed by your doctor. Keep track of your
next dose.

• If you miss your weekly injection within 7 days, take your next scheduled dose.
• If you miss your alternate-week injection within 7 days, take the missed dose as soon as you remember and subsequent doses as scheduled.
• If you miss your weekly or alternate-week injection for more than 7 days or are unsure when to inject Avtozma, call your doctor or pharmacist.

If an adolescent with AIGp misses or forgets a dose
It is very important to use Avtozma exactly as prescribed by your doctor. Keep track of the
next dose.

• If a dose has been missed and less than 7 days have passed since the missed dose, inject a dose as soon as you remember and administer the next one regularly on the scheduled day and time.
• If a dose has been missed and more than 7 days have passed since the missed dose, or you are unsure when to inject Avtozma, contact your doctor or pharmacist.

If you stop treatment with Avtozma
You should not stop treatment with Avtozma without first talking to your doctor.
If you have any further questions about using this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, Avtozma can cause side effects, although not everybody gets them.
Side effects can occur up to 3 months or more after stopping Avtozma.

Serious possible side effects: tell your doctor immediately.

These are common: may affect up to 1 in 10 people

Allergic reactionsduring or after the injection:

• difficulty breathing, chest tightness or dizziness;
• skin rash, itching, hives, swelling of the lips, tongue or face. If you notice any of these symptoms, tell your doctor immediately.

Signs of serious infections:

• fever and chills
• blisters in the mouth or on the skin
• stomach pain

Signs and symptoms of liver toxicity

These can affect up to 1 in 1000 users

• fatigue
• abdominal pain
• jaundice (yellowing of the skin and the white of the eyes)

If you notice any of these symptoms, tell your doctor as soon as possible.

Very common side effects:

May affect 1 in 10 or more patients

• upper respiratory tract infections with typical symptoms such as cough, stuffy nose, runny nose, sore throat and headache
• high levels of fats in the blood (cholesterol)
• reactions related to the injection site.

Common side effects:

May affect up to 1 in 10 patients

• lung infection (pneumonia)
• shingles (herpes zoster)
• cold sores (oral herpes simplex), blister formation
• skin infections (cellulitis) sometimes associated with fever and chills
• skin rash and itching, hives
• allergic reactions (hypersensitivity)
• eye infection (conjunctivitis)
• headache, dizziness, high blood pressure
• mouth ulcers, stomach pain
• fluid retention (edema) in the lower legs, weight gain
• cough, shortness of breath
• low number of white blood cells as shown by blood tests (neutropenia, leucopenia)
• abnormalities in liver function tests (increased transaminases)
• increased bilirubin as shown by blood tests
• low levels of fibrinogen in the blood (a protein involved in blood clotting).

Uncommon side effects:

May affect up to 1 in 100 patients

• diverticulitis (fever, nausea, diarrhea, constipation, stomach pain)
• red and swollen areas in the mouth
• high levels of fats in the blood (triglycerides)
• gastric ulcer
• kidney stones
• hypothyroidism.

Rare side effects:

These can affect up to 1 in 1000 users

• Stevens-Johnson syndrome (skin rash, which may involve severe blistering and peeling of the skin)
• life-threatening allergic reactions (anaphylaxis [fatal])
• inflammation of the liver (hepatitis), jaundice.

Very rare side effects:

May affect up to 1 in 10,000 patients

• low number of white blood cells, red blood cells and platelets in blood tests
• liver failure.

Side effects in children and adolescents with AIGs or AIGp
Side effects observed in children and adolescents with AIGs or AIGp are generally
similar to those recorded in adults. Some side effects are found more often in
children and adolescents: inflammation of the nose and throat, headache, feeling unwell
(nausea) and lower counts of white blood cells.

Reporting of side effects
If you get any side effect, even if not listed in this leaflet, tell your
doctor, pharmacist or nurse. 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 Avtozma

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 pack and on the label of the
pre-filled pen (Exp). The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C-8 °C). Do not freeze. Once removed from the refrigerator, the pen
pre-filled can be stored for a maximum of 3 weeks at a temperature equal to or below
30°C.
Keep the pre-filled pens in the outer packaging to protect them from light and moisture.
The medicine should not be used if the solution is cloudy or contains particles, if it is not transparent
or has a colour different from yellow, or if any part of the pre-filled syringe appears
damaged.
The pen must not be shaken. After removing the cap, the injection must be started
within 3 minutes to prevent the medicine from drying and blocking the needle. If the pre-filled pen is not
used within 3 minutes of removing the cap, it must be disposed of in a puncture-resistant container and a new pre-filled pen used.
If after pressing the needle cover the orange indicator does not move, the pre-filled pen must be discarded in a puncture-resistant container. Do notattempt to reuse the pen
pre-filled. When attempting to reuse it, the pre-filled pen is locked and the needle is covered
inside the needle cover. Do not repeat the injection with another pre-filled pen. Contact
your healthcare professional for assistance.

6. Contents of the pack and other information

What Avtozma contains

• The active substance is tocilizumab. Each pre-filled pen contains 162 mg of tocilizumab in 0.9 mL.
• The other ingredients are L-histidine, L-threonine, L-methionine, polysorbate 80 and water for injections.

Description of Avtozma and contents of the pack
Avtozma is an injectable solution. The solution is from clear to yellow.
Avtozma is supplied in a pre-filled pen containing 0.9 mL with 162 mg of tocilizumab solution
for injection.
The Avtozma pre-filled pen for patient use is available in packs containing:

• 1 pre-filled pen
• 4 pre-filled pens
• 12 (3 packs of 4) pre-filled pens (multipack)

Not all pack sizes may be marketed.
Marketing Authorisation Holder
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B tower
Hungary

Manufacturer
Nuvisan France SARL
2400, Route des Colles,
06410, Biot,
France
Midas Pharma GmbH
Rheinstr. 49,
55218 Ingelheim,
Germany
KYMOS S.L.
Ronda Can Fatjó, 7B.
08290 Cerdanyola del Vallès,
Barcelona,
Spain
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

Lietuva
Celltrion Healthcare Hungary Kft.
Tel.: +36 1 231 0493

България
Celltrion Healthcare Hungary Kft.
Тел.: +36 1 231 0493

België/Belgique/Belgien
Celltrion Healthcare Belgium BVBA
Tél/Tel: +32 2 643 71 81
[email protected]

Luxembourg/Luxemburg
Celltrion Healthcare Belgium BVBA
Tél/Tel: +32 2 643 71 81
[email protected]

Česká republika
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Magyarország
Celltrion Healthcare Hungary Kft.
Tel:. +36 1 231 0493

Danmark
Celltrion Healthcare Hungary Kft.
Tlf: +36 1 231 0493

Malta
Mint Health Ltd.
Tel: +356 2093 9800

Deutschland
Celltrion Healthcare Deutschland GmbH
Tel: +49 (0)30 346494150
[email protected]

Nederland
Celltrion Healthcare Netherlands B.V.
Tel: + 31 20 888 7300
[email protected]

Eesti
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Norge
Celltrion Healthcare Hungary Kft.
Tlf: +36 1 231 0493

España
CELLTRION FARMACEUTICA (ESPAÑA)
S.L.
Tel: +34 919 94 23 90

Österreich
Astro-Pharma GmbH
Tel: +43 1 97 99 860

Ελλάδα
ΒΙΑΝΕΞ Α.Ε.
Τηλ: +30 210 8009111

Polska
Celltrion Healthcare Hungary Kft.
Tel.: +36 1 231 0493

France
Celltrion Healthcare France SAS
Tél.: +33 (0)1 71 25 27 00

Portugal
CELLTRION PORTUGAL, UNIPESSOAL
LDA.
Tel: +351 21 936 8542

Hrvatska
Oktal Pharma d.o.o.
Tel: +385 1 6595 777

România
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Ireland
Celltrion Healthcare Ireland Limited
Tel: +353 1 223 4026

Slovenija
OPH Oktal Pharma d.o.o.
Tel.: +386 1 519 29 22

Ísland
Celltrion Healthcare Hungary Kft.
Sími: +36 1 231 0493

Slovenská republika
Celltrion Healthcare Hungary Kft.
Tel: +36 1 231 0493

Italia
Celltrion Healthcare Italy S.r.l.
Tel: +39 02 47927040

Suomi/Finland
Celltrion Healthcare Finland Oy.
Puh/Tel: +358 29 170 7755

Κύπρος
C.A. Papaellinas Ltd
Τηλ: +357 22741741

Sverige
Celltrion Sweden AB
[email protected]

Latvija
Celltrion Healthcare Hungary Kft.
Tālr.: +36 1 231 0493

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

7. Instructions for Use

Read and follow the instructions for use included with your Avtozma prefilled pen before starting to
use it each time you receive a refill. There may be new information. Before using
Avtozma for the first time, a healthcare professional will show you how to do it correctly.

Important Information

• Do notremove the pen cap until you are ready to inject Avtozma.
• Do notever try to disassemble the prefilled pen.
• Do notreuse the same pen.
• Do notshake the prefilled pen.
• Do notuse the prefilled pen if it has been dropped or appears damaged.
• Patient instructions on hypersensitivity reactions (or anaphylaxis):in the event that, during or following an injection, you develop at any time, while not in the clinic, symptoms such as, but not limited to, skin rash, itching, chills, swelling of the face, lips, tongue or throat, chest pain, wheezing, difficulty breathing or swallowing, dizziness or fainting, you should immediately go to the emergency room.

Storage of Avtozma

• Store the unused prefilled pen in its original packaging and in a refrigerator at a temperature between 2 °C and 8 ºC. Do notfreeze.
• Once removed from the refrigerator, Avtozma can be stored for a maximum of 3 weeks at a temperature equal to or below 30 °C. If not used within 3 weeks, Avtozma must be discarded.
• Keep the prefilled pen away from direct sunlight.
• Do notremove the prefilled pen from its original packaging during storage.
• Do notleave the prefilled pen unattended.
• Keep the prefilled pen out of the reach of children. Contains small parts.

Parts of the Avtozma prefilled pen (see Figure A).

Before use
After use
Expiration date
Body
Indicator
orange

“injection
complete”
Window
Cover
Cover
blue needle
(locked and needle
of the needle
blue (needle
inside)
inside)
Orange
cap

Figure A
Injection preparation

1. Obtain everything necessary for the injection.

• a.Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.
• b.Remove the package containing the prefilled pen from the refrigerator.
• c.Make sure you have the following items available (see Figure B):
• Package containing the prefilled Avtozma pen

Not included in the package:

• Cotton ball or gauze
• Adhesive bandage
• Sharps container
• Alcohol swab

Figure B

2. Inspect the package

• a.Examine the package and make sure you have the correct (Avtozma) medication and dosage.
• b.Check the expiration date printed on the package to ensure it has not passed.

• Do notuse the prefilled pen if the expiration date has already passed.
• If you are opening the package for the first time, make sure it is properly sealed.
• Do notuse the prefilled pen if it seems that the package has been opened or is damaged.

Figure C

3. Inspect the prefilled pen.

• a.Open the package and remove 1 single-dose prefilled pen. Return any remaining Avtozma prefilled pens in the package to the refrigerator.
• b.Check the expiry date printed on the Avtozma prefilled pen ( see Figure D).
• Do notuse the prefilled pen if the expiry date has passed. If the expiry date has passed, discard the prefilled pen in a sharps container and take a new one.
• c.Check the prefilled pen to ensure it is not damaged and there are no signs of liquid leakage.
• Do notuse the prefilled pen if it has been dropped, is damaged, or if there is liquid leakage. Note: a small space between the orange cap and the injector body is normal.

Figure D

4. Wait 45 minutes.

• a.Leave the pre-filled pen out of its case at room temperature (between 20 °C and 25 °C) for 45 minutes to allow it to warm up (see Figure E).
• Do notheat the pre-filled pen using heat sources such as hot water or a microwave.
• Do notexpose the pre-filled pen to direct sunlight.
• Do notremove the cap while the pre-filled pen reaches room temperature.
• If the pre-filled pen does not reach room temperature, you may experience discomfort.

45
minutes
Figure E

5. Inspect the medicine.

• a.Hold Avtozma with the cap pointing downwards.
• b.Observe the medicine and make sure the liquid is from transparent to slightly opalescent and from colorless to yellow and that it does not contain particles or flakes (see Figure F).
• Do notuse the prefilled pen if the liquid is cloudy, discolored, or if it contains particles or flakes. Dispose of the prefilled pen in a sharps container and use a new one.
• The presence of air bubbles is normal.

Figure F

6. Wash your hands.

• a.Wash your hands thoroughly with water and soap and dry them (see Figure G).

Figure G

7. Choose an appropriate injection site (see

Figure H).

• a.The sites where you can administer the injection are:
• the front of the thighs;
• the abdomen, except for the area within 5 cm around the navel;
• the outer area of the upper arms (only if the injection is performed by the person providing assistance or the healthcare professional).

• Do notself-administer the injection in the outer area of the upper arms.
• Each time you administer an injection, a different site must be used, at least 2.5 cm away from the area used for the previous injection.
• Do notinject into moles, scars, bruises, or areas where the skin appears sore, red, or hardened.

Figure H

8. Clean the injection site.

• a.Disinfect the injection site using a swab soaked in alcohol and allow it to dry (see Figure I). This will reduce the risk of infection.
• Make sure you do nottouch this area before performing the injection.
• Do notblow on or fan the disinfected area.

Figure I
Injection administration

9. Remove the cap.

• a.Hold the pre-filled pen in one hand, grasping it by the injector body with the cap inserted. With the other hand, gently pull the cap off horizontally (see Figure J). Note: if you are unable to remove the cap, ask the person assisting you for help or contact your healthcare professional.
• b.Immediately dispose of the cap in a sharps container (see step 14and Figure O)
• Do notreinsert the cap onto the pre-filled pen.
• Do nottouch the needle safety sleeve located on the tip of the pre-filled pen to avoid accidental needle stick injury.
• Once the cap is removed, the pre-filled pen is ready for use. If not used within 3 minutes of cap removal, the pre-filled pen must be disposed of in a sharps container and a new pre-filled pen must be used.

Needle
Cover
Figure J

10. Insert the prefilled pen into the injection site.

• a.With one hand, hold the prefilled pen comfortably so that you can see the window (see Figure K).
• b.Without pinching or pulling the skin, insert the prefilled pen into the skin at a 90° angle (see Figure L).

Note: choosing the correct angle of inclination is
important as it ensures that the medicine is
released under the skin (into the fatty tissue); otherwise
the injection may be painful and the
medicine ineffective.

• Do notinject the medicine into the muscle or into a Figure Kblood vessel.

90°
OR
90°
Figure L

11. Perform the injection.

• a.Press the prefilled pen firmly against the skin to start the injection.
• b.When the injection begins, you will hear the first “click” and the orange indicator will begin to fill the window (see Figure M).
• c.Keep the prefilled pen pressed firmly against the skin until you hear the second “click”.
• d.After hearing the second “click”, continue to keep the prefilled pen pressed firmly against the skin and count slowly to 5to ensure the entire dose is delivered (see Figure M).
• e.Follow the orange indicator until it stops moving and reaches the end of the window to make sure you have injected the complete dose of the medicine. Note: if the orange indicator does not move, discard the prefilled pen and use a new one.

1st
click
2nd
click
Then count
slowly to 5
Figure M

12. Remove the prefilled pen from the site of

injection.

• a.When the orange indicator stops, lift the prefilled pen from the injection site at a 90° angle to extract the needle from the skin.
• The needle cover will automatically emerge and lock, covering the needle (see Figure N). Note: if the window has not completely turned orange or if it is still injecting the medicine, it means you have not received the entire dose. Carefully replace the prefilled pen in a sharps container and contact your healthcare professional immediately.

Figure N• Do nottouch the needle cover of the prefilled pen.

• Do notattempt to reuse the prefilled pen.
• Do notrepeat the injection with another prefilled pen.

After the injection

13. Injection site care.

• a.If you notice any drops of blood, you can treat the injection site by gently pressing, without rubbing, a cotton ball or gauze on the site and apply a bandage, if necessary.
• Do notrub the injection site.

14. Disposal of Avtozma.

• a.Replace the pre-filled pen into the sharps container immediately after use (see Figure O).

Note: if the injection is administered by another person, that person must be careful when removing the pre-filled syringe and disposing of it to avoid accidental needle stick injury and transmission of infection.

• Do notreuse the pre-filled pen.
• Do notreplace the cap on the pre-filled pen.
• Do notdispose of the used sharps container in household waste.
• Do notrecycle the used sharps container.
• Keep the Avtozma pre-filled pen and the sharps container out of the reach of children.
• Dispose of the full container following the instructions received from the healthcare professional or pharmacist. If you do not have a sharps container, you can use a closable and puncture-resistant household waste container. Unused medicine and waste from that medicine must be disposed of in accordance with current local regulations.

15. Injection Recording.

• a.Note the date, time, and specific part of the body where you administered the injection. Figure O