NORDIMET 7.5 mg Injectable solution

Зміст інструкції

1. Nordimet 7.5 mg injectable solution in pre-filled pen, 10 mg injectable solution in pre-filled pen, 12.5 mg injectable solution in pre-filled pen, 15 mg injectable solution in pre-filled pen, 17.5 mg injectable solution in pre-filled pen, 20 mg injectable solution in pre-filled pen, 22.5 mg injectable solution in pre-filled pen
   1. What is Nordimet and what is it used for
   2. What you need to know before using Nordimet
   3. How to use Nordimet
   4. Possible side effects
   5. How to store Nordimet
   6. Package Contents and Other Information
2. Nordimet 7.5 mg injectable solution in pre-filled syringe, 10 mg injectable solution in pre-filled syringe, 12.5 mg injectable solution in pre-filled syringe, 15 mg injectable solution in pre-filled syringe, 17.5 mg injectable solution in pre-filled syringe, 20 mg injectable solution in pre-filled syringe
   1. What is Nordimet and what is it used for
   2. What you need to know before using Nordimet
   3. How to use Nordimet
   4. Possible side effects
   5. How to store Nordimet
   6. Package contents and other information

Nordimet 7.5 mg injectable solution in pre-filled pen, 10 mg injectable solution in pre-filled pen, 12.5 mg injectable solution in pre-filled pen, 15 mg injectable solution in pre-filled pen, 17.5 mg injectable solution in pre-filled pen, 20 mg injectable solution in pre-filled pen, 22.5 mg injectable solution in pre-filled pen

Nordimet 25 mg injectable solution in pre-filled pen
methotrexate

Read this leaflet carefully before you start to use 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 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 you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is Nordimet and what is it used for

Nordimet contains the active ingredient methotrexate which is indicated for:

• reducing inflammation or swelling and
• reducing the activity of the immune system (the body's defense mechanism). An overactive immune system has been linked to inflammatory diseases.

Nordimet is a medicine used to treat various inflammatory diseases:

• active rheumatoid arthritis, in adult patients. Active rheumatoid arthritis is an inflammatory condition affecting the joints;
• severe active juvenile idiopathic arthritis, affecting five or more joints (for this reason the disease is called polyarticular), in patients with inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs);
• moderate to severe plaque psoriasis in adults candidates for systemic therapy as well as severe psoriasis that also affects the joints (psoriatic arthritis) in adult patients;
• inducing remission in adults with moderate Crohn's disease, steroid-dependent, in association with corticosteroids;
• maintaining remission of Crohn's disease, in adults who have responded to methotrexate, as monotherapy.

2. What you need to know before using Nordimet

Do not use Nordimet if:

• you are allergic to methotrexate or any of the other ingredients of this medicine

(listed in section 6)

• you have a severe kidney disease (your doctor will know if you have a severe kidney disease)
• you have a severe liver disease (your doctor will know if you have a severe liver disease)
• you have a dysfunction of the system with which the body produces blood cells
• you consume a lot of alcohol
• your immune system is compromised
• you have a severe or pre-existing infection, e.g., tuberculosis or HIV
• you have a gastrointestinal ulcer
• if you are pregnant or breastfeeding (see section “Pregnancy, breastfeeding and fertility”)
• you are receiving a vaccination with live vaccines at the same time as treatment.

Warnings and precautions
Cases of acute pulmonary bleeding have been reported in patients with rheumatological disease and treated with methotrexate. If you observe blood in your saliva or following coughing fits, contact your doctor immediately.
An enlargement of the lymph nodes (lymphoma) may occur and the therapy must be stopped.
Diarrhea can be a toxic effect of Nordimet and requires discontinuation of therapy. If you suffer from diarrhea, talk to your doctor.
Certain brain disorders (encephalopathy/leucoencephalopathy) have been reported in patients with cancer receiving methotrexate. Such undesirable effects cannot be excluded when methotrexate is used to treat other diseases.
If you, your partner or the person assisting you notices the appearance or worsening of neurological symptoms, including general muscle weakness, visual disturbances, changes in thinking, memory and orientation, resulting in confusion and personality changes, consult your doctor immediately as these may be symptoms of a very rare and serious brain infection called progressive multifocal leukoencephalopathy (PML).
Methotrexate can increase the skin's sensitivity to sunlight. Avoid intense sun exposure and do not use sunbeds or tanning lamps without your doctor's advice. To protect your skin from intense sun exposure, wear appropriate clothing or use a sunscreen with a high protection factor.
Important warnings about the dosage of Nordimet
In the treatment of rheumatic diseases, skin diseases and Crohn's disease, methotrexate must be used once a week. An incorrect dose of methotrexate can cause serious side effects, which can be fatal. Read section 3 of this leaflet very carefully.
Talk to your doctor before using Nordimet if:

• you have diabetes mellitus and are being treated with insulin
• you have inactive, long-lasting infections (e.g., tuberculosis, hepatitis B or C, shingles [herpes zoster])
• you have/have had a liver or kidney disease
• you have problems with lung function
• you are severely overweight
• you have an abnormal accumulation of fluid in the abdomen or in the cavity between the lungs and the chest wall (ascites, pleural effusion)
• you are dehydrated or in a situation that causes dehydration (e.g., dehydration due to vomiting, diarrhea or inflammation of the mouth and lips)

If you have had skin problems after radiation therapy (radiation-induced dermatitis) or a sunburn; these conditions may recur during treatment with Nordimet.
Children, adolescents and the elderly
Instructions on the dose depend on the patient's weight.
Use in children under 3 years of age is not recommended, because there is insufficient data available on the use of this medicine in this age group.
Children, adolescents and the elderly treated with Nordimet must be carefully monitored by the doctor to identify possible side effects as early as possible.
In elderly patients, the dose must be reduced due to the reduction in liver and kidney function caused by age.
Special precautions for treatment with Nordimet
Methotrexate temporarily affects the production of sperm and eggs. Methotrexate can cause abortion and serious birth defects. During treatment with methotrexate and for at least 6 months after the end of treatment with methotrexate, if you are a woman, you must avoid becoming pregnant. If you are a man, during treatment with methotrexate and for at least 3 months after the end of treatment with methotrexate, you must avoid fathering a child. Also consult the section “Pregnancy, breastfeeding and fertility”.
Skin changes caused by psoriasis may worsen during treatment with Nordimet, when exposed to ultraviolet rays.
Recommended check-ups and precautions
Even if methotrexate is used at low doses, serious side effects can occur. To identify them in time, the doctor must perform check-ups and laboratory tests.
Before starting therapy:
Before starting treatment, your blood will be checked to see if you have enough blood cells. Your blood will also be analyzed to check your liver function and to find out if you have hepatitis. In addition, serum albumin (a protein present in the blood), the state of hepatitis (liver infection) and kidney function will be checked. The doctor may also decide to perform other liver tests, some of which may be images of the liver and others may require a small sample of tissue to be taken from the liver for more in-depth examination.
The doctor may also check if you have tuberculosis and may perform a chest X-ray or a pulmonary function test.
During treatment:
The doctor may perform the following tests:

• examination of the oral cavity and pharynx to identify any changes in the mucosa, such as inflammation or ulcerations
• blood tests/blood count with number of blood cells and measurement of methotrexate levels in the serum
• blood tests to monitor liver function
• imaging tests to monitor liver conditions
• small sample of tissue taken from the liver for more in-depth examination
• blood tests to monitor kidney function
• monitoring of the respiratory tract and, if necessary, pulmonary function tests

It is very important that you attend these scheduled examinations.
If the results of one of these tests are significant, the doctor will adjust the treatment accordingly.

Other medicines and Nordimet
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines..
It is especially important that you tell your doctor if you are taking:

• other medicines for rheumatoid arthritis or psoriasis such as leflunomide, sulfasalazine (a medicine that is also used for the treatment of ulcerative colitis, in addition to the treatment of arthritis and psoriasis), aspirin, phenylbutazone or amidopyrine
• cyclosporine (to suppress the immune system)
• azathioprine (medicine used to prevent rejection after an organ transplant)
• retinoids (used for the treatment of psoriasis and other skin diseases)
• anticonvulsant medicines (used to prevent seizures), such as phenytoin, valproate or carbamazepine
• cancer treatments
• barbiturates (injections for anesthesia)
• tranquilizers
• oral contraceptives
• probenecid (used for the treatment of gout)
• antibiotics (e.g. penicillin, glycopeptides, trimethoprim-sulfamethoxazole, sulfonamides, ciprofloxacin, cefalotin, tetracyclines, chloramphenicol)
• pyrimethamine (used for the prevention and treatment of malaria)
• vitamin preparations containing folic acid
• proton pump inhibitors (medicines that reduce the production of stomach acids, used to treat severe heartburn or ulcers), such as omeprazole or pantoprazole
• theophylline (used for the treatment of asthma)
• cholestyramine (used to treat high cholesterol, itching or diarrhea)
• NSAIDs, non-steroidal anti-inflammatory drugs (used to treat pain or inflammation)
• p-aminobenzoic acid (used to treat skin disorders)
• any vaccination with a live vaccine (must be avoided), such as those against measles, mumps or yellow fever
• metamizole (synonyms novaminsulfon and dipyrone) (medicine to relieve severe pain and/or fever)

Nordimet with food, drinks and alcohol
During treatment with Nordimet, you should not drink alcohol and avoid drinking too much coffee, caffeinated beverages and black tea, which may increase side effects or interfere with the effectiveness of Nordimet. In addition, during treatment with Nordimet you should drink plenty of fluids to prevent dehydration (reduction of fluids in the body), which may increase the toxicity of Nordimet.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor before taking this medicine.
Pregnancy
Do not use Nordimet during pregnancy or if you are trying to become pregnant. Methotrexate can cause birth defects, be harmful to the fetus or cause abortion. It is associated with malformations that can affect the skull, face, heart and blood vessels, brain and limbs. Therefore, it is very important that patients who are expecting a child or who desire a pregnancy are not treated with methotrexate. Therefore, in women of childbearing potential, the possibility of pregnancy must be excluded during treatment, by taking appropriate measures, for example, performing a pregnancy test, before starting treatment. During treatment with methotrexate and for at least 6 months after the end of treatment, you must avoid becoming pregnant, using a reliable method of contraception (see also the section “Warnings and precautions”).
If you notice or suspect you are pregnant during treatment, consult your doctor as soon as possible, who will advise you on the risk of harmful effects to the baby for the duration of treatment.
If you wish to become pregnant, you should consult your doctor, who may refer you to a specialist before the planned start of treatment.
Breastfeeding
Do not breastfeed during treatment with methotrexate, as methotrexate passes into breast milk. If your doctor considers treatment with methotrexate absolutely necessary during breastfeeding, you must stop breastfeeding your baby.
Male fertility
Available data do not indicate an increased risk of malformations or abortions if the father takes less than 30 mg of methotrexate per week. However, the risk cannot be completely excluded. Methotrexate may be genotoxic. That is, this medicine can cause genetic mutations. Methotrexate can affect sperm production with the possibility of causing birth defects. Therefore, while using methotrexate and for at least 3 months after the end of treatment, you must avoid fathering a child or donating sperm. Treatment with methotrexate may cause infertility.

Driving and using machines
Side effects on the central nervous system, such as fatigue and dizziness, may occur during treatment with Nordimet. In some cases, the ability to drive vehicles and/or use machines may be impaired. If you feel tired or dizzy, do not drive or use machines.

Nordimet contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.

3. How to use Nordimet

Important warnings about Nordimet dosage
Use Nordimet only once a week for the treatment of rheumatoid arthritis, active juvenile idiopathic arthritis, psoriasis, psoriatic arthritis and Crohn's disease that require a single
weekly dose. Taking an excessive dose of Nordimet can be fatal. Read carefully before
taking this medicine.
Use this medicine following the doctor's instructions exactly. If you have any doubts, consult your
doctor or pharmacist.
Nordimet must be administered only once a week. You can decide with your doctor the
suitable day for the injection, which must be the same every week.
Incorrect administration of methotrexate can cause serious side effects, which can
become fatal.
The recommended dose is:
Dose in adult patients with rheumatoid arthritis
The recommended starting dose is 7.5 mg of methotrexate once a week.
The doctor may increase the dose if the one used is not effective, but well tolerated. The average
weekly dose is 15-20 mg. In general, the weekly dose should not exceed 25 mg. After
obtaining the desired therapeutic effect, the doctor may gradually reduce the dose of Nordimet
until reaching the lowest possible effective dose for maintenance therapy.
Generally, an improvement of symptoms is expected after 4-8 weeks of treatment. Symptoms may
reappear if treatment with Nordimet is stopped.
Use in adult patients with moderate to severe plaque psoriasis and severe psoriatic arthritis.
The doctor will administer a single test dose of 5-10 mg to evaluate the appearance of possible
side effects.
If the test dose is well tolerated, treatment will be continued after one week with a dose of
approximately 7.5 mg.
Generally, a response to treatment is expected after 2-6 weeks. Based on the effects of treatment and the
results of blood and urine tests, therapy should be continued or discontinued.
Dose in adult patients with Crohn's disease:
Your doctor will prescribe an initial weekly dose of 25 mg. Generally, the response to
treatment is predictable after 8-12 weeks. Depending on the effects of treatment over time, your
doctor may decide to reduce the dose to 15 mg/week.
Use in children and adolescents under 16 years of age with polyarticular forms of juvenile
idiopathic arthritis
The doctor will calculate the necessary dose based on the child's body surface area (m²). The
dose is indicated in mg/m².
Use in children under 3 years of age is not recommended due to insufficient data for this
age group.
Method and duration of administration
Nordimet is administered by subcutaneous injection (under the skin). It must be injected once
a week and it is recommended to perform the Nordimet injection always on the same day of the
week.
At the beginning of treatment, Nordimet will be injected by medical personnel. However, your doctor
may decide that you are able to learn how to perform Nordimet injections yourself. In
this case you will receive adequate training. In no case should you attempt to perform the injection by
yourself before receiving adequate training.
The duration of treatment will be established by the attending physician.
Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, plaque psoriasis,
psoriatic arthritis and Crohn's disease with Nordimet is a long-term treatment.

How to perform Nordimet injections yourself
If you have difficulty using the pen, contact your doctor or pharmacist. Do not attempt to perform the injection
yourself if you have not received training on how to do it. If you are unsure about what to do, contact
your doctor or nurse immediately.

Before performing a Nordimet injection yourself

• Check the expiry date of the medicine. Do not use the medicine if the expiry date has passed.
• Verify that the pen is not damaged and that the medicine contained is a transparent, yellow solution. If not, use another pen.
• Check the site of the last injection for redness, changes in skin color, swelling, discharge, or pain. If you notice one or more of these problems, contact your doctor or nurse.
• Decide where to perform the injection. Change the injection site each time.

Instructions on how to perform Nordimet injections yourself

• 1) Wash your hands thoroughly with soap and water.
• 2) Sit or lie down in a relaxed and comfortable position. Make sure that the skin area where you intend to perform the injection is visible.
• 3) The pen is pre-filled and ready to use. Visually inspect the pen. You should see a yellow liquid through the inspection window. You may see a small air bubble, but this does not affect the injection and is not dangerous.

A drop of liquid may appear on the tip of the needle. This is normal.

• 4) Choose a site for the injection and clean it with the alcohol swab included. It takes 30-60 seconds for the disinfection to be effective. Suitable sites for injection are the skin of the abdomen and the front of the thigh.
• 5) Holding the body of the pen with your hand, remove the green protective cap by pulling it straight off the unit, without rotating or bending it. After removing the cap, hold the pen in your hand. The pen must not touch anything to ensure that it is not accidentally activated and that the needle remains clean.

• 6) At the injection site, form a skin fold by pinching the skin between your thumb and index finger. You must maintain the fold for the duration of the injection.
• 7) Bring the pen to the skin fold (injection site) with the needle shield facing directly towards the injection site. Position the yellow needle shield on the injection site so that the entire edge of the needle shield is in contact with the skin.

• 8) Press the pen down against the skin until you feel and hear a “click”. This activates the pen and the solution is automatically injected into the skin.

• 9) The injection process lasts a maximum of 10 seconds. When the injection is complete, you will feel and hear a second “click”.
• 10) Wait 2-3 seconds before removing the pen from the skin. The pen's safety shield is now locked to prevent needle stick injuries. You can now release the skin fold.

• 11) Visually inspect the pen through the inspection window. The green plastic must be visible. This means that all the liquid has been injected. Dispose of the used pen in the sharps container provided. Close the container lid tightly and place it in a place out of reach of children. If methotrexate accidentally comes into contact with skin or soft tissues, wash the area with plenty of water.

If you use more Nordimet than you should
Follow the dose recommendations provided by your doctor. Do not change the dose without consulting
your doctor.
If you think you have used too much Nordimet, contact your doctor or the nearest hospital immediately.
An excessive dose of methotrexate can cause serious toxic reactions. Symptoms of an overdose
include easy bruising or bleeding, unusual weakness, sore mouth, nausea, vomiting, black or bloody stools, coughing up blood or vomiting coffee-ground-like material, and
decreased urine output. See also section 4.

If you forget to use Nordimet
Do not use a double dose to make up for a missed dose, but continue to use the prescribed dose as usual. Ask your doctor for advice.

If you stop using Nordimet
Do not stop or discontinue treatment with Nordimet before talking to your doctor. If
you think you have a side effect, contact your doctor immediately for advice.
If you have any doubts about using this medicine, contact your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If you notice sudden wheezing, difficulty breathing, swelling of the eyelids, face or lips, a skin rash or itching (especially all over the body), contact your doctor immediately.

Serious side effects
Contact your doctor immediately if you notice one or more of the following side effects:

• lung inflammation (symptoms may include general malaise, dry and irritating cough, shortness of breath, breathlessness at rest, chest pain or fever)
• blood in saliva or after coughing
• severe skin peeling or blistering
• unusual bleeding (including vomiting blood) or bruising
• severe diarrhea
• mouth ulcers
• black or tarry stools
• blood in urine or stools
• red spots on the skin
• fever
• yellowing of the skin (jaundice)
• pain or difficulty urinating
• thirst and/or frequent urination
• seizures
• loss of consciousness
• blurred or decreased vision

The following side effects have also been reported:

Very common(may affect more than 1 in 10 people)
Loss of appetite, nausea, stomach pain, inflammation of the oral mucosa, digestive disorders and increased liver enzyme levels.

Common(may affect up to 1 in 10 people)
Decrease in the formation of blood cells with a reduction in the number of white blood cells and/or red blood cells and/or platelets (leukopenia, anemia, thrombocytopenia), headache, fatigue, drowsiness, lung inflammation (pneumonia) with dry, unproductive cough, shortness of breath, fever, mouth ulcers, diarrhea, skin rashes, skin redness, itching.

Uncommon(may affect up to 1 in 100 people)
Decrease in the number of blood cells and platelets, inflammation of the throat, dizziness, confusion, depression, inflammation of blood vessels, ulcers and bleeding of the digestive tract, intestinal inflammation, vomiting, inflammation of the pancreas, liver disorders, diabetes, decrease in blood proteins, herpes-like rash, hives, sunburn-like reactions due to increased skin sensitivity to sunlight, hair loss, increased rheumatoid nodules, skin ulcers, shingles, joint or muscle pain, osteoporosis (decreased bone mass), inflammation and ulcers of the bladder (with possibility of blood in the urine), reduced kidney function, painful urination, inflammation and ulcers of the vagina.

Rare(may affect up to 1 in 1,000 people)
Infection (incl. reactivation of inactive chronic infection), sepsis, red eyes, allergic reactions, anaphylactic shock, decrease in the number of antibodies in the blood, inflammation of the membrane surrounding the heart, accumulation of fluid in the membrane surrounding the heart, obstruction of cardiac filling due to the presence of fluid in the membrane around the heart, visual disturbances, mood changes, low blood pressure, blood clot formation, formation of scar tissue in the lungs (pulmonary fibrosis), pneumonia from Pneumocystis jiroveci,respiratory arrest, asthma, accumulation of fluid in the membrane lining the lungs, inflamed gums, acute hepatitis (inflammation of the liver), browning of the skin, acne, red or purplish spots due to bleeding of blood vessels, allergic inflammation of blood vessels, bone fractures, kidney failure, reduced amount of urine or absence of urine, electrolyte disturbances, fever, delayed wound healing.

Very rare(may affect up to 1 in 10,000 people)
Reduction of certain white blood cells (agranulocytosis), severe bone marrow failure, liver failure, swollen glands, insomnia, pain, muscle weakness, sensation of numbness or tingling/decreased sensitivity to stimulation than normal, changes in taste (metallic taste), seizures, inflammation of the brain lining causing paralysis or vomiting, visual disturbances, damage to the retina of the eye, vomiting blood, toxic megacolon (enlargement of the colon with severe pain), abnormal sperm formation (oligospermia), Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), increased nail pigmentation, loss of sexual desire, erectile dysfunction, infections around the nails, severe gastrointestinal complications, pimples, visible enlargement of small blood vessels in the skin, menstrual disorders, vaginal discharge, infertility, increased breast volume in men (gynecomastia), lymphoproliferative disorders (excessive growth of white blood cells).

Frequency not known(cannot be estimated from the available data)
Increase in the number of certain white blood cells (eosinophilia), certain brain disorders (encephalopathy/leukoencephalopathy), nosebleeds, pulmonary bleeding, bone damage affecting the mandible/jaw (secondary to excessive growth of white blood cells), protein in the urine, feeling of weakness, destruction of tissue at the injection site, redness and scaling of the skin, swelling.
In the treatment with Nordimet, only mild local skin reactions have been observed, which have decreased during therapy.
Nordimet can cause a reduction in the number of white blood cells and its resistance to infections may decrease. If you develop an infection with symptoms such as fever and a severe worsening of your general condition, or fever with local symptoms of infection such as sore throat/pharynx/mouth, or urinary problems, consult your doctor immediately. A blood test will be performed to check for a possible reduction in the number of white blood cells (agranulocytosis). It is important that you tell your doctor that you are using Nordimet.
It is known that methotrexate causes bone problems, such as joint and muscle pain and osteoporosis. The frequency of these risks in children is not known.
Nordimet can cause serious side effects (which can sometimes be fatal). Your doctor will perform tests to check if changes are developing in the blood (e.g., reduction in the number of white blood cells, platelets, lymphoma) and changes affecting the kidneys and liver.
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 detailed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Nordimet

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 of the pre-filled pen and on the carton box after SCAD. The expiry date refers to the last day of that month.
Store at a temperature below 25°C.
Store the pre-filled pen in the outer carton to protect it from light.
Do not freeze.
Do not use this medicine if the solution is not clear and if it contains suspended particles.
Nordimet is for single use only. All used pens 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 Nordimet contains
The active ingredient is methotrexate. 1.0 mL of solution contains 25 mg of methotrexate.
The other ingredients are sodium chloride, sodium hydroxide and water for injections.
The following pens are available:
Prefilled pens containing 0.3 mL with 7.5 mg of methotrexate
Prefilled pens containing 0.4 mL with 10 mg of methotrexate
Prefilled pens containing 0.5 mL with 12.5 mg of methotrexate
Prefilled pens containing 0.6 mL with 15 mg of methotrexate
Prefilled pens containing 0.7 mL with 17.5 mg of methotrexate
Prefilled pens containing 0.8 mL with 20 mg of methotrexate
Prefilled pens containing 0.9 mL with 22.5 mg of methotrexate
Prefilled pens containing 1.0 mL with 25 mg of methotrexate

Description of Nordimet’s appearance and package contents
The prefilled pens of Nordimet contain a transparent, yellow-colored injectable solution.
Nordimet is available in packs containing 1 or 4 prefilled pens and 1 or 4 alcohol-soaked pads and in multiple packs, with 4 or 6 cardboard boxes, containing respectively 1 prefilled pen and an alcohol-soaked pad.
Nordimet is also available in multiple packs with 3 cardboard boxes, containing respectively 4 prefilled pens and alcohol-soaked pads.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Nordic Group B.V.
Siriusdreef 41
2132 WT Hoofddorp
Netherlands

Manufacturer
CENEXI - Laboratoires Thissen
Rue de la Papyrée 2-6
B-1420 Braine-l’Alleud
Belgium
Sever Pharma Solutions AB
Agneslundsvagen 27
P.O. Box 590
SE-201 25 Malmo
Sweden
FUJIFILM Diosynth Biotechnologies Denmark ApS
Biotek Allé 1
3400 Hillerød
Denmark

Other sources of information
More detailed information on this medicine is available on the website of the European Agency

Nordimet 7.5 mg injectable solution in pre-filled syringe, 10 mg injectable solution in pre-filled syringe, 12.5 mg injectable solution in pre-filled syringe, 15 mg injectable solution in pre-filled syringe, 17.5 mg injectable solution in pre-filled syringe, 20 mg injectable solution in pre-filled syringe

Nordimet 22.5 mg injectable solution in pre-filled syringe
Nordimet 25 mg injectable solution in pre-filled syringe
methotrexate

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.
• 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 may be harmful
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What is Nordimet and what is it used for

Nordimet contains the active ingredient methotrexate indicated for:

• reducing inflammation or swelling and
• reducing the activity of the immune system (the body's defense mechanism). An overactive immune system has been linked to inflammatory diseases.

Nordimet is a medicine used to treat various inflammatory diseases:

• active rheumatoid arthritis, in adult patients. Active rheumatoid arthritis is an inflammatory condition affecting the joints;
• severe active juvenile idiopathic arthritis affecting five or more joints (for this reason the disease is called polyarticular), in patients with inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs);
• moderate to severe plaque psoriasis in adults candidates for systemic therapy, as well as severe psoriasis that also affects the joints (psoriatic arthritis) in adult patients;
• inducing remission in adult patients with moderate Crohn's disease, steroid-dependent, in adults, in association with corticosteroids;
• maintaining remission of Crohn's disease in adults who have responded to methotrexate, as monotherapy.

2. What you need to know before using Nordimet

Do not use Nordimet if:

• you are allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6)
• you have a severe kidney disease (your doctor will know if you have a severe kidney disease)
• you have a severe liver disease (your doctor will know if you have a severe liver disease)
• you have a dysfunction of the system with which the body produces blood cells
• you consume a lot of alcohol
• your immune system is compromised
• you have a severe or pre-existing infection, e.g. tuberculosis or HIV
• you have a gastrointestinal ulcer
• you are pregnant or breastfeeding (see section “Pregnancy, breastfeeding and fertility”)
• you are receiving a vaccination with live vaccines at the same time as treatment.

Warnings and precautions
Cases of acute pulmonary bleeding have been reported in patients with rheumatological disease and treated with methotrexate. If you observe blood in your saliva or following coughing, contact your doctor immediately.
An enlargement of the lymph nodes (lymphoma) may occur and therapy must be discontinued.
Diarrhea can be a toxic effect of Nordimet and requires discontinuation of therapy. If you suffer from diarrhea, talk to your doctor.
Certain brain disorders (encephalopathy/leukoencephalopathy) have been reported in patients with cancer receiving methotrexate. Such undesirable effects cannot be ruled out when methotrexate is used to treat other diseases.
If you, your partner or the person assisting you notices the appearance or worsening of neurological symptoms, including general muscle weakness, visual impairment, changes in thinking, memory and orientation, resulting in confusion and personality changes, consult your doctor immediately as these may be symptoms of a very rare and serious brain infection called progressive multifocal leukoencephalopathy (PML).
Methotrexate may increase the skin's sensitivity to sunlight. Avoid intense sun exposure and do not use sunbeds or tanning lamps without your doctor's advice. To protect your skin from intense sun, wear appropriate clothing or use a sunscreen with a high protection factor.
Important warnings about the dosage of Nordimet
In the treatment of rheumatic diseases, skin diseases and Crohn's disease, methotrexate must be used once a week. An incorrect dose of methotrexate can cause serious side effects, which can be fatal. Read section 3 of this leaflet very carefully.
Talk to your doctor before using Nordimet if:

• you have diabetes mellitus and are being treated with insulin
• you have inactive, long-lasting infections (e.g. tuberculosis, hepatitis B or C, shingles [herpes zoster])
• you have/have had a liver or kidney disease
• you have problems with lung function
• you are severely overweight
• you have an abnormal accumulation of fluid in the abdomen or in the cavity between the lungs and the chest wall (ascites, pleural effusion)
• you are dehydrated or are in a situation that causes dehydration (e.g. dehydration due to vomiting, diarrhea or inflammation of the mouth and lips)

If you have had skin problems after radiation therapy (radiation dermatitis) or a sunburn, these conditions may recur during treatment with Nordimet.
Children, adolescents and the elderly
Instructions on the dose depend on the patient's weight.
Use in children under 3 years of age is not recommended, because there is insufficient data available on the use of this medicine in this age group.
Children, adolescents and the elderly treated with Nordimet must be carefully monitored by the doctor to identify possible side effects as early as possible.
In elderly patients, the dose must be reduced due to the reduction in liver and kidney function caused by age.
Special precautions for treatment with Nordimet
Methotrexate temporarily affects the production of sperm and eggs. Methotrexate can cause abortion and serious birth defects. During treatment with methotrexate and for at least 6 months after the end of treatment with methotrexate, if you are a woman, you must avoid becoming pregnant. If you are a man, while undergoing treatment with methotrexate and for at least 3 months after the end of treatment with methotrexate, you must avoid conceiving a child. Also consult the section “Pregnancy, breastfeeding and fertility”.
Skin changes caused by psoriasis may worsen during treatment with Nordimet if exposed to ultraviolet rays.
Recommended control tests and precautions
Even if methotrexate is used at low doses, serious side effects can occur. To identify them in time, the doctor must perform control tests and laboratory tests.
Before starting therapy:
Before starting treatment, your blood will be checked to see if you have enough blood cells. Your blood will also be analyzed to check your liver function and to find out if you have hepatitis. In addition, serum albumin (a protein present in the blood), the state of hepatitis (liver infection) and kidney function will be checked. The doctor may also decide to perform other liver tests, some of these may be images of the liver and others may require a small sample of tissue taken from the liver to examine it more thoroughly.
The doctor may also check if you have tuberculosis and may take a chest X-ray or a pulmonary function test.
During treatment:
The doctor may perform the following tests:

• examination of the oral cavity and pharynx to identify any changes in the mucosa, such as inflammation or ulceration
• blood tests/blood count with number of blood cells and measurement of methotrexate levels in the serum
• blood tests to monitor liver function
• imaging tests to monitor liver conditions
• small sample of tissue taken from the liver to examine it more thoroughly
• blood tests to monitor kidney function
• monitoring of the respiratory tract and, if necessary, pulmonary function tests

It is very important that you attend these scheduled examinations.
If the results of one of these tests are significant, the doctor will adjust the treatment accordingly.

Other medicines and Nordimet
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
It is especially important that you tell your doctor if you are taking:

• other medicines for rheumatoid arthritis or psoriasis such as leflunomide, sulfasalazine (a medicine that is also used for the treatment of ulcerative colitis, in addition to the treatment of arthritis and psoriasis), aspirin, phenylbutazone or amidopyrine
• cyclosporine (to suppress the immune system)
• azathioprine (medicine used to prevent rejection after an organ transplant)
• retinoids (used for the treatment of psoriasis and other skin diseases)
• anticonvulsant medicines (used to prevent seizures), such as phenytoin, valproate or carbamazepine
• cancer treatments
• barbiturates (injections for anesthesia)
• tranquilizers
• oral contraceptives
• probenecid (used for the treatment of gout)
• antibiotics (e.g. penicillin, glycopeptides, trimethoprim-sulfamethoxazole, sulfonamides, ciprofloxacin, cefalotin, tetracyclines, chloramphenicol)
• pyrimethamine (used for the prevention and treatment of malaria)
• vitamin preparations containing folic acid
• proton pump inhibitors (medicines that reduce the production of stomach acids, used to treat severe heartburn or ulcers), such as omeprazole or pantoprazole
• theophylline (used for the treatment of asthma)
• cholestyramine (used to treat high cholesterol, itching or diarrhea)
• NSAIDs, non-steroidal anti-inflammatory drugs (used to treat pain or inflammation)
• p-aminobenzoic acid (used to treat skin disorders)
• any vaccination with a live vaccine (should be avoided), such as those against measles, mumps or yellow fever.
• metamizole (synonyms novaminsulfon and dipyrone) (medicine to relieve severe pain and/or fever)
• nitrous oxide (a gas used in general anesthesia)

Nordimet with food, beverages and alcohol
During treatment with Nordimet, you should not drink alcohol and avoid drinking too much coffee, caffeinated beverages and black tea, which may increase side effects or interfere with the effectiveness of Nordimet. In addition, during treatment with Nordimet you should drink plenty of fluids to prevent dehydration (reduction of fluids in the body), which can increase the toxicity of Nordimet.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant or are planning a pregnancy, ask your doctor before taking this medicine.
Pregnancy
Do not use Nordimet during pregnancy or if you are trying to become pregnant. Methotrexate can cause birth defects, be harmful to the fetus or cause abortion. It is associated with malformations that can affect the skull, face, heart and blood vessels, brain and limbs. For these reasons, it is very important that patients who are expecting a baby or who desire a pregnancy are not treated with methotrexate. Therefore, in women of childbearing potential, the possibility of pregnancy must be excluded during treatment, adopting appropriate measures, for example, performing a pregnancy test, before starting treatment. During treatment with methotrexate and for at least 6 months after the end of treatment, you must avoid pregnancy, using a reliable contraceptive method (see also the section “Warnings and precautions”).
If you become pregnant during treatment, consult your doctor as soon as possible, who will provide you with medical advice on the risk of harmful effects to the baby throughout the duration of treatment.
If you wish to become pregnant, you should consult your doctor, who may refer you to a specialist before the planned start of treatment.
Breastfeeding
Do not breastfeed during treatment with methotrexate, as methotrexate passes into breast milk.
Male fertility
Available data do not indicate an increased risk of malformations or abortion if the father takes less than 30 mg of methotrexate per week. However, the risk cannot be completely ruled out. Methotrexate may be genotoxic. That is, this medicine can cause genetic mutations. Methotrexate can affect the production of sperm with the possibility of causing birth defects. Therefore, while using methotrexate and for at least 3 months after the end of treatment, you should avoid fathering a child or donating sperm.

Driving and using machines
Side effects on the central nervous system, such as fatigue and dizziness, may occur during treatment with Nordimet. In some cases, the ability to drive vehicles and/or use machines may be impaired. If you feel tired or dizzy, do not drive or use machines.

Nordimet contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.

3. How to use Nordimet

Important warnings about the dosage of Nordimet
Use Nordimet only once a weekfor the treatment of rheumatoid arthritis, active juvenile idiopathic arthritis, psoriasis, psoriatic arthritis and Crohn's disease that
require a single weekly dose. Overuse of Nordimet can be fatal.
pharmacist before taking this medicine.
Use this medicine following the doctor's instructions exactly. If you have any doubts, contact your doctor or
pharmacist.
Nordimet must be administered only once a week. You can decide with your doctor the
suitable day for the injection, which must be the same every week.
Incorrect administration of methotrexate can cause serious side effects, which can
become fatal.
The recommended dose is:
Dose in adult patients with rheumatoid arthritis
The recommended initial dose is 7.5 mg of methotrexate once a week.
The doctor may increase the dose if the one used is not effective, but well tolerated. The weekly dose
average is 15-20 mg. In general, the weekly dose should not exceed 25 mg.
After obtaining the desired therapeutic effect, the doctor may gradually reduce the dose of
Nordimet until reaching the lowest possible effective dose for maintenance therapy.
Generally, an improvement of symptoms is expected after 4-8 weeks of treatment. Symptoms may
reappear if treatment with Nordimet is stopped.
Use in adult patients with moderate to severe plaque psoriasis and severe psoriatic arthritis.
The doctor will administer a single test dose of 5-10 mg to assess the appearance of possible
side effects.
If the test dose is well tolerated, treatment will be continued after one week with a dose of
about 7.5 mg.
Generally, a response to treatment is expected after 2-6 weeks. Based on the effects of treatment and the
results of blood and urine tests, therapy should be continued or discontinued.
Dose in adult patients with Crohn's disease:
Your doctor will prescribe an initial weekly dose of 25 mg. Generally, the response to
treatment is predictable after 8-12 weeks. Depending on the effects of treatment over time, your
doctor may decide to reduce the dose to 15 mg/week.
Use in children and adolescents under 16 years of age with polyarticular forms of juvenile idiopathic arthritis
The doctor will calculate the necessary dose based on the child's body surface area (m²). The
dose is indicated in mg/m².
Use in children under 3 years of age is not recommended due to insufficient data for this
age group.
Method and duration of administration
Nordimet is administered by subcutaneous injection (under the skin). It must be injected once
a week and it is recommended to perform the Nordimet injection on the same day of the
week.
At the beginning of treatment, Nordimet will be injected by medical personnel. However, the doctor may
decide that you are able to learn how to perform Nordimet injections yourself. In this case
you will receive adequate training. In no case should you attempt to perform the injection yourself,
before receiving adequate training.
The duration of treatment will be established by the attending physician. Treatment of rheumatoid arthritis,
juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis and Crohn's disease
with Nordimet is a long-term treatment.

How to perform Nordimet injections yourself
If you have difficulty using the syringe, contact your doctor or pharmacist. Do not attempt to perform
the injection yourself if you have not received training on how to do it. If you are unsure what to do, contact your doctor or nurse immediately.

Before performing a Nordimet injection yourself

• Check the expiry date of the medicine. Do not use the medicine if the expiry date has been exceeded.
• Verify that the syringe is not damaged and that the medicine contained is a transparent solution, yellow in color. If not, use another syringe.
• Check the injection site of the last injection for redness, changes in skin color, swelling, discharge, or pain. If you notice one or more of these problems, contact your doctor or nurse.
• Decide where to perform the injection of the medicine. Change the injection site each time.

Instructions on how to perform Nordimet injections yourself

• 1) Wash your hands thoroughly with soap and water.
• 2) Sit or lie down in a relaxed and comfortable position. Make sure the skin area where you intend to perform the injection is visible.
• 3) The syringe is pre-filled and ready to use. Open the blister by completely removing the upper layer as shown in the figure.

Blister
Upper layer

• 4) Caution: DO NOT lift the product by gripping the plunger or the cap. Remove the syringe from the box by gripping the body as shown in the figure below.

• 5) Visually inspect the syringe. You should see a yellow fluid through the inspection window. You may see an air bubble that does not negatively affect the injection and is not dangerous.
• 6) Choose a site for the injection and clean it with the alcohol swab included. It takes 30-60 seconds for the disinfection to be effective. Suitable injection sites are the skin of the abdomen and the front of the thigh.
• 7) Holding the body of the syringe firmly, remove the cap.

Donot press the plunger before giving yourself the injection to eliminate air bubbles. This may
lose some of the medicine. After removing the cap, hold the syringe. Do not touch anything with
the syringe to ensure that the needle remains clean.

• 8) Hold the syringe with the hand you write with, (as if it were a pencil) and with the other hand, at the injection site, form a skin fold, pinching the skin between your thumb and index finger. You must maintain the fold for the entire duration of the injection.
• 9) Bring the syringe to the skin fold (injection site) with the needle guard pointing directly at the injection site. Insert the needle completely into the skin fold.
• 10) Press the plunger with your finger until the syringe is empty. This will inject the medicine under the skin.

• 11) Remove the needle by pulling it out straight. This will cause the syringe guard to automatically cover the needle, preventing puncture injuries. Now you can release the skin fold.

Note: the safety system that releases the safety guard can only be activated if the syringe
has been completely emptied by fully pressing down the plunger.

• 12) Dispose of the used syringe using the sharps container provided. Close the container lid tightly and place it in a place out of reach of children. If methotrexate accidentally comes into contact with the skin or soft tissues, wash the affected area with plenty of water.

If you use more Nordimet than you should
Follow the dosage recommendations given to you by your doctor. Do not change the dose without consulting
the doctor.
If you think you have used too much Nordimet, contact your doctor or the nearest hospital immediately.
An overdose of methotrexate can cause serious toxic reactions. Symptoms of an overdose
include easy bruising or bleeding, unusual weakness, sore mouth, nausea, vomiting, black or bloody stools, coughing up blood or vomiting coffee-ground-like material, and
decreased urine output. See also section 4.

If you forget to use Nordimet
Do not use a double dose to make up for a missed dose, but continue to use the prescribed dose as always. Ask your doctor for advice.

If you stop using Nordimet
Do not stop or discontinue treatment with Nordimet before talking to your doctor. If
you think you have a side effect, contact your doctor immediately for advice.
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.
If you notice sudden wheezing, difficulty breathing, swelling of eyelids, face or lips, a skin rash or itching (especially all over the body), contact your doctor immediately.

Serious side effects
Contact your doctor immediately if you notice any of the following side effects:

• lung inflammation (symptoms may include feeling generally unwell, dry and irritating cough, shortness of breath, breathlessness at rest, chest pain or fever)
• blood in saliva or after coughing
• severe skin peeling or blistering
• unusual bleeding (including vomiting blood) or bruising
• severe diarrhoea
• mouth ulcers
• black or tarry stools
• blood in urine or stools
• red spots on the skin
• fever
• yellowing of the skin (jaundice)
• pain or difficulty urinating
• thirst and/or needing to urinate frequently
• convulsions
• loss of consciousness
• blurred or decreased vision

The following side effects have also been reported:

Very common(may affect more than 1 in 10 people)
Loss of appetite, nausea, stomach pain, inflammation of the oral mucosa, digestive disorders and increased liver enzyme levels.

Common(may affect up to 1 in 10 people)
Decrease in the formation of blood cells with reduction in the number of white blood cells and/or red blood cells and/or platelets (leukopenia, anemia, thrombocytopenia), headache, fatigue, drowsiness, lung inflammation (pneumonia) with dry, unproductive cough, shortness of breath, fever, mouth ulcers, diarrhoea, skin rashes, skin redness, itching.

Uncommon(may affect up to 1 in 100 people)
Decrease in the number of blood cells and platelets, inflammation of the throat, dizziness, confusion, depression, inflammation of blood vessels, ulcers and bleeding of the digestive tract, intestinal inflammation, vomiting, inflammation of the pancreas, liver disorders, diabetes, decrease in blood proteins, herpes-like skin rash, urticaria, sunburn-like reactions due to increased skin sensitivity to sunlight, hair loss, increased rheumatoid nodules, skin ulcers, shingles, joint or muscle pain, osteoporosis (reduced bone mass), inflammation and ulcers of the bladder (with possibility of blood in the urine), reduced kidney function, painful urination, inflammation and vaginal ulcers.

Rare(may affect up to 1 in 1,000 people)
Infection (incl. reactivation of inactive chronic infection), sepsis, red eyes, allergic reactions, anaphylactic shock, decrease in the number of antibodies in the blood, inflammation of the membrane surrounding the heart, accumulation of fluid in the membrane surrounding the heart, obstruction of cardiac filling due to the presence of fluid in the membrane around the heart, visual disturbances, mood changes, low blood pressure, blood clot formation, formation of scar tissue in the lungs (pulmonary fibrosis), pneumonia due to Pneumocystis jiroveci,interruption of breathing, asthma, accumulation of fluid in the membrane lining the lungs, inflamed gums, acute hepatitis (inflammation of the liver), browning of the skin, acne, red or purplish spots due to bleeding from blood vessels, allergic inflammation of blood vessels, bone fractures, kidney failure, reduced amount of urine or absence of urine, electrolyte disturbances, fever, delayed wound healing.

Very rare(may affect up to 1 in 10,000 people)
Reduction of certain white blood cells (agranulocytosis), severe bone marrow failure, liver failure, swollen glands, insomnia, pain, muscle weakness, sensation of numbness or tingling/decreased sensitivity to stimulation than normal, changes in taste (metallic taste), convulsions, inflammation of the brain lining causing paralysis or vomiting, visual disturbances, damage to the retina of the eye, vomiting blood, toxic megacolon (enlargement of the colon with severe pain), abnormal sperm formation (oligospermia), Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), increased nail pigmentation, loss of sexual desire, erectile dysfunction, infections around the nails, severe gastrointestinal complications, pimples, visible enlargement of small blood vessels in the skin, menstrual disorders, vaginal discharge, infertility, increased breast volume in men (gynecomastia), lymphoproliferative disorders (excessive growth of white blood cells).

Frequency not known(cannot be estimated from the available data)
Increase in the number of certain white blood cells (eosinophilia), certain brain disorders (encephalopathy/leukoencephalopathy), nosebleeds, pulmonary bleeding, bone damage affecting the mandible/jaw (secondary to excessive growth of white blood cells), protein in the urine, feeling of weakness, destruction of tissue at the injection site, redness and peeling of the skin, swelling.
With Nordimet treatment, only mild local skin reactions have been observed which have decreased during therapy.
Nordimet can cause a reduction in the number of white blood cells and its resistance to infections may decrease. If you develop an infection with symptoms such as fever and a significant worsening of your general condition, or fever with local symptoms of infection such as sore throat/pharynx/mouth, or urinary problems, consult your doctor immediately. A blood test will be performed to check for a possible reduction in the number of white blood cells (agranulocytosis). It is important that you tell your doctor that you are using Nordimet.
It is known that methotrexate causes bone problems, such as joint and muscle pain and osteoporosis. The frequency of these risks in children is not known.
Nordimet can cause serious side effects (which can sometimes be fatal). Your doctor will have you undergo tests to check if changes are developing in the blood (e.g. reduction in the number of white blood cells, platelets, lymphoma) and changes affecting the kidneys and liver.
Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. 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 Nordimet

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 of the pre-filled syringe
and on the cardboard box after EXP. The expiry date refers to the last day of
that month.
Store at a temperature below 25°C.
Store the syringe in the outer carton to protect it from light.
Do not freeze.
Do not use this medicine if the solution is not clear and if it contains suspended particles.
Nordimet is for single use only. All used syringes must be disposed of.
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 Nordimet contains
The active ingredient is methotrexate. 1.0 mL of solution contains 25 mg of methotrexate.
The other ingredients are sodium chloride, sodium hydroxide and water for injections.
The following pre-filled syringes are available:
Pre-filled syringes of 0.3 mL containing 7.5 mg of methotrexate.
Pre-filled syringes of 0.4 mL containing 10 mg of methotrexate
Pre-filled syringes of 0.5 mL containing 12.5 mg of methotrexate
Pre-filled syringes of 0.6 mL containing 15 mg of methotrexate
Pre-filled syringes of 0.7 mL containing 17.5 mg of methotrexate
Pre-filled syringes of 0.8 mL containing 20 mg of methotrexate
Pre-filled syringes of 0.9 mL containing 22.5 mg of methotrexate
Pre-filled syringes of 1.0 mL containing 25 mg of methotrexate

Description of the appearance of Nordimet and contents of the pack
The pre-filled syringes of Nordimet contain a transparent injectable solution, of yellow colour.
Nordimet is available in packs containing 1 pre-filled syringe and two alcohol-soaked swabs
and in multiple packs with 4, 6 or 12 cardboard boxes containing respectively 1 syringe
pre-filled and two alcohol-soaked swabs.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Nordic Group B.V.
Siriusdreef 41
2132 WT Hoofddorp
The Netherlands

Manufacturer
CENEXI - Laboratoires Thissen
Rue de la Papyrée 2-6
B-1420 Braine-l’Alleud
Belgium
Sever Pharma Solutions AB
Agneslundsvagen 27
P.O. Box 590
SE-201 25 Malmo
Sweden

Other sources of information
More detailed information on this medicine is available on the website of the European Agency

ANNEX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR VARIATION OF THE
MARKETING AUTHORISATION
Scientific conclusions
Taking into account the assessment of the Pharmacovigilance and Risk Assessment Committee
(PRAC) of the Periodic Safety Update Report (PSUR) for methotrexate, the scientific conclusions of the PRAC are as follows:
In light of the available data on photosensitivity reactions in spontaneous cases, including one fatal case, and in the literature, the PRAC considers that the drug reaction represented by photosensitivity reactions should be added or modified and that a warning about the risk of photosensitivity should be included in the information on medicines containing methotrexate.
In light of the available data on the pharmacological interaction between methotrexate and metamizole from spontaneous reports and the literature, the PRAC considers that the concomitant use of methotrexate and metamizole may increase hematotoxicity, especially in elderly patients.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products
(CHMP) agrees with the general conclusions and with the justification of the recommendation.

Justification for variation of the terms of the marketing authorisation
Based on the scientific conclusions on methotrexate, the CHMP considers that the benefit/risk ratio of the medicines containing methotrexate remains unchanged subject to the proposed changes to the medicine information.
The CHMP recommends the variation of the terms of the marketing authorisation.