Package leaflet: Information for the user

Nordimet 7.5 mg solution for injection in pre-filled pen

Nordimet 10 mg solution for injection in pre-filled pen

Nordimet 12.5 mg solution for injection in pre-filled pen

Nordimet 15 mg solution for injection in pre-filled pen

Nordimet 17.5 mg solution for injection in pre-filled pen

Nordimet 20 mg solution for injection in pre-filled pen

Nordimet 22.5 mg solution for injection in pre-filled pen

Nordimet 25 mg solution for injection in pre-filled pen

Methotrexate

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

- Keep this leaflet. You may need to read it again.

- If you have any further questions, ask your doctor or pharmacist.

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in 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 Nordimet is and what it is used for

Nordimet contains the active substance methotrexate which works by:

- reducing inflammation or swelling, and

- reducing the activity of the immune system (the body’s own defense mechanism). An overactive immune system has been linked to inflammatory diseases.

Nordimet is a medicine used to treat a range of inflammatory diseases:

- active rheumatoid arthritis in adults. Active rheumatoid arthritis is an inflammatory condition that affects the joints;

- severe, active juvenile idiopathic arthritis in five or more joints (the condition is therefore called polyarthritic), in patients who have had an inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs);

- a severe form of treatment resistant psoriasis (also called severe recalcitrant disabling psoriasis), in adult patients who have had an inadequate response to other treatments including phototherapy (light therapy), PUVA (ultraviolet light therapy), and retinoids (group of medicines derived from vitamin A).

2. What you need to know before you use Nordimet

Do not use Nordimet if:

- you are allergic (hypersensitive) to methotrexate or any of the other ingredients of this medicine (listed in section 6)

- you have severe kidney disease (your doctor will be able to tell you if you have severe kidney disease)

- you have severe liver disease (your doctor will be able to tell you if you have severe liver disease)

- you have disorders of the blood-forming system

- your alcohol consumption is high

- you have an impaired immune system

- you have a severe or existing infection, e.g. tuberculosis or HIV

- you have gastrointestinal ulcers

- you are pregnant or breastfeeding (see section “Pregnancy, breastfeeding and fertility”)

- you receive vaccinations with live vaccines at the same time.

Warnings and precautions

Important warning about the dosing of Nordimet

Methotrexate for the therapy of rheumatic diseases or diseases of the skin must only be used once weekly. Incorrect dosing of methotrexate may lead to serious adverse effects which may be fatal. Please read section 3 of this package leaflet very carefully.

Talk to your doctor before using Nordimet if:

- you have diabetes mellitus are being treated with insulin

- you have inactive, prolonged infections (e.g. tuberculosis, hepatitis B or C, shingles [herpes zoster])

- you have/had any liver or kidney disease

- you have problems with lung function

- you are severely overweight

- you have abnormal accumulation of liquid in the abdomen or in the cavity between the lungs and chest wall (ascites, pleural effusions)

- you are dehydrated or suffer from conditions leading to dehydration (e.g. dehydration as a result of vomiting, diarrhoea or inflammation of the mouth and lips)

If you have experienced problems with your skin after radiation therapy (radiation induced dermatitis) or sun-burn, these conditions can reappear when taking Nordimet.

Children, adolescents and elderly

Dose instructions depend on the patient’s body weight.

Use in children under 3 years of age is not recommended due to insufficient experience of using this medicine in this age group.

Children, adolescents and the elderly being treated with Nordimet should be kept under close medical surveillance to identify possible side effects as early as possible.

The dose for elderly patients should be lowered due to age-related reduced liver and kidney function.

Special precautionary measures for treatment with Nordimet

Methotrexate temporarily affects sperm and egg production. You must avoid becoming pregnant or fathering children when using methotrexate and for at least six months after treatment has stopped. See also section “Pregnancy, breast-feeding and fertility”.

Skin changes caused by psoriasis can worsen during treatment with Nordimet if exposed to ultraviolet irradiation.

Before the start of treatment and recommended follow-up examinations and precautions Before treatment is started your doctor may carry out blood tests, and also check how well your kidneys and liver are working. You may also have a chest X-ray. Further tests may also be done during and after treatment. Do not miss appointments for blood tests.

If the results of any of these tests are abnormal, treatment will only be resumed when all readings are back to normal.

Even when Nordimet is used at low doses, serious side effects can occur. Your doctor will carry out blood and urine tests to make sure that any side effects are identified quickly.

Other medicines and Nordimet

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription and herbal or natural medicinal products.

It is especially important to tell your doctor if you are taking:

- other treatments for rheumatoid arthritis or psoriasis such as leflunomide, sulphasalazine (a medicine that besides arthritis and psoriasis is also used to treat and ulcerative colitis), aspirin, phenylbutazone, or amidopyrine

- alcohol (drinking alcohol should be avoided while you are taking Nordimet)

- azathioprine (used to prevent rejection after an organ transplant)

- retinoids (used to treat psoriasis and other skin disorders)

- anticonvulsant medicines (used to prevent fits), such as phenytoin, valproate or carbamazepine

- cancer treatments

- barbiturates (sleeping injection)

- tranquillisers

- oral contraceptives

- probenecid (used to treat gout)

- antibiotics

- pyrimethamine (which is used to prevent and treat malaria)

- vitamin preparations containing folic acid

- proton-pump inhibitors (medicines that reduce the production of gastric acid and that are used to treat severe heartburn or ulcers), such as omeprazole

- theophylline (used to treat asthma)

- any vaccination with a live vaccine (must be avoided), such as measles, mumps, influenza or yellow fever vaccines.

Using Nordimet with food, drink and alcohol

During treatment with Nordimet, you must not drink any alcohol and should avoid excessive consumption of coffee, soft drinks containing caffeine and black tea as this may enhance side effects or interfere with the efficacy of Nordimet. Also, make sure you drink plenty of liquids during treatment with Nordimet because dehydration (reduction in body water) can increase the toxicity of Nordimet.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

Do not use Nordimet during pregnancy or if you are trying to become pregnant. Methotrexate can cause birth defects, harm unborn babies or cause miscarriages, and so it is very important that it is not given to pregnant patients or patients planning to become pregnant. In women of child-bearing age any possibility of pregnancy must be excluded with appropriate measures, e.g. a pregnancy test before starting treatment. You must avoid becoming pregnant whilst taking methotrexate and for at least 6 months after treatment is stopped by using reliable contraception throughout this time (see also section “Warnings and precautions”).

If you do become pregnant during treatment, you should be offered advice regarding the risk of harmful effects on the child through treatment.

If you wish to become pregnant you should consult your doctor, who may refer you for specialist advice before the planned start of treatment, because methotrexate may be genotoxic, which means that the medicine may cause genetic mutation.

Breast-feeding

Do not breast-feed during treatment because methotrexate passes into breast milk. If your doctor considers treatment with methotrexate absolutely necessary during the lactation period, you must stop breast-feeding.

Male fertility

Methotrexate may be genotoxic. This means that the medicine may cause genetic mutation. Methotrexate can affect sperm production with the potential to cause birth defects. Therefore, you must avoid fathering a child whilst taking methotrexate and for at least 6 months after treatment is stopped. Since treatment with methotrexate may lead to infertility, it may be advisable to get advice about sperm preservation before starting treatment (see also section “Warnings and precautions”).

Driving and using machines

Side effects affecting the central nervous system, such as tiredness 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, you should not drive or use machines.

Nordimet contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, and so is essentially “sodium-free”.

3. How to use Nordimet

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Nordimet is administered once a week only. You and your doctor can decide on a suitable day each week to receive your injection.

Incorrect administration of Nordimet can lead to severe side effects that may be fatal.

The usual dose is:

Dose in patients with rheumatoid arthritis

The recommended starting dose is 7.5 mg methotrexate once a week.

The doctor may increase the dose if the used dose is not effective but tolerated well. The average weekly dose is 15-20 mg. Generally, a weekly dose of 25 mg should not be exceeded. Once Nordimet starts working, the doctor may reduce the dose gradually to the lowest possible effective maintenance dose.

Generally, improvement of symptoms can be expected after 4-8 weeks of treatment. Symptoms may return if treatment with Nordimet is stopped.

Dose in children and adolescents below 16 years with polyarthritic forms of juvenile idiopathic arthritis

The doctor will calculate the dose required from the child’s body surface area (m2), and the dose is expressed as mg/m2.

Use in children under < 3 years is not recommended due to insufficient experience in this age group.

Use in adults with severe forms of psoriasis vulgaris or psoriatic arthritis

Your doctor will give you a single test dose of 5-10 mg, in order to assess possible side effects. If the test dose is well tolerated, treatment will be continued after a week with a dose of approximately 7.5 mg.

Response to treatment can generally be expected after 2-6 weeks. Depending on the effects of treatment and results of blood and urine tests, the therapy is then continued or stopped.

Method and duration of administration

Nordimet is given as injection under the skin (subcutaneously). It must be injected once weekly and it is recommended to always inject Nordimet on the same day of the week.

At the start of your treatment, Nordimet may be injected by medical staff. However, your doctor may decide that you can learn how to inject Nordimet yourself. You will receive appropriate training for you to do this. Under no circumstances should you attempt to inject yourself unless you have been trained to do so.

The duration of treatment is determined by the treating physician. Treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis vulgaris and psoriatic arthritis with Nordimet is a long-term treatment.

How to give yourself an injection of Nordimet

If you have difficulty handling the pen, ask your doctor or pharmacist. Do not try to inject yourself if you have not been trained on how to do so. If you are not sure what to do, talk to your doctor or nurse immediately.

Before injecting yourself with Nordimet

- Check the expiry date on the medicine. Do not use if the date has passed.

- Check the pen is not damaged and the medicine in it is a clear, yellow solution. If not, use another pen.

- Check your last injection site to see if the last injection caused any redness, change in skin colour, swelling, oozing or is still painful, if so talk to your doctor or nurse.

- Decide where you are going to inject the medicine. Change the place where you inject each time.

Instructions on injecting yourself with Nordimet

1) Wash your hands thoroughly with soap and water.

2) Sit or lie in a relaxed, comfortable position. Make sure you can see the skin area you are going to inject.

3) The pen is pre-filled and ready to use. Remove the pen from the box and ensure that the

tamper-evident seal between the white body of the pen and the green cap is intact. If the tamper-evident seal is broken, return the pen and box to the pharmacist who supplied it and use another pen for the injection.

Visually inspect the pen. You should see a yellow fluid through the viewing window. You may see a small air bubble, this does not affect the injection and will not harm you.

A droplet may appear at the tip of the needle. This is normal.

4) Wipe the area that you will inject with the alcohol swab provided.

5) While holding the body of the pen, pull the cap off. Once you have taken the cap off, keep the pen in your hand. Do not allow the pen to touch anything else. This is to make sure that the pen is not accidentally activated and that the needle stays clean.

6) Make a fold in the skin by gently pinching the skin of the injection place with your forefinger and thumb. Make sure you hold the skin fold throughout the injection.

7) Move the pen towards the skin fold (site of injection) with the needle shield pointing directly at the site of injection. Place the yellow needle shield against the area of injection so that the entire rim of the needle shield is touching the skin.

8) Apply downward pressure on the pen on to your skin until you hear and feel a “click”. This activates the pen and the solution will inject automatically into the skin.

9) The injection lasts for a maximum of 10 seconds. You will feel and hear a second “click” once the injection is completed.

10) Wait another 2-3 seconds before removing the pen from your skin. The safety shield on the pen is now locked to prevent any needle stick injuries. You can now let go of the skin fold.

11) Visually inspect the pen through the viewing window. You should see green plastic. This means that all the fluid has been injected. Discard the used pen into the sharps bin provided. Close the container lid tightly and place the container out of reach of children. If you accidently get

methotrexate on the surface of the skin or soft tissues you must rinse with plenty of water. If you use more Nordimet than you should

Follow the dose recommendations of your treating doctor. Do not change the dose without your doctor’s recommendation.

If you suspect that you have used too much Nordimet, tell your doctor or contact the nearest hospital immediately. Take your medicine package and this leaflet with you if you go to a doctor or hospital.

An overdose of methotrexate can lead to severe toxic reactions. Overdose symptoms may include easy bruising or bleeding, unusual weakness, mouth sores, nausea, vomiting, black or bloody stools, coughing up blood or vomit that looks like coffee grounds, and decreased urinating. See also section 4.

If you forget to use Nordimet

Do not take a double dose to make up for a forgotten dose, but continue taking the prescribed dose as normal. Ask your doctor for advice.

If you stop taking Nordimet

You should not interrupt or discontinue Nordimet treatment before discussing with your doctor. If you suspect that you are experiencing side effects, contact your doctor immediately for advice.

If you have any further questions on 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.

Tell your doctor straight away if you get any sudden wheeziness, difficulty in breathing, swelling of the eyelids, face or lips, rash or itching (especially affecting your whole body).

Serious side effects

If you develop any of the following side effects, contact your doctor immediately:

- inflammation of the lungs (symptoms may be general illness, dry, irritating cough, shortness of breath, breathlessness at rest, chest pain, or fever)

- severe peeling or blistering of the skin

- unusual bleeding (including vomiting blood) or bruising

- severe diarrhoea

- ulcers in mouth

- black or tarry stools

- blood in the urine or stools

- tiny red spots on the skin

- fever

- yellowing of the skin (jaundice)

- pain or difficulty in passing urine

- thirst and/or frequent urination

- fits (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 (feeling sick), vomiting, tummy pain, inflammation and ulcers in the mouth and throat, and increase in liver enzymes.

Common (may affect up to 1 in 10 people):

Reduced blood cell formation with decrease in white and/or red blood cells and/or platelets (leukopenia, anaemia, thrombocytopenia), headache, tiredness, drowsiness, inflammation of the lungs (pneumonia) with dry, non-productive cough, shortness of breath and fever, diarrhoea, rash, reddening of the skin, itching.

Uncommon (may affect up to 1 in 100 people):

Decrease in the number of blood cells and platelets , dizziness, confusion, depression, fits, inflammation of blood vessels, lung damage, ulcers and bleeding in the digestive tract, liver disorders, diabetes, decreased blood protein, nettle rash, light sensitivity, brown skin, hair loss, increase of rheumatic nodules, shingles, painful psoriasis, joint or muscle pain, osteoporosis (reduction of bone mass), inflammation and ulcers of the bladder (possibly with blood in the urine), painful urination, severe allergic reactions, inflammation and ulcers of the vagina, slow wound healing.

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

Inflammation of the sac around the heart, fluid in the sac around the heart, severe visual disturbance, mood fluctuations, low blood pressure, blood clots, sore throat, interruption of breathing, asthma, inflammation of the digestive tract, bloody stools, inflamed gums, abnormal digestion, acute hepatitis (inflammation of the liver), changed colour of nails, acne, red or purple spots due to vessel bleeding, bone fracture, kidney failure, decrease or absence of urine, electrolyte disturbances, defective sperm formation, menstruation disorders.

Very rare (may affect up to 1 in 10,000 people):

Infections, severe failure of the bone marrow, liver failure, swollen glands, sleeplessness, pain, muscle weakness, pins and needles, changes in sense of taste (metallic taste), inflammation of the lining of the brain causing paralysis or vomiting, red eyes, damage to the retina of the eye, fluid in the lungs, vomiting blood, cold sores, protein in the urine, fever, loss of sex drive, problems having an erection, infection around a fingernail, severe complications of the gastrointestinal tract, boils, small blood vessels in the skin, fungal infections, damage to the blood vessels of the skin, vaginal discharge, infertility, male breast enlargement (gynaecomastia), inflammation of the brain.

Only mild local skin reactions were observed with Nordimet and these decreased during therapy.

Nordimet may cause a reduction in the number of white blood cells and your resistance to infection may be decreased. If you experience an infection with symptoms such as fever and serious deterioration of your general condition, or fever with local infection symptoms such as sore throat/sore pharynx/sore mouth or urinary problems you should see your doctor immediately. A blood test will be taken to check for possible reduction of white blood cells (agranulocytosis). It is important to tell your doctor that you are taking Nordimet.

Methotrexate is known to cause bone disorders such as joint and muscle pain and osteoporosis. The frequency of these risks in children is not known.

Nordimet may cause serious (sometimes life-threatening) side effects. Your doctor will do tests to check for abnormalities developing in the blood (e.g. low white blood cells, low platelets, lymphoma) and changes in the kidney and the liver.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via:

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Ireland

HPRA Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: [email protected]

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 the carton after EXP. The expiry date refers to the last day of that month.

Store below 25°C.

Keep the pen in the outer carton in order to protect from light.

You must not use Nordimet if the solution is not clear and contains particles.

Nordimet is for single use only. Any used pen should be discarded.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer require. These measures will help protect the environment.

6. Contents of the pack and other information

What Nordimet contains

The active substance is methotrexate. 1 ml of solution contains 25 mg methotrexate.

The other ingredients are sodium chloride, sodium hydroxide and water for injections.

The following pens are available:

Pre-filled pens of 0.3 ml containing 7.5 mg methotrexate.

Pre-filled pens of 0.4 ml containing 10 mg methotrexate

Pre-filled pens of 0.5 ml containing 12.5 mg methotrexate

Pre-filled pens of 0.6 ml containing 15 mg methotrexate

Pre-filled pens of 0.7 ml containing 17.5 mg methotrexate

Pre-filled pens of 0.8 ml containing 20 mg methotrexate

Pre-filled pens of 0.9 ml containing 22.5 mg methotrexate

Pre-filled pens of 1.0 ml containing 25 mg methotrexate

What Nordimet looks like and contents of the pack

Nordimet pre-filled pens contain a clear, yellow solution for injection. The pre-filled pens are designed to prevent needlestick injury and reuse.

Nordimet is available in packs containing 1 pre-filled pen of 0.3 ml, 0.4 ml, 0.5 ml, 0.6 ml, 0.7 ml, 0.8 ml, 0.9 ml or 1.0 ml solution for injection with attached needle and one alcohol swab and in multipacks of 4 and 6 carton, each containing 1 pre-filled pen solution for injection with attached needle and one alcohol swab.