Metotrexat Medac
Package leaflet: Informationfor the user
Metotrexat Medac50 mg/ml solution for injection, pre-filled syringe
Methotrexate
Read all of this leaflet carefully before you start using this medicinebecause it contains important information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, please 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 Metotrexat Medacis and what it is used for
2. What you need to know before you use Metotrexat Medac
3. How to use Metotrexat Medac
4. Possible side effects
5. How to store Metotrexat Medac
6. Contents of the pack and other information
1. What Metotrexat Medac is and what it is used for
Metotrexat Medac contains methotrexate as active substance.
Methotrexate is a substance with the following properties:
• it interferes with the growth of certain cells in the body that reproduce quickly
• it reduces the activity of the immune system (body’s own defence mechanism)
• it has anti-inflammatory effects
Metotrexat Medac is indicated for the treatment of
• active rheumatoid arthritis in adult patients.
• severe recalcitrant disabling psoriasis, which is not adequately responsive to other forms of therapy such as phototherapy, PUVA, and retinoids, and severe psoriatic arthritis in adult patients.
Rheumatoid arthritis (RA)is a chronic collagen disease, characterised by inflammation of the synovial membranes (joint membranes). These membranes produce a fluid which acts as a lubricant for many joints. The inflammation causes thickening of the membrane and swelling of the joint.
Psoriatic arthritis is a kind of arthritis with psoriatric lesions of the skin and nails, especially at the joints of fingers and toes.
Psoriasis is a common chronic skin disease, characterised by red patches covered by thick, dry, silvery, adherent scales.
Metotrexat Medacmodifies and slows down the progression of the disease.
2. What you need to know beforeyou use Metotrexat Medac
Do not use Metotrexat Medac
• if youare allergic to methotrexate or any of the other ingredients of this medicine (listed in section 6).
• if you suffer from severe liver or kidney diseases or blood diseases.
• if you regularly drink large amounts of alcohol.
• if you suffer from a severe infection, e.g. tuberculosis, HIV or other immunodeficiency syndromes.
• if you suffer from ulcers in the mouth, stomach ulcer or intestinal ulcer.
• if you are pregnant or breast‑feeding.
• if you receive vaccinations with live vaccines at the same time.
Warnings and precautions
Talk to your doctor or pharmacist before using Metotrexat Medac.
Take special care with Metotrexat Medac
• if you are elderly or if you feel generally unwell and weak.
• if your liver function is impaired.
• if you suffer from dehydration (water loss).
Recommended follow‑up examinations and safety measures
Even when Metotrexat Medacis administered in low doses, severe side effects can occur. In order to detect them in time, check‑ups and laboratory tests have to be carried out by your doctor.
Before therapy
Before starting the treatment, blood samples will be taken in order to check that you have enough blood cells, tests to check your liver function, serum albumin (a protein in the blood) and kidney function. Your doctor will also check if you suffer from tuberculosis (infectious disease in combination with little nodules in the affected tissue) and a chest X‑ray will be taken.
During therapy
You will have the following tests at least once a month during the first six months and at least every three months thereafter:
• Examination of the mouth and throat for alterations of the mucosa
• Blood tests
• Check of liver function
• Check of kidney function
• Check of respiratory system and if necessary lung function test
Methotrexate may affect your immune system and vaccination results. It may also affect the result of immunological tests. Inactive, chronic infections (e.g. herpes zoster [shingles], tuberculosis, hepatitis B or C) may flare up. During therapy with Metotrexat Medacyou must not be vaccinated with live vaccines.
Radiation-induced dermatitis and sun-burn can reappear under methotrexate therapy (recall-reaction). Psoriatic lesions can exacerbate during UV-irradiation and simultaneous administration of methotrexate.
Enlarged lymph nodes (lymphoma) may occur and therapy must then be stopped.
Diarrhoea can be a toxic effect of Metotrexat Medacand requires an interruption of therapy. If you suffer from diarrhoea please speak to your doctor.
Encephalopathy (a brain disorder) / leukoencephalopathy (a special disorder of the white brain substance) have been reported in cancer patients receiving methotrexate therapy and cannot be excluded for methotrexate therapy in other diseases.
Other medicines and Metotrexat Medac
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
The effect of the treatment may be affected if Metotrexat Medacis administered at the same time as certain other medicines:
• Medicines harming the liver or the blood count, e.g. leflunomide
• Antibiotics (medicines to prevent/fight certain infections) such as: tetracyclines, chloramphenicol, and non-absorbable broad-spectrum antibiotics, penicillines, glycopeptides, sulphonamides (sulphur containing medicines that prevent/fight certain infections), ciprofloxacin and cefalotin
• Non-steroidal anti-inflammatory drugs or salicylates (medicines against pain and/or inflammation)
• Probenecid (medicine against gout)
• Weak organic acids like loop diuretics (“water tablets”) or some medicines used for treatment of pain and inflammatory diseases (e.g. acetylsalicylic acid, diclofenac and ibuprofen) and pyrazole (e.g. metamizol for treating pain)
• Medicines which may have adverse effects on the bone marrow, e.g. trimethoprim-sulphamethoxazole (an antibiotic) and pyrimethamine
• Sulphasalazine (antirheumatic medicine)
• Azathioprine (an immunosuppressive agent sometimes used in severe forms of rheumatoid arthritis)
• Mercaptopurine (a cytostatic agent)
• Retinoids (medicine against psoriasis and other dermatological diseases)
• Theophylline (medicine against bronchial asthma and other lung diseases)
• Proton-pump inhibitors (medicines against stomach trouble)
• Hypoglycaemics (medicines that are used to lower the blood sugar)
Vitamins containing folic acid may impair the effect of your treatment and should only be taken when advised by your doctor.
Vaccination with live vaccine must be avoided.
Metotrexat Medac with food. drink and alcohol
Alcohol as well as large amounts of coffee, caffeine-containing soft drinks and black tea should be avoided during treatment with Metotrexat Medac
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 or pharmacist for advice before taking this medicine.
You must not take Metotrexat Medac during pregnancy. There is a risk of harm to the foetus and miscarriage. Men and women should use an effective method of birth control during treatment and for a further six months after treatment with Metotrexat Medac has been discontinued.
In women of child-bearing age, any existing pregnancy must be excluded with certainty by taking appropriate measures, e.g. pregnancy test, prior to therapy.
Breast-feeding should be stopped prior to and during treatment with Metotrexat Medac.
As methotrexate can be genotoxic, all women who wish to become pregnant are advised to consult a genetic counselling centre, if possible, already prior to therapy, and men should seek advice about the possibility of sperm preservation before starting therapy.
Driving and using machines
Treatment with Metotrexat Medacmay cause adverse reactions affecting the central nervous system, e.g. tiredness and dizziness. Thus the ability to drive a vehicle and/or to operate machines may, in certain cases, be compromised. If you feel tired or drowsy you should not drive or use machines.
Metotrexat Medac contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.
3. How to use Metotrexat Medac
Metotrexat Medacis administered by or under the supervision of a physician or healthcare staff as an injection once a week only. Together with your doctor you decide on a suitable weekday each week on which you receive your injection. Metotrexat Medacmay be injected intramuscularly (in a muscle), intravenously (in a vein) or subcutaneously (under the skin).
The manner of handling and disposal must be consistent with that of other cytostatic preparations in accordance with local requirements. Pregnant health care personnel should not handle and/or administer Metotrexat Medac.
Methotrexate should not come into contact with the surface of the skin or mucosa. In the event of contamination, the affected area must be rinsed immediately with plenty of water.
Your doctor decides on the dosage, which is adapted individually to you. Usually it takes 4 – 8 weeks before there is any effect of the treatment. The duration of the treatment is decided by your doctor. For further information see section 6.
If you have the impression that the effect of Metotrexat Medacis too strong or too weak, you should talk to your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The frequency as well as the degree of severity of the side effects depends on the dosage level and the frequency of administration. As severe side effects may occur even at low dosage, it is important that you are monitored regularly by your doctor.
The most relevant side effects are effects on the blood forming system and the gastrointestinal tract.
The following side effects may occur:
Very common (may affect more than 1 out of 10 people):
• Mouth inflammation, indigestion, nausea (feeling sick), loss of appetite
• Increase in liver enzymes
Common (may affect up to 1 in 10 people):
• Mouth ulcers, diarrhoea
• Rash, reddening of the skin, itching
• Headache, tiredness, drowsiness
• Pneumonia ([allergic] inflammation of the lungs) may occur (symptoms are: dry, non-productive cough, shortness of breath and fever)
• Reduced blood cell formation with decrease in white and/or red blood cells and/or platelets (leukopenia, anaemia, thrombocytopenia)
Uncommon (may affect up to 1 in 100 people):
• Throat inflammation, inflammation of the bowels, vomiting
• Increased sensitivity to light, loss of hair, increased number of rheumatic nodules, shingles, inflammation of blood vessels, herpes-like skin rash, hives
• Onset of diabetes mellitus
• Dizziness, confusion, depression
• Liver cirrhosis (chronic liver damage), formation of scar tissue of the liver, fatty degeneration of the liver, decrease in serum albumin
• Decrease in the number of blood cells and platelets
• Inflammation and ulcer of the urinary bladder or vagina, reduced kidney function, disturbed urination
• Joint pain, muscle pain, osteoporosis (reduction of bone mass)
Rare (may affect up to 1 in 1,000 people):
• Gastrointestinal ulcers
• Increased skin pigmentation, acne, blue spots due to vessel bleeding
• Allergic reactions, allergic shock, allergic inflammation of blood vessels, fever, red eyes, infection, blood poisoning, wound-healing impairment, decreased number of anti-bodies in the blood
• Visual disturbances
• Acute hepatitis (inflammation of the liver)
• Inflammation of the sac around the heart, accumulation of fluid in the sac around the heart
• Low blood pressure, occlusion of a blood vessel by dislodged blood clot (thromboembolic events)
• Lung fibrosis, pneumonia with a specific germ (Pneumocystis cariniipneumonia), shortness of breath and bronchial asthma, accumulation of fluid in the sac around the lung
• Kidney failure, decrease or absence of urine, electrolyte disturbances
Very rare (may affect up to 1 in 10,000 people):
• Haematemesis (vomiting blood), profuse bleeding, toxic megacolon (acute toxic dilatation of the gut)
• Skin blisters in connection with fever, burned skin syndrome, increased pigmentation of the nails, inflammation of the cuticles, furunculosis (deep infection of hair follicles), visible enlargement of small blood vessels
• Local damage (formation of sterile abscess, changes in the fatty tissue) of injection site following administration into a muscle or under the skin
• Impaired vision, pain, loss of strength or sensation of numbness or tingling in arms and legs, changes in taste (metallic taste), convulsions, paralysis, severe headache with fever
• Retinopathy (noninflammatory eye disorder)
• Liver failure
• Sharp fall in white blood cells, severe bone marrow depression
• Loss of sexual drive, impotence, male breast enlargement (gynaecomastia), defective sperm formation, menstrual disorder, vaginal discharge
• Enlargement of lymphatic nodes (lymphoma)
Not known:frequency cannot be estimated from the available data:
• Leukoencephalopathy (a disease of the white brain substance)
When methotrexate is given by the intramuscular route, local undesirable effects (burning sensation) or damage (formation of sterile abscess, destruction of fatty tissue) at the site of injection can occur commonly. Subcutaneous application of methotrexate is locally well tolerated. Only mild local skin reactions were observed, decreasing during therapy.
Metotrexat Medac 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 inform your doctor about your medicine.
Methotrexate may cause serious (sometimes life-threatening) side effects. Therefore, 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.
Reportingof 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 (see details below). By reporting side effects you can help provide more information on the safety of this medicine.
[To be completed nationally]
5. Howto store Metotrexat Medac
Keep this medicine out of the sight and reach of children.
Store below 25 °C.
Keep the pre-filled syringes in the outer carton in order to protect from light.
Do not use after the expiry date which is stated on the packaging. The expiry date refers to the last day of that month.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6. Contents of the pack and other information
What Metotrexat Medac contains
• The active substance is methotrexate. 1 ml of solution contains methotrexate disodium corresponding to 50 mg methotrexate.
• The other ingredients are sodium chloride, sodium hydroxide and water for injections.
What Metotrexat Medac looks like and contents of the pack
Metotrexat Medac pre‑filled syringes contain a clear, yellow-brown solution.
The following pack sizes are available:
Pre-filled syringes with embedded sc. injection needles, graduation and alcohol pads containing 0.15 ml, 0.20 ml, 0.30 ml, 0.40 ml, and 0.50 ml solution for injection in packs of 1, 4, 6, 12, and 24 pre‑filled syringes.
Pre-filled syringes with enclosed sc. injection needles, graduation and alcohol pads containing 0.15 ml, 0.20 ml, 0.30 ml, 0.40 ml, and 0.50 ml solution for injection in packs of 1, 4, 6, 12, and 24 pre‑filled syringes. Not all pack sizes may be marketed.
For i.m and i.v. use, a needle suitable for these routes of administration must be used: The needle enclosed in the pack is suitable for s.c. use only.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
medac Gesellschaft für klinische Spezialpräparate mbH
Fehlandtstr. 3
20354 Hamburg
Germany
Phone: +49 4103 8006-0
Fax: +49 4103 8006-100
Manufacturer:
medac Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Phone: +49 4103 8006-0
Fax: +49 4103 8006-100
This medicinal product is authorised in the Member States of the EEA under the following names:
Ireland Metoject 50 mg/ml Solution for injection, pre-filled syringe
Sweden Metotrexat medac, 50 mg/ml, Injektionsvätska, lösning, förfylld spruta
This leaflet was last revised in 19 February 2014.