Methotrexate 25 Mg/Ml Solution For Injection
Methotrexate - Pack Insert - GBR - (Bordon)
PACKAGE LEAFLET:
INFORMATION FOR THE USER
METHOTREXATE 25 MG/ML SOLUTION FOR INJECTION
(METHOTREXATE)
Read all of this leaflet carefully before you are given
Methotrexate 25 mg/ml Solution for Injection.
- Keep this leaflet. You may want to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
methotrexate treatment may not be appropriate.
Special care should be taken:
• if you have a stomach ulcer or ulcerative colitis (inflammation and ulceration of the gut)
• if you have a medical condition which causes a build up of fluid in the lining of your lungs or in your abdomen (the fluid will need to be drained before methotrexate treatment is started)
• if you are to have radiotherapy (risk of tissue and bone damage may be increased)
• if you are to have any vaccinations (methotrexate can reduce the effect of vaccines)
• if you suffer from alcoholism
• if you have an infectious disease
• if you have a problem with your immune system
• if you are suffering from diarrhoea
• if you are weak or infirm
Taking other medicines:
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicine obtained without a prescription.
• pain-killers such as salicylates (e.g. aspirin), amidopyrine derivatives, phenylbutazone, non-steroidal anti-inflammatory drugs (NSAIDs; medications against “rheumatism”, e.g. indomethacin, ibuprofen)
• drugs used to treat seizures and anxiety, diphenylhydantoins (e.g. phenytoin), barbiturates and tranquillisers (sedative agents)
• antibiotics (medication used against bacteria and other microorganisms) e.g. penicillins (amoxicillin, carbenicillin and mezlocillin), sulphonamides, co-trimoxazole (trimethoprim), tetracycline, chloramphenicol and p-aminobenzoic acid (used in sun creams)
• cytostatics (medication against cancer) e.g. doxorubicin, mercaptopurine, procarbazine, cisplatin, L-asparaginase and 5-fluorouracil
• probenecid (used in the prophylaxis of gout)
• pyrimethamine (medication against malaria)
• cholestyramine (lipid-lowering agent)
• acitretin or other retinoids (for psoriasis or skin disorders)
• theophylline (used mainly in bronchial asthma)
• erythrocyte concentrates (for blood transfusion)
• nitrous oxide-based anaesthetics
• tetrahydrofolic acid preparations
• p-aminohippuric acid (substance to check kidney function)
• oral antidiabetics (medications to treat high blood sugar) and diuretics-water tablets e.g. furosemide (increase urine output for treatment high blood pressure)
• other medicinal products with nephrotoxic and hepatotoxic potential (including alcohol)
• vitamin preparations containing folic acid or its derivates azathioprine (drug to decrease the immunity)
• omeprazole (drug to treat stomach ulcer)
Inform your doctor if you are receiving UV rays for the treatment of psoriasis (skin disorder) as the lesions may worsen.
Taking with food and drink:
You should not drink alcohol whilst receiving methotrexate therapy.
Pregnancy and breast-feeding:
Ask your doctor or pharmacist for advice before taking any medicine.
Tell your doctor at once if you think you have become pregnant.
Methotrexate can harm unborn babies. You should not receive methotrexate if you are pregnant or trying to become pregnant or your partner is trying to become pregnant.
Methotrexate should not be given to you if you are breast-feeding, because methotrexate passes into the mother’s breast milk and can cause side-effects in breast-feeding infants.
Avoid becoming pregnant or fathering children for at least six months after stopping your treatment with methotrexate due to the temporary effect of methotrexate on sperm and egg production.
Driving and using machines:
Do not drive or use machines:
• if you feel drowsy
• if you experience any other effect which may impair your ability to drive or use machines
3. HOW METHOTREXATE 25 MG/ML SOLUTION FOR INJECTION IS GIVEN
Methotrexate will be given to you under the supervision of a doctor experienced in its use. Methotrexate will usually be given to you by a nurse or doctor as an injection either, into a vein (intravenously), or artery (intraarterially), or into a muscle (intramuscularly).
The dose of medicine given to you will depend on the disease being treated, your medical condition, your age, your body weight or body surface area in square meter (m1 2 3 4 5 6 7), how well your kidneys are working and the way that you will be given the drug. The amount of methotrexate you are given will also depend on the condition being treated and whether methotrexate is being given on its own or with one of several medicines. Your doctor will decide on the correct amount of Methotrexate Injection which you should receive.
Before treatment is started your doctor may carry out blood tests to check the levels of cells in your blood, and also to check how well your kidneys and liver are working. You may have tests before, during and after your treatment to ensure that Methotrexate is working properly and your kidneys are getting rid of the drug that is not required. You may also have a chest X-ray. Further tests may also be done during and after treatment. Do not miss appointments for these tests.
As this medicine will be given to you whilst you are in hospital, it is unlikely that you will be given too much or too little, however, tell your doctor or pharmacist if you have any concerns.
4. POSSIBLE SIDE EFFECTS
Like all medicines, methotrexate can cause side effects although not every body gets them.
Methotrexate is a very toxic medicine which has the potential for serious, sometime fatal toxicity. During treatment you should watch for any side effects and report them to the doctor.
Methotrexate may affect some of the other cells in your body as well as the cancer cells and you will probably suffer from some side effects. Side effects increase with a higher dose of methotrexate.
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Methotrexate - Pack Insert - GBR - (Bordon)
The most common side effects are nausea, a painful or swollen abdomen, soreness or ulceration of the mouth and lips, and leucopenia and thrombocytopenia (a blood disorder that may be characterised by fever or chills) and sore throat or ulcers in your mouth or throat.
Unwanted effects of Methotrexate 25 mg/ml Solution for Injection are:
• Blood function changes - e.g. your vulnerability for infections may increase, you may suffer from unusual bleeding or bruising and you may observe signs of anaemia (weakness, tiredness, difficulties in breathing), palpable lymph nodes
• Gastrointestinal: disorders of the mouth, stomach and intestines like mucositis (mucous membrane inflammation, e.g. inflammation of the gums, tongue, throat, mouth, intestines as well as ulcerations), lack of appetite, feeling sick, vomiting, diarrhoea, unusual bleeding from the mouth, stomach and intestines, inflammation of the pancreas, increased risk of perforation, melaena (red to black stools), malabsorption (disturbances of uptake of nutrition with consequences such as body weight loss & malnutrition), and toxic megacolon (severe complication with massive dilatation of the colon and severe pain)
• Kidney and urinary functions: renal failure (less passage of urine or no urine), impairment of renal function, inflammation of the urinary bladder, blood in the urine, reduced or faulty formation of sperm and egg cells, menstrual dysfunction (periods may become less frequent or even stop completely or irregular), infertility, abortion, malformations of the foetus and pain or difficulty in passing urine, inflammation & itching at female reproductive organ.
• Liver and gall functions: damage to the liver such as fibrosis (increase in the connective tissue formation), cirrhosis (transformation of the tissue with hardening and abolition of the normal structure of the organ), hepatitis (inflammation of the liver), acute liver cell death, fatty degeneration of the liver or other histologic (tissue) changes in the liver, marked changes laboratory investigations and elevations in liver enzymes (transaminases, alkaline phosphatase) & bilirubin.
• Respiratory functions: damage to the lungs such as inflammation and fibrosis (increase in the connective tissue); the pulmonary toxicity may manifest as fever, cough (especially dry and nonproductive), difficulties or increase in the frequency of breathing, chest pain, hypoxaemia (lack of oxygen in the blood).
• Dermatologic (skin) reaction: adverse reactions of the skin such as formation of blisters, becoming red and inflamed, loss/ detachment of skin tissue, vasculitis (inflammation of blood vessels), extensive herpetiform skin eruptions (erythematous, urticarial plaques), rash, itching, nettle rash, inflammatory skin eruption, photosensitivity, pigmentary changes (discolouration of the skin), telangiectasia (expansion of small superficial blood vessels in the skin), acne, formation of boils, pointlike or small flat bleeding, loss of hair, worsening of psoriasis (with concomitant UV therapy), increased colouration or inflammation or detachment of the nails, tender infection and inflammation around the base of nail, a “recall” of radiation dermatitis (inflammation of the skin) and sunburn
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• Nervous system: leucoencephalopathy (inflammation of the brain), manifested by ventricular enlargement (expansion of the fluid spaces inside the brain), confusion, shaking, irritability, sleepiness, ataxia (disturbance of balance and co-ordination), dementia, feeling sick, fever, and occasionally seizures or coma, significant intellectual deficit, headache, drowsiness, speech disorder, incomplete palsy affecting one or both sides of the body, fits, dizziness, vomiting, mental disturbance, pain, muscle weakness, paraesthesia (pins-and-needles sensation), subtle cognitive dysfunction (easily disturbed attention), mood swings, unusual sensations in the head, and even death, cerebral oedema (swelling of the brain).
• Eye: unwanted reactions of the eyes like swelling, inflammation of the eyelid edges, conjunctivitis (inflammation of the eye conjunctiva), unusual formation of tears, photophobia, and impairment of vision
• Other side effects: allergic reactions, haematoma, nodulosis (formation of nodules under the skin), loss of interest in sex / impotence, chills, fever without any detectable cause, decreased resistance to infection, upper respiratory tract infection, abnormal tissue cell changes, metabolic disorders, hyperuricaemia (increased blood levels of uric acid, possibly leading to gout), diabetes, osteoporosis and other bone disorders, including aseptic necrosis of the femoral head (loss of bone tissue in the hip joint), pains in the joints, muscle pain, malaise and undue fatigue, development of the breast gland in males, ringing in the ears, sweating, vaginal discomfort, in rare cases pericarditis (inflammation of the outer lining of the heart), pericardial effusion and tamponing (collection of fluid and blood, respectively, in the space between the outer lining of the heart and the heart muscle), low blood pressure, complications resulting from the formation of blood clots in veins and arteries, tumour lysis syndrome (renal failure due to massive destruction of rapidly growing tumour cells) and even sudden death
• in cases of acute lymphocytic leukaemia, Methotrexate can cause pain in the left epigastric region (the area overlying the stomach, below the left lower border of the rib cage; inflammation of the space above the spleen due to destruction of the leukaemic cells)
• other possible complications from administration into the central nervous system include Guillain-Barre syndrome (inflammation of the central nervous system), nerve palsies, and cerebellar dysfunction, arachnoiditis (inflammation of one of the membranes surrounding the spinal cord) manifested as headache, back pain, neck stiffness, and/or fever, subacute myelopathy (disorder affecting the spinal cord) manifested as complete or incomplete palsy of the lower limbs (paraparesis or paraplegia) following intrathecal administration.
• Methotrexate can reduce your resistance to infection (opportunistic infections). If you think you have an infection, sore throat, fever, chills or aches you should contact your doctor.
o Sometimes fatal opportunistic infections (pneumocystis carinii pneumonia, norcardiosis, histoplasmosis, cryptococcosis, herpes zoster, herpes simplex hepatitis, disseminated herpes simplex) have been reported. o It has been suggested that children with Down’s syndrome are less able to tolerate methotrexate therapy.
o Osteopathy may occur with Methotrexate therapy in patients (adults and children) for treatment of acute lymphocytic leukaemia, osteosarcoma.
• There have been reports on the manifestation of lymphomas which were, in some cases, reversible after discontinuing methotrexate therapy. The potential of Methotrexate to produce other cancers in humans has been evaluated in several studies, but the results do not confirm a cancerogenic risk.
If you notice any side effects not mentioned in this leaflet, please tell your doctor or pharmacist.
If you experience any other unexpected effects, which you think may be due to receiving this injection, inform your doctor.
5. HOW TO STORE METHOTREXATE 25 MG/ML SOLUTION FOR INJECTION
Keep Methotrexate 25 mg/ml Solution for Injection out of the reach and sight of children.
The vials should not be stored above 25°C. Do not freeze. Keep vial in outer carton in order to protect from light
The medicine should not be used after the expiry date (e.g. Expiry) printed on the vial and carton. The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. FURTHER INFORMATION
What Methotrexate 25 mg/ml Solution for Injection contains
The active substance is Methotrexate. Each 1 ml of solution contains 25 mg of methotrexate.
The other ingredients are sodium chloride, sodium hydroxide, hydrochloric acid and water for injection.
What Methotrexate 25 mg/ml Solution for Injection looks like and contents of the pack
This medicine is a yellowish solution for injection, presented in glass containers called vials. Each vial of 40 ml of solution contains 1 g methotrexate. The vials contain 25 mg of methotrexate (as methotrexate sodium formed in situ) per ml (millilitre). Methotrexate 25 mg/ml Solution for Injection is available as 1g in 40 ml fill in 50 ml vials.
Marketing Authorisation Holder and Manufacturer Fresenius Kabi Oncology Plc
Lion Court
Farnham Road, Bordon Hampshire GU35 0NF United Kingdom
This leaflet was last approved in July 2011
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In this leaflet:
What Methotrexate 25 mg/ml Solution for Injection is and what it is used for
Before you are given Methotrexate 25 mg/ml Solution for Injection
How Methotrexate 25 mg/ml Solution for Injection is given
Possible side effects
How to store Methotrexate 25 mg/ml Solution for Injection
Further Information
1. WHAT METHOTREXATE 25 MG/ML SOLUTION FOR INJECTION IS AND WHAT IT IS USED FOR
Methotrexate Injection is an antimetabolite medicine (medicine which affects the growth of body cells) and immunosuppressant (medicine which reduces the activity of the immune system).
Methotrexate is used in large doses (on its own or in combination with other medicines) to treat certain types of cancer. In smaller doses it can be used to treat severe psoriasis (a skin disease with thickened patches of inflamed red skin, often covered by silvery scales), when it has not responded to other treatments.
2. BEFORE YOU ARE GIVEN METHOTREXATE 25 MG/ ML SOLUTION FOR INJECTION
You should not be given methotrexate:
• if you have shown signs of hypersensitivity (severe allergy) to methotrexate or any of the other ingredients on previous occasions
• if you have a significant liver problem including liver disease, fibrosis, recent or active hepatitis (inflammation of the liver)
• if you have a significant kidney problem
• if you have a blood disorder which may be characterised by fever or chills, sore throat, ulcers in the mouth or throat, unusual tiredness or weakness, unusual bleeding or unexplained bruising or an abnormal blood count or low levels of RBCs (Red blood cells), WBCs (White blood cells) or platelets.
• if you are pregnant, or trying to become pregnant or if your partner is trying to become pregnant.
• if you are breast-feeding
Check with your doctor if any of the above apply to you as