Methotrexate 2.5mg/Ml Solution For Injection
(1,1) -1- PB Methotrexate 2.5mg_ml.indd 01.04.2008, 08:09:36
Package leaflet: Information for the patient
Read all of this leaflet carefully before this medicine is administered to you.
Keep this leaflet. You may need to read it again.
If you have 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.
In this leaflet:
1. What Methotrexate 2.5 mg/ml solution for injection is and what it is used for
2. Before receiving Methotrexate 2.5 mg/ml solution for injection
3. How Methotrexate 2.5 mg/ml solution for injection is administered
4. Possible side effects
5. How to store Methotrexate 2.5 mg/ml solution for injection
6. Further Information
Methotrexate 2.5 mg/ml solution for injection
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1. What Methotrexate 2.5 mg/ml solution for injection is and what it is used for
Methotrexate is one of a group of medicines known as antimetabolites. It is used in the treatment of cancer as well as psoriasis including psoriatic arthritis. It stops a substance called dihydrofolate reductase from working. This substance is an enzyme, which is important in “cell growth (replication)”. By inhibiting the enzyme, cancer cells will eventually “die”.
Methotrexate helps patients with psoriasis by killing the cells in the skin that are growing too fast. It is these rapidly growing cells that cause the raised patches of skin in psoriasis.
2. Before receiving Methotrexate 2.5 mg/ml solution for Injection
You should not receive Methotrexate 2.5 mg/ml solution for injection
• if you have ever had any allergic reaction to methotrexate
or any of the ingredients of this product
• if you have severe problems with your kidneys
• if you have severe problems with your liver, including alcoholic liver disease, abnormal blood counts, fibrosis, cirrhosis or recent active hepatitis
• if you suffer from alcoholism
• if you have any serious blood disorders (anaemia, a reduction in white cell number (leucopenia) or platelet number (thrombocytopenia))
• if you have an active infection
• if you have a medical condition, or are receiving medication, which lowers your resistance to infection
• if you are pregnant or intend to become pregnant, or are breast-feeding, as the drug can harm unborn and breastfed infants.
Take special care with Methotrexate 2.5 mg/ml solution for injection
• if you have impaired respiratory function
• if you have mild to moderate kidney or liver problems, or a mild to moderate blood disorder
• if you have diarrhoea
• if you have ulcers in your mouth, stomach or intestine (large bowel)
• if you have ascites (collection of liquid in the free abdominal cavity) and/or pleural effusions (collection of liquid in the pleural cavity)
• if you are receiving or intend to receive any vaccine, as methotrexate can reduce their effect
• if you have had radio- or chemotherapy before (especially of the pelvis), or are receiving radiotherapy concurrently
• if you have an impaired general condition (if you feel weak or infirm)
• if you are of advanced age
• if Methotrexate 2.5 mg/ml solution for injection is given to very young children.
This medicinal product contains 0.16 mmol (or 3.7 mg) sodium per ml. To be taken into consideration by patients on a controlled sodium diet.
Please consult your doctor, even if these statements were applicable to you at any time in the past.
Taking other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Medications which can be influenced by or can influence the effect of methotrexate negatively
• pain-killers such as salicylates (e.g. aspirin), amidopyrine derivatives, phenylbutazone and leflunomide
• diphenylhydantoins (e.g. phenytoin, an anti-epileptic agent)
• barbiturates and tranquillisers (sedative agents)
• antibiotics (medication against bacteria), e.g. tetracyclines, penicillins, chloramphenicol, cotrimoxazole and sulphonamides
• cytostatics (medication against cancer), e.g. doxorubicin, mercaptopurine, procarbazine, cisplatin, L-asparaginase and 5-fluorouracil
• Disease-modifying antirheumatic drugs (DMARD; drugs that are used to treat rheumatoid arthritis)
• probenecid (uricosuric agent used in the prophylaxis of gout)
• p-aminobenzoic acid (used in sun creams)
• non-steroidal anti-inflammatory drugs (NSAIDs; medications against “rheumatism”, e.g. indomethacin, ibuprofen)
• anti-folate drugs (e.g. nitrous oxide or co-trimoxazole)
• p-aminohippuric acid (substance to check kidney function)
• pyrimethamine (medication against malaria)
• acitretin or other retinoids (for psoriasis or skin disorders)
• theophylline (used mainly in bronchial asthma)
• erythrocyte concentrates (for blood transfusion)
• nitrous oxide-based anaesthetics
• omeprazole (used in the therapy of gastric ulcers)
• sulphasalazine (for ulcerative colitis)
• tetrahydrofolic acid preparations
• oral antidiabetics (medications to treat diabetes) and diuretics (increase urine output)
• hypoglycaemics (lower blood sugar levels)
• other medicinal products with nephrotoxic and hepatotoxic potential (incl. alcohol)
• vaccinations
• azathioprine (an immunosuppressive drug)
• vitamin preparations containing folic acid or its derivates Please note that these statements may also apply to products used some time ago or at some time in the future.
Pregnancy and breast-feeding
Do not take Methotrexate 2.5 mg/ml solution for injection if you are pregnant because it causes a variety of malformations or even the death of the foetus.
Women must not get pregnant during treatment with Methotrexate 2.5 mg/ml solution for injection. If you get pregnant during treatment with Methotrexate 2.5 mg/ml solution for injection, please inform your doctor immediately!
Special indications for contraception:
Methotrexate temporarily influences sperm and egg production. During treatment and up to 6 months after treatment is stopped, you must practice effective contraception. In this respect, it is of no importance whether the male or the female partner takes Methotrexate 2.5 mg/ml solution for injection!
Do not take Methotrexate 2.5 mg/ml solution for injection during breast-feeding, since methotrexate is excreted into the breast milk. Methotrexate can seriously harm breast-fed infants.
Ask your doctor for advice before taking any medicine.
3. How Methotrexate 2.5 mg/ml solution for injection is administered
Dosage
Your doctor will decide on a suitable dose for you. Doses vary considerably and will depend on the underlying disease.
Your doctor may instruct you to take sodium bicarbonate or acetazolamide tablets while receiving your injections to help make sure that methotrexate is not concentrated in the kidneys. If you receive methotrexate in high doses, you will receive calcium folinate as well to lessen the side effects of methotrexate.
It is possible that you will only get methotrexate. In the case of cancer, it is also possible that you will receive so-called combination therapy in which you must take several medications.
Your body weight, age, general condition of health, your response to the drug and whether other medicines are required at the same time will also influence the dose you receive.
Method of administration
Your doctor or nurse will give you Methotrexate 2.5 mg/ml solution for injection injecting it either into the central nervous system (intraventricular or intrathecal administration), into one of your veins (e.g. as bolus or infusion), arteries, or a muscle.
Tests during treatment with Methotrexate 2.5 mg/ml solution for injection
During your treatment, you will have a number of tests, such as regular blood tests to check that appropriate blood levels of methotrexate are attained and that your kidneys are eliminating excess drug properly.
Other tests are performed routinely at the start and during the course of therapy (e.g. chest X-ray, liver function test, full blood count and urinalysis).
4. Possible Side Effects
Like all medicines Methotrexate 2.5 mg/ml solution for injection can cause side effects, although not everybody gets them.
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uisease-moaiTying anurneumauc arugs (dmakd; arugs inai are used to treat rheumatoid arthritis) probenecid (uricosuric agent used in the prophylaxis of gout)
p-aminobenzoic acid (used in sun creams) non-steroidal anti-inflammatory drugs (NSAIDs; medications against “rheumatism”, e.g. indomethacin, ibuprofen) anti-Tolate drugs (e.g. nitrous oxide or co-trimoxazole) p-aminohippuric acid (substance to check kidney Tunction) pyrimethamine (medication against malaria) cholestyramine (lipid-lowering agent)
Like all medicines Methotrexate 2.5 mg/ml solution for injection can cause side effects, although not everybody gets them.
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The frequency of side effects is classified into the following categories:
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Very common |
in more than 1 in 10 patients |
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Common |
in more than 1 in 100 patients, but less than 1 in 10 patients |
|
Uncommon |
in more than 1 in 1,000 patients, but less than 1 in 100 patients |
|
Rare |
in more than 1 in 10,000 patients, but less than 1 in 1,000 patients |
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Very rare |
in less than 1 in 10,000 patients, including isolated reports |
Methotrexate has the potential for serious, sometimes fatal toxicity. Because the toxic reactions can occur at any time during therapy, your doctor should observe you closely and must inform you of early signs and symptoms of toxicity.
If you think you have an infection, a sore throat, fever or chills during treatment, you should tell your doctor immediately.
The most common undesirable effects are ulcerative stomatitis, leucopenia, nausea, and abdominal discomfort.
Undesirable effects of Methotrexate 2.5 mg/ml solution for injection are
Neoplasms
Uncommon: Lymphoma
Very rare: Tumour lysis syndrome (renal failure due to massive destruction of rapidly growing tumour cells)
Blood disorders
Common: Blood picture 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)
Immune system disorder
Uncommon: Allergic reactions, decreased resistance to infection
Metabolism and endocrine disorders Uncommon: Diabetes
Rare: Hyperuricaemia (increased blood levels of uric acid, possibly leading to gout)
Psychiatric disorders Rare: Mood swings, irritability
Nervous system disorders
Common: Headache, drowsiness, sleepiness
Uncommon: Seizures, leucoencephalopathy (inflammation of
the brain), manifested by ventricular enlargement (expansion
of the fluid spaces inside the brain), incomplete palsy affecting
one or both sides of the body, confusion, dizziness
Rare: Speech disorder, subtle cognitive dysfunction (easily
disturbed attention), mental disturbance
Very Rare: Unusual sensations in the head, pain,
paraesthesia (pins-and-needles sensation), muscle
weakness, significant intellectual deficit, dementia, cerebral
oedema (swelling of the brain) after administration into the
central nervous system possibly leading to vomiting, fits,
coma and even death
Eve disorders
Rare: Impairment of vision
Very rare: Swelling, inflammation of the eyelid edges, conjunctivitis (inflammation of the eye conjunctiva), unusual formation of tears, photophobia
Ear disorders
Rare: Ringing in the ears
Cardiac disorders
Rare: Low blood pressure, 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)
Vascular disorders
Uncommon: Vasculitis (inflammation of blood vessels)
Rare: Haematoma, point-like or small flat bleeding, complications resulting from the formation of blood clots in veins and arteries
Lung disorders
Common: 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), and/or abnormal findings on chest radiography and/or tests of respiratory function
Rare: Upper respiratory tract infection Gastro-intestinal disorders
Very common: Disorders of the mouth, stomach and intestines like mucositis (mucus membrane inflammation, e.g. inflammation of the gums, tongue, throat, mouth, intestines), lack of appetite, feeling sick Common: Diarrhoea
Uncommon: Vomiting, gastrointestinal ulcerations, inflammation of the pancreas
Rare: Malabsorption (disturbances of uptake of nutrition with consequences such as body weight loss), melaena (red to black stools)
Very rare: Unusual bleeding from the mouth, stomach and intestines, increased risk of perforation and toxic megacolon (severe complication with massive dilatation of the colon and severe pain
Liver and gall bladder disorders
Uncommon: Fibrosis (increase in the connective tissue), cirrhosis (transformation of the tissue with hardening and abolition of the normal structure of the organ), fatty degeneration of the liver or other histologic (tissue) changes in the liver
Rare: Hepatitis (inflammation of the liver)
Very rare: Acute liver cell death inflammation
Uncommon: Loss of hair, nettle rash, photosensitivity, pigmentary changes (discolouration of the skin), loss of skin tissue
Rare: Acne, an increase in rheumatic nodules, increased colouration or inflammation or detachment of the nails, nodulosis (formation of nodules under the skin)
Very rare: Telangiectasia (expansion of small superficial blood vessels in the skin), worsening of psoriasis (with concomitant UV therapy), formation of boils, a ..recall" of radiation dermatitis (inflammation of the skin) and sunburn
Musculoskeletal disorders
Uncommon: Osteoporosis, pain in the joints, muscle pain Very rare: aseptic necrosis of the femoral head (loss of bone tissue in the hip joint)
Renal and urinary disorders
Common: Impairment of renal function
Uncommon: Renal failure, inflammation of the urinary bladder,
pain or difficulty in passing urine
Very rare: blood in the urine
Pregnancy and lactation:
Uncommon: Malformations of the foetus Rare: Abortion
Reproductive and breast disorders
Uncommon: Vaginal discomfort
Rare: Menstrual dysfunction (periods may become less
frequent or even stop completely)
Very rare: Reduced or faulty formation of sperm and egg cells, infertility, loss of interest in sex / impotence, development of the breast gland in males
General disorders
Uncommon: Fever without any detectable cause Rare: Chills, malaise and undue fatigue, sweating Very rare: 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 like ataxia (disturbance of balance and co-ordination), 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).
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 any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.
5. How to store Methotrexate 2.5 mg/ml solution for injection
• Keep the medicine out of the reach and sight of children.
• Keep the vial in the outer carton in order to protect from light.
• Do not store above 25°C.
• For single dose use only. Discard any unused solution immediately and safely after initial use.
• This medicine should only be administered by a medically qualified person, e.g. a doctor.
• Methotrexate 2.5 mg/ml solution for injection should not be used after the expiry date printed on the label.
• Any unused product or waste should be disposed of in accordance with local requirements for example by incineration.
6. FURTHER INFORMATION
What Methotrexate 2.5 mg/ml solution for injection contains
The active substance is Methotrexate.
Each 1 ml of this sterile solution for injection contains 2.5 milligrams methotrexate.
The other ingredients are sodium chloride, sodium hydroxide, water for injections and nitrogen.
What Methotrexate 2.5 mg/ml solution for injection looks like and contents of the pack
Methotrexate 2.5 mg/ml solution for injection is a yellowish and sterile solution in clear glass vials.
Each pack contains 1,5 or 10 vials of 2 ml solution.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
medac Gesellschaft fur klinische Spezialpraparate mbH,
Fehlandtstrafte 3, 20354 Hamburg, Germany
Manufacturer:
Haupt Pharma Wolfratshausen GmbH, Pfaffenrieder Str. 5, 82515 Wolfratshausen, Germany
This leaflet was last approved in 04/2008.
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Skin disorders
ivianuidciurer.
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severe pain Liver and aall bladder disorders Uncommon: Fibrosis (increase in the connective tissue), cirrhosis (transformation of the tissue with hardening and abolition of the normal structure of the organ), fatty degeneration of the liver or other histologic (tissue) changes |
ivanuidciurer. Haupt Pharma Wolfratshausen GmbH, Pfaffenrieder Str. 5, 82515 Wolfratshausen, Germany |
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in the liver Rare: Hepatitis (inflammation of the liver) Very rare: Acute liver cell death |
This leaflet was last approved in 04/2008. |
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Skin disorders Common: Rash, itching, formation of blisters, redness and |
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PB Methotrexate 2.5mg_ml.indd 2 |
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