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METHOTREXATE is a brand name for Methotrexate. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Methotrexate 100 mg/ml solution for injection may be used for the following indications: • Acute lymphocytic leukaemias (ALL) - in combination with other cytotoxic medicinal products • Non-Hodgkin’s lymphomas - in combination with other cytotoxic medicinal products in adult patients with Non-Hodgkin’s lymphomas of…
Verbatim from this product's MHRA label. Tap a section to expand.
Note:
Methotrexate 100 mg/ml solution for injection is a hypertonic presentation and therefore not suitable for intrathecal and intraventricular use. Methotrexate 100 mg/ml solution for injection should only be prescribed by physicians with experience in antimetabolite chemotherapy and the management of the approved indications.
The treatment regimen should be decided on an individual patient basis, with reference to current treatment protocols. Methotrexate can be applied in the form of an intravenous, intramuscular, or intra-arterial injection as well as an intravenous infusion.
Within the scope of therapy with high doses, methotrexate is administered as a continuous intravenous infusion (glucose, isotonic saline). Doses are usually based on the patient’s body weight or body surface area (BSA). Total doses greater than 100 mg are usually given by intravenous infusion.
Pharmaceutical forms with the lowest possible strength should be used. Fatal cases of intoxication have been reported after intravenous administration of incorrectly calculated doses. Therefore, doses must be carefully calculated in all patients.
Before beginning combination therapy involving high-dose methotrexate the leukocyte and thrombocyte count should exceed the respective minimum values (leukocytes 1 000 to 1 500/μl, thrombocytes 50 000 to 100 000/μl). When applying high-dose methotrexate therapy, the serum methotrexate concentration must be checked at regular intervals.
The sampling times and the maximum values for toxic serum methotrexate concentrations which require measures such as an increase in the calcium folinate dose or the intravenous fluid supply can be taken from the individual therapy protocols.
6. Skin and mucous membrane contact with methotrexate should be avoided. If methotrexate contaminates the skin it should be washed off immediately using copious amounts of running water for at least ten minutes. For methotrexate treatment measurement of serum methotrexate level is absolutely necessary.
It is useful to separate the treatment with methotrexate according to the following regimen. Low-dose therapy Single dose under 100 mg/m² Medium-dose therapy Single dose between 100 mg/m² and 1 000 mg/m² High-dose therapy Single dose above 1 000 mg/m² For methotrexate doses exceeding approx.
Occurrence and severity of undesirable effects depend on dose level and frequency of methotrexate administration. However, as severe adverse reactions may occur even at lower doses, it is indispensable that the doctor monitors patients regularly at short intervals.
Most undesirable effects are reversible if recognised early. In very rare cases severe adverse reactions mentioned below can be fatal. 9). Methotrexate therapy should only be resumed with caution, under close assessment of the necessity for treatment and with increased alertness for possible reoccurrence of toxicity.
Myelosuppression and mucositis are the predominant dose-limiting toxic effects of methotrexate. The severity of these reactions depends on the dose, mode and duration of application of methotrexate. Mucositis generally appears about 3 to 7 days after methotrexate application, leucopenia and thrombocytopenia follow a few days later.
In patients with unimpaired elimination mechanisms, myelosuppression and mucositis are generally reversible within 14 to 28 days. The most common undesirable effects are ulcerative stomatitis, leucopenia, thrombocytopenia, nausea, vomiting, anorexia and abdominal discomfort.
Especially during the first 24–48 hours after methotrexate administration decreased creatinine clearance and increase in liver enzymes (ALAT, ASAT, alkaline phosphatase, bilirubin) occur. The following undesirable effects have been observed and reported during treatment with methotrexate with the following frequencies: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
The following adverse reactions may occur:
4. During treatment with methotrexate patients require careful monitoring to avoid severe toxicity. The application and dose recommendation for the administration of methotrexate for different indications varies considerably. Some common doses and therapy protocols, which have proved to be efficacious in the therapy of the disorder in each case, are given below.
Current published protocols should always be consulted for posology and method and sequence of administration. g. hydatidiform mole and chorioadenoma destruens) The following regimens have been used. Reference should always be made to current published protocols.
Low risk patients 15–30 mg/m² intramuscularly for five days in combination with folinic acid. Usually, such courses may be repeated 3 to 5 times as required, with rest periods of one or more weeks interposed between the courses, until any manifesting toxic symptoms subside.
High risk patients Combination therapy:
Methotrexate IV as single doses of 300 mg/m² body surface area. Detailed information can be found in current published treatment protocols such as EMA/CO- protocol. Breast cancer Methotrexate has been used at a dose of 40 mg/m² intravenously on the first and eighth day of the cycle in combination with oral or IV cyclophosphamide and IV fluorouracil with regard to the CMF-protocol.
Head and neck cancer Monotherapy: 40–60 mg/m² body surface area methotrexate can be given once weekly as intravenous bolus injection. Reference should always be made to current published treatment protocols. Non-Hodgkin’s lymphomas Methotrexate is used for the treatment of Non-Hodgkin’s lymphoma in children and adults within the scope of complex therapy protocols.
Methotrexate is applied according to the phase of the disease, age and the histological type within the scope of various polychemotherapies. Reference should always be made to current published therapy protocols. Paediatric population Dose range for therapy with methotrexate at medium or high dose: single doses from 300– 5 000 mg/m² as an intravenous infusion.
g. 6), - renal insufficiency (creatinine clearance less than 60 ml/min), - alcohol abuse, - stomatitis, gastrointestinal ulceration.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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100 mg/m² as a single dose, the methotrexate treatment must be followed by application of calcium folinate (see calcium folinate rescue). High-dose methotrexate therapy (>1 000 mg/m² body surface area) High doses may cause the precipitation of methotrexate or its metabolites in the renal tubules.
g. g. 500 mg orally four times a day) is recommended as a preventative measure. High-dose methotrexate therapy should only be carried out if the creatinine concentration is within the normal range. g. marked adverse reactions from prior therapy with methotrexate or impairment of urine flow), the creatinine clearance must be determined.
Current published protocols should be consulted for posology and method and sequence of administration. 4). Posology in patients with renal impairment Since methotrexate is predominately eliminated renally, in patients with impaired creatinine clearance, delayed elimination is to be expected, which can lead to severe adverse reactions.
In patients with impaired renal function, the dose regimens must be adjusted according to the creatinine clearance and serum methotrexate concentrations. Renal function can be adversely affected by the application of methotrexate. Methotrexate should be used with caution in patients with impaired renal function.
The following dose adjustments have been used. Reference should be made to current published treatment protocols. Creatinine clearance >80 ml/min: 100% of the recommended standard dose Creatinine clearance = 80 ml/min: 75% of the recommended standard dose Creatinine clearance = 60 ml/min: 63% of the recommended standard dose Creatinine clearance <60 ml/min: Use alternative therapy Posology in patients with pathological fluid accumulation Methotrexate elimination is reduced in patients with pathological fluid accumulation (third space fluids) such as ascites or pleural effusions that may lead to prolonged methotrexate plasma elimination half-life and unexpected toxicity.
Pleural effusions and ascites should be drained prior to initiation of methotrexate treatment. Methotrexate dose should be reduced according to the serum methotrexate concentrations. Elderly patients Methotrexate should be used with extreme caution in elderly patients.
Elderly patients should be monitored closely for early signs of methotrexate toxicity. Dose reduction should be considered in elderly patients due to reduced liver and kidney function as well as lower folate reserves which occur with increased age.
g. for the treatment of ALL. Paediatric population Methotrexate should be used with caution in the paediatric population. Standard therapy protocols should be consulted for posology and method and sequence of administration. Fatal cases of intoxication have been reported after intravenous administration of incorrectly calculated doses.
Therefore, posology must be carefully calculated in the paediatric population. For detailed information about recommended examinations and safety measures see section
Infections and infestations Common: herpes zoster Uncommon: opportunistic infections (sometimes fatal), including pneumonia Rare: sepsis Very rare: nocardiosis, histoplasmosis, cryptococcosis, herpes simplex hepatitis, disseminated herpes simplex, cytomegalovirus infection, cytomegalovirus pneumonia, septicaemia Neoplasms benign, malignant and unspecified (incl.
g. g. cough, dyspnoea, impaired pulmonary function test), pneumocystis carinii pneumonia Not known: acute pulmonary oedema Gastrointestinal disorders Very common: stomatitis, abdominal pain, anorexia, nausea, vomiting Common: diarrhoea Uncommon: ulcerative stomatitis, haemorrhagic gastroenteritis, pancreatitis Rare: enteritis, gingivitis, melena Very rare: haematemesis Not known: toxic megacolon When stomatitis or diarrhoea occur, therapy with methotrexate should be discontinued due to the danger of haemorrhagic enteritis or perforation or dehydration.
Hepatobiliary disorders Common: elevated transaminases, bilirubin and alkaline phosphatase Uncommon: chronic cirrhosis and fibrosis, decrease in serum albumins, fatty liver Rare: hepatotoxicity, acute hepatitis Very rare: acute liver necrosis, liver failure, reactivation of chronic hepatitis Not known: reactivation of hepatitis B, worsening of hepatitis C Skin and subcutaneous tissue disorders Common: erythema, pruritus, exanthema Uncommon: alopecia, Stevens-Johnson syndrome, extensive herpetiform skin eruptions, toxic epidermic necrolysis (Lyell syndrome), urticaria, photosensitivity reactions, pigmentary changes, impaired wound healing Rare: acne, ecchymoses, erythema multiforme, nodulosis, hyperpigmentation of the nails, onycholysis, increase in rheumatic nodules Very rare: acute paronychia, furunculosis, telangiectasia Not known skin exfoliation/dermatitis exfoliative, skin necrosis, petechiae With concomitant UV therapy psoriatic lesions can worsen.
Radiation dermatitis and sunburn may be “recalled” by the use of methotrexate. Musculoskeletal and connective tissue disorders Uncommon: arthralgia, myalgia, osteoporosis Rare: stress fractures Not known: aseptic necrosis of the femoral […]
g. NHL-BFM working group. Adults (intermediate and high malignancy) Methotrexate is used in combination therapy with prednisone, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin and vincristine as single dose of 120 mg/m² BSA.
5 g/m²–4 g/m² IV given as single dose in mono- or combination therapy was used. Detailed information can be found in current published therapy protocols. Acute lymphocytic leukaemias (ALL) The following regimens have been used. Reference should always be made to current published protocols.
In low doses, methotrexate is applied within the scope of complex therapy protocols for maintaining remission in children and adults with acute lymphocytic leukaemias. Normal single doses lie within the range of 20–40 mg/m² methotrexate.
The choice of an adequate combination therapy may be influenced by factors such as risk group, age and immunologic subgroups. For ALL of B-cell type special therapy protocols are used. ALL in children Usual single dose is 1 g/m²–5 g/m² BSA (during consolidation therapy).
Detailed information can be found in current published therapy protocol ALL-BFM. 5 g/m² BSA regarding to the therapy protocol GMALL. Cancer of the bladder Methotrexate is used in combination therapy with vinblastine, doxorubicin and cisplatin (M- VAC regimen) at a dose of 30 mg/m² BSA.
g. M-VAC. Osteosarcoma Effective adjuvant chemotherapy requires the administration of several cytotoxic chemotherapeutic medicinal products. Methotrexate is used intravenously in high doses (6– 12 g/m²) once weekly. Calcium folinate rescue is necessary.
g. COSS. g. 6), - renal insufficiency (creatinine clearance less than 60 ml/min), - alcohol abuse, - stomatitis, gastrointestinal ulceration. 4 Special warnings and precautions for use Methotrexate 100 mg/ml solution for injection should only be prescribed by physicians with experience in antimetabolite chemotherapy and the management of the approved indications.
Because of the possibility of fatal or severe intoxication during methotrexate therapy medium or high doses should only be used in patients with life-threatening tumour diseases. Rare cases of death have been reported after methotrexate tumour therapy.
Patients undergoing methotrexate therapy should be closely monitored to prevent intoxication and to ensure fast identification of toxic adverse reactions. g. following prior radio- or chemotherapy), impaired general condition as well as advanced age and in very young children.
Patients should be fully informed by the physician about risks and benefits of the therapy, of the need to inform the physician immediately if toxic signs occur and about necessary examinations and safety measures during treatment.
Discontinuation of methotrexate therapy did not always result in a complete recovery from toxic effects. For […]