The active ingredient is Methotrexate.
Methotrexate is an antineoplastic agent which acts as an antimetabolite of folic acid. It also has immunosuppressant properties. Within the cell, folic acid is reduced to dihydrofolic and then tetrahydrofolic acid. Methotrexate competitively inhibits the enzyme dihydrofolate reductase and prevents the formation of tetrahydrofolate which is necessary for purine and pyrimidine synthesis and consequently the formation of DNA and RNA.
When given in low doses, Methotrexate is rapidly absorbed from the gastro-intestinal tract, but higher doses are less well absorbed. Methotrexate is distributed to tissues and extracellular fluid. It penetrates ascitic fluid and effusions which may act as a depot and thus enhance toxicity. Methotrexate does not appear to undergo significant metabolism at low doses.
Methotrexate is used to produce regression in a wide range of neoplastic conditions, including acute leukaemias, non-Hodgkin's lymphoma, soft tissue and osteogenic sarcomas and solid tumors particularly breast, lung, head and neck, bladder, cervical, ovarian and testicular carcinomas. Methotrexate is of value in the treatment of psoriasis but because of the risks associated with this use, it should only be given when the disease is severe and has not responded to other forms of treatment.
Single doses, not exceeding 30 mg/m2, on not more than 5 successive days are recommended. A rest period of 2 weeks is recommended between treatments, in order to allow normal functioning of the bone marrow.
Methotrexate may be used alone or in combination chemotherapy with radiotherapy or surgery. Dosage regimens may therefore vary considerably.
Folinic acid (Leucovorin) is used to counteract the folate antagonist action of Methotrexate and thus speed recovery from Methotrexate induced mucositis or myelosuppression. Dosage regimens for Leucovorin rescue vary, depending on the dose of Methotrexate administered. In general up to 120 mg in divided doses over 12 to 24 hours by intramuscular or intravenous injection or infusion, followed by 12 to 15 mg intramuscularly or 15 mg by mouth every 6 hours for the next 48 hours are recommended. The dosage of Methotrexate should be reduced during combination chemotherapy.
Single weekly doses of 10 to 25 mg may be given by mouth in the treatment of psoriasis. Dosage should be adjusted according to the patient's response and the haematological toxicity.
Leucovorin is indicated to diminish the toxicity and counteract the effect of inadvertently administered overdosages of Methotrexate. Leucovorin administration should begin as promptly as possible. As the time interval between Methotrexate administration and leucovorin initiation increases, the effectiveness of Leucovorin in counteracting toxicity decreases. Monitoring of the serum Methotrexate concentration is essential in determining the optimal dose and duration of treatment with Leucovorin.
In cases of massive overdosage, hydration and urinary alkalinisation may be necessary to prevent the precipitation of Methotrexate and/or its metabolites in the renal tubules. Neither hemodialysis nor peritoneal dialysis has been shown to improve Methotrexate elimination.
Methotrexate is contra-indicated in the presence of severe renal or hepatic impairment and serious anaemia, leucopenia or thrombocytopenia.
Methotrexate should be administered under the supervision of physician experienced in the use of cancer chemotherapeutic agent.
Methotrexate should be used with great care in patients with hepatic or renal impairment. It should also be used cautiously in alcoholics or those with ulcerative disorders of the gastro-intestinal tract. With high-dose regimens, plasma concentrations of Methotrexate and urinary excretion should be monitored. Regular monitoring of complete blood count with the different platelet counts as well as liver function is advisable.
Precipitation of Methotrexate or its metabolites in the renal tubules may be prevented by alkalinisation of the urine.
Using sodium bicarbonate and maintaining an adequate urine flow. Pleural or ascetic effusions may act as a depot for Methotrexate and produce enhanced toxicity.
Use in Pregnancy: Methotrexate is teratogenic, and should not ordinarily be administered during pregnancy.
Use in Lactation: Methotrexate should not be administered to mothers who are breast-feeding.
Pregnancy: Methotrexate is teratogenic, and should not ordinarily be administered during pregnancy.
Breast-feeding: Methotrexate should not be administered to mothers who are breast-feeding.
Early signs of toxicity with Methotrexate include leucopenia, thrombocytopenia, anaemia, ulceration of the mouth, and gastro-intestinal effects, stomatitis or diarrhoea are signs that treatment should be interrupted, otherwise haemorrhagic enteritis and intestinal perforation may follow. Bone-marrow depression may occur abruptly; megaloblastic anaemia has been reported. Methotrexate is immunosuppressant and hypogammaglobulinaemia may occur. Liver damage has been reported, especially in patients given high-dose therapy or long-term treatment; it may occur in the absence of other signs of Methotrexate toxicity. Kidney damage, osteoporosis, effects on skin and nails, and pulmonary reactions, including interstitial pneumonitis, have developed.
Fatalities have occurred. Methotrexate may cause defective oogenesis and spermatogenesis, and fertility may be impaired. Metabolic alterations, including precipitation of diabetes, have been reported. Neurotoxic reactions may occur, especially after the intrathecal use of Methotrexate. Teratogenic effects and foetal deaths have been reported.
The effects of Methotrexate may be enhanced by concurrent administration of aminobenzoic acid, chloramphenicol, phenylbutazone, phenytoin, probenecid, salicylates, sulphonamides, and tetracyclines. Fatal toxicity has occurred in patients given non-steroidal anti-inflammatory drugs concurrently with Methotrexate.
Methotrexate tablets should be stored below 25°C, protected from light and moisture.
L04AX03 - methotrexate ; Belongs to the class of other immunosuppressants.
Methotrexate 2.5 mg tab 2.5 mg
10 × 10's
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