Methotrexate is indicated in the management of selected adults with severe, active, rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis.
Folic acid antagonist; Antineoplastic
Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this
enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of purine nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of methotrexate. When cellular proliferation in malignant tissues is greater than in most normal tissues, methotrexate may impair malignant growth without irreversible damage to normal tissues. In psoriasis, the rate of production of epithelial cells in the skin is greatly increased over normal skin. This difference in proliferation rates is the basis for the use of methotrexate to control the psoriatic process.
15 to 30 mg IM or orally daily for 5 days. Repeat courses 3 to 5 times with a rest period of greater than or equal to 1 week between courses, until any manifesting toxic symptoms subside.
NSAIDs: Should not be administered prior to or concomitantly with high doses of methotrexate, such as used in the treatment of osteosarcoma
Salicylates, Phenylbutazone, Phenytoin and Sulfonamides: Toxicity may be increased Penicillin, Theophylline, Probenecid, Azathioprine, Retinoids,
Sulfasalazine: Should be closely monitored for possible increased risk of hepatotoxicity
Cisplatin: Caution must be exercised if high-dose methotrexate is administered in combination
Mercaptopurine: Methotrexate increases the plasma levels of mercaptopurine
Tetracycline, Chloramphenicol and Nonabsorbable Broad Spectrum Antibiotics: May decrease intestinal absorption of methotrexate
Vitamin preparations containing folic acid or its derivatives: Decreases responses to systemically administered methotrexate
Trimethoprim/Sulfamethoxazole: Rarely increases bone marrow suppression
Severe renal or hepatic impairment, preexisting profound bone marrow suppression in patients w/ psoriasis or rheumatoid arthritis, alcoholic liver disease, AIDS, pre-existirig blood dyscrasias, pregnancy (in patients w/ psoriasis or rheumatoid arthritis), breastfeeding. Hepatic or renal impairment, bone marrow depression, elderly, neonates. Ulcerative disorders of the GI tract. Monitor haematological, renal & hepatic function, & GI toxicity regularly.
Ulceration of the mouth & GI disturbances (e.g. stomatitis & diarrhoea), bone marrow depression, hepatotoxicity, renal failure, skin reactions, alopecia, ocular irritation, arachnoiditis in intrathecal use, megaloblastic anaemia, osteoporosis, precipitation of diabetes, arthralgias, necrosis of soft tissue & bone, anaphylaxis, impaired fertility. Pulmonary reactions (e.g. interstitial lung disease); neurotoxicity (e.g. leukoencephalopathy, paresis, demyelination) w/ intrathecal use; foetal deaths.
This drug can cause teratogenic effects or fetal death when administered to a pregnant woman. Use is contraindicated during breastfeeding.
Leucovorin is indicated to diminish the toxicity and counteract the effect of inadvertently administered overdosages of methotrexate and its administration should begin as promptly as possible.
Store at a temperature not exceeding 30°C in a dry place. Protect from light & moisture.
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