• Induction dose: 3.3 mg/m2 in combination with prednisone 60 mg/m2 daily for 4 to 6 weeks
• Maintenance dose: Orally or IM administration 2 times a week in total weekly doses of 30 mg/m2
• Alternate maintenance dose: 2.5 mg/kg IV every 14 days. If and when relapse does occur, reinduction of remission can again usually be obtained by repeating the initial induction regimen

• Burkitt's tumor Stages I to II: 10 to 25 mg once a day for 4 to 8 days
• Burkitt's tumor Stage III: Methotrexate is commonly given concomitantly with other antitumor agents
• Duration of therapy: All stages usually require several courses of therapy interposed with 7 to 10 day rest periods
• Lymphosarcoma Stage III: 0.625 to 2.5 mg/kg daily as a part of combination chemotherapy

Mycosis Fungoides: Early stage dosing: 5 to 50 mg once a week; alternatively, 15 to 37.5 mg 2 times a week may be used in patients who have responded poorly to weekly therapy

Breast Cancer: 40 mg/m 2 intravenously on the 1 st and 8 th day every 4 weeks in combination with cyclophosphamide and fluoracil for 6-12 cycles

Head and Neck Cancer: 40 mg/m2 IV weekly until disease progression or unacceptable toxicity (3 weeks equals one cycle; goal is to complete at least six cycles).

Adult Rheumatoid Arthritis: Single doses of 7.5 mg once per week, Maximum dose: 20 mg/week in adults

Polyarticular-Course Juvenile Rheumatoid Arthritis: 10 mg/m2 once weekly

Psoriasis: Single dose: 10 to 25 mg once per week, maximum dose: 30 mg/week

• 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

• Alcoholism, alcoholic liver disease or other chronic liver disease
• Immunodeficiency syndromes
• Pre-existing blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia
• Hypersensitivity to methotrexate
• Pregnant women with psoriasis or rheumatoid arthritis
• Women of childbearing potential
• Nursing mothers
• Pregnancy should be avoided if either partner is receiving methotrexate; during and for a minimum of three months after therapy for male patients, and during and for at least one ovulatory cycle after therapy for female patients

• The most frequently reported adverse reactions include ulcerative stomatitis, leukopenia, nausea and abdominal distress
• Other frequently reported adverse effects are malaise, undue fatigue, chills and fever, dizziness and decreased resistance to infection
• Methotrexate has been reported to cause impairment of fertility, oligospermia and menstrual dysfunction in humans, during and for a short period after cessation of therapy

• Methotrexate formulations and diluents containing preservatives must not be used for intrathecal or high dose methotrexate therapy
• It is necessary to follow patients on methotrexate closely for toxic effects
• If adverse reactions occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken. If necessary, this could include the use of leucovorin calcium
• If methotrexate therapy is reinstituted, it should be carried out with caution, with adequate consideration of further need for the drug and increased alertness as to possible recurrence of toxicity
• Persistent liver function test abnormalities, &/or depression of serum albumin may be indicators of serious liver toxicity & require evaluation
• Folate deficiency: May increase methotrexate toxicity