Indications & Dose: BREAST CANCER Combination therapy IV Adult 10-60mg/m2 with cyclophosphamide & fluorouracil | BURKITT’S LYMPHOMA & LYMPHOSARCOMA Combination therapy PO Adult 10-25mg/day 4-8 days in stages I & II, in stage III 0.625-2.5mg/kg/day with other neoplastic drugs. Patients in all stages usually require several courses of therapy, with 7-10 day rest periods between courses | CROHN’S DISEASE PO Adult 12.5-22.5mg once weekly upto 1 yr | IM Adult 25mg once weekly 16wk | LYMPHOBLASTIC LEUKEMIA Combination therapy PO Adult 3.3mg/m2/day of methotrexate with prednisone 60mg/m2/day 4-6 wk, followed by 30mg/m2 of methotrexate weekly in two divided doses | Acute IV Adult 2.5mg/kg q14days | MENINGEAL LEUKEMIA IT Adult 12mg/m2 or an empiric dose of 15mg at an interval of 2-5 days, may be repeat until CSF cell counts normal Child > 1 yr: 6mg, 1yr: 8mg, 2 yr: 10mg, >3 yr: Same as adult dose | OSTEOSARCOMA Combination therapy/Adjuvant therapy IV Adult Initially 12g/m2 as inf over 4h (followed by leucovorin orally) on postoperative wks 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44 & 45 on a schedule with other chemotherapy agents (doxorubicin, cisplatin, the combination of bleomycin, cyclophosphamide & dactinomycin), if serum methotrexate level <454µg/mL then dose may be increased to 15gm/m2 for subsequent therapy. Leucovorin rescue must start 24h after methotrexate inf begins, if patient intolerate to oral leucovorin, dose must be given by IM/IV | PSORIASIS PO/IV/IM Adult 10-25mg single dose once weekly, max 30mg/wk & adjust dose by response | RHEUMATOID ARTHRITIS PO Adult 7.5mg once weekly or divided as 2.5mg thrice weekly at 12h intervals, may adjust the dose by response, max 20mg/wk | TROPHOBLASTIC NEOPLASMS PO/IM Adult 15-30mg/day 5 days, may repeat course 3-5 times with an interval of at least 1 wk between courses, until signs & symptoms of toxicity disappear

Precautions: Osteosarcoma, preexisting liver impairment, hepatotoxic agents, PUD, UC, elderly, mild-to-moderate hepatic/renal impairment, avoid contact with skin & mucous

ADR: Serious: Bone-marrow depression, hepatic fibrosis & cirrhosis, hepatotoxicity, renal failure, tubular necrosis, neurotoxicity, blood disorders, leukoencephalopathy, liver damage, cranial irradiation, megaloblastic anemia, necrosis of soft tissue & bone, anaphylaxis, pulmonary reactions, arthralgia, defective oogenesis & spermatogenesis, impaired fertility, osteoporosis, seizure, blurred vision, hyperuricemia, Others: stomatitis, diarrhea, fever, chills, alopecia, hyperpigmentation of skin, pharyngitis, vasculitis, cystitis, GI disturbances, mouth ulceration, dizziness, malaise, encephalopathy

DDI: Serious Fluorouracil antagonizes drug effects, Theophylline clearance decreased, Vancomycin delayed drug excretion & leads to toxicity, Triamterene increase bone marrow suppressive effects, Probenecid increases drug levels, Cisplatin/Aminosalicylate/NSAIDs/Tetracycline increases drug toxicity, Isoniazid increases risk of liver function abnormalities, Nitrous oxide increases stomatitis & other toxic effects, Ciprofloxacin leads to drug toxicity, Sulfasalazine leads to folate-deficiency anemias, Cefotiam leads to pancytopenia & pseudomembranous colitis, Trimethoprim/Cotrimoxazole leads to severe bone marrow depression, Etretinate leads to severe liver toxicity, Phenytoin/Fosphenytoin levels decreased, Vaccines (Live) may causes generalized infect, Penicillins reduced drug clearance & leads to drug toxicity, Aminoglycosides reduces drug absorption, Prednisolone reduces drug clearance

Monitor: CBC, BUN, SeCr, LFTs, chest x-ray, pulmonary function test, hepatitis B or C test, methotrexate levels & urine pH