Zexate

MTX Na

Gestational choriocarcinoma, chorioadenoma destruens & hydatidiform mole; meningeal leukemia. Monotherapy or in combination w/ other anticancer agents for breast cancer, head & neck epidermoid cancers, advanced mycosis fungoides (cutaneous T cell lymphoma), & squamous & small cell type of lung cancer. In combination w/ other chemotherapeutic agents for advanced stage non-Hodgkin's lymphomas; followed by leucovorin rescue in prolonging relapse-free survival in patients w/ non-metastatic osteosarcoma who have undergone surgical resection or amputation for primary tumor. Symptomatic control of severe, recalcitrant, disabling psoriasis. Management of selected adults w/ severe, active RA (ACR criteria), or childn w/ active polyarticular-course juvenile RA, who had insufficient therapeutic response to, or are intolerant of, adequate trial of 1st-line therapy of NSAIDs. Prophylaxis of meningeal leukemia & as maintenance therapy in combination w/ other chemotherapeutic agents in patients w/ acute lymphocytic leukemia.

Intraarterial/IM/IV Choriocarcinoma & similar trophoblastic diseases 15-30 mg daily PO or IM for 5-day course repeated 3-5 times w/ ≥1 wk rest period. Induction of remission in acute lymphoblastic leukemia 3.3 mg/m² in combination w/ prednisone 60 mg/m² daily w/in 4-6 wk. Maintenance: Total wkly dose of 30 mg/m² twice wkly PO or IM, or 2.5 mg/kg IV every 14 days. Meningeal leukemia Administer as intrathecal at 2-5 day interval. Patient ≥3 yr 12 mg, 2 yr 10 mg, 1 yr 8 mg, <1 yr 6 mg. Max: 15 mg. Stage I-II Burkitt's tumor 10-25 mg daily PO for 4-8 days w/ 7-10 day rest period. Stage III lymphosarcoma 0.625-2.5 mg/kg daily. Mycosis fungoides (cutaneous T cell lymphoma) 5-50 mg once wkly or 15-37.5 mg twice wkly. Osteosarcoma Initially 12 g/m² as 4-hr IV infusion, may be increased to 15 g/m² subsequently & followed by leucovorin 15 mg PO every 6 hr for 10 doses starting at 24 hr after MTX infusion (Wk 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, 45). Administer in combination w/ single drug doxorubicin 30 mg/m² daily IV for 3 days (Wk 8 & 17), doxorubicin 50 mg/m² IV + cisplatin 100 mg/m² IV (Wk 20, 23, 33, 36), bleomycin 15 u/m² IV + cyclophosphamide 600 mg/m² IV + dactinomycin 0.6 mg/m² IV. All doses given for 2 days (Wk 2, 13, 26, 39, 42). Recommended starting dose: RA Adult 7.5 mg once wkly or 2.5 mg in divided doses at 12-hr interval for 3 doses given as once wkly course. Polyarticular-course juvenile RA 10 mg/m² once wkly. Max dose: 20-30 mg/m²/wk as IM or SC. Psoriasis 10-25 mg once wkly as PO, IM or IV, or 2.5 mg in divided doses at 12-hr interval for 3 doses. Max: 30 mg/wk.

Hypersensitivity. Psoriasis or RA w/ alcoholism, alcoholic or other chronic liver disease; immunodeficiency syndromes; preexisting blood dyscrasias eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia. Women of childbearing potential. Avoid during pregnancy; during & for min of 3 mth after therapy for men & at least 1 ovulatory cycle after therapy for women. Lactation.

Not to be used as intrathecal in preserved formulation. Delay treatment if WBC count <1,500/microliter, neutrophil count <200/microliter, platelet count <75,000/microliter, serum bilirubin level >1.2 mg/dL, SGPT level >450 u, presence of mucositis & persistent pleural effusion. Discontinue treatment if vomiting, diarrhea, or stomatitis occur resulting in dehydration; significant drop in blood counts; persistent abnormal LFTs. Interrupt therapy in pulmonary symptoms (especially dry non-productive cough) or non-specific pneumonitis. Potential for & possible recurrence of serious toxicity. Depression of serum albumin. Serious neurotoxicity & generalized or focal seizures in ped patients w/ acute lymphoblastic leukemia; chronic leukoencephalopathy; transient acute neurologic syndrome. Pneumocystis carinii pneumonia. Severe, occasionally fatal, dermatologic reactions eg, TEN, SJS, exfoliative dermatitis, skin necrosis & erythema multiforme. Patient w/ malignancy & preexisting hematopoietic impairment; profound granulocytopenia & fever. Presence of active infection & debility. Exposure to UV radiation. Continue hydration & urinary alkalinization. Closely monitor fluid & electrolyte status; MTX plasma level. Assess hematologic, hepatic, renal & pulmonary function before beginning, periodically during, & before reinstitution of therapy; baseline CBC w/ differential & platelet counts, hepatic enzymes, renal function tests, & chest X-ray. Folate supplementation in chronic use. Perform LFT at baseline at 4-8 wk interval; pre-treatment liver biopsy in patients w/ history of excessive alcohol consumption, persistent abnormal baseline LFT values or chronic hepatitis B or C infection. Concomitant use w/ PPIs eg, omeprazole, esomeprazole & pantoprazole; NSAIDs; RT. Not recommended in immunization w/ live virus vaccines. May affect ability to drive or operate machinery. Acute (elevated transaminases) & chronic (fibrosis & cirrhosis) hepatotoxicity; presence of pre-existing liver damage or hepatic impairment. Acute renal failure; nephrotoxicity. Embryotoxicity, abortion & fetal defects; impairment of fertility, oligospermia & menstrual dysfunction. Childn <1 mth (fatal gasping syndrome). Elderly.

Ulcerative stomatitis, leukopenia, nausea, abdominal distress, malaise, undue fatigue, chills & fever, dizziness, decreased resistance to infection. Erythema multiforme, TEN, SJS, skin necrosis & ulceration, exfoliative dermatitis.

Elevated & prolonged serum level w/ NSAIDs. Increased toxicity w/ salicylates, phenylbutazone, phenytoin & sulfonamides; nitrous oxide anesth. Diminished renal tubular transport w/ probenecid. Concomitant use w/ potentially nephrotoxic chemotherapeutic agent eg, cisplatin. Increased plasma levels of mercaptopurine. Decreased intestinal absorption or interference w/ enterohepatic circulation w/ oral antibiotics eg, tetracycline, chloramphenicol & nonabsorbable broad spectrum antibiotics. Reduced renal clearance & increased serum conc w/ penicillins. Increased hepatotoxicity w/ other potential hepatotoxins eg, azathioprine, retinoids, sulfasalazine. Decreased clearance of theophylline. Decreased responses w/ vit prep containing folic acid or its derivatives. Increased bone marrow suppression w/ trimethoprim/sulfamethoxazole.

Cytotoxic Chemotherapy

L01BA01 - methotrexate ; Belongs to the class of antimetabolites, folic acid analogues. Used in the treatment of cancer.

S