methotrexate sodium
Pregnancy Risk Category X
How supplied
Tablets (scored): 2.5 mg
Injection: 20-mg, 25-mg, 50-mg, 100-mg, 250-mg vials, lyophilized powder, preservative free; 25-mg/ml vials, preservative-free solution; 2.5-mg/ml, 25-mg/ml vials, lyophilized powder, preserved
Action
Prevents reduction of folic acid to tetrahydrofolate by binding to dihydrofolate reductase.
Indications & dosage
Trophoblastic tumors (choriocarcinoma, hydatidiform mole)--
Adults: 15 to 30 mg P.O. or I.M. daily for 5 days. Repeated after 1 or more weeks, based on response or toxicity. Number of courses is three to five, not to exceed five.
Acute lymphocytic leukemia--
Adults and children: 3.3 mg/m2/day P.O., I.M., or I.V. for 4 to 6 weeks or until remission occurs; then 20 to 30 mg/m2 P.O. or I.M. weekly in two divided doses or 2.5 mg/kg I.V. q 14 days.
Meningeal leukemia--
Adults and children: 12 mg/m2 or less (maximum 15 mg) intrathecally q 2 to 5 days until CSF is normal; then one additional dose.
Burkitt's lymphoma (stage I, II, or III)--
Adults: 10 to 25 mg P.O. daily for 4 to 8 days with 1-week rest intervals.
Lymphosarcoma (stage III)--
Adults: 0.625 to 2.5 mg/kg daily P.O., I.M., or I.V.
Osteosarcoma--
Adults: initially, 12 g/m2 I.V. as 4-hour infusion. Subsequent doses 12 to 15 g/m2 I.V. as 4-hour I.V. infusion given at postoperative weeks 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, and 45. Given with leucovorin, 15 mg P.O., I.M., or I.V. q 6 hours for 10 doses, beginning 24 hours after start of methotrexate infusion.
Mycosis fungoides--
Adults: 2.5 to 10 mg P.O. daily; or 50 mg I.M. weekly; or 25 mg I.M. twice weekly.
Psoriasis--
Adults: 10 to 25 mg P.O., I.M., or I.V. as single weekly dose; or 2.5 mg P.O. every 12 hours for three doses. Dosage
shouldn't exceed 30 mg/week.
Rheumatoid arthritis--
Adults: initially, 7.5 mg P.O. weekly, either in single dose or divided as 2.5 mg P.O. q 12 hours for three doses once weekly. Dosage may be gradually increased to maximum of 20 mg weekly.
Adverse reactions
CNS: arachnoiditis within hours of intrathecal use, subacute neurotoxicity possibly beginning few weeks later, leukoencephalopathy, demyelination, malaise, fatigue, dizziness, headache, aphasia, hemiparesis, drowsiness, seizures.
EENT: pharyngitis, blurred vision.
GI: gingivitis, stomatitis, diarrhea, abdominal distress, anorexia, GI ulceration and bleeding, enteritis, nausea, vomiting.
GU: nephropathy, tubular necrosis, renal failure, hematuria, menstrual dysfunction, defective spermatogenesis, infertility, abortion, cystitis.
Hematologic: WBC and platelet count nadirs occurring on day 7; anemia, leukopenia, thrombocytopenia.
Hepatic: acute toxicity, chronic toxicity, including cirrhosis and hepatic fibrosis.
Musculoskeletal: arthralgia, myalgia; osteoporosis in children on long-term therapy.
Respiratory: pulmonary fibrosis; pulmonary interstitial infiltrates; pneumonitis; dry, nonproductive cough.
Skin: urticaria, pruritus, hyperpigmentation, erythematous rashes, ecchymoses, rash, photosensitivity, alopecia, acne, psoriatic lesions aggravated by exposure to sun.
Other: fever, chills, reduced resistance to infection, septicemia, hyperuricemia, diabetes, sudden death.
Interactions
Drug-drug. Acyclovir: concurrent use with intrathecal MTX may cause neurologic abnormalities. Monitor closely.
Digoxin: may decrease serum digoxin levels. Monitor closely.
Folic acid derivatives: antagonized methotrexate effect. Avoid concomitant use, except for leucovorin rescue with high-dose methotrexate therapy.
Hepatotoxic drugs: may increase risk of hepatotoxicity. Monitor closely.
NSAIDs, phenylbutazone, probenecid, salicylates, sulfonamides: increased methotrexate toxicity. Avoid use together.
Oral antibiotics: may decrease absorption of methotrexate. Monitor closely.
Phenytoin: may decrease serum phenytoin levels. Monitor closely.
Theophylline: may increase level of theophylline. Monitor closely.
Vaccines: immunizations may be ineffective; risk of disseminated infection with live virus vaccines. Defer immunization, if possible.
Drug-food. Any food: may delay absorption and reduce peak level of methotrexate. Avoid concomitant use.
Drug-lifestyle. Alcohol use: may increase hepatotoxicity. Discourage concomitant use.
Sun exposure: photosensitivity reactions may occur. Take precautions.
Effects on diagnostic tests
Drug may alter results of laboratory assay for folate, thus interfering with detection of folic acid deficiency.
Contraindications
Contraindicated in patients with hypersensitivity to drug and in those with psoriasis or rheumatoid arthritis who also have alcoholism, alcoholic liver, chronic liver disease, immunodeficiency syndromes, or preexisting blood dyscrasias; also contraindicated in pregnant or breast-feeding women.
Nursing considerations
I.V. administration
Patient teaching
*Liquid contains alcohol. **May contain tartrazine. †Canada ‡Australia §U.K. OTCOver the counter
Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE-THREATENING