Methotrexate, Methotrexate sodium
Methotrexate, Methotrexate sodium (Rheumatrex Dose Pack)
Methotrexate
(meth-oh- TREKS-ayt)
Pregnancy Category: D (X for pregnant psoriatic or rheumatoid arthritis clients) Amethopterin Folex PFS Rheumatrex Dose Pack (Abbreviation: MTX) (Rx)

Classification: Antineoplastic, antimetabolite (folic acid analog)

See Also: See also Antineoplastic Agents .

Action/Kinetics: Cell-cycle specific for the S phase of cell division. Acts by inhibiting dihydrofolate reductase, which prevents reduction of dihydrofolate to tetrahydrofolate; this results in decreased synthesis of purines and consequently DNA. The most sensitive cells are bone marrow, fetal cells, dermal epithelium, urinary bladder, buccal mucosa, intestinal mucosa, and malignant cells. When used for rheumatoid arthritis it may affect immune function. Variable absorption from GI tract. Peak serum levels, IM: 30-60 min; PO: 1-2 hr. t 1/2: initial, 1 hr; intermediate, 2-3 hr; final, 8-12 hr. May accumulate in the body. Excreted by kidney (55%-92% in 24 hr). Renal function tests are recommended before initiation of therapy; perform daily leukocyte counts during therapy.

Uses: Uterine choriocarcinoma (curative), chorioadenoma destruens, hydatidiform mole, acute lymphocytic and lymphoblastic leukemia, lymphosarcoma, and other disseminated neoplasms in children; meningeal leukemia, some beneficial effect in regional chemotherapy of head and neck tumors, breast tumors, and lung cancer. In combination for advanced stage non-Hodgkin's lymphoma. Advanced mycosis fungoides. High doses followed by leucovorin rescue in combination with other drugs for prolonging relapse-free survival in nonmetastatic osteosarcoma in individuals who have had surgical resection or amputation for the primary tumor. Severe, recalcitrant, disabling psoriasis. Rheumatoid arthritis (severe, active, classical, or definite) in clients who have had inadequate response to NSAIDs and at least one or more antirheumatic drugs (disease modifying). Investigational: Severe corticosteroid-dependent asthma to reduce corticosteroid dosage; adjunct to treat osteosarcoma. Psoriatic arthritis and Reiter's disease.

Contraindications: Psoriasis clients with kidney or liver disease; blood dyscrasias as hypoplasia, thrombocytopenia, anemia, or leukopenia. Alcoholism, alcoholic liver disease, or other chronic liver disease. Immunodeficiency syndromes. Pregnancy and lactation.

Special Concerns: Use with caution in impaired renal function and elderly clients. Use with extreme caution in the presence of active infection and in debilitated clients. Safety and efficacy have not been established for juvenile rheumatoid arthritis.

Additional Side Effects: Severe bone marrow depression. Hepatotoxicity, fibrosis, cirrhosis. Hemorrhagic enteritis, intestinal ulceration or perforation acne, ecchymosis, hematemesis, melena, increased pigmentation, diabetes, leukoencephalopathy, chronic interstitial obstructive pulmonary disease, acute renal failure. Intrathecal use may result in chemical arachnoiditis, transient paresis, or seizures. Concomitant exposure to sunlight may aggravate psoriasis. Bone and soft tissue necrosis following radiation therapy.

Overdose Management: Symptoms: See Antineoplastic Agents Chapter 2. Treatment: Leucovorin, given as soon as possible, may decrease toxic effects. The dose used is 10 mg/m ² PO or parenterally followed by 10 mg/m ² PO q 6 hr for 72 hr. Charcoal hemoperfusion will reduce serum levels. In massive overdosage, hydration and urinary alkalinization are needed to prevent precipitation of methotrexate and metabolites in the renal tubules.

Drug Interactions: Alcohol, ethyl / Additive hepatotoxicity; combination can coma Aminoglycosides, oral / Absorption of PO methotrexate Anticoagulants, oral / Additive hypoprothrombinemia Chloramphenicol / Methotrexate effect by plasma protein binding Doxycycline / GI and hematologic toxicity after high dose methotrexate Etretinate / Possible hepatotoxicity if used together for psoriasis Folic acid-containing vitamin preparations / Methotrexate response Ibuprofen / Methotrexate effect by renal secretion NSAIDs / Possible fatal interaction PABA / Methotrexate effect by plasma protein binding Phenylbutazone / Methotrexate effect by renal secretion Phenytoin / Methotrexate effect by plasma protein binding Probenecid / Methotrexate effect by renal clearance Procarbazine / Possible nephrotoxicity Pyrimethamine / Methotrexate toxicity Salicylates (aspirin) / Methotrexate effect by plasma protein binding; also, salicylates methotrexate renal excretion Smallpox vaccination / Methotrexate impairs immunologic response to smallpox vaccine Sulfonamides / Methotrexate effect by plasma protein binding Tetracyclines / Methotrexate effect by plasma protein binding Thiopurines / Plasma drug levels

How Supplied: Injection: 25 mg/mL; Powder for injection: 20 mg, 1 g; Tablet: 2.5 mg

Dosage
?Tablets (Methotrexate). IM, IV, IA, Intrathecal (Methotrexate Sodium) Choriocarcinoma and similar trophoblastic diseases.
Dose individualized. PO, IM: 15-30 mg/day for 5 days. May be repeated 3-5 times with 1-week rest period between courses.
Acute lymphatic (lymphoblastic) leukemia.
Initial: 3.3 mg/m ² (with 60 mg/m ² prednisone daily); maintenance: PO, IM, 30 mg/m ² 2 times/week or IV, 2.5 mg/kg q 14 days.
Meningeal leukemia.
Intrathecal: 12 mg/m ² q 2-5 days until cell count returns to normal.
Lymphomas.
PO: 10-25 mg/day for 4-8 days for several courses of treatment with 7- to 10-day rest periods between courses.
Mycosis fungoides.
PO: 2.5-10 mg/day for several weeks or months; alternatively, IM: 50 mg once weekly or 25 mg twice weekly.
Lymphosarcoma.
0.625-2.5 mg/kg/day in combination with other drugs.
Osteosarcoma.
Used in combination with other drugs, including doxorubicin, cisplatin, bleomycin, cyclophosphamide, and dactinomycin. Usual IV starting dose for methotrexate: 12 g/m ²; dose may be increased to 15 g/m ² to achieve a peak serum level of 10 - ³ mol/L at the end of the methotrexate infusion.
Psoriasis.
Adults, usual: PO, IM, IV, 10-25 mg/week, continued until beneficial response observed. Weekly dose should not exceed 50 mg. Alternate regimens: PO, 2.5 mg q 12 hr for three doses or q 8 hr for four doses each week (not to exceed 30 mg/week); or PO 2.5 mg daily for 5 days followed by 2 days of rest (dose should not exceed 6.25 mg/day). Once beneficial effects are noted, reduce dose to lowest possible level with longest rest periods between doses.
Rheumatoid arthritis.
Initial: Single PO doses of 7.5 mg/week or divided PO doses of 2.5 mg at 12-hr intervals for three doses given once a week; then, adjust dosage to achieve optimum response, not to exceed a total weekly dose of 20 mg. Once response has been reached, reduce the dose to the lowest possible effective dose.