meth-o-TREX-ate 
Absorption: Small doses are well absorbed from the GI tract. Larger doses incompletely absorbed.
Distribution: Actively transported across cell membranes, widely distributed. Does not reach therapeutic concentrations in the CSF. Crosses placenta; enters breast milk in low concentrations. Absorption in children is variable (23–95%) and dose-dependent.
Metabolism/Excretion: Excreted mostly unchanged by the kidneys.
Half-life: Low dose — 3–10 hr; high dose — 8–15 hr (↑ in renal impairment).
Contraindicated in:
Use Cautiously in:
60 mL/min prior to therapy)Derm: ERYTHEMA MULTIFORME, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, alopecia, painful plaque erosions (during psoriasis treatment), photosensitivity, pruritus, rash, skin ulceration, soft tissue necrosis, urticaria.
EENT: blurred vision, dysarthria, transient blindness.
GI: GI PERFORATION, HEPATOTOXICITY, anorexia, diarrhea, nausea, stomatitis, vomiting.
GU: nephropathy, acute renal failure, ↓ fertility, menstrual abnormalities, oligospermia.
Hemat: APLASTIC ANEMIA, anemia, leukopenia, thrombocytopenia.
Metab: hyperuricemia.
MS: hemiparesis, osteonecrosis, stress fracture.
Neuro: SEIZURES, arachnoiditis (IT use only), confusion, dizziness, drowsiness, headache, leukoencephalopathy, malaise.
Resp: INTERSTITIAL PNEUMONITIS, interstitial pneumonitis.
Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTIONS, SECONDARY MALIGNANCY, chills, fever, tumor lysis syndrome.
Drug-Drug:
Drug-Natural Products:
Acute Lymphoblastic Leukemia
Meningeal Leukemia
9 yr): 12–15 mg given at intervals of 2 or more days up to twice weekly (for treatment) and no more than once weekly (for prophylaxis).Non-Hodgkin's Lymphoma
Osteosarcoma
Breast Cancer
Squamous Cell Carcinoma of Head and Neck
Gestational Trophoblastic Neoplasia
Rheumatoid Arthritis
Polyarticular Juvenile Idiopathic Arthritis
Psoriasis
Therapy may be preceded by a 5–10-mg test dose
IV Administration:
Otrexup, Rasuvo, Rheumatrex, Trexall, Xatmep
Therapeutic Classification: antineoplastics, antirheumatics (DMARDs), Immunosuppressant agents
Pharmacologic Classification: antimetabolites
(Generic available)
(effects on blood counts)
| ROUTE | ONSET | PEAK | DURATION |
|---|---|---|---|
| PO, IM, IV | 4–7 days | 7–14 days | 21 days |
| Subcut | unknown | unknown | unknown |
500 mg/m2), patient must receive leucovorin rescue within 24–48 hr to prevent fatal toxicity. May be considered for intermediate doses of 100 mg/m2 to <500 mg/m2. Administer IV fluids starting before 1st dose and continuing through therapy to maintain adequate hydration and urine output. Administer glucarpidase in patients who have toxic plasma methotrexate concentrations (>1 micromole per liter) and delayed methotrexate clearance due to impaired renal function. Glucarpidase may be used for patients with impaired renal function. If glucarpidase is used, do not administer leucovorin within 2 hrs before or after glucarpidase because leucovorin is a substrate for glucarpidase. In cases of massive overdose, hydration and urinary alkalinization with sodium bicarbonate are required to prevent renal tubule damage. Leucovorin and levoleucovorin are indicated to diminish the toxicity and counteract the effect of inadvertently administered overdoses of methotrexate. Monitor fluid and electrolyte status; patients must be well hydrated. Intermittent hemodialysis using a high-flux dialyzer may be used for clearance until levels are <0.05 micromolar. Methotrexate should be delayed until recovery if WBC <1500/mcL, neutrophil count <200/mcL, platelet count <75,000/mcL, serum bilirubin level >1.2 mg/dL, AST level >450 IU/L, mucositis is present, until evidence of healing, persistent pleural effusion is present, should be drained dry prior to infusion. Adequate renal function is required. Serum creatinine must be normal, CCr must be >60 mL/min, before initiation of therapy. Serum creatinine must be measured before each course of therapy. If ↑ by 50% of a prior value, CCr must be >60 mL/min, even if serum creatinine is within normal range.NDC Code*