|•||PO, IM (Adults): 15–30 mg/day for 5 days; repeat after 1 or more weeks for 3–5 courses.|
|•||IV (Adults): 40 mg/m² on days 1 and 8 (with other agents; many regimens are used).|
|•||PO (Adults): Induction — 3.3 mg/m²/day, usually with prednisone.|
|•||PO, IM (Adults): Maintenance — 20–30 mg/m² twice weekly.|
|•||IV (Adults): 2.5 mg/kg q 2 wk.|
|•||IT (Adults): 12 mg/m² or 15 mg .|
|•||IT (Children 3 yr): 12 mg.|
|•||IT (Children 2 yr): 10 mg.|
|•||IT (Children 1 yr): 8 mg.|
|•||IT (Children <1 yr): 6 mg.|
|•||IV (Adults): 12 g/m² as a 4-hr infusion followed by leucovorin rescue, usually as part of a combination chemotherapeutic regimen (or increase dose until peak serum methotrexate level is 1 × 10-3 M/L but not to exceed 15 g/m²; 12 courses are given starting 4 wk after surgery and repeated at scheduled intervals.|
Therapy may be preceded by a 5–10-mg test dose
|•||PO (Adults): 2.5–5 mg q 12 hr for 3 doses or q 8 hr for 4 doses once weekly (not to exceed 30 mg/wk) .|
|•||PO, IM, IV (Adults): 10–25 mg/weekly (not to exceed 30 mg/wk).|
Therapy may be preceded by a 5–10-mg test dose in adults
|•||PO (Adults): 7.5 mg weekly (2.5 mg q 12 hr for 3 doses or single dose, not to exceed 20 mg/wk); when response is obtained, dosage should be decreased .|
|•||PO (Children): 10 mg/m² once weekly initially, may be increased up to 20–30 mg/m², however response may be better if doses >20 mg/m² are given IM or subcut.|
|•||PO, IM, SC (Adults): 5–50 mg once weekly, if response is poor, dose may be changed to 15–37.5 mg twice weekly .|
|•||IM (Adults): 50 mg once weekly or 25 mg twice weekly.|
Use in nursing mothers. In patients with psoriasis or rheumatoid arthritis, methotrexate is contraindicated in pregnancy, alcoholism, alcoholic liver disease, chronic liver disease, overt or laboratory evidence of immunodeficiency syndrome, and preexisting blood dyscrasias (eg, leukopenia, thrombocytopenia); hypersensitivity to the drug.
Use Cautiously in:
|•||Renal impairment (CCr must be 60 ml/min prior to therapy).|
|•||Patients with childbearing potential.|
|•||Decreased bone marrow reserve.|
|•||Geri: Geriatric patients or patients with other chronic debilitating illnesses.|
CNS: Dizziness (1% to 3%); fatigue; headache; aphasia; hemiparesis; paresis; convulsions; leukoencephalopathy (IV after craniospinal irradiation); chemical arachnoiditis; transient paresis; neurotoxicity.
DERM: Erythematous rashes, pruritus, alopecia (1% to 3%); urticaria; photosensitivity; pigmentary changes; ecchymosis; telangiectasia; acne; furunculosis; aggravation of psoriasis by ultraviolet light; Stevens-Johnson syndrome.
EENT: Blurred vision; ulcerative stomatitis; gingivitis; pharyngitis.
GI: Nausea, vomiting (10%); enteritis, stomatitis (3% to 10%); diarrhea (1% to 3%); abdominal distress (common); anorexia; hematemesis; melena; GI ulceration and bleeding.
GU: Renal failure; azotemia; cystitis; hematuria; severe nephropathy; reproductive disorders; infertility; abortion; fetal defects.
HEMA: Thrombocytopenia (3% to 10%); leukopenia, pancytopenia (1% to 3%); bone marrow depression; anemia; hypogammaglobulinemia; hemorrhage; septicemia.
HEPA: Elevated LFTs (15%); hepatotoxicity; hepatic cirrhosis and fibrosis.
RESP: Deaths from interstitial pneumonitis; chronic interstitial obstructive pulmonary disease.
OTHER: Malaise; chills; fever; lower resistance to infections; arthralgia; myalgia; diabetes; osteoporosis; anaphylactoid reaction; sudden death.
Deaths have occurred.
Rheumatoid arthritis treatment:
Restrict use to patients with severe, recalcitrant, disabling disease not adequately responsive to other forms of therapy.
Fetal death or congenital anomalies have occurred.
Periodically monitor for toxicity, including CBC with differential and platelet counts and liver and renal function.
Methotrexate may cause hepatotoxicity, fibrosis, and cirrhosis.
Lung disease, a potentially dangerous lesion, may occur any time during therapy.
Unexpectedly severe and sometimes fatal marrow suppression, aplastic anemia, and GI toxicity have been reported with coadministration of NSAIDs.
Use with caution because methotrexate elimination will be prolonged.
Severe and occasionally fatal skin reactions have been reported.
Potentially fatal opportunistic infections may occur.
The risk of soft tissue necrosis and osteonecrosis may be increased by concurrent radiotherapy.
Death from intestinal perforation may occur. Diarrhea and ulcerative stomatitis require interruption of therapy.
Do not use methotrexate formulations and diluents containing preservatives for intrathecal or experimental high-dose methotrexate therapy.
Malignant lymphomas, which may regress following discontinuation of methotrexate, may occur.
Tumor lysis syndrome:
May occur in patients with rapidly growing tumors.
Acitretin, etretinate, NSAIDs, penicillins, probenecid, salicylates, sulfonamides, tetracyclines
May increase methotrexate blood levels and toxicity.
Antibiotics (oral) such as chloramphenicol, nonabsorbable broad spectrum antibiotics (eg, neomycin), and tetracycline
May decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation.
May reduce methotrexate efficacy.
May reduce serum digoxin levels and actions.
May decrease responses to systemically administered methotrexate.
May reduce plasma levels.
Plasma concentrations may be increased by methotrexate.
Methotrexate decreases Cl of theophylline.
May increase risk of methotrexate-induced bone marrow suppression and megaloblastic anemia.
Therapeutic Classification: antineoplastics, antirheumatics (DMARDs) , Immunosuppressant agents
Pharmacologic Classification: antimetabolites
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 (increased in renal impairment).
|ORAL||4-7 DAYS||7-14 DAYS||21 DAYS|
|INTRAMUSCULAR||4-7 DAYS||7-14 DAYS||21 DAYS|
|INTRAVENOUS||4-7 DAYS||7-14 DAYS||21 DAYS|