Classifications: antineoplastic agent; antimetabolite, antifolate; immunosuppressant; Therapeutic: antineoplastic; immunosuppressant; antifolate
Pregnancy Category: X
2.5 mg tablets; 2.5 mg/mL, 25 mg/mL injection
Antimetabolite and folic acid antagonist. Blocks folic acid participation in nucleic acid synthesis, thereby interfering
with mitotic process. Rapidly proliferating tissues (malignant cells, bone marrow) are sensitive to interference of the
mitotic process by this drug.
In psoriasis, reproductive rate of epithelial cells is higher than in normal cells. Induces remission slowly; use often
preceded by other antineoplastic therapies. Also has immunosuppressant effects.
Principally in combination regimens to maintain induced remissions in neoplastic diseases. Effective in treatment of gestational
choriocarcinoma and hydatidiform mole and as immunosuppressant in kidney transplantation, for acute and subacute leukemias
and leukemic meningitis, especially in children. Used in lymphosarcoma, in certain inoperable tumors of head, neck, and
pelvis, and in mycosis fungoides. Also used to treat severe psoriasis nonresponsive to other forms of therapy, rheumatoid
Psoriatic arthritis, SLE, polymyositis.
Pregnancy (category X), men and women in childbearing age; lactation; hepatic and renal insufficiency; concomitant administration
of hepatotoxic drugs and hematopoietic depressants; alcohol; ultraviolet exposure to psoriatic lesions; pre-existing blood
Infections; peptic ulcer, ulcerative colitis; very young or old patients; cancer patients with preexisting bone marrow impairment;
poor nutritional status.
Route & Dosage
Adult: PO/IM 1530 mg/d for 5 d, repeat for 35 courses
Adult: IM/IV Loading Dose 3.3 mg/m2/d PO/IM/IV Maintenance Dose 30 mg/m2 weekly in 2 doses
Child: Intrathecal 1015 mg/m2
Adult: PO 1025 mg/kg for 48 d
Adult: IV 12 g/m2, dose repeated at weeks 4, 5, 6, 7, 11, 12, 15, 16, 29, 39, 44, 45
Adult: PO 2.5 mg q12h for 3 doses each wk or 7.5 mg once/wk
Child: PO/IM 515 mg/m2/wk as single dose or in 3 divided doses 12 h apart
Adult: PO/IM 550 mg weekly
- Give 1 h before or 2 h after meals.
- Use a test dose (510 mg parenterally) 1 wk before therapy for treatment of psoriasis.
- Avoid skin exposure and inhalation of drug particles.
- Note: Verify correct IV concentration and rate of infusion for administration to children with physician.
PREPARE: Direct: Reconstitute powder vial by adding 2 mL of NS or D5W without preservatives to each 5 mg to yield 2.5 mg/mL. Reconstitute
1 g high-dose vial with 19.4 mL D5W or NS to yield 50 mg/mL. IV Infusion: Further dilute contents of 1 g high-dose vial in D5W or NS.
ADMINISTER: Direct: Give at rate of 10 mg or fraction thereof over 60 sec. IV Infusion: Give over 14 h or as prescribed.
INCOMPATIBILITIES Solution/additive: Bleomycin, metoclopramide, prednisolone, ranitidine. Y-site: Chlorpromazine, droperidol, gemcitabine, idarubicin, ifosfamide, midazolam, nalbuphine, promethazine, propofol.
- Preserve drug in tight, light-resistant container.
Adverse Effects (≥1%)CNS: Headache,
drowsiness, blurred vision, dizziness, aphasia, hemiparesis; arachnoiditis, convulsions (after intrathecal administration
mental confusion, tremors, ataxia, coma. GI: Hepatotoxicity,
GI ulcerations and hemorrhage, ulcerative stomatitis, glossitis, gingivitis,
pharyngitis, nausea, vomiting, diarrhea
, hepatic cirrhosis. Urogenital:
Defective oogenesis or spermatogenesis, nephropathy, hematuria, menstrual dysfunction, infertility, abortion, fetal defects. Hematologic: Leukopenia, thrombocytopenia, anemia
, marked myelosuppression, aplastic bone marrow,
telangiectasis, thrombophlebitis at intraarterial catheter
, and hyperuricemia. Skin: Erythematous
rashes, pruritus, urticaria, folliculitis, vasculitis, photosensitivity, depigmentation, hyperpigmentation,
. Body as a Whole: Malaise
, undue fatigue
, systemic toxicity
and intraarterial administration
), chills, fever, decreased
resistance to infection
, septicemia, osteoporosis, metabolic changes precipitating diabetes
and sudden death, pneumonitis, pulmonary fibrosis.
Diagnostic Test Interference
Severe reactions may occur when live vaccines are administered because of immunosuppressive activity of methotrexate.
InteractionsDrug: Acitretin, alcohol, azathioprine, sulfasalazine
increase risk of hepatotoxicity; chloramphenicol, etretinate, salicylates
, phenylbutazone, phenytoin, tetracyclines
, PABA, penicillin, probenecid
may increase methotrexate levels with increased toxicity
; folic acid
may alter response to methotrexate. May increase theophylline
enhances methotrexate clearance. Herbal: Echinacea
may increase risk of hepatotoxicity. Food: Caffeine
>180 mg/d (34 cups) may decrease effectiveness for rheumatoid arthritis
Readily absorbed from GI tract. Peak:
0.52 h IM/IV; 14 h PO. Distribution:
Widely distributed with highest concentrations in kidneys, gallbladder, spleen, liver, and skin; minimal passage across
bloodbrain barrier; crosses placenta; distributed into breast milk. Metabolism:
In liver. Elimination:
Primarily in urine. Half-Life:
Assessment & Drug Effects
- Lab tests: Obtain baseline liver and kidney function, CBC with differential, platelet count, and chest x-rays. Repeat weekly
during therapy. Monitor blood glucose and HbA1C periodically in diabetics.
- Prolonged treatment with small frequent doses may lead to hepatotoxicity, which is best diagnosed by liver biopsy.
- Monitor for and report ulcerative stomatitis with glossitis and gingivitis, often the first signs of toxicity. Inspect mouth
daily; report patchy necrotic areas, bleeding and discomfort, or overgrowth (black, furry tongue).
- Monitor I&O ratio and pattern. Keep patient well hydrated (about 2000 mL/24 h).
- Prevent exposure to infections or colds during periods of leukopenia. Be alert to onset of agranulocytosis (cough, extreme
fatigue, sore throat, chills, fever) and report symptoms promptly.
- Be alert for and report symptoms of thrombocytopenia (e.g., ecchymoses, petechiae, epistaxis, melena, hematuria, vaginal
bleeding, slow and protracted oozing following trauma).
Patient & Family Education
- Report promptly any abnormal symptoms to physician.
- Avoid or moderate alcohol ingestion, which increases the incidence and severity of methotrexate hepatotoxicity.
- Practice fastidious mouth care to prevent infection, provide comfort, and maintain adequate nutritional status.
- Do not self-medicate with vitamins. Some OTC compounds may include folic acid (or its derivatives), which alters methotrexate
- Use contraceptive measures during and for at least 8 wk following therapy.
- Avoid exposure to sunlight and ultraviolet light. Wear sunglasses and sunscreen.