meth-o-TREX-ate
Therapeutic Classification: antineoplastics, antirheumatics (DMARDs), Immunosuppressant agents
Pharmacologic Classification: antimetabolites
High Alert
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. Absorption in children is variable (23–95%) and dose-dependent.
Half-Life: Low dose: 3–10 hr; High dose: 8–15 hr (↑ in renal impairment).
(effects on blood counts)
| ROUTE | ONSET | PEAK | DURATION |
|---|---|---|---|
| PO, IM, IV | 4–7 days | 7–14 days | 21 days |
| SUBQ | unknown | unknown | unknown |
Contraindicated in:
Pregnancy
;Use Cautiously in:
Derm: alopecia, ERYTHEMA MULTIFORME, painful plaque erosions (during psoriasis treatment), photosensitivity, pruritus, rash, skin ulceration, soft tissue necrosis, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), urticaria
EENT: blurred vision, transient blindness
GI: anorexia,
, nausea, , , GI PERFORATION, HEPATOTOXICITYGU:
nephropathy
, ↓fertility, , menstrual abnormalities, oligospermiaHemat:
,leukopenia
, , APLASTIC ANEMIAMS: hemiparesis, osteonecrosis, stress fracture
Neuro: arachnoiditis (IT use only), confusion, dizziness, drowsiness, dysarthria, headache, leukoencephalopathy, malaise, SEIZURES
Resp: INTERSTITIAL PNEUMONITIS
Misc: chills, fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTION, SECONDARY MALIGNANCY, tumor lysis syndrome
Drug-drug:
Drug-Natural Products:
Acute Lymphoblastic Leukemia
Meningeal Leukemia
Non-Hodgkin Lymphoma
Osteosarcoma
Breast Cancer
Squamous Cell Carcinoma of Head and Neck
Gestational Trophoblastic Neoplasia
Mycosis Fungoides
Rheumatoid Arthritis
Polyarticular Juvenile Idiopathic Arthritis
Psoriasis
Monitor for abdominal pain, diarrhea, or stomatitis; therapy may need to be discontinued.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums; bruising; petechiae; guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for ↑ fatigue, dyspnea, and orthostatic hypotension.
Monitor for signs and symptoms of infection (fever, chills, cough, headache, malaise, flu-like symptoms, dysuria, hematuria, cellulitis, erythematous nonhealing wound). Dose interruption or discontinuation and supportive therapy may be necessary based on severity.
Assess for rash periodically during therapy. May cause SJS and TEN. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, or eosinophilia.
Lab Test Considerations:
Verify negative pregnancy test prior to starting therapy.
Monitor CBC with differential prior to and at least monthly during therapy and at least daily for high-dose regimens. The nadir of leukopenia and thrombocytopenia occurs in 7–14 days. Leukocyte and platelet counts usually recover 7 days after the nadirs. Discontinue methotrexate immediately for any sudden ↓ in values.
Monitor renal (BUN and serum creatinine) prior to and every 1–2 mo during therapy. Urine pH should be monitored prior to high-dose methotrexate therapy and every 6 hr during leucovorin rescue. Urine pH should be maintained at >7.0 from before 1st dose through therapy to prevent renal damage.
Monitor hepatic function (AST, ALT, bilirubin, and LDH) prior to and every 1–2 mo during therapy.
Toxicity and Overdose:
IV Administration:
Instruct patient to notify health care provider promptly if rash, fever, chills, cough, hoarseness, sore throat, signs of infection, lower back or side pain, painful or difficult urination, ↑ fatigue, dyspnea, or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections.
Instruct patient to notify health care provider promptly if bleeding gums; bruising; petechiae; or blood in stools, urine, or emesis occurs. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or other NSAIDs; may precipitate gastric bleeding.
May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for 6 mo after last dose and avoid breastfeeding during and for 1 wk after last dose of therapy. Advise men with female partners of reproductive potential to use effective contraception during and for 3 mo after therapy. Advise patient to notify health care provider if pregnancy is planned or suspected. May impair fertility in both men and women.
NDC Code