methotrexate (methopterin, MTX) Nursing Considerations & Management

 Drug Name

Generic Name : methotrexate (methopterin, MTX)

Brand Name: Apo-Methotrexate (CAN), ratio-Methotrexate (CAN), Rheumatrex, Rheumatrex Dose Padk, Trexall

Classification: Antimetabolite, Antineoplastic, Antipsoriatic, Antirheumatic

Pregnancy Category X 

Dosage & Route

Available forms : Tablets—2.5, 5, 7.5, 10, 15 mg; powder for injection—20 mg, 1 g per vial; injection—25 mg/mL

  • Choriocarcinoma and other trophoblastic diseases: 15–30 mg PO or IM daily for a 5-day course. Repeat courses three to five times with rest periods of 1 wk or more between courses until toxic symptoms subside. Continue one to two courses of methotrexate after chorionic gonadotropin hormone levels are normal.
  • Leukemia: Induction: 3.3 mg/m2 of methotrexate PO or IM with 60 mg/m2 of prednisone daily for 4–6 wk. Maintenance: 30 mg/m2 methotrexate PO or IM twice weekly or 2.5 mg/kg IV every 14 days. If relapse occurs, return to induction doses.
  • Meningeal leukemia: Give methotrexate intrathecally in cases of lymphocytic leukemia as prophylaxis. 12 mg/m2 intrathecally at intervals of 2–5 days and repeat until cell count of CSF is normal.
  • Lymphomas: Burkitt’s tumor, stages I and II: 10–25 mg/day PO for 4–8 days. In stage III, combine with other neoplastic drugs. All usually require several courses of therapy with 7- to 10-day rest periods between doses.
  • Mycosis fungoides: 2.5–10 mg/day PO for weeks or months or 50 mg IM once weekly or 25 mg IM twice weekly. Alternatively, in early stage, 5-50 mg PO or IM once weekly, or 15-37.5 mg PO or IM twice weekly; can also give IV with combination chemotherapy regimens in advanced disease.
  • Osteosarcoma: Starting dose is 12 g/m2 or up to 15 g/m2 IV to give a peak serum concentration of 1,000 micromol. Must be used as part of a cytotoxic regimen with leucovorin rescue.
  • Severe psoriasis: 10–25 mg/wk PO, IM, or IV as a single weekly dose. Do not exceed 30 mg/wk. Or 2.5 mg/day PO at 12-hr intervals for three doses. Do not exceed 30 mg/wk. Alternatively, 2.5 mg/day PO for 5 days followed by at least 2 days rest. Do not exceed 30 mg/wk. After optimal clinical response is achieved, reduce dosage to lowest possible with longest rest periods and consider return to conventional, topical therapy.
  • Severe rheumatoid arthritis: Starting dose: Single doses of 7.5 mg/wk PO or divided dosage of 2.5 mg PO at 12-hr intervals for three doses given as a course once weekly. Dosage may be gradually increased, based on response. Do not exceed 20 mg/wk. Therapeutic response usually begins within 3–6 wk, and improvement may continue for another 12 wk. Improvement may be maintained for up to 2 yr with continued therapy.
  • Meningeal leukemia: < 1 yr: 6 mg intrathecally q 2–5 days.
    • 1–2 yr: 8 mg intrathecally q 2–5 days.
    • 2–3 yr: 10 mg intrathecally q 2–5 days.
    • > 3 yr: 12 mg intrathecally q 2–5 days.
  • Polyarticular course juvenile rheumatoid arthritis (2–16 yr): Initially, 10 mg/m2 PO weekly. Dosage may be increased based on patient response. Maximum 20 mg/m2/wk. Therapeutic response usually begins in 3–6 wk.
Therapeutic actions
  • Methotrexate is a folic acid antagonist that inhibits DNA synthesis. It irreversibly binds to dihydrofolate reductase, inhibiting the formation of reduced folates, and thymidylate synthetase, resulting in inhibition of purine and thymidylic acid synthesis.
  • Treatment of gestational choriocarcinoma, chorioadenoma destruens, hydatidiform mole
  • Treatment and prophylaxis of meningeal leukemia
  • Symptomatic control of severe, recalcitrant, disabling psoriasis
  • Management of severe, active, classical, or definite rheumatoid arthritis
  • Management of polyarticular course juvenile rheumatoid arthritis
  • High-dose regimen followed by leucovorin rescue for adjuvant therapy of nonmetastatic osteosarcoma (orphan drug designation)
  • Unlabeled uses: To reduce corticosteroid requirements in patients with severe corticosteroid-dependent asthma; as a maintenance regimen for Wegener agranulomatosis, dermatomyositis, relapsing-remitting MS, myositis, ulcerative colitis, refractory Crohn’s disease, uveitis, SLE, psoriatic arthritis
Adverse effects
  • Ulceration of the mouth and GI disturbances (e.g. stomatitis and diarrhoea), bone marrow depression, hepatotoxicity, renal failure, skin reactions, alopecia, ocular irritation, arachnoiditis in intrathecal use, megaloblastic anaemia, osteoporosis, precipitation of diabetes, arthralgias, necrosis of soft tissue and bone, anaphylaxis, impaired fertility.
  • Potentially Fatal: Pulmonary reactions (e.g. interstitial lung disease); neurotoxicity (e.g. leukoencephalopathy, paresis, demyelination) with intrathecal use; foetal deaths.
  • Severe renal or hepatic impairment, pre-existing profound bone marrow suppression in patients with psoriasis or rheumatoid arthritis, alcoholic liver disease, AIDS, pre-existing blood dyscrasias, pregnancy (in patients with psoriasis or rheumatoid arthritis), breast-feeding.
Nursing considerations
  • History: Allergy to methotrexate, hematopoietic depression, severe hepatic or renal disease, infection, peptic ulcer, ulcerative colitis, debility, psoriasis, pregnancy, lactation
  • Physical: Weight; T; skin lesions, color; hair; vision, speech, orientation, reflexes, sensation; R, adventitious sounds; mucous membranes, liver evaluation, abdominal examination; CBC, differential; LFTs, renal function tests; urinalysis, blood and urine glucose, glucose tolerance test, chest X-ray
  • BLACK BOX WARNING: Arrange for tests to evaluate CBC, urinalysis, renal and liver function tests, chest X-ray before therapy, during therapy, and for several weeks after therapy.
  • BLACK BOX WARNING: Ensure that patient is not pregnant before administering this drug; counsel patient about the severe risks of fetal abnormalities associated with this drug.
  • WARNING: Reduce dosage or discontinue if renal failure occurs.
  • Reconstitute powder for intrathecal use with preservative-free sterile sodium chloride injection; intended for one dose only; discard remainder. The solution for injection contains benzyl alcohol and should not be given intrathecally.
  • WARNING: Arrange to have leucovorin readily available as antidote for methotrexate overdose or when large doses are used. In general, doses of leucovorin (calcium leucovorin) should be equal or higher than doses of methotrexate and should be given within the first hour. Up to 75 mg IV within 12 hr, followed by 12 mg IM q 6 hr for four doses. For average doses of methotrexate that cause adverse effects, give 6–12 mg leucovorin IM, q 6 hr for four doses or 10 mg/m2 PO followed by 10 mg/m2 q 6 hr for 72 hr.
  • Arrange for an antiemetic if nausea and vomiting are severe.
  • Arrange for adequate hydration during therapy to reduce the risk of hyperuricemia.
  • Do not administer any other medications containing alcohol.
Teaching points
  • Prepare a calendar of treatment days.
  • This drug may cause birth defects or miscarriages. Use birth control while taking this drug and for 3 months thereafter. Men using this drug should also use barrier contraceptives.
  • Avoid alcohol; serious side effects may occur.
  • Arrange for frequent, regular medical follow-up visits, including blood tests to follow the drug’s effects.
  • You may experience these side effects: Nausea, vomiting (request medication; eat frequent small meals); numbness, tingling, dizziness, drowsiness, blurred vision, difficulty speaking (drug effects; seek dosage adjustment; avoid driving or operating dangerous machinery); mouth sores (frequent mouth care is needed); infertility; loss of hair (obtain a wig or other suitable head covering; keep the head covered at extremes of temperature); rash, sensitivity to sun and ultraviolet light (avoid sun; use a sunscreen and protective clothing).
  • Report black, tarry stools; fever; chills; sore throat; unusual bleeding or bruising; cough or shortness of breath; darkened or bloody urine; abdominal, flank, or joint pain; yellow color to the skin or eyes; mouth sores.