Educational use only. Drug cards are AI-assisted study material for NCLEX preparation.
Methotrexate (Trexall, Otrexup, Rasuvo)
Mechanism of action
Inhibits dihydrofolate reductase, blocking thymidine and purine synthesis. Cell-cycle (S-phase) specific. Used at high doses for chemotherapy (leukemia, lymphoma, choriocarcinoma) and at LOW doses (weekly, not daily) for rheumatoid arthritis, psoriasis, and other autoimmune conditions. Also for ectopic pregnancy.
Adverse effects
Life-threatening / NCLEX-tested
- Severe bone marrow suppression — pancytopenia (life-threatening)
- Hepatotoxicity (acute and chronic; cirrhosis with cumulative dose)
- Pulmonary toxicity (pneumonitis, fibrosis)
- Nephrotoxicity (acidic urine precipitates the drug — alkalinize for high-dose chemo)
- Mucositis and severe stomatitis
- Teratogenic — absolute contraindication in pregnancy (also for ectopic-pregnancy treatment, the patient must avoid future pregnancy for ~3 months after)
- Severe skin reactions including SJS/TEN
Side effects
Common — what to teach
- Nausea, anorexia
- Fatigue, malaise
- Mild alopecia
- Headache
- Sun sensitivity
- Mouth ulcers (early sign of mucositis)
Food & drug interactions
MOST DANGEROUS: NSAIDs, salicylates, and TMP-SMX raise methotrexate levels and risk fatal toxicity in low-dose regimens — counsel rheumatology patients carefully. Probenecid, penicillins, and proton pump inhibitors also raise levels. Folic acid 1 mg daily REDUCES side effects in low-dose regimens (does not work for high-dose chemo). Live vaccines are contraindicated.
Nursing implications
Assessment, monitoring, patient teaching
- Verify dose and frequency carefully — fatal errors occur when weekly doses are mistakenly given daily. Independent two-nurse verification on every dose
- For low-dose RA/psoriasis: ALWAYS counsel "weekly, not daily" — write the day on the calendar, take folic acid 1 mg daily on the other six days (or per protocol)
- Baseline and ongoing CBC, LFTs, BUN/Cr; periodic chest X-ray and PFTs for chronic use
- Counsel: avoid NSAIDs, aspirin, alcohol, and TMP-SMX
- Aggressive pregnancy prevention (both partners) — methotrexate is teratogenic and abortifacient
- For high-dose chemo: leucovorin rescue, urine alkalinization, vigorous hydration; check methotrexate levels per protocol
- Teach to report mouth ulcers, fever, easy bruising, jaundice, dyspnea, or new cough
When to hold / contraindications
- Significant pancytopenia or any neutropenia/thrombocytopenia per protocol
- Significant LFT elevation
- Pregnancy or planning pregnancy (for either partner)
- Active major infection
- Acute kidney injury
- New stomatitis, mucositis, dyspnea/cough, or rash — assess before next dose
Memory anchor
Methotrexate for RA = WEEKLY, never daily. Folic acid on the off-days. Avoid NSAIDs and Bactrim. Pregnancy is absolutely contraindicated. "M.T.X. = Marrow, Liver, Lungs hit."
Practice Methotrexate questions
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