Nurses Compass
Drug Guide
Methotrexate
Classification
Therapeutic: Antineoplastic agent, Immunosuppressant
Pharmacological: Folate antagonist
FDA Approved Indications
- Cancer (e.g., osteosarcoma, leukemias, lymphomas, breast cancer)
- Rheumatoid arthritis
- Psoriasis
- Ectopic pregnancy (as part of medical management)
Mechanism of Action
Methotrexate inhibits dihydrofolate reductase, interfering with DNA synthesis, repair, and cellular replication, particularly affecting rapidly dividing cells.
Dosage and Administration
Adult: Dose varies based on condition; for rheumatoid arthritis, typically 7.5-20 mg once weekly; for cancer, doses are significantly higher and individualized.
Pediatric: Doses depend on the condition and weight; for leukemia, dose is based on body surface area.
Geriatric: Careful dose selection and monitoring due to increased risk of toxicity.
Renal Impairment: Reduce dose; consult specific guidelines.
Hepatic Impairment: Use with caution; liver function tests recommended before and during therapy.
Pharmacokinetics
Absorption: Variable; oral bioavailability approximately 50%.
Distribution: Widely distributed, crosses blood-brain barrier.
Metabolism: Minimal hepatic metabolism; small fraction undergoes hepatic conversion to active metabolites.
Excretion: Primarily renal excretion as unchanged drug.
Half Life: 3 to 10 hours; prolonged in renal impairment.
Contraindications
- Pregnancy (category X), breastfeeding, liver disease, alcoholism, immunodeficiency, blood dyscrasias, renal impairment.
Precautions
- Regular monitoring of CBC, liver and renal function; folic acid supplementation may be used to reduce toxicity; avoid in active infections.
Adverse Reactions - Common
- Mucositis, nausea, vomiting (Frequent)
- Myelosuppression (anemia, leukopenia, thrombocytopenia) (Frequent)
- Liver toxicity (Frequent)
Adverse Reactions - Serious
- Severe myelosuppression leading to bleeding or infection (Rare)
- Liver fibrosis/cirrhosis (Rare)
- Pneumonitis, pulmonary fibrosis (Rare)
- Gastrointestinal perforation (Rare)
Drug-Drug Interactions
- NSAIDs, penicillins, salicylates, antibiotics like trimethoprim, other hepatotoxic drugs
Drug-Food Interactions
N/ADrug-Herb Interactions
N/ANursing Implications
Assessment: Baseline CBC, liver and renal function tests; monitor for signs of infection, bleeding, hepatotoxicity.
Diagnoses:
- Risk for infection
- Imbalanced nutrition: less than body requirements
- Impaired tissue integrity
Implementation: Administer as prescribed; ensure adequate hydration; educate patient about signs of toxicity.
Evaluation: Regular laboratory monitoring and clinical assessment for adverse effects.
Patient/Family Teaching
- Take medication exactly as prescribed, once weekly, not daily.
- Report signs of infection, bleeding, unusual fatigue.
- Avoid alcohol and hepatotoxic drugs.
- Use effective contraception during treatment and for at least 6 months after.
Special Considerations
Black Box Warnings:
- Risk of severe and potentially fatal myelosuppression, hepatotoxicity, and tumor lysis syndrome.
- Folic acid supplementation recommended to reduce some adverse effects.
Genetic Factors: Variants in drug metabolism pathways can affect toxicity.
Lab Test Interference: Can cause falsely elevated serum transaminases and bilirubin.
Overdose Management
Signs/Symptoms: Severe myelosuppression, mucositis, renal failure, hepatotoxicity, coma.
Treatment: Leucovorin (folinic acid) rescue therapy; gastric lavage; activated charcoal if early; supportive care in ICU.
Storage and Handling
Storage: Store at room temperature, away from light.
Stability: Stable for shelf-life specified by manufacturer.