Generic Name

Methotrexate Sodium

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Classification

FDA Approved Indications

• Cancer (e.g., osteosarcoma, leukemias, lymphoma, breast cancer, lung cancer)
• Autoimmune diseases (e.g., rheumatoid arthritis, psoriasis, Crohn's disease)
• Ectopic pregnancy (off-label use)

Mechanism of Action

Methotrexate inhibits dihydrofolate reductase, an enzyme involved in tetrahydrofolate synthesis, thereby disrupting DNA and RNA synthesis, leading to cell death, particularly in rapidly dividing cells.

Dosage and Administration

Adult: Dose varies widely based on indication; for rheumatoid arthritis, typically 7.5-25 mg once weekly; for cancer, doses are higher and administered under supervision by an oncologist.

Pediatric: Dosing depends on body surface area or weight; specifically for juvenile rheumatoid arthritis, lower doses are used.

Geriatric: Use with caution; adjust dose based on renal function and comorbidities.

Renal Impairment: Reduce dose; monitor renal function closely.

Hepatic Impairment: Use with caution; monitor liver function tests.

Pharmacokinetics

Absorption: Variable; oral bioavailability approximately 50%.

Distribution: Widely distributed, crosses the blood-brain barrier in high doses.

Metabolism: Minimal hepatic metabolism; most is eliminated unchanged.

Excretion: Primarily renal; elimination half-life 3-10 hours, prolonged in renal impairment.

Half Life: Approximately 3-10 hours depending on dose and clearance.

Contraindications

• Pregnancy (category X), breastfeeding, hepatic insufficiency, renal impairment, alcoholism, blood dyscrasias, immunodeficiency, pre-existing blood disorders.

Precautions

• Monitor liver, kidney function, and blood counts regularly.
• Use in patients with active infections or peptic ulcer disease should be cautious.

Adverse Reactions - Common

• Stomatitis (Frequent)
• Myelosuppression (Frequent)
• Nausea, vomiting (Common)
• Alopecia (Common)

Adverse Reactions - Serious

• Liver toxicity and cirrhosis (Uncommon)
• Pulmonary toxicity (pneumonitis, fibrosis) (Rare)
• Bone marrow suppression causing severe cytopenias (Serious)
• Anaphylaxis (rare) (Rare)

Drug-Drug Interactions

• Penicillin (risk of nephrotoxicity), NSAIDs (increase toxicity), live vaccines (contraindicated)

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Take medication exactly as prescribed, usually once weekly.
• Report signs of infection, bleeding, mouth sores or symptoms of liver toxicity.
• Use effective contraception during and for at least 6 months after therapy.
• Avoid alcohol and hepatotoxic drugs.

Special Considerations

Black Box Warnings:

• Folate antagonists like methotrexate can cause severe toxicity including hepatotoxicity, myelosuppression, and nephrotoxicity.

Genetic Factors: Some genetic polymorphisms (e.g., MTHFR gene variants) may affect drug toxicity and response.

Lab Test Interference: Methotrexate can interfere with certain lab tests, including folate assays.

Overdose Management

Signs/Symptoms: Severe myelosuppression, mucositis, hepatic toxicity, renal failure.

Treatment: Leucovorin (folinic acid) rescue therapy is the mainstay; emergency hemodialysis may be considered for severe overdose.

Storage and Handling

Storage: Store at room temperature, away from moisture and light.

Stability: Stable under recommended storage conditions.