Za Pharmacy
Drugs, Supplies and Delivery
Methotrexate
Methotrexate is a versatile medication with applications in oncology and autoimmune diseases. As a folate antagonist, it inhibits DNA synthesis and modulates immune responses, making it a cornerstone in treating conditions such as cancer, rheumatoid arthritis (RA), and psoriasis. This article synthesizes information from the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to detail methotrexate’s mechanism, uses, dosing, side effects, precautions, and interactions.
Methotrexate acts as a competitive inhibitor of dihydrofolate reductase (DHFR), an enzyme required to convert folate into tetrahydrofolate, a critical cofactor in DNA and RNA synthesis. By depleting intracellular folate stores, methotrexate:
- Impairs cell division: Blocks thymidine and purine synthesis, particularly in rapidly dividing cells (e.g., cancer cells, immune cells).
- Modulates inflammation: At low doses, promotes adenosine release, which exerts anti-inflammatory effects in autoimmune diseases (Lippincott, Lange).
In oncology, high-dose methotrexate directly targets proliferating malignant cells. In autoimmune conditions, its immunomodulatory effects reduce inflammation and tissue damage (BNF).
- Oncology:
- Acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, breast cancer, and choriocarcinoma (BNF).
- Autoimmune Diseases:
- Rheumatoid arthritis, psoriasis, psoriatic arthritis, and juvenile idiopathic arthritis (Lippincott).
- Ectopic Pregnancy and Medical Abortion:
- Used in gestational trophoblastic disease and early pregnancy termination (Lange).
- Oncology:
- High-dose regimens: 10–12 g/m² intravenously over 24 hours, followed by leucovorin rescue to mitigate toxicity (BNF).
- Low-dose protocols: 15–30 mg/m² weekly for maintenance therapy (Lippincott).
- Rheumatoid Arthritis/Psoriasis:
- 7.5–25 mg orally or subcutaneously once weekly, adjusted based on response and tolerance (Lange).
- Medical Abortion:
- 50 mg/m² intramuscularly as a single dose (BNF).
Administration:
- Oral, intramuscular, intravenous, or subcutaneous routes.
- Folate supplementation (e.g., folic acid 1–5 mg daily) reduces toxicity without compromising efficacy (Lippincott).
- Common: Mucositis, nausea, fatigue, and elevated liver enzymes (Lippincott).
- Serious:
- Myelosuppression: Leukopenia, thrombocytopenia, and anemia (Lange).
- Hepatotoxicity: Fibrosis or cirrhosis with long-term use (BNF).
- Pulmonary Toxicity: Interstitial pneumonitis or fibrosis (Lippincott).
- Teratogenicity: Contraindicated in pregnancy due to fetal malformations (Lange).
- Pregnancy: Strictly contraindicated; effective contraception required during and for 6 months after treatment (BNF).
- Renal/Hepatic Impairment: Dose reduction necessary; avoid if severe dysfunction (Lippincott).
- Monitoring: Regular full blood counts, liver function tests (LFTs), and renal function tests (Lange).
- Hypersensitivity: Rare but severe reactions, including Stevens-Johnson syndrome (BNF).
- NSAIDs (e.g., ibuprofen): Reduce renal excretion, increasing methotrexate toxicity (Lippincott).
- Proton Pump Inhibitors (e.g., omeprazole): May impair renal clearance (Lange).
- Trimethoprim/Sulfonamides: Synergistic folate antagonism, raising myelosuppression risk (BNF).
- Live Vaccines: Avoid due to immunosuppression (Lippincott).
Methotrexate is the generic name. Brand names include Trexall®, Rheumatrex®, and Otrexup®. Available as tablets (2.5 mg, 5 mg, 10 mg), injectable solutions, and auto-injectors for subcutaneous use.
