Methotrexate

# Methotrexate ## Overview - **Classification**: Antimetabolite, Antifolate, Disease-Modifying Antirheumatic Drug (DMARD) - **Mechanism**: Inhibits dihydrofolate reductase and enzymes in purine/pyrimidine synthesis, preventing DNA and RNA synthesis; increases extracellular adenosine leading to anti-inflammatory effects[1][2][5]. ## Primary Indications 1. **Rheumatoid arthritis** - Reduces inflammation and slows joint damage by immunosuppression. 2. **Psoriasis and Psoriatic arthritis** - Controls skin lesion proliferation and joint inflammation. 3. **Various cancers** (e.g., leukemia, lymphoma) - Inhibits rapidly dividing malignant cells. ## Adult Dosing ### Standard Dosing **Rheumatoid arthritis & autoimmune diseases** - **Dose**: 7.5–25 mg - **Frequency**: Once weekly - **Route**: Oral or subcutaneous - **Duration**: Long-term, based on clinical response **Oncology indications** (varies by cancer type) - **Dose**: High-dose protocols vary widely, e.g., 15 mg/m² IV daily for 5 days (high-dose methotrexate) - **Frequency**: As per protocol - **Route**: Intravenous or intrathecal ### Dose Adjustments - **Renal impairment**: Reduce dose with CrCl <50 mL/min; avoid if CrCl <30 mL/min due to toxicity risks. - **Hepatic impairment**: Use with caution; monitor liver function; avoid in severe liver disease. - **Elderly patients**: Start at lower doses; monitor closely for toxicity due to decreased clearance. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: Variable by indication; oncology dosing often starts around 10-20 mg/m²/dose - **Frequency**: Per protocol (often weekly or as infusion schedule) - **Maximum**: Based on body surface area (BSA) calculations and toxicity monitoring - **Special Notes**: Neonates have immature renal/hepatic function; careful monitoring required. ### Infants (1-12 months) - **Dose**: Approx. 10-20 mg/m²/dose depending on indication - **Frequency**: Weekly or as indicated - **Maximum**: Adjust per adult equivalent; monitor for toxicity ### Children (1-12 years) - **Dose**: 10-20 mg/m² once weekly for autoimmune diseases; higher doses for cancer based on protocols - **Frequency**: Weekly or as per chemo regimen - **Maximum**: Do not exceed adult dose equivalents without specialist oversight ### Adolescents (13-18 years) - **Dose**: Adult dosing approach typically used for autoimmune and cancer indications - **Maximum**: Adult doses apply; monitor adjacently for toxicity ## Safety Information ### Contraindications - **Absolute**: - Pregnancy (teratogenic, fetal demise) - Severe renal or hepatic impairment - Active serious infections - **Relative**: - Pre-existing bone marrow suppression - Peptic ulcer disease or GI ulcers ### Common Adverse Effects - **Very Common (>10%)**: Nausea, stomatitis, mucositis, mild alopecia - **Common (1-10%)**: Elevated liver enzymes, cytopenias (anemia, leukopenia), fatigue - **Serious but Rare**: Severe bone marrow suppression, pulmonary fibrosis, hepatotoxicity, severe infections, renal failure ### Key Drug Interactions - **NSAIDs, sulfonamides, trimethoprim**: Increase methotrexate toxicity (renal clearance interference) - **Live vaccines**: Contraindicated during immunosuppression - **Other folate antagonists**: Increased risk of toxicity - **Leucovorin (folinic acid)**: Used as antidote in toxicity or rescue after high-dose methotrexate ## Monitoring & Follow-up - **Before Treatment**: CBC, liver function tests (LFTs), renal function, chest X-ray (if lung disease risk) - **During Treatment**: CBC, LFTs, renal function every 1-3 months; monitor for mucosal ulcers, respiratory symptoms, infections - **Clinical Signs**: Watch for mucositis, unusual bruising/bleeding, persistent cough, jaundice ## Clinical Pearls - 💡 **Dose weekly, never daily** except in specific cancer regimens to avoid fatal toxicity - 💡 **Folic acid supplementation** reduces side effects without impairing efficacy in autoimmune diseases - 💡 **Patient counseling**: Emphasize adherence to dosing schedule and prompt reporting of mouth sores, signs of infection, or unusual bleeding > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.