Att%2525252520drugs

# Methotrexate ## Overview Methotrexate is an antimetabolite (folate antagonist) used as an immunosuppressant, chemotherapeutic agent, and disease-modifying antirheumatic drug (DMARD). It inhibits dihydrofolate reductase, preventing DNA synthesis and cellular replication. ## Primary Indications * **Oncology:** Acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma, osteosarcoma. * **Autoimmune:** Rheumatoid arthritis (RA), severe psoriasis, Crohn’s disease. * **Other:** Ectopic pregnancy (off-label). ## Adult Dosing * **RA:** 7.5–25 mg orally, SC, or IM **once weekly**. * **Psoriasis:** 10–25 mg orally **once weekly**. * **Oncology (Non-high dose):** Varies significantly by protocol; often 20–75 mg/m² weekly. * **Oncology (High dose):** Requires leucovorin rescue protocols (e.g., 1–12 g/m² IV). ## Pediatric Dosing * **ALL:** Varies by protocol (e.g., 20–40 mg/m² weekly for maintenance; up to 5 g/m² for intensive phases). * **Juvenile Idiopathic Arthritis (JIA):** 10–15 mg/m²/week (max 20–25 mg/week). ## Dose Adjustments * **Renal Impairment:** Requires significant reduction or avoidance based on creatinine clearance (CrCl). If CrCl < 30 mL/min, use with extreme caution or avoid. * **Hepatic Impairment:** Avoid in chronic liver disease (risk of fibrosis). ## Contraindications * Pregnancy (teratogenic / abortifacient). * Breastfeeding. * Pre-existing bone marrow suppression (leukopenia, thrombocytopenia). * Severe renal or hepatic impairment. * Alcoholism or chronic liver disease. * Active infectious disease or immunodeficiency syndromes. ## Adverse Effects * **Common:** Stomatitis, nausea, vomiting, elevated transaminases, alopecia. * **Severe:** Bone marrow suppression (myelosuppression), hepatotoxicity, pulmonary fibrosis (pneumonitis), renal failure, severe skin reactions (Stevens-Johnson syndrome). ## Key Drug Interactions * **NSAIDs:** Reduce renal excretion, increasing risk of fatal toxicity (use with caution; monitor closely). * **Trimethoprim/Sulfamethoxazole:** Increases risk of pancytopenia due to additive folate antagonism. * **Probenecid:** Increases methotrexate levels. * **Hepatotoxins:** Increased risk of liver damage when used with other hepatotoxic drugs. ## Monitoring * **Baseline/Intermittent:** CBC with differential, LFTs, serum creatinine, BUN, chest X-ray (if indicated for pulmonary symptoms). * **Routine:** Folic acid supplementation (standard for RA/psoriasis patients to reduce toxicity). * **High Dose:** Methotrexate serum levels are mandatory to guide leucovorin rescue timing. ## Clinical Pearls * **Fatal Medication Errors:** Ensure the patient understands **weekly** dosing. Daily dosing for non-oncologic conditions is a common, often fatal medication error. * **Leucovorin Rescue:** Essential for high-dose regimens to bypass metabolic blockade in healthy cells. * **Photosensitivity:** Advise patients to use sun protection during treatment. *** **Educational Disclaimer:** Clinical practice varies by institution, regional protocols, and specific patient risk factors. Always verify prescribing information, contraindications, and dosing ratios via institutional pharmacy policies or current drug monographs (e.g., Lexicomp, UpToDate) before finalizing orders.