Methimazole

# Methimazole ## Overview Thionamide antithyroid agent that inhibits thyroid peroxidase, blocking synthesis of thyroid hormones. Does not affect existing stored hormone; therapeutic onset in 1–3 weeks. ## Primary Indications - Hyperthyroidism (Graves’ disease, toxic nodular goiter) - Preoperative thyroidectomy preparation - Pre-radioactive iodine therapy adjunct ## Adult Dosing **Initial**: 15–40 mg/day PO divided every 8 hours. **Maintenance**: 5–15 mg/day once daily (once euthyroid, typically 4–8 weeks). **Maximum**: 40 mg/day initial; up to 60 mg/day in severe hyperthyroidism. ## Pediatric Dosing **Initial**: 0.25–1 mg/kg/day PO divided every 8–12 hours. **Maintenance**: 0.25–0.5 mg/kg/day once daily. **Maximum**: 30 mg/day. ## Dose Adjustments - **Hepatic impairment**: No universal guidelines; monitor LFTs closely; may reduce dose. - **Elderly**: Start at lower end of dose range. - **Pregnancy**: Use lowest effective dose; risk of fetal hypothyroidism. - **Discontinuation**: Taper over months if remission achieved; not required for adverse events—stop immediately. ## Contraindications - Hypersensitivity to methimazole or thionamides - Severe hepatic injury (unless hyperthyroidism is life-threatening) - Breastfeeding (relative contraindication; use with caution, lowest dose) ## Adverse Effects **Common**: Rash, pruritus, urticaria, arthralgia, nausea, hypothyroidism (overtreatment). **Serious (rare, <0.5%)**: Agranulocytosis (fever, sore throat, infection), hepatotoxicity, vasculitis, aplastic anemia. **Periodic**: Monitor for signs of infection; instruct patient to stop drug and seek care if fever or severe pharyngitis. ## Key Drug Interactions - **Warfarin**: Potentiation (hyperthyroidism increases clotting factor clearance; corrections decrease warfarin dose). - **Beta-blockers**: Reduce clearance; adjust dose as thyroid function normalizes. - **Amiodarone, lithium**: Interfere with thyroid function; may require dose changes. - **Digoxin**: Increased sensitivity in hyperthyroidism; monitor levels as thyroid hormone normalizes. ## Monitoring - **Baseline**: CBC with differential, LFTs, thyroid panel (TSH, free T4, total T3). - **Regular**: Thyroid panel every 4–6 weeks until euthyroid, then every 2–3 months. CBC with differential if symptoms of infection (fever, pharyngitis). LFTs if symptoms of hepatotoxicity. ## Clinical Pearls - **Agranulocytosis**: Explain absolute risk (<0.5%) and cardinal symptoms; no evidence supports routine CBC monitoring in asymptomatic patients. - **Pregnancy**: Methimazole preferred to propylthiouracil in first trimester only if other options fail; associated with cutis aplasia. Use minimal effective dose. - **Once-daily dosing** is effective due to long intrathyroidal half-life. - **Hypothyroidism**: Rapid overtreatment can cause goiter; titrate down gradually. - **Preoperative**: Achieve euthyroid state (typically 4–8 weeks). Potassium iodide may be added 10–14 days preop. --- **Disclaimer**: This information is for educational use only. Drug dosing and safety profiles evolve; always verify with current prescribing information, institutional protocols, and product labeling before clinical application.