methimazole
Brand: Tapazole
Prototype Drug
Drug Class: antithyroid
Drug Family: antithyroid
Subclass: thionamide
Organ Systems: endocrine
Mechanism of Action
Inhibits thyroid peroxidase, blocking oxidation of iodide to iodine and organification (coupling of iodine to tyrosine residues) — thereby preventing thyroid hormone (T3, T4) synthesis; does NOT affect existing thyroid hormone stores (delayed onset of effect).
thyroid peroxidase
Indications
- hyperthyroidism (Graves' disease — first-line antithyroid therapy)
- preparation for thyroid surgery or radioiodine therapy
- thyroid storm (high doses)
Contraindications
- first trimester of pregnancy (use PTU instead — methimazole causes aplasia cutis and choanal atresia)
- hypersensitivity to methimazole
Adverse Effects
Common
- rash
- pruritus
- nausea
- arthralgias
- mild leukopenia
Serious
- agranulocytosis (0.1–0.5% — most dangerous; usually within first 3 months)
- hepatotoxicity (cholestatic jaundice)
- hypothyroidism (with excessive dosing)
- ANCA-positive vasculitis (rare, usually with PTU)
- teratogenicity (aplasia cutis with first-trimester exposure)
Pharmacokinetics (ADME)
| Absorption | Rapid and complete oral absorption |
| Distribution | Concentrates in thyroid gland; protein binding minimal |
| Metabolism | Hepatic |
| Excretion | Renal |
| Half-life | 4–6 hours; but biological effect lasts much longer (dosing every 8–24 hours depending on dose) |
| Onset | 1–2 weeks for clinical effect (existing thyroid hormone must be consumed) |
| Peak | 0.5–1 hour |
| Duration | 8–24 hours |
| Protein Binding | minimal |
| Vd | ~0.6 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| warfarin | hyperthyroid state increases warfarin metabolism; normalization with methimazole increases warfarin effect — INR may rise significantly | major |
| beta-blockers | hyperthyroid state increases beta-blocker clearance; levels normalize as euthyroidism is achieved | moderate |
| digoxin | hypothyroidism increases digoxin sensitivity; monitor digoxin levels | moderate |
Nursing Considerations
- Instruct patient to report sore throat, fever, or mouth sores immediately — these are signs of agranulocytosis; obtain CBC with differential urgently; hold methimazole pending results
- Monitor CBC and LFTs at baseline and periodically; CBC before initiation establishes baseline WBC
- Monitor thyroid function tests (TSH, free T4) every 4–6 weeks during initial titration; TSH may remain suppressed for months after achieving euthyroidism — use free T4 to guide dose adjustments initially
- Use PTU (not methimazole) in first trimester of pregnancy; switch to methimazole after first trimester (PTU carries hepatotoxicity risk)
Clinical Pearls
- Methimazole is preferred over PTU except in first-trimester pregnancy because it has once-daily dosing (vs PTU TID), lower hepatotoxicity risk, and equivalent efficacy — the ATA guidelines recommend methimazole as first-line for Graves' disease
- Agranulocytosis from methimazole is idiosyncratic (not dose-dependent), can develop suddenly, and is potentially life-threatening — patients must be educated about this risk and instructed to present immediately for CBC if febrile or ill
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.