TAPAZOLE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TAPAZOLE (TAPAZOLE).
Inhibits thyroid peroxidase, thereby blocking the synthesis of thyroid hormones (T3 and T4) and reducing iodine organification and coupling of iodotyrosines.
| Metabolism | Primarily hepatic metabolism via CYP450 enzymes (minor); main metabolite is methimazole sulfonate. |
| Excretion | Primarily renal, approximately 65% excreted in urine as metabolites and unchanged drug; <10% eliminated in feces via biliary excretion. |
| Half-life | 3-6 hours; clinically, effects persist longer due to intrathyroidal accumulation. |
| Protein binding | Plasma protein binding: 0% (negligible). |
| Volume of Distribution | 0.6 L/kg; indicates distribution into total body water, with accumulation in thyroid gland. |
| Bioavailability | Oral: 80-95%. |
| Onset of Action | Oral: 30-60 minutes for inhibition of thyroid hormone synthesis; full effect in 3-4 weeks. |
| Duration of Action | 12-24 hours; duration of TSH suppression and T4/T3 reduction lasts up to 2-3 weeks after discontinuation due to inhibition of thyroperoxidase. |
15-40 mg per day orally in 3 divided doses; maintenance: 5-15 mg per day orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required; primarily hepatically cleared. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use. |
| Pediatric use | Initial: 0.4-0.7 mg/kg/day orally in 3 divided doses; maintenance: 0.2-0.4 mg/kg/day orally once daily. |
| Geriatric use | Start at lower end of dosing range (15-30 mg/day) due to increased sensitivity; monitor thyroid function and leukocyte count closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TAPAZOLE (TAPAZOLE).
| Breastfeeding | Methimazole is excreted into breast milk in low concentrations (M/P ratio approximately 1). Short-term use is considered compatible with breastfeeding, but monitoring of infant thyroid function and development is recommended. Highest risk in premature infants or those with hepatic or renal impairment. |
| Teratogenic Risk | FDA Pregnancy Category D. Methimazole crosses the placenta and is associated with congenital malformations including aplasia cutis, choanal atresia, esophageal atresia, and other defects, particularly when used in the first trimester. Risk of neonatal hypothyroidism and goiter with use in later trimesters. Dose-dependent risk; lowest effective dose recommended. |
■ FDA Black Box Warning
Agranulocytosis: can be severe and life-threatening; requires regular monitoring of white blood cell counts.
| Serious Effects |
["Hypersensitivity to methimazole","Breastfeeding (relative contraindication; small amounts excreted in milk)","Severe hepatic impairment (relative)","Previous agranulocytosis from thionamide therapy"]
| Precautions | ["Agranulocytosis: monitor WBC counts regularly; discontinue if severe neutropenia occurs.","Hepatotoxicity: can cause hepatic injury; monitor liver function tests.","Hypoprothrombinemia/hypoglycemia (rare)","Cross-allergy with propylthiouracil possible","Pregnancy: use only if clearly needed and at lowest effective dose due to risk of fetal goiter and hypothyroidism."] |
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| Fetal Monitoring | Maternal: Thyroid function tests (TSH, free T4) every 2-4 weeks, liver function tests, CBC with differential (risk of agranulocytosis). Fetal: Ultrasound for growth and anatomy (especially scalp defects), neonatal thyroid function screening at birth. |
| Fertility Effects | Untreated maternal hyperthyroidism can impair fertility; methimazole treatment restores euthyroidism and improves fertility. No direct adverse effects on fertility in animal studies, but human data limited. |