Side Effects of Tapazole (Methimazole)
Methimazole (Tapazole) can cause potentially life-threatening adverse reactions including agranulocytosis, hepatotoxicity, and vasculitis, requiring immediate medical attention if symptoms develop. 1
Common Side Effects
- Gastrointestinal disturbances including nausea and vomiting 2
- Skin reactions such as pruritus and rash 2
- Dose-dependent hypothyroidism requiring routine monitoring of thyroid function 1
- Arthralgias (joint pain) in 1-5% of patients 2
Serious Adverse Effects
Hematologic Toxicity
- Agranulocytosis - potentially life-threatening reaction typically occurring within the first three months of treatment with an incidence of 3 per 10,000 patients 2
- Leukopenia and thrombocytopenia may occur 1
- Isolated thrombocytopenia can develop even after long-term use of low-dose methimazole 4
- Aplastic anemia (pancytopenia) - rare but serious 1, 2
Hepatotoxicity
- Liver dysfunction with symptoms including anorexia, pruritus, and right upper quadrant pain 1
- Elevated liver enzymes (ALT, AST) exceeding 3 times the upper limit of normal require immediate discontinuation 1
- Risk of hepatotoxicity appears to be lower with methimazole than with propylthiouracil, especially in pediatric populations 1
Vasculitis
- Can result in severe complications including:
- Leukocytoclastic cutaneous vasculitis
- Acute kidney injury and glomerulonephritis
- Alveolar/pulmonary hemorrhage
- CNS vasculitis and neuropathy 1
- Often associated with anti-neutrophilic cytoplasmic antibodies (ANCA)-positive vasculitis 1
- May require treatment with corticosteroids, immunosuppressants, and plasmapheresis in severe cases 1
Teratogenic Effects
- First trimester use associated with congenital malformations including:
- Aplasia cutis
- Craniofacial malformations (facial dysmorphism, choanal atresia)
- Gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula)
- Omphalocele and abnormalities of the omphalomesenteric duct 1
- Propylthiouracil is generally preferred during the first trimester of pregnancy due to lower teratogenic risk 2, 5
Monitoring and Management
Monitoring Recommendations
- Regular assessment of thyroid function (TSH and free T4) to prevent hypothyroidism 1
- Complete blood count monitoring, especially during the first three months of treatment 3
- Liver function tests if symptoms of hepatic dysfunction develop 1
Management of Side Effects
- For minor skin reactions (rash, pruritus), switching from methimazole to propylthiouracil may be considered, though cross-reactions can occur 2
- For patients with non-serious side effects to methimazole (excluding agranulocytosis and hepatotoxicity), desensitization under allergist supervision is a potential option 6
- For agranulocytosis, immediate discontinuation of the drug is required 1
- Granulocyte colony-stimulating factor (G-CSF) can hasten recovery and reduce morbidity 7
- For vasculitis, discontinue therapy and initiate appropriate intervention 1
Important Precautions
- Patients should be instructed to immediately report symptoms of agranulocytosis (fever, sore throat), hepatotoxicity (anorexia, right upper quadrant pain), or vasculitis 1
- Arthralgias may be the first symptom of more serious immunologic side effects and may warrant drug discontinuation 2
- Cross-reactivity between methimazole and carbimazole should be expected as carbimazole is rapidly metabolized to methimazole 2