Most Common Side Effects of Methimazole and Their Relative Frequencies
Methimazole commonly causes gastrointestinal side effects, skin reactions, and rarely but seriously can cause agranulocytosis, hepatotoxicity, and vasculitis. Based on the FDA drug label and research evidence, here is a comprehensive table of methimazole's side effects and their relative frequencies:
| Side Effect Category | Specific Side Effects | Frequency |
|---|---|---|
| Gastrointestinal | Nausea | Common |
| Vomiting | Common | |
| Metallic taste | Common | |
| Loss of appetite | Common | |
| Abdominal pain | Common | |
| Dermatologic | Rash | Common |
| Pruritus (itching) | Common (8% in pediatric patients) [1] | |
| Hives | Common (8% in pediatric patients) [1] | |
| Allergic dermatitis | Uncommon | |
| Hematologic | Agranulocytosis | Rare but potentially life-threatening [2] |
| Leukopenia | Rare | |
| Thrombocytopenia | Rare | |
| Aplastic anemia (pancytopenia) | Rare | |
| Hepatic | Hepatotoxicity | Uncommon (less than with propylthiouracil) [2] |
| Cholestatic jaundice | Rare [3,4] | |
| Acute liver failure | Rare [2] | |
| Endocrine | Hypothyroidism | Dose-dependent |
| Immunologic | Vasculitis | Rare but severe [2] |
| Stevens-Johnson syndrome | Rare (3% in pediatric patients) [1] | |
| Musculoskeletal | Arthralgia/joint pain | Uncommon (3% in pediatric patients) [1] |
Timing and Risk Factors
- Most adverse events occur within the first few months of therapy, with an average onset at 17±7 weeks 1
- Cholestatic jaundice typically appears within the first month of treatment 4
- No specific risk factors for developing adverse reactions have been identified 1
Serious Adverse Effects
Agranulocytosis
- Potentially life-threatening reaction
- Patients should immediately report symptoms like fever or sore throat 2
- Requires immediate discontinuation of the medication and monitoring of bone marrow indices 2
Hepatotoxicity
- Warning signs include anorexia, pruritus, right upper quadrant pain
- Requires liver function monitoring (bilirubin, alkaline phosphatase, ALT, AST)
- Treatment should be discontinued if transaminases exceed 3 times the upper limit of normal 2
Vasculitis
- Can result in severe complications including leukocytoclastic cutaneous vasculitis, acute kidney injury, glomerulonephritis, alveolar/pulmonary hemorrhage, CNS vasculitis, and neuropathy
- Often associated with ANCA-positive vasculitis
- May require discontinuation and additional treatments including corticosteroids, immunosuppressants, and plasmapheresis 2
Pediatric Considerations
In pediatric patients with Graves' disease, adverse events were observed in 19% of patients, with the most common being pruritus and hives (8%), followed by arthralgia (3%) and Stevens-Johnson syndrome (3%) 1.
Management of Side Effects
- Minor skin reactions may be managed by switching to propylthiouracil or through desensitization to methimazole under allergist supervision 5
- For serious reactions like agranulocytosis, hepatotoxicity, or vasculitis, immediate discontinuation is required 2
- Patients should be educated about potential side effects and instructed to report concerning symptoms promptly
This comprehensive overview should help clinicians anticipate, recognize, and manage potential adverse effects of methimazole therapy.