What are the side effects of methimazole?

Side Effects of Methimazole

Methimazole can cause serious adverse effects including agranulocytosis, hepatotoxicity, vasculitis, and congenital malformations when used during pregnancy, requiring careful monitoring and immediate discontinuation if concerning symptoms develop. 1

Common Side Effects

• Gastrointestinal effects:

  • Nausea
  • Vomiting
  • Loss of appetite
  • Abdominal pain 2

• Skin reactions:

  • Rash
  • Pruritus (itching)
  • These typically occur within the first few weeks of treatment 2

• Dose-dependent hypothyroidism:

  • Requires routine monitoring of TSH and free T4 levels 1

Serious Adverse Effects

Blood Disorders

• Agranulocytosis:

  • Potentially life-threatening
  • Incidence: 3 per 10,000 patients
  • Typically occurs during first three months of treatment
  • Warning signs: fever, sore throat, malaise 2
  • Requires immediate discontinuation of medication 1

• Other hematologic effects:

  • Leukopenia
  • Thrombocytopenia
  • Aplastic anemia (pancytopenia)
  • Hemolytic anemia
  • Eosinophilia 1

Hepatotoxicity

• Less common with methimazole than with propylthiouracil, especially in pediatric population
• Can range from asymptomatic transient increase in liver enzymes to severe liver injury
• Warning signs: anorexia, pruritus, right upper quadrant pain, jaundice
• Requires monitoring of liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (ALT, AST)
• Discontinue immediately if liver abnormalities occur 1, 3

Vasculitis

• Can result in severe complications:
  • Leukocytoclastic cutaneous vasculitis
  • Acute kidney injury and glomerulonephritis
  • Alveolar/pulmonary hemorrhage
  • CNS vasculitis
  • Neuropathy
• Often associated with anti-neutrophilic cytoplasmic antibodies (ANCA)-positive vasculitis
• May require treatment with corticosteroids, immunosuppressants, or plasmapheresis 1

Other Serious Effects

• Arthralgias (joint pain) in 1-5% of patients
  • May be first symptom of more serious immunologic side effects 2
• Cholestatic jaundice (rare but severe)
  • Can develop within days to weeks of starting treatment
  • Symptoms: severe pruritus, jaundice, dark urine, light-colored stool 3, 4

Pregnancy and Breastfeeding Concerns

• Pregnancy Category D - potential hazard to fetus 1
• First trimester use associated with congenital malformations:
  • Aplasia cutis
  • Craniofacial malformations (facial dysmorphism, choanal atresia)
  • Gastrointestinal malformations
  • Omphalocele
• Crosses placental membranes and can cause fetal goiter and cretinism 1
• Distributed into breast milk - discontinue nursing or the drug 1

Drug Interactions

• Anticoagulants: May increase activity of oral anticoagulants (e.g., warfarin)
• Beta-blockers: Hyperthyroidism may increase clearance of beta-blockers; dose reduction may be needed when patient becomes euthyroid
• Digitalis glycosides: Serum levels may increase when patient becomes euthyroid
• Theophylline: Clearance may decrease when patient becomes euthyroid 1

Monitoring Recommendations

1. Complete blood count: Regularly monitor for agranulocytosis, especially during first 3 months
2. Liver function tests: At baseline and periodically during treatment
3. Thyroid function tests: Every 4-6 weeks initially, then every 3-6 months once stable 5
4. Prothrombin time: Monitor before surgical procedures 1

Patient Education

Patients should be instructed to immediately report:

• Fever or sore throat (possible agranulocytosis)
• Abdominal pain, jaundice (possible liver injury)
• New rash, hematuria, decreased urine output (possible vasculitis)
• Dyspnea or hemoptysis (possible pulmonary complications) 1

Management of Side Effects

If mild skin reactions occur, switching between thioimidazoles and propylthiouracil may be considered, though cross-reactions can occur. For serious adverse effects, immediate discontinuation of the medication is required 2, 6.