Can methimazole cause hyperthermia (high fever) and pharyngitis (sore throat)?

Methimazole Can Cause High Fever and Sore Throat as Warning Signs of Life-Threatening Agranulocytosis

Yes, methimazole can cause high fever and sore throat, and these symptoms represent a medical emergency requiring immediate discontinuation of the drug and urgent evaluation for agranulocytosis. 1

Critical Warning: Agranulocytosis

Patients taking methimazole must immediately stop the medication and seek emergency medical care if they develop fever or sore throat, as these are cardinal symptoms of agranulocytosis—a potentially life-threatening complication. 1

Why This Matters

• Agranulocytosis (neutrophil count <500/µL) is the most serious adverse reaction to methimazole, characterized by severe depletion of white blood cells that leaves patients defenseless against infections 1
• The FDA drug label explicitly warns that patients must be instructed to "immediately report to their physicians any symptoms suggestive of agranulocytosis, such as fever or sore throat" 1
• The drug must be discontinued immediately in the presence of agranulocytosis, and bone marrow indices should be monitored 1

Clinical Presentation

Methimazole-induced agranulocytosis typically presents with: 2, 3

• Fever (often high-grade, >103°F) 4
• Sore throat with mucosal inflammation or ulceration 2
• Fatigue and general malaise 1, 2
• Risk of overwhelming sepsis if not recognized and treated promptly 4

Immediate Management Algorithm

Step 1: Discontinue Methimazole Immediately

• Stop the drug as soon as fever or sore throat develops—do not wait for laboratory confirmation 1

Step 2: Obtain Emergency Laboratory Testing

• Complete blood count with differential to assess for agranulocytosis (neutrophil count <500/µL) 1
• White blood cell count may be profoundly depressed (as low as 0.4 × 10³/µL) 4

Step 3: Initiate Infection Control Measures

• Administer broad-spectrum intravenous antibiotics empirically if local or systemic infection is suspected 2, 4
• Consider reverse isolation for severely neutropenic patients 4
• Add antifungal coverage if no improvement occurs within several days 4

Step 4: Consider G-CSF Therapy

• Granulocyte colony-stimulating factor (filgrastim) should be limited to patients with poor prognostic factors 2
• Recovery of granulocyte count may take 5-6 days even with G-CSF therapy 4

Step 5: Monitor Until Recovery

• Close monitoring is required until neutrophil count returns to normal 2
• Never re-expose the patient to methimazole after agranulocytosis—this is absolutely contraindicated 2

Additional Serious Complications

Beyond agranulocytosis, methimazole can cause other severe reactions that may present with fever: 1, 3

• Hepatotoxicity with fever, jaundice, and right upper quadrant pain 1, 5
• Aplastic anemia (pancytopenia) requiring immediate drug discontinuation 1, 3
• Vasculitis with fever, rash, kidney injury, or pulmonary hemorrhage 1

Common Pitfall to Avoid

Do not attribute fever and sore throat in a patient on methimazole to a simple viral pharyngitis or streptococcal infection without first ruling out agranulocytosis. 1 The FDA label specifically requires that patients be under close surveillance and cautioned to report these symptoms immediately, as they may herald life-threatening bone marrow suppression rather than a benign infection 1. White blood cell and differential counts must be obtained urgently to determine whether agranulocytosis has developed 1.

Patient Education Requirement

All patients prescribed methimazole must be counseled at the time of prescribing to: 1

• Immediately report fever, sore throat, skin eruptions, headache, or general malaise
• Stop the medication and seek emergency care if these symptoms develop
• Understand that re-exposure after agranulocytosis is dangerous and must be avoided 2