Who should not take methimazole (antithyroid medication)?

Who Should Not Take Methimazole

Methimazole is absolutely contraindicated in women during the first trimester of pregnancy due to severe teratogenic risks, and should be avoided in patients with a history of agranulocytosis, aplastic anemia, or severe hepatotoxicity from prior thionamide use. 1

Absolute Contraindications

First Trimester Pregnancy

• Methimazole causes congenital malformations when used in the first trimester, including aplasia cutis (scalp defects), craniofacial abnormalities (facial dysmorphism, choanal atresia), gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula), omphalocele, and abnormalities of the omphalomesenteric duct 1
• Propylthiouracil (PTU) is the preferred antithyroid drug in the first trimester due to lower teratogenic risk 2, 3
• Methimazole becomes the preferred agent in the second and third trimesters because PTU carries higher hepatotoxicity risk with prolonged use 2, 3

Prior Severe Hematologic Reactions

• Patients who previously developed agranulocytosis or aplastic anemia (pancytopenia) from methimazole must never receive it again 1
• Agranulocytosis occurs in approximately 3 per 10,000 patients and is potentially life-threatening 2, 4
• Cross-reactivity exists between methimazole and PTU for agranulocytosis, so neither thionamide should be used if agranulocytosis occurred with either drug 5

Prior Severe Hepatotoxicity

• Patients with documented methimazole-induced acute liver failure or severe hepatotoxicity should not receive the drug again 1
• While methimazole carries lower hepatotoxicity risk than PTU (especially in pediatric populations), severe cases including cholestatic jaundice have been reported 1, 6

Relative Contraindications Requiring Extreme Caution

Active Liver Disease

• Patients with pre-existing hepatic dysfunction should avoid methimazole when possible, as the drug can cause hepatotoxicity ranging from transaminase elevation to acute liver failure 1
• If methimazole must be used in patients with underlying liver disease, discontinue immediately if hepatic transaminases exceed 3 times the upper limit of normal 1

ANCA-Positive Vasculitis History

• Methimazole can cause severe vasculitis including leukocytoclastic cutaneous vasculitis, acute kidney injury with glomerulonephritis, alveolar/pulmonary hemorrhage, CNS vasculitis, and neuropathy 1
• Most cases are associated with anti-neutrophilic cytoplasmic antibodies (ANCA) 1
• Discontinue methimazole immediately if vasculitis is suspected and initiate corticosteroids, immunosuppressants, or plasmapheresis as needed 1

Special Populations Requiring Dose Adjustment or Monitoring

Pregnancy Beyond First Trimester

• Methimazole crosses the placenta and can cause fetal goiter and cretinism at any gestational age 1
• Use the lowest possible dose to control maternal hyperthyroidism while maintaining euthyroid state 1
• Women of childbearing age must receive preconception counseling, as methimazole normalizes ovulatory function and increases unplanned pregnancy risk 7

Patients with Prior Minor Allergic Reactions

• Patients who developed rash, pruritus, or urticaria (but not agranulocytosis or hepatotoxicity) may be candidates for desensitization under allergist supervision 8, 9
• After long-term disease control with PTU, some patients can tolerate low-dose methimazole (5 mg twice weekly to 5 mg daily) without recurrent allergic reactions 9
• Eight of 9 patients in one series successfully transitioned to low-dose methimazole after years of PTU therapy 9

Critical Monitoring Requirements for All Patients

Baseline and Ongoing Assessment

• Patients must be instructed to immediately report fever, sore throat, or signs of infection (agranulocytosis warning signs) 1
• Monitor for hepatic dysfunction symptoms: anorexia, pruritus, right upper quadrant pain, jaundice, dark urine, or light-colored stools 1, 6
• Discontinue methimazole promptly if clinically significant liver abnormality develops 1
• Monitor thyroid function (TSH, free T4) every 4-6 weeks during initial treatment to prevent iatrogenic hypothyroidism 4

Common Pitfalls to Avoid

• Do not assume methimazole is safe throughout pregnancy—switch to PTU in first trimester if pregnancy occurs 2, 3
• Do not continue methimazole if agranulocytosis develops—both thionamides are contraindicated, requiring definitive therapy (radioactive iodine or thyroidectomy) 5
• Do not ignore minor hematologic changes—leukopenia and thrombocytopenia can progress to severe complications even with low-dose, long-term use 1, 10
• Do not rechallenge with methimazole after severe hepatotoxicity or agranulocytosis—these are permanent contraindications 1