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Methimazole

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Methimazole, Tapazole

  • See Also
  1. Thionamide
  2. Propylthiouracil
  3. Hyperthyroidism
  4. Hyperthyroidism Management
  • Indications
  1. Thionamide (Methimazole or Propylthiouracil) Indications
    1. Hyperthyroidism in children and adolescents
    2. Hyperthyroidism in Pregnancy (first trimester for PTU, Methimazole after)
    3. Severe Grave's Disease (e.g. Thyroid Storm)
    4. Subclinical Hyperthyroidism
  2. Methimazole is the preferred first-line Thionamide (over PTU) in most cases due to lower hepatotoxicity
  3. Reasons to use Propylthiouracil (PTU) instead of Methimazole
    1. Lactation
    2. Pregnancy (both PTU and Methimazole are Pregnancy Category D)
      1. Use Propylthiouracil (PTU) in first trimester
      2. Use Methimazole in second and third trimester
  • Contraindications
  1. First Trimester pregnancy
  • Mechanism
  1. Thionamides block T3 and T4 synthesis (by inhibiting Thyroid peroxidase)
    1. Thyroid peroxidase normally converts inorganic Iodide ions to organic Iodine
    2. Organic Iodine is required for Thyroxine synthesis
  • Medications
  1. Methimazole (Tapazole) 5 mg and 10 mg tablets
  1. Target dose to Free T4 high end of normal range
  2. Start
    1. Subclinical Hyperthyroidism: 5 mg orally daily
    2. Mild Hyperthyroidism: 5 mg orally three times daily
    3. Moderate Hyperthyroidism: 10 mg orally three times daily
    4. Severe Hyperthyroidism: 20 mg orally three times daily
  3. Maintenance
    1. Titrate Methimazole dose down after 4 to 6 weeks
    2. Reduce dose to 5-10 mg per day
    3. Goal: maintain normal Thyroid function
    4. Range: 5 to 30 mg/day
  1. Target dose to Free T4 high end of normal range
  2. Start: 0.4 mg/kg/day divided every 8 hours orally
  3. Maximum: 30 mg/day
  4. Maintenance
    1. Titrate Methimazole dose down after 4 to 6 weeks
    2. Reduce dose to 50% of starting dose (e.g. 0.2 mg/kg/day divided every 8 hours)
    3. Goal: maintain normal Thyroid function
  • Adverse effects (3 per 1000 patients)
  1. Drug-Induced Agranulocytosis (more common with PTU)
    1. Risk increases over age 40 years
    2. Occurs in 0.17% of those on Methimazole
    3. Presentation: Infection (e.g. Pharyngitis)
    4. Obtain Complete Blood Count if suspected
    5. Course
      1. Resolves within 2-3 weeks after drug stopped
      2. Severe, refractory course may occur
    6. Contraindication to further Antithyroid Drugs
  2. Jaundice
    1. Cholestatic Jaundice
    2. Occurs more commonly with Methimazole
  3. Hepatitis
    1. Occurs with both Methimazole and Propylthiouracil (PTU)
      1. However, PTU is higher risk of liver injury, making Methimazole preferred in most cases
    2. Methimazole associated hepatitis
      1. Incidence: 3.17 per 1000 person-years
      2. Acute Hepatic Failure: 0.32 per 1000 person-years
    3. Propylthiouracil (PTU) is associated with severe liver injury
      1. Adults: 1 in 10,000
      2. Children: 1 in 2,000
  4. Vasculitis
  5. Lupus-Like Syndrome
  6. Aplastic Anemia
  7. Rash or Pruritus
    1. Switch from PTU to Methimazole if severe
  8. Arthralgia or Polyarthritis
  9. Fever
  10. Congenital abnormalities possible with Methimazole
  • Safety
  1. Lactation
    1. Considered safe in Lactation (preferred Thionamide over PTU)
  2. Pregnancy Category D (applies to both PTU and Methimazole)
    1. Methimazole is preferred Thionamide in second and third trimester of pregnancy
    2. Methimazole is contraindicated in first trimester due to congenital defect risk
      1. Esophageal atresia
      2. Choanal Atresia
      3. Aplasia cutis
      4. Abdominal wall defects
      5. Ventricular Septal Defect
  • Monitoring
  1. Repeat examination every 3 months
  2. Pregnancy Test before starting therapy
  3. Lab Testing while on antithyroid medications: Monthly for 6 to 12 months
    1. Complete Blood Count (CBC)
      1. Obtain at baseline
      2. Repeat if Pharyngitis or fever occur (need not be done without symptoms or signs)
    2. Liver Function Tests
      1. Obtain at baseline and if symptoms develop
    3. Thyroid Function Tests (baseline, then every 4-8 weeks, then after stabilizing, every 3 months)
      1. Thyroid Stimulating Hormone (TSH) after stabilizing, once on every 3 month schedule
      2. Free T4
      3. Free T3
  4. Lab Testing after completing antithyroid medications
    1. Obtain Thyroid Function Tests every 1-3 months for 6-12 months
  5. Indications to discontinue medication (via taper)
    1. Total treatment course of 12-18 months AND
    2. TSH normalized for 6-12 months
  6. Indications to consider Thyroid ablation
    1. Inadequate suppression at 12 months from initiation
  • Efficacy
  1. Methimazole advantages over Propylthiouracil (PTU)
    1. Once daily dosing
    2. Decreases T4 and T3 levels more rapidly
    3. Much safer than PTU
      1. Lower risk of Agranulocytosis at moderate doses
      2. Does not carry the same liver toxicity risk as PTU
  2. Predictors of Relapse with Thionamides (occurs in 30-70% of cases within first year)
    1. Tobacco Abuse
    2. Large Goiter
    3. Thyroid Stmulating Antibody high at end of treatment
  • Resources
  1. Methimazole (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ca8c1028-216d-485a-90df-b54818451bc3
  • References
  1. Kravets (2016) Am Fam Physician 93(5): 363-70 [PubMed]