Usage
Methimazole is prescribed for the treatment of hyperthyroidism, a condition characterized by an overactive thyroid gland. It is also used to prepare patients for thyroidectomy (surgical removal of the thyroid) or radioactive iodine therapy. Its pharmacological classification is antithyroid agent. Methimazole works by inhibiting the synthesis of thyroid hormones, specifically by blocking the enzyme thyroid peroxidase, which is essential for the production of thyroxine (T4) and triiodothyronine (T3).
Alternate Names
An alternate name for Methimazole is Thiamazole. A popular brand name under which it is marketed is Tapazole.
How It Works
Pharmacodynamics: Methimazole decreases the production of thyroid hormones, leading to a reduction in the symptoms of hyperthyroidism.
Pharmacokinetics:
- Absorption: Methimazole is readily absorbed from the gastrointestinal tract.
- Metabolism: It is metabolized in the liver.
- Elimination: Primarily excreted in the urine.
Mode of Action: Methimazole inhibits thyroid peroxidase, the enzyme responsible for the iodination and coupling of tyrosine residues in thyroglobulin, preventing the formation of T3 and T4.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Methimazole’s primary mechanism is enzyme inhibition (thyroid peroxidase).
Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
Initial dosage:
- Mild hyperthyroidism: 15 mg daily
- Moderate hyperthyroidism: 30-40 mg daily
- Severe hyperthyroidism: 60 mg daily
Maintenance dosage: 5-15 mg daily. The total daily dose is usually divided into three equal doses administered every 8 hours.
Children:
Initial dosage: 0.4 mg/kg of body weight daily, divided into three equal doses every 8 hours.
Maintenance dosage: Approximately half the initial dose. It’s crucial to monitor children’s growth and development during treatment due to the risk of growth retardation.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 20-30 mg daily as a single dose or divided), considering potential age-related decline in organ function. Closely monitor thyroid function and adjust the dose accordingly.
- Patients with Renal Impairment: Dosage adjustments are necessary. Use the lowest effective dose and monitor closely.
- Patients with Hepatic Dysfunction: Use the lowest effective dose and monitor closely due to the risk of hepatotoxicity.
- Patients with Comorbid Conditions: Consider the patient’s overall health status and adjust accordingly.
Clinical Use Cases
Methimazole is not typically used in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary role is in managing hyperthyroidism in a non-acute setting.
Dosage Adjustments
Dose adjustments are based on thyroid function tests (TSH and free T4 levels) and clinical response. An elevated TSH level indicates the need for a dosage reduction.
Side Effects
Common Side Effects
- Skin rash, itching, hives
- Nausea, vomiting, upset stomach
- Headache, dizziness, drowsiness
- Numbness or tingling sensation
- Muscle or joint pain
- Hair loss
- Decreased sense of taste
- Swelling of salivary glands or lymph nodes
Rare but Serious Side Effects
- Agranulocytosis (dangerously low white blood cell count)
- Aplastic anemia (bone marrow failure)
- Hepatotoxicity (liver damage)
- Vasculitis (inflammation of blood vessels)
- Jaundice
- Severe allergic reactions (anaphylaxis)
Long-Term Effects
Chronic complications from prolonged use are rare but can include growth retardation in children.
Adverse Drug Reactions (ADR)
Agranulocytosis is a clinically significant ADR requiring immediate discontinuation of methimazole and supportive care.
Contraindications
- Hypersensitivity to methimazole
- Severe liver impairment
- History of acute pancreatitis after methimazole administration
- Breastfeeding (relative contraindication – weigh benefits against risks)
- First trimester of pregnancy (relative contraindication due to risk of congenital malformations)
Drug Interactions
- Warfarin: Methimazole can enhance the anticoagulant effect of warfarin.
- Beta-blockers: Methimazole can increase beta-blocker concentrations.
- Digoxin: Methimazole can increase digoxin levels.
- Theophylline: Methimazole can increase theophylline levels.
- CYP450 interactions: Methimazole may interact with drugs metabolized by CYP450 enzymes, particularly CYP2D6.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D
- Fetal risks: Congenital malformations (especially during the first trimester), fetal goiter, and cretinism.
- Breastfeeding: Methimazole is excreted in breast milk. Although some studies have not shown adverse effects in breastfed infants, monitoring is essential. Consider alternative treatment options or close monitoring of infant thyroid function.
Drug Profile Summary
- Mechanism of Action: Inhibits thyroid peroxidase, blocking thyroid hormone synthesis.
- Side Effects: Common: rash, nausea, headache. Serious: agranulocytosis, hepatotoxicity.
- Contraindications: Hypersensitivity, severe liver disease, breastfeeding.
- Drug Interactions: Warfarin, beta-blockers, digoxin, theophylline.
- Pregnancy & Breastfeeding: Category D; potential fetal risks; excreted in breast milk.
- Dosage: Adults: 15-60 mg initially, 5-15 mg maintenance. Children: 0.4 mg/kg initially, 0.2 mg/kg maintenance.
- Monitoring Parameters: TSH, free T4, complete blood count (CBC), liver function tests.
Popular Combinations
Methimazole is often used in combination with beta-blockers (e.g., propranolol) to manage the peripheral symptoms of hyperthyroidism, such as tachycardia and tremor.
Precautions
- General Precautions: Monitor for blood count abnormalities, liver function changes, and allergic reactions.
- Specific Populations: Close monitoring during pregnancy and breastfeeding; careful dosing in children and the elderly.
- Lifestyle Considerations: No specific lifestyle restrictions are typically necessary.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Methimazole?
A: Adults: Initial 15-60 mg daily divided into three doses, maintenance 5-15 mg daily. Children: Initial 0.4 mg/kg/day divided into three doses, maintenance 0.2 mg/kg/day.
Q2: What are the most common side effects?
A: Skin rash, itching, nausea, headache, and joint pain.
Q3: What are the serious side effects I should watch out for?
A: Agranulocytosis, hepatotoxicity, and severe allergic reactions.
Q4: Can Methimazole be used during pregnancy?
A: It’s generally avoided in the first trimester due to the risk of birth defects. Its use in later trimesters requires careful risk-benefit assessment.
Q5: Is it safe to breastfeed while taking Methimazole?
A: It’s excreted in breast milk, and although serious side effects in infants are rare, close monitoring of the infant’s thyroid function is recommended.
Q6: What are the contraindications for using Methimazole?
A: Hypersensitivity to methimazole, severe liver disease, and history of acute pancreatitis following methimazole administration.
Q7: What other medications interact with Methimazole?
A: Warfarin, beta-blockers, digoxin, and theophylline.
Q8: How does Methimazole work?
A: It inhibits the enzyme thyroid peroxidase, thereby blocking thyroid hormone synthesis.
Q9: How long does treatment with Methimazole typically last?
A: 12-18 months, though some patients may require longer-term treatment.
Q10: What should be monitored during treatment?
A: Thyroid function tests (TSH, free T4), complete blood count (CBC), and liver function tests.
