Generic Name

Methimazole

Brand Names

Tapazole, Profactil, Morons) is a thioamide antithyroid medication used primarily for the management of hyperthyroidism.

Mechanism

• Inhibition of thyroid hormone synthesis – Methimazole binds to the active site of thyroid peroxidase (TPO), a key enzyme in iodination and coupling of iodotyrosines during thyroid hormone formation.
• Prevents organification of iodine – By blocking TPO, iodine cannot be added to thyroglobulin, halting the production of T3 and T4.
• Irreversible inhibition – Its effect persists for the lifespan of the affected thyrocytes (~7–10 days).

Pharmacokinetics

• Absorption – Rapid, complete oral absorption (~100% bioavailability); peak plasma concentrations reached within 30–60 min.
• Distribution – Widely distributed; freely diffuses into thyroid tissue, peripheral tissues, and across the blood‑brain barrier.
• Metabolism – Primarily hepatic via glucuronidation; minor oxidation pathways.
• Elimination – Renally excreted (≈80% in urine, remainder in feces).
• Half‑life – Approximately 11–14 hours; steady‑state achieved in ~3–5 days with oral dosing.

Indications

• Graves disease – First‑line therapy for mild‑to‑moderate cases.
• Thyrotoxic periodic paralysis – Reduces thyrotoxic drive and paralysis episodes.
• Pre‑surgical preparation – Reduces thyroid hormone levels before thyroidectomy or radioactive iodine therapy.
• Transient hyperthyroidism (e.g., thyroid storm, subacute thyroiditis) – Often used if other agents unavailable.

Contraindications

• Allergy to methimazole, thionamides, or sulfonamides – Cross‑reactivity in penicillamine, sulfonamides, and other thioamides.
• Hypersensitivity – Avoid in patients with known hypersensitivity.
• Pregnancy – Category C; use only if benefits outweigh risks (alternative: propylthiouracil).
• Neonatal lupus – Avoid in pregnant women with a history of neonatal lupus or congenital heart block.
• Severe hepatic impairment – Dose adjustment or monitoring; risk of hepatotoxicity.
• Concurrent use of iodinated contrast – May attenuate drug efficacy; consider timing.

Dosing

• Administration – Take with food to reduce GI upset.
• Compliance – Adherence critical; missed doses may precipitate thyrotoxicosis rebound.

Adverse Effects

Common (≥ 1 % incidence)
• Rash, pruritus, mild erythema
• Headache, dizziness, nausea
• Altered taste sensation (dysgeusia)

Serious (≤ 1 % incidence)
• Hepatotoxicity – Acute hepatitis, jaundice, elevation in ALT/AST; monitor liver enzymes.
• Agranulocytosis – Sudden drop in neutrophils; risk is 0.3–0.6 % in hyperthyroid patients.
• Drug‑induced lupus – Rare; presents with arthralgia, rash, serositis.
• Severe dermatitis – Stevens–Johnson syndrome, exfoliative dermatitis.

Monitoring

• Baseline & follow‑up labs
• Complete blood count (CBC) – every 4 weeks in first 3 months, then every 8–12 weeks.
• Liver function tests (LFTs) – baseline, then at 3 months, then every 6–12 months.
• Thyroid function tests (T3, T4, TSH) – baseline, 4–6 weeks after initiation, then every 6 weeks until euthyroid, thereafter every 12–16 weeks.
• Clinical assessment
• Watch for signs of agranulocytosis (fever, sore throat).
• Evaluate liver dysfunction (jaundice, dark urine).

Clinical Pearls

• “Take with food” – Reduces gastrointestinal upset; improves adherence.
• Rapid titration strategy – Target a serum TSH level within 1–2 μIU/ml to avoid over‑ or undertreatment; avoid alternating to procainamide or potassium iodide.
• Agranulocytosis vigilance – Emphasize to students the importance of patient education regarding early signs; prompt interruption of therapy and referral to hematology.
• Be wary of hepatotoxicity in pregnancy – While often necessary, careful monitoring and multidisciplinary discussion is advised.
• Use in thyrotoxic periodic paralysis – A single initial dose can sometimes control paralysis, but long‑term therapy is essential to avoid recurrence.
• Avoid combination with iodinated agents – Iodine competes with methimazole’s action; consider postponing radioactive iodine or adjust dosing.

--
• *This drug card summarizes clinically relevant aspects of Methimazole for rapid reference. For definitive dosing and safety, always consult up‑to‑date prescribing guidelines and individual patient factors.*