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Sunday, July 27, 2025

Carbimazole


Carbimazole is an antithyroid medication primarily used in the management of hyperthyroidism, particularly Graves’ disease and toxic nodular goitre. It is a prodrug that is rapidly converted in the body to its active form, methimazole (also known as thiamazole), which inhibits the synthesis of thyroid hormones by interfering with the incorporation of iodine into thyroglobulin. Carbimazole is widely prescribed in the UK, Europe, and many other regions but is not available in the United States, where methimazole is used directly.

This in-depth profile explores carbimazole’s pharmacological characteristics, clinical indications, dosage regimens, contraindications, adverse effects, precautions, drug interactions, and considerations for special populations.

Pharmacological Classification

  • Therapeutic class: Antithyroid agent

  • Pharmacologic class: Thionamide derivative

  • ATC code: H03BB01

  • Active metabolite: Methimazole (thiamazole)

Brand Names and Formulations

  • Neo-Mercazole®

  • Carbimazole Teva®, Carbimazole Milpharm®

  • Carbazin®, Thyrozol® (various brands by region)

  • Available strengths: 5 mg and 20 mg tablets

  • Route of administration: Oral only

Mechanism of Action

Carbimazole is a prodrug that is rapidly converted to methimazole after absorption. Its active form acts by:

  • Inhibiting the enzyme thyroid peroxidase (TPO), which catalyzes:

    • The iodination of tyrosine residues in thyroglobulin

    • The coupling of iodotyrosines to form thyroxine (T₄) and triiodothyronine (T₃)

  • No effect on the release of preformed thyroid hormones, so clinical improvement typically takes 1–3 weeks after initiation.

  • In higher doses, may also inhibit peripheral conversion of T₄ to T₃ to a small extent.

Indications

Approved Uses

  • Graves’ disease (autoimmune hyperthyroidism)

  • Toxic multinodular goitre

  • Toxic adenoma

  • Pre-operative preparation for thyroidectomy in hyperthyroid patients

  • Prior to radioiodine therapy to render patients euthyroid

  • Neonatal thyrotoxicosis (off-label, specialist use)

  • Hyperthyroidism during pregnancy (with strict monitoring)

Dosage and Administration

Initial Dosing (Adults)

  • Mild to moderate hyperthyroidism:

    • 15–20 mg daily in divided doses

  • Moderate to severe disease:

    • 30–40 mg/day in divided doses

  • Maximum dose: up to 60 mg/day in severe cases

Maintenance Therapy

  • Reduce gradually to 5–15 mg/day after achieving euthyroid state

  • Administer once daily or in divided doses depending on formulation and tolerance

  • Monitor TSH, free T₄, and T₃ regularly to guide dose adjustment

Duration of Treatment

  • Typically 12–18 months for initial course in Graves’ disease

  • Evaluate remission after this period; 40–50% may relapse

  • Some patients may require long-term or indefinite therapy

Paediatric Dosing

  • Initial: 0.4–0.8 mg/kg/day in divided doses

  • Adjust based on thyroid hormone levels

  • Used only under specialist supervision

Pre-operative Use

  • Treat until euthyroid (usually 4–8 weeks)

  • May combine with beta-blockers for rapid symptom control

Pharmacokinetics

  • Absorption: Rapid and nearly complete after oral administration

  • Bioavailability: ~85%

  • Plasma half-life: ~5–6 hours (longer in hypothyroidism)

  • Time to effect: 1–3 weeks for symptom relief

  • Metabolism: Hepatic and extrahepatic conversion to methimazole

  • Excretion: Primarily renal, partly as metabolites

Contraindications

  • Known hypersensitivity to carbimazole or methimazole

  • Pre-existing bone marrow depression

  • History of agranulocytosis from previous antithyroid therapy

  • Severe hepatic dysfunction

  • Pregnancy in the first trimester, unless clinically justified

  • Lactation, unless benefits outweigh risks and infant is monitored

Warnings and Precautions

  • Agranulocytosis is a serious but rare side effect (see below)

    • Risk highest in first 3 months

    • Onset is idiosyncratic, not dose-dependent

    • Patients should be advised to report sore throat, fever, mouth ulcers promptly

  • Liver toxicity: monitor liver function if jaundice or fatigue occurs

  • Vasculitis: rare, can be associated with anti-neutrophil cytoplasmic antibodies (ANCA)

  • Teratogenicity: associated with congenital malformations (especially at high doses during first trimester)

  • Hypothyroidism: may result from overtreatment

  • Goitre enlargement: due to increased TSH if hormone levels fall too low

Adverse Effects

Common (1–10%)

  • Nausea, mild GI upset, epigastric pain

  • Headache

  • Rash, pruritus, urticaria

  • Taste disturbance

  • Arthralgia

Uncommon (<1%)

  • Mild leukopenia

  • Hair thinning

  • Elevated liver enzymes

  • Menstrual irregularities

Rare but Serious (<0.1%)

  • Agranulocytosis (absolute neutrophil count <500/mm³)

  • Aplastic anemia, pancytopenia

  • Hepatotoxicity, cholestatic jaundice

  • Vasculitis (ANCA-positive)

  • Interstitial nephritis

  • Severe cutaneous reactions (e.g., Stevens-Johnson syndrome)

Drug Interactions

  • Warfarin: Anticoagulant effect may be reduced as thyroid hormone levels normalize; monitor INR closely

  • Beta-blockers: Often co-administered; may mask symptoms of hyperthyroidism

  • Theophylline: Clearance is reduced as thyroid function normalizes

  • Digitalis glycosides: Dose requirements may decrease

  • Radioactive iodine: Discontinue carbimazole 3–5 days before and resume 3–7 days after treatment

  • Lithium: May potentiate antithyroid effects or cause hypothyroidism

Use in Pregnancy and Breastfeeding

Pregnancy

  • Category D (UK) – Risk of fetal harm

  • Crosses placenta; associated with scalp defects (aplasia cutis), choanal atresia, tracheoesophageal fistula, facial anomalies

  • Propylthiouracil (PTU) preferred during first trimester

  • Carbimazole may be resumed in second and third trimester if needed

  • Goal: lowest possible dose to maintain maternal free T₄ in upper normal range

Breastfeeding

  • Excreted in breast milk

  • Low doses (≤15 mg/day) generally considered safe with monitoring of infant's thyroid function

  • Prefer single daily dose after breastfeeding

Use in Special Populations

  • Elderly: May require lower doses; monitor for hepatic or hematologic complications

  • Pediatrics: Specialist-only use; requires regular lab monitoring

  • Renal/hepatic impairment: Use with caution; no specific dosing guidelines, but monitor for accumulation and toxicity

Patient Counseling Points

  • Take tablets at the same time daily, preferably after meals

  • Continue taking until doctor advises stopping; do not self-adjust dose

  • Alert clinician immediately if:

    • Fever

    • Sore throat

    • Mouth ulcers

    • Fatigue or yellowing of eyes/skin

  • Inform all healthcare providers, including dentists, that you are taking carbimazole

  • Keep regular appointments for thyroid function and blood count monitoring

  • Women of childbearing potential must use effective contraception

  • Do not stop the medicine abruptly; thyroid hormone levels may rebound quickly

Monitoring Requirements

  • Baseline:

    • Full blood count (FBC)

    • Liver function tests (LFTs)

    • Thyroid function tests (TFTs)

  • Ongoing:

    • TFTs every 4–6 weeks initially

    • Adjust dose to keep free T₄ in normal range

    • Monitor FBC if signs of infection appear

    • Monitor LFTs if jaundice or hepatic symptoms occur




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