Carbimazole Chemical formula
Synonyms: Carbimazol; Carbimazolum; Karbimatsoli; Karbimazol; Karbimazolas. Ethyl 3-methyl-2-thioxo-4-imidazoline-1-carboxylate.
Cyrillic synonym: Карбимазол.

💊 Chemical information

Chemical formula: C7H10N2O2S = 186.2.
CAS — 22232-54-8.
ATC — H03BB01.
ATC Vet — QH03BB01.


In Chin. and Eur..

Ph. Eur. 6.2

(Carbimazole). A white or yellowish-white crystalline powder. Slightly soluble in water; soluble in alcohol and in acetone.

💊 Adverse Effects and Precautions

Adverse effects from carbimazole and other thiourea antithyroid drugs occur most frequently during the first 8 weeks of treatment. The most common minor adverse effects are nausea and vomiting, gastric discomfort, headache, arthralgia, skin rashes, and pruritus. Hair loss has also been reported. Bone-marrow depression may occur and mild leucopenia is common. Rarely, agranulocytosis can develop, and is the most serious adverse reaction associated with this class of drugs. Patients or their carers should be told how to recognise such toxicity and should be advised to seek immediate medical attention if mouth ulcers or sore throat, fever, bruising, malaise, or nonspecific illness develop. Full blood counts should be performed, and treatment should be stopped immediately if there is any clinical or laboratory evidence of neutropenia. Aplastic anaemia or isolated thrombocytopenia have been reported rarely, as has hypoprothrombinaemia. There have been several reports of liver damage, most commonly jaundice, in patients taking thiourea antithyroid drugs; the drug should be withdrawn if hepatic effects occur. Other adverse effects sometimes observed with the thiourea antithyroid compounds include fever, a lupuslike syndrome, myopathy, vasculitis and nephritis, and taste disturbances. Creatine phosphokinase values should be measured if patients experience myalgia. Excessive doses of antithyroid drugs may cause hypothyroidism and goitre. High doses in pregnancy may result in fetal hypothyroidism and goitre (see Pregnancy, below). An immune mechanism has been implicated in many of these reactions and cross-sensitivity between the thiourea antithyroid drugs may occur.

Breast feeding.

The safety of breast feeding during maternal treatment depends partly on how much drug is distributed into the breast milk. Thiourea antithyroid drugs may be used with care in breast-feeding mothers; neonatal development and thyroid function of the infant should be closely monitored and the lowest effective dose used. Propylthiouracil has been preferred to carbimazole or thiamazole since it enters breast milk less readily.1-3 In a small study4 of breast-feeding mothers taking doses of propylthiouracil as high as 750 mg daily for Graves’ disease, no adverse effects were observed on the thyroid status of their infants. Thiamazole enters breast milk freely, with plasma to milk ratios of almost one.3,5 The infant’s intake of thiamazole after maternal use of carbimazole (or thiamazole) might be greatly reduced by discarding the breast milk produced 2 to 4 hours after a dose,6since the highest concentration was found at this time. Two studies found no adverse effects on thyroid function,7,8 thyroid hormone levels,7 or physical and intellectual development, in breast fed infants during up to 6 months7 to 1 year8 of maternal treatment with thiamazole. Maximum maternal daily doses of 10 mg of thiamazole,3 15 mg of carbimazole, and 150 mg of propylthiouracil9 have been recommended, although thiamazole 20 to 30 mg has been given to thyrotoxic lactating women for the first month of a year of therapy with no observable adverse effects on the thyroid function of their breast-fed infants.10 Despite stating that goitre has been associated with the use of carbimazole, the American Academy of Pediatrics considers the use of all three drugs to be compatible with breast feeding.11
1. Kampmann JP, et al. Propylthiouracil in human milk: revision of a dogma. Lancet 1980; i: 736–8
2. Johansen K, et al. Excretion of methimazole in human milk. Eur J Clin Pharmacol 1982; 23: 339–41
3. Cooper DS. Antithyroid drugs: to breast-feed or not to breastfeed. Am J Obstet Gynecol 1987; 157: 234–5
4. Momotani N, et al. Thyroid function in wholly breast-feeding infants whose mothers take high doses of propylthiouracil. Clin Endocrinol (Oxf) 2000; 53: 177–81
5. Cooper DS, et al. Methimazole pharmacology in man: studies using a newly developed radioimmunoassay for methimazole. J Clin Endocrinol Metab 1984; 58: 473–9
6. Rylance GW, et al. Carbimazole and breastfeeding. Lancet 1987; i: 928
7. Azizi F. Effect of methimazole treatment of maternal thyrotoxicosis on thyroid function in breast-feeding infants. J Pediatr 1996; 128: 855–8
8. Azizi F, et al. Thyroid function and intellectual development of infants nursed by mothers taking methimazole. J Clin Endocrinol Metab 2000; 85: 3233–8
9. Lamberg B-A, et al. Antithyroid treatment of maternal hyperthyroidism during lactation. Clin Endocrinol (Oxf) 1984; 21: 81–7
10. Azizi F, Hedayati M. Thyroid function in breast-fed infants whose mothers take high doses of methimazole. J Endocrinol Invest 2002; 25: 493–6
11. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108: 776–89. Correction. ibid.; 1029. Also available at: pediatrics%3b108/3/776 (accessed 18/05/05)

Effects on the blood.

While leucopenia is considered to be a common adverse effect of the thiourea antithyroid drugs, occurring in up to a quarter of patients, it is usually mild and improves as treatment continues.1 Agranulocytosis, a more serious hazard, is usually reported to affect 0.03% of patients in Europe,2 who are mostly treated with carbimazole. However, the incidence has been reported to be higher (0.4%) in areas where thiamazole is used.3,4 Fatalities have been reported.1,2,4,5 Although a direct toxic effect had been suggested, the agranulocytosis associated with the thiourea drugs is generally considered to be immunologically mediated.1,6 The onset of agranulocytosis is usually rapid and monitoring of the blood count is not always of predictive value;3 routine monitoring is not indicated.2 Agranulocytosis has occurred in patients receiving propylthiouracil for a second time who had no such complications in their first course of therapy.7 There is limited evidence that agranulocytosis is more common at higher doses, and in older patients. However, this has not been proved conclusively.1 There have been some case reports of aplastic anaemia being produced by antithyroid drugs, but the excess risk associated with their use is considered to be very low6,8 and complete recovery has been reported after withdrawal of the antithyroid drug. An immune mechanism has been implicated. Carbimazole has produced haemolytic anaemia.9 In this case the immune reaction was specific to carbimazole and could not be demonstrated with thiamazole. On very rare occasions patients taking propylthiouracil have experienced a reduction in prothrombin values and bleeding.10-12 In one patient bleeding was linked to propylthiouracil-induced thrombocytopenia.13
1. Bartalena L et al. Adverse effects of thyroid hormone preparations and antithyroid drugs. Drug Safety 1996; 15: 53–63
2. Committee on Safety of Medicines/Medicines Control Agency. Reminder: agranulocytosis with antithyroid drugs. Current Problems 1999; 25: 3. Also available at: http:// dDocName=CON2023233&RevisionSelectionMethod= LatestReleased (accessed 17/05/06
3. Tajiri J, et al. Antithyroid drug-induced agranulocytosis: the usefulness of routine white blood cell count monitoring. Arch Intern Med 1990; 150: 621–4
4. Anonymous. Elaboration: drug-induced agranulocytosis–monitoring antithyroid treatment. Drug Ther Bull 1997; 35: 88
5. Anonymous. Drug-induced agranulocytosis. Drug Ther Bull 1997; 35: 49–52
6. International Agranulocytosis and Aplastic Anaemia Study. Risk of agranulocytosis and aplastic anaemia in relation to use of antithyroid drugs. BMJ 1988; 297: 262–5
7. Shiran A, et al. Propylthiouracil-induced agranulocytosis in four patients previously treated with the drug. JAMA 1991; 266: 3129–30
8. Bishara J. Methimazole-induced aplastic anemia. Ann Pharmacother 1996; 30: 684
9. Salama A, et al. Carbimazole-induced immune haemolytic anaemia: role of drug-red blood cell complexes for immunization. Br J Haematol 1988; 68: 479–82
10. D’Angelo G, Le Gresley LP. Severe hypoprothrombinaemia after propylthiouracil therapy. Can Med Assoc J 1959; 81: 479–81
11. Naeye RL, Terrien CM. Hemorrhagic state after therapy with propylthiouracil. Am J Clin Pathol 1960; 34: 254–7
12. Gotta AW, et al. Prolonged intraoperative bleeding caused by propylthiouracil-induced hypoprothrombinemia. Anesthesiology 1972; 37: 562–3
13. Ikeda S, Schweiss JF. Excessive blood loss during operation in the patient treated with propylthiouracil. Can Anaesth Soc J 1982; 29: 477–80.

Effects on the ears.

Earache, high-frequency hearing loss, and tinnitus in a patient with Graves’ disease were attributed to hypersensitivity to carbimazole;1 hearing loss, but not the tinnitus, resolved when carbimazole was replaced with propylthiouracil.
1. Hill D, et al. Hearing loss and tinnitus with carbimazole BMJ 1994; 309: 929.

Effects on the kidneys.

Glomerulonephritis associated with the development of antineutrophil cytoplasmic antibodies has been reported in patients receiving thiourea antithyroid drugs.1-5
1. Vogt BA, et al. Antineutrophil cytoplasmic autoantibody-positive crescentic glomerulonephritis as a complication of treatment with propylthiouracil in children. J Pediatr 1994; 124: 986–8
2. D’Cruz D, et al. Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis associated with anti-thyroid drug treatment. Br J Rheumatol 1995; 34: 1090–1
3. Yuasa S, et al. Antineutrophil cytoplasmic antibodies (ANCA)associated crescentic glomerulonephritis and propylthiouracil therapy. Nephron 1996; 73: 701–3
4. Kudoh Y, et al. Propylthiouracil-induced rapidly progressive glomerulonephritis associated with antineutrophil cytoplasmic autoantibodies. Clin Nephrol 1997; 48: 41–3
5. Prasad GVR, et al. Propylthiouracil-induced diffuse proliferative lupus nephritis: review of immunological complications. J Am Soc Nephrol 1997; 8: 1205–10.

Effects on the liver.

Jaundice, usually cholestatic, has been reported with thiamazole and carbimazole.1-5 An immune-mediated mechanism rather than a toxic reaction has been proposed. Hepatitis (sometimes progressing to cirrhosis6) and hepatic necrosis have been associated with propylthiouracil,6-9 sometimes with fatal consequences.7,8 However, in one study10 almost 30% of patients being treated with propylthiouracil developed asymptomatic liver changes (increased alanine aminotransferase values). Dose reduction resulted in a return to normal values in 13 of the 15 patients affected. Despite reports of liver damage, propylthiouracil has been investigated in the treatment of patients with alcoholic liver disease.
1. Becker CE, et al. Hepatitis from methimazole during adrenal steroid therapy for malignant exophthalmos. JAMA 1968; 206: 1787–9
2. Fischer MG, et al. Methimazole-induced jaundice. JAMA 1973; 223: 1028–9
3. Blom H, et al. A case of carbimazole-induced intrahepatic cholestasis. Arch Intern Med 1985; 145: 1513–15
4. Schmidt G, et al. Methimazole-associated cholestatic liver injury: case report and brief literature review. Hepatogastroenterology 1986; 33: 244–6
5. Arab DM, et al. Severe cholestatic jaundice in uncomplicated hyperthyroidism treated with methimazole. J Clin Endocrinol Metab 1995; 80: 1083–5
6. Özenírler S, et al. Propylthiouracil-induced hepatic damage. Ann Pharmacother 1996; 30: 960–3
7. Hanson JS. Propylthiouracil and hepatitis. Two cases and a review of the literature. Arch Intern Med 1984; 144: 994–6
8. Limaye A, Ruffolo PR. Propylthiouracil-induced fatal hepatic necrosis. Am J Gastroenterol 1987; 82: 152–4
9. Ichiki Y, et al. Propylthiouracil-induced severe hepatitis: a case report and review of the literature. J Gastroenterol 1998; 33: 747–50
10. Liaw Y-F, et al. Hepatic injury during propylthiouracil therapy in patients with hyperthyroidism. Ann Intern Med 1993; 118: 424–8.

Effects on the lungs.

Diffuse interstitial pneumonitis occurred in 2 patients given propylthiouracil1 and a hypersensitivity reaction was suggested. Propylthiouracil was also implicated in 2 cases of alveolar haemorrhage associated with antineutrophil cytoplasmic antibody.2,3
1. Miyazono K, et al. Propylthiouracil-induced diffuse interstitial pneumonitis. Arch Intern Med 1984; 144: 1764–5
2. Ohtsuka M, et al. Propylthiouracil-induced alveolar haemorrhage associated with antineutrophil cytoplasmic antibody. Eur Respir J 1997; 10: 1405–7
3. Dhillon SS, et al. Diffuse alveolar hemorrhage and pulmonary capillaritis due to propylthiouracil. Chest 1999; 116: 1485–8.

Effects on the muscles.

Myositis with pain, weakness, and increased creatine kinase concentrations has been reported with carbimazole.1,2 This effect might be explained by ‘tissue hypothyroidism’, and might respond to dosage reduction.3
1. Page SR, Nussey SS. Myositis in association with carbimazole therapy. Lancet 1989; i: 964
2. Pasquier E, et al. Biopsy-proven myositis with microvasculitis in association with carbimazole. Lancet 1991; 338: 1082–3
3. O’Malley B. Carbimazole-induced cramps. Lancet 1989; i: 1456.


Many of the adverse effects associated with the thiourea antithyroid drugs appear to have an immune basis. These effects may be associated with polyarthritis1 or hypersensitivity vasculitis.2-7 The latter is sometimes severe and multisystemic, and fatalities have occurred. Hypersensitivity reactions may also be associated with the development of antineutrophil cytoplasmic antibodies (ANCA), or sometimes with a lupus-like syndrome with or without the presence of antinuclear antibodies.2,5 Serum sickness with arthralgias and raised immunoglobulin M (IgM) concentrations has been reported with thiamazole,8 and the production of antibodies to insulin, resulting in episodes of hypoglycaemia, has been associated with thiamazole9 and carbimazole.10 The thiourea antithyroid drugs all contain a thioamide group and cross-sensitivity between them might be expected. In particular, complete cross-reactivity may be expected between thiamazole and carbimazole since the latter is converted in vivo to thiamazole, although one report11 suggests this is not necessarily the case. Cross-sensitivity between propylthiouracil and carbimazole12 or thiamazole13 has been reported but the incidence and clinical importance is not clear. Although it has been suggested that carbimazole or thiamazole may be substituted for propylthiouracil in hypersensitive patients, it is safer to stop antithyroid drugs in such patients.12
1. Bajaj S, et al. Antithyroid arthritis syndrome. J Rheumatol 1998; 25: 1235–9
2. Kawachi Y, et al. ANCA-associated vasculitis and lupus-like syndrome caused by methimazole. Clin Exp Dermatol 1995; 20: 345–7
3. Chastain MA, et al. Propylthiouracil hypersensitivity: report of two patients with vasculitis and review of the literature. J Am Acad Dermatol 1999; 41: 757–64
4. Gunton JE, et al. Clinical case seminar: antithyroid drugs and antineutrophil cytoplasmic antibody positive vasculitis. A case report and review of the literature. J Clin Endocrinol Metab 1999; 84: 13–16
5. Mathieu E, et al. Systemic adverse effect of antithyroid drugs. Clin Rheumatol 1999; 18: 66–8
6. Dolman KM, et al. Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy. Lancet 1993; 342: 651–2
7. ten Holder SM, et al. Cutaneous and systemic manifestations of drug-induced vasculitis. Ann Pharmacother 2002; 36: 130–47
8. Van Kuyk M, et al. Methimazole-induced serum sickness. Acta Clin Belg 1983; 38: 68–9
9. Hakamata M, et al. Insulin autoimmune syndrome after the third therapy with methimazole. Intern Med 1995; 34: 410–12
10. Burden AC, Rosenthal FD. Methimazole and insulin autoimmune syndrome. Lancet 1983; ii: 1311
11. Kroll H, et al. Drug-dependent antibodies against the prodrug carbimazole do not react with the metabolite thiamazole. Blood 2001; 97: 2186–7
12. Smith A, et al. Cross sensitivity to antithyroid drugs. BMJ 1989; 298: 1253
13. De Weweire A, et al. Failure to control hyperthyroidism with a thionamide after potassium perchlorate withdrawal in a patient with amiodarone associated thyrotoxicosis. J Endocrinol Invest 1987; 10: 529.


Thiourea antithyroid drugs have been used successfully in pregnancy. Thiamazole (the metabolite of carbimazole) has been the drug most frequently involved in the few reports of congenital defects following maternal use of such compounds. Several infants exposed to thiamazole in utero have been born with scalp defects (aplasia cutis congenita—a localised absence of skin at birth)1,2 although hyperthyroidism itself may give rise to such defects.3 Individual cases of other congenital defects associated with thiamazole have included choanal atresia (an upper respiratory-tract defect), oesophageal atresia, and tracheo-oesophageal fistula3 but the incidence of congenital abnormalities is not increased compared with the general population.4 Gastroschisis (an abdominal wall defect) has been reported in an infant after maternal exposure to carbimazole.5 There have been some reports of neonates exposed to thiourea antithyroid drugs in utero displaying signs of hypothyroidism including goitre.6,7
1. Milham S. Scalp defects in infants of mothers treated for hyperthyroidism with methimazole or carbimazole during pregnancy. Teratology 1985; 32: 321
2. Vogt T, et al. Aplasia cutis congenita after exposure to methimazole: a causal relationship? Br J Dermatol 1995; 133: 994–6
3. Johnsson E, et al. Severe malformations in infant born to hyperthyroid woman on methimazole. Lancet 1997; 350: 1520
4. Wing DA, et al. A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy. Am J Obstet Gynecol 1994; 170: 90–5
5. Guignon A-M, et al. Carbimazole-related gastroschisis. Ann Pharmacother 2003; 37: 829–31
6. O’Doherty MJ, et al. Treating thyrotoxicosis in pregnant or potentially pregnant women. BMJ 1999; 318: 5–6
7. Masiukiewicz US, Barrow GN. Hyperthyroidism in pregnancy: diagnosis and treatment. Thyroid 1999; 9: 647–52.

💊 Pharmacokinetics

The pharmacokinetics of carbimazole and thiamazole can be considered together since carbimazole is rapidly and completely metabolised to thiamazole in the body. The antithyroid activity of carbimazole is dependent upon this conversion to thiamazole. Carbimazole and other thiourea antithyroid drugs are rapidly absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 1 to 2 hours after oral doses. They are concentrated in the thyroid gland; since their duration of action is more closely related to the intrathyroidal drug concentration than their plasma half-life, prolonged antithyroid activity results from single daily doses. Thiamazole is not bound to plasma proteins. Thiamazole has an elimination half-life from plasma of about 3 to 6 hours and is metabolised, probably by the liver, and excreted in the urine. Less than 12% of a dose of thiamazole may be excreted as unchanged drug. 3-Methyl-2-thiohydantoin has been identified as a metabolite of thiamazole. The elimination half-life may be increased in hepatic and renal impairment. Thiamazole crosses the placenta and is distributed into breast milk.
1. Skellern GG, et al. The pharmacokinetics of methimazole after oral administration of carbimazole and methimazole, in hyperthyroid patients. Br J Clin Pharmacol 1980; 9: 137–43
2. Kampmann JP, Hansen JM. Clinical pharmacokinetics of antithyroid drugs. Clin Pharmacokinet 1981; 6: 401–28
3. Jansson R, et al. Intrathyroidal concentrations of methimazole in patients with Graves’ disease. J Clin Endocrinol Metab 1983; 57: 129–32
4. Cooper DS, et al. Methimazole pharmacology in man: studies using a newly developed radioimmunoassay for methimazole. J Clin Endocrinol Metab 1984; 58: 473–9
5. Jansson R, et al. Pharmacokinetic properties and bioavailability of methimazole. Clin Pharmacokinet 1985; 10: 443–50.

💊 Uses and Administration

Carbimazole is a thiourea antithyroid drug that acts by blocking the production of thyroid hormones. It is used in the management of hyperthyroidism, including the treatment of Graves’ disease, the preparation of hyperthyroid patients for thyroidectomy, as an adjunct to radio-iodine therapy, and in the treatment of thyroid storm. Carbimazole is completely metabolised to thiamazole and it is this metabolite that is responsible for the antithyroid activity of carbimazole. Carbimazole is given orally in a typical initial dosage of 15 to 40 mg daily, in divided doses; occasionally up to 60 mg daily may be required. Control of symptoms is usually achieved in 1 to 2 months. When the patient is euthyroid the dose is gradually reduced to the smallest amount that will maintain the euthyroid state. Typical maintenance doses are 5 to 15 mg daily, which may be given as a single daily dose. Treatment in children should be undertaken by a specialist. The BNFC recommends an initial dose of 250 micrograms/kg three times daily for neonates and children up to 12 years of age. Children aged 12 to 18 years may be given 10 mg three times daily initially. Doses are adjusted according to response; higher initial doses may be needed in thyrotoxic crisis. Carbimazole is also given orally in a dose of 20 to 60 mg daily, with supplemental levothyroxine, as a blocking-replacement regimen. Either form of maintenance treatment is usually continued for at least a year, and often for 18 months; up to 2 years of treatment may be required.

💊 Preparations

BP 2008: Carbimazole Tablets.

Proprietary Preparations

Austral.: Neo-Mercazole; Austria: Carbistad; Denm.: Neo-Mercazole; Fin.: Ty r a zo l ; Fr.: Neo-Mercazole; Ger.: Car; Neo-Thyreostat†; Gr.: Thyrostat; Hong Kong: Cazole; India: Neo-Mercazole; Indon.: Neo-Mercazole; Irl.: Neo-Mercazole; Malaysia: Camazol†; Norw.: Neo-Mercazole; NZ: Neo-Mercazole; Philipp.: Neo-Mercazole; S.Afr.: Neo-Mercazole; Singapore: Camazol; Cazole†; Spain: Neo Tomizol; Switz.: Neo-Mercazole; UK: Neo-Mercazole.
Published October 12, 2018.