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Uses and Administration
Carbimazole is a thiourea antithyroid drug that acts by blocking the production of thyroid hormones (see Refer to ). It is used in the management of hyperthyroidism ( Refer to ), 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. Higher initial doses may be needed in thyroid storm.
Carbimazole is also given orally in a dose of 20 to 60 mg daily, with supplemental levothyroxine, as ablocking-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.
For the use of carbimazole in children and adolescents, see Refer to .
(last reviewed 2011-08-23; last modified 2011-07-12)
Administration in children
For the treatment of hyperthyroidism (including Graves' disease) in neonates and children up to 11 years of age, the BNFC recommends an initial oral dose of carbimazole 750 micrograms/kg (up to a maximum of 30 mg) daily, in divided doses or as a single dose. Children aged 12 to 17 years may be given 30 mg daily initially, in single or divided doses. Doses are adjusted according to response; higher initial doses may be needed in thyroid storm.
(last reviewed 2011-08-23; last modified 2017-01-05)
Adverse Effects, Treatment and Precautions
Adverse effects from carbimazole and other thiourea antithyroid drugs occur most frequently during the first 8 weeks of treatment. An immune mechanism has been implicated in many of these reactions and cross-sensitivity between the thiourea antithyroid drugs may occur.
The most common minor adverse effects are nausea and vomiting, gastric discomfort, headache, arthralgia, rashes, and pruritus. These effects are usually self-limiting and may not require therapy to be stopped. However, propylthiouracil should be stopped if arthralgia occurs, as severe transient migratory polyarthritis may develop. Similarly, urticaria with propylthiouracil may herald a serious hypersensitivity reaction and the drug should be stopped; cross-sensitivity for this adverse effect is uncommon and an alternative thiourea drug may be tried.
Bone marrow depression including neutropenia, leucopenia, eosinophilia, and agranulocytosis has been reported. Agranulocytosis is the most serious adverse effect associated with this class of drugs, and fatalities have occurred. 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 non-specific 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 have haemolytic anaemia and hypoprothrombinaemia.
Hepatotoxicity can occur with the thiourea drugs, and can be serious. Jaundice is the most common presentation with carbimazole; there have been rare reports of fulminant hepatitis, hepatic necrosis, encephalopathy, and death with propylthiouracil and thiamazole. Therapy should be withdrawn if hepatic disorders occur.
Other adverse effects sometimes seen with the thiourea antithyroid compounds include hair loss, a lupus-like syndrome, myopathy, vasculitis, nephritis, and taste disturbances. Drowsiness, paraesthesia, neuritis, oedema, skin pigmentation changes, sialadenopathy, and lymphadenopathy can also occur. Creatine phosphokinase values should be measured if patients develop myalgia.
Excessive doses of antithyroid drugs may cause hypothyroidism and goitre; the dose should be reduced, or therapy interrupted. High doses in pregnancy may result in fetal hypothyroidism and goitre (see Pregnancy, Refer to ).
(last reviewed 2011-08-23; last modified 2011-08-13)
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 seen 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,6 since 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,315 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 last available guidance from the American Academy of Pediatrics considered the use of all three drugs to be compatible with breast feeding.11
(last reviewed 2011-08-23; last modified 2011-07-12)
References
1. Kampmann JP, et al.. Propylthiouracil in human milk: revision of a dogma.Lancet. 1980; i: 736–8. PubMed
2. Johansen K, et al.. Excretion of methimazole in human milk.Eur J Clin Pharmacol. 1982; 23: 339–41. PubMed
3. Cooper DS. Antithyroid drugs: to breast-feed or not to breast-feed.Am J Obstet Gynecol. 1987; 157: 234–5. PubMed
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. PubMed
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. PubMed
6. Rylance GW, et al.. Carbimazole and breastfeeding.Lancet. 1987; i: 928. PubMed
7. Azizi F. Effect of methimazole treatment of maternal thyrotoxicosis on thyroid function in breast-feeding infants.J Pediatr. 1996; 128: 855–8. PubMed
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. PubMed
9. Lamberg B-A, et al.. Antithyroid treatment of maternal hyperthyroidism during lactation.Clin Endocrinol (Oxf). 1984; 21: 81–7. PubMed
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. PubMed
11. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk.Pediatrics ibid.. 2001; 108: 776–89. PubMed online
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.3,4Fatalities have been reported.1,2,4,5Although 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 proven conclusively.1In fact, life-threatening agranulocytosis and hepatotoxicity during initiation of a standard dose of carbimazole has been described.8
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 low6,9 and complete recovery has been reported after withdrawal of the antithyroid drug. An immune mechanism has been implicated.
Carbimazole has produced haemolytic anaemia.10 In this case the immune reaction was specific to carbimazole and could not be shown with thiamazole.
On very rare occasions patients taking propylthiouracil have had a reduction in prothrombin values and bleeding.11-13 In one patient bleeding was linked to propylthiouracil-inducedthrombocytopenia.14
(last reviewed 2011-08-23; last modified 2016-10-31)
References
1. Bartalena L et al.. Adverse effects of thyroid hormone preparations and antithyroid drugs.Drug Safety. 1996; 15: 53–63. PubMed
2. CSM/MCA. Reminder: agranulocytosis with antithyroid drugs.Current Problems. 1999; 25: 3. online
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. PubMed
4. Anonymous. Elaboration: drug-induced agranulocytosis–monitoring antithyroid treatment.Drug Ther Bull. 1997; 35: 88. PubMed
5. Anonymous. Drug-induced agranulocytosis.Drug Ther Bull. 1997; 35: 49–52. PubMed
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. PubMed
7. Shiran A, et al.. Propylthiouracil-induced agranulocytosis in four patients previously treated with the drug.JAMA. 1991; 266: 3129–30. PubMed
8. Vilchez FJ, et al.. Concomitant agranulocytosis and hepatotoxicity after treatment with carbimazole.Ann Pharmacother. 2006; 40: 2059–63. PubMed
9. Bishara J. Methimazole-induced aplastic anemia.Ann Pharmacother. 1996; 30: 684. PubMed
10. 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. PubMed
11. D'Angelo G, Le Gresley LP. Severe hypoprothrombinaemia after propylthiouracil therapy.Can Med Assoc J. 1959; 81: 479–81.
12. Naeye RL, Terrien CM. Hemorrhagic state after therapy with propylthiouracil.Am J Clin Pathol. 1960; 34: 254–7.
13. Gotta AW, et al.. Prolonged intraoperative bleeding caused by propylthiouracil-induced hypoprothrombinemia.Anesthesiology. 1972; 37: 562–3. PubMed
14. Ikeda S, Schweiss JF. Excessive blood loss during operation in the patient treated with propylthiouracil.Can Anaesth Soc J. 1982; 29: 477–80. PubMed
Effects on the cardiovascular system
A study found that the use of antithyroid drugs was associated with a threefold increased risk of sudden cardiac death. The authors stated that, while this effect might be caused directly by the drugs, this was unlikely since different drugs were involved and a plausible biological mechanism was lacking. Underlying poorly controlled hyperthyroidism was suggested as a more likely cause, since some treated patients were found to have had low thyroid-stimulating hormone concentrations shortly before death.1
(last reviewed 2011-08-23; last modified 2011-07-12)
References
1. van Noord C, et al.. Population-based studies of antithyroid drugs and sudden cardiac death.Br J Clin Pharmacol. 2009; 68: 447–54. PubMed
Effects on the ears
Earache, high-frequency hearing loss, and tinnitus in a patient with Graves' disease were attributed to hypersensitivity to carbimazole;1hearing loss, but not the tinnitus, resolved when carbimazole was replaced with propylthiouracil. However, in another case,2propylthiouracil was associated with bilateral sensorineural hearing loss, which was thought to be caused by cochlear dysfunction from small-vessel vasculitis that locally compromised inner ear blood flow. Antineutrophil cytoplasmic antibodies (ANCA) were seen in the serum. ANCA concentrations returned to within normal limits and hearing loss was greatly improved after propylthiouracil was stopped and high-dose methylprednisolone was given,
(last reviewed 2011-08-23; last modified 2011-07-12)
References
1. Hill D, et al.. Hearing loss and tinnitus with carbimazole.BMJ. 1994; 309: 929. PubMed
2. Sano M, et al.. Progressive bilateral sensorineural hearing loss induced by an antithyroid drug.ORL J Otorhinolaryngol Relat Spec. 2004; 66: 281–5. PubMed
Effects on the kidneys
Glomerulonephritis associated with the development of antineutrophil cytoplasmic antibodies has been reported in patients receiving thiourea antithyroid drugs.1-6
(last reviewed 2011-08-23; last modified 2011-08-09)
References
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. PubMed
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. PubMed
3. Yuasa S, et al.. Antineutrophil cytoplasmic antibodies (ANCA)-associated crescentic glomerulonephritis and propylthiouracil therapy.Nephron. 1996; 73: 701–3. PubMed
4. Kudoh Y, et al.. Propylthiouracil-induced rapidly progressive glomerulonephritis associated with antineutrophil cytoplasmic autoantibodies.Clin Nephrol. 1997; 48: 41–3. PubMed
5. Prasad GVR, et al.. Propylthiouracil-induced diffuse proliferative lupus nephritis: review of immunological complications.J Am Soc Nephrol. 1997; 8: 1205–10. PubMed
6. Trimeche Ajmi S, et al.. Benzylthiouracil-induced glomerulonephritis.Case Report Med. 2009; 2009: 687285. PubMed
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. Hepatotoxicity with agranulocytosis has been reported with carbimazole (see Effects on the Blood Refer to ). Hepatitis (sometimes progressing to cirrhosis6) and hepatic necrosis have been associated with propylthiouracil,6-9 sometimes with fatal consequences.7,8 The FDA has evaluated postmarketing adverse events from 1969 to 2009 and identified 34 cases of severe liver injury associated with propylthiouracil.10 These included 23 adult cases where 13 resulted in death and 5 patients needed a liver transplant. There were also 11 paediatric reports, including 2 deaths and 7 children needing a transplant. In one study11 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 (see Refer to ).
(last reviewed 2011-08-23; last modified 2010-09-02)
References
1. Becker CE, et al.. Hepatitis from methimazole during adrenal steroid therapy for malignant exophthalmos.JAMA. 1968; 206: 1787–9. PubMed
2. Fischer MG, et al.. Methimazole-induced jaundice.JAMA. 1973; 223: 1028–9. PubMed
3. Blom H, et al.. A case of carbimazole-induced intrahepatic cholestasis.Arch Intern Med. 1985; 145: 1513–15. PubMed
4. Schmidt G, et al.. Methimazole-associated cholestatic liver injury: case report and brief literature review.Hepatogastroenterology. 1986; 33: 244–6. PubMed
5. Arab DM, et al.. Severe cholestatic jaundice in uncomplicated hyperthyroidism treated with methimazole.J Clin Endocrinol Metab. 1995; 80: 1083–5. PubMed
6. Özenírler S, et al.. Propylthiouracil-induced hepatic damage.Ann Pharmacother. 1996; 30: 960–3. PubMed
7. Hanson JS. Propylthiouracil and hepatitis. Two cases and a review of the literature.Arch Intern Med. 1984; 144: 994–6. PubMed
8. Limaye A, Ruffolo PR. Propylthiouracil-induced fatal hepatic necrosis.Am J Gastroenterol. 1987; 82: 152–4. PubMed
9. Ichiki Y, et al.. Propylthiouracil-induced severe hepatitis: a case report and review of the literature.J Gastroenterol. 1998; 33: 747–50. PubMed
10. FDA. Drug Safety Communication: new boxed warning on severe liver injury with propylthiouracil (issued 21st April, 2010). Available at: Link (accessed 29/06/10)
11. Liaw Y-F, et al.. Hepatic injury during propylthiouracil therapy in patients with hyperthyroidism.Ann Intern Med. 1993; 118: 424–8. PubMed
Effects on the lungs
Diffuse interstitial pneumonitis occurred in 2 patients given propylthiouracil1 and a hypersensitivity reaction was suggested. Propylthiouracil and benzylthiouracil have also been implicated in cases of pulmonary haemorrhage associated with antineutrophil cytoplasmic antibody (ANCA) vasculitis.2-5
(last reviewed 2011-08-23; last modified 2011-08-09)
References
1. Miyazono K, et al.. Propylthiouracil-induced diffuse interstitial pneumonitis.Arch Intern Med. 1984; 144: 1764–5. PubMed
2. Ohtsuka M, et al.. Propylthiouracil-induced alveolar haemorrhage associated with antineutrophil cytoplasmic antibody.Eur Respir J. 1997; 10: 1405–7. PubMed
3. Dhillon SS, et al.. Diffuse alveolar hemorrhage and pulmonary capillaritis due to propylthiouracil.Chest. 1999; 116: 1485–8. PubMed
4. Thabet F, et al.. ANCA-associated diffuse alveolar hemorrhage due to benzylthiouracil.Eur J Pediatr. 2006; 165: 435–6. PubMed
5. Tu Y-L, et al.. Occult pulmonary hemorrhage as a rare presentation of propylthiouracil-induced vasculitis.Pediatrics. 2011; 127: 245–e249. PubMed
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
(last reviewed 2011-08-23; last modified 2004-03-24)
References
1. Page SR, Nussey SS. Myositis in association with carbimazole therapy.Lancet. 1989; i: 964. PubMed
2. Pasquier E, et al.. Biopsy-proven myositis with microvasculitis in association with carbimazole.Lancet. 1991; 338: 1082–3. PubMed
3. O'Malley B. Carbimazole-induced cramps.Lancet. 1989; i: 1456. PubMed
Hypersensitivity
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 convertedin 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
(last reviewed 2011-08-23; last modified 2006-11-25)
References
1. Bajaj S, et al.. Antithyroid arthritis syndrome.J Rheumatol. 1998; 25: 1235–9. PubMed
2. Kawachi Y, et al.. ANCA-associated vasculitis and lupus-like syndrome caused by methimazole.Clin Exp Dermatol. 1995; 20: 345–7. PubMed
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. PubMed
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. PubMed
5. Mathieu E, et al.. Systemic adverse effect of antithyroid drugs.Clin Rheumatol. 1999; 18: 66–8. PubMed
6. Dolman KM, et al.. Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy.Lancet. 1993; 342: 651–2. PubMed
7. ten Holder SM, et al.. Cutaneous and systemic manifestations of drug-induced vasculitis.Ann Pharmacother. 2002; 36: 130–47. PubMed
8. Van Kuyk M, et al.. Methimazole-induced serum sickness.Acta Clin Belg. 1983; 38: 68–9. PubMed
9. Hakamata M, et al.. Insulin autoimmune syndrome after the third therapy with methimazole.Intern Med. 1995; 34: 410–12. PubMed
10. Burden AC, Rosenthal FD. Methimazole and insulin autoimmune syndrome.Lancet. 1983; ii: 1311. PubMed
11. Kroll H, et al.. Drug-dependent antibodies against the prodrug carbimazole do not react with the metabolite thiamazole.Blood. 2001; 97: 2186–7. PubMed
12. Smith A, et al.. Cross sensitivity to antithyroid drugs.BMJ. 1989; 298: 1253. PubMed
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. PubMed
Pregnancy
Thiourea antithyroid drugs have been used successfully in pregnancy, although there are risks associated with their use (see Hyperthyroidism, Refer to ).
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
Aplasia cutis congenita and choanal atresia (the latter with coarctation of the aorta) have also been reported after maternal exposure to carbimazole in the first trimester.5Other reported major malformations have included abdominal wall defects such as gastroschisis (or laparoschisis)5,6 and omphalocele; digestive malformation has occurred, manifesting as a patent omphalomesenteric duct.5 Other reported malformations include facial dysmorphisms, a high-arched palate, and an anomalous ear helix.5
A controlled cohort study concluded that propylthiouracil did not appear to be a major human teratogen.7However, the risk is unclear, due to a lack of data,8 and US licensed product information states that cases of maternal and neonatal liver failure sometimes fatal, have been associated with the use of propylthiouracil. As with carbimazole and thiamazole, aplasia cutis congenita has also been reported after maternal use of propylthiouracil.9A case-control analysis8 found maternal propylthiouracil exposure in the first trimester to be associated with situs inversus with or without dextrocardia, unilateral kidney agenesis or dysgenesis, and cardiac outflow defects. However, further studies were considered necessary to evaluate these associations because of the low number of affected subjects. The use of carbimazole or thiamazole was found to be significantly associated with omphalocele and choanal atresia, which was consistent with previous reports.
There have been some reports of neonates exposed to thiourea antithyroid drugs in utero displaying signs of hypothyroidism including goitre.7,10,11
(last reviewed 2011-08-23; last modified 2011-12-07)
References
1. Milham S. Scalp defects in infants of mothers treated for hyperthyroidism with methimazole or carbimazole during pregnancy.Teratology. 1985; 32: 321. PubMed
2. Vogt T, et al.. Aplasia cutis congenita after exposure to methimazole: a causal relationship?Br J Dermatol. 1995; 133: 994–6. PubMed
3. Johnsson E, et al.. Severe malformations in infant born to hyperthyroid woman on methimazole.Lancet. 1997; 350: 1520. PubMed
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. PubMed
5. Koenig D, et al.. Birth defects observed with maternal carbimazole treatment: six cases reported to Nice's Pharmacovigilance Center.Ann Endocrinol (Paris). 2010; 71: 535–42. PubMed
6. Guignon A-M, et al.. Carbimazole-related gastroschisis.Ann Pharmacother. 2003; 37: 829–31. PubMed
7. Rosenfeld H, et al.. Pregnancy outcome, thyroid dysfunction and fetal goitre after in utero exposure to propylthiouracil: a controlled cohort study.Br J Clin Pharmacol. 2009; 68: 609–17. PubMed
8. Clementi M, et al.. SAFE-Med Study Group. Treatment of hyperthyroidism in pregnancy and birth defects.J Clin Endocrinol Metab. 2010; 95: 337–E341. PubMed
9. Löllgen RM, et al.. Aplasia cutis congenita in surviving co-twin after propylthiouracil exposure in utero.J Pediatr Endocrinol Metab. 2011; 24: 215–18. PubMed
10. O'Doherty MJ, et al.. Treating thyrotoxicosis in pregnant or potentially pregnant women.BMJ. 1999; 318: 5–6. PubMed
11. Masiukiewicz US, Barrow GN. Hyperthyroidism in pregnancy: diagnosis and treatment.Thyroid. 1999; 9: 647–52. PubMed
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 thiamazole are rapidly absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 1 to 2 hours after oral doses.
Thiamazole is concentrated in the thyroid gland; since duration of action is more closely related to the intrathyroidal drug concentration than plasma half-life, prolonged antithyroid activity results from single daily doses. Thiamazole is moderately 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.
(last reviewed 2011-08-23; last modified 2011-07-21)
References to the pharmacokinetics of carbimazole and thiamazole.
(last reviewed 2011-08-23; last modified 2011-07-12)
References
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. PubMed
2. Kampmann JP, Hansen JM. Clinical pharmacokinetics of antithyroid drugs.Clin Pharmacokinet. 1981; 6: 401–28. PubMed
3. Jansson R, et al.. Intrathyroidal concentrations of methimazole in patients with Graves' disease.J Clin Endocrinol Metab. 1983; 57: 129–32. PubMed
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. PubMed
5. Jansson R, et al.. Pharmacokinetic properties and bioavailability of methimazole.Clin Pharmacokinet. 1985; 10: 443–50. PubMed
Preparations: Single-Ingredient
The following preparations list represents a compilation of all available salt forms or related substances for this drug product.
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.
AUSTRALIA: Neo-Mercazole;AUSTRIA: Carbistad¤;DENMARK: Neo-Mercazole;FINLAND: Tyrazol;FRANCE: Neo-Mercazole;GERMANY: Car¤; neo-morphazole¤; Neo-Thyreostat¤;GREECE: Thyrostat;HONG KONG: Carbiroid; Cazole¤; Neo-Mercazole;INDIA: Anti-Thyrox; Neo-Mercazole;INDONESIA: Neo-Mercazole;IRELAND: Neo-Mercazole;MALAYSIA: Camazol; Thymazole;NETHERLANDS: Basolest¤;NORWAY: Neo-Mercazole;NEW ZEALAND: Neo-Mercazole;PHILIPPINES: Anti-Thyrox¤; Carbinom; Neomercazole; Neomerdin;SOUTH AFRICA: Neo-Mercazole¤;SINGAPORE: Camazol; Cazole¤; Neo-Mercazole¤;SPAIN: Neo Tomizol;SWEDEN: Neo-Mercazole¤;SWITZERLAND: Neo-Mercazole;UNITED KINGDOM: Neo-Mercazole¤;UKRAINE: Espa-Carb (Эспа-карб);
Preparations: Pharmacopoeial
The following preparations list represents a compilation of all available salt forms or related substances for this drug product.
Therapeutic Use
- Thyroid and Antithyroid Drugs
Last Updated 1/21/20
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