Carbimazole

Carbimazole
Names
Trade namesNeo-mercazole
IUPAC name
  • ethyl 3-methyl-2-sulfanylidene-imidazole-1-carboxylate
Clinical data
Routes of
use		By mouth[1]
External links
AHFS/Drugs.comInternational Drug Names
US NLMCarbimazole
Legal
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetics
Protein binding85%
Elimination half-life5.3h
Excretion>90%Kidney
Identifiers
CAS Number
  • 22232-54-8 checkY
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ATC code
Chemical and physical data
FormulaC7H10N2O2S
Molar mass186.23 g·mol−1
3D model (JSmol)
Melting point122 to 125 °C (252 to 257 °F)
SMILES
  • S=C1N(\C=C/N1C(=O)OCC)C
InChI
  • InChI=1S/C7H10N2O2S/c1-3-11-7(10)9-5-4-8(2)6(9)12/h4-5H,3H2,1-2H3 checkY
  • Key:CFOYWRHIYXMDOT-UHFFFAOYSA-N checkY

Carbimazole is a prescribed antithyroid medicine used to treat overactive thyroid or Grave's disease.[1] It acts to reduce the amount of thyroid hormones released from the thyroid gland and can take up to a month before symptoms are better.[1] Treatment generally lasts around 1 - 2 years, during which thyroid blood tests are checked every 4-8 weeks, the dose of carbimazole adjusted accordingly, and after which up to 40% remain well for 10 years after stopping.[2]

Serious but rare side effects include a sudden sore throat due to a drop in blood cells: neutropenia and agranulocytosis.[1] Although still used in pregnancy, carbimazole can cross the placenta in pregnant women.[1] As a result, birth defects can occur, although rare.[3]

Along with propylthiouracil, it is a type of thioamide,[4] and is a pro-drug as after absorption it is converted to the active form, methimazole.[3] Methimazole prevents thyroid peroxidase enzyme from iodinating and coupling the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4 (thyroxine).[4]

It is on the World Health Organization's List of Essential Medicines.[5] In the UK, it is the first choice of antithyroid medicine.[2]

Medical uses

Medical therapy for hyperthyroidism typically involves either titrating the dose of carbimazole until the person becomes euthyroid or maintaining a high dose of carbimazole to suppress endogenous thyroid production, and then replacing thyroid hormone with levothyroxine ("block and replace").[2] Treatment is usually given for 1-2 years followed by a trial withdraw.[2]

The onset of anti-thyroid effect is rapid but the onset of clinical effects on thyroid hormone levels in the blood is much slower. This is because the large store of pre-formed T3 and T4 in the thyroid gland and bound to thyroid binding globulin (99% bound) has to be depleted before any beneficial clinical effect occurs.

Side effects

Whilst rashes and pruritus are common, these can often be treated with antihistamines without stopping the carbimazole. For those patients where sensitivity reactions cannot be controlled, propylthiouracil may be used as an alternative; cross-sensitivity between these drugs is rare.

Its most serious rare side effect is bone marrow suppression causing neutropenia and agranulocytosis. This may occur at any stage during treatment and without warning; monitoring of white cell count is not useful. Patients are advised to immediately report symptoms of infection, such as sore throat or fever, so that a full blood count test may be arranged. If this confirms a low neutrophil count, discontinuation of the drug leads to recovery. However failure to report suggestive symptoms or delays in considering the possibility of immunosuppression and its testing, can lead to fatalities.

Precautions

Some people are allergic to azole(s). Some azole drugs have adverse side-effects. Some azole drugs may disrupt estrogen production in pregnancy, affecting pregnancy outcome.[6]

Carbimazole should be used judiciously in pregnancy as it crosses the placenta. It has (rarely) been associated with congenital defects, including aplasia cutis of the neonate but is not contra-indicated. However, it more predictably may cause fetal hypothyroidism so (in minimal doses) it can be used in order to control maternal hyperthyroidism. There are reported cases of goiter and choanal atresia in fetus.[7] Furthermore, breast feeding is possible but only if lowest effective dose is used and neonatal development is closely monitored.

For the above reasons, it is preferable to use PTU in pregnancy, especially in the first trimester, with the possibility of changing to Carbimazole for the second and third trimesters.[8]

Brand names

  • Neo-mercazole[9]
  • Vidalta
  • Thyrocab
  • Neomerdin

References

  1. 1 2 3 4 5 Ritter, James M.; Flower, Rod; Henderson, Graeme; Loke, Yoon Kong; Rang, Humphrey P. (2020). "35. Drugs affecting major organ systems". Rang & Dale's Pharmacology. Elsevier. pp. 452–453. ISBN 978-0-7020-7448-6. Archived from the original on 2021-08-28. Retrieved 2021-10-08.
  2. 1 2 3 4 Wiffen, Philip; Stoner, Nicola (2017). "20. Therapy-related issues: endocrine". Oxford Handbook of Clinical Pharmacy. Oxford: Oxford University Press. pp. 499–500. ISBN 978-0-19-873582-3. LCCN 2016945512. Archived from the original on 2021-10-09. Retrieved 2021-10-08.
  3. 1 2 Francis, Thanuya; Francis, Niroshan; Lazarus, John H.; Okosieme, Onyebuchi E. (3 May 2020). "Safety of antithyroid drugs in pregnancy: update and therapy implications". Expert Opinion on Drug Safety. 19 (5): 565–576. doi:10.1080/14740338.2020.1748007. ISSN 1474-0338.
  4. 1 2 Dong, Betty J. (2020). "38. Thyroid and antithyroid drugs". In Katzung, Bertram G.; Trevor, Anthony J. (eds.). Basic and Clinical Pharmacology 15e. New York: McGraw-Hill. pp. 718–719. ISBN 978-1-260-45231-0. Archived from the original on 2021-10-10. Retrieved 2021-10-10.
  5. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  6. ↑ Kragie L, Turner SD, Patten CJ, Crespi CL, Stresser DM (August 2002). "Assessing pregnancy risks of azole antifungals using a high throughput aromatase inhibition assay". Endocrine Research. 28 (3): 129–40. doi:10.1081/ERC-120015045. PMID 12489563. S2CID 8282678.
  7. ↑ Brunton L, Chabner BA, Knollman B (2011). Goodman & Gilman's pharmacological basis of therapeutics (12th ed.). McGraw-Hill. ISBN 978-0-07-162442-8.
  8. ↑ Bahn RS, Burch HS, Cooper DS, Garber JR, Greenlee CM, Klein IL, Laurberg P, McDougall IR, Rivkees SA, Ross D, Sosa JA, Stan MN (July 2009). "The Role of Propylthiouracil in the Management of Graves' Disease in Adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration". Thyroid. 19 (7): 673–4. doi:10.1089/thy.2009.0169. PMID 19583480.
  9. ↑ "Neo-Mercazole Carbimazole". Nicholas Laboratories Indonesia. Archived from the original on 2016-03-04. Retrieved 2021-06-22.
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