Carbimazole

Carbimazole
Clinical data
Trade names	Neo-Mercazole, Anti-Thyrox, etc.
AHFS/Drugs	International Drug Names
Pregnancy; category	AU:D; ;
Routes of; administration	By mouth
ATC code	H03BB01(WHO);
Legal status
Legal status	In general: ℞ (Prescription only);
Pharmacokineticdata
Protein binding	85%
Eliminationhalf-life	5.3h
Excretion	Kidney>90%
Identifiers
	IUPAC name ethyl 3-methyl-2-sulfanylidene-imidazole-1-carboxylate;
CAS Number	22232-54-8;
PubChemCID	31072;
DrugBank	DB00389;
ChemSpider	28829;
UNII	8KQ660G60G;
KEGG	D07616;
ChEBI	CHEBI:617099;
ChEMBL	ChEMBL508102;
CompTox Dashboard(EPA)	DTXSID9022736;
ECHA InfoCard	100.040.762
Chemical and physical data
Formula	C7H10N2O2S
Molar mass	186.23g·mol−1
3D model (JSmol)	Interactive image;
Melting point	122 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; Key:CFOYWRHIYXMDOT-UHFFFAOYSA-N;
	(verify)

Carbimazole(brand names Neo-Mercazole, Anti-Thyrox, etc.) is used to treathyperthyroidism.Carbimazole is apro-drugas after absorption it is converted to the active form,methimazole.Methimazole preventsthyroid peroxidaseenzyme from iodinating and coupling thetyrosineresidues onthyroglobulin,hence reducing the production of the thyroid hormonesT₃and T₄(thyroxine).

It is on theWorld Health Organization's List of Essential Medicines.^[2]

Medical uses

Medical therapy for hyperthyroidism typically involves either titrating the dose of carbimazole until the patient becomes euthyroid or maintaining a high dose of carbimazole to suppress endogenous thyroid production, and then replacing thyroid hormone with levothyroxine ( "block and replace" ). Treatment is usually given for 18–24 months followed by a trial withdraw.^[3]

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 T₃and T₄in the thyroid gland and bound tothyroid binding globulin(99% bound) has to be depleted before any beneficial clinical effect occurs.

Adverse effects

Whilstrashesandpruritusare common, these can often be treated withantihistamineswithout stopping the carbimazole. For those patients where sensitivity reactions cannot be controlled,propylthiouracilmay be used as an alternative; cross-sensitivity between these drugs is rare.

Its most serious rare side effect isbone marrow suppressioncausingneutropeniaandagranulocytosis.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 assore throator fever, so that afull blood counttest 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 toazole(s). Some azole drugs have adverseside-effects.Some azole drugs may disruptestrogenproduction inpregnancy,affecting pregnancy outcome.^[4]^{[verification needed]}

Carbimazole should be used judiciously in pregnancy as it crosses the placenta. It has (rarely) been associated with congenital defects, includingaplasia cutisof the neonate but is not contra-indicated. However, it more predictably may cause fetalhypothyroidismso (in minimal doses) it can be used in order to control maternalhyperthyroidism.There are reported cases of goiter andchoanal atresiain fetus.^[5]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 usePTUin pregnancy, especially in the first trimester, with the possibility of changing to carbimazole for the second and third trimesters.^[6]

Brand names

Neo-mercazole^[7]
Vidalta
Thyrocab
Neomerdin

References

^"Updates to the Prescribing Medicines in Pregnancy database".Therapeutic Goods Administration (TGA).12 May 2022.Retrieved13 May2022.
^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.
^Lawrence N, Cheetham T, Elder C (September 2019)."How do paediatricians use and monitor antithyroid drugs in the UK? A clinician survey"(PDF).Clinical Endocrinology.91(3):417–423.doi:10.1111/cen.14046.PMID 31179554.S2CID 182948575.
^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):129–140.doi:10.1081/ERC-120015045.PMID 12489563.S2CID 8282678.
^Brunton L, Chabner BA, Knollman B (2011).Goodman & Gilman's pharmacological basis of therapeutics(12th ed.). McGraw-Hill.ISBN 978-0-07-162442-8.
^Bahn RS, Burch HS, Cooper DS, Garber JR, Greenlee CM, Klein IL, et al. (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):673–674.doi:10.1089/thy.2009.0169.PMID 19583480.
^"Neo-Mercazole Carbimazole".Nicholas Laboratories Indonesia. Archived fromthe originalon 2016-03-04.Retrieved2021-06-22.