Ondansetron

Structural formula
	1: 1 mixture of the ( S ) -form (above) ; and the ( R ) -form (below)
General
Non-proprietary name	Ondansetron
other names	( RS ) -2,3-Dihydro-9-methyl-3 - [(2-methylimidazol-1-yl) methyl] carbazol-4 (1 H ) -one; (±) -2,3-Dihydro-9-methyl-3 - [(2-methylimidazol-1-yl) methyl] carbazol-4 (1 H ) -one;
Molecular formula	C 18 H 19 N 3 O (ondansetron) ; C 18 H 19 N 3 O HCl 2H 2 O (ondansetron monohydrochloride dihydrate) ;
External identifiers / databases
ECHA InfoCard	100.110.918
PubChem	4595
DrugBank	DB00904
Wikidata	Q410011
Drug information
ATC code	A04 AA01 ,
Drug class	Antiemetic
Mechanism of action	selective blockade of central 5-HT 3 receptors
properties
Molar mass	293.37 g · mol -1 (ondansetron) ; 365.85 g · mol -1 (ondansetron monohydrochloride dihydrate) ;
Melting point	231–232 ° C (ondansetron) ; 178.5–179.5 ° C (ondansetron monohydrochloride dihydrate) ;
pK s value	10.4
solubility	Hydrochloride: slightly soluble in water and ethanol
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Hydrochloride dihydrate; danger
H and P phrases	H: 301
	P: 301 + 310
Toxicological data	94.90 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Ondansetron is a drug that is effective against nausea, nausea and vomiting (anti- emetic ). The substance from the group of the Setrons mediates its (antagonistic) effect via the selective blockade of the central 5-HT ₃ receptors (serotonin receptors).

pharmacology

application areas

Ondansetron is used as an antiemetic concomitant medication in the cytostatics used to fight tumors or during radiation therapy. It is also indicated for the treatment of postoperative vomiting . For these applications, ondansetron is in the form of tablets , solution for injection and as orodispersible tablet available.

So far, there is no approval for use in what is known as vomiting . It is warned against taking in the first trimester because of the risk of malformations. As with other 5-HT ₃ receptors , a positive effect on irritable bowel syndrome has been proven. However, ondansetron is rarely used in irritable bowel therapy.

Mechanism of action

In contrast to other antiemetics, ondansetron does not show any significant effects on dopamine , histamine or muscarinic receptors .

Ondansetron mediates its anti-vomiting effects by inhibiting the effect of serotonin on 5-HT ₃ receptors. Serotonin is released in large quantities from enterochromaffin cells , especially as a result of cytostatic or radiation therapy. The released serotonin activates 5-HT ₃ receptors in the visceral afferent vagus and also activates the vomiting reflex in the vomiting center of the central nervous system . Ondansetron therefore shows good antiemetic efficacy in chemotherapy or radiation therapy for tumor diseases, but only little effect in the treatment of motion sickness .

Side effects

While using ondansetron, headaches , a feeling of warmth, flushing , movement disorders and cramps can occur. Visual disturbances and disorders of the oculomotor system are also possible. The occasional occurrence of cardiac arrhythmias due to prolongation of the QT time has also been reported, which is why approval was restricted in July / August 2012 (maximum 16 mg intravenously over at least 15 minutes). In July 2013, the manufacturer GlaxoSmithKline Deutschland (GSK) again published important information for specialist groups on ondansetron (ZOFRAN® and generics) for the dose-dependent extension of the QTc interval in an information letter.

The slowing of the passage of the colon as a result of the inhibition of prokinetic 5-HT ₃ receptors in the gastrointestinal tract can lead to constipation .

In October 2019, a Rote-Hand-Brief was published according to which ondansetron can lead to malformations in the mouth and face of the unborn child if administered during the first trimester of pregnancy.

Interactions

Ondansetron is metabolized by the cytochrome P450 enzyme system , particularly CYP3A4, CYP2D6 and CYP1A2. Nevertheless, there are no significant interactions with drugs that are usually used at the same time. However, CYP3A4 inducers such as phenytoin , carbamazepine, and rifampicin may accelerate the breakdown of ondansetron.

Chemistry and isomerism

Ondansetron contains a stereocenter, so there are enantiomers . It is commercially available as a racemate (1: 1 mixture of the ( R ) and ( S ) forms), although the different pharmacological effects of enantiomers are generally accepted.

Trade names

Monopreparations

Axisetron (D), Cellondan (D), Ondansan (A), Zofran (D, A, CH), Zotrix (A), numerous generics (D, A, CH)

Web links

Red Hand Letter October 2019 on Ondansetron

Individual evidence

^ ^A ^b The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .
↑ ^a ^b Entry on Ondansetron. In: Römpp Online . Georg Thieme Verlag, accessed on July 20, 2019.
↑ ^a ^b ^c data sheet Ondansetron hydrochloride dihydrate from Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).
↑ BfArM - Rote-Hand-Briefe and Informationsbriefe - Rote-Hand-Brief on Ondansetron: Increased risk of orofacial malformations when used in the first trimester of pregnancy. Retrieved October 4, 2019 .
↑ Avoxa-Mediengruppe Deutscher Apotheker GmbH: Study: Setron in irritable bowel syndrome. Retrieved October 16, 2019 .
↑ Information letter on Zofran® (ondansetron) and generics: Risk of QTc prolongation. BfArM , July 18, 2013, accessed October 29, 2017 .
↑ GlaxoSmithKline: Important information for specialist groups , (PDF; 545 kB).
↑ Rote-Hand-Brief on Ondansetron: Increased risk of orofacial malformations when used in the first trimester of pregnancy. Federal Institute for Drugs and Medical Devices , October 1, 2019, accessed on October 2, 2019 .
↑ EJ Ariëns: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology , European Journal of Clinical Pharmacology 26 (1984) 663-668. doi: 10.1007 / BF00541922 .

[MERCK_Index-1] A ^b The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .

[römpp-2] Entry on Ondansetron. In: Römpp Online . Georg Thieme Verlag, accessed on July 20, 2019.

[Sigma-3] ta sheet Ondansetron hydrochloride dihydrate from Sigma-Aldrich , accessed on April 16, 2011 ( PDF ).

[4] BfArM - Rote-Hand-Briefe and Informationsbriefe - Rote-Hand-Brief on Ondansetron: Increased risk of orofacial malformations when used in the first trimester of pregnancy. Retrieved October 4, 2019 .

[5] Avoxa-Mediengruppe Deutscher Apotheker GmbH: Study: Setron in irritable bowel syndrome. Retrieved October 16, 2019 .

[6] Information letter on Zofran® (ondansetron) and generics: Risk of QTc prolongation. BfArM , July 18, 2013, accessed October 29, 2017 .

[7] GlaxoSmithKline: Important information for specialist groups , (PDF; 545 kB).

[8] Rote-Hand-Brief on Ondansetron: Increased risk of orofacial malformations when used in the first trimester of pregnancy. Federal Institute for Drugs and Medical Devices , October 1, 2019, accessed on October 2, 2019 .

[Ariëns-9] EJ Ariëns: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology , European Journal of Clinical Pharmacology 26 (1984) 663-668. doi: 10.1007 / BF00541922 .