Granisetron

Structural formula
General
Non-proprietary name	Granisetron
other names	1-methyl- N - ((1 R , 3 r , 5 S ) -9-methyl-9-azabicyclo [3.3.1] nonan-3-yl) -1 H -indazole-3-carboxamide ( IUPAC )
Molecular formula	C 18 H 24 N 4 O
Brief description	colorless solid (hydrochloride)
External identifiers / databases
ECHA InfoCard	100.212.327
PubChem	3510
DrugBank	DB00889
Wikidata	Q596708
Drug information
ATC code	A04 AA02
Drug class	Antiemetic
Mechanism of action	selective blockade of central 5-HT 3 receptors
properties
Molar mass	312.41 g mol −1
Melting point	152-154 ° C; 284–290 ° C (hydrochloride);
pK s value	9.4
solubility	soluble in water (> 10 g · l −1 , hydrochloride) poorly soluble in methanol , slightly soluble in dichloromethane
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 Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	> 2000 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 .

Granisetron is an active ingredient from the group of 5-HT ₃ antagonists , which is used as an antiemetic for the treatment of nausea and vomiting in connection with cytostatic therapy or for postoperative nausea and vomiting . Granisetron is marketed under various trade names as film-coated tablets and as an infusion solution; transdermal patches are also on the market in the USA .

Clinical information

Application areas (indications)

The administration of cytostatics as part of chemotherapy often leads to nausea and vomiting ( chemotherapy-induced nausea and vomiting , CINV) and can be therapy-limiting. 5-HT ₃ antagonists have shown effective efficacy in numerous studies, also in conjunction with other antiemetics, and are listed in current guidelines. They are effective both for nausea that occurs quickly and for nausea that occurs after a delay.

Postoperative nausea and vomiting ( postoperative nausea and vomiting , PONV) occur as side effects of anesthesia , particularly general anesthesia on (anesthesia). PONV is caused by various factors (influence of medication, personal disposition, external influences), the mechanism of development is not understood in detail. The frequency of nausea and vomiting with general anesthesia without prophylactic measures is 20–30%. A multimodal treatment concept can at least reduce the incidence. 5-HT ₃ antagonists play a central role here; they are the most well-studied group of substances for the treatment of postoperative nausea, and there is high evidence for their effectiveness, also for granisetron .

No dose adjustment is required in the case of hepatic or renal insufficiency. Due to a lack of data, its use is not recommended during pregnancy and breastfeeding, but there is no evidence that it is harmful.

Contraindications (contraindications) and interactions

The only contraindication is hypersensitivity to the active ingredient. There are no clinically relevant interactions.

Adverse effects (side effects)

Side effects can often include headache , constipation , flu-like symptoms with fever and chills, occasionally hypersensitivity reactions or a temporary increase in liver transaminases . ECG changes, including QT prolongation, are occasionally seen in setrons . These are considered to be clinically irrelevant, but special attention should be given to cardiac risk patients.

Pharmacological properties

Granisetron, as a potent antagonist at the 5-HT ₃ receptor, inhibits the action of serotonin on structures in the central nervous system, especially in the chemoreceptor trigger zone of the area postrema and the nucleus tractus solitarii , which are involved in the development of nausea and vomiting. Granisetron acts almost exclusively on this one receptor, in contrast to other 5-HT ₃ antagonists such as ondansetron , which has been shown to also act on other receptors. Nevertheless, ondansetron and tropisetron are also highly selective for the 5-HT ₃ receptor. In contrast, active ingredients such as metoclopramide, renzaprid and zacoprid are hardly selective.

The bioavailability after oral ingestion is about 60%. Granisetron is metabolized hepatically, the breakdown products are excreted about half each hepatically and renally. The mean plasma half-life is around nine hours, but it can vary greatly from person to person.

Trade names

Kevatril , axigran , ribosetron , Kytril , Sancuso (transdermal patch, USA), various generics

Individual evidence

↑ ^a ^b ^c ^d ^e Data sheet Granisetron hydrochloride, ≥ 98% (HPLC), solid from Sigma-Aldrich , accessed on January 8, 2012 ( PDF ).
↑ Patent US2008242696 : Crystalline Granistron base and production process therefor. Published October 2, 2008 , Applicant: Chemagis Ltd., Inventor: Yael Gafni, Alex Weisman, Itai Adin. ‌
↑ ^a ^b Entry on Granisetron. In: Römpp Online . Georg Thieme Verlag, accessed on July 10, 2019.
↑ Entry on Granisetron in the DrugBank of the University of Alberta , accessed November 18, 2019.
↑ ^a ^b ^c ^d ^e Granisetron specialist information (various manufacturers), accessed 01/2012.
↑ ^a ^b M. Aapro: Granisetron: an update on its clinical use in the management of nausea and vomiting. Review. In: Oncologist . 9 (6), 2004, pp. 673-686. PMID 15561811 .
^ F. Kazemi-Kjellberg, I. Henzi, MR Tramèr: Treatment of established postoperative nausea and vomiting: a quantitative systematic review. In: BMC anesthesiology. Volume 1, Number 1, 2001, p. 2. PMID 11734064 . PMC 60651 (free full text).
↑ D. Rüsch, LH Eberhart, J. Wallenborn, P. Ill people: Nausea and vomiting after operations under general anesthesia: an evidence-based overview of risk assessment, prophylaxis and therapy. In: Dtsch Arztebl Int. 107 (42), Oct 2010, pp. 733-741. PMID 21079721 .
^ AJ Freeman, KT Cunningham, MB Tyers: Selectivity of 5-HT3 receptor antagonists and anti-emetic mechanisms of action. Review. In: Anti-Cancer Drugs . Volume 3, Number 2, April 1992, pp. 79-85. PMID 1525396

[Sigma-1] Data sheet Granisetron hydrochloride, ≥ 98% (HPLC), solid from Sigma-Aldrich , accessed on January 8, 2012 ( PDF ).

[2] Patent US2008242696 : Crystalline Granistron base and production process therefor. Published October 2, 2008 , Applicant: Chemagis Ltd., Inventor: Yael Gafni, Alex Weisman, Itai Adin. ‌

[römpp-3] Entry on Granisetron. In: Römpp Online . Georg Thieme Verlag, accessed on July 10, 2019.

[4] Entry on Granisetron in the DrugBank of the University of Alberta , accessed November 18, 2019.

[FI-5] Granisetron specialist information (various manufacturers), accessed 01/2012.

[Aapro-6] M. Aapro: Granisetron: an update on its clinical use in the management of nausea and vomiting. Review. In: Oncologist . 9 (6), 2004, pp. 673-686. PMID 15561811 .

[7] F. Kazemi-Kjellberg, I. Henzi, MR Tramèr: Treatment of established postoperative nausea and vomiting: a quantitative systematic review. In: BMC anesthesiology. Volume 1, Number 1, 2001, p. 2. PMID 11734064 . PMC 60651 (free full text).

[8] D. Rüsch, LH Eberhart, J. Wallenborn, P. Ill people: Nausea and vomiting after operations under general anesthesia: an evidence-based overview of risk assessment, prophylaxis and therapy. In: Dtsch Arztebl Int. 107 (42), Oct 2010, pp. 733-741. PMID 21079721 .

[9] AJ Freeman, KT Cunningham, MB Tyers: Selectivity of 5-HT3 receptor antagonists and anti-emetic mechanisms of action. Review. In: Anti-Cancer Drugs . Volume 3, Number 2, April 1992, pp. 79-85. PMID 1525396