Granisetron

Last updated

Granisetron
Granisetron structure.svg
Granisetron 3D.png
Clinical data
Trade names Kytril, Sancuso, others
AHFS/Drugs.com Monograph
MedlinePlus a601211
License data
Pregnancy
category
  • AU:B1
Routes of
administration
By mouth, intravenous, transdermal
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability 60%
Protein binding 65%
Metabolism Hepatic
Elimination half-life 3–14 hours
Excretion Renal 11–12%, faecal 38%
Identifiers
  • 1-Methyl-N-((1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)-1H-indazole-3-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.212.327 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H24N4O
Molar mass 312.417 g·mol−1
3D model (JSmol)
  • CN4[C@@H]1CCC[C@H]4C[C@H](C1)NC(=O)c3nn(C)c2ccccc23
  • InChI=1S/C18H24N4O/c1-21-13-6-5-7-14(21)11-12(10-13)19-18(23)17-15-8-3-4-9-16(15)22(2)20-17/h3-4,8-9,12-14H,5-7,10-11H2,1-2H3,(H,19,23)/t12-,13+,14- Yes check.svgY
  • Key:MFWNKCLOYSRHCJ-BTTYYORXSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy and radiotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors.

Contents

Granisetron was developed by chemists working at the British drug company Beecham c.1985 and is available as a generic. It is produced by Roche Laboratories under the trade name Kytril. The drug was approved in the United Kingdom in 1991 and in United States in 1994 by the FDA.

A granisetron transdermal patch with the trade name Sancuso was approved by the US FDA on September 12, 2008. [1] Sancuso is manufactured by 3M Drug Delivery Systems for Kyowa Kirin, Inc.

It was patented in 1985 and approved for medical use in 1991. [2] It is on the World Health Organization's List of Essential Medicines. [3]

Medical uses

Chemotherapy

It may be used for chemotherapy-induced nausea and vomiting and appears to work about the same as ondansetron. [4] The most common side-effects of chemotherapy treatment are nausea, vomiting and diarrhea. This is one type of drug that a doctor can prescribe to prevent, lessen, or relieve discomfort.[ citation needed ]

Post operative

A number of medications including granisetron appear to be effective in controlling post-operative nausea and vomiting (PONV). [5] It is unclear if it is more or less effective than other agents such as droperidol, metoclopramide, or ondansetron. [6]

Gastroparesis

The granisetron patch (Sancuso) has been studied for use in gastroparesis, [7] though it is not FDA approved for this indication. [8]

Other

Adverse effects

Granisetron is a well-tolerated drug with few side effects. Headache, dizziness, and constipation are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drug's use. It is broken down by the liver's cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system.[ citation needed ]

Extended release

An extended release injectable version of granisetron, known as Sustol is also available in the United States as of 2016. [9] The long acting form is used for the treatment of both acute and delayed CINV in moderately emetogenic chemotherapy and anthrocycline and/or cyclophosphamide (AC) highly emetogenic regimens. In its review, the FDA did not grant the broad HEC label to the drug citing the focus on AC regimens, primarily breast-cancer, and lack of data. [10]

Related Research Articles

An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may be used for severe cases of gastroenteritis, especially if the patient is dehydrated.

<span class="mw-page-title-main">Quetiapine</span> Atypical antipsychotic medication

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its sedating effect, the benefits of such use do not appear to generally outweigh the side effects. It is taken orally.

<span class="mw-page-title-main">Metoclopramide</span> Medication

Metoclopramide is a medication used for stomach and esophageal problems. It is commonly used to treat and prevent nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying, and to help with gastroesophageal reflux disease. It is also used to treat migraine headaches.

Postoperative nausea and vomiting (PONV) is the phenomenon of nausea, vomiting, or retching experienced by a patient in the post-anesthesia care unit (PACU) or within 24 hours following a surgical procedure. PONV affects about 10% of the population undergoing general anaesthesia each year. PONV can be unpleasant and lead to a delay in mobilization and food, fluid, and medication intake following surgery.

<span class="mw-page-title-main">Triptan</span> Class of pharmaceutical drugs

Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual headaches, they do not provide preventive treatment and are not considered a cure. They are not effective for the treatment of tension–type headache, except in persons who also experience migraines. Triptans do not relieve other kinds of pain.

<span class="mw-page-title-main">Domperidone</span> Peripheral D2 receptor antagonist

Domperidone, sold under the brand name Motilium among others, is a dopamine antagonist medication which is used to treat nausea and vomiting and certain gastrointestinal problems like gastroparesis. It raises the level of prolactin in the human body and is used to induce and promote breast milk production. It may be taken by mouth or rectally.

<span class="mw-page-title-main">Ondansetron</span> Medication to prevent nausea and vomiting

Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, or surgery. It is also effective for treating gastroenteritis. It can be given orally, intramuscularly, or intravenously.

<span class="mw-page-title-main">Levomepromazine</span> Typical antipsychotic medication

Levomepromazine, also known as methotrimeprazine, is a phenothiazine neuroleptic drug. Brand names include Nozinan, Levoprome, Detenler, Hirnamin, Levotomin and Neurocil. It is a low-potency antipsychotic with strong analgesic, hypnotic and antiemetic properties that are primarily used in palliative care.

<span class="mw-page-title-main">Nabilone</span> Synthetic cannabinoid

Nabilone, sold under the brand name Cesamet among others, is a synthetic cannabinoid with therapeutic use as an antiemetic and as an adjunct analgesic for neuropathic pain. It mimics tetrahydrocannabinol (THC), the primary psychoactive compound found naturally occurring in Cannabis.

<span class="mw-page-title-main">Dolasetron</span> Pharmaceutical drug

Dolasetron (trade name Anzemet) is a serotonin 5-HT3 receptor antagonist used to treat nausea and vomiting following chemotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata. It does not have much antiemetic effect when symptoms are due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors.

<span class="mw-page-title-main">Droperidol</span> Antidopaminergic drug

Droperidol is an antidopaminergic drug used as an antiemetic and as an antipsychotic. Droperidol is also often used as a rapid sedative in intensive-care treatment, and where "agitation aggression or violent behavior" are present.

<span class="mw-page-title-main">Asenapine</span> Medication to treat schizophrenia

Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder.

<span class="mw-page-title-main">Palonosetron</span> Pharmaceutical drug

Palonosetron, sold under the brand name Aloxi, is a medication used for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is a 5-HT3 antagonist.

5-HT<sub>3</sub> antagonist Anti-nausea group of medications

The 5-HT3 antagonists, informally known as "setrons", are a class of drugs that act as receptor antagonists at the 5-HT3 receptor, a subtype of serotonin receptor found in terminals of the vagus nerve and in certain areas of the brain. With the notable exceptions of alosetron and cilansetron, which are used in the treatment of irritable bowel syndrome, all 5-HT3 antagonists are antiemetics, used in the prevention and treatment of nausea and vomiting. They are particularly effective in controlling the nausea and vomiting produced by cancer chemotherapy and are considered the gold standard for this purpose.

<span class="mw-page-title-main">Metopimazine</span> Chemical compound

Metopimazine, sold under the brand names Vogalen and Vogalene, is an antiemetic of the phenothiazine group which is used to treat nausea and vomiting. It is marketed in Europe, Canada, and South America. As of August 2020, metopimazine has been repurposed and is additionally under development for use in the United States for the treatment of gastroparesis.

A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action of serotonin and serotonergic drugs at serotonin (5-HT) receptors.

<span class="mw-page-title-main">Nausea</span> Medical symptom or condition

Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.

Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of many cancer treatments. Nausea and vomiting are two of the most feared cancer treatment-related side effects for cancer patients and their families. In 1983, Coates et al. found that patients receiving chemotherapy ranked nausea and vomiting as the first and second most severe side effects, respectively. Up to 20% of patients receiving highly emetogenic agents in this era postponed, or even refused, potentially curative treatments. Since the 1990s, several novel classes of antiemetics have been developed and commercialized, becoming a nearly universal standard in chemotherapy regimens, and helping to better manage these symptoms in a large portion of patients. Efficient mediation of these unpleasant and sometimes debilitating symptoms results in increased quality of life for the patient, and better overall health of the patient, and, due to better patient tolerance, more effective treatment cycles.

<span class="mw-page-title-main">Cancer and nausea</span>

Cancer and nausea are associated in about fifty percent of people affected by cancer. This may be as a result of the cancer itself, or as an effect of the treatment such as chemotherapy, radiation therapy, or other medication such as opiates used for pain relief. About 70 to 80% of people undergoing chemotherapy experience nausea or vomiting. Nausea and vomiting may also occur in people not receiving treatment, often as a result of the disease involving the gastrointestinal tract, electrolyte imbalance, or as a result of anxiety. Nausea and vomiting may be experienced as the most unpleasant side effects of cytotoxic drugs and may result in patients delaying or refusing further radiotherapy or chemotherapy.

<span class="mw-page-title-main">Indisetron</span> Chemical compound

Indisetron is a drug used for prophylaxis of chemotherapy-induced nausea and vomiting. It was approved by Japan's Pharmaceuticals and Medical Devices Agency in 2004.

References

  1. "FDA Approves Sancuso, the First and Only Patch for Preventing Nausea and Vomiting in Cancer Patients Undergoing Chemotherapy". PRNewswire. September 12, 2008.
  2. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 448. ISBN   9783527607495.
  3. 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.
  4. Billio A, Morello E, Clarke MJ (January 2010). Billio A (ed.). "Serotonin receptor ntagonists for highly emetogenic chemotherapy in adults". The Cochrane Database of Systematic Reviews (1): CD006272. doi:10.1002/14651858.CD006272.pub2. PMID   20091591. (Retracted, see doi:10.1002/14651858.cd006272.pub3)
  5. Ngo, AL; Orhurhu, V; Urits, I; Delfin, EO; Sharma, M; Jones, MR; Viswanath, O; Urman, RD (July 2019). "Extended release granisetron: Review of pharmacologic considerations and clinical role in the perioperative setting". Saudi Journal of Anaesthesia. 13 (3): 231–236. doi: 10.4103/sja.SJA_817_18 . PMC   6625288 . PMID   31333369.
  6. Carlisle JB, Stevenson CA (July 2006). Carlisle J (ed.). "Drugs for preventing postoperative nausea and vomiting". The Cochrane Database of Systematic Reviews. 2006 (3): CD004125. doi:10.1002/14651858.CD004125.pub2. PMC   6463839 . PMID   16856030. (Retracted, see doi:10.1002/14651858.cd004125.pub3)
  7. Midani D, Parkman HP (October 2016). "Granisetron Transdermal System for Treatment of Symptoms of Gastroparesis: A Prescription Registry Study". Journal of Neurogastroenterology and Motility. 22 (4): 650–655. doi:10.5056/jnm15203. PMC   5056574 . PMID   27400689.
  8. "Sancuso Full Prescribing Information" (PDF). U.S. Food and Drug Administration. September 2015. Retrieved November 29, 2019.
  9. Drugs.com Heron Therapeutics Announces FDA Approval of Sustol (granisetron) Extended-Release Injection for the Prevention of Chemotherapy-Induced Nausea and Vomiting
  10. FDA.gov Sustol Prescribing Information.

Further reading