Dolasetron

Dolasetron
Names
IUPAC name
  • (3R)-10-oxo-8-azatricyclo[5.3.1.03,8]undec-5-yl 1H-indole-3-carboxylate
Clinical data
Drug class5-HT3 receptor blocker[1]
Main usesPostoperative and chemotherapy-induced nausea and vomiting[1][2]
Side effectsHeadache, tiredness, dizziness, diarrhea, QT prolongation, anaphylaxis[1][2]
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Pregnancy
category
  • B (US)
Routes of
use		Intravenous, by mouth
External links
AHFS/Drugs.comMonograph
MedlinePlusa601001
Legal
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetics
Protein binding69 to 77%
Elimination half-life8.1 hours
Chemical and physical data
FormulaC19H20N2O3
Molar mass324.380 g·mol−1
3D model (JSmol)
SMILES
  • [H]C35C[C@@]4([H])CC(OC(=O)c1c[nH]c2ccccc12)C[C@@]([H])(C3)N4CC5=O
InChI
  • InChI=1S/C19H20N2O3/c22-18-10-21-12-5-11(18)6-13(21)8-14(7-12)24-19(23)16-9-20-17-4-2-1-3-15(16)17/h1-4,9,11-14,20H,5-8,10H2/t11-,12+,13-,14- checkY
  • Key:UKTAZPQNNNJVKR-YXSUXZIUSA-N checkY

Dolasetron, sold under the brand name Anzemet, is a medication used for postoperative and chemotherapy-induced nausea and vomiting.[1][2] Other uses may include gastroenteritis and hyperemesis gravidarum.[1] It does not work for motion sickness.[1] It is taken by mouth; and less commonly by injection into a vein.[2]

Common side effects include headache, tiredness, dizziness, and diarrhea.[1] Other side effects may include QT prolongation and anaphylaxis.[1][2] While there is no evidence of harm in pregnancy, such use is not well studied.[3] It is a 5-HT3 receptor blocker.[1]

Dolasetron was patented in 1986 and approved for medical use in 1997.[4] It is on the World Health Organization's List of Essential Medicines.[5] It is available as a generic medication.[1] In the United States it costs about 75 USD per dose.[6] Some versions have been discontinued in the United States.[7]

Medical uses

  • Chemotherapy-induced nausea and vomiting
    • 5-HT3 receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting. Many times they are given intravenously about 30 minutes before beginning therapy.
  • Post-operative and post-radiation nausea and vomiting
  • Is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis
  • Unlike most other 5HT3 antagonists, data is lacking for use of dolasetron with aprepitant in chemotherapy-induced nausea and vomiting (CINV).
  • It is also sometimes used as an antiemetic (anti-vomiting medication) in veterinary medicine for dogs and cats.

Dosage

In adults it may be used at a dose of 100 mg by mouth or 12.5 mg by injection into a vein.[2]

Side effects

Dolasetron 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 is a potential for prolonging of the QT interval to occur as well. There have been no significant drug interactions reported with this drug's use. Dolasetron is broken down by the liver's cytochrome P450 system and has little effect on the metabolism of other drugs broken down by this system.

Intravenous dolasetron is contraindicated in Chemotherapy-induced nausea and vomiting (CINV). Doxorubicin and cyclophosphamide are as emetogenic as cisplatin, and preventive drugs should always be considered. The 5HT3 agonists are the mainstays of prevention and are frequently used in combination with other drugs such as corticosteroids and the NK1 receptor antagonist aprepitant. However, the FDA recently issued a drug communication stating that the injection form of dolasetron, a 5HT3 agonist, should no longer be used in adult or pediatric patients with CINV.[8] Dolasetron injection can increase the risk of developing torsade de pointes, a potentially fatal abnormal heart rhythm. Patients with underlying heart conditions or existing heart rate or rhythm problems are at increased risk. Although the oral form of this agent can still be used, careful monitoring and correction of potassium and magnesium levels should be initiated prior to and during treatment. In addition, in older patients and in patients with heart failure, a slow heart rate, underlying cardiac disease, and those with renal impairment, monitoring with electrocardiography is indicated when this drug is used. Congenital long-QT syndrome and drugs that prolong the PR or QRS interval are contraindications to dolasetron therapy. Dolasetron injection may still be used for the prevention and treatment of postoperative nausea and vomiting, per Food and Drug Administration guidelines.

Mechanism of action

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. This drug does not have any effect on dopamine receptors or muscarinic receptors.

History

References

  1. 1 2 3 4 5 6 7 8 9 10 "Serotonin 5-HT3 Receptor Antagonists". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. Archived from the original on 8 May 2021. Retrieved 26 December 2021.
  2. 1 2 3 4 5 6 "Dolasetron Monograph for Professionals". Drugs.com. Archived from the original on 22 January 2021. Retrieved 26 December 2021.
  3. ↑ "Dolasetron (Anzemet) Use During Pregnancy". Drugs.com. Archived from the original on 24 November 2020. Retrieved 26 December 2021.
  4. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 448. ISBN 9783527607495. Archived from the original on 2021-09-30. Retrieved 2020-11-28.
  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. ↑ "Anzemet Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 26 December 2021.
  7. ↑ "Drugs@FDA: FDA-Approved Drugs". www.accessdata.fda.gov. Archived from the original on 22 March 2021. Retrieved 26 December 2021.
  8. ↑ "Abnormal heart rhythms associated with use of Anzemet (dolasetron mesylate)". FDA Drug Safety Communication. U.S. Food and Drug Administration. 3 August 2017. Archived from the original on 24 April 2019. Retrieved 28 November 2020.
Identifiers:
  • Katzung BG (2004). Basic and Clinical Pharmacology (9th ed.). ISBN 0-07-141092-9.
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