Ondansetron

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Zofran
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Ondansetron
Clinical data
Trade namesZofran, Atossa,[1][unreliable source?] others[2]
AHFS/Drugs.comMonograph
MedlinePlusa601209
License data
Pregnancy
category
Routes of
administration		orally (by mouth), rectal, intravenous, intramuscular, thin film
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability~60%
Protein binding70–76%
MetabolismLiver (CYP3A4, CYP1A2, CYP2D6)
Elimination half-life5.7 hours
ExcretionKidney
Identifiers
  • (RS)-9-Methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-2,3-dihydro-1H-carbazol-4(9H)-one
JSmol)
  • O=C1c2c3ccccc3n(C)c2CCC1Cn4ccnc4C
  • InChI=1S/C18H19N3O/c1-12-19-9-10-21(12)11-13-7-8-16-17(18(13)22)14-5-3-4-6-15(14)20(16)2/h3-6,9-10,13H,7-8,11H2,1-2H3 checkY
  • Key:FELGMEQIXOGIFQ-UHFFFAOYSA-N checkY
  (verify)

Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent

intravenously (injection into a vein).[9]

Common

dopamine receptors or muscarinic acetylcholine receptors.[12]

Ondansetron was patented in 1984 and approved for medical use in 1990.

generic medication.[9] In 2021, it was the 79th most commonly prescribed medication in the United States, with more than 8 million prescriptions.[15][16]

Medical uses

Ondansetron is

indicated for the prevention of chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting.[7][17]

Pregnancy

Ondansetron is used

off-label to treat morning sickness and hyperemesis gravidarum of pregnancy. It is typically used after other antinausea drugs have failed.[18]

A large multi-center cohort study found no association between ondansetron exposure and fetal risk compared to other antiemetic drugs. [19]

Cyclic vomiting syndrome

Ondansetron is one of several antiemetic drugs used during the vomiting phase of cyclic vomiting syndrome.[20]

Gastroenteritis

Trials in emergency department settings support the use of ondansetron to reduce vomiting associated with gastroenteritis and dehydration.[21] A retrospective review found it was used commonly for this purpose, being administered in over 58% of cases. Its use reduced hospital admissions, but was also associated with higher rates of return visits to the emergency department. Furthermore, people who had initially received ondansetron were more likely to be admitted on the return visit than people who had not received the drug. However, this effect may simply be due to the agent being used more frequently in people who present with more severe illness. Its use was not found to mask serious diagnoses.[22]

Irritable bowel syndrome (IBS)

In a study of patients diagnosed as having IBS with diarrhea (IBS-D), ondansetron showed statistically significant effects on stool consistency, frequency, urgency and bloating, but not on pain scores.[23] This was confirmed in a later trial and meta-analysis[24] and is included in international guidelines.[25]

Special populations

Children

Ondansetron has rarely been studied in people under 4 years of age. As such, little data is available to guide dosage recommendations.[7]

Three open non-comparative studies have been conducted to assess the safety and efficacy of ondansetron in children receiving a variety of chemotherapy regimens.

Ondansetron was well tolerated and none of the patients experienced extrapyramidal symptoms.[26]

Adverse effects

Headache is the most common adverse effect.[7] A review of use for post-operative nausea and vomiting found that for every 36 people treated, one would experience headache, which could be severe.[27]

Constipation, diarrhea, and dizziness are other commonly reported side effects.[9] It is broken down by the hepatic cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system. Anecdotally, ototoxicity has also been reported if injected too quickly.[9]

QT prolongation

Use of ondansetron has been associated with prolongation of the QT interval, which can lead to a potentially fatal heart rhythm known as torsades de pointes. Although this may happen in any person with any formulation, the risk is most salient with the injectable (intravenous) form of the drug and increases with dose. The risk is also higher in people taking other medicines that prolong the QT interval, as well as in people with congenital long QT syndrome, congestive heart failure, and/or bradyarrhythmias. As such, single doses of injectable ondansetron should not exceed 16 mg at one time. (Oral dosing recommendations remain intact, including the recommendation of a single 24 mg oral dose when indicated.) Electrolyte imbalances should be corrected before the use of injectable ondansetron. People are cautioned to seek immediate medical care if symptoms such as irregular heartbeat/palpitations, shortness of breath, dizziness, or fainting occur while taking ondansetron.[28]

Overdose

No specific treatment is available for ondansetron overdose; people are managed with supportive measures. An antidote to ondansetron is not known.[7]

Pharmacology

Pharmacodynamics

Ondansetron is a highly

vomiting reflex. It is thought that ondansetron's antiemetic action is mediated mostly via antagonism of vagal afferents with a minor contribution from antagonism of central receptors.[29]

Pharmacokinetics

Ondansetron may have a degree of peripheral selectivity due to binding to P-glycoprotein and efflux out of the brain at the blood–brain barrier.[30][31][32]

History

A vial of Zofran 4 mg containing ondansetron for intravenous injection

Ondansetron (marketed under the brand name Zofran) was developed in the mid-1980s by

orodispersible form of the drug.[39]

Society and culture

Publication bias

In 1997, ondansetron was the subject of a

British Medical Journal. Researchers examined 84 trials, with 11,980 people receiving ondansetron, published between 1991 and September 1996. Intravenous ondansetron 4 mg versus placebo was investigated in 16 reports and three further reports which had been duplicated a total of six times. The number needed to treat (NNT) to prevent vomiting within 24 hours was 9.5, with 95% confidence interval 6.9 to 15, in the 16 nonduplicated reports. In the three duplicated reports, the NNT was significantly lower at 3.9 (3.3 to 4.8). When all 25 reports were combined, the apparent NNT improved to 4.9 (4.4 to 5.6). Inclusion of duplicate reports led to a 23% overestimation of ondansetron's antiemetic efficacy.[40]

In addition, the authors found the covert duplication of reports on ondansetron was not easy to detect, because of lack of cross-referencing between papers, and reports containing duplicate findings were cited in eight reviews of the drug.

Journal of the American Medical Association in 1999.[41]

Availability

Ondansetron is a

generic medication and is available in many countries under many brand names.[2]

References

  1. ^ "Atossa". MedicinesFAQ. 2022. Archived from the original on 28 August 2022. Retrieved 28 August 2022.
  2. ^ a b "Ondansetron international". Drugs.com. 2 September 2020. Archived from the original on 21 February 2014. Retrieved 2 February 2014.
  3. ^ "Ondansetron Use During Pregnancy". Drugs.com. 3 October 2019. Archived from the original on 18 September 2020. Retrieved 7 September 2020.
  4. ^ "Zofran Product and Consumer Medicine Information Licence". TGA eBS. Archived from the original on 29 August 2022. Retrieved 28 August 2022.
  5. ^ "Zofran Product information". Health Canada. 25 April 2012. Archived from the original on 29 August 2022. Retrieved 28 August 2022.
  6. ^ "Zofran Tablets 4 mg - Summary of Product Characteristics (SmPC)". (emc). 19 January 2022. Archived from the original on 29 August 2022. Retrieved 28 August 2022.
  7. ^ a b c d e "Zofran- ondansetron hydrochloride tablet, film coated". DailyMed. 24 June 2020. Archived from the original on 6 August 2020. Retrieved 7 September 2020.
  8. ^ "List of nationally authorised medicinal products : Active substance: ondansetron :Procedure no.: PSUSA/00002217/202102" (PDF). Ema.europa.eu. Retrieved 5 March 2022.
  9. ^ a b c d e f g h i "Ondansetron Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 3 May 2016. Retrieved 11 February 2017.
  10. S2CID 9334264
    .
  11. PMID 23877938
    .
  12. ISBN 978-1-60795-111-7. Archived
    from the original on 1 February 2016.
  13. ISBN 9783527607495. Archived
    from the original on 12 January 2023. Retrieved 25 August 2020.
  14. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  15. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  16. ^ "Ondansetron - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  17. ^ "Ondansetron hydrochloride injection". DailyMed. 19 October 2022. Archived from the original on 8 July 2023. Retrieved 8 July 2023.
  18. ^ Smith JA, Refuerzo JS, Ramin SM. "Treatment and outcome of nausea and vomiting of pregnancy". UpToDate. Archived from the original on 3 December 2013.
  19. PMID 33890993
    .
  20. S2CID 8718836. Archived
    from the original on 28 August 2021. Retrieved 4 November 2018.
  21. S2CID 13712069
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  26. PMID 1831631. Archived
    from the original on 8 July 2023. Retrieved 8 July 2023.
  27. S2CID 8049193
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  28. ^ US Food and Drug Administration. (2012). FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran). Retrieved from "FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran)". Food and Drug Administration. Archived from the original on 14 December 2012. Retrieved 29 November 2012.
  29. PMID 26578870
    .
  30. PMID 8647944
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  31. S2CID 211035717
    .
  32. S2CID 44405604
    .
  33. ^ US patent 4695578, Coates IH, Bell JA, Humber DC, Ewan GB, "1,2,3,9-tetrahydro-3-imidazol-1-ylmethyl-4H-carbazol-4-ones, composition containing them, and method of using them to treat neuronal 5HT function disturbances", issued 22 September 1987, assigned to Glaxo Group Limited 
  34. ^ US patent 4753789, Tyers MB, Coates IH, Humber DC, Ewan GB, Bell JA, "Method for treating nausea and vomiting", issued 28 June 1988, assigned to Glaxo Group Limited 
  35. ^ US patent 5578628, Tyers MB, Coates IH, Humber DC, Ewan GB, Bell JA, "Medicaments for the treatment of nausea and vomiting", issued 26 November 1996, assigned to Glaxo Group Limited 
  36. ^ "One Year Post-Pediatric Exclusivity Post-marketing Adverse Event Review: Drug Use Data Zofran" (PDF). Memorandum. U.S. Food and Drug Administration. 7 March 2006. Archived (PDF) from the original on 24 September 2015.
  37. ^ IHS. (2006). Generics firms line up to enter Zofran market. Retrieved from "Generics Firms Line Up to Enter Zofran Market". Archived from the original on 1 February 2014. Retrieved 20 January 2014.
  38. ^ "FDA Approves First Generic Ondansetron Tablets, Orally Disintegrating Tablets and Oral Solution" (Press release). U.S. Food and Drug Administration. 17 December 2006. Archived from the original on 18 June 2014.
  39. ^ "Sabia que um remédio para enjoo traz 90% dos royalties que a USP recebe? - Agência USP de Inovação" (in Brazilian Portuguese). Retrieved 6 October 2020.
  40. ^
    PMID 9310564
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  41. PMID 10568651
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