Ondansetron

Ondansetron

Trade names	Zofran
Clinical data
Drug class	Anti-emetic
Uses	Prevention and treatment of chemo-induced, radiation induced nausea and vomiting, prevention of postoperative nausea and vomiting
Contraindications	Prolonged QT intervals, patients taking apomorphine
Routes of administration	PO, IM, IV
Dosage
Ondansetron Adult dosing 4 mg IV 2 mL of 2 mg/mL More information about this dose Weight kglbg Height cmminft Age yrmowk SexFM Indication  Indication: Postoperative nausea & vomiting Route  Route: IntravenousOral Preparation  Preparation: 2 mg/mL Maximum recommended daily dose 16 mg due to QT prolongation risk Reduced to 8 mg in patients with severe hepatic impairment Griddine A, Bush JS. Ondansetron. [Updated 2022 Sep 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499839/
Pharmacodynamics
Mechanism of action	5HT3 antagonist
Adverse effects	cardiac arrhythmias, cardiac arrest, constipation, headaches
Pharmacokinetics
Metabolism	Liver oxidation followed by glucuronidation and sulfate conjugation
Elimination half-life	4 hours
Physical and chemical data
Article quality
Editor rating	Comprehensive
User likes	0

Ondansetron is a 5HT₃ receptor antagonist that is commonly used for the treatment and prophylaxis of chemo induced nausea and vomiting, radiation induced nausea and vomiting, and postoperative nausea and vomiting.

Uses

• treatment and prevention of chemo-induced nausea and vomiting
• treatment and prevention of radiation induced nausea and vomiting
• Prevention of postoperative nausea and vomiting
• off-label use for the prevention of nausea and vomiting associated with pregnancy

Contraindications

Absolute contraindications

• Prolonged QT intervals
• Patients taking apomorphine as it can cause hypotension and loss of consciousness

Precautions

• Maximum dose of 16 mg IV due to risk of QT prolongation and arrhythmias
• Maximum dose decreased to 8 mg IV or 8 mg PO in severe hepatic impairment
• Dissolving tablets formulations contain phenylalanine which can lead to irreversible neurological damage in phenylketonuria (PKU)

Pharmacology

Pharmacodynamics

• Metabolized by CYP2D6, CYP3A4, CYP2E1, CYP1A2 initially with oxidation followed by glucuronide and sulfate conjugations
  • Many polymorphisms with four different phenotypes
    • Poor metabolizer (no functional allele)
    • Intermediate metabolizer (less activity than one functional allele)
    • Extensive metabolizer (two functional allele, most common phenotype)
    • Ultrarapid metabolizer (three functional allele)

Mechanism of action

• Antagonism of the 5HT₃ receptors
• Centrally, ondansetron antagonizes the 5HT₃ receptors in the area postrema
• Peripherally, ondansetron antagonizes the 5HT₃ receptors on the vagus nerve within the GI tracts which forms synapses within the nucleus tracts solitarius (a region also responsible for vomiting)
  • Predominant mechanism for its anti-emetic effect

Adverse effects

• Cardiac arrhythmia
• Cardiac arrest
• Constipation
• Headache
• dry mouth
• malaise
• drowsiness
• sedation
• pruritus
• transient elevation in liver function test

Pharmacokinetics

• Peak plasma concentration about 1.5 hours after an 8 mg PO dose

• Plasma half life is approximately 4 hours

Chemistry and formulation

Available in PO, intramuscular (IM), and intravenous (IV).

References

Zabirowicz, Eric S.; Gan, Tong J. (2019), "Pharmacology of Postoperative Nausea and Vomiting", Pharmacology and Physiology for Anesthesia, Elsevier, pp. 671–692, retrieved 2023-01-05

Griddine, Alexandria; Bush, Jeffrey S. (2022), "Ondansetron", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29763014, retrieved 2023-01-05