ondansetron

5-HT3 receptor antagonist· Brands: Ondansetron, Ondemet, ZofranIMIVPO

Mechanism of action

Ondansetron is a selective antagonist of serotonin 5-HT3 receptors. It blocks these receptors both centrally in the chemoreceptor trigger zone of the area postrema and peripherally on vagal afferents in the gastrointestinal tract, thereby inhibiting the vomiting reflex.

Pharmacokinetics

Ondansetron is well absorbed after oral administration but undergoes extensive first-pass metabolism, giving a bioavailability of about 60%. It is metabolised by hepatic cytochrome P450 enzymes, mainly CYP3A4 and CYP2D6, and has a plasma half-life of approximately 3 to 4 hours. Metabolites are excreted in the urine.

Indications & dosing

Chemotherapy-induced nausea and vomiting

Give 30 minutes before chemotherapy. Follow with 8 mg PO every 12 hours for up to 5 days.

adult · IV: 8 mg once · Give 30 minutes before chemotherapy. Follow with 8 mg PO every 12 hours for up to 5 days.

Postoperative nausea and vomiting

Give at the end of surgery. Alternatively, 4 mg PO 1 hour before surgery.

adult · IV: 4 mg once · Give at the end of surgery. Alternatively, 4 mg PO 1 hour before surgery.

Radiotherapy-induced nausea and vomiting

Alternative route: IV 8 mg if oral not possible.

adult · PO: 8 mg 12 hourly · Alternative route: IV 8 mg if oral not possible.

Contraindications & precautions

Hypersensitivity to ondansetron or any component of the formulation · Includes anaphylaxis or other allergic reactions.
Concurrent use with apomorphine · Risk of profound hypotension and loss of consciousness.
Congenital long QT syndrome · May increase risk of QT prolongation and arrhythmias.
Use with caution in patients with cardiac conduction abnormalities or electrolyte disturbances, as ondansetron can prolong the QT interval.
Caution in patients with severe hepatic impairment; consider dose reduction.
Avoid in patients with hereditary fructose intolerance if the formulation contains sorbitol.

Adverse effects

Headache
Constipation
Flushing
QT prolongationserious
Serotonin syndromeserious
Anaphylaxisserious
Bronchospasmserious

Renal & hepatic adjustment

Hepatic impairment (moderate): Reduce dose; maximum 8 mg per day.
Hepatic impairment (severe): Reduce dose; maximum 8 mg per day.

Monitoring, pregnancy & toxicity

ECG (QTc interval) · At baseline and during treatment in patients at risk of QT prolongation
Signs of serotonin syndrome · During treatment, especially with other serotonergic drugs
Allergic reactions · During treatment
Pregnancy: May be used during pregnancy when clinically indicated; benefits usually outweigh risks. Data suggest a small increase in risk of orofacial clefts with first-trimester exposure, so specialist advice may be sought.
Toxicity: Dose-related QT prolongation; may be associated with arrhythmias · Monitor ECG, correct electrolytes; consider cardiac monitoring in overdose.
Toxicity: Serotonin syndrome (especially with other serotonergic drugs) · Supportive care; discontinue offending agents.
Toxicity: Overdose: drowsiness, headache, visual disturbances, hypotension · Supportive treatment; no specific antidote.

Clinical notes

Ondansetron is used to prevent and treat nausea and vomiting caused by chemotherapy, radiotherapy, and surgery. It may be given orally or intravenously. Common adverse effects include headache, constipation, and dizziness. Caution is needed in patients with prolonged QT interval as it may cause QT prolongation. Dose adjustments may be required in hepatic impairment.

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BNF; local formulary