Ondansetron (Zofran) | Medication Reference

Bedside Snapshot

Widely used antiemetic in ED/ICU for nausea and vomiting from many causes: gastroenteritis, medication-induced, post-operative, chemotherapy, pregnancy (with caution), and as part of multimodal antiemetic regimens.

Routes: IV, IM (off-label in some regions), PO tablets, orally disintegrating tablets (ODT), and oral film. IV is common in ED/ICU; ODT/PO often used once IV access is not required
Typical adult ED dose: 4 mg IV slow push, may repeat once after ~10–15 minutes if needed (institution-dependent), or 4–8 mg ODT/PO
Onset: IV within ~10–30 minutes; ODT/PO ~30 minutes
Duration: Antiemetic effect around 4–8 hours
Dose cap: Many protocols cap routine single IV doses at 4 mg due to QT risk
Key concerns: Dose- and concentration-dependent QTc prolongation and risk of torsades (especially with IV >16 mg, electrolyte derangements, or other QT-prolonging drugs); rare serotonin syndrome when combined with other serotonergic agents; constipation and headache are common
Clinical note: For most ED/ICU adults, 4 mg IV is sufficient; in refractory cases, repeat dosing or alternative/add-on agents should be considered rather than simply escalating ondansetron indefinitely

Brand & Generic Names

Generic Name: Ondansetron hydrochloride
Brand Names: Zofran, Zofran ODT, Zuplenz, generics

Medication Class

Selective 5-HT3 (serotonin) receptor antagonist; antiemetic

Pharmacology

Mechanism of Action:

Selectively blocks 5-HT3 (serotonin type 3) receptors located peripherally on vagal nerve terminals in the GI tract and centrally in the chemoreceptor trigger zone of the area postrema
Prevents serotonin-mediated activation of vagal afferents and central pathways involved in the vomiting reflex, reducing nausea and vomiting from chemotherapy, anesthesia, radiation, and many other triggers
Has minimal effect on dopamine receptors and therefore does not cause extrapyramidal side effects typical of dopamine-antagonist antiemetics

Pharmacokinetics:

Onset: IV ~10–30 minutes; peak effect within ~1–2 hours. Oral/ODT onset ~30 minutes; peak ~1.5–2 hours
Duration: Antiemetic effect typically 4–8 hours; may vary with etiology of nausea and repeated dosing
Bioavailability: Oral bioavailability ~60% due to first-pass metabolism, but clinical dosing is similar between IV and PO/ODT in many settings
Distribution: Volume of distribution ~2.5 L/kg; ~70–76% protein bound
Metabolism: Extensive hepatic metabolism via CYP3A4, CYP2D6, and CYP1A2 to inactive metabolites
Elimination: Primarily renal excretion of metabolites; elimination half-life ~3–6 hours in adults, prolonged in severe hepatic impairment

Indications

Symptomatic treatment of nausea and vomiting of multiple etiologies: gastroenteritis, medication-induced, post-operative, migraine-associated, and others
Adjunct treatment/prevention of chemotherapy-induced or radiation-induced nausea and vomiting (often using higher or scheduled dosing in oncology protocols)
Prevention or treatment of post-anesthesia nausea and vomiting in perioperative or PACU settings
Pregnancy-related nausea and vomiting (hyperemesis gravidarum) as a second-line agent when other therapies (e.g., doxylamine/pyridoxine) are inadequate; use is somewhat controversial and should follow OB guidance

Dosing & Administration

Available Forms:

IV solution: commonly 2 mg/mL in 2 mL or 4 mL vials (4 mg or 8 mg total). Given IV push or short infusion
Oral tablets: 4 mg, 8 mg; orally disintegrating tablets (ODT) 4 mg and 8 mg
Oral soluble film: 4 mg, 8 mg (regional availability dependent)
Oral solution: e.g., 4 mg/5 mL for pediatric or patients with swallowing difficulties

Adult Dosing (ED/ICU - Always follow local protocol):

Indication	Typical Dose & Route	Frequency	Notes
General ED nausea/vomiting (IV)	4 mg IV slow push (over 2–5 min)	May repeat once after 10–15 min if needed	Higher IV doses increase QT risk; many centers cap single IV doses at 4 mg
General ED nausea/vomiting (PO/ODT)	4–8 mg PO/ODT	Every 8 hours as needed	ODT useful for nausea/vomiting when swallowing is difficult
Post-op or post-anesthesia nausea (PACU/ICU)	4 mg IV once	May repeat q4–6h as needed, per protocol	Often used with other agents (e.g., dexamethasone, droperidol) in high-risk patients
Chemotherapy-induced N/V (simple ED dosing)	8–16 mg IV or PO	Given 30 min before chemo; may be repeated per oncology protocol	Total single IV dose should generally not exceed 16 mg due to QT risk
Pregnancy-related N/V (hyperemesis; after first-line therapy)	4–8 mg IV or PO/ODT	Every 8 hours as needed	Use per OB guidance; data on fetal safety are mixed but generally reassuring
Maximum typical adult daily dose	Up to 24 mg/day (IV/PO combined); QT risk increases with higher total daily doses, especially IV

Contraindications

Contraindications:

Known hypersensitivity to ondansetron or any component of the formulation (including rare cross-reactivity with other 5-HT3 antagonists)
Concurrent use with apomorphine (risk of profound hypotension and loss of consciousness)

Major Precautions:

QT prolongation and torsades risk: avoid or use cautiously in patients with congenital long QT syndrome, existing QT prolongation, uncompensated heart failure, bradyarrhythmias, or concomitant QT-prolonging drugs (e.g., certain antiarrhythmics, antipsychotics, macrolides)
Electrolyte abnormalities (hypokalemia, hypomagnesemia) increase torsades risk; correct prior to IV dosing when possible in high-risk patients
Hepatic impairment: in severe hepatic dysfunction, maximum total daily dose is typically reduced (e.g., ≤8 mg/day) due to decreased clearance
Serotonin syndrome: rare but reported when combined with other serotonergic agents (SSRIs, SNRIs, MAOIs, linezolid, etc.); monitor for agitation, clonus, hyperreflexia, hyperthermia in high-risk combinations
Use in pregnancy should follow OB and institutional guidance; although widely used off-label, many guidelines recommend first-line use of doxylamine/pyridoxine for N/V of pregnancy

QT Warning: Be especially cautious with IV ondansetron in patients who already have risk factors for QT prolongation (elderly, HF, electrolyte derangements, multiple QT-prolonging medications).

Adverse Effects

Common:

Headache
Constipation or, less commonly, diarrhea
Fatigue, malaise
Transient elevation in liver enzymes
Dizziness or lightheadedness

Serious:

QTc prolongation and torsades de pointes, especially with high-dose IV use, underlying QT risk, or multiple QT-prolonging drugs
Serotonin syndrome when combined with other serotonergic medications (rare)
Severe hypersensitivity reactions, including anaphylaxis and bronchospasm (rare)

Special Populations

Severe Hepatic Impairment:

Maximum total daily dose typically reduced to ≤8 mg/day
Prolonged elimination half-life increases drug exposure
Monitor for adverse effects and QT prolongation

Patients with QT Risk Factors:

Elderly patients, heart failure, bradyarrhythmias
Correct electrolytes (K⁺, Mg²⁺) before dosing when possible
Consider baseline ECG in high-risk patients
Limit total IV dose and avoid high-dose regimens

Pregnancy:

Use should follow OB and institutional guidance
Second-line agent for hyperemesis gravidarum after doxylamine/pyridoxine
Data on fetal safety are mixed but generally reassuring

Patients on Serotonergic Medications:

Monitor for signs of serotonin syndrome when combined with SSRIs, SNRIs, MAOIs, linezolid, etc.
Watch for agitation, clonus, hyperreflexia, hyperthermia

Monitoring

Clinical Monitoring:

Clinical response: reduction in nausea/vomiting episodes and improved tolerance of oral intake
Baseline and/or follow-up ECG in patients receiving IV ondansetron who have risk factors for QT prolongation or who are receiving high cumulative doses
Serum electrolytes (K⁺, Mg²⁺) in high-risk patients, especially if on diuretics, with GI losses, or with known QT prolongation
Monitoring for signs of serotonin syndrome when used with multiple serotonergic agents
Liver function tests in patients receiving repeated or high-dose therapy, particularly those with pre-existing liver disease

Clinical Pearls

Optimal Dosing: In most ED nausea cases, 4 mg IV or 4–8 mg ODT is sufficient; if there's no response, consider an alternate antiemetic mechanism (dopamine antagonist, antihistamine, anticholinergic) rather than just escalating ondansetron.

QT Caution: Be especially cautious with IV ondansetron in patients who already have risk factors for QT prolongation (elderly, HF, electrolyte derangements, multiple QT-prolonging meds).

Migraine-Associated Nausea: For migraine-associated nausea, pairing ondansetron with migraine-directed therapy (e.g., triptans, NSAIDs, anti-dopaminergic agents) is often more effective than ondansetron alone.

Hyperemesis Gravidarum: In hyperemesis gravidarum, ondansetron can be very effective as second-line therapy, but always loop in OB and be aware of evolving data and local practice patterns regarding fetal safety.

Routine Prophylaxis: When using ondansetron as 'routine' prophylaxis (e.g., for every opioid order), be aware of QT and constipation burden; targeted use is generally preferred over blanket use.

References

1. Lexicomp. (2025). Ondansetron: Drug information. Wolters Kluwer.
2. DrugBank Online. (2024). Ondansetron. https://go.drugbank.com/
3. U.S. Food and Drug Administration. (2012). Zofran (ondansetron): Drug safety communication – Abnormal heart rhythms may be associated with use. FDA Safety Announcement.
4. Gan, T. J., Meyer, T. A., Apfel, C. C., et al. (2007). Consensus guidelines for managing postoperative nausea and vomiting. Anesthesia & Analgesia, 105(6), 1615–1628. https://doi.org/10.1213/01.ane.0000295230.55439.f4
5. Carstairs, S. D. (2016). Ondansetron use in pregnancy and birth defects: A systematic review. Obstetrics & Gynecology, 127(5), 878–883. https://doi.org/10.1097/AOG.0000000000001388