Antiemetic
Ondansetron (Zofran)
Also called Zofran
Indications
- Prevention of postoperative nausea and vomiting, and treatment when no 5-HT3 antagonist was given as prophylaxis
- Prevention of chemotherapy-induced nausea and vomiting, and of radiotherapy-induced nausea (oral)
- Nausea and vomiting from opioids, gastroenteritis or other causes in the ED and ICU (off-label)
- Nausea and vomiting of pregnancy when first-line drugs fail (off-label)
- Spinal-induced hypotension and bradycardia at cesarean delivery (off-label)
Dosing
| Where | Dose |
|---|---|
| Other common pushes | Ondansetron: 4 mg IV; QT caution |
| Antiemetics | Ondansetron: 5-HT₃ antagonist. 4 mg IV over 2–5 min or IM (PONV, end of surgery); chemo 8 mg or 0.15 mg/kg, max 16 mg IV; QT, constipation |
On the quick cards
- Ondansetron (Zofran)EMS Field Drugs: Analgesia and comfort: antiemetic
- Other common pushesPush and Emergency Meds: Analgesia, antiemetics, steroids, diuretics, TXA
- AntiemeticsPush and Emergency Meds: Class, typical adult dose and the caution that matters
Mechanism of action
Ondansetron is a selective, competitive antagonist of the 5-HT3 receptor, a pentameric ligand-gated cation channel and the only ionotropic serotonin receptor. Chemotherapy, surgery and gut distension release serotonin from enterochromaffin cells; it opens 5-HT3 channels on vagal afferents, which depolarize and signal the nucleus tractus solitarius and the chemoreceptor trigger zone in the area postrema. Blocking these receptors peripherally and centrally interrupts the vomiting reflex. It does not block dopamine receptors, so it causes no extrapyramidal effects.
Pharmacology
- GI: prevents vomiting more reliably than nausea (Tramèr 1997); repeated doses slow colonic transit and constipate (label)
- Cardiovascular: dose-related QTc prolongation by hERG block, 5.6 ms after 8 mg vs 19.5 ms after 32 mg IV (label); blunts the Bezold–Jarisch reflex
- CNS: headache in about 17%, dizziness; little sedation
- Other: transient transaminase rises
Pharmacokinetics
| Onset | Minutes IV; for PONV prophylaxis it is given near the end of surgery (Gan 2020) |
|---|---|
| Peak | 10 min after an IV infusion; 41 min after IM injection (label) |
| Half-life | 3.5–4 h in younger adults; 4.7–5.5 h over 60 (label) |
| Distribution | Vd about 1.9 L/kg; log P 1.9–2.4; enters red cells |
| Protein binding | 70–76% |
| Metabolism | Liver: hydroxylation, mainly by CYP3A4 with CYP1A2 and CYP2D6, then glucuronide or sulfate conjugation |
| Elimination | About 5% unchanged in urine |
| Organ failure | Child-Pugh C: half-life about 20 h, maximum 8 mg/day; no renal dose change |
| Bioavailability | Oral about 56% |
| Pharmacogenomics | CYP2D6 ultrarapid metabolizers respond less; CPIC 2017 suggests granisetron instead |
Chemistry
- A carbazolone with a 2-methylimidazole side chain; its indole-containing carbazole echoes serotonin's indole
- Racemic (one chiral center at C3); both enantiomers block 5-HT3 receptors, the R form more potently in some tissues
- Weak base, pKa 7.4 (imidazole), so about half ionized at body pH; the hydrochloride dihydrate is water-soluble but precipitates in alkaline solutions (label)
- Injection: 2 mg/mL, pH 3.3–4.0; multi-dose vials add parabens; protect from light; push over at least 30 s, preferably 2–5 min
Adverse effects and cautions
In the one-pagers
- Toxins, Stings and Anaphylaxis in the FieldHidden or delayed drug toxicity: Loperamide, high dose: Self-treated withdrawal; wide QRS, long QT, polymorphic VT: Pads; torsades: magnesium 1-2 g IV; no ondansetron
- Abdominal, GI Bleeding, GU and Dialysis EmergenciesEvery abdomen: first steps: Treat pain: analgesia does not hide the diagnosis (Merck). Fentanyl and ondansetron doses: ems-pharmacology. Ketorolac 15 mg IV or 30 mg IM, not with hypotension, kidney disease, peptic ulcer or pregnancy (NASEMSO).
- Common EMS MedicationsPain, sedation, nausea and bleeding: Ondansetron, 5-HT3 antagonist: Nausea, vomiting: 4 mg IV/IM or ODT: Long QT, apomorphine use
- Obstetric EmergenciesAmniotic fluid embolism: A-OK (atropine, ondansetron, ketorolac) rests on case reports; AHA 2025 advises against atropine without bradycardia, and an expert panel (Pacheco 2026) advises against routine use.
- Rhythm GalleryVentricular rhythms and wide-complex tachycardia: Torsades is polymorphic VT twisting around the baseline on a long QT, typically started by a short–long–short sequence. Risk rises with QTc over 500 ms, female sex, bradycardia, low K⁺ or Mg²⁺, heart failure and QT drugs (class IA and III antiarrhythmics, haloperidol, ondansetron, macrolides, fluoroquinolones, methadone). Sustained polymorphic VT g
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Sources
- FDA label: ondansetron injection (2022)
- Gan 2020 (PONV consensus)
- CPIC 2017 (CYP2D6 and ondansetron)
- Tramèr 1997 (PONV efficacy)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.