Generic Name

Zofran

Mechanism

Zofran (ondansetron) is a highly selective blocker of 5‑hydroxytryptamine type 3 (5‑HT3) receptors.
• It antagonizes serotonin released from enterochromaffin cells in the GI tract and from presynaptic vagal afferents in the chemoreceptor trigger zone.
• By inhibiting postsynaptic 5‑HT3 receptors on vagal afferent neurons, it prevents the transmission of nausea and vomiting signals to the vomiting center in the medulla.
• The drug produces a rapid onset of action (30‑60 min) and a short half‑life (4‑5 h), suitable for acute anti‑emetic therapy.

Pharmacokinetics

• Absorption: Oral bioavailability 60‑90 %; peak plasma concentration 30–60 min. IV bioavailability 100 %.
• Distribution: Plasma protein binding ~20 %; Vd ≈ 3 L/kg.
• Metabolism: Primarily via CYP3A4/2C9‑mediated N‑oxidation and glucuronidation.
• Elimination: Renally excreted (~60 %) and hepatically eliminated. Half‑life 4‑5 h.
• Special populations: Clearance ↓ in severe renal impairment; caution in hepatic disease. No routine dose adjustment for mild‑moderate renal or hepatic dysfunction.

Indications

• Prevention of acute chemotherapy‑induced nausea and vomiting (CINV) for moderate‑to‑high‑risk regimens.
• Prevention of post‑operative nausea and vomiting (PONV).
• Prevention of nausea/vomiting during radiation therapy or radiation‑plus‑chemotherapy.
• Short‑term treatment of acute non‑chemotherapy nausea/vomiting in hospitalized patients.

Contraindications

• Known hypersensitivity to *ondansetron* or any excipient.
• QTc prolongation risk: contraindicated in congenital long QT syndrome or severe QTc (>450 ms in men, >460 ms in women).
• Caution with drugs that prolong QTc (e.g., amiodarone, macrolides, fluoroquinolones).
• Pregnancy: Use only if benefits outweigh risks; classified B in third trimester.
• Pediatric: FDA label limited to 12 months–12 years for chemotherapy anti‑emesis; use cautiously in infants <12 months.
• Liver disease: Monitor liver function; rare hepatotoxicity reported.

Dosing

• Infusion: Dilute in 100 mL normal saline; administer over ≥30 s; avoid rapid push.

Adverse Effects

Common (≈ > 1 %)
• Headache
• Dizziness
• Constipation
• Fatigue
• Transient elevation of aminotransferases

Serious
• QTc prolongation → torsades de pointes, syncope, fatal arrhythmia
• Hypersensitivity reactions (rash, pruritus, angioedema)
• Hepatotoxicity (rare, cholestatic pattern)
• Seizures, neutropenia, thrombotic microangiopathy (extremely rare)

Monitoring

• ECG: Baseline and repeat if patient is on other QTc‑prolonging agents.
• Liver function tests (LFTs): Baseline and periodically in hepatic patients or after >2 weeks of therapy.
• Renal function: Serum creatinine/CrCl before initiation and as clinically indicated.
• Observation for allergic reaction: First 30‑60 min after IV dosing.
• Pediatric: Watch for dizziness or light‑headedness after dosing.

Clinical Pearls

• Triple‑agent prophylaxis: For highly emetogenic chemotherapy, combine ondansetron with dexamethasone and an NK1 antagonist; monotherapy is sufficient for moderate‑to‑low risk regimens.
• Optimal timing: Administer ondansetron 30 min before chemotherapy or anesthesia; avoid giving within 30 min post‑procedure to reduce nausea breakthrough.
• Slow infusion: Rapid IV push (65 and concurrent QTc‑prolonging drugs pose higher arrhythmia risk; consider baseline ECG and close observation.

--
• *End of drug card – for quick reference by medical students, residents, and practicing clinicians.*