Generic Name

Zofran ODT

Mechanism

• Competitive antagonist at peripheral and central 5‑HT3 receptors
• *Peripheral*: blocks receptors on vagal afferent nerves in the gut, preventing emetic signaling.
• *Central*: antagonizes receptors in the chemoreceptor trigger zone (CTZ) of the medulla oblongata, inhibiting nausea/vomiting reflex.
• Inhibition of the serotonin surge that occurs after cytotoxic therapy, surgery, or motion stimulus.
• Results in a rapid reduction of nausea and vomiting without central nervous system depression.

Pharmacokinetics

• Absorption: Rapid, with peak plasma concentrations (Tmax) at ~2–3 h for tablets; ODT may reach peak slightly earlier due to faster dissolution.
• Bioavailability: 65–70 % after oral administration; unaffected by food.
• Distribution: Volume of distribution ≈ 10 L; highly protein‑bound (~90 %).
• Metabolism: Primarily hepatic via CYP1A2 and CYP3A4; minor role of CYP2D6.
• Elimination: Renally excreted; 30–40 % unchanged, 60–70 % as metabolites.
• Half‑life: ~3.5 h (range 3–4 h).
• Drug interactions: Moderately potent CYP1A2 inhibitor—use with caution when co‑administered with substrates (e.g., clozapine, carbamazepine).

Indications

• Chemotherapy‑induced nausea and vomiting (CINV):
• *Highly emetogenic* regimens (e.g., cisplatin).
• *Moderately emetogenic* regimens (e.g., anthracycline‑taxane).
• Post‑operative nausea and vomiting (PONV): When combined with dexamethasone or NK1 antagonists.
• Radiation‑induced nausea in pelvic or head‑and‑neck fields.
• Acute migraine‑related nausea (off‑label).
• Motion sickness (limited evidence, off‑label).

Contraindications

• Contraindications:
• Known hypersensitivity to ondansetron or any excipients.
• Pre‑existing congenital long‑QT syndrome.
• Warnings:
• QT prolongation / torsades de pointes – risk elevated with concurrent use of other QT‑prolonging drugs (e.g., haloperidol, cisapride, cisapride, citalopram).
• Serotonin syndrome – caution when combined with agents that increase serotonin (e.g., SSRIs, SNRIs, MAOIs).
• Seizure risk – rare in patients with pre‑existing seizure disorder when overdosed.

Dosing

• Timing: Administer within 30 min before chemotherapy or 60 min before surgery.
• Oral Solution: May be used for patients who cannot swallow tablets.

Adverse Effects

Common (≤10 %)
• Headache
• Dizziness
• Constipation or diarrhea
• Blurred vision
• Mild rash or pruritus

Serious (≤1 %)
• QT prolongation → torsades de pointes, ventricular arrhythmia
• Serotonin syndrome (hypercervical rigidity, tremor, hyperthermia) when combined with serotonergic drugs
• Seizures in predisposed individuals
• Neurotoxicity: rare cases of encephalopathy or neuropathy
• Allergic reactions: urticaria, angioedema, anaphylaxis
• Hypotension: rarely symptomatic bradycardia or low blood pressure

Monitoring

• Baseline EKG if QT prolongation risk factors present.
• Serial EKGs when using multiple QT‑prolonging agents or high‑risk patients.
• Serotonergic drug combinations: monitor for signs of serotonin syndrome.
• Renal/hepatic function: adjust dosing if necessary.
• Vital signs: watch for hypotension in septic or hypovolemic patients.

Clinical Pearls

• Best Timing is Key: Give Zofran ODT 30 min prior to chemotherapy or anesthesia for optimal protection.
• OTD Advantage: Ideal when patients are nauseated enough to avoid swallowing tablets; dissolves in 80 %.
• QT Risk in Polypharmacy: In patients on citalopram, haloperidol, or ondansetron concurrently, consider a lower dose (4 mg) or add a short‑acting antipsychotic for breakthrough nausea.
• Renal Impairment: Ondansetron clearance is modestly reduced; in CrCl < 30 mL/min, monitor for accumulation but no formal dose reduction is required.
• Pediatric Dosing Simplified: Weight‑based 0.1 mg/kg, with a 4 mg ceiling; 0.2 mg/kg if high‑risk regimen.
• Serotonin Syndrome Alert: If patient on MAO‑I or SSRI, discontinue ondansetron or switch to a different antiemetic.
• Storage: Keep at room temperature, protect from moisture; shelf life 36 months after manufacture.

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• Zofran ODT remains a cornerstone antiemetic for chemotherapeutic, peri‑operative, and radiation‑induced nausea. Its rapid action, ease of use, and well‑characterized safety profile make it a go‑to option for clinicians seeking reliable prophylaxis of nausea and vomiting.