Generic Name

Ondansetron

Mechanism

Ondansetron is a potent, selective antagonist of the 5‑hydroxytryptamine type 3 (5‑HT₃) receptor.
• Binds to presynaptic 5‑HT₃ receptors on vagal afferents in the gastrointestinal tract, preventing serotonin‑mediated emetic signaling.
• Inhibits postsynaptic 5‑HT₃ receptors in the central nervous system (area postrema) and medullary vomiting center, thereby interrupting the emetic reflex.
• Result: rapid inhibition of nausea and vomiting with minimal metabolic or CNS side‑effects.

Pharmacokinetics

• Absorption: Oral bioavailability ≈ 50%; peak plasma concentrations reached 30‑60 min after PO dosing.
• Distribution: Highly protein‑bound (~70 %); crosses the placenta and breast milk.
• Metabolism: Primarily hepatic via CYP2D6 and CYP3A4; minor glucuronidation.
• Excretion: Renal (≈ 25 %) and fecal; steady‑state half‑life ≈ 4–6 h (IV) and 7–8 h (PO).
• Drug interactions:
• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) ↑ plasma levels.
• Concurrent serotonergic drugs (SSRIs, MAOIs) ↑ risk of serotonin syndrome.
• QT‑prolonging agents (e.g., amiodarone, macrolides) should be used cautiously.

Indications

• Chemotherapy‑induced nausea and vomiting (CINV):
• *Acute*: ≤ 24 h post‑chemotherapy.
• *Delayed*: > 24 h post‑chemotherapy.
• Radiation‑induced nausea for abdominal or pelvic irradiation.
• Post‑operative nausea and vomiting (PONV) prophylaxis and treatment.
• Surgery‑related nausea from IV anesthetics (e.g., propofol).
• Short‑course gastrointestinal disorders (e.g., gastroenteritis in pediatric patients).
• Pre‑operative antiemetic in patients with high risk of nausea.

Contraindications

• Absolute contraindications:
• Known hypersensitivity to ondansetron or other 5‑HT₃ antagonists.
• Relative contraindications / warnings:
• *Congenital* or *acquired* long‑QT syndrome; co‑administration with other QT‑prolonging drugs.
• Significant electrolyte disturbances (hypokalemia, hypomagnesemia).
• Severe hepatic impairment (CYP2D6/CYP3A4 dysfunction).
• Pregnant women in the first trimester (safety data limited).
• Use with caution in patients on serotonergic agents to mitigate serotonin syndrome risk.

Dosing

• IV formulation: 4 mg in a 20‑mL solution, infused over 2 min.
• PO tablets: 4 mg or 8 mg, depending on the indication.
• Adjustments: No dose adjustment for mild‑moderate renal impairment; caution in severe hepatic dysfunction.

Monitoring

• Cardiac: QTc interval (baseline & after 2‑3 doses if QT‑prolonging agents co‑administered).
• Electrolytes: Serum potassium and magnesium; correct deficiencies.
• Serotonin activity: Watch for clonus, hyperreflexia if on SSRIs/MAOIs.
• Kidney/ liver: Baseline function tests if chronic hepatic or renal disease; adjust if needed.

Clinical Pearls

• “Double‑dose bailout.” If a patient vomits within 30 min after a 4‑mg IV dose, give an immediate 2‑mg IV repeat and reassess; this keeps plasma levels adequate for most chemo regimens.
• “The 8‑mg trick.” For high‑risk patients (e.g., administering a 5‑FU + leucovorin regimen), pre‑emptively give 8 mg PO 30 min before chemotherapy; decreases acute CINV by ~50 %.
• “Avoid the ‘QT‑pitfall’.” In patients on amiodarone or macrolide antibiotics, obtain a baseline ECG or consider an alternative antiemetic (e.g., dexamethasone, hyoscine).
• “Know the metabolism.” Ondansetron is metabolized by CYP2D6; patients who are poor CYP2D6 metabolizers may have higher exposure leading to QT prolongation—use 1‑half dose in this subgroup.
• “Pediatric Suc‑creations.” For kids < 12 yrs, advise parents to keep the tablet in a sealed blister pack; avoid crushing as the tablet contains a disintegrant that can alter bioavailability in severe illness.

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