Ondansetron

Hypersensitivity reactions (including anaphylaxis and bronchospasm) have been reported; discontinue if hypersensitivity occurs. Use with caution in patients allergic to other 5-HT3 receptor antagonists; cross-reactivity has been reported.

ECG changes, including dose-dependent QT interval prolongation, have been observed with ondansetron use. Cases of torsade de pointes have also been reported. Selective 5-HT3 antagonists, including ondansetron, have been associated with a number of dose-dependent increases in ECG intervals (eg, PR, QRS duration, QT/QTc, JT), usually occurring 1 to 2 hours after IV administration. Single doses >16 mg ondansetron IV are no longer recommended due to the potential for an increased risk of QT prolongation. In most patients, these changes are not clinically relevant; however, when used in conjunction with other agents that prolong these intervals or in those at risk for QT prolongation, arrhythmia may occur. When used with agents that prolong the QT interval (eg, Class I and III antiarrhythmics) or in patients with cardiovascular disease, clinically relevant QT interval prolongation may occur resulting in torsades de pointes. A number of trials have shown that 5-HT3 antagonists produce QT interval prolongation to variable degrees. Avoid ondansetron use in patients with congenital long QT syndrome. Use caution and monitor ECG in patients with other risk factors for QT prolongation (eg, medications known to prolong QT interval, electrolyte abnormalities [hypokalemia or hypomagnesemia], heart failure, bradyarrhythmias, and cumulative high-dose anthracycline therapy). Reduction in heart rate may also occur with the 5-HT3 antagonists. IV formulations of 5-HT3 antagonists have more associ

Serotonin syndrome has been reported with 5-HT3 receptor antagonists, predominantly when used in combination with other serotonergic agents (eg, SSRIs, SNRIs, MAOIs, mirtazapine, fentanyl, lithium, tramadol, and/or methylene blue). Some of the cases have been fatal. The majority of serotonin syndrome reports due to 5-HT3 receptor antagonist have occurred in a postanesthesia setting or in an infusion center. Serotonin syndrome has also been reported following overdose of ondansetron. Monitor patients for signs of serotonin syndrome, including mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis, dizziness, flushing, hyperthermia); neuromuscular changes (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination); gastrointestinal symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. If serotonin syndrome occurs, discontinue 5-HT3 receptor antagonist treatment and begin supportive management. Disease-related concerns:

Dose limitations are recommended for patients with severe hepatic impairment (Child-Pugh class C); use with caution in mild-moderate hepatic impairment; clearance is decreased and half-life increased in hepatic impairment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Orally-disintegrating tablets contain phenylalanine. Other warnings/precautions:

Antiemetics are most effective when used prophylactically (Roila 2016). If emesis occurs despite optimal antiemetic prophylaxis, re-evaluate emetic risk, disease, concurrent morbidities and medications to assure antiemetic regimen is optimized (ASCO [Hesketh 2016]).

Ondansetron does not stimulate gastric or intestinal peristalsis (do not use in place of nasogastric suction). Ondansetron may mask progressive ileus and/or gastric distension; monitor for decreased bowel activity.