Ondansetron (3 brand names, 3 dosage forms, 2 routes)
Available dosage forms: TABLET, ORALLY DISINTEGRATING, FILM, INJECTABLE.
Routes of administration: ORAL, INJECTION.
Brand Names
- ONDANSETRON
- ZOFRAN ODT
- ZUPLENZ
Indications and Usage
Ondansetron orally disintegrating tablets are indicated for the prevention of nausea and vomiting associated with: highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m 2 initial and repeat courses of moderately emetogenic cancer chemotherapy radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen Ondansetron orally disintegrating tablets also indicated for the prevention of postoperative nausea and/or vomiting.
Contraindications
Ondansetron orally disintegrating tablets are contraindicated in patients: known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any of the components of the formulation [see Adverse Reactions (6.2)] receiving concomitant apomorphine due to the risk of profound hypotension and loss of consciousness
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1)] QT Prolongation [see Warnings and Precautions (5.2)] Serotonin Syndrome [see Warnings and Precautions (5.3)] Myocardial Ischemia [see Warnings and Precautions (5.4)] Masking of Progressive Ileus and Gastric Distension [see Warnings and Precautions (5.5)]
Mechanism of Action
Ondansetron is a selective 5-HT 3receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT 3type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. It is not certain whether ondansetron’s antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine. In humans, urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion increases after cisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferents through the 5-HT 3receptors and initiate the vomiting reflex.
Overdosage
There is no specific antidote for ondansetron overdose. Patients should be managed with appropriate supportive therapy. In addition to the adverse reactions listed above, the following adverse reactions have been described in the setting of ondansetron overdose: “Sudden blindness” (amaurosis) of 2 to 3 minutes’ duration plus severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as a single dose. Hypotension (and faintness) occurred in a patient that took 48 mg of ondansetron tablets. Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed. In all instances, the adverse reactions resolved completely. Pediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of ondansetron (exceeding estimated ingestion of 5 mg per kg) in young children. Reported symptoms included somnolence, agitation, tachycardia, tachypnea, hypertension, flushing, mydriasis, diaphoresis, myoclonic movements, horizontal nystagmus, hyperreflexia, and seizure. Patients required supportive care, including intubation in some cases, with complete recovery without sequelae within 1 to 2 days.