Ondansetron

Ondansetron 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/m2
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 tablets are also indicated for the prevention of postoperative nausea and/or vomiting.

The recommended dosage regimens for adult and pediatric patients are described in Table 1 and Table 2, respectively.

Corresponding doses of ondansetron tablets, ondansetron orally disintegrating tablets and ondansetron oral solution may be used interchangeably.

Table 1: Adult Recommended Dosage Regimen for Prevention of Nausea and Vomiting
Indication
Dosage Regimen

Highly Emetogenic Cancer Chemotherapy
A single 24-mg dose administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin greater than or equal to 50 mg/m2.

Moderately Emetogenic Cancer Chemotherapy
8 mg administered 30 minutes before the start of chemotherapy, with a subsequent 8-mg dose 8 hours after the first dose.
Then administer 8 mg twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.

Radiotherapy
For total body irradiation: 8 mg administered 1 to 2 hours before each fraction of radiotherapy each day.
For single high-dosefraction radiotherapy to the abdomen: 8 mg administered 1 to 2 hours before radiotherapy, with subsequent 8-mg doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.
For daily fractionated radiotherapy to the abdomen: 8 mg administered 1 to 2 hours before radiotherapy, with subsequent 8-mg doses every 8 hours after the first dose for each day radiotherapy is given.

Postoperative
16 mg administered 1 hour before induction of anesthesia.

Table 2: Pediatric Recommended Dosage Regimen for Prevention of Nausea and Vomiting
Indication
Dosage Regimen

Moderately Emetogenic Cancer Chemotherapy
12 to 17 years of age: 8 mg administered 30 minutes before the start of chemotherapy, with a subsequent 8-mg dose 8 hours after the first dose.

Then administer 8 mg twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.

4 to 11 years of age: 4 mg administered 30 minutes before the start of chemotherapy, with a subsequent 4-mg dose 4 and 8 hours after the first dose.

Then administer 4 mg three times a day for 1 to 2 days after completion of chemotherapy.
The safety and effectiveness of orally administered ondansetron tablets have been established in pediatric patients 4 years and older for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy. Use of ondansetron in these age-groups is supported by evidence from adequate and well-controlled studies of ondansetron in adults with additional data from 3 open-label, uncontrolled, non-US trials in 182 pediatric patients aged 4 to 18 years with cancer who were given a variety of cisplatin or noncisplatin regimens [see Dosage and Administration (2.2), Clinical Studies (14.1)].
The safety and effectiveness of orally administered ondansetron have not been established in pediatric patients for:

prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy
prevention of nausea and vomiting associated with radiotherapy
prevention of postoperative nausea and/or vomiting

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.

Published epidemiological studies on the association between ondansetron use and major birth defects have reported inconsistent findings and have important methodological limitations that preclude conclusions about the safety of ondansetron use in pregnancy (see Data). Available postmarketing data have not identified a drug-associated risk of miscarriage or adverse maternal outcomes. Reproductive studies in rats and rabbits did not show evidence of harm to the fetus when ondansetron was administered during organogenesis at approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, based on body surface area (BSA), respectively (see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriages, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriages, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Ondansetron is unlikely to result in clinically relevant exposure in breastfed infants when administered intravenously at doses up to 4 mg/day to women who are breastfeeding. Available data from a lactation study involving pharmacokinetic samples from 80 lactating women and 20 infants indicate that ondansetron is present at low levels in human milk and in the plasma of breastfed infants. Both the estimated daily infant dose (DID) of ondansetron (0.002 mg/kg/day), and the relative infant dose (RID) (3.7%) were low (see Data)
In the same study, no adverse eff ects attributed to ondansetron were reported in infants exposed to ondansetron through breast milk. There are no data on the eff ects on ondansetron on milk production.