These Highlights Do Not Include All The Information Needed To Use Ondansetron Tablets Safely And Effectively. See Full Prescribing Information For Ondansetron Tablets

Ondansetron is 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 is also indicated for the prevention of postoperative nausea and/or vomiting.

• See full prescribing information for the recommended dosage in adults and pediatrics. (2)
• Patients with severe hepatic impairment: do not exceed a total daily dose of 8 mg. (2.2, 8.6)

Ondansetron Tablets USP, 4 mg (ondansetron hydrochloride USP dihydrate equivalent to 4 mg of ondansetron), are yellow, film coated oval convex tablets debossed with "TARO" on one side and "OND4" on the other side.

Ondansetron Tablets USP, 8 mg (ondansetron hydrochloride USP dihydrate equivalent to 8 mg of ondansetron), are white, film coated oval convex tablets debossed with "TARO" on one side and "OND8" on the other side.

Ondansetron Tablets USP, 24 mg (ondansetron hydrochloride USP dihydrate equivalent to 24 mg of ondansetron), are pink, film coated oval convex tablets debossed with "TARO" on one side and "OND24" on the other side.

Ondansetron is 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.

The active ingredient in ondansetron tablets, USP is ondansetron hydrochloride as the dihydrate, the racemic form of ondansetron and a selective blocking agent of the serotonin 5-HT₃ receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one, monohydrochloride, dihydrate. It has the following structural formula:

The empirical formula is C₁₈H₁₉N₃O∙HCl∙2H₂O, representing a molecular weight of 365.9.

Ondansetron HCl dihydrate is a white to off-white powder that is soluble in water and normal saline.

Each 4-mg ondansetron tablet for oral administration contains ondansetron HCl USP dihydrate equivalent to 4 mg of ondansetron. Each 8-mg ondansetron tablet for oral administration contains ondansetron HCl USP dihydrate equivalent to 8 mg of ondansetron. Each 24-mg ondansetron tablet for oral administration contains ondansetron HCl USP dihydrate equivalent to 24 mg of ondansetron. Each tablet also contains the inactive ingredients lactose, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, polyethylene glycol, pregelatinized starch, talc and titanium dioxide. In addition, the 4 mg also contains yellow iron oxide and the 24 mg also contains FD&C blue #2 aluminum lake and iron oxide red.

The safety and effectiveness of orally administered ondansetron 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)].

Additional information on the use of ondansetron in pediatric patients may be found in ondansetron injection prescribing information.

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.

Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in U.S.- and foreign-controlled clinical trials, for which there were subgroup analyses, 938 (19%) were aged 65 years and older.

No overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger subjects. A reduction in clearance and increase in elimination half-life were seen in patients older than 75 years compared with younger subjects [see Clinical Pharmacology (12.3)]. There were an insufficient number of patients older than 75 years of age and older in the clinical trials to permit safety or efficacy conclusions in this age-group. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dosage adjustment is needed in elderly patients.

Carcinogenic effects were not seen in 2-year studies in rats and mice with oral ondansetron doses up to 10 mg/kg per day and 30 mg/kg per day, respectively (approximately 4 and 6 times the maximum recommended human oral dose of 24 mg per day, based on body surface area).

Ondansetron was not mutagenic in standard tests for mutagenicity.

Oral administration of ondansetron up to 15 mg/kg per day (approximately 6 times the maximum recommended human oral dose of 24 mg per day, based on body surface area) did not affect fertility or general reproductive performance of male and female rats.

The most common adverse reactions in adults for the:

• prevention of chemotherapy-induced (greater than or equal to 5%) are: headache, malaise/fatigue, constipation, diarrhea. (6.1)
• prevention of radiation-induced nausea and vomiting (greater than or equal to 2%) are: headache, constipation, and diarrhea. (6.1)
• prevention of postoperative nausea and vomiting (greater than or equal to 9%) are: headache and hypoxia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

Animal studies have shown that ondansetron is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.

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

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

Ondansetron Tablets USP, 4 mg (ondansetron hydrochloride USP dihydrate equivalent to 4 mg of ondansetron), are yellow, film coated oval convex tablets debossed with "TARO" on one side and "OND4" on the other side.

Ondansetron Tablets USP, 8 mg (ondansetron hydrochloride USP dihydrate equivalent to 8 mg of ondansetron), are white, film coated oval convex tablets debossed with "TARO" on one side and "OND8" on the other side.

Ondansetron Tablets USP, 24 mg (ondansetron hydrochloride USP dihydrate equivalent to 24 mg of ondansetron), are pink, film coated oval convex tablets debossed with "TARO" on one side and "OND24" on the other side.

Ondansetron is a selective 5-HT₃ receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT₃ type 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-HT₃ receptors and initiate the vomiting reflex.

In healthy subjects, single intravenous doses of 0.15 mg/kg of ondansetron had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time. Multiday administration of ondansetron has been shown to slow colonic transit in healthy subjects. Ondansetron has no effect on plasma prolactin concentrations.

• Hypersensitivity reactions including anaphylaxis and bronchospasm: Discontinue ondansetron if suspected. Monitor and treat promptly per standard of care until signs and symptoms resolve. (5.1)
• QT interval prolongation and Torsade de Pointes: Avoid in patients with congenital long QT syndrome; monitor with electrocardiograms (ECGs) if concomitant electrolyte abnormalities, cardiac failure or arrhythmias, or use of other QT prolonging drugs. (5.2)
• Serotonin syndrome: Reported with 5-HT₃ receptor antagonists alone but particularly with concomitant use of serotonergic drugs. If such symptoms occur, discontinue ondansetron and initiate supportive treatment. If concomitant use of ondansetron with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome. (5.3)
• Masking of progressive ileus and/or gastric distention following abdominal surgery or chemotherapy-induced nausea and vomiting: Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction. (5.4)

Bottles: Store at 20˚ to 25˚C (68˚ to 77˚F) [see USP Controlled Room Temperature]. Protect from light. Dispense in tight, light-resistant container as defined in the USP.

Unit Dose Packs: Store at 20˚ to 25˚C (68˚ to 77˚F) [see USP Controlled Room Temperature]. Protect from light. Store blisters in cartons.

NDC 51672-4108-6

30 Tablets

Ondansetron

Tablets USP,

4 mg*

TARO

Rx only

Ondansetron is 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 is also indicated for the prevention of postoperative nausea and/or vomiting.

• See full prescribing information for the recommended dosage in adults and pediatrics. (2)
• Patients with severe hepatic impairment: do not exceed a total daily dose of 8 mg. (2.2, 8.6)

Ondansetron Tablets USP, 4 mg (ondansetron hydrochloride USP dihydrate equivalent to 4 mg of ondansetron), are yellow, film coated oval convex tablets debossed with "TARO" on one side and "OND4" on the other side.

Ondansetron Tablets USP, 8 mg (ondansetron hydrochloride USP dihydrate equivalent to 8 mg of ondansetron), are white, film coated oval convex tablets debossed with "TARO" on one side and "OND8" on the other side.

Ondansetron Tablets USP, 24 mg (ondansetron hydrochloride USP dihydrate equivalent to 24 mg of ondansetron), are pink, film coated oval convex tablets debossed with "TARO" on one side and "OND24" on the other side.

Ondansetron is 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.

The safety and effectiveness of orally administered ondansetron 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)].

Additional information on the use of ondansetron in pediatric patients may be found in ondansetron injection prescribing information.

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.

Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in U.S.- and foreign-controlled clinical trials, for which there were subgroup analyses, 938 (19%) were aged 65 years and older.

No overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger subjects. A reduction in clearance and increase in elimination half-life were seen in patients older than 75 years compared with younger subjects [see Clinical Pharmacology (12.3)]. There were an insufficient number of patients older than 75 years of age and older in the clinical trials to permit safety or efficacy conclusions in this age-group. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dosage adjustment is needed in elderly patients.

Carcinogenic effects were not seen in 2-year studies in rats and mice with oral ondansetron doses up to 10 mg/kg per day and 30 mg/kg per day, respectively (approximately 4 and 6 times the maximum recommended human oral dose of 24 mg per day, based on body surface area).

Ondansetron was not mutagenic in standard tests for mutagenicity.

Oral administration of ondansetron up to 15 mg/kg per day (approximately 6 times the maximum recommended human oral dose of 24 mg per day, based on body surface area) did not affect fertility or general reproductive performance of male and female rats.

The most common adverse reactions in adults for the:

• prevention of chemotherapy-induced (greater than or equal to 5%) are: headache, malaise/fatigue, constipation, diarrhea. (6.1)
• prevention of radiation-induced nausea and vomiting (greater than or equal to 2%) are: headache, constipation, and diarrhea. (6.1)
• prevention of postoperative nausea and vomiting (greater than or equal to 9%) are: headache and hypoxia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

The active ingredient in ondansetron tablets, USP is ondansetron hydrochloride as the dihydrate, the racemic form of ondansetron and a selective blocking agent of the serotonin 5-HT₃ receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one, monohydrochloride, dihydrate. It has the following structural formula:

The empirical formula is C₁₈H₁₉N₃O∙HCl∙2H₂O, representing a molecular weight of 365.9.

Ondansetron HCl dihydrate is a white to off-white powder that is soluble in water and normal saline.

Each 4-mg ondansetron tablet for oral administration contains ondansetron HCl USP dihydrate equivalent to 4 mg of ondansetron. Each 8-mg ondansetron tablet for oral administration contains ondansetron HCl USP dihydrate equivalent to 8 mg of ondansetron. Each 24-mg ondansetron tablet for oral administration contains ondansetron HCl USP dihydrate equivalent to 24 mg of ondansetron. Each tablet also contains the inactive ingredients lactose, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, polyethylene glycol, pregelatinized starch, talc and titanium dioxide. In addition, the 4 mg also contains yellow iron oxide and the 24 mg also contains FD&C blue #2 aluminum lake and iron oxide red.

Animal studies have shown that ondansetron is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.

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

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

Ondansetron Tablets USP, 4 mg (ondansetron hydrochloride USP dihydrate equivalent to 4 mg of ondansetron), are yellow, film coated oval convex tablets debossed with "TARO" on one side and "OND4" on the other side.

Ondansetron Tablets USP, 8 mg (ondansetron hydrochloride USP dihydrate equivalent to 8 mg of ondansetron), are white, film coated oval convex tablets debossed with "TARO" on one side and "OND8" on the other side.

Ondansetron Tablets USP, 24 mg (ondansetron hydrochloride USP dihydrate equivalent to 24 mg of ondansetron), are pink, film coated oval convex tablets debossed with "TARO" on one side and "OND24" on the other side.

Ondansetron is a selective 5-HT₃ receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT₃ type 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-HT₃ receptors and initiate the vomiting reflex.

In healthy subjects, single intravenous doses of 0.15 mg/kg of ondansetron had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time. Multiday administration of ondansetron has been shown to slow colonic transit in healthy subjects. Ondansetron has no effect on plasma prolactin concentrations.

• Hypersensitivity reactions including anaphylaxis and bronchospasm: Discontinue ondansetron if suspected. Monitor and treat promptly per standard of care until signs and symptoms resolve. (5.1)
• QT interval prolongation and Torsade de Pointes: Avoid in patients with congenital long QT syndrome; monitor with electrocardiograms (ECGs) if concomitant electrolyte abnormalities, cardiac failure or arrhythmias, or use of other QT prolonging drugs. (5.2)
• Serotonin syndrome: Reported with 5-HT₃ receptor antagonists alone but particularly with concomitant use of serotonergic drugs. If such symptoms occur, discontinue ondansetron and initiate supportive treatment. If concomitant use of ondansetron with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome. (5.3)
• Masking of progressive ileus and/or gastric distention following abdominal surgery or chemotherapy-induced nausea and vomiting: Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction. (5.4)

Bottles: Store at 20˚ to 25˚C (68˚ to 77˚F) [see USP Controlled Room Temperature]. Protect from light. Dispense in tight, light-resistant container as defined in the USP.

Unit Dose Packs: Store at 20˚ to 25˚C (68˚ to 77˚F) [see USP Controlled Room Temperature]. Protect from light. Store blisters in cartons.

NDC 51672-4108-6

30 Tablets

Ondansetron

Tablets USP,

4 mg*

TARO

Rx only