1 INDICATIONS AND USAGE Ondansetron is a 5-HT 3 receptor antagonist 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 .

( 1 ) nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

( 1 ) nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.

( 1 ) postoperative nausea and/or vomiting.

( 1 ) 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 are also indicated for the prevention of postoperative nausea and/or vomiting.

6 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 )] The most common adverse reactions in adults for the: prevention of chemotherapy-induced (≥ 5%) are: headache, malaise/fatigue, constipation, diarrhea.

( 6.1 ) prevention of radiation-induced nausea and vomiting (≥ 2%) are: headache, constipation, and diarrhea.

( 6.1 ) prevention of postoperative nausea and vomiting (≥ 9%) are: headache and hypoxia.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ipca at 1-888-472-2651 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse reactions have been reported in clinical trials of patients treated with ondansetron, the active ingredient of ondansetron tablets.

A causal relationship to therapy with ondansetron was unclear in many cases.

Prevention of Chemotherapy-Induced Nausea and Vomiting The most common adverse reactions reported in greater than or equal to 4% of 300 adults receiving a single 24-mg dose of ondansetron tablet orally in 2 trials for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy (cisplatin greater than or equal to 50 mg/m 2 ) were: headache (11%) and diarrhea (4%).

The most common adverse reactions reported in 4 trials in adults for the prevention of nausea and vomiting associated with moderately emetogenic chemotherapy (primarily cyclophosphamide-based regimens) are shown in Table 3.

Table 3: Most Common Adverse Reactions in Adults a for the Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Chemotherapy [Primarily Cyclophosphamide-based Regimens] a Reported in greater than or equal to 5% of patients treated with ondansetron and at a rate that exceeded placebo.

Adverse Reaction Ondansetron 8 mg Twice Daily (n = 242) Placebo (n = 262) Headache 58 (24%) 34 (13%) Malaise/Fatigue 32 (13%) 6 (2%) Constipation 22 (9%) 1 (< 1%) Diarrhea 15 (6%) 10 (4%) Less Common Adverse Reactions Central Nervous System: Extrapyramidal reactions (less than 1% of patients).

Hepatic: Aspartate transaminase (AST) and/or alanine transaminase (ALT) values exceeded twice the upper limit of normal in approximately 1% to 2% of 723 patients receiving ondansetron tablets and cyclophosphamide-based chemotherapy in US clinical trials.

The increases were transient and did not appear to be related to dose or duration of therapy.

On repeat exposure, similar transient elevations in transaminase values occurred in some courses, but symptomatic hepatic disease did not occur.

The role of cancer chemotherapy in these biochemical changes is unclear.

Liver failure and death has been reported in cancer patients receiving concurrent medications, including potentially hepatotoxic cytotoxic chemotherapy and antibiotics.

The etiology of the liver failure is unclear.

Integumentary: Rash (approximately 1% of patients).

Other (less than 2%): Anaphylaxis, bronchospasm, tachycardia, angina, hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures.

Except for bronchospasm and anaphylaxis, the relationship to ondansetron is unclear.

Prevention of Radiation-Induced Nausea and Vomiting The most common adverse reactions (greater than or equal to 2%) reported in patients receiving ondansetron tablets and concurrent radiotherapy were similar to those reported in patients receiving ondansetron tablets and concurrent chemotherapy and were headache, constipation, and diarrhea.

Prevention of Postoperative Nausea and/or Vomiting The most common adverse reactions reported in adults in trial(s) of prevention of postoperative nausea and vomiting are shown in Table 4.

In these trial(s), patients were receiving multiple concomitant perioperative and postoperative medications in both treatment groups.

Table 4: Most Common Adverse Reactions in Adults a for the Prevention of Postoperative Nausea and Vomiting a Reported in greater than or equal to 5% of patients treated with ondansetron and at a rate that exceeded placebo.

Ondansetron 16 mg as a Single Dose Placebo Adverse Reaction (n = 550) (n = 531) Headache 49 (9%) 27 (5%) Hypoxia 49 (9%) 35 (7%) Pyrexia 45 (8%) 34 (6%) Dizziness 36 (7%) 34 (6%) Gynecological disorder 36 (7%) 33 (6%) Anxiety/Agitation 33 (6%) 29 (5%) Urinary retention 28 (5%) 18 (3%) Pruritus 27 (5%) 20 (4%) In a crossover study with 25 subjects, headache was reported in 6 subjects administered ondansetron orally disintegrating tablets with water (24%) as compared with 2 subjects administered ondansetron orally disintegrating tablets without water (8%).

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ondansetron.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular Arrhythmias (including ventricular and supraventricular tachycardia, premature ventricular contractions, and atrial fibrillation), bradycardia, electrocardiographic alterations (including second-degree heart block, QT/QTc interval prolongation, and ST segment depression), palpitations, and syncope.

Rarely and predominantly with intravenous ondansetron, transient ECG changes, including QT interval prolongation have been reported.

Myocardial ischemia was reported predominately with intravenous administration [see Warnings and Precautions ( 5.4 )].

General Flushing : Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylactic reactions, angioedema, bronchospasm, shortness of breath, hypotension, laryngeal edema, stridor) have also been reported.

Laryngospasm, shock, and cardiopulmonary arrest have occurred during allergic reactions in patients receiving injectable ondansetron.

Hepatobiliary Liver enzyme abnormalities.

Lower Respiratory Hiccups.

Neurology Oculogyric crisis, appearing alone, as well as with other dystonic reactions.

Skin Urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Eye Disorders Cases of transient blindness, predominantly during intravenous administration, have been reported.

These cases of transient blindness were reported to resolve within a few minutes up to 48 hours.