INDICATIONS AND USAGE • Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥ 50 mg/m 2 .

• Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

• Prevention of 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.

• Prevention of postoperative nausea and/or vomiting.

As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively.

In patients where nausea and/or vomiting must be avoided postoperatively, ondansetron tablets, USP are recommended even where the incidence of postoperative nausea and/or vomiting is low.

WARNINGS Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT receptor antagonists.

ADVERSE REACTIONS The following have been reported as adverse events in clinical trials of patients treated with ondansetron, the active ingredient of ondansetron tablets, USP.

A causal relationship to therapy with ondansetron tablets, USP have been unclear in many cases.

Chemotherapy-Induced Nausea and Vomiting The adverse events in Table 5 have been reported in ≥ 5% of adult patients receiving a single 24-mg ondansetron tablet, USP in 2 trials.

These patients were receiving concurrent highly emetogenic cisplatin-based chemotherapy regimens (cisplatin dose ≥ 50 mg/m ).

Event Ondansetron 24 mg q.d.n = 300 Ondansetron 8 mg b.i.d.n = 124 Ondansetron32 mg q.d.n = 117 Headache 33 (11%) 16 (13%) 17 (15%) Diarrhea 13 (4%) 9 (7%) 3 (3%) The adverse events in Table 6 have been reported in ≥ 5% of adults receiving either 8 mg of ondansetron tablets, USP 2 or 3 times a day for 3 days or placebo in 4 trials.

These patients were receiving concurrent moderately emetogenic chemotherapy, primarily cyclophosphamide-based regimens.

Event Ondansetron 8 mg b.i.d.n = 242 Ondansetron 8 mg t.i.d.n = 415 Placebon = 262 Headache 58 (24%) 113 (27%) 34 (13%) Malaise/fatigue 32 (13%) 37 (9%) 6 (2%) Constipation 22 (9%) 26 (6%) 1 (<1%) Diarrhea 15 (6%) 16 (4%) 10 (4%) Dizziness 13 (5%) 18 (4%) 12 (5%) There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving ondansetron.

In 723 patients receiving cyclophosphamide-based chemotherapy in US clinical trials, AST and/or ALT values have been reported to exceed twice the upper limit of normal in approximately 1% to 2% of patients receiving ondansetron tablets, USP.

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 cannot be clearly determined.

There have been reports of liver failure and death in patients with cancer receiving concurrent medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics.

The etiology of the liver failure is unclear.

Rash has occurred in approximately 1% of patients receiving ondansetron.

Rare cases of anaphylaxis, bronchospasm, tachycardia, angina (chest pain), hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures have been reported.

Except for bronchospasm and anaphylaxis, the relationship to ondansetron tablets, USP were unclear.

Radiation-Induced Nausea and Vomiting The adverse events reported in patients receiving ondansetron tablets, USP and concurrent radiotherapy were similar to those reported in patients receiving ondansetron tablets, USP and concurrent chemotherapy.

The most frequently reported adverse events were headache, constipation, and diarrhea.

Postoperative Nausea and Vomiting The adverse events in Table 7 have been reported in ≥ 5% of patients receiving ondansetron tablets, USP at a dosage of 16 mg orally in clinical trials.

With the exception of headache, rates of these events were not significantly different in the ondansetron and placebo groups.

These patients were receiving multiple concomitant perioperative and postoperative medications.

Adverse Event Ondansetron 16 mg(n = 550) Placebo(n = 531) Wound problem 152 (28%) 162 (31%) Drowsiness/sedation 112 (20%) 122 (23%) 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%) Bradycardia 32 (6%) 30 (6%) Shiver(s) 28 (5%) 30 (6%) Urinary retention 28 (5%) 18 (3%) Hypotension 27 (5%) 32 (6%) Pruritus 27 (5%) 20 (4%) Observed During Clinical Practice In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of oral formulations of ondansetron tablets, USP.

Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.

The events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to ondansetron tablets, USP.

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

Flushing.

Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis/anaphylactoid 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.

Liver enzyme abnormalities Hiccups Oculogyric crisis, appearing alone, as well as with other dystonic reactions Urticaria 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.