FDA label 4e2e7072-cfc2-437b-e054-00144ff88e88

WARNINGS Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT 3 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. A causal relationship to therapy with ondansetron tablets 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 in 2 trials. These patients were receiving concurrent highly emetogenic cisplatin-based chemotherapy regimens (cisplatin dose ≥ 50 mg/m 2 ). Table 5. Principal Adverse Events in US Trials: Single Day Therapy With 24-mg Ondansetron tablets (Highly Emetogenic Chemotherapy) Event Ondansetron Ondansetron Ondansetron 24 mg q.d. 8 mg b.i.d. 32 mg q.d. n = 300 N = 124 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 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. Table 6. Principal Adverse Events in US Trials: 3 Days of Therapy With 8-mg Ondansetron tablets (Moderately Emetogenic Chemotherapy) Event Ondansetron 8 mg b.i.d. Ondansetron 8 mg t.i.d. Placebo n = 242 n = 415 n = 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%) Central Nervous System There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving ondansetron. Hepatic 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. 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. Integumentary Rash has occurred in approximately 1% of patients receiving ondansetron. Other 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 were unclear. Radiation-Induced Nausea and Vomiting The adverse events reported in patients receiving ondansetron tablets and concurrent radiotherapy were similar to those reported in patients receiving ondansetron tablets 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 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. Table 7. Frequency of Adverse Events From Controlled Studies With Ondansetron tablets (Postoperative Nausea and Vomiting) Adverse Event Ondansetron 16 mg Placebo (n = 550) (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. 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. Cardiovascular Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported. General 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. Hepatobiliary Liver enzyme abnormalities Lower Respiratory Hiccups Neurology: Oculogyric crisis, appearing alone, as well as with other dystonic reactions Skin Urticaria Special Senses 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.

<table width="590"> <caption> Table 5. Principal Adverse Events in US Trials: Single Day Therapy With 24-mg Ondansetron tablets (Highly Emetogenic Chemotherapy)</caption> <tbody> <tr> <td> Event</td> <td> Ondansetron </td> <td> Ondansetron </td> <td> Ondansetron</td> </tr> <tr> <td/> <td> 24 mg q.d.</td> <td> 8 mg b.i.d.</td> <td> 32 mg q.d.</td> </tr> <tr> <td/> <td> n = 300</td> <td> N = 124</td> <td> n = 117</td> </tr> <tr> <td>Headache</td> <td>33 (11%)</td> <td>16 (13%)</td> <td>17 (15%)</td> </tr> <tr> <td>Diarrhea</td> <td>13 (4%)</td> <td>9 (7%)</td> <td>3 (3%)</td> </tr> </tbody> </table>

<table width="631"> <caption> Table 6. Principal Adverse Events in US Trials: 3 Days of Therapy With 8-mg Ondansetron tablets (Moderately Emetogenic Chemotherapy)</caption> <tbody> <tr> <td> Event</td> <td> Ondansetron 8 mg b.i.d.</td> <td> Ondansetron 8 mg t.i.d.</td> <td> Placebo</td> </tr> <tr> <td/> <td> n = 242</td> <td> n = 415</td> <td> n = 262</td> </tr> <tr> <td>Headache</td> <td>58 (24%)</td> <td>113 (27%)</td> <td>34 (13%)</td> </tr> <tr> <td>Malaise/fatigue</td> <td>32 (13%)</td> <td>37 (9%)</td> <td>6 (2%)</td> </tr> <tr> <td>Constipation</td> <td>22 (9%)</td> <td>26 (6%)</td> <td>1 (&lt;1%)</td> </tr> <tr> <td>Diarrhea</td> <td>15 (6%)</td> <td>16 (4%)</td> <td>10 (4%)</td> </tr> <tr> <td>Dizziness</td> <td>13 (5%)</td> <td>18 (4%)</td> <td>12 (5%)</td> </tr> </tbody> </table>

<table width="590"> <caption> Table 7. Frequency of Adverse Events From Controlled Studies With Ondansetron tablets (Postoperative Nausea and Vomiting)</caption> <tbody> <tr> <td> Adverse Event</td> <td> Ondansetron 16 mg</td> <td> Placebo</td> </tr> <tr> <td/> <td> (n = 550)</td> <td> (n = 531)</td> </tr> <tr> <td>Wound problem</td> <td>152 (28%)</td> <td>162 (31%)</td> </tr> <tr> <td>Drowsiness/sedation</td> <td>112 (20%)</td> <td>122 (23%)</td> </tr> <tr> <td>Headache</td> <td>49 (9%)</td> <td>27 (5%)</td> </tr> <tr> <td>Hypoxia</td> <td>49 (9%)</td> <td>35 (7%)</td> </tr> <tr> <td>Pyrexia</td> <td>45 (8%)</td> <td>34 (6%)</td> </tr> <tr> <td>Dizziness</td> <td>36 (7%)</td> <td>34 (6%)</td> </tr> <tr> <td>Gynecological disorder</td> <td>36 (7%)</td> <td>33 (6%)</td> </tr> <tr> <td>Anxiety/agitation</td> <td>33 (6%)</td> <td>29 (5%)</td> </tr> <tr> <td>Bradycardia</td> <td>32 (6%)</td> <td>30 (6%)</td> </tr> <tr> <td>Shiver(s)</td> <td>28 (5%)</td> <td>30 (6%)</td> </tr> <tr> <td>Urinary retention</td> <td>28 (5%)</td> <td>18 (3%)</td> </tr> <tr> <td>Hypotension</td> <td>27 (5%)</td> <td>32 (6%)</td> </tr> <tr> <td>Pruritus</td> <td>27 (5%)</td> <td>20 (4%)</td> </tr> </tbody> </table>