FDA label eaf9d55f-60bd-4db7-8919-3e2d7103a4e6

WARNINGS Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT 3 receptor antagonists.

ADVERSE REACTIONS Chemotherapy-Induced Nausea and Vomiting: The adverse events in Table 12 have been reported in adults receiving ondansetron at a dosage of three 0.15-mg/kg doses or as a single 32-mg dose in clinical trials. These patients were receiving concomitant chemotherapy, primarily cisplatin, and IV. fluids. Most were receiving a diuretic. Table 12. Principal Adverse Events in Comparative Trials in Adults Number of Adult Patients With Event Ondansetron Injection 0.15 mg/kg x 3 n = 419 Ondansetron Injection 32 mg x 1 n = 220 Metoclopramide n = 156 Placebo n = 34 Diarrhea 16% 8% 44% 18% Headache 17% 25% 7% 15% Fever 8% 7% 5% 3% Akathisia 0% 0% 6% 0% Acute dystonic reactions * 0% 0% 5% 0% * See Neurological. The following have been reported during controlled clinical trials: Cardiovascular: Rare cases of angina (chest pain), electrocardiographic alterations, hypotension, and tachycardia have been reported. In many cases, the relationship to ondansetron injection was unclear. Gastrointestinal: Constipation has been reported in 11% of chemotherapy patients receiving multiday ondansetron. Hepatic: In comparative trials in cisplatin chemotherapy patients with normal baseline values of aspartate transaminase (AST) and alanine transaminase (ALT), these enzymes have been reported to exceed twice the upper limit of normal in approximately 5% of patients. 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. Integumentary: Rash has occurred in approximately 1% of patients receiving ondansetron. Neurological: There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving ondansetron injection, and rare cases of grand mal seizure. The relationship to ondansetron was unclear. Other: Rare cases of hypokalemia have been reported. The relationship to ondansetron injection was unclear. Postoperative Nausea and Vomiting: The adverse events in Table 13 have been reported in ≥2% of adults receiving ondansetron at a dosage of 4 mg I.V. over 2 to 5 minutes in clinical trials. 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 13. Adverse Events in ≥ 2% of Adults Receiving Ondansetron at a Dosage of 4 mg I.V. over 2 to 5 Minutes in Clinical Trials Ondansetron Injection 4 mg I.V. n = 547 patients Placebo n = 547 patients Headache 92 (17%) 77 (14%) Dizziness 67 (12%) 88 (16%) Musculoskeletal pain 57 (10%) 59 (11%) Drowsiness/sedation 44 (8%) 37 (7%) Shivers 38 (7%) 39 (7%) Malaise/fatigue 25 (5%) 30 (5%) Injection site reaction 21 (4%) 18 (3%) Urinary retention 17 (3%) 15 (3%) Postoperative CO 2 -related pain * 12 (2%) 16 (3%) Chest pain (unspecified) 12 (2%) 15 (3%) Anxiety/agitation 11 (2%) 16 (3%) Dysuria 11 (2%) 9 (2%) Hypotension 10 (2%) 12 (2%) Fever 10 (2%) 6 (1%) Cold sensation 9 (2%) 8 (1%) Pruritus 9 (2%) 3 (<1%) Paresthesia 9 (2%) 2 (<1%) * Sites of pain included abdomen, stomach, joints, rib cage, shoulder. Pediatric Use: The adverse events in Table 14 were the most commonly reported adverse events in pediatric patients receiving ondansetron (a single 0.1-mg/kg dose for pediatric patients weighing 40 kg or less, or 4 mg for pediatric patients weighing more than 40 kg) administered intravenously over at least 30 seconds. 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 14. Frequency of Adverse Events From Controlled Studies in Pediatric Patients 2 to 12 Years of Age Adverse Event Ondansetron n = 755 Patients Placebo n = 731 Patients Wound problem 80 (11%) 86 (12%) Anxiety/agitation 49 (6%) 47 (6%) Headache 44 (6%) 43 (6%) Drowsiness/sedation 41 (5%) 56 (8%) Pyrexia 32 (4%) 41 (6%) The adverse events in Table 15 were the most commonly reported adverse events in pediatric patients, 1 month to 24 months of age, receiving a single 0.1-mg/kg I.V. dose of ondansetron. The incidence and type of adverse events were similar in both the ondansetron and placebo groups. These patients were receiving multiple concomitant perioperative and postoperative medications. Table 15. Frequency of Adverse Events (Greater Than or Equal to 2% in Either Treatment Group) in Pediatric Patients 1 Month to 24 Months of Age Adverse Event Ondansetron n = 336 Patients Placebo n = 334 Patients Pyrexia 14 (4%) 14 (4%) Bronchospasm 2 (< 1%) 6 (2%) Post-procedural pain 4 (1%) 6 (2%) Diarrhea 6 (2%) 3 (< 1%) Observed During Clinical Practice: In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of intravenous formulations of ondansetron. 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. Cardiovascular: Arrhythmias (including ventricular and supraventricular tachycardia, premature ventricular contractions, and atrial fibrillation), bradycardia, electrocardiographic alterations (including second-degree heart block, QT interval prolongation, and ST segment depression), palpitations, and syncope. General: Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis/anaphylactoid reactions, angioedema, bronchospasm, cardiopulmonary arrest, hypotension, laryngeal edema, laryngospasm, shock, shortness of breath, stridor) have also been reported. Hepatobiliary: Liver enzyme abnormalities have been reported. Liver failure and death have been reported in patients with cancer receiving concurrent medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is unclear. Local Reactions: Pain, redness, and burning at site of injection. Lower Respiratory: Hiccups Neurological: Oculogyric crisis, appearing alone, as well as with other dystonic reactions. Skin: Urticaria Special Senses: Transient dizziness during or shortly after I.V. infusion. Eye Disorders: Transient blurred vision, in some cases associated with abnormalities of accommodation. 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 ID="id_c2c55122-0ccf-4cf8-8d00-59d4069b5887" width="483"> <caption ID="id_ecbb2f2c-1954-4981-8e90-99aebd13a326">Table 12. Principal Adverse Events in Comparative Trials in Adults</caption> <col width="25.1%"/> <col width="22.8%"/> <col width="17.0%"/> <col width="20.5%"/> <col width="14.7%"/> <tfoot ID="id_7bb217f9-adc7-4af4-9eab-c8b3888e4743"> <tr> <td align="left" colspan="5" styleCode="Botrule" valign="top"/> </tr> </tfoot> <tbody> <tr ID="id_4b723843-9e1a-466e-9169-a3916ea7444a"> <td align="center" styleCode="Botrule Toprule Rrule Lrule" valign="top"/> <td align="center" colspan="4" styleCode="Botrule Rrule" valign="top"> <content styleCode="bold">Number of Adult Patients With Event</content> </td> </tr> <tr ID="id_e334f3e9-63db-4c50-ada5-aa83455bda5a"> <td align="center" styleCode="Lrule Botrule Rrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"> <paragraph> <content styleCode="bold">Ondansetron Injection</content> </paragraph> <paragraph> <content styleCode="bold">0.15 mg/kg x 3</content> </paragraph> <content styleCode="bold">n = 419</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <paragraph> <content styleCode="bold">Ondansetron Injection</content> </paragraph> <paragraph> <content styleCode="bold">32 mg x 1</content> </paragraph> <content styleCode="bold">n = 220</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <paragraph> </paragraph> <paragraph> <content styleCode="bold">Metoclopramide</content> </paragraph> <content styleCode="bold">n = 156</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <paragraph> </paragraph> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <content styleCode="bold">n = 34</content> </td> </tr> <tr ID="id_839ab42e-76f4-4f09-ae45-655519027973"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Diarrhea</td> <td align="center" styleCode="Botrule Rrule" valign="top">16%</td> <td align="center" styleCode="Botrule Rrule" valign="top">8%</td> <td align="center" styleCode="Botrule Rrule" valign="top">44%</td> <td align="center" styleCode="Botrule Rrule" valign="top">18%</td> </tr> <tr ID="id_1a64f1a7-753e-48cf-bb06-80f7d7c11008"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Headache</td> <td align="center" styleCode="Botrule Rrule" valign="top">17%</td> <td align="center" styleCode="Botrule Rrule" valign="top">25%</td> <td align="center" styleCode="Botrule Rrule" valign="top">7%</td> <td align="center" styleCode="Botrule Rrule" valign="top">15%</td> </tr> <tr ID="id_123857ad-cad7-4b6a-9393-65292f03452d"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Fever</td> <td align="center" styleCode="Botrule Rrule" valign="top">8%</td> <td align="center" styleCode="Botrule Rrule" valign="top">7%</td> <td align="center" styleCode="Botrule Rrule" valign="top">5%</td> <td align="center" styleCode="Botrule Rrule" valign="top">3%</td> </tr> <tr ID="id_7528f3d4-74a0-40b4-a6d0-282af93be6a5"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Akathisia</td> <td align="center" styleCode="Botrule Rrule" valign="top">0%</td> <td align="center" styleCode="Botrule Rrule" valign="top">0%</td> <td align="center" styleCode="Botrule Rrule" valign="top">6%</td> <td align="center" styleCode="Botrule Rrule" valign="top">0%</td> </tr> <tr ID="id_3bfa2fc5-ada6-4921-b681-4c8f6e6a7bd1"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Acute dystonic reactions^* </td> <td align="center" styleCode="Rrule" valign="top">0%</td> <td align="center" styleCode="Rrule" valign="top">0%</td> <td align="center" styleCode="Rrule" valign="top">5%</td> <td align="center" styleCode="Botrule Rrule" valign="top">0%</td> </tr> </tbody> </table>

<table ID="id_3ac538dc-2d7b-4532-ac09-358dcba4fe67" width="571"> <caption ID="id_35c718c1-ceb2-4d89-8f75-2146edfd0764">Table 13. Adverse Events in &#x2265; 2% of Adults Receiving Ondansetron at a Dosage of 4 mg I.V. over 2 to 5 Minutes in Clinical Trials</caption> <col width="43.3%"/> <col width="33.6%"/> <col width="23.1%"/> <tbody> <tr ID="id_c123ef58-65d2-4f17-9082-1db729a5cc5d"> <td align="center" styleCode="Botrule Toprule Rrule Lrule" valign="top"/> <td align="center" styleCode="Botrule Rrule" valign="top"> <paragraph> <content styleCode="bold">Ondansetron Injection</content> </paragraph> <paragraph> <content styleCode="bold">4 mg I.V.</content> </paragraph> <content styleCode="bold">n = 547 patients</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <paragraph> </paragraph> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <content styleCode="bold">n = 547 patients</content> </td> </tr> <tr ID="id_159fabaf-767a-4509-8cee-c4ae41a0cd53"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Headache</td> <td align="center" styleCode="Botrule Rrule" valign="top">92 (17%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">77 (14%)</td> </tr> <tr ID="id_1cc6b770-132d-40fe-920d-87fbc8e4bc19"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Dizziness</td> <td align="center" styleCode="Botrule Rrule" valign="top">67 (12%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">88 (16%)</td> </tr> <tr ID="id_44bc8d74-10d7-46cd-b030-8643b5c0b1c8"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Musculoskeletal pain</td> <td align="center" styleCode="Botrule Rrule" valign="top">57 (10%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">59 (11%)</td> </tr> <tr ID="id_c38d7d53-273f-4a33-853a-72b8c158b078"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Drowsiness/sedation</td> <td align="center" styleCode="Botrule Rrule" valign="top">44 (8%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">37 (7%)</td> </tr> <tr ID="id_e3158aa4-4c19-46fb-ae6f-694955d43242"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Shivers</td> <td align="center" styleCode="Botrule Rrule" valign="top">38 (7%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">39 (7%)</td> </tr> <tr ID="id_6881385d-e1f2-40b4-9477-32178145e4b3"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Malaise/fatigue</td> <td align="center" styleCode="Botrule Rrule" valign="top">25 (5%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">30 (5%)</td> </tr> <tr ID="id_8bcaa3c6-29a6-4334-9df2-d6b17ca5ab20"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Injection site reaction</td> <td align="center" styleCode="Botrule Rrule" valign="top">21 (4%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">18 (3%)</td> </tr> <tr ID="id_eef7aad0-bd4f-4ad4-bf44-d648961c085a"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Urinary retention</td> <td align="center" styleCode="Botrule Rrule" valign="top">17 (3%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">15 (3%)</td> </tr> <tr ID="id_4c96e1e5-c1a1-4065-b31a-580b3f79912f"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Postoperative CO₂-related pain^* </td> <td align="center" styleCode="Botrule Rrule" valign="top">12 (2%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">16 (3%)</td> </tr> <tr ID="id_179925ef-5d06-480e-a1af-a2b917980547"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Chest pain (unspecified)</td> <td align="center" styleCode="Botrule Rrule" valign="top">12 (2%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">15 (3%)</td> </tr> <tr ID="id_ef3e4b87-1ac9-45cd-bb53-8e5dbae350c2"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Anxiety/agitation</td> <td align="center" styleCode="Botrule Rrule" valign="top">11 (2%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">16 (3%)</td> </tr> <tr ID="id_ee6dee67-8027-4294-8cfc-5f8a770b112b"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Dysuria</td> <td align="center" styleCode="Botrule Rrule" valign="top">11 (2%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">9 (2%)</td> </tr> <tr ID="id_69babde6-83b6-4a11-aa34-eeda0d21cdc3"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Hypotension</td> <td align="center" styleCode="Botrule Rrule" valign="top">10 (2%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">12 (2%)</td> </tr> <tr ID="id_bdaabcaa-d604-41ad-88d3-072ec7cf9d89"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Fever</td> <td align="center" styleCode="Botrule Rrule" valign="top">10 (2%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">6 (1%)</td> </tr> <tr ID="id_d26a1b27-0d8b-449b-8167-619eb98b293b"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Cold sensation</td> <td align="center" styleCode="Botrule Rrule" valign="top">9 (2%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">8 (1%)</td> </tr> <tr ID="id_a9b9cd98-d7b7-4f91-a3b4-51d719397680"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Pruritus</td> <td align="center" styleCode="Botrule Rrule" valign="top">9 (2%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">3 (&lt;1%)</td> </tr> <tr ID="id_91f19bc1-f3d4-4d1e-870d-b0d47845a088"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Paresthesia</td> <td align="center" styleCode="Rrule" valign="top">9 (2%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">2 (&lt;1%)</td> </tr> </tbody> </table>

<table ID="id_8d37a48e-5a67-4a6e-b930-3bb1e76d6ea7" border="single" width="494"> <caption ID="id_bd968075-6002-4a10-9e84-524788060eee">Table 14. Frequency of Adverse Events From Controlled Studies in Pediatric Patients 2 to 12 Years of Age</caption> <col width="34.4%"/> <col width="37.9%"/> <col width="27.7%"/> <tbody> <tr ID="id_9093fdd5-a491-46ac-b340-b67f54163e7b"> <td align="left" styleCode="Botrule Toprule Rrule Lrule" valign="top"> <paragraph> </paragraph> <content styleCode="bold">Adverse Event</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <paragraph> <content styleCode="bold">Ondansetron</content> </paragraph> <content styleCode="bold">n = 755 Patients</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <content styleCode="bold">n = 731 Patients</content> </td> </tr> <tr ID="id_ee49d27f-e014-4576-bde1-4fece14121e9"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Wound problem</td> <td align="center" styleCode="Botrule Rrule" valign="top">80 (11%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">86 (12%)</td> </tr> <tr ID="id_c38c43f7-23b5-4bdf-88c3-b686911b695a"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Anxiety/agitation</td> <td align="center" styleCode="Botrule Rrule" valign="top">49 (6%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">47 (6%)</td> </tr> <tr ID="id_46789832-5f54-423c-a9d6-e4e6736bc7aa"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Headache</td> <td align="center" styleCode="Botrule Rrule" valign="top">44 (6%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">43 (6%)</td> </tr> <tr ID="id_6abf230d-7a74-40f5-95ea-7ee20fa1751f"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Drowsiness/sedation</td> <td align="center" styleCode="Botrule Rrule" valign="top">41 (5%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">56 (8%)</td> </tr> <tr ID="id_200ba06e-5c29-40da-aa86-2533107381fc"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Pyrexia</td> <td align="center" styleCode="Rrule" valign="top">32 (4%)</td> <td align="center" styleCode="Botrule Rrule" valign="top">41 (6%)</td> </tr> </tbody> </table>