1 INDICATIONS AND USAGE Ondansetron Injection, USP is a 5-HT 3 receptor antagonist indicated for the prevention of: nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy.

( 1.1 ) postoperative nausea and/or vomiting.

( 1.2 ) 1.1 Prevention of Nausea and Vomiting Associated with Initial and Repeat Courses of Emetogenic Cancer Chemotherapy Ondansetron Injection, USP is indicated for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including high-dose cisplatin.

Ondansetron Injection, USP is approved for patients aged 6 months and older.

1.2 Prevention of Postoperative Nausea and/or Vomiting Ondansetron Injection, USP is indicated for the 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 in whom nausea and/or vomiting must be avoided postoperatively, Ondansetron Injection, USP is recommended even when the incidence of postoperative nausea and/or vomiting is low.

For patients who do not receive prophylactic Ondansetron Injection, USP and experience nausea and/or vomiting postoperatively, Ondansetron Injection, USP may be given to prevent further episodes.

Ondansetron Injection, USP is approved for patients aged 1 month and older.

6 ADVERSE REACTIONS Chemotherapy-Induced Nausea and Vomiting – The most common adverse reactions (≥7%) in adults are diarrhea, headache, and fever.

( 6.1 ) Postoperative Nausea and Vomiting – The most common adverse reaction (≥10%) which occurs at a higher frequency compared with placebo in adults is headache.

( 6.1 ) The most common adverse reaction (≥2%) which occurs at a higher frequency compared with placebo in pediatric patients aged 1 to 24 months is diarrhea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Athenex Pharmaceutical Division, LLC.

at 1-855-273-0154 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 clinical practice.

The following adverse reactions have been reported in clinical trials of adult patients treated with ondansetron, the active ingredient of intravenous ondansetron injection across a range of dosages.

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

Chemotherapy-induced Nausea and Vomiting Table 2.

Adverse Reactions Reported in >5% of Adult Patients Who Received Ondansetron at a Dosage of Three 0.15-mg/kg Doses Adverse Reaction Number of Adult Patients with Reaction Ondansetron Injection 0.15 mg/kg x 3 (n = 419) Metoclopramide (n = 156) Placebo (n = 34) Diarrhea 16% 44% 18% Headache 17% 7% 15% Fever 8% 5% 3% Cardiovascular: Rare cases of angina (chest pain), electrocardiographic alterations, hypotension, and tachycardia have been reported.

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.

Other: Rare cases of hypokalemia have been reported.

Postoperative Nausea and Vomiting The adverse reactions in Table 3 have been reported in ≥2% of adults receiving ondansetron at a dosage of 4 mg intravenous over 2 to 5 minutes in clinical trials.

Table 3.

Adverse Reactions Reported in ≥2% (and with Greater Frequency than the Placebo Group) of Adult Patients Receiving Ondansetron at a Dosage of 4 mg Intravenous over 2 to 5 Minutes a Adverse reactions: Rates of these reactions were not significantly different in the ondansetron and placebo groups.

b Patients were receiving multiple concomitant perioperative and postoperative medications.

Adverse Reaction a,b Ondansetron Injection 4 mg Intravenous (n = 547) Placebo (n = 547) Headache 92 (17%) 77 (14%) Drowsiness/sedation 44 (8%) 37 (7%) Injection site reaction 21 (4%) 18 (3%) Fever 10 (2%) 6 (1%) Cold sensation 9 (2%) 8 (1%) Pruritus 9 (2%) 3 (< 1%) Paresthesia 9 (2%) 2 (< 1%) Pediatric Use: Rates of adverse reactions were similar in both the ondansetron and placebo groups 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.

Diarrhea was seen more frequently in patients taking ondansetron injection (2%) compared with placebo (<1%) in the 1-month to 24-month age-group.

These patients were receiving multiple concomitant perioperative and postoperative medications.

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval 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.

The reactions 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/QTc interval prolongation, and ST segment depression), palpitations, and syncope.

Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT/QTc interval prolongation have been reported [see Warnings and Precautions ( 5.2 )] .

General Flushing.

Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylactic reactions, angioedema, bronchospasm, cardiopulmonary arrest, hypotension, laryngeal edema, laryngospasm, shock, shortness of breath, stridor) have also been reported.

A positive lymphocyte transformation test to ondansetron has been reported, which suggests immunologic sensitivity to ondansetron.

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.

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.

Transient dizziness during or shortly after intravenous infusion.

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.

Transient blurred vision, in some cases associated with abnormalities of accommodation, have also been reported.