Ondansetron

ONDANSETRON- ondansetron hydrochloride injection
Fosun Pharma USA Inc.

1 INDICATIONS AND USAGE

1.1 Prevention of Nausea and Vomiting Associated With Initial and Repeat Courses of Emetogenic Cancer Chemotherapy

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

1.2 Prevention of Postoperative Nausea and/or Vomiting

Ondansetron Injection 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 is recommended even when the incidence of postoperative nausea and/or vomiting is low. For patients who do not receive prophylactic Ondansetron Injection and experience nausea and/or vomiting postoperatively, Ondansetron Injection may be given to prevent further episodes.

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

2 DOSAGE AND ADMINISTRATION

2.1 Prevention of Nausea and Vomiting Associated With Initial and Repeat Courses of Emetogenic Chemotherapy

Important Preparation Instructions
• Dilution of ondansetron injection in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection is required before administration to adult and pediatric patients for the prevention of nausea and vomiting associated with emetogenic chemotherapy.

For pediatric patients between 6 months and 1 year of age and/or 10 kg or less:
Depending on the fluid needs of the patient, ondansetron injection may be diluted in 10 to 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection.

• Occasionally, ondansetron precipitates at the stopper/vial interface in vials stored upright. Potency and safety are not affected. If a precipitate is observed, resolubilize by shaking the vial vigorously.

• Do not mix ondansetron injection with solutions for which physical and chemical compatibility has not been established. In particular, this applies to alkaline solutions as a precipitate may form.

• Inspect the diluted ondansetron injection solution for particulate matter and discoloration before administration; discard if present.

• Storage: After dilution, do not use beyond 24 hours. Although ondansetron injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain preservative.

• Compatibility: Ondansetron injection is compatible and stable at room temperature under normal lighting conditions for 48 hours after dilution with the following intravenous fluids: 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, and 3% Sodium Chloride Injection.

Dosage and Administration
The recommended dosage for adult and pediatric patients 6 months of age and older for prevention of nausea and vomiting associated with emetogenic chemotherapy is 0.15-mg/kg per dose for 3 doses (maximum of 16 mg per dose).

Caution: Dilution of ondansetron injection is required in adult and pediatric patients prior to administration.

Infuse intravenously over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy and then repeat 4 and 8 hours after the first dose.

2.2 Prevention of Postoperative Nausea and Vomiting

Important Preparation Instructions
• Dilution of ondansetron injection is not required before administration to adult and pediatric patients.

• Inspect ondansetron injection visually for particulate matter and discoloration before administration; discard if present.

Dosage and Administration
The recommended dose and administration instructions for adult and pediatric patients 1 month of age and older for prevention of postoperative nausea and vomiting are shown in Table 1. Table 1: Recommended Dose and Administration of Ondansetron Injection for Prevention of Postoperative Nausea and Vomiting

Population	Recommended Single Dose	Administration Instructions	Timing of Administration
Adults and pediatric patients older than 12 years of age	4 mg a	May be administered intravenously or intramuscularly: Intravenously: infuse undiluted syringe contents (4 mg) over at least 30 seconds and preferably longer (over 2 to 5 minutes). Intramuscularly: inject undiluted syringe contents (4 mg).	Administer immediately before induction of anesthesia, or postoperatively if the patient did not receive prophylactic antiemetics and experiences nausea and/or vomiting occurring within 2 hours after surgery b,c
Pediatric patients 1 month to 12 years and more than 40 kg	4 mg	Infuse intravenously over at least 30 seconds and preferably longer (over 2 to 5 minutes).
Pediatric patients 1 month to 12 years and 40 kg or less	0.1 mg/kg	Infuse intravenously over at least 30 seconds and preferably longer (over 2 to 5 minutes).

^a Few patients above 80 kg have been studied.

^b Administration of a second intravenous dose of 4 mg ondansetron postoperatively in adult patients who received a 4 mg prophylactic dose does not provide additional control of nausea and vomiting [see Clinical Studies (14.3)].

^c For pediatric patients (1 month to 12 years) prevention of nausea and vomiting was only studied in patients who had not received prophylactic ondansetron.

2.3 Dosage Adjustment for Patients With Hepatic Impairment

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), a single maximal daily dose of 8 mg infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron in these patients [see Use in Specific Populations (8.6)].

3 DOSAGE FORMS AND STRENGTHS

Ondansetron Injection, USP 2 mg per mL is a clear, colorless, nonpyrogenic, sterile solution available as a 2 mL single-dose vial and 20 mL multi-dose vial.

4 CONTRAINDICATIONS

Ondansetron injection is contraindicated for patients known to have hypersensitivity (e.g., anaphylaxis) to this product or any of its components. Anaphylactic reactions have been reported in patients taking ondansetron [see Adverse Reactions (6.2)].

The concomitant use of apomorphine with ondansetron is contraindicated based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron.

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported in patients who have exhibited hypersensitivity to other selective 5-HT ₃ receptor antagonists.

5.2 QT Prolongation

Ondansetron prolongs the QT interval in a dose-dependent manner [see Clinical Pharmacology (12.2)]. In addition, postmarketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ondansetron injection in patients with congenital long QT syndrome. Electrocardiogram (ECG) monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or patients taking other medicinal products that lead to QT prolongation.

5.3 Serotonin Syndrome

The development of serotonin syndrome has been reported with 5-HT ₃ receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of ondansetron alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT ₃ receptor antagonist use occurred in a post-anesthesia care unit or an infusion center.

Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of ondansetron injection and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue ondansetron injection and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if ondansetron injection is used concomitantly with other serotonergic drugs [see Drug Interactions (7.5), Overdosage (10)].