Ondansetron Hydrochloride
FDA Drug Information • Also known as: Ondansetron, Ondansetron Hydrochloride
- Brand Names
- Ondansetron, Ondansetron Hydrochloride
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION The active ingredient of Ondansetron Injection, USP is ondansetron hydrochloride, a selective blocking agent of the serotonin 5-HT 3 receptor type. Its chemical name is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one, monohydrochloride, dihydrate. It has the following structural formula: The empirical formula is C 18 H 19 N 3 O
What Is Ondansetron Hydrochloride Used For?
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.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy ( 2.1 ): 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. Adults and pediatric patients 6 months of age and older: The recommended dosage is 0.15 mg/kg per dose for 3 doses (maximum of 16 mg per dose), infused intravenously over 15 minutes. Administer the first dose 30 minutes before the start of chemotherapy and subsequent doses 4 and 8 hours after the first dose. Prevention of postoperative nausea and/or vomiting ( 2.2 ) : Dilution of Ondansetron Injection is not required before administration to adult and pediatric patients. See full prescribing information for the recommended dosage and administration instructions for adult and pediatric patients 1 month of age and older. Patients with severe hepatic impairment ( 2.3 ) : Do not exceed a total daily dose of 8 mg. 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...
Side Effects (Adverse Reactions)
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...
Drug Interactions
7 DRUG INTERACTIONS 7.1 Drugs Affecting Cytochrome P-450 Enzymes Ondansetron does not appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver. Because ondansetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of ondansetron [see Clinical Pharmacology ( 12.3 )] . On the basis of limited available data, no dosage adjustment is recommended for patients on these drugs. 7.2 Apomorphine Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with ondansetron is contraindicated [see Contraindications ( 4 )] . 7.3 Phenytoin, Carbamazepine, and Rifampin In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampin), the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. However, on the basis of available data, no dosage adjustment for ondansetron is recommended for patients on these drugs [see Clinical Pharmacology ( 12.3 )] . 7.4 Tramadol Although there are no data on pharmacokinetic drug interactions between ondansetron and tramadol, data from two small trials indicate that concomitant use of ondansetron may result in reduced analgesic activity of tramadol. Patients on concomitant ondansetron self administered tramadol more frequently in these trials, leading to an increased cumulative dose in patient-controlled administration (PCA) of tramadol. 7.5 Serotonergic Drugs Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT 3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) [see Warnings and Precautions ( 5.3 )] . 7.6 Chemotherapy In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron. In a crossover trial in 76 pediatric patients, intravenous ondansetron did not increase blood levels of high-dose methotrexate. 7.7 Temazepam The coadministration of ondansetron had no effect on the pharmacokinetics and pharmacodynamics of temazepam. 7.8 Alfentanil and Atracurium Ondansetron does not alter the respiratory depressant effects produced by alfentanil or the degree of neuromuscular blockade produced by atracurium. Interactions with general or local anesthetics have not been studied.
Contraindications
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. Patients known to have hypersensitivity (e.g., anaphylaxis) to this product or any of its components. ( 4 ) Concomitant use of apomorphine. ( 4 , 7.2 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data do not reliably inform the association of ondansetron and adverse fetal outcomes. Published epidemiological studies on the association between ondansetron and fetal outcomes have reported inconsistent findings and have important methodological limitations hindering interpretation [see Data ] . Reproductive studies in rats and rabbits did not show evidence of harm to the fetus when ondansetron was administered intravenously during organogenesis at approximately 3.6 and 2.9 times the maximum recommended human intravenous dose of 0.15 mg/kg given three times a day, based on body surface area, respectively [see Data ] . The background risk of major birth defects and miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Methodological limitations of the epidemiology studies preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of ondansetron in pregnancy. Two large retrospective cohort studies of ondansetron use in pregnancy have been published. In one study with 1,349 infants born to women who reported the use of ondansetron or received an ondansetron prescription in the first trimester, no increased risk for major congenital malformations was seen in aggregate analysis. In this same study, however, a sub-analysis for specific malformations reported an association between ondansetron exposure and cardiovascular defect (odds ratio (OR) 1.62 [95% CI (1.04, 2.14)]) and cardiac septal defect (OR 2.05 [95% CI (1.19, 3.28)]). The second study examined 1970 women who received ondansetron prescription during pregnancy and reported no association between ondansetron exposure and major congenital malformations, miscarriage or stillbirth, and infants of low birth weight or small for gestational age. Important...
Overdosage
10 OVERDOSAGE There is no specific antidote for ondansetron overdose. Patients should be managed with appropriate supportive therapy. Individual intravenous doses as large as 150 mg and total daily intravenous doses as large as 252 mg have been inadvertently administered without significant adverse events. These doses are more than 10 times the recommended daily dose. In addition to the adverse reactions listed above, the following events have been described in the setting of ondansetron overdose: “Sudden blindness” (amaurosis) of 2 to 3 minutes' duration plus severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as a single dose. Hypotension (and faintness) occurred in another patient that took 48 mg of ondansetron hydrochloride tablets. Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed. In all instances, the events resolved completely. Pediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of ondansetron (exceeding estimated ingestion of 5 mg/kg) in young children. Reported symptoms included somnolence, agitation, tachycardia, tachypnea, hypertension, flushing, mydriasis, diaphoresis, myoclonic movements, horizontal nystagmus, hyperreflexia, and seizure. Patients required supportive care, including intubation in some cases, with complete recovery without sequelae within 1 to 2 days.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Ondansetron Injection, USP, 2 mg per mL, is supplied as follows: Ondansetron Injection, USP (Preservative-free) NDC (2 mg per mL) Package Factor 70860-776-02 4 mg per 2 mL Single-Dose Vial 25 vials per carton Ondansetron Injection, USP (Preservative) NDC (2 mg per mL) Package Factor 70860-777-20 40 mg per 20 mL Multi-Dose Vial 1 vial per carton Storage Conditions Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light. Retain in carton until time of use. Sterile, Nonpyrogenic. The container closure is not made with natural rubber latex.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.