ondansetron hydrochloride
Tablet, Film Coated · Oral, Intramuscular, Intravenous
Uses
Ondansetron is a 5-HT 3 receptor antagonist indicated for the prevention of: nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m 2 . ( 1 ) nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. ( 1 ) nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen. ( 1 ) postoperative nausea and/or vomiting. ( 1 ) Ondansetron tablets are indicated for the prevention of nausea and vomiting associated with: highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m 2 initial and repeat courses of moderately emetogenic cancer chemotherapy radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen Ondansetron tablets are also indicated for the prevention of postoperative nausea and/or vomiting.
Dosage and administration
See full prescribing information for the recommended dosage in adults and pediatrics ( 2 ) Patients with severe hepatic impairment: do not exceed a total daily dose of 8 mg. ( 2.2 , 8.6 ) 2.1 Recommended Dosage The recommended dosage regimens for adult and pediatric patients are described in Table 1 and Table 2, respectively. Corresponding doses of ondansetron tablets, ondansetron orally disintegrating tablets and ondansetron oral solution may be used interchangeably. Table 1: Adult Recommended Dosage Regimen for Prevention of Nausea and Vomiting Indication Dosage Regimen Highly Emetogenic Cancer Chemotherapy A single 24-mg dose administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin greater than or equal to 50 mg/m 2 . Moderately Emetogenic Cancer Chemotherapy 8 mg administered 30 minutes before the start of chemotherapy, with a subsequent 8-mg dose 8 hours after the first dose. Then administer 8 mg twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy. Radiotherapy For total body irradiation: 8 mg administered 1 to 2 hours before each fraction of radiotherapy each day. For single high-dose fraction radiotherapy to the abdomen: 8 mg administered 1 to 2 hours before radiotherapy, with subsequent 8-mg doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy. For daily fractionated radiotherapy to the abdomen: 8 mg administered 1 to 2 hours before radiotherapy, with subsequent 8-mg doses every 8 hours after the first dose for each day radiotherapy is given. Postoperative 16 mg administered 1 hour before induction of anesthesia. Table 2: Pediatric Recommended Dosage Regimen for Prevention of Nausea and Vomiting Indication Dosage Regimen Moderately Emetogenic Cancer Chemotherapy 12 to 17 years of age : 8 mg administered 30 minutes before the start of chemotherapy, with a subsequent 8-mg dose 8 hours after the first dose. Then administer 8 mg twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy. 4 to 11 years of age : 4 mg administered 30 minutes before the start of chemotherapy, with a subsequent 4-mg dose 4 and 8 hours after the first dose. Then administer 4 mg three times a day for 1 to 2 days after completion of chemotherapy. 2.2 Dosage in Hepatic Impairment In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), do not exceed a total daily dose of 8 mg [see Use in Specific Populations ( 8.6 ), Clinical Pharmacology ( 12.3 )] .
Dosage forms and strengths
Tablets: 4 mg and 8 mg. ( 3 ) Ondansetron tablets USP are available in the following strengths: 4 mg – yellow colored, round shaped, biconvex, film coated tablets debossed with 'I' on one side and '55' on other side. 8 mg – yellow colored, round shaped, biconvex, film coated tablets debossed with 'I' on one side and '54' on other side.
Contraindications
Patients known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any components of the formulation. ( 4 ) Concomitant use of apomorphine. ( 4 ) Ondansetron tablets are contraindicated in patients: known to have hypersensitivity (e.g., anaphylaxis) to ondansetron or any of the components of the formulation [see Adverse Reactions ( 6.2 )] receiving concomitant apomorphine due to the risk of profound hypotension and loss of consciousness
Warnings and precautions
Hypersensitivity Reactions Including Anaphylaxis and Bronchospasm: Discontinue ondansetron tablets if suspected. Monitor and treat promptly per standard of care until signs and symptoms resolve. ( 5.1 ) QT Interval Prolongation and Torsade de Pointes : Avoid ondansetron in patients with congenital long QT syndrome; monitor with electrocardiograms (ECGs) if concomitant electrolyte abnormalities, cardiac failure or arrhythmias, or use of other QT prolonging drugs. ( 5.2 ) Serotonin Syndrome: Reported with 5-HT 3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs. If such symptoms occur, discontinue ondansetron tablets and initiate supportive treatment. If concomitant use of ondansetron with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome. ( 5.3 ) Myocardial Ischemia : Monitor or advise patients for signs and symptoms of myocardial ischemia after oral administration. ( 5.4 ) Masking of Progressive Ileus and/or Gastric Distension Following Abdominal Surgery or Chemotherapy-Induced Nausea and Vomiting : Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction. ( 5.5 ) 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. If hypersensitivity reactions occur, discontinue use of ondansetron tablets; treat promptly per standard of care and monitor until signs and symptoms resolve [see Contraindications ( 4 )]. 5.2 QT Prolongation Electrocardiogram (ECG) changes, including QT interval prolongation have been seen in patients receiving ondansetron. In addition, postmarketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ondansetron in patients with congenital long QT syndrome. 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 [see Clinical Pharmacology ( 12.2 )]. 5.3 Serotonin Syndrome The development of serotonin syndrome has been reported with 5-HT 3 receptor antagonists alone. 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 tablets 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 tablets and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue ondansetron tablets and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if ondansetron tablets are used concomitantly with other serotonergic drugs [see Drug Interactions ( 7.1 ), Overdosage ( 10 )] . 5.4 Myocardial Ischemia Myocardial ischemia has been reported in patients treated with ondansetron. In some cases, predominantly during intravenous administration, the symptoms appeared immediately after administration but resolved with prompt treatment. Coronary artery spasm appears to be the most common underlying cause. Therefore, monitor or advise patients for signs or symptoms of myocardial ischemia after oral administration of ondansetron tablets [see Adverse Reactions ( 6.2 )] . 5.5 Masking of Progressive Ileus and Gastric Distension The use of ondansetron in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distension. Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction. Ondansetron is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction.
Side effects
The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] QT Prolongation [see Warnings and Precautions ( 5.2 )] Serotonin Syndrome [see Warnings and Precautions ( 5.3 )] Myocardial Ischemia [see Warnings and Precautions ( 5.4 )] Masking of Progressive Ileus and Gastric Distension [see Warnings and Precautions ( 5.5 )] The most common adverse reactions in adults for the: prevention of chemotherapy-induced (≥ 5%) are: headache, malaise/fatigue, constipation, diarrhea. ( 6.1 ) prevention of radiation-induced nausea and vomiting (≥ 2%) are: headache, constipation, and diarrhea. ( 6.1 ) prevention of postoperative nausea and vomiting (≥ 9%) are: headache and hypoxia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ipca at 1-888-472-2651 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 practice. The following adverse reactions have been reported in clinical trials of patients treated with ondansetron, the active ingredient of ondansetron tablets. A causal relationship to therapy with ondansetron tablets was unclear in many cases. Prevention of Chemotherapy-Induced Nausea and Vomiting The most common adverse reactions reported in greater than or equal to 4% of 300 adults receiving a single 24-mg dose of ondansetron tablet orally in 2 trials for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy (cisplatin greater than or equal to 50 mg/m 2 ) were: headache (11%) and diarrhea (4%). The most common adverse reactions reported in 4 trials in adults for the prevention of nausea and vomiting associated with moderately emetogenic chemotherapy (primarily cyclophosphamide-based regimens) are shown in Table 3. Table 3: Most Common Adverse Reactions in Adults 1 for the Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Chemotherapy [Primarily Cyclophosphamide-based Regimens] 1 Reported in greater than or equal to 5% of patients treated with ondansetron and at a rate that exceeded placebo. Ondansetron 8 mg Twice Daily Placebo Adverse Reaction (n = 242) (n = 262) Headache 58 (24%) 34 (13%) Malaise/Fatigue 32 (13%) 6 (2%) Constipation 22 (9%) 1 (< 1%) Diarrhea 15 (6%) 10 (4%) Less Common Adverse Reactions Central Nervous System: Extrapyramidal reactions (less than 1% of patients). Hepatic: Aspartate transaminase (AST) and/or alanine transaminase (ALT) values exceeded twice the upper limit of normal in approximately 1% to 2% of 723 patients receiving ondansetron tablets and cyclophosphamide-based chemotherapy in US clinical trials. 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 is unclear. Liver failure and death has been reported in cancer patients receiving concurrent medications, including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is unclear. Integumentary: Rash (approximately 1% of patients). Other (less than 2%): Anaphylaxis, bronchospasm, tachycardia, angina, hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures. Except for bronchospasm and anaphylaxis, the relationship to ondansetron is unclear. Prevention of Radiation-Induced Nausea and Vomiting The most common adverse reactions (greater than or equal to 2%) reported in patients receiving ondansetron tablets and concurrent radiotherapy were similar to those reported in patients receiving ondansetron tablets and concurrent chemotherapy and were headache, constipation, and diarrhea. Prevention of Postoperative Nausea and/or Vomiting The most common adverse reactions reported in adults in trial(s) of prevention of postoperative nausea and vomiting are shown in Table 4. In these trial(s), patients were receiving multiple concomitant perioperative and postoperative medications in both treatment groups. Table 4: Most Common Adverse Reactions in Adults 1 for the Prevention of Postoperative Nausea and Vomiting 1 Reported in greater than or equal to 5% of patients treated with ondansetron and at a rate that exceeded placebo. Ondansetron 16 mg as a Single Dose Placebo Adverse Reaction (n = 550) (n = 531) 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%) Urinary retention 28 (5%) 18 (3%) Pruritus 27 (5%) 20 (4%) 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. 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 interval prolongation have been reported. Myocardial ischemia was reported predominately with intravenous administration [see Warnings and Precautions ( 5.4 )] .
Drug interactions
7.1 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 SSRIs and SNRIs. Monitor for the emergence of serotonin syndrome. If symptoms occur, discontinue ondansetron tablets and initiate supportive treatment [see Warnings and Precautions ( 5.3 )] . 7.2 Drugs Affecting Cytochrome P-450 Enzymes Ondansetron does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver [see Clinical Pharmacology ( 12.3 )] . 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. 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 )] . 7.3 Tramadol Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed, data from 2 small trials indicate that when used together, ondansetron may increase patient-controlled administration of tramadol. Monitor patients to ensure adequate pain control when ondansetron is administered with tramadol. 7.4 Chemotherapy Carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron. In a crossover trial in 76 pediatric patients, intravenous ondansetron did not increase systemic concentrations of high-dose methotrexate. 7.5 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.
Use in specific populations
8.1 Pregnancy Risk Summary Published epidemiological studies on the association between ondansetron use and major birth defects have reported inconsistent findings and have important methodological limitations that preclude conclusions about the safety of ondansetron use in pregnancy (see Data) . Available postmarketing data have not identified a drug-associated risk of miscarriage or adverse maternal outcomes. Reproductive studies in rats and rabbits did not show evidence of harm to the fetus when ondansetron was administered during organogenesis at approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, based on body surface area (BSA), respectively (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriages, or other adverse outcomes. 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 Available data on ondansetron use in pregnant women from several published epidemiological studies preclude an assessment of a drug-associated risk of adverse fetal outcomes due to important methodological limitations, including the uncertainty of whether women who filled a prescription actually took the medication, the concomitant use of other medications or treatments, recall bias, and other unadjusted confounders. Ondansetron exposure in utero has not been associated with overall major congenital malformations in aggregate analyses. One large retrospective cohort study examined 1970 women who received a prescription for ondansetron during pregnancy and reported no association between ondansetron exposure and major congenital malformations, miscarriage, stillbirth, preterm delivery, infants of low birth weight, or infants small for gestational age. Two large retrospective cohort studies and one case-control study have assessed ondansetron exposure in the first trimester and risk of cardiovascular defects with inconsistent findings. Relative risks (RR) ranged from 0.97 (95% CI 0.86 to 1.10) to 1.62 (95% CI 1.04, 2.54). A subset analysis in one of the cohort studies observed that ondansetron was specifically associated with cardiac septal defects (RR 2.05, 95% CI 1.19, 3.28); however, this association was not confirmed in other studies. Several studies have assessed ondansetron and the risk of oral clefts with inconsistent findings. A retrospective cohort study of 1.8 million pregnancies in the US Medicaid Database showed an increased risk of oral clefts among 88,467 pregnancies in which oral ondansetron was prescribed in the first trimester (RR 1.24, 95% CI 1.03, 1.48), but no such association was reported with intravenous ondansetron in 23,866 pregnancies (RR 0.95, 95% CI 0.63, 1.43). In the subgroup of women who received both forms of administration, the RR was 1.07 (95% CI 0.59, 1.93). Two case-control studies, using data from birth defects surveillance programs, reported conflicting associations between maternal use of ondansetron and isolated cleft palate (OR 1.6 [95% CI 1.1, 2.3] and 0.5 [95% CI 0.3, 1.0]). It is unknown whether ondansetron exposure in utero in the cases of cleft palate occurred during the time of palate formation (the palate is formed between the 6th and 9th weeks of pregnancy). Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of ondansetron up to 15 mg/kg/day and 30 mg/kg/day, respectively, during the period of organogenesis. With the exception of a slight decrease in maternal body weight gain in the rabbits, there were no significant effects of ondansetron on the maternal animals or the development of the offspring. At doses of 15 mg/kg/day in rats and 30 mg/kg/day in rabbits, the maternal exposure margin was approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, respectively, based on BSA. In a pre- and postnatal developmental toxicity study, pregnant rats received oral doses of ondansetron up to 15 mg/kg/day from Day 17 of pregnancy to litter Day 21. With the exception of a slight reduction in maternal body weight gain, there were no effects upon the pregnant rats and the pre- and postnatal development of their offspring, including reproductive performance of the mated F1 generation. At a dose of 15 mg/kg/day in rats, the maternal exposure margin was approximately 6 times the maximum recommended human oral dose of 24 mg/day, based on BSA. 8.2 Lactation Risk Summary Ondansetron is unlikely to result in clinically relevant exposure in breastfed infants when administered intravenously at doses up to 4 mg/day to women who are breastfeeding. Available data from a lactation study involving pharmacokinetic samples from 80 lactating women and 20 infants indicate that ondansetron is present at low levels in human milk and in the plasma of breastfed infants. Both the estimated daily infant dose (DID) of ondansetron (0.002 mg/kg/day), and the relative infant dose (RID) (3.7%) were low ( see Data ) In the same study, no adverse eff ects attributed to ondansetron were reported in infants exposed to ondansetron through breast milk. There are no data on the eff ects on ondansetron on milk production. Data A pharamacokinetic study utilizing opportinistic sampling of a convenience sample of 80 lactatingwomen receiving intravenous ondansetron for the treatment of post-operative nausea and vomiting and 20 breastfed infants showed that ondasetron was present in breast milk with an average milk to plasma ratio of 0.91 following a median (range) dose of ondansetron of 4 (4 to 8) mg/dose. Using the average milk concentration over 24 hours to estimate the DID and the RID, the DID was 0.002 mg/kg/day and the RID was 3.7% of a weight-adjusted single maternal dose of 4 mg.
Pregnancy
8.1 Pregnancy Risk Summary Published epidemiological studies on the association between ondansetron use and major birth defects have reported inconsistent findings and have important methodological limitations that preclude conclusions about the safety of ondansetron use in pregnancy (see Data) . Available postmarketing data have not identified a drug-associated risk of miscarriage or adverse maternal outcomes. Reproductive studies in rats and rabbits did not show evidence of harm to the fetus when ondansetron was administered during organogenesis at approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, based on body surface area (BSA), respectively (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriages, or other adverse outcomes. 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 Available data on ondansetron use in pregnant women from several published epidemiological studies preclude an assessment of a drug-associated risk of adverse fetal outcomes due to important methodological limitations, including the uncertainty of whether women who filled a prescription actually took the medication, the concomitant use of other medications or treatments, recall bias, and other unadjusted confounders. Ondansetron exposure in utero has not been associated with overall major congenital malformations in aggregate analyses. One large retrospective cohort study examined 1970 women who received a prescription for ondansetron during pregnancy and reported no association between ondansetron exposure and major congenital malformations, miscarriage, stillbirth, preterm delivery, infants of low birth weight, or infants small for gestational age. Two large retrospective cohort studies and one case-control study have assessed ondansetron exposure in the first trimester and risk of cardiovascular defects with inconsistent findings. Relative risks (RR) ranged from 0.97 (95% CI 0.86 to 1.10) to 1.62 (95% CI 1.04, 2.54). A subset analysis in one of the cohort studies observed that ondansetron was specifically associated with cardiac septal defects (RR 2.05, 95% CI 1.19, 3.28); however, this association was not confirmed in other studies. Several studies have assessed ondansetron and the risk of oral clefts with inconsistent findings. A retrospective cohort study of 1.8 million pregnancies in the US Medicaid Database showed an increased risk of oral clefts among 88,467 pregnancies in which oral ondansetron was prescribed in the first trimester (RR 1.24, 95% CI 1.03, 1.48), but no such association was reported with intravenous ondansetron in 23,866 pregnancies (RR 0.95, 95% CI 0.63, 1.43). In the subgroup of women who received both forms of administration, the RR was 1.07 (95% CI 0.59, 1.93). Two case-control studies, using data from birth defects surveillance programs, reported conflicting associations between maternal use of ondansetron and isolated cleft palate (OR 1.6 [95% CI 1.1, 2.3] and 0.5 [95% CI 0.3, 1.0]). It is unknown whether ondansetron exposure in utero in the cases of cleft palate occurred during the time of palate formation (the palate is formed between the 6th and 9th weeks of pregnancy). Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of ondansetron up to 15 mg/kg/day and 30 mg/kg/day, respectively, during the period of organogenesis. With the exception of a slight decrease in maternal body weight gain in the rabbits, there were no significant effects of ondansetron on the maternal animals or the development of the offspring. At doses of 15 mg/kg/day in rats and 30 mg/kg/day in rabbits, the maternal exposure margin was approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, respectively, based on BSA. In a pre- and postnatal developmental toxicity study, pregnant rats received oral doses of ondansetron up to 15 mg/kg/day from Day 17 of pregnancy to litter Day 21. With the exception of a slight reduction in maternal body weight gain, there were no effects upon the pregnant rats and the pre- and postnatal development of their offspring, including reproductive performance of the mated F1 generation. At a dose of 15 mg/kg/day in rats, the maternal exposure margin was approximately 6 times the maximum recommended human oral dose of 24 mg/day, based on BSA.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of orally administered ondansetron tablets have been established in pediatric patients 4 years and older for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy. Use of ondansetron in these age-groups is supported by evidence from adequate and well-controlled studies of ondansetron in adults with additional data from 3 open-label, uncontrolled, non-US trials in 182 pediatric patients aged 4 to 18 years with cancer who were given a variety of cisplatin or noncisplatin regimens [see Dosage and Administration ( 2.2 ), Clinical Studies ( 14.1 )] . Additional information on the use of ondansetron in pediatric patients may be found in ondansetron injection prescribing information. The safety and effectiveness of orally administered ondansetron have not been established in pediatric patients for: prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy prevention of nausea and vomiting associated with radiotherapy prevention of postoperative nausea and/or vomiting
Geriatric use
8.5 Geriatric Use Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in US- and foreign-controlled clinical trials, for which there were subgroup analyses, 938 (19%) were aged 65 years and older. No overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger subjects. A reduction in clearance and increase in elimination half-life were seen in patients older than 75 years compared with younger subjects [see Clinical Pharmacology ( 12.3 )] . There were an insufficient number of patients older than 75 years of age and older in the clinical trials to permit safety or efficacy conclusions in this age group. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dosage adjustment is needed in elderly patients.
Overdosage
There is no specific antidote for ondansetron overdose. Patients should be managed with appropriate supportive therapy. In addition to the adverse reactions listed above, the following adverse reactions 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 a patient that took 48 mg of ondansetron 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 adverse reactions resolved completely. Pediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of ondansetron (exceeding estimated ingestion of 5 mg per 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.
Description
The active ingredient in ondansetron tablets USP is ondansetron hydrochloride USP as the dihydrate, the racemic form of ondansetron and a selective blocking agent of the serotonin 5-HT 3 receptor type. Chemically it 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
• HCl
• 2H 2 O, representing a molecular weight of 365.86 g/mol. Ondansetron hydrochloride USP is a white to off-white powder that is sparingly soluble in water and alcohol. Each 4 mg ondansetron tablet USP for oral administration contains ondansetron hydrochloride USP equivalent to 4 mg of ondansetron. Each 8 mg ondansetron tablet USP for oral administration contains ondansetron hydrochloride USP equivalent to 8 mg of ondansetron. Each tablet also contains the inactive ingredients anhydrous lactose, ferric oxide yellow, hypromellose, magnesium stearate, microcrystalline cellulose, pregelatinized starch, titanium dioxide, and triacetin. Product meets USP Dissolution Test # 4. MM1
Mechanism of action
12.1 Mechanism of Action Ondansetron is a selective 5-HT 3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT 3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. It is not certain whether ondansetron's antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine. In humans, urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion increases after cisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferents through the 5-HT 3 receptors and initiate the vomiting reflex.
How supplied
Ondansetron Tablets USP 4 mg (ondansetron hydrochloride USP equivalent to 4 mg of ondansetron), are yellow colored, round shaped, biconvex, film coated tablets debossed with 'I' on one side and '55' on other side and are available as follows: NDC 83980-017-97 Bottles of 10 tablets NDC 83980-017-13 Bottles of 30 tablets NDC 83980-017-10 Bottles of 1,000 tablets Ondansetron Tablets USP 8 mg (ondansetron hydrochloride USP equivalent to 8 mg of ondansetron), are yellow colored, round shaped, biconvex, film coated tablets debossed with 'I' on one side and '54' on other side and are available as follows: NDC 83980-018-97 Bottles of 10 tablets NDC 83980-018-13 Bottles of 30 tablets NDC 83980-018-10 Bottles of 1,000 tablets Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP. You may report side effects to FDA at 1-800-FDA-1088.
Patient information
Hypersensitivity Reactions Inform patients that ondansetron may cause hypersensitivity reactions, some as severe as anaphylaxis and bronchospasm. Instruct patients to immediately report any signs and symptoms of hypersensitivity reactions, including fever, chills, rash, or breathing problems to their healthcare provider [see Warnings and Precautions ( 5.1 )] . QT Prolongation Inform patients that ondansetron may cause serious cardiac arrhythmias, such as QT prolongation. Instruct patients to tell their healthcare provider right away if they perceive a change in their heart rate, if they feel lightheaded, or if they have a syncopal episode [see Warnings and Precautions ( 5.2 )] . Drug Interactions Instruct the patient to report the use of all medications, especially apomorphine, to their healthcare provider. Concomitant use of apomorphine and ondansetron may cause a significant drop in blood pressure and loss of consciousness. Advise patients of the possibility of serotonin syndrome with concomitant use of ondansetron and another serotonergic agent, such as medications to treat depression and migraines. Advise patients to seek immediate medical attention if the following symptoms occur: changes in mental status, autonomic instability, neuromuscular symptoms with or without gastrointestinal symptoms [see Warnings and Precautions ( 5.3 )] . Myocardial Ischemia Inform patients that ondansetron may cause myocardial ischemia. Advise patients to seek immediate medical help if any symptoms suggestive of a myocardial ischemia occur, such as sudden chest pain or chest tightness [see Warnings and Precautions ( 5.4 )] . Masking of Progressive Ileus and Gastric Distension Inform patients following abdominal surgery or those with chemotherapy-induced nausea and vomiting that ondansetron may mask signs and symptoms of bowel obstruction. Instruct patients to immediately report any signs or symptoms consistent with a potential bowel obstruction to their healthcare provider [see Warnings and Precautions ( 5.5 )] .
Label text from the FDA structured product label by Ipca Laboratories Limited (revised Jul 22, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Ondansetron Hydrochloride in 79 products
ondansetron hydrochloride NDC products (79)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-3178 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | A-S Medication Solutions | ANDA |
| 50090-3185 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | A-S Medication Solutions | ANDA |
| 50090-4671 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | A-S Medication Solutions | ANDA |
| 50090-6342 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | A-S Medication Solutions | ANDA |
| 68084-220 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | American Health Packaging | ANDA |
| 68084-221 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | American Health Packaging | ANDA |
| 71610-119 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 76420-915 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Asclemed USA, Inc. | ANDA |
| 76420-917 | Ondansetron Hydrochloride 24 mg/1 Tablet, Film Coated | Asclemed USA, Inc. | ANDA |
| 76420-916 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Asclemed USA, Inc. | ANDA |
| 65862-188 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 65862-187 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 65862-189 | Ondansetron Hydrochloride 24 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 50268-622 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | AvPAK | ANDA |
| 50268-621 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | AvPAK | ANDA |
| 36000-012 | Ondansetron Hydrochloride 2 mg/mL Solution | Baxter Healthcare Corporation | ANDA |
| 72162-2365 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 72162-2364 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 71335-1855 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 71335-1596 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 71335-1357 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 71335-0205 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 55154-4453 | Ondansetron Hydrochloride 2 mg/mL Solution | Cardinal Health 107, LLC | ANDA |
| 68999-555 | Ondansetron Hydrochloride 4 mg/5mL Solution | Chartwell Governmental & Specialty RX, LLC. | ANDA |
| 62135-555 | Ondansetron Hydrochloride 4 mg/5mL Solution | Chartwell RX, LLC. | ANDA |
| 67046-1242 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Coupler LLC | ANDA |
| 55111-155 | Ondansetron Hydrochloride 16 mg/1 Tablet, Film Coated | Dr. Reddy's Laboratories Limited | ANDA |
| 0054-0064 | Ondansetron Hydrochloride 4 mg/5mL Solution | Hikma Pharmaceuticals USA Inc. | ANDA |
| 83980-018 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Ipca Laboratories Limited | ANDA |
| 83980-017 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Ipca Laboratories Limited | ANDA |
| 0615-8185 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | NCS HealthCare of KY, LLC dba Vangard Labs | ANDA |
| 51655-933 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Northwind Health Company, LLC | ANDA |
| 51655-813 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Northwind Health Company, LLC | ANDA |
| 51655-415 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Northwind Health Company, LLC | ANDA |
| 51655-016 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Northwind Health Company, LLC | ANDA |
| 68071-4966 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | NUCARE PHARMACEUTICALS INC | ANDA |
| 68071-5047 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-1742 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-2053 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-4705 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-4328 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | NuCare Pharmceuticals,Inc. | ANDA |
| 83270-160 | Ondansetron Hydrochloride 2 mg/mL Injection | Onesource Specialty Pharma Limited | ANDA |
| 83270-161 | Ondansetron Hydrochloride 2 mg/mL Injection | Onesource Specialty Pharma Limited | ANDA |
| 72789-034 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 43063-792 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 54348-821 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Pharmpak, Inc. | ANDA |
| 85509-1057 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | PHOENIX RX LLC | ANDA |
| 85509-1075 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | PHOENIX RX LLC | ANDA |
| 85509-1076 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | PHOENIX RX LLC | ANDA |
| 68094-763 | Ondansetron Hydrochloride 4 mg/5mL Solution | Precision Dose Inc. | ANDA |
| 68788-8651 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Preferred Pharmaceuticals Inc. | ANDA |
| 68788-8582 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Preferred Pharmaceuticals Inc. | ANDA |
| 68788-9368 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Preferred Pharmaceuticals, Inc. | ANDA |
| 68788-9402 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Preferred Pharmaceuticals, Inc. | ANDA |
| 71205-744 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Proficient Rx LP | ANDA |
| 82804-257 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Proficient Rx LP | ANDA |
| 63187-636 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Proficient Rx LP | ANDA |
| 63187-709 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Proficient Rx LP | ANDA |
| 42708-044 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | QPharma, Inc. | ANDA |
| 42708-059 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | QPharma, Inc. | ANDA |
| 42708-179 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | QPharma, Inc. | ANDA |
| 55700-631 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Quality Care Products LLC | ANDA |
| 55700-627 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Quality Care Products LLC | ANDA |
| 83008-074 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Quality Care Products, LLC | ANDA |
| 67296-1562 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Redpharm Drug | ANDA |
| 70518-4145 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | REMEDYREPACK INC. | ANDA |
| 70518-1585 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | REMEDYREPACK INC. | ANDA |
| 70518-3511 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | REMEDYREPACK INC. | ANDA |
| 57237-076 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Rising Pharma Holdings, Inc. | ANDA |
| 57237-075 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Rising Pharma Holdings, Inc. | ANDA |
| 85766-006 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Sportpharm LLC | ANDA |
| 85766-053 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Sportpharm LLC | ANDA |
| 60760-658 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | St. Mary's Medical Park Pharmacy | ANDA |
| 60760-878 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | St. Mary's Medical Park Pharmacy | ANDA |
| 60760-636 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | St. Mary's Medical Park Pharmacy | ANDA |
| 62756-130 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Sun Pharmaceutical Industries, Inc. | ANDA |
| 62756-131 | Ondansetron Hydrochloride 8 mg/1 Tablet, Film Coated | Sun Pharmaceutical Industries, Inc. | ANDA |
| 87441-064 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Unit Dose Solutions, Inc. | ANDA |
| 87441-088 | Ondansetron Hydrochloride 4 mg/1 Tablet, Film Coated | Unit Dose Solutions, Inc. | ANDA |
ondansetron hydrochloride recalls
- D-0146-2024 Dec 13, 2023 · Class II · Completed
Failed pH Specifications - D-1103-2022 Jun 15, 2022 · Class II · Terminated
cGMP deviations: Temperature abuse
Frequently asked questions
What is ondansetron hydrochloride used for?
Ondansetron is a 5-HT 3 receptor antagonist indicated for the prevention of: nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/m 2 . ( 1 ) nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. ( 1 ) nausea and vomiting associated with radiotherapy in patients…
What are the side effects of ondansetron hydrochloride?
The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] QT Prolongation [see Warnings and Precautions ( 5.2 )] Serotonin Syndrome [see Warnings and Precautions ( 5.3 )] Myocardial Ischemia [see Warnings and Precautions ( 5.4 )] Masking of Progressive Ileus and Gastric Distension [see Warnings… See the full label for the complete list.
Who makes ondansetron hydrochloride?
ondansetron hydrochloride is listed by 38 labelers in the FDA NDC directory, including A-S Medication Solutions, American Health Packaging, Aphena Pharma Solutions - Tennessee, LLC, Asclemed USA, Inc..
Has ondansetron hydrochloride been recalled?
The FDA enforcement database lists 2 recalls for ondansetron hydrochloride, most recently D-0146-2024 (class ii): Failed pH Specifications