Ondansetron (ondansetron hydrochloride 8 mg) Dailymed

Clinical Trials

Chemotherapy-Induced Nausea and Vomiting

Highly Emetogenic Chemotherapy

In 2 randomized, double-blind, monotherapy trials, a single 24 mg ondansetron tablet was superior to a relevant historical placebo control in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m². Steroid administration was excluded from these clinical trials. More than 90% of patients receiving a cisplatin dose ≥50 mg/m² in the historical placebo comparator experienced vomiting in the absence of antiemetic therapy.

The first trial compared oral doses of ondansetron 24 mg once-a-day, 8 mg twice-a-day, and 32 mg once-a-day in 357 adult cancer patients receiving chemotherapy regimens containing cisplatin ≥50 mg/m². A total of 66% of patients in the ondansetron 24 mg once-a-day group, 55% in the ondansetron 8 mg twice-a-day group, and 55% in the ondansetron 32 mg once-a-day group completed the 24-hour study period with 0 emetic episodes and no rescue antiemetic medications, the primary endpoint of efficacy. Each of the 3 treatment groups was shown to be statistically significantly superior to a historical placebo control.

In the same trial, 56% of patients receiving oral ondansetron 24 mg once-a-day experienced no nausea during the 24-hour study period, compared with 36% of patients in the oral ondansetron 8 mg twice-a-day group (p = 0.001) and 50% in the oral ondansetron 32 mg once-a-day group.

In a second trial, efficacy of the oral ondansetron 24 mg once-a-day regimen in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m², was confirmed.

Moderately Emetogenic Chemotherapy

In 1 double-blind US study in 67 patients, ondansetron tablets 8 mg administered twice-a-day were significantly more effective than placebo in preventing vomiting induced by cyclophosphamide-based chemotherapy containing doxorubicin. Treatment response is based on the total number of emetic episodes over the 3-day study period. The results of this study are summarized in Table 3:

Table 3. Emetic Episodes: Treatment Response

	Ondansetron 8 mg b.i.d . Ondansetron Tablets The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. An 8 mg ondansetron tablet was administered twice-a-day for 2 days after completion of chemotherapy.	Placebo	p Value
Number of patients	33	34
Treatment response 0 Emetic episodes 1-2 Emetic episodes	20 (61%) 6 (18%)	2 (6%) 8 (24%)	<0.001
More than 2 emetic episodes/withdrawn	7 (21%)	24 (71%)	<0.001
Median number of emetic episodes	0.0	UndefinedMedian undefined since at least 50% of the patients were withdrawn or had more than 2 emetic episodes.
Median time to first emetic episode (h)	UndefinedMedian undefined since at least 50% of patients did not have any emetic episodes.	6.5

In 1 double-blind US study in 336 patients, ondansetron tablets 8 mg administered twice-a-day were as effective as ondansetron tablets 8 mg administered 3 times a day in preventing nausea and vomiting induced by cyclophosphamide-based chemotherapy containing either methotrexate or doxorubicin. Treatment response is based on the total number of emetic episodes over the 3-day study period. The results of this study are summarized in Table 4:

Table 4. Emetic Episodes: Treatment Response

	Ondansetron
	8 mg b.i.d . Ondansetron Tablets The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. An 8 mg ondansetron tablet was administered twice-a-day for 2 days after completion of chemotherapy.	8 mg t.i.d . Ondansetron Tablets The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. An 8 mg ondansetron tablet was administered 3 times a day for 2 days after completion of chemotherapy.
Number of patients	165	171
Treatment response 0 Emetic episodes 1-2 Emetic episodes More than 2 emetic episodes/withdrawn	101 (61%) 16 (10%) 48 (29%)	99 (58%) 17 (10%) 55 (32%)
Median number of emetic episodes	0.0	0.0
Median time to first emetic episode (h)	UndefinedMedian undefined since at least 50% of patients did not have any emetic episodes.	Undefined
Median nausea scores (0-100)Visual analog scale assessment: 0 = no nausea, 100 = nausea as bad as it can be.	6	6

Re-treatment

In uncontrolled trials, 148 patients receiving cyclophosphamide-based chemotherapy were retreated with ondansetron tablets 8 mg 3 times daily during subsequent chemotherapy for a total of 396 re-treatment courses. No emetic episodes occurred in 314 (79%) of the re-treatment courses, and only 1 to 2 emetic episodes occurred in 43 (11%) of the re-treatment courses.

Pediatric Studies

Three open-label, uncontrolled, foreign trials have been performed with 182 pediatric patients 4 to 18 years old with cancer who were given a variety of cisplatin or noncisplatin regimens. In these foreign trials, the initial dose of ondansetron HCl injection ranged from 0.04 to 0.87 mg/kg for a total dose of 2.16 to 12 mg. This was followed by the administration of ondansetron tablets ranging from 4 to 24 mg daily for 3 days. In these studies, 58% of the 170 evaluable patients had a complete response (no emetic episodes) on day 1. Two studies showed the response rates for patients less than 12 years of age who received ondansetron tablets 4 mg 3 times a day to be similar to those in patients 12 to 18 years of age who received ondansetron tablets 8 mg 3 times daily. Thus, prevention of emesis in these pediatric patients was essentially the same as for patients older than 18 years of age. Overall, ondansetron tablets were well tolerated in these pediatric patients.

Radiation-Induced Nausea and Vomiting

Total Body Irradiation

In a randomized, double-blind study in 20 patients, ondansetron tablets (8 mg given 1.5 hours before each fraction of radiotherapy for 4 days) were significantly more effective than placebo in preventing vomiting induced by total body irradiation. Total body irradiation consisted of 11 fractions (120 cGy per fraction) over 4 days for a total of 1,320 cGy. Patients received 3 fractions for 3 days, then 2 fractions on day 4.

Single High-Dose Fraction Radiotherapy

Ondansetron was significantly more effective than metoclopramide with respect to complete control of emesis (0 emetic episodes) in a double-blind trial in 105 patients receiving single high-dose radiotherapy (800 to 1,000 cGy) over an anterior or posterior field size of ≥80 cm² to the abdomen. Patients received the first dose of ondansetron tablets (8 mg) or metoclopramide (10 mg) 1 to 2 hours before radiotherapy. If radiotherapy was given in the morning, 2 additional doses of study treatment were given (1 tablet late afternoon and 1 tablet before bedtime). If radiotherapy was given in the afternoon, patients took only 1 further tablet that day before bedtime. Patients continued the oral medication on a 3 times a day basis for 3 days.

Daily Fractionated Radiotherapy

Ondansetron was significantly more effective than prochlorperazine with respect to complete control of emesis (0 emetic episodes) in a double-blind trial in 135 patients receiving a 1- to 4-week course of fractionated radiotherapy (180 cGy doses) over a field size of ≥100 cm² to the abdomen. Patients received the first dose of ondansetron tablets (8 mg) or prochlorperazine (10 mg) 1 to 2 hours before the patient received the first daily radiotherapy fraction, with 2 subsequent doses on a 3 times a day basis. Patients continued the oral medication on a 3 times a day basis on each day of radiotherapy.

Postoperative Nausea and Vomiting

Surgical patients who received ondansetron 1 hour before the induction of general balanced anesthesia (barbiturate: thiopental, methohexital, or thiamylal; opioid: alfentanil, sufentanil, morphine, or fentanyl; nitrous oxide; neuromuscular blockade: succinylcholine/curare or gallamine and/or vecuronium, pancuronium, or atracurium; and supplemental isoflurane or enflurane) were evaluated in 2 double-blind studies (1 US study, 1 foreign) involving 865 patients. Ondansetron tablets (16 mg) were significantly more effective than placebo in preventing postoperative nausea and vomiting.

The study populations in all trials thus far consisted of women undergoing inpatient surgical procedures. No studies have been performed in males. No controlled clinical study comparing ondansetron tablets to ondansetron injection has been performed.

Indications And Usage

• 1.Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m².
• 2.Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
• 3.Prevention of 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.
• 4.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 where nausea and/or vomiting must be avoided postoperatively, ondansetron tablets, USP are recommended even where the incidence of postoperative nausea and/or vomiting is low.

Contraindications

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.

Ondansetron tablets are contraindicated for patients known to have hypersensitivity to the drug.

Warnings

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT₃ receptor antagonists.

ECG changes including QT interval prolongation has been seen in patients receiving ondansetron. In addition, post-marketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid ondansetron tablets 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.

The development of serotonin syndrome has been reported with 5-HT3 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 alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT3 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 and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue ondansetron and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if ondansetron is used concomitantly with other serotonergic drugs (see PRECAUTIONS and OVERDOSAGE ).

Precautions

General

Ondansetron is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction. 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.

Serotonin Syndrome

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.

Drug Interactions

Ondansetron does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver (see CLINICAL PHARMACOLOGY: Pharmacokinetics ). 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. On the basis of available data, no dosage adjustment is recommended for patients on these drugs.

Apomorphine

Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, concomitant use of apomorphine with ondansetron is contraindicated (see CONTRAINDICATIONS ).

Phenytoin, Carbamazepine, and Rifampicin

In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampicin), 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.^{1 ,3}

Serotonergic Drugs

Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) (see WARNINGS ).

Tramadol

Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed, data from 2 small studies indicate that ondansetron may be associated with an increase in patient controlled administration of tramadol.^{4 ,5}

Chemotherapy

Tumor response to chemotherapy in the P-388 mouse leukemia model is not affected by ondansetron. In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.

In a crossover study in 76 pediatric patients, I.V. ondansetron did not increase blood levels of high-dose methotrexate.

Use in Surgical Patients

The coadministration of ondansetron had no effect on the pharmacokinetics and pharmacodynamics of temazepam.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenic effects were not seen in 2-year studies in rats and mice with oral ondansetron doses up to 10 and 30 mg/kg/day, respectively. Ondansetron was not mutagenic in standard tests for mutagenicity. Oral administration of ondansetron up to 15 mg/kg/day did not affect fertility or general reproductive performance of male and female rats.

Pregnancy

Teratogenic Effects

Pregnancy Category B

Reproduction studies have been performed in pregnant rats and rabbits at daily oral doses up to 15 and 30 mg/kg/day, respectively, and have revealed no evidence of impaired fertility or harm to the fetus due to ondansetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Ondansetron is excreted in the breast milk of rats. It is not known whether ondansetron is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ondansetron is administered to a nursing woman.

Pediatric Use

Little information is available about dosage in pediatric patients 4 years of age or younger (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION sections for use in pediatric patients 4 to 18 years of age).

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 were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and 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. Dosage adjustment is not needed in patients over the age of 65 (see CLINICAL PHARMACOLOGY ).

Adverse Reactions

The following have been reported as adverse events in clinical trials of patients treated with ondansetron, the active ingredient of ondansetron tablets. A causal relationship to therapy with ondansetron has been unclear in many cases.

Chemotherapy-Induced Nausea and Vomiting

The adverse events in Table 5 have been reported in ≥5% of adult patients receiving a single 24 mg ondansetron tablet in 2 trials. These patients were receiving concurrent highly emetogenic cisplatin-based chemotherapy regimens (cisplatin dose ≥50 mg/m²).

Table 5. Principal Adverse Events in US Trials: Single Day Therapy With 24 mg Ondansetron Tablets (Highly Emetogenic Chemotherapy)

Event	Ondansetron 24 mg q.d . (n=300)	Ondansetron 8 mg b.i.d . (n=124)	Ondansetron 32 mg q.d . (n=117)
Headache	33 (11%)	16 (13%)	17 (15%)
Diarrhea	13 (4%)	9 (7%)	3 (3%)

The adverse events in Table 6 have been reported in ≥5% of adults receiving either 8 mg of ondansetron tablets 2 or 3 times a day for 3 days or placebo in 4 trials. These patients were receiving concurrent moderately emetogenic chemotherapy, primarily cyclophosphamide-based regimens.

Table 6. Principal Adverse Events in US Trials: 3 Days of Therapy With 8 mg Ondansetron Tablets (Moderately Emetogenic Chemotherapy)

Event	Ondansetron 8 mg b.i.d . (n=242)	Ondansetron 8 mg t.i.d . (n=415)	Placebo (n=262)
Headache	58 (24%)	113 (27%)	34 (13%)
Malaise/fatigue	32 (13%)	37 (9%)	6 (2%)
Constipation	22 (9%)	26 (6%)	1 (<1%)
Diarrhea	15 (6%)	16 (4%)	10 (4%)
Dizziness	13 (5%)	18 (4%)	12 (5%)

Central Nervous System

There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving ondansetron.

Hepatic

In 723 patients receiving cyclophosphamide-based chemotherapy in US clinical trials, AST and/or ALT values have been reported to exceed twice the upper limit of normal in approximately 1% to 2% of patients receiving ondansetron tablets. 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 cannot be clearly determined.

There have been reports of liver failure and death in patients with cancer receiving concurrent medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is unclear.

Integumentary

Rash has occurred in approximately 1% of patients receiving ondansetron.

Other

Rare cases of anaphylaxis, bronchospasm, tachycardia, angina (chest pain), hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures have been reported. Except for bronchospasm and anaphylaxis, the relationship to ondansetron was unclear.

Radiation-Induced Nausea and Vomiting

The adverse events reported in patients receiving ondansetron tablets and concurrent radiotherapy were similar to those reported in patients receiving ondansetron tablets and concurrent chemotherapy. The most frequently reported adverse events were headache, constipation, and diarrhea.

Postoperative Nausea and Vomiting

The adverse events in Table 7 have been reported in ≥5% of patients receiving ondansetron tablets at a dosage of 16 mg orally in clinical trials. With the exception of headache, 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 7. Frequency of Adverse Events From Controlled Studies With Ondansetron Tablets (Postoperative Nausea and Vomiting)

Adverse Event	Ondansetron 16 mg (n=550)	Placebo (n=531)
Wound problem	152 (28%)	162(31%)
Drowsiness/sedation	112 (20%)	122 (23%)
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%)
Bradycardia	32 (6%)	30 (6%)
Shiver(s)	28 (5%)	30 (6%)
Urinary retention	28 (5%)	18 (3%)
Hypotension	27 (5%)	32 (6%)
Pruritus	27 (5%)	20 (4%)

Observed During Clinical Practice

In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of oral 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

Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported.

General

Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis/anaphylactoid reactions, angioedema, bronchospasm, shortness of breath, hypotension, laryngeal edema, stridor) have also been reported. Laryngospasm, shock, and cardiopulmonary arrest have occurred during allergic reactions in patients receiving injectable ondansetron.

Hepatobiliary

Liver enzyme abnormalities

Lower Respiratory

Hiccups

Neurology

Oculogyric crisis, appearing alone, as well as with other dystonic reactions

Skin

Urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Special Senses

Drug Abuse And Dependence

Animal studies have shown that ondansetron is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.

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 events uled 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 1 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 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.

Dosage And Administration

Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy

The recommended adult oral dosage of ondansetron is 24 mg given as three 8 mg tablets administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥50 mg/m². Multiday, single-dose administration of a 24 mg dosage has not been studied.

Pediatric Use

There is no experience with the use of a 24 mg dosage in pediatric patients.

Geriatric Use

The dosage recommendation is the same as for the general population.

Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Cancer Chemotherapy

The recommended adult oral dosage is one 8 mg ondansetron tablet given twice-a-day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8 mg ondansetron tablet should be administered twice-a-day (every 12 hours) for 1 to 2 days after completion of chemotherapy.

Pediatric Use

For pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4 mg ondansetron tablet given 3 times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4 mg ondansetron tablet should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy.

Geriatric Use

The dosage is the same as for the general population.

Prevention of Nausea and Vomiting Associated With Radiotherapy, Either Total Body Irradiation, or Single High-Dose Fraction or Daily Fractions to the Abdomen

The recommended oral dosage is one 8 mg ondansetron tablet given 3 times a day.

For total body irradiation, one 8 mg ondansetron tablet should be administered 1 to 2 hours before each fraction of radiotherapy administered each day.

For single high-dose fraction radiotherapy to the abdomen, one 8 mg ondansetron tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.

For daily fractionated radiotherapy to the abdomen, one 8 mg ondansetron tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.

Pediatric Use

There is no experience with the use of ondansetron tablets in the prevention of radiation-induced nausea and vomiting in pediatric patients.

Geriatric Use

The dosage recommendation is the same as for the general population.

Postoperative Nausea and Vomiting

The recommended dosage is 16 mg given as two 8 mg ondansetron tablets, 1 hour before induction of anesthesia.

Pediatric Use

There is no experience with the use of ondansetron tablets in the prevention of postoperative nausea and vomiting in pediatric patients.

Geriatric Use

The dosage is the same as for the general population.

Dosage Adjustment for Patients With Impaired Renal Function

The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.

Dosage Adjustment for Patients With Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh² score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life. In such patients, a total daily dose of 8 mg should not be exceeded.

How Supplied

Ondansetron tablets, USP, for oral administration, are available as:

4 mg: (ondansetron HCl, USP equivalent to 4 mg of ondansetron) round, white, film-coated tablets, debossed GG on one side and 927 on the reverse side. They are supplied as follows:

NDC 0781-1679-31 in bottles of 30

NDC 0781-1679-33 in unit of use package of 3

8 mg: (ondansetron HCl, USP equivalent to 8 mg of ondansetron) round, yellow, film-coated tablets, debossed GG on one side and 928 on the reverse side. They are supplied as follows:

NDC 0781-1681-31 in bottles of 30

NDC 0781-1681-33 in unit of use package of 3

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light.

Dispense in a tight, light-resistant container as defined in the USP.

References

• 1.Britto MR, Hussey EK, Mydlow P, et al. Effect of enzyme inducers on ondansetron (OND) metabolism in humans. Clin Pharmacol Ther . 1997;61:228.
• 2.Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Brit J Surg. 1973;60:646-649.
• 3.Villikka K, Kivisto KT, Neuvonen PJ. The effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron. Clin Pharmacol Ther. 1999;65:377-381.
• 4.De Witte JL, Schoenmaekers B, Sessler DI, et al. Anesth Analg . 2001;92:1319-1321.
• 5.Arcioni R, della Rocca M, Romanò R, et al. Anesth Analg. 2002;94:1553-1557.

02-2015M

7333

Sandoz Inc.

Princeton, NJ 08540

Repackaging Information

Please reference the How Supplied section uled above for a description of individual tablets. This drug product has been received by Aphena Pharma - TN in a manufacturer or distributor packaged configuration and repackaged in full compliance with all applicable cGMP regulations. The package configurations available from Aphena are uled below:

Count	8 mg
900	43353-881-88

Store between 20°-25°C (68°-77°F). See USP Controlled Room Temperature. Dispense in a tight light-resistant container as defined by USP. Keep this and all drugs out of the reach of children.

Repackaged by: Cookeville, TN 38506 20171214JH

Principal Display Panel - 8 Mg

NDC 43353-881 - Ondansetron HCl 8 mg - Rx Only