population. prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy: the recommended adult oral dosage is one 8 mg ondansetron orally disintegrating 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 orally disintegrating 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 orally disintegrating 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 orally disintegrating 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 orally disintegrating tablets given 3 times a day. for total body irradiation , one 8 mg ondansetron orally disintegrating 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 orally disintegrating 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 orally disintegrating 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 orally disintegrating 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 orally disintegrating tablets 1 hour before induction of anesthesia. pediatric use: there is no experience with the use of ondansetron orally disintegrating 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-pugh 2 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.

r 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 greater than or equal to 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

in synthesis, bilateral abdominal vagotomy and greater splanchnic nerve section, or pretreatment with a serotonin 5-ht 3 receptor antagonist. in normal volunteers, single intravenous doses of 0.15 mg/kg of ondansetron had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time. multiday administration of ondansetron has been shown to slow colonic transit in normal volunteers. ondansetron has no effect on plasma prolactin concentrations. 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. pharmacokinetics ondansetron is well absorbed from the gastrointestinal tract and undergoes some first-pass metabolism. mean bioavailability in healthy subjects, following administration of a single 8 mg tablet, is approximately 56%. ondansetron systemic exposure does not increase proportionately to dose. auc from a 16 mg tablet was 24% greater than predicted from an 8 mg tablet dose. this may reflect some reduction of first-pass metabolism at higher oral doses. bioavailability is also slightly enhanced by the presence of food but unaffected by antacids. ondansetron is extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered as the parent compound from the urine. the primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation. although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of ondansetron. in vitro metabolism studies have shown that ondansetron is a substrate for human hepatic cytochrome p-450 enzymes, including cyp1a2, cyp2d6, and cyp3a4. in terms of overall ondansetron turnover, cyp3a4 played the predominant role. because of the multiplicity of metabolic enzymes capable of metabolizing ondansetron, it is likely that inhibition or loss of one enzyme (e.g., cyp2d6 genetic deficiency) will be compensated by others and may result in little change in overall rates of ondansetron elimination. ondansetron elimination may be affected by cytochrome p-450 inducers. in a pharmacokinetic study of 16 epileptic patients maintained chronically on cyp3a4 inducers, carbamazepine, or phenytoin, reduction in auc, c max , and t ½ of ondansetron was observed. 1 this resulted in a significant increase in clearance. however, on the basis of available data, no dosage adjustment for ondansetron is recommended (see precautions: drug interactions). in humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron. gender differences were shown in the disposition of ondansetron given as a single dose. the extent and rate of ondansetron's absorption is greater in women than men. slower clearance in women, a smaller apparent volume of distribution (adjusted for weight), and higher absolute bioavailability resulted in higher plasma ondansetron levels. these higher plasma levels may in part be explained by differences in body weight between men and women. it is not known whether these gender-related differences were clinically important. more detailed pharmacokinetic information is contained in tables 1 and 2 taken from 2 studies.