Mean bioavailability in healthy subjects, following administration of a single 8-mg tablet, is approximately 56%. Drugs with large volumes of distribution usually due to lipid solubility and low plasma protein binding are poorly diliazable. Instruct patients to immediately report any signs and symptoms of hypersensitivity reactions, including fever, chills, rash, or breathing problems to their healthcare provider.Inform patients following abdominal surgery or those with chemotherapy‑induced nausea and vomiting that Zofran may mask signs and symptoms of bowel obstruction. Oral administration of ondansetron up to 15 mg/kg per day (approximately 6 times the maximum recommended human oral dose of 24 mg per day, based on body surface area) did not affect fertility or general reproductive performance of male and female rats.In 2 randomized, double-blind, monotherapy trials, a single 24-mg oral dose of ZOFRAN was superior to a relevant historical placebo control in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/mThe first trial compared oral doses of ondansetron 24 mg as a single dose, 8 mg every 8 hours for 2 doses, and 32 mg as a single dose in 357 adult cancer patients receiving chemotherapy regimens containing cisplatin greater than or equal to 50 mg/mIn the same trial, 56% of patients receiving a single 24-mg oral dose of ondansetron experienced no nausea during the 24-hour trial period, compared with 36% of patients in the oral ondansetron 8-mg twice-a-day group (In a second trial, efficacy of a single 24-mg oral dose of ZOFRAN for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin greater than or equal to 50 mg/mA randomized, placebo-controlled, double-blind trial was conducted in the US in 67 patients receiving a cyclophosphamide-based chemotherapy regimen containing doxorubicin. A causal relationship to therapy with ZOFRAN was unclear in many cases.The most common adverse reactions reported in greater than or equal to 4% of 300 adults receiving a single 24-mg dose of ZOFRAN orally in 2 trials for the prevention of nausea and vomiting associated with highly emetogenic chemotherapy (cisplatin greater than or equal to 50 mg/mThe 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. Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported.Flushing. 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 body surface area.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. 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.Carcinogenic effects were not seen in 2-year studies in rats and mice with oral ondansetron doses up to 10 mg/kg per day and 30 mg/kg per day, respectively (approximately 4 and 6 times the maximum recommended human oral dose of 24 mg per day, based on body surface area).Ondansetron was not mutagenic in standard tests for mutagenicity. Circulating drug also distributes into erythrocytes.In vitro metabolism studies have shown that ondansetron is a substrate for human hepatic cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. (The most common adverse reactions in adults for the: ZOFRAN is indicated for the prevention of nausea and vomiting associated with:ZOFRAN is also indicated for the prevention of postoperative nausea and/or vomiting.The recommended dosage regimens for adult and pediatric patients are described in Table 1 and Table 2, respectively.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/m8 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.16 mg administered 1 hour before induction of anesthesia.Then administer 8 mg twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.Then administer 4 mg three times a day for 1 to 2 days after completion of chemotherapy.In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), do not exceed a total daily dose of 8 mg Do not attempt to push ZOFRAN ODT tablets through the foil backing.