ONDANSETRON
DESCRIPTION
The active ingredient in EMESET Tablets is ondansetron hydrochloride (HCl) 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.
The empirical formula is C 18 H 19 N 3 O·HCl·2H 2 O, representing a molecular weight of 365.9.
Ondansetron HCl dihydrate is a white to off-white powder that is soluble in water and normal saline.
The active ingredient in EMESET ODT Orally Disintegrating Tablets is ondansetron base, 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.
The empirical formula is C 18 H 19 N 3 O representing a molecular weight of 293.4.
Pharmacodynamics: 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' 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-HIAA (5-hydroxyindoleacetic acid) 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.
In animals, the emetic response to cisplatin can be prevented by pretreatment with an inhibitor of serotonin 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 extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered from the urine as the parent compound. 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.
Ondansetron is a substrate for human hepatic cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. Because of the multiplicity of metabolic enzymes capable of metabolizing ondansetron, inhibition or loss of one enzyme (e.g., CYP2D6 genetic deficiency) results in little change in overall rates of ondansetron elimination.
Ondansetron is passively and completely absorbed from the gastrointestinal tract and undergoes some first-pass metabolism. Mean bioavailability in healthy subjects has ranged from 48% to 75%.
Gender differences were shown in the disposition of ondansetron given as a single dose. The extent and rate of ondansetron' 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.
A reduction in clearance and increase in elimination half-life are seen in patients over 75 years of age. In clinical trials with cancer patients, safety and efficacy was similar in patients over 65 years of age and those under 65 years of age; there was an insufficient number of patients over 75 years of age to permit conclusions in that age-group. No dosage adjustment is recommended in the elderly.
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.
In patients with severe hepatic impairment (Child-Pugh 1 score of 10 or greater), clearance is reduced twofold to threefold and apparent volume of distribution is increased with a resultant increase in half-life to 20 hours and bioavailability approaching 100%. In such patients, a total daily dose of 8 mg should not be exceeded.
Ondansetron oral plasma clearance was reduced 50% (95% Cl 22% to 68%) in patients with severe renal impairment (creatinine clearance <30 mL/min). This reduction in clearance is variable and was not consistent with an increase in half-life. No reduction in dose or dosing frequency in these patients is warranted.
Plasma protein binding of ondansetron as measured in vitro was 70% to 76% over the concentration range of 10 to 500 ng/mL. Circulating drug also distributes into erythrocytes.
Four- and 8-mg doses of either EMESET Oral Solution or EMESET ODT Orally Disintegrating Tablets are bioequivalent to corresponding doses of EMESET Tablets and may be used interchangeably. One 24-mg EMESET Tablet is bioequivalent to and interchangeable with three 8-mg EMESET Tablets.
CLINICAL TRIALS
Chemotherapy-Induced Nausea and Vomiting: Highly Emetogenic Chemotherapy: In two randomized, double-blind, monotherapy trials, a single 24-mg EMESET 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/m 2 . Steroid administration was excluded from these clinical trials. More than 90% of patients receiving a cisplatin dose >/=50 mg/m 2 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/m 2 . 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 zero emetic episodes and no rescue antiemetic medications, the primary endpoint of efficacy. Each of the three 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/m 2 , was confirmed.
Moderately Emetogenic Chemotherapy: In one double-blind US study in 67 patients, EMESET 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 below in Table 3.
Table 3: Emetic Episodes: Treatment Response Ondansetron
8-mg b.i.d.
EMESET Tablets * Placebo P Value
Number of patients 33 34
Treatment response
0 Emetic episodes 20 (61%) 2 (6%) <0.001
1-2 Emetic episodes 6 (18%) 8 (24%)
More than 2 emetic episodes/withdrawn 7 (21%) 24 (71%) <0.001
Median number of emetic episodes 0.0 Undefined #
Median time to first emetic episode (h) Undefined & 6.5
* 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 EMESET Tablet was administered twice a day for 2 days after completion of chemotherapy.
# Median undefined since at least 50% of the patients were withdrawn or had more than two emetic episodes.
& Median undefined since at least 50% of patients did not have any emetic episodes.
In one double-blind US study in 336 patients, EMESET Tablets 8 mg administered twice a day were as effective as EMESET Tablets 8 mg administered three 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 below in Table 4.
Table 4: Emetic Episodes: Treatment Response Ondansetron
8-mg b.i.d.
EMESET Tablets * 8-mg t.i.d.
EMESET Tablets #
Number of patients 165 171
Treatment response
0 Emetic episodes 101 (61%) 99 (58%)
1-2 Emetic episodes 16 (10%) 17 (10%)
More than 2 emetic episodes/withdrawn 48 (29%) 55 (32%)
Median number of emetic episodes 0.0 0.0
Median time to first emetic episode (h) Undefined & Undefined &
Median nausea scores (0-100) § 6 6
* 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 EMESET Tablet was administered twice a day for 2 days after completion of chemotherapy.
# 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 EMESET Tablet was administered three times a day for 2 days after completion of chemotherapy.
& Median undefined since at least 50% of patients did not have any emetic episodes.
§ Visual analog scale assessment: 0 = no nausea, 100 = nausea as bad as it can be.
Re-treatment: In uncontrolled trials, 148 patients receiving cyclophosphamide-based chemotherapy were re-treated with EMESET Tablets 8 mg t.i.d. of oral ondansetron 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 one to two emetic episodes occurred in 43 (11%) of the re-treatment courses.
Pediatric Studies: Three open-label, uncontrolled, foreign trials have been performed with 182 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 EMESET® (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 EMESET 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 EMESET Tablets 4 mg three times a day to be similar to those in patients 12 to 18 years of age who received EMESET Tablets 8 mg three times daily. Thus, prevention of emesis in these children was essentially the same as for patients older than 18 years of age. Overall, EMESET 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, EMESET 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 1320 cGy. Patients received three fractions for 3 days, then two 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 1000 cGy) over an anterior or posterior field size of >/=80 cm 2 to the abdomen. Patients received the first dose of EMESET Tablets (8 mg) or metoclopramide (10 mg) 1 to 2 hours before radiotherapy. If radiotherapy was given in the morning, two additional doses of study treatment were given (one tablet late afternoon and one tablet before bedtime). If radiotherapy was given in the afternoon, patients took only one further tablet that day before bedtime. Patients continued the oral medication on a t.i.d. 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 cm 2 to the abdomen. Patients received the first dose of EMESET Tablets (8 mg) or prochlorperazine (10 mg) 1 to 2 hours before the patient received the first daily radiotherapy fraction, with two subsequent doses on a t.i.d. basis. Patients continued the oral medication on a t.i.d. 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 two double-blind studies (one US study, one foreign) involving 865 patients. EMESET 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 EMESET Tablets to EMESET Injection has been performed.
INDICATIONS AND USAGE
Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin >/=50 mg/m 2 .
Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
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.
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, EMESET Tablets, EMESET ODT Orally Disintegrating Tablets, and EMESET Oral Solution are recommended even where the incidence of postoperative nausea and/or vomiting is low.
CONTRAINDICATIONS
EMESET Tablets, EMESET ODT Orally Disintegrating Tablets, and EMESET Oral Solution 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-HT 3 receptor antagonists.
PRECAUTIONS
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.
Information for Patients: Phenylketonurics: Phenylketonuric patients should be informed that EMESET ODT Orally Disintegrating Tablets contain phenylalanine (a component of aspartame). Each 4-mg and 8-mg orally disintegrating tablet contains <0.03 mg phenylalanine.
Patients should be instructed not to remove EMESET ODT Tablets from the blister until just prior to dosing. The tablet should not be pushed through the foil. With dry hands, the blister backing should be peeled completely off the blister. The tablet should be gently removed and immediately placed on the tongue to dissolve and be swallowed with the saliva. Peelable illustrated stickers are affixed to the product carton that can be provided with the prescription to ensure proper use and handling of the product.
Drug Interactions: Ondansetron does not itself 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, 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. 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.
Ondansetron has no effect on the pharmacokinetics 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 per day, respectively. Ondansetron was not mutagenic in standard tests for mutagenicity. Oral administration of ondansetron up to 15 mg/kg per 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 per 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 children 4 years of age or younger (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION sections for use in children 4 to 18 years of age).
Geriatric Use: Of the total number of subjects enrolled in cancer chemotherapy-induced and post-operative 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 EMESET. A causal relationship to therapy with EMESET has been unclear in many cases.
Chemotherapy-Induced Nausea and Vomiting: The following adverse events have been reported in >/=5% of adult patients receiving a single 24-mg EMESET Tablet in two trials. These patients were receiving concurrent highly emetogenic cisplatin-based chemotherapy regimens (cisplatin dose >/=50 mg/m 2 ).
Table 5: Principal Adverse Events in US Trials: Single Day Therapy
With 24-mg EMESET Tablets
(Highly Emetogenic Chemotherapy) Event
Ondansetron 24 mg q.d. Ondansetron 8 mg b.i.d. Ondansetron 32 mg q.d.
n = 300 n = 124 n = 117
Headache 33 (11%) 16 (13%) 17 (15%)
Diarrhea 13 (4%) 9 (7%) 3 (3%)
The following adverse events have been reported in >/=5% of adults receiving either 8 mg of EMESET Tablets two or three times a day for 3 days or placebo in four 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 EMESET Tablets
(Moderately Emetogenic Chemotherapy) Event
Ondansetron 8 mg b.i.d. Ondansetron 8 mg t.i.d. Placebo
n = 242 n = 415 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 EMESET 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 EMESET was unclear.
Radiation-Induced Nausea and Vomiting: The adverse events reported in patients receiving EMESET Tablets and concurrent radiotherapy were similar to those reported in patients receiving EMESET Tablets and concurrent chemotherapy. The most frequently reported adverse events were headache, constipation, and diarrhea.
Postoperative Nausea and Vomiting: The following adverse events have been reported in >/=5% of patients receiving EMESET 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 EMESET Tablets
(Postoperative Nausea and Vomiting) Adverse Event
Ondansetron 16 mg Placebo
(n = 550) (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%)
Preliminary observations in a small number of subjects suggest a higher incidence of headache when EMESET ODT Orally Disintegrating Tablets are taken with water, when compared to without water.
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 EMESET. 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 EMESET.
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
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 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 a patient that took 48 mg of EMESET 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.
DOSAGE AND ADMINISTRATION
Instructions for Use/Handling EMESET ODT Orally Disintegrating Tablets: Do not attempt to push EMESET ODT Tablets through the foil backing. With dry hands, PEEL BACK the foil backing of one blister and GENTLY remove the tablet. IMMEDIATELY place the EMESET ODT Tablet on top of the tongue where it will dissolve in seconds, then swallow with saliva. Administration with liquid is not necessary.
Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy: The recommended adult oral dosage of EMESET is a single 24-mg tablet administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin >/=50 mg/m 2 . Multi-day, single-dose administration of EMESET 24-mg Tablets has not been studied.
Pediatric Use: There is no experience with the use of 24-mg EMESET Tablets in children.
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 EMESET Tablet or one 8-mg EMESET ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of EMESET Oral Solution 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 EMESET Tablet or one 8-mg EMESET ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of EMESET Oral Solution should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.
Pediatric Use: For patients 12 years of age and older, the dosage is the same as for adults. For patients 4 through 11 years of age, the dosage is one 4-mg EMESET Tablet or one 4-mg EMESET ODT Tablet or 5 mL (1 teaspoonful equivalent to 4 mg of ondansetron) of EMESET Oral Solution given three 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 EMESET Tablet or one 4-mg EMESET ODT Tablet or 5 mL (1 teaspoonful equivalent to 4 mg of ondansetron) of EMESET Oral Solution should be administered three 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 EMESET Tablet or one 8-mg EMESET ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of EMESET Oral Solution given three times a day.
For total body irradiation, one 8-mg EMESET Tablet or one 8-mg EMESET ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of EMESET Oral Solution 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 EMESET Tablet or one 8-mg EMESET ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of EMESET Oral Solution 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 EMESET Tablet or one 8-mg EMESET ODT Tablet or 10 mL (2 teaspoonfuls equivalent to 8 mg of ondansetron) of EMESET Oral Solution 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 EMESET Tablets, EMESET ODT Tablets, or EMESET Oral Solution in the prevention of radiation-induced nausea and vomiting in children.
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 EMESET Tablets or two 8-mg EMESET ODT Tablets or 20 mL (4 teaspoonfuls equivalent to 16 mg of ondansetron) of EMESET Oral Solution 1 hour before induction of anesthesia.
Pediatric Use: There is no experience with the use of EMESET Tablets, EMESET ODT Tablets, or EMESET Oral Solution in the prevention of postoperative nausea and vomiting in children.
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 according to Child-Pugh 1 criteria, clearance is reduced, apparent volume of distribution is increased with a resultant increase in plasma half-life, and bioavailability approaches 100%. In such patients, a total daily dose of 8 mg should not be exceeded.