Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1272
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Ondansetron (Tablet, Orally Disintegrating)
|
| dailymed-instance:dosage |
Instructions for Use/Handling Ondansetron Orally Disintegrating Tablets:: Do not attempt to push ondansetron orally disintegrating tablets through the foil backing. With dry hands, PEEL BACK the foil backing of 1 blister and GENTLY remove the tablet. IMMEDIATELY place the ondansetron orally disintegrating tablet on top of the tongue where it will dissolve in seconds, then swallow with saliva. Administration with liquid is not necessary.<br/>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/m. 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.<br/>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.<br/>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.<br/>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.<br/>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.<br/>Dosage Adjustment for Patients with
Impaired Hepatic Function:: In patients with severe hepatic impairment (Child-Pughscore 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.
|
| dailymed-instance:descripti... |
The active ingredient in ondansetron orally disintegrating tablets is ondansetron base, the racemic form of ondansetron, and a selective blocking agent of the serotonin 5-HTreceptor type. Chemically it is (��)1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one. It has the following structural formula: The empirical formula is CHNO representing a molecular weight of 293.4. Each 4 mg ondansetron orally disintegrating tablets for oral administration contains 4 mg ondansetron base. Each 8 mg ondansetron orally disintegrating tablets for oral administration contains 8 mg ondansetron base. Each ondansetron orally disintegrating tablet also contains the inactive ingredients aspartame, colloidal silicon dioxide, croscarmellose sodium, glycerol distearate, magnesium stearate, mannitol, talc and strawberry flavor. Ondansetron orally disintegrating tablets are orally administered formulation of ondansetron which rapidly disintegrates on the tongue and does not require water to aid dissolution or swallowing. USP disintegration test pending.
|
| dailymed-instance:clinicalP... |
Pharmacodynamics: Ondansetron is a selective 5-HTreceptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HTtype 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-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-HTreceptors 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-HTreceptor 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.<br/>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, Cand Tof ondansetron
was observed.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. Table 1. Pharmacokinetics in Normal Volunteers: Single 8 mg Ondansetron Tablet Dose Table 2. Pharmacokinetics in Normal Volunteers:
Single 24 mg Ondansetron Tablet Dose 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. In patients with mild-to-moderate hepatic impairment, clearance is reduced 2-fold and mean half-life
is increased to 11.6 hours compared to 5.7 hours in normals. In patients with severe hepatic impairment (Child-Pughscore of 10 or greater), clearance is reduced 2-fold to 3-fold and apparent volume of distribution is increased with a resultant increase in half-life to 20 hours. In patients with severe hepatic impairment, a total daily dose of 8 mg should not be exceeded. Due to the very small contribution (5%) of renal clearance to the overall clearance, renal impairment was not expected to significantly influence the total clearance of ondansetron. However, ondansetron
oral mean plasma clearance was reduced by about 50% 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. 4 mg and 8 mg doses of either ondansetron oral Solution or ondansetron orally disintegrating
tablets are bioequivalent to corresponding doses of ondansetron tablets and may be used interchangeably. One 24 mg ondansetron tablet is bioequivalent to and interchangeable with three 8 mg ondansetron tablets.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Ondansetron orally disintegrating tablets are contraindicated for patients known to have hypersensitivity to the drug.
|
| dailymed-instance:supply |
Ondansetron orally disintegrating tablets, 4 mg (as 4 mg ondansetron base) are white to off white, oval, uncoated tablets debossed with "240" on one side, plain on the other side in unit dose packs of 30 tablets (NDC 62756-240-64). Ondansetron orally disintegrating tablets, 8 mg (as 8 mg ondansetron base) are white to off white, oval, uncoated tablets debossed with "241" on one side, plain on the other side in unit dose packs of 30 tablets (NDC 62756-356-64), and unit dose packs of 10 tablets (NDC 62756-356-66). Store between 20��- 25��C (68��- 77��F). [see USP Controlled Room Temperature].
|
| dailymed-instance:genericDr... | |
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:precautio... |
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. Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported.<br/>Information for Patients: Phenylketonurics: Phenylketonuric patients should be informed that ondansetron orally disintegrating tablets contain phenylalanine (a component of aspartame). Each 4 mg and 8 mg orally disintegrating tablet contains<0.04 mg phenylalanine. Patients should be instructed not to remove ondansetron orally disintegrating 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.<br/>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 inhibitorsof 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. 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. 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. 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.<br/>Use in Surgical Patients: The coadministration of ondansetron had no effect on the pharmacokinetics and pharmacodynamics of temazepam.<br/>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.<br/>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.<br/>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.<br/>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).<br/>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 identifieddifferences 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).
|
| dailymed-instance:overdosag... |
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 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.
|
| dailymed-instance:genericMe... |
ondansetron
|
| dailymed-instance:fullName |
Ondansetron (Tablet, Orally Disintegrating)
|
| dailymed-instance:adverseRe... |
The following have been reported as adverse events in clinical trials of patients treated with ondansetron. A causal relationship to therapy with ondansetron has been unclear in many cases.<br/>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/m). Table 5. Principal Adverse Events in US Trials: Single Day Therapy With 24 mg Ondansetron Tablets (Highly Emetogenic Chemotherapy) 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) 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.<br/>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.<br/>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) Preliminary observations in a small number of subjects suggest a higher incidence of headache when ondansetron orally disintegrating tablets are taken with water, when compared to without water<br/>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 Special Senses: Eye Disorders: Cases of transient blindness, predominantly during intravenous administration, have been reported. These cases of transient blindness were reported to resolve within a few minutes up to 48 hours.
|
| dailymed-instance:warning |
Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HTreceptor antagonists.
|
| dailymed-instance:indicatio... |
1. 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. 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 orally disintegrating tablets are recommended even where the incidence of postoperative
nausea and/or vomiting is low.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Ondansetron
|