Ondansetron Information
Ondansetron (Ondansetron) Description
The active ingredient in Ondansetron (Ondansetron) orally disintegrating tablets is Ondansetron (Ondansetron) base, the racemic form of Ondansetron (Ondansetron) , and a selective blocking agent of the serotonin 5-HT receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1 H-imidazol- 1-yl)methyl]-4H-carbazol-4-one. It has the following structural formula:
The molecular formula is CHNO representing a molecular weight of 293.4.
USP disintegration test pending.
Each Ondansetron (Ondansetron) orally disintegrating tablet intended for oral administration contains 4 mg or 8 mg of Ondansetron (Ondansetron) base. In addition, each Ondansetron (Ondansetron) orally disintegrating tablet contains the following inactive ingredients: aspartame, calcium stearate, colloidal silicon dioxide, mannitol, microcrystalline cellulose, polacrilin potassium, sodium starch glycolate, strawberry flavor and talc. Ondansetron (Ondansetron) orally disintegrating tablets are a orally administered formulation of Ondansetron (Ondansetron) which rapidly disintegrates on the tongue and does not require water to aid dissolution or swallowing.
Ondansetron (Ondansetron) Clinical Pharmacology
Ondansetron (Ondansetron) is a selective 5-HT receptor antagonist. While its mechanism of action has not been fully characterized, Ondansetron (Ondansetron) is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT 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 (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-HT 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 receptor antagonist.
In normal volunteers, single intravenous doses of 0.15 mg/kg of Ondansetron (Ondansetron) had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time. Multiday administration of Ondansetron (Ondansetron) has been shown to slow colonic transit in normal volunteers. Ondansetron (Ondansetron) has no effect on plasma prolactin concentrations.
Ondansetron (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.
Ondansetron (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 (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 (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 (Ondansetron) .
In vitro metabolism studies have shown that Ondansetron (Ondansetron) is a substrate for human hepatic cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. In terms of overall Ondansetron (Ondansetron) turnover, CYP3A4 played the predominant role. Because of the multiplicity of metabolic enzymes capable of metabolizing Ondansetron (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 (Ondansetron) elimination. Ondansetron (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, and T of Ondansetron (Ondansetron) was observed. This resulted in a significant increase in clearance. However, on the basis of available data, no dosage adjustment for Ondansetron (Ondansetron) is recommended ().
In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of Ondansetron (Ondansetron) .
Gender differences were shown in the disposition of Ondansetron (Ondansetron) given as a single dose. The extent and rate of Ondansetron (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 (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 (Ondansetron) Hydrochloride Tablet Dose
Table 2. Pharmacokinetics in Normal Volunteers: Single 24-mg Ondansetron (Ondansetron) Hydrochloride 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-Pugh2 score 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 (Ondansetron) . However, Ondansetron (Ondansetron) oral mean plasma clearance was reduced by about 50% in patients with severe renal impairment (creatinine clearance
Plasma protein binding of Ondansetron (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 Ondansetron (Ondansetron) hydrochloride oral solution or Ondansetron (Ondansetron) orally disintegrating tablets are bioequivalent to corresponding doses of Ondansetron (Ondansetron) hydrochloride tablets and may be used interchangeably. One 24-mg Ondansetron (Ondansetron) hydrochloride tablet is bioequivalent to and interchangeable with three 8-mg Ondansetron (Ondansetron) hydrochloride tablets.
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Ondansetron (Ondansetron) Principal Display Panel
Ondansetron (Ondansetron)
Orally Disintegrating Tablets
4 mg
10 Tablets
