Ondansetron Medicine uses, is a serotonin 5-HT3 receptor antagonist used to prevent nausea and vomiting in cancer chemotherapy and postoperatively. A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties.
Commonly formulated as oral tablets, orally disintegrating tablets, and injections, and available as generic products as well, FDA withdrew its approval for the use of all intravenous drug products containing more than 16 mg of ondansetron hydrochloride in a single dose, due to a high risk of QT prolongation.
Ondansetron Medicine uses
In the {adult patient} population:
- i) orally administered ondansetron tablets and orally disintegrating tablets (ODT) are indicated for: – the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, including high dose (ie. greater than or equal to 50 mg/m2) cisplatin therapy, and radiotherapy, and – the prevention and treatment of postoperative nausea and vomiting
- ii) intravenously administered ondansetron injection formulations are indicated for: – the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, including high dose (ie. greater than or equal to 50 mg/m2) cisplatin therapy, and – the prevention and treatment of postoperative nausea and vomiting
In the {pediatric 4-18 years of age} patient population:
- i) ondansetron was effective and well tolerated when given to children 4-12 years of age for the treatment of post-chemotherapy induced nausea and vomiting,
- ii) ondansetron tablets, ondansetron ODT, ondansetron injection are {not indicated} for the treatment of {children 3 years} of age or younger.
- iii) ondansetron tablets, ondansetron ODT, ondansetron injection are not indicated for use in any age group of the pediatric population for the treatment of postoperative nausea and vomitting or post-radiotherapy induced nausea and vomiting.
In the geriatric (>65 years of age) patient population:
- i) efficacy and tolerance of ondansetron were similar to that observed in younger adults for the treatment of post-chemotherapy and radiotherapy-induced nausea and vomiting.
- ii) clinical experience in the use of ondansetron in the prevention and treatment of postoperative nausea and vomiting is limited and is not indicated for use in the geriatric patient population.
Pharmacodynamics:
Ondansetron is a highly specific and selective serotonin 5-HT3 receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors. The serotonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin,
as well as the efficacy of antiemetic agents, suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.
Mechanism of action
Ondansetron is a selective antagonist of the serotonin receptor subtype, 5-HT3.
Absorption
Ondansetron is absorbed from the gastrointestinal tract and undergoes some limited first-pass metabolism 10. Mean bioavailability in healthy subjects, following administration of a single 8-mg tablet, was recorded as being approximately 56% to 60% . Bioavailability is also slightly enhanced by the presence of food.
Volume of distribution
The volume of distribution of ondansetron has been recorded as being approximately 160L.
Protein binding
The plasma protein binding associated with ondansetron was documented as approximately 73% .
Metabolism
In vitro metabolism studies have shown that ondansetron is a substrate for human hepatic cytochrome P450 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 enzyme deficiency) will be compensated by others and may result in little change in overall rates of ondansetron clearance.
Half-life
The half-life of ondansetron after either an 8 mg oral dose or intravenous dose was approximately 3-4 hours and could be extended to 6-8 hours in the elderly.
Route of elimination
Following oral or IV administration, ondansetron is extensively metabolised and excreted in the urine and faece.
Clearance
The clearance values determined for ondansetron approximately 0.38 L/h/kg in normal adult.
Toxicity
There is little information concerning overdosage with ondansetron , there have been certain cases of adverse effects associated with particular dosages of ondansetron used.
“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 another patient that took 48 mg of oral ondansetron.
Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed.
Neuromuscular abnormalities, autonomic instability, somnolence, and a brief generalized tonic-clonic seizure (which resolved after a dose of benzodiazepine) were observed in a 12-month-old infant who ingested seven or eight 8-mg ondansetron tablets (approximately forty times,, the recommended 0.1-0.15 mg/kg dose for a pediatric patient).
Food Interactions
Take with or without food. The absorption is unaffected by food.
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