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For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory

Ondansetron Mouth Dissolving Tablets 

Composition

Each tablet contains :
Ondansetron ……………… 4 mg/8 mg 

Therapeutic Category: Antiemetic

Pharmacology

Pharmacodynamics

Ondansetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 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'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-HT3 receptors and initiate the vomiting reflex.

The mechanism of action in post-operative nausea and vomiting is not known but there may be common pathways with cytotoxic-induced nausea and vomiting.

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. 

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. 

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.

In patients with mild-to-moderate hepatic impairment, clearance is reduced twofold and mean half-life is increased to 11.6 hours compared to 5.7 hours in normal individuals. In patients with severe hepatic impairment, clearance is reduced twofold to threefold 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 is 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. 

Indications

Ondansetron is indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy, and for the prevention and treatment of post-operative nausea and vomiting (PONV).

Contraindications

Hypersensitivity to any component of the preparation.

Side effects/Adverse reactions

Ondansetron is known to increase large bowel transit time and may cause constipation in some patients. The following side effects can occur: headache, a sensation of flushing or warmth in the head and epigastrium, and occasional transient asymptomatic increases in aminotransferase and possible extrapyramidal reactions. It does not appear to affect plasma prolactin concentrations.
There have been rare reports of immediate hypersensitivity reactions including anaphylaxis. Rare cases of transient visual disturbances (e.g. blurred vision) have been reported during rapid intravenous administration of ondansetron.

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. 

Ondansetron is not teratogenic in animals. There is no experience in humans. As with other medications, ondansetron should not be used during pregnancy, especially during the first trimester, unless the expected benefit to the patient is thought to outweigh any possible risk to the foetus.

Tests have shown that ondansetron is secreted in breast milk. It is therefore recommended that mothers receiving ondansetron should not breastfeed their babies.

Clearance of ondansetron is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg should not be exceeded.

Warnings

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists. 

Dosage and Administration

Adults

Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy
The recommended adult dose is 24 mg ondansetron as a single oral dose administered 30 minutes before the start of chemotherapy.

Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy 
The recommended adult dose is 8 mg ondansetron orally 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. 8 mg should be administered twice a day (every 12 hours) orally for 1 to 2 days after completion of chemotherapy. 

Prevention of nausea and vomiting associated with radiotherapy 
The recommended dose is 8 mg ondansetron orally three times a day.

Postoperative Nausea and Vomiting 
The recommended dose is 8 mg ondansetron orally 1 hour before induction of anesthesia followed by further two doses of 8 mg at intervals of 8 hours. 

Pediatric Use

For prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy, in 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 4 mg ondansetron orally 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. 4 mg should be administered orally three times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy. There is limited experience with the use of oral ondansetron in the other indication in paediatric patients.

Geriatric Use 

The dosage recommendation is the same as for adults. 

Patients with renal impairment

No alteration of daily dosage or frequency of dosing or route of administration are required.

Patients with hepatic impairment

Clearance of ondansetron is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients a total daily dose of 8 mg should not be exceeded.

Symptoms and treatment of 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. 

Storage conditions, user instructions and pharmaceutical precautions

Storage condition :
Expiry :

Presentation
Blister pack of 10 tablets