Onsat IM/IV Injection: Each 4 ml ampoule contains Ondansetron Hydrochloride USP equivalent to Ondansetron 8 mg.
Ondansetron is a potent, highly selective 5HT₃ receptor-antagonist. Its precise mode of action in the control of nausea and vomiting is not known. Chemotherapeutic agents and radiotherapy may cause release of 5HT in the small intestine initiating a vomiting reflex by activating vagal afferents via 5HT₃ receptors. Ondansetron blocks the initiation of this reflex. Activation of vagal afferents may also cause a release of 5HT in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism. Thus, the effect of ondansetron in the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is probably due to antagonism of 5HT₃ receptors on neurons located both in the peripheral and central nervous system. The mechanisms of action in post-operative nausea and vomiting are not known but there may be common pathways with cytotoxic induced nausea and vomiting.
Chemotherapy and radiotherapy
Adults: The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used. The route of administration and dose of ondansetron should be flexible in the range of 8-32 mg a day and selected as shown below:
Emetogenic chemotherapy and radiotherapy: Ondansetron can be given either by rectal, oral (tablets or syrup), intravenous or intramuscular administration.
For most patients receiving emetogenic chemotherapy or radiotherapy, ondansetron 8 mg should be administered as a slow intravenous or intramuscular injection immediately before treatment, followed by 8 mg orally twelve hourly.
To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with ondansetron should be continued for up to 5 days after a course of treatment.
Highly emetogenic chemotherapy: For patients receiving highly emetogenic chemotherapy, eg, high-dose cisplatin, ondansetron can be given either by rectal, intravenous or intramuscular administration. Ondansetron has been shown to be equally effective in the following dose schedules over the first 24 hours of chemotherapy:
A single dose of 8 mg by slow intravenous or intramuscular injection immediately before chemotherapy.
A dose of 8 mg by slow intravenous or intramuscular injection immediately before chemotherapy, followed by two further intravenous or intramuscular doses of 8 mg two to four hours apart, or by a constant infusion of 1 mg/hour for up to 24 hours.
A single dose of 32 mg diluted in 50-100 ml of saline or other compatible infusion fluid and infused over not less than 15 minutes immediately before chemotherapy.
The selection of dose regimen should be determined by the severity of the emetogenic challenge.
The efficacy of ondansetron in highly emetogenic chemotherapy may be enhanced by the addition of a single intravenous dose of dexamethasone sodium phosphate, 20 mg administered prior to chemotherapy.
To protect against delayed or prolonged emesis after the first 24 hours, oral or rectal treatment with ondansetron should be continued for up to 5 days after a course of treatment.
Children: Ondansetron may be administered as a single intravenous dose of 5 mg/m² immediately before chemotherapy, followed by 4 mg orally twelve hours later. 4 mg orally twice daily should be continued for up to 5 days after the end of chemotherapy.
Elderly: Ondansetron is well tolerated by patients over 65 years and no alteration of dosage, dosing frequency or route of administration are required.
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.
Post-operative nausea and vomiting (PONV):
Adults: For the prevention of PONV ondansetron can be administered orally or by intravenous or intramuscular injection. Ondansetron may be administered as a single dose of 4 mg given by intramuscular or slow intravenous injection at induction of anaesthesia. For treatment of established PONV a single dose of 4 mg given by intramuscular or slow intravenous injection is recommended.
Children (aged 2 years and over): For prevention of PONV in paediatric patients having surgery performed under general anaesthesia, ondansetron may be administered by slow intravenous injection at a dose of 0.1 mg/kg up to a maximum of 4 mg either prior to, at or after induction of anaesthesia. For treatment of established PONV in paediatric patients, ondansetron may be administered by slow intravenous injection at a dose of 0.1 mg/kg up to a maximum of 4 mg.
There is limited data on the use of ondansetron in the prevention and treatment of PONV in children under 2 years of age.
Elderly: There is limited experience in the use of ondansetron in the prevention and treatment of PONV in the elderly, however ondansetron is well tolerated in patients over 65 years receiving chemotherapy.
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.
Patients with poor sparteine/debrisquine metabolism: The elimination half-life of ondansetron is not altered in subjects classified as poor metabolisers of sparteine and debrisquine. Consequently in such patients repeat dosing will give drug exposure levels no different from those of the general population.
No alteration of daily dosage or frequency of dosing are required.
The safety of ondansetron for use in human pregnancy has not been established. Evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to the development of the embryo, or fo.
Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5HT3 receptor antagonists.
Very rarely and predominantly with intravenous ondansetron, transient ECG changes including QT interval prolongation have been reported. Therefore, caution should be exercised in patients with cardiac rhythm or conduction disturbances, in patients treated with anti-arrhythmic agents or beta-adrenergic blocking agents and in patients with significant electrolyte disturbances.
As ondansetron is known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.
High risk group