THE CATHAY DRUG CO., INC.
Each mL contains:
Ondansetron hydrochloride USP
eq to ondansetron ………………………………… 2 mg
Medicines affecting autonomic functions. Serotonin antagonists.
Ondansetron is a selective 5-HT3 receptor antagonist. Chemotherapeutic agents and radiotherapy may cause release of 5-HT in the small intestine initiating a vomiting reflex by activating vagal afferents via 5-HT3 receptors. The initiation of this reflex is blocked by ondansetron. Activation of vagal afferents may also cause a release of 5-HT 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 chemotherapy and radiotherapy may be due to the antagonism of 5-HT3 receptors on neurons located both in the peripheral and central nervous system. In psychomotor testing, ondansetron does not cause sedation nor impair performance.
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.
An 8 mg infusion of ondansetron resulted in peak plasma levels of 80 – 100 ng/mL. A continuous IV infusion of 1 mg/hour after the initial 8 mg loading dose of ondansetron maintained plasma levels over 30 ng/mL during the following 24 hour period.
The absolute bioavailability of ondansetron was approximately 60% and the plasma protein binding was approximately 73%. Following IV administration, ondansetron is extensively metabolized and excreted in the urine and feces. In humans, less than 10% of the dose is excreted unchanged in the urine. The major urinary metabolites are glucoronide conjugates (45%), sulphate conjugates (20%) and hydroxylation products (10%). The half-life of ondansetron after an 8 mg intravenous dose was approximately 3-4 hours and may be extended to 6 – 8 hours in the elderly.
In a pharmacokinetic study of 16 epileptic patients maintained chronically on carbamazepine or phenytoin, reduction in AUC, Cmax and t ½ of ondansetron was observed. This resulted in a significant increase in clearance. However, on the basis of available data, no dosage adjustment is recommended.
ONDANSETRON is indicated for the management of nausea and vomiting induced by chemotherapy and radiotherapy. ONDANSETRON is also indicated for the prevention and treatment of postoperative nausea and/or vomiting. Routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and vomiting will occur.
DOSAGE AND DIRECTIONS FOR USE
Chemotherapy and radiotherapy induced nausea and vomiting
The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens used.
Emetogenic chemotherapy and radiotherapy:
Ondansetron injection should be given by intravenous route. For most patients receiving emetogenic chemotherapy or radiotherapy, ondansetron 8 mg should be administered as a slow intravenous injection immediately before treatment.
Highly emetogenic chemotherapy
- For patients receiving highly emetogenic chemotherapy, ondansetron injection can be given by IV administration.
- A single dose of 8 mg by slow IV injection before chemotherapy, followed by two further IV doses of 8 mg 2 – 4 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 less than 15 minutes immediately before chemotherapy.
- The selection of dose regimen should be determined by the severity of the emetogenic challenge.
Ondansetron may be administered as a single intravenous dose of 5 mg/m2 body-surface immediately before chemotherapy, followed by 4 mg orally twelve hours later. A dose of 4 mg orally twice daily should be continued up to 5 days after a course of treatment.
For prevention of postoperative nausea and vomiting in paediatric patients two years and older having surgery performed under general anesthesia, ondansetron may be administered by slow intravenous injection at a dose of 0.1 mg/kg up to a maximum of 4 mg.
Repeat dosing for paediatric patients who continue to experience nausea and/or vomiting has not been studies and thus should not be given.
Efficacy and tolerance in patients aged over 65 years was similar to that seen in younger adults indicating no need to alter dosage or route of administration in the elderly.
POST-OPERATIVE NAUSEA AND VOMITING (PONV)
For the prevention of PONV ondansetron can be administered by intravenous injection. Ondansetron may be administered as a single dose of 4 mg given by slow IV injection at induction of anesthesia. For treatment of established PONV a single dose of 4 mg given by slow IV injection is recommended.
Children aged 2 years and older
For prevention of PONV in paediatric patients having surgery performed under general anesthesia, 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, at, or after induction of anesthesia.
There is limited data on the use of ondansetron in the prevention and treatment of PONV in children under 2 years of age.
The dosage recommendation is the same as for the general population.
Patients with renal impairment
The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of ondansetron.
Patients with hepatic impairment
In patients with severe impairment (Child-Pugh2 score of 10 or greater), a single maximal daily dose of 8 mg to be infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron. Or as prescribed by the physician.
Ondansetron injection should not be administered in the same syringe or infusion as any other medication.
Ondansetron injection ampules should not be autoclaved.
Single dose. Discard any remaining portion.
Ondansetron injection is contraindicated in patients known to have hypersensitivity to ondansetron or any of the ingredients of the preparation. The use of ondansetron injection for postoperative nausea and vomiting is contraindicated in pregnancy.
Patients with hepatic impairment: in patients with moderate or severe impairment of hepatic function, clearance of ondansetron is significantly reduced and serum half-life significantly prolonged. In such patients, a total daily dose of 8 mg should not be exceeded.
Ondansetron and other 5-HT3 antagonists may cause headache, a sensation of flushing or warmth, hiccups and constipation. A transient rise in liver enzymes has occasionally occurred. There have been rare reports of immediate hypersensitivity reactions including anaphylaxis. Chest pain, hypotension, tachycardia and bradycardia have been reported rarely. Dizziness and transient disturbances such as blurred vision have been reported during rapid intravenous injection.
Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists. Patients with signs of subacute intestinal obstructions should be monitored following administration, as ondansetron is known to increase large bowel transit time.
5-HT3 antagonists should generally not be used in patients who have had a hypersensitivity reaction to a member of this drug class.
They should be used with care in patients with signs of subacute intestinal obstruction of ileus. Ondansetron should be given in reduced doses to patients with moderate to severe hepatic impairment.
PREGNANCY AND LACTATION
Safety in pregnancy has not been established. Tests have shown that ondansetron passes into the milk of lactating animals. It is therefore recommended that mothers receiving ondansetron should not breastfeed their babies.
Ondansetron does not itself appear to induce or inhibit the cytochrome P450 drug metabolizing enzyme system of the liver. Because ondansetron is metabolized by hepatic cytochrome P450 drug metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inducers or inhibitors of these enzymes may change the clearance and hence, the half-life of ondansetron. On the basis of available data, no dosage adjustment for ondansetron is recommended for patients on these drugs.
Store at temperatures not exceeding 30°C. Protect from light. Keep out of reach of children.
4 mL (USP Type I) clear and colorless ampule (Box of 5’s).