Monograph: |
Palonosetron
Physicochemical Characteristics
Stability.
The stability of palonosetron hydrochloride at concentrations of 5 and 30 micrograms/mL was assessed in polyvinyl chloride bags of the following 4 infusion solutions: glucose 5%, sodium chloride 0.9%, glucose 5% in sodium chloride 0.45%, and glucose 5% in lactated Ringer's solution. All solutions were considered to be physically and chemically stable for at least 48 hours at room temperature exposed to light, and for 14 days under refrigeration.
Adverse Effects and Precautions
As for Ondansetron, although no dosage reduction is considered necessary in hepatic impairment. Diarrhoea, fatigue, and abdominal pain may also occur. Patients with a history of constipation or signs of subacute intestinal obstruction should be monitored if given palonosetron. Palonosetron should be used with caution in patients who have or may develop prolongation of the QT interval.
Effects on the cardiovascular system.
For a discussion of the effects of 5-HT3 antagonists on the cardiovascular system, see under Ondansetron.
Interactions
Palonosetron should be used with caution in patients taking drugs that prolong the QT interval.
Pharmacokinetics
Palonosetron has a volume of distribution of around 7 to 8 litres/kg; plasma protein binding is about 62%. About 50% of a dose is metabolised in the liver by cytochrome P450 isoenzymes (notably CYP2D6, but also CYP3A4 and CYP1A2). About 80% of a dose is recovered in the urine within 144 hours, as palonosetron and its metabolites. The mean elimination half-life is reported to be about 40 hours.
Uses and Administration
Palonosetron is a 5-HT3 antagonist used in the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy. Palonosetron is given as the hydrochloride but doses are expressed in terms of the base; 280.8 micrograms of palonosetron hydrochloride is equivalent to about 250 micrograms of palonosetron. A dose of 250 micrograms is given intravenously over 30 seconds about 30 minutes before chemotherapy. Repeated dosing within 7 days is not recommended.
|