DESCRIPTION
Mechanism of Action
• Competitive, highly selective antagonist of 5-HT3 receptors.
• 5-HT3 receptors are present centrally, in the chemoreceptor trigger
zone of the area postrema of brain, and peripherally, on vagal nerve
terminals. Antiemetic action of palonosetron may be mediated centrally,
peripherally, or at both sites.
• Does not have direct dopamine-receptor antagonist activity.
• Effective in both acute and delayed nausea and vomiting.
Absorption
Not available for oral use and is administered only via the parenteral
route.
Distribution
Nearly 60% of circulating drug is bound to plasma proteins.
Metabolism
Undergoes metabolism by multiple routes, with about 50% of parent
drug metabolized to two main metabolites, N-oxide-palonosetron and
P 6-S-hydroxy-palonosetron. Each of these metabolites has less than 1% of the
5-HT3 receptor antagonist activity of the parent compound. In vitro studies
show that CYP2D6 is the main liver microsomal enzyme involved in palonosetron
metabolism. The mean elimination half-life in adult cancer
patients is 40 hours.
Indications
1. Prevention of acute nausea and vomiting associated with initial and
repeat courses of moderately or highly emetogenic cancer
chemotherapy.
2. Prevention of delayed nausea and vomiting associated with initial
and repeat courses of moderately emetogenic cancer chemotherapy.
Dosage Range
Recommended dose is a single 0.25 mg IV dose administered 30 minutes
before chemotherapy. Repeat dosing of drug within a 7-day interval is not
recommended, as the safety and efficacy of consecutive and/or alternate dosing
in patients has not been evaluated.
Special Considerations
1. Use with caution in patients who have or may develop prolongation
of cardiac conduction intervals, especially QTc, which include
patients with hypokalemia or hypomagnesemia, patients taking
diuretics with potential for inducing electrolyte abnormalities,
patients with QT syndrome, patients taking antiarrhythmic drugs or
other drugs that lead to QT prolongation, and patients who have had
a cumulative high-dose of anthracycline therapy.
2. Palonosetron may cause hypersensitivity reactions as have been
observed with other 5-HT3 receptor antagonists. Patients should be
warned of this possibility and be advised to contact their physician at
the first sign of a skin rash or any other sign of hypersensitivity.
3. Dose reduction is not required in patients with impaired liver and/or
renal dysfunction.
4. Pregnancy category B. Breastfeeding should be avoided.
Toxicity 1
Headache occurs in 10% of patients.
Toxicity 2
Constipation, diarrhea, and/or abdominal pain.
Toxicity 3
Transient elevations in LFTs. Usually clinically asymptomatic.
Toxicity 4
Somnolence, dizziness, insomnia, and fatigue. Anxiety and euphoria
have also been observed.
Toxicity 5
Hypersensitivity reactions have been reported in rare instances.
SPECIFICATION
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