Usage
Palonosetron is primarily prescribed for the prevention of nausea and vomiting, specifically:
- Chemotherapy-induced nausea and vomiting (CINV): Used for both acute and delayed CINV associated with moderately and highly emetogenic chemotherapy.
- Postoperative nausea and vomiting (PONV): Effective for preventing PONV for up to 24 hours following surgery.
Pharmacological Classification: Palonosetron is classified as a 5-HT3 receptor antagonist, a type of antiemetic.
Mechanism of Action: Palonosetron works by selectively blocking serotonin-3 (5-HT3) receptors in the central nervous system (CNS), particularly in the chemoreceptor trigger zone (CTZ) and the vagal afferents in the gastrointestinal (GI) tract. This action inhibits serotonin, a neurotransmitter that plays a key role in the initiation of the vomiting reflex.
Alternate Names
- Generic Name: Palonosetron hydrochloride
- Brand Names: Aloxi®, Akynzeo® (in combination with netupitant)
How It Works
Pharmacodynamics: Palonosetron exerts its antiemetic effect by antagonizing 5-HT3 receptors. It has a high affinity for these receptors and a long duration of action, which contributes to its efficacy in preventing both acute and delayed nausea and vomiting.
Pharmacokinetics:
- Absorption: After intravenous administration, palonosetron is rapidly absorbed and distributed.
- Metabolism: Palonosetron is primarily metabolized in the liver via multiple cytochrome P450 (CYP) enzymes, including CYP2D6, CYP3A4, and CYP1A2.
- Elimination: Palonosetron is eliminated through both renal (urine) and hepatic (bile) routes. It has a relatively long elimination half-life (approximately 40 hours), allowing for once-daily dosing.
Mode of Action: Palonosetron binds to 5-HT3 receptors, preventing serotonin from binding and activating these receptors. This blocks the initiation of the vomiting reflex.
Elimination Pathways: Palonosetron is eliminated through both renal and hepatic pathways, including metabolism by CYP enzymes.
Dosage
Standard Dosage
Adults:
- CINV: 0.25 mg IV administered over 30 seconds, approximately 30 minutes before chemotherapy.
- PONV: 0.075 mg IV administered over 10 seconds, immediately before induction of anesthesia.
Children:
- CINV: 20 mcg/kg (maximum 1.5 mg) IV infused over 15 minutes, approximately 30 minutes before chemotherapy.
- PONV: Safety and efficacy have not been established in pediatric patients for PONV.
Special Cases:
- Elderly Patients: Dose adjustment is not generally necessary.
- Patients with Renal Impairment: Dose adjustment is not required.
- Patients with Hepatic Dysfunction: Dose adjustment is not required.
- Patients with Comorbid Conditions: No specific dose adjustments are routinely recommended, but clinical judgment should be exercised.
Clinical Use Cases
- Intubation: Palonosetron can be used to prevent nausea and vomiting associated with intubation procedures.
- Surgical Procedures: It is effective for preventing PONV following various surgical procedures.
- Mechanical Ventilation: Can be used in patients undergoing mechanical ventilation to prevent nausea and vomiting.
- Intensive Care Unit (ICU) Use: May be used in ICU settings to manage nausea and vomiting.
- Emergency Situations: Not typically used in acute emergency situations like status epilepticus or cardiac arrest.
Dosage Adjustments
No routine dosage adjustments are recommended for renal or hepatic impairment, elderly patients, or patients with comorbid conditions. However, individualized dosing may be considered based on patient-specific factors and clinical judgment.
Side Effects
Common Side Effects:
- Headache
- Constipation
- Dizziness
Rare but Serious Side Effects:
- Hypersensitivity reactions (including anaphylaxis and anaphylactic shock)
- QT interval prolongation
- Serotonin syndrome
Long-Term Effects:
Limited data are available on long-term effects.
Adverse Drug Reactions (ADR):
Clinically significant ADRs include hypersensitivity reactions and QT prolongation, requiring immediate intervention.
Contraindications
- Hypersensitivity to palonosetron or any of its components.
Drug Interactions
- Drugs that prolong the QT interval should be used with caution.
- Serotonergic drugs may increase the risk of serotonin syndrome.
Pregnancy and Breastfeeding
- Pregnancy: Palonosetron should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.
- Breastfeeding: It is unknown if palonosetron is excreted in human milk. Caution should be exercised when administering to breastfeeding mothers.
Drug Profile Summary
- Mechanism of Action: 5-HT3 receptor antagonist.
- Side Effects: Headache, constipation, dizziness, hypersensitivity reactions, QT prolongation.
- Contraindications: Hypersensitivity to palonosetron.
- Drug Interactions: QT prolonging drugs, serotonergic drugs.
- Pregnancy & Breastfeeding: Use with caution.
- Dosage: Refer to the Dosage section above.
- Monitoring Parameters: Monitor for hypersensitivity reactions, QT prolongation, and serotonin syndrome.
Popular Combinations
Palonosetron is often used in combination with dexamethasone for enhanced antiemetic efficacy, especially in the setting of highly emetogenic chemotherapy.
Precautions
- General Precautions: Pre-screening for allergies and cardiac conditions, especially those associated with QT prolongation, is recommended.
- Specific Populations: Use cautiously in pregnant or breastfeeding women, elderly patients, and those with cardiac conditions.
- Lifestyle Considerations: No specific lifestyle restrictions are generally associated with palonosetron use.
FAQs
Q1: What is the recommended dosage for Palonosetron?
A: Please refer to the detailed dosage section above for specific adult, pediatric, and special population dosing.
Q2: How is Palonosetron administered?
A: Palonosetron is administered intravenously, either as a bolus injection or a short infusion.
Q3: What are the common side effects of Palonosetron?
A: Common side effects include headache, constipation, and dizziness.
Q4: What are the serious side effects of Palonosetron?
A: Rare but serious side effects include hypersensitivity reactions and QT prolongation.
Q5: Can Palonosetron be used in pregnant women?
A: Palonosetron should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.
Q6: Can Palonosetron be used in breastfeeding mothers?
A: It is unknown if palonosetron is excreted in human milk. Caution should be exercised.
Q7: Does Palonosetron interact with other medications?
A: Yes, it can interact with drugs that prolong the QT interval and serotonergic medications. Consult the Drug Interactions section for more details.
Q8: What is the mechanism of action of Palonosetron?
A: Palonosetron is a 5-HT3 receptor antagonist.
Q9: What are the indications for Palonosetron?
A: Prevention of CINV and PONV.
Q10: How long does the antiemetic effect of Palonosetron last?
A: It can provide effective antiemetic coverage for up to 24 hours following administration.
