What is the recommended dose of palonosetron (5-HT3 receptor antagonist) for chemotherapy-induced nausea and vomiting (CINV) or postoperative nausea and vomiting (PONV)?

Recommended Dosing of Palonosetron for Nausea and Vomiting

For chemotherapy-induced nausea and vomiting (CINV), the recommended dose of palonosetron is 0.25 mg IV administered over 30 seconds approximately 30 minutes before the start of chemotherapy. For postoperative nausea and vomiting (PONV), the recommended dose is 0.075 mg IV administered over 10 seconds immediately before anesthesia induction. 1

Chemotherapy-Induced Nausea and Vomiting (CINV)

Dosing for CINV

• Palonosetron is administered as a single 0.25 mg IV dose over 30 seconds, approximately 30 minutes before chemotherapy initiation 1, 2
• Palonosetron is only available as an intravenous formulation for CINV 3
• No schedule has been proven better than a single dose beginning before chemotherapy 3

Efficacy for CINV

• Palonosetron is indicated for:
  • Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy 1, 4
  • Prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy 1, 5
• Palonosetron has demonstrated superior efficacy compared to ondansetron and dolasetron in preventing both acute and delayed CINV 4, 6
• A meta-analysis of eight trials concluded there is no difference in efficacy between the 0.25 mg and 0.75 mg doses of palonosetron 3

Combination Therapy for CINV

• For highly emetogenic chemotherapy, a three-drug regimen is recommended including:
  • Palonosetron 0.25 mg IV
  • Dexamethasone (12 mg when used with aprepitant)
  • Aprepitant (125 mg on day 1, followed by 80 mg on days 2-3) 3
• For moderately emetogenic chemotherapy, palonosetron can be used alone or in combination with dexamethasone 3

Postoperative Nausea and Vomiting (PONV)

Dosing for PONV

• For prevention of PONV, the recommended dose is 0.075 mg IV administered over 10 seconds immediately before the induction of anesthesia 1
• Efficacy for PONV has been demonstrated for up to 24 hours following surgery 1
• Clinical trials showed that palonosetron 0.075 mg significantly reduced the severity of nausea compared to placebo 1

Clinical Considerations

Pharmacological Properties

• Palonosetron is a second-generation 5-HT3 receptor antagonist with distinct pharmacological properties:
  • Higher receptor-binding affinity than first-generation agents 5, 2
  • Longer half-life (43.7-128 hours) compared to other 5-HT3 antagonists 5, 7
  • These properties contribute to its efficacy in preventing both acute and delayed CINV 4

Common Side Effects

• The most common adverse reactions in CINV (incidence ≥5%) are headache and constipation 1, 2
• The most common adverse reactions in PONV (incidence ≥2%) are QT prolongation, bradycardia, headache, and constipation 1

Special Populations

• Safety and effectiveness in patients below 18 years of age have not been established 1
• The potential for clinically significant drug interactions with palonosetron appears to be low 1

Important Caveats

• Palonosetron is contraindicated in patients with known hypersensitivity to the drug or any of its components 1
• Hypersensitivity reactions may occur in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists 1
• Unlike other 5-HT3 receptor antagonists, palonosetron is specifically indicated for prevention of delayed nausea and vomiting associated with moderately emetogenic chemotherapy 4
• When treating breakthrough vomiting, consider adding a medication from a different class, such as a dopamine antagonist 8