Vomiren

Approved Indications:

• Chemotherapy-Induced Nausea and Vomiting (CINV):
• Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC)
• Prevention of acute nausea and vomiting associated with highly emetogenic chemotherapy (HEC)
• Postoperative Nausea and Vomiting (PONV):
• Prevention of postoperative nausea and vomiting (single 0.075 mg IV dose administered immediately before induction of anesthesia)

Clinically Accepted Off-Label Uses:

• Delayed CINV prophylaxis beyond 72 hours (especially in HEC regimens with anthracycline/cyclophosphamide)
• Breakthrough CINV (when other agents are inadequate)
• Pediatric use in CINV (age ≥1 month approved in some jurisdictions)

Route: Intravenous (IV) or Oral (where available)

Chemotherapy-Induced Nausea and Vomiting (Adults):

• IV: 0.25 mg IV over 30 seconds, administered 30 minutes prior to chemotherapy on Day 1
• Oral (Capsule): 0.5 mg orally approximately 1 hour before chemotherapy (if available)

Postoperative Nausea and Vomiting (Adults):

• IV: 0.075 mg IV as a single dose administered immediately before induction of anesthesia

Pediatrics (CINV):

• ≥1 month to 17 years:
• IV: 20 mcg/kg (maximum 1.5 mg) as a single dose, administered 30 minutes before chemotherapy

Special Populations:

• Renal Impairment: No dosage adjustment required
• Hepatic Impairment: No dosage adjustment required
• Elderly: No dosage adjustment necessary
• Obese patients: No specific recommendations; standard dosing applicable

Palonosetron is a highly selective serotonin (5-HT3) receptor antagonist that binds to 5-HT3 receptors located on vagal nerve terminals in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. It inhibits serotonin-mediated emetogenic signals, particularly those triggered by chemotherapy. Palonosetron’s high receptor-binding affinity and long plasma half-life contribute to its efficacy in both acute and delayed phases of chemotherapy-induced nausea and vomiting.

• Absorption: Rapid distribution following IV administration
• Bioavailability (oral): ~97% (oral capsule, where available)
• Tmax:
• IV: immediate
• Oral: ~5.1 hours
• Distribution:
• Volume of distribution: ~8.3 L/kg
• Protein binding: ~62%
• Metabolism:
• Primarily hepatic via CYP2D6; minor metabolism via CYP3A4 and CYP1A2
• Elimination:
• ~40% excreted unchanged in urine
• Half-life: ~40 hours (IV); extended to ~48 hours in elderly
• Clearance: ~160 mL/h/kg

• Pregnancy:
• FDA Category B (older classification): Animal studies have not demonstrated harm, but human data are insufficient
• Use during pregnancy only if clearly needed
• Lactation:
• Unknown if palonosetron is excreted in breast milk
• Use caution; consider withholding breastfeeding for 24 hours after administration due to long half-life
• Risk-benefit assessment recommended

• Primary Class: Antiemetic
• Subclass: 5-HT3 Receptor Antagonist (Second-Generation)

• Known hypersensitivity to palonosetron or any of its components
• Concurrent use with other 5-HT3 antagonists (risk of serotonin syndrome)
• History of severe hypersensitivity to other 5-HT3 antagonists (e.g., ondansetron, granisetron)

• Serotonin Syndrome:
• Possible when used with serotonergic agents (e.g., SSRIs, SNRIs, MAOIs)
• Monitor for agitation, hallucinations, tachycardia, muscle rigidity
• Hypersensitivity Reactions:
• Rare anaphylaxis and anaphylactoid reactions reported
• QT Prolongation:
• Generally minimal risk, but caution in patients with known QT prolongation or on QT-prolonging drugs
• Pediatric Caution:
• Approved in some regions for pediatric CINV; use only under specialist guidance

Very Common (≥10%):

• Headache
• Constipation

Common (1–10%):

• Dizziness
• Fatigue
• Diarrhea
• Injection site reactions
• Insomnia
• Anorexia

Rare/Serious (<1%):

• Anaphylaxis
• Bradycardia
• Hypokalemia
• Serotonin syndrome
• ECG changes (QT prolongation)

Onset & Severity:

• Most adverse events are mild to moderate and transient
• Onset typically within hours of administration

• Serotonergic Agents (SSRIs, SNRIs, Tramadol, MAOIs):
• May increase risk of serotonin syndrome
• Other 5-HT3 Antagonists (e.g., ondansetron):
• Avoid combination; no added benefit and increased side effect risk
• QT-Prolonging Agents:
• Monitor ECG when combined (e.g., methadone, amiodarone, antipsychotics)
• CYP450 Interactions:
• Palonosetron is metabolized mainly by CYP2D6 with minor contributions from CYP3A4 and CYP1A2
• No significant enzyme inhibition or induction

• NCCN and MASCC Guidelines:
• Continue to recommend palonosetron as a first-line agent for acute and delayed CINV prevention with MEC and HEC regimens
• FDA Labeling (Recent):
• Strengthened caution regarding serotonin syndrome
• Added pediatric pharmacokinetic and efficacy data
• Clinical Shift Toward Second-Generation Agents:
• Palonosetron preferred due to longer duration of action and improved delayed-phase CINV control

• IV Formulations:
• Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C
• Protect from light
• Do not freeze
• Handling:
• Inspect visually for particulate matter and discoloration prior to administration
• Compatible with common IV fluids (e.g., 0.9% NaCl)
• Oral Capsules (if available):
• Store at room temperature (20°C to 25°C) in original packaging