Palonosetron (Monograph)

Brand name: Posfrea
Drug class: 5-HT3 Receptor Antagonists

Medically reviewed by Drugs.com on Sep 10, 2025. Written by ASHP.

Introduction

Antiemetic; selective, second-generation inhibitor of type 3 serotonergic (5-HT₃) receptors.^{1 34 35}

Uses for Palonosetron

Chemotherapy-induced Nausea and Vomiting

Used IV for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.^{1 24 34 35 36}

Also used IV for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.^{1 34 35 37 38}

For prevention of nausea and vomiting associated with highly emetogenic chemotherapy regimens, American Society of Clinical Oncology (ASCO) recommends a 4-drug antiemetic regimen consisting of a neurokinin 1 (NK₁) receptor antagonist, a 5-HT₃ receptor antagonist, dexamethasone, and olanzapine.⁴⁰⁰

ASCO recommends a 3-drug antiemetic regimen (a NK₁ receptor antagonist, a 5-HT₃ receptor antagonist, and dexamethasone) for carboplatin (AUC ≥4 mg/mL per minute), and a 2-drug antiemetic regimen (a 5-HT₃ receptor antagonist and dexamethasone) for other moderately emetogenic regimens.⁴⁰⁰

For chemotherapy regimens with a low emetogenic risk, ASCO recommends administration of a single dose of a 5-HT₃ receptor antagonist or dexamethasone.⁴⁰⁰

Postoperative Nausea and Vomiting

Used IV for the prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery.¹ Efficacy of the drug beyond 24 hours not demonstrated.^{1 34 40}

Routine prophylaxis not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively.^{1 34}

Recommended for patients in whom nausea and/or vomiting must be avoided postoperatively, even when anticipated incidence is low.^{1 34}

Experts state that 5-HT₃ receptor antagonists, including palonosetron, may be included in the multimodal drug therapy approach to PONV prevention.³⁰⁰

Palonosetron Dosage and Administration

General

Patient Monitoring

• Monitor for manifestations of serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms), especially with concomitant use of another serotonergic agent.^{1 34}

Administration

IV Administration

Administer IV.¹

Commercially available as a 0.05 mg/mL injection.¹ Dilution not required.^{1 34} Do not mix with other drugs; flush IV line with 0.9% sodium chloride injection before and after administration.^{1 34}

Rate of Administration

Prevention of chemotherapy-induced nausea and vomiting in adults: administer IV over 30 seconds approximately 30 minutes before chemotherapy.^{1 34}

Prevention of chemotherapy-induced nausea and vomiting in pediatric patients (1 month to <17 years of age): administer IV over 15 minutes beginning approximately 30 minutes before chemotherapy.^{1 34}

Prevention of PONV in adults: administer IV over 10 seconds immediately before induction of anesthesia.^{1 34}

Dosage

Available as palonosetron hydrochloride; dosage expressed in terms of palonosetron.^{1 34}

Pediatric Patients

Chemotherapy-induced Nausea and Vomiting

Prevention

IV

Pediatric patients 1 month to <17 years of age: 20 mcg/kg (up to a maximum of 1.5 mg) as a single dose administered by IV infusion beginning approximately 30 minutes before administration of chemotherapy.^{1 34}

Adults

Chemotherapy-induced Nausea and Vomiting

Prevention

IV

0.25 mg as a single dose administered IV beginning approximately 30 minutes before administration of chemotherapy.^{1 34}

PONV

Prevention

IV

0.075 mg as a single dose administered IV immediately before induction of anesthesia.^{1 34}

Special Populations

Hepatic Impairment

No dosage adjustments required.^{1 34}

Renal Impairment

No dosage adjustments required.^{1 34}

Geriatric Patients

No dosage adjustments required.^{1 34}

Cautions for Palonosetron

Contraindications

• Known hypersensitivity to palonosetron or any ingredient in the formulation.^{1 34}

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and anaphylactic shock, reported in palonosetron-treated patients with or without known hypersensitivity to other 5-HT₃ receptor antagonists.^{1 34} Discontinue palonosetron if hypersensitivity occurs and initiate appropriate treatment.^{1 34} Do not re-initate in patients with a history of hypersensitivity.^{1 34}

Serotonin Syndrome

Serotonin syndrome (in some cases fatal) reported in patients receiving 5-HT₃ receptor antagonists.^{1 34} Most cases occurred in a post-anesthesia care unit or infusion center and were associated with concomitant use of other serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs, mirtazapine, fentanyl, lithium, tramadol, IV methylene blue).^{1 35}

Serotonin syndrome occurring with overdosage of another 5-HT₃ receptor antagonist alone also reported.^{1 35 35}

Manifestations may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), and seizures with or without GI symptoms (e.g., nausea, vomiting, diarrhea).^{1 35}

Monitor patients for serotonin syndrome, particularly with concomitant use of other serotonergic drugs.^{1 35} If symptoms of serotonin syndrome occur, discontinue palonosetron and initiate supportive treatment.^{1 34}

Specific Populations

Pregnancy

No available clinical data regarding use of palonosetron in pregnant women.^{1 34} In animal studies, no adverse embryofetal effects observed.^{1 34}

Lactation

Not known whether palonosetron is distributed into human milk or whether the drug has any effects on milk production or on the breastfed infant.^{1 34}

Consider developmental and health benefits of breastfeeding along with the mother's clinical need for palonosetron and any potential adverse effects on the nursing infant from the drug or underlying maternal condition.^{1 34}

Pediatric Use

Safety and efficacy established in pediatric patients 1 month to <17 years of age for prevention of chemotherapy-induced nausea and vomiting.^{1 34} Safety and efficacy not established in neonates <1 month of age for this use.^{1 34}

Safety and efficacy not established in pediatric patients for prevention of PONV.^{1 34}

Geriatric Use

No substantial differences in safety and efficacy observed relative to younger adult patients; however, increased sensitivity in geriatric patients cannot be ruled out.¹

Hepatic Impairment

Hepatic impairment does not substantially affect total body clearance.^{1 34} No dosage adjustment necessary in patients with any degree of hepatic impairment.^{1 34}

Renal Impairment

Pharmacokinetics not substantially affected by mild to moderate renal impairment.^{1 34} Total systemic exposure approximately 28% higher in patients with severe renal impairment.^{1 34}

No dosage adjustment necessary in patients with any degree of renal impairment.^{1 34}

Common Adverse Effects

Adverse effects (≥5%) in adults receiving palonosetron for prevention of chemotherapy-induced nausea and vomiting include headache and constipation.^{1 34}

Adverse effects (≥2%) in adults receiving palonosetron for PONV include QT prolongation, bradycardia, headache, constipation.^{1 34}

Drug Interactions

Metabolized principally by CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2.^{1 34}

Does not inhibit CYP1A2, 2A6, 2B6, 2C9, 2D6, 2E1, or 3A4/5; effect on CYP2C19 undetermined.¹ Does not induce CYP1A2, 2D6, or 3A4/5.^{1 34}

Drugs Associated with Serotonin Syndrome

Potentially serious, sometimes fatal, serotonin syndrome can occur with concomitant use of other serotonergic agents.^{1 34}

Monitor patients for serotonin syndrome.^{1 34} If serotonin syndrome occurs, immediately discontinue palonosetron and initiate supportive treatment.^{1 34}

Specific Drugs

Palonosetron Pharmacokinetics

Absorption

Bioavailability

After IV dosing of palonosetron in healthy subjects and cancer patients, initial rapid decline in plasma concentrations is followed by a slow elimination.^{1 34}

Mean peak plasma concentration and AUC are generally dose-proportional over the dose range of 0.3–90 mcg/kg.^{1 34}

Special Populations

Pediatric patients: exposure increases dose-proportionally; peak plasma concentrations are variable in pediatric patients and generally lower in children <6 years of age compared with older children.^{1 34}

Distribution

Extent

Not known whether distributed into human milk.^{1 34}

Plasma Protein Binding

Approximately 62%.^{1 34}

Elimination

Metabolism

Principally metabolized by CYP2D6 (and to a lesser extent by CYP3A4 and CYP1A2) to 2 metabolites with minimal activity.^{1 34}

Elimination Route

Eliminated principally in urine (approximately 80% in 144 hours, about 40% as palonosetron).^{1 34}

Half-life

Mean terminal elimination half-life approximately 40 hours in adults.^{1 34}

Median half-life 30 hours in pediatric patients.^{1 34}

Special Populations

Hepatic impairment: Total body clearance not substantially affected.^{1 34}

Mild to moderate renal impairment: Pharmacokinetics not substantially affected.^{1 34}

Severe renal impairment: Total systemic exposure increased by approximately 28%.^{1 34}

Geriatric patients: No differences in pharmacokinetics observed between cancer patients ≥65 years of age and younger cancer patients (18–64 years of age).^{1 34}

Japanese patients: total body clearance was 25% higher than in white patients (not clinically meaningful).^{1 34}

Pharmacogenomic considerations: Pharmacokinetics not substantially different between poor and extensive CYP2D6 metabolizers.^{1 34}

Stability

Storage

Parenteral

Injection

20–25°C (may be exposed to 15–30°C).^{1 34 35} Protect from light; do not freeze.^{1 34 35}

Actions

• Antiemetic activity in acute nausea and vomiting appears to be mediated via inhibition of serotonin activity both centrally (in area postrema and chemoreceptor trigger zone) and peripherally (in GI tract).^{2 3 4 6 18 19 20}

• Alternative mechanisms appear to be responsible for delayed nausea and vomiting.^{2 3 6 7 9 10 12 13} Risk of delayed nausea and vomiting may be decreased by effective prevention of acute nausea and vomiting in the same chemotherapy cycle.^{13 20}

• PONV is influenced by a number of patient-, surgical-, and anesthesia-related factors and is triggered by a release of serotonin in a cascade of neuronal events involving both the CNS and GI tract.^{1 34}

Advice to Patients

• Advise patients that hypersensitivity reactions, including serious cases of anaphylaxis and anaphylactic shock, have occurred with palonosetron, even in those without a known allergy to other 5-HT₃ receptor antagonists.^{1 34} Advise patients to seek immediate medical attention if any signs of a hypersensitivity reaction appear.^{1 34}

• Advise patients about the risk of serotonin syndrome, particularly when palonosetron is used in combination with other serotonergic drugs, such as those for depression or migraines.^{1 34} Instruct patients to seek immediate medical attention if they experience changes in mental status, autonomic instability, or neuromuscular symptoms with or without GI issues.^{1 34}

• Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.^{1 34}

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.^{1 34}

• Advise patients of other important precautionary information.^{1 34}

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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