Version May 2024
Chemotherapy-induced nausea and vomiting, prevention (moderately and highly emetogenic chemotherapy):
IV: 0.25 mg as a single dose beginning ~30 minutes prior to the start of chemotherapy.
Capsule [Canadian product]: Moderately emetogenic chemotherapy: Oral: 0.5 mg ~1 hour prior to the start of chemotherapy.
Guideline recommendations: Prevention of chemotherapy-induced nausea and vomiting:
American Society of Clinical Oncology (Ref):
High emetic risk, including most anthracyclines combined with cyclophosphamide regimens; antiemetic regimen also includes dexamethasone (days 1 to 4), an NK1 receptor antagonist, and olanzapine (days 1 to 4):
IV: 0.25 mg on day 1 prior to chemotherapy.
Oral: 0.5 mg [Canadian product] on day 1 prior to chemotherapy.
Moderate emetic risk; antiemetic regimen also includes dexamethasone (days 1 to 3) [and an NK1 receptor antagonist for carboplatin doses of AUC ≥4]:
IV: 0.25 mg on day 1 prior to chemotherapy.
Oral: 0.5 mg [Canadian product] on day 1 prior to chemotherapy.
Low emetic risk:
IV: 0.25 mg prior to chemotherapy.
Oral: 0.5 mg [Canadian product] prior to chemotherapy.
Postoperative nausea and vomiting, prevention: IV: 0.075 mg as a single dose immediately prior to anesthesia induction.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment is necessary.
No dosage adjustment is necessary.
Hypersensitivity reactions: Discontinue palonosetron and manage appropriately; do not reinitiate in patients who have previously experienced hypersensitivity symptoms.
Serotonin syndrome: Discontinue palonosetron and begin supportive management.
No dosage adjustment necessary. Refer to adult dosing.
(For additional information see "Palonosetron: Pediatric drug information")
Note: Dosing presented in both mcg and mg; use extra caution to verify correct units
Chemotherapy-induced nausea and vomiting, prevention: Note: Use in combination with or without dexamethasone and aprepitant depending upon patient age, chemotherapy emetogenic potential, and drug-interaction profile (refer to specific protocols or guidelines) (Ref).
Infants, Children, and Adolescents <17 years: IV: 20 mcg/kg as a single dose administered ~30 minutes prior to the start of chemotherapy; maximum dose: 1,500 mcg/dose (1.5 mg/dose)
Adolescents ≥17 years:
IV: 0.25 mg as a single dose administered ~30 minutes before chemotherapy
Oral [Canadian product]: Limited data available: 0.5 mg as a single dose administered prior to chemotherapy (Ref)
Postoperative nausea and vomiting (PONV), prevention: Note: Expert recommendations for PONV management do not include palonosetron as a therapeutic option for the prevention or treatment of PONV in pediatric patients (Ref).
Infants, Children, and Adolescents <17 years: Limited data available; efficacy results variable: IV: 1 mcg/kg as a single dose; maximum dose: 75 mcg/dose (0.075 mg/dose) immediately prior to anesthesia induction; dosing based on a double-blind randomized comparative trial with ondansetron which showed complete response in 78.2% of the palonosetron group and 82.7% of the ondansetron; however, palonosetron efficacy data did not meet noninferiority margin; safety analysis showed no unexpected adverse effects, similar data as adult patients.
Adolescents ≥17 years: Limited data available in 17 years of age: IV: 0.075 mg immediately prior to anesthesia induction
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: No dosage adjustment is necessary.
Infants, Children, and Adolescents: No dosage adjustment is necessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequencies reported for both indications (chemotherapy-associated nausea and vomiting and postoperative nausea and vomiting) and in adults unless otherwise noted.
1% to 10%:
Cardiovascular: Bradycardia (chemotherapy-associated: ≤1%; PONV: ≤1% to 4%), hypotension (≤1%), prolonged QT interval on ECG (chemotherapy-associated: ≤1%; PONV: ≤1% to 5%), sinus bradycardia (PONV: ≤1%), tachycardia (may be nonsustained; ≤1%)
Dermatologic: Pruritus (PONV: ≤1%)
Endocrine & metabolic: Hyperkalemia (chemotherapy-associated: ≤1%)
Gastrointestinal: Constipation (chemotherapy-associated: 5%; PONV: 2%), diarrhea (≤1%), flatulence (≤1%)
Genitourinary: Urinary retention (≤1%)
Hepatic: Increased serum alanine aminotransferase (≤1%; may be transient), increased serum aspartate aminotransferase (≤1%; may be transient)
Nervous system: Anxiety (chemotherapy-associated: ≤1%), dizziness (adults ≤1%; infants, children, adolescents <1%), headache (chemotherapy-associated: adults 3% to 9%; infants, children, and adolescents <1%)
Neuromuscular & skeletal: Asthenia (chemotherapy-associated: ≤1%)
<1%, postmarketing, and/or case reports: Abdominal pain, allergic dermatitis, amblyopia, anaphylactic shock, anaphylaxis, anemia, anorexia, arthralgia, cardiac arrhythmia, chills, decreased appetite, decreased gastrointestinal motility, decreased platelet count, dermatological disease (infants, children, and adolescents), distended vein, drowsiness, dyskinesia (infants, children, and adolescents), dyspepsia, electrolyte disturbance, epistaxis, euphoria, extrasystoles, eye irritation, fatigue, fever, flattened T wave on ECG, flu-like symptoms, glycosuria, hiccups, hot flash, hyperglycemia, hypersensitivity reaction (including bronchospasm, dyspnea, edema, erythema of skin, swelling, urticaria), hypersomnia, hypertension, hypokalemia, hypoventilation, increased bilirubin (transient), increased liver enzymes, infusion site pain (infants, children, and adolescents), injection site reaction (includes burning sensation at injection site, discomfort at injection site, induration at injection site, pain at injection site), insomnia, ischemic heart disease, laryngospasm, limb pain, metabolic acidosis, motion sickness, paresthesia, serotonin syndrome, sialorrhea, sinoatrial nodal rhythm disorder, sinus tachycardia, skin rash, supraventricular extrasystole, tinnitus, vein discoloration, ventricular premature contractions, xerostomia
Known hypersensitivity to palonosetron or any component of the formulation.
Concerns related to adverse effects:
• ECG effects: Selective 5-HT3 receptor antagonists have been associated with dose-dependent increases in ECG intervals (eg, PR, QRS duration, QT/QTc, JT). At doses of 9 times the maximum recommended adult dose, palonosetron does not prolong the QT interval to any clinically relevant extent. A thorough QT/QTc study evaluating the effect of palonosetron on QT/QTc demonstrated a magnitude of effect less than the threshold for regulatory concern (Morganroth 2016). Reduction in heart rate may occur with the 5-HT3 antagonists, including palonosetron (Gonullu 2012).
• Hypersensitivity: Hypersensitivity reactions (including anaphylaxis and anaphylactic shock) have been reported in patients with or without known hypersensitivity to other 5-HT3 receptor antagonists.
• Serotonin syndrome: Serotonin syndrome (SS) has been reported with 5-HT3 receptor antagonists, predominantly when used in combination with other serotonergic agents (eg, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and/or methylene blue). Some of the cases have been fatal. The majority of SS reports due to 5-HT3 receptor antagonists have occurred in a post-anesthesia setting or in an infusion center. SS has also been reported following overdose of another 5-HT3 receptor antagonist. Signs of SS include mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile BP, diaphoresis, dizziness, flushing, hyperthermia); neuromuscular changes (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures.
Other warnings/precautions:
• Chemotherapy-associated emesis: Antiemetics are most effective when used prophylactically (MASCC/ESMO [Roila 2016]). If emesis occurs despite optimal antiemetic prophylaxis, reevaluate emetic risk, disease status, concurrent morbidities, and current medications to assure antiemetic regimen is optimized (ASCO [Hesketh 2020]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Aloxi: 0.25 mg/5 mL (5 mL [DSC]) [contains edetate (edta) disodium dihydrate]
Generic: 0.25 mg/5 mL (5 mL)
Solution, Intravenous [preservative free]:
Aloxi: 0.25 mg/5 mL (5 mL [DSC]) [contains edetate (edta) disodium]
Generic: 0.25 mg/2 mL (2 mL); 0.25 mg/5 mL (5 mL)
Solution Prefilled Syringe, Intravenous:
Generic: 0.25 mg/5 mL (5 mL)
Yes
Solution (Palonosetron HCl Intravenous)
0.25 mg/2 mL (per mL): $24.00
0.25 mg/5 mL (per mL): $1.44 - $74.69
Solution Prefilled Syringe (Palonosetron HCl Intravenous)
0.25 mg/5 mL (per mL): $12.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Aloxi: 0.5 mg
Solution, Intravenous:
Aloxi: 0.25 mg/5 mL (5 mL) [contains edetate (edta) disodium]
IV: Flush IV line with NS prior to and following palonosetron administration. Do not mix with other medications.
Prevention of chemotherapy-induced nausea and vomiting: Infuse over 30 seconds, beginning ~30 minutes prior to the start of chemotherapy.
Capsule [Canadian product]: Administer ~1 hour prior to the start of chemotherapy. May be administered with or without food.
Prevention of postoperative nausea and vomiting: Infuse over 10 seconds immediately prior to anesthesia induction.
Parenteral: Flush IV line with NS prior to and following administration. Do not use the prefilled syringe for doses <0.25 mg.
Prevention of chemotherapy-induced nausea and vomiting:
Infants, Children, and Adolescents <17 years: May administer IV undiluted or further dilute (Ref) and infuse over 15 minutes, beginning ~30 minutes prior to the start of chemotherapy
Adolescents ≥17 years: Administer IV undiluted, infuse over 30 seconds, beginning ~30 minutes prior to the start of chemotherapy
Prevention of postoperative nausea and vomiting: May administer IV undiluted and infuse over 10 seconds immediately prior to anesthesia induction
Oral: Capsule [Canadian product]: May be administered with or without food.
Chemotherapy-induced nausea and vomiting:
Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses in adults treated with moderately emetogenic cancer chemotherapy.
Prevention of acute nausea and vomiting associated with initial and repeat courses in adults treated with highly emetogenic cancer chemotherapy.
Prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy (including highly emetogenic chemotherapy) in pediatric patients 1 month to <17 years of age.
Capsules [Canadian product]: Prevention of acute nausea and vomiting associated with moderately emetogenic cancer chemotherapy in adults.
Postoperative nausea and vomiting: Prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery in adults (efficacy beyond 24 hours has not been demonstrated).
Limitations of use: Routine prophylaxis for PONV in patients with minimal expectation of nausea and/or vomiting is not recommended, although palonosetron is recommended in patients when nausea and vomiting must be avoided in the postoperative period, even if the incidence of PONV is low.
Aloxi may be confused with Eloxatin, oxaliplatin
Palonosetron may be confused with dolasetron, granisetron, ondansetron
Substrate of CYP1A2 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
Serotonergic Agents (High Risk): Antiemetics (5HT3 Antagonists) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
TraMADol: Antiemetics (5HT3 Antagonists) may enhance the serotonergic effect of TraMADol. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Information related to use of palonestron for the prevention of postoperative nausea and vomiting in patients undergoing cesarean delivery has been evaluated (Swaro 2018).
It is not known if palonosetron is present in breast milk.
According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, the benefits of treatment to the mother, and the underlying maternal condition.
Monitor for signs/symptoms of hypersensitivity and serotonin syndrome.
Palonosetron is a selective 5-HT3 receptor antagonist, blocking serotonin, both on vagal nerve terminals in the periphery and centrally in the chemoreceptor trigger zone.
Absorption: Capsules [Canadian product]: Well absorbed.
Distribution: Vd:
Children 1 month to 17 years: Mean range: 5.3 to 6.3 L/kg.
Adults: 8.3 ± 2.5 L/kg.
Protein binding: ~62%.
Metabolism: ~50% metabolized via CYP enzymes (and likely other pathways) to relatively inactive metabolites (N-oxide-palonosetron and 6-S-hydroxy-palonosetron); CYP1A2, 2D6, and 3A4 contribute to its metabolism.
Bioavailability: Capsules [Canadian product]: 97%.
Half-life elimination: IV: Children 1 month to 17 years: Median: 29.5 hours (range: 20 to 30 hours); Adults: ~40 hours.
Time to peak (plasma): Capsules [Canadian product]: 5.1 ± 5.9 hours.
Excretion: Urine (~80%; ~40% as unchanged drug).
Clearance:
Infants and children <2 years: 0.31 L/hour/kg.
Children 2 to <12 years: Mean range: 0.19 to 0.23 L/hour/kg.
Children ≥12 years, Adolescents, and Adults: 0.16 L/hour/kg.
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