Your activity: 244 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

Palonosetron: Drug information

Palonosetron: Drug information
(For additional information see "Palonosetron: Patient drug information" and see "Palonosetron: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Aloxi [DSC]
Brand Names: Canada
  • Aloxi
Pharmacologic Category
  • Antiemetic;
  • Selective 5-HT3 Receptor Antagonist
Dosing: Adult
Prevention of chemotherapy-induced nausea and vomiting

Prevention of chemotherapy-induced nausea and vomiting (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 (ASCO [Hesketh 2020]):

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.

Prevention of postoperative nausea and vomiting

Prevention of postoperative nausea and vomiting: 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.

Dosing: Kidney Impairment: Adult

No dosage adjustment is necessary.

Dosing: Hepatic Impairment: Adult

No dosage adjustment is necessary.

Dosing: Pediatric

(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

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) (POGO [Patel 2017]).

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 (POGO [Patel 2017])

Postoperative nausea and vomiting; prevention

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 (SAA [Gan 2014]).

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.

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents: No dosage adjustment is necessary.

Dosing: Hepatic Impairment: Pediatric

Infants, Children, and Adolescents: No dosage adjustment is necessary.

Dosing: Older Adult

No dosage adjustment necessary. Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

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.

Dosage Forms: US

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)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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]

Administration: Adult

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.

Administration: Pediatric

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 (Trissel 2004) 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.

Use: Labeled Indications

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.

Medication Safety Issues
Sound-alike/look-alike issues:

Aloxi may be confused with Eloxatin, oxaliplatin

Palonosetron may be confused with dolasetron, granisetron, ondansetron

Adverse Reactions

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

Contraindications

Known hypersensitivity to palonosetron or any component of the formulation.

Warnings/Precautions

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]).

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

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

Pregnancy Considerations

Information related to use of palonestron for the prevention of postoperative nausea and vomiting in patients undergoing cesarean delivery has been evaluated (Swaro 2018).

Breastfeeding Considerations

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.

Monitoring Parameters

Monitor for signs/symptoms of hypersensitivity and serotonin syndrome.

Mechanism of Action

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.

Pharmacokinetics

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.

Pricing: US

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.

Brand Names: International
  • Aloxi (AT, AU, BB, BE, BG, BH, CH, CY, CZ, DE, DK, EE, EG, ES, FI, FR, GB, GR, HK, HR, HU, IE, IS, IT, JP, KR, KW, LB, LT, LU, LV, MT, MY, NL, NO, PH, PL, PT, RO, RU, SE, SG, SI, SK, TH, TR, TW);
  • Avonil (BD);
  • Emegrand (EG);
  • Ferant (HR);
  • Lowvo (CN);
  • Nausetron (EG);
  • Okmilon (TW);
  • Onicit (AR, BR, CL, CO, EC, MX, PE, VE);
  • Palnox (BD);
  • Palorex (BD);
  • Paloxi (BD, IL, KR);
  • Paloxiron (BD);
  • Palzen (IN);
  • Vinaltro (CR, DO, GT, HN, NI, PA, SV);
  • Viqet (CR, DO, GT, HN, NI, PA, SV);
  • Zhiruo (CN)


For country code abbreviations (show table)
  1. Aapro MS, Grunberg SM, Manikhas GM, et al, “A Phase III, Double-Blind, Randomized Trial of Palonosetron Compared With Ondansetron in Preventing Chemotherapy-Induced Nausea and Vomiting Following Highly Emetogenic Chemotherapy,” Ann Oncol, 2006, 17(9):1441-9. [PubMed 16766588]
  2. Aloxi (palonosetron) [prescribing information]. Iselin, NJ: Helsinn Therapeutics (US) Inc; April 2020.
  3. Aloxi (palonosetron) [product monograph]. Pickering, Ontario, Canada: Perdue Pharma; April 2019.
  4. Gan TJ, Diemunsch P, Habib AS, et al. Consensus guidelines for the management of postoperative nausea and vomiting [published corrections appear in Anesth Analg. 2015;120(2):494 and Anesth Analg. 2014;118(3):689]. Anesth Analg. 2014;118(1):85-113. [PubMed 24356162]
  5. Gonullu G, Demircan S, Demirag MK, et al. Electrocardiographic findings of palonosetron in cancer patients. Support Care Cancer. 2012;20(7):1435-1439. [PubMed 21773677]
  6. Gralla R, Lichinister M, Van Der Vegt S, et al, “Palonosetron Improves Prevention of Chemotherapy-Induced Nausea and Vomiting Following Moderately Emetogenic Chemotherapy: Results of a Double-Blind Randomized Phase III Trial Comparing Single Doses of Palonosetron With Ondansetron,” Ann Oncol, 2003, 14(10):1570-7. [PubMed 14504060]
  7. Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020;38(24):2782-2797. doi:10.1200/JCO.20.01296 [PubMed 32658626]
  8. Kupiec TC, Trusley C, Ben M, et al, “Physical and Chemical Stability of Palonosetron Hydrochloride With Five Common Parenteral Drugs During Simulated Y-Site Administration,” Am J Health-Syst Pharm, 2008, 65(18):1735-9. [PubMed 18769000]
  9. Morganroth J, Flaharty KK, Parisi S, et al. Effect of single doses of IV palonosetron, up to 2.25 mg, on the QTc interval duration: a double-blind, randomized, parallel group study in healthy volunteers. Support Care Cancer. 2016;24(2):621-627. [PubMed 26111957]
  10. Morganroth L, Parisi S, Spinelli T, et al. High dose palonosetron does not alter ECG parameters including QTc interval in healthy subjects: results of a dose-response, double-blind, randomized, parallel E14 study of palonosetron vs. moxifloxacin or placebo. Presented at the 14th European Conference of Clinical Oncology (ECCO), September 2007; Barcelona, Spain.
  11. Palonosetron hydrochloride [prescribing information]. Lake Zurich, IL: Fresenius Kabi; June 2018.
  12. Patel P, Robinson PD, Thackray J, et al. Guideline for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric cancer patients: A focused update [published online April 28, 2017]. Pediatr Blood Cancer. 2017. [PubMed 28453189]
  13. Roila F, Molassiotis A, Herrstedt J, et al. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 2016;27(Suppl 5):S119-S133. [PubMed 27664248]
  14. Swaro S, Karan D, Banerjee A. Comparison of palonosetron, dexamethasone, and palonosetron plus dexamethasone as prophylactic antiemetic and antipruritic drug in patients receiving intrathecal morphine for lower segment cesarean section. Anesth Essays Res. 2018;12(2):322-327. doi:10.4103/aer.AER_183_17 [PubMed 29962591]
  15. Tang J, D'Angelo R, White PF, et al, “The Efficacy of RS-25259, A Long-Acting Selective 5-HT3 Receptor Antagonist, for Preventing Postoperative Nausea and Vomiting After Hysterectomy Procedures,” Anesth Analg, 1998, 87(2):462-7. [PubMed 9706951]
  16. Trissel LA and Xu QA, “Physical and Chemical Stability of Palonosetron HCl in 4 Infusion Solutions,” Ann Pharmacother, 2004a, 38(10):1608-11. [PubMed 15328393]
  17. Zambelli A, Sagrada P, and Pavesi L, “Seizure Associated With Palonosetron,” Support Care Cancer, 2009, 17(3):217. [PubMed 19139929]
Topic 9944 Version 244.0