Skip to Content

Palonosetron

Pronunciation

(pal oh NOE se tron)

Index Terms

  • Palonosetron Hydrochloride
  • Palonosetron, inj
  • RS-25259
  • RS-25259-197

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Aloxi: 0.25 mg/5 mL (5 mL) [contains edetate disodium]

Brand Names: U.S.

  • Aloxi

Pharmacologic Category

  • Antiemetic
  • Selective 5-HT3 Receptor Antagonist

Pharmacology

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

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

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: 0.160 L/hour/kg

Time to Peak

Plasma: Capsules [Canadian product]: 5.1 ± 5.9 hours

Half-Life Elimination

IV: Children 1 month to 17 years: Median: 29.5 hours (range: 20 to 30 hours); Adults: ~40 hours

Protein Binding

~62%

Use: Labeled Indications

Chemotherapy-induced nausea and vomiting: Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses in patients treated with moderately emetogenic cancer chemotherapy in adults; prevention of acute nausea and vomiting associated with initial and repeat courses in patients treated with highly emetogenic cancer chemotherapy in adults; 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.

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.

Limitations of use: Routine prophylaxis for PONV in patients with minimal expectation of nausea and/or vomiting is not recommended, although use is recommended in patients when nausea and vomiting must be avoided in the postoperative period, even if the incidence of PONV is low.

Off Label Uses

Chemotherapy-induced nausea and vomiting, moderately emetogenic chemotherapy (pediatrics)

Based on the Pediatric Oncology Group of Ontario Guideline for the Prevention of Acute Chemotherapy-Induced Nausea and Vomiting in Pediatric Cancer Patients focused update, palonosetron is recommended in pediatric patients (in combination with dexamethasone) to prevent nausea and vomiting associated with moderately emetogenic chemotherapy regimens.

Contraindications

Known hypersensitivity to palonosetron or any component of the formulation

Dosing: Adult

Prevention of chemotherapy-induced nausea and vomiting (moderately and highly emetogenic chemotherapy): IV: 0.25 mg 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.

Prevention of postoperative nausea and vomiting: IV: 0.075 mg immediately prior to anesthesia induction

Dosing: Geriatric

No dosage adjustment necessary. Refer to adult dosing.

Dosing: Pediatric

Prevention of chemotherapy-induced nausea and vomiting (highly emetogenic chemotherapy): Infants ≥1 month, Children, and Adolescents <17 years: IV: 20 mcg/kg (maximum dose: 1.5 mg) beginning ~30 minutes prior to the start of chemotherapy

Pediatric guideline recommendations:

Prevention of chemotherapy-induced nausea and vomiting for highly emetogenic chemotherapy (Patel 2017):

Infants ≥1 month to 6 months: IV: 20 mcg/kg once prior to chemotherapy (maximum: 1.5 mg/dose). Antiemetic regimen also includes dexamethasone (if no contraindications to corticosteroids).

Infants ≥6 months, Children and Adolescents <17 years: IV: 20 mcg/kg once prior to chemotherapy (maximum: 1.5 mg/dose). Antiemetic regimen also includes aprepitant (if no potential drug interactions) and dexamethasone (if no contraindications to corticosteroids).

Adolescents ≥17 years:

IV: 0.25 mg once prior to chemotherapy. Antiemetic regimen also includes aprepitant (if no potential drug interactions) and dexamethasone (if no contraindications to corticosteroids).

Oral [Canadian product]: 0.5 mg once prior to chemotherapy. Antiemetic regimen also includes aprepitant (if no potential drug interactions) and dexamethasone (if no contraindications to corticosteroids).

Prevention of chemotherapy-induced nausea and vomiting for moderately emetogenic chemotherapy (off-label; Patel 2017):

Infants ≥1 month to 6 months: IV: 20 mcg/kg once prior to chemotherapy (maximum: 1.5 mg/dose. Antiemetic regimen also includes dexamethasone (if no contraindications to corticosteroids).

Infants ≥6 months, Children and Adolescents <17 years: IV: 20 mcg/kg once prior to chemotherapy (maximum: 1.5 mg/dose). Antiemetic regimen also includes dexamethasone; if patient cannot receive corticosteroids, antiemetic regimen may include aprepitant (if no potential drug interactions).

Adolescents ≥17 years:

IV: 0.25 mg once prior to chemotherapy. Antiemetic regimen also includes dexamethasone; if patient cannot receive corticosteroids, antiemetic regimen may include aprepitant (if no potential drug interactions).

Oral [Canadian product]: 0.5 mg once prior to chemotherapy. Antiemetic regimen also includes dexamethasone; if patient cannot receive corticosteroids, antiemetic regimen may include aprepitant (if no potential drug interactions).

Dosing: Renal Impairment

No dosage adjustment is necessary.

Dosing: Hepatic Impairment

No dosage adjustment is necessary.

Administration

Flush IV line with NS prior to and following administration.

Prevention of chemotherapy-induced nausea and vomiting:

Children: Infuse over 15 minutes, beginning ~30 minutes prior to the start of chemotherapy

Adults: Infuse over 30 seconds, beginning ~30 minutes prior to the start of chemotherapy

Capsule [Canadian product]: May be administered with or without food.

Prevention of postoperative nausea and vomiting: Infuse over 10 seconds immediately prior to anesthesia induction

Storage

Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze. Protect from light. Solutions of 5 mcg/mL and 30 mcg/mL in NS, D5W, D51/2NS, and D5LR injection are stable for 48 hours at room temperature and 14 days under refrigeration (Trissel 2004).

Capsules [Canadian product]: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Avoid combination

Serotonin Modulators: Antiemetics (5HT3 Antagonists) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy

Tapentadol: Antiemetics (5HT3 Antagonists) may diminish the analgesic effect of Tapentadol. Monitor therapy

TraMADol: Antiemetics (5HT3 Antagonists) may diminish the analgesic effect of TraMADol. Monitor therapy

Adverse Reactions

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: Prolonged Q-T interval on ECG (PONV 1% to 5%; chemotherapy-associated <1%), bradycardia (chemotherapy-associated 1%), sinus bradycardia (PONV: 1%), tachycardia (may be nonsustained; 1%), hypotension (≤1%)

Central nervous system: Headache (chemotherapy-associated: Adults 9%; infants, children, and adolescents <1%), anxiety (chemotherapy-associated: 1%), dizziness (infants, children, adolescents, and adults ≤1%)

Dermatologic: Pruritus (PONV: 1%)

Endocrine & metabolic: Hyperkalemia (chemotherapy-associated: 1%)

Gastrointestinal: Constipation (chemotherapy-associated: 5%), diarrhea (≤1%), flatulence (≤1%)

Genitourinary: Urinary retention (≤1%)

Hepatic: Increased serum ALT (≤1%; may be transient), increased serum AST (≤1%; may be transient)

Neuromuscular & skeletal: Weakness (chemotherapy-associated: 1%)

<1% (Limited to important or life-threatening): Amblyopia, anasarca, anemia, anorexia, arthralgia, chills, decreased appetite, decreased blood pressure, decreased gastrointestinal motility, decreased platelet count, dermatological disease (infants, children, and adolescents), distended vein, drowsiness, dyskinesia (infants, children, and adolescents), dyspepsia, epistaxis, erythema, euphoria, extrasystoles, eye irritation, flattened T wave on ECG, flu-like symptoms, hiccups, hot flash, hyperglycemia, hypersensitivity (very rare), hypertension, hypokalemia, hypoventilation, increased bilirubin (transient), increased liver enzymes, infusion site pain (infants, children, and adolescents), injection site reaction (very rare; includes burning sensation at injection site, discomfort at injection site, induration at injection site, pain at injection site), insomnia, ischemic heart disease, limb pain, metabolic acidosis, motion sickness, paresthesia, serotonin syndrome, sialorrhea, sinus arrhythmia, sinus tachycardia, supraventricular extrasystole, tinnitus, vein discoloration, ventricular premature contractions

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). 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 reactions: Hypersensitivity (including anaphylaxis) has been reported in patients with or without known hypersensitivity to other 5-HT3 receptor antagonists.

• Serotonin syndrome: Serotonin syndrome has been reported with 5-HT3 receptor antagonists, predominantly when used in combination with other serotonergic agents (eg, SSRIs, SNRIs, MAOIs, mirtazapine, fentanyl, lithium, tramadol, and/or methylene blue). Some of the cases have been fatal. The majority of serotonin syndrome reports due to 5-HT3 receptor antagonists have occurred in a post-anesthesia setting or in an infusion center. Serotonin syndrome has also been reported following overdose of another 5-HT3 receptor antagonist. Monitor patients for signs of serotonin syndrome, including mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis, dizziness, flushing, hyperthermia); neuromuscular changes (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination); gastrointestinal symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. If serotonin syndrome occurs, discontinue 5-HT3 receptor antagonist treatment and begin supportive management.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Chemotherapy-associated emesis: Antiemetics are most effective when used prophylactically (Roila 2016). If emesis occurs despite optimal antiemetic prophylaxis, re-evaluate emetic risk, disease, concurrent morbidities and medications to assure antiemetic regimen is optimized (Basch 2011).

• Postoperative nausea and vomiting: Use is not recommended if there is little expectation of postoperative nausea and vomiting (PONV); may use for low expectation of PONV if it is essential to avoid nausea and vomiting in the postoperative period.

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Use during pregnancy only if clearly needed.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache or constipation. Have patient report immediately to prescriber angina, passing out, bradycardia, chills, pharyngitis, difficult urination, difficulty with motor activity, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Hide