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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

Selective 5-HT3 receptor antagonist, blocking serotonin, both on vagal nerve terminals in the periphery and centrally in the chemoreceptor trigger zone

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

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.

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.

Contraindications

Hypersensitivity to palonosetron or any component of the formulation

Dosing: Adult

Prevention of chemotherapy-induced nausea and vomiting: IV: 0.25 mg beginning ~30 minutes 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: 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

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

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

Compatibility

Stable in D5W, NS, D51/2NS, and D5LR.

Y-site administration: Incompatible with fosaprepitant, methylprednisolone sodium succinate.

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, 2004a).

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: Although other selective 5-HT3 receptor antagonists have been associated with dose-dependent increases in ECG intervals (eg, PR, QRS duration, QT/QTc, JT), palonosetron has not been shown to significantly affect the QT/QTc interval (Gonullu, 2012; Morganroth, 2008). 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, 2010). 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.

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