Palonosetron (Aloxi) is a serotonin receptors antagonist that is used in the treatment and prevention of chemotherapy-induced nausea and vomiting.

Palonosetron (Aloxi) Uses:

• Chemotherapy-induced nausea and vomiting:

  • Prevention of acute and delayed nausea and vomiting secondary to initial and repeat courses in patients treated with moderately emetogenic cancer chemotherapy in adults.
  • prevention of acute nausea and vomiting secondary to initial and repeat courses in patients treated with highly emetogenic cancer chemotherapy in adults.
  • prevention of acute nausea and vomiting secondary to 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 secondary to 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.

Palonosetron (Aloxi) Dose in Adults

Palonosetron (Aloxi) Dose in the Prevention of chemotherapy-induced nausea and vomiting (moderately and highly emetogenic chemotherapy):

• IV: 0.25 mg beginning ~30 minutes before beginning chemotherapy
• Capsule [Canadian product]:
  • Moderately emetogenic chemotherapy: Oral: 0.5 mg ~1 hour before beginning chemotherapy.

Guideline recommendations:

• Prevention of chemotherapy-induced nausea and vomiting:

• American Society of Clinical Oncology:

  • High emetic risk, including most anthracyclines combined with cyclophosphamide regimens; antiemetic regimen also includes dexamethasone (days 1 to 4), an NK receptor antagonist, and olanzapine (days 1 to 4):

    • IV: 0.25 mg on day 1 before chemotherapy
    • Oral: 0.5 mg [Canadian product] on day 1 before chemotherapy

  • Moderate emetic risk; antiemetic regimen also includes dexamethasone (days 1 to 3) [and an NK receptor antagonist for carboplatin AUC ≥4]:

    • IV: 0.25 mg on day 1 before chemotherapy
    • Oral: 0.5 mg [Canadian product] on day 1 before chemotherapy

  • Low emetic risk:

    • IV: 0.25 mg before chemotherapy
    • Oral: 0.5 mg [Canadian product] before chemotherapy

• Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO):

  • • Highly emetic chemotherapy, (antiemetic regimen includes dexamethasone and aprepitant/ fosaprepitant/ rolapitant):

      • IV: 0.25 mg on day 1 before chemotherapy
      • Oral: 0.5 mg [Canadian product] on day 1 before chemotherapy

    • Moderately emetic chemotherapy (antiemetic regimen includes dexamethasone [and aprepitant/ fosaprepitant/ rolapitant for AC chemotherapy regimen]):

      • IV: 0.25 mg on day 1 before chemotherapy
      • Oral: 0.5 mg [Canadian product] on day 1 before chemotherapy

    • Low emetic risk:

      • 25 mg IV or 0.5 mg orally [Canadian product] before chemotherapy on day 1 may be considered

Palonosetron (Aloxi) Dose in the Prevention of postoperative nausea and vomiting:

• IV: 0.075 mg immediately before anesthesia induction

Palonosetron (Aloxi) Dose in Childrens

Note: Dosing presented in both mcg and mg; use extreme caution to verify correct units

Palonosetron (Aloxi) Dose in the Prevention of Chemotherapy-induced nausea and vomiting:

Note: Use in combination with or without dexamethasone and aprepitant according to patient age, chemotherapy emetogenic potential, and drug-interaction profile (refer to specific protocols or guidelines).

• Infants, Children, and Adolescents <17 years:

  • IV: 20 mcg/kg as a single dose administered ~30 minutes before beginning 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 before chemotherapy.

Palonosetron (Aloxi) Dose in the Prevention of Postoperative nausea and vomiting (PONV):

Note: Expert recommendations for PONV management do not include palonosetron as a therapeutic option for the prevention or treatment of PONV in pediatric patients.

• 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 before anesthesia induction

Pregnancy Risk Factor B

• Animal reproduction studies have not shown any adverse events.
• Only use during pregnancy if absolutely necessary.

Palonosetron use during breastfeeding:

• It is unknown if palonosetron secreted in breastmilk.
• The manufacturer suggests that the mother decide whether to stop breastfeeding or discontinue palonosetron because of the possibility of adverse reactions in breastfed babies.
• This decision will depend on the importance to the mother.

Dose in Kidney Disease:

No dosage adjustment required.

Dose in Liver Disease:

No dosage adjustment required.

Side Effects of Palonosetron (Aloxi):

• Cardiovascular:

  • Prolonged Q-T Interval On ECG
  • Bradycardia
  • Sinus Bradycardia
  • Tachycardia
  • Hypotension

• Central Nervous System:

  • Headache
  • Anxiety
  • Dizziness

• Dermatologic:

  • Pruritus

• Endocrine & Metabolic:

  • Hyperkalemia

• Gastrointestinal:

  • Constipation
  • Diarrhea
  • Flatulence

• Genitourinary:

  • Urinary Retention

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST

• Neuromuscular & Skeletal:

  • Weakness

Contraindications to Palonosetron (Aloxi):

Hypersensitivity to palonosetron and any component of the formulation

Warnings and precautions

• ECG effects

  • Certain 5-HT receptor antagonists have been shown to cause dose-dependent increases of ECG intervals (eg PR, QRS durations, QT/QTc and JT).
  • An extensive QT/QTc analysis evaluating the effects of palonosetron QT/QTc showed a lesser magnitude of the regulatory concern threshold.
  • Bradycardia can occur when you take 5-HT-3 antagonists such as palonosetron.

• Hypersensitivity reactions

  • Patients with known hypersensitivity to 5-HT-3 receptor antagonists have been found to be hypersensitive (including anaphylaxis).

• Serotonin syndrome:

  • Serotonin syndrome has been linked to 5-HT-3 receptor antagonists. This is most common when they are used with serotonergic agents such as SSRIs and SNRIs. Some cases were fatal.
  • Most reports of serotonin syndrome due to 5-HT-3 antagonists occurred in a post-anesthesia setting, or in an infusion centre.
  • Serotonin syndrome can also be caused by overdose of another 5-HT-3 antagonist.
  • Serotonin syndrome symptoms include mental changes such as agitation, hallucinations and delirium, coma; autonomic instability (eg tachycardia or labile pressure, dizziness, flushing or hyperthermia), neuromuscular changes (eg tremors, rigidity, myoclonus hyperreflexia, seizures) and gastrointestinal symptoms such as nausea, vomiting, diarrhea.
  • Stop 5-HT-3 antagonist treatment if you have serotonin syndrome. Get supportive care instead.

Palonosetron: Drug Interaction

Monitoring Parameters:

None mentioned.

How to administer Palonosetron (Aloxi)?

IV:

• Flush IV line with NS before and after administration.

Prevention of chemotherapy-induced nausea and vomiting:

• Infuse over 30 seconds, beginning ~30 minutes before beginning chemotherapy

Capsule [Canadian product]:

• May be administered with or without meals.

Prevention of postoperative nausea and vomiting:

• Infuse over 10 seconds immediately before anesthesia induction

Mechanism of action of Palonosetron (Aloxi):

Palonosetron, a selective 5-HT-3 receptor antagonist blocks serotonin on both the peripheral and central vagal nerve terminals of the chemoreceptor trigger area.

Absorption:

• Capsules [Canadian Product]: Well absorbed

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)

International Brand Names of Palonosetron:

• Aloxi
• Avonil
• Emegrand
• Lowvo
• Nausetron
• Onicit
• Palnox
• Palorex
• Paloxi
• Paloxiron
• Palzen
• Prosmol
• Vinaltro
• Viqet
• Zhiruo

Palonosetron Brand Names in Pakistan:

• Omotil 0.25 mg/ 5ml