Palonosetron is a medication primarily used to prevent nausea and vomiting caused by cancer chemotherapy and surgery. It belongs to a class of drugs known as serotonin 5-HT3 receptor antagonists. This drug works by blocking the action of serotonin, a natural substance in the body that can trigger nausea and vomiting.

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

Palonosetron (Aloxi) Uses:

• Postoperative nausea and vomiting:
  • preventing postoperative nausea and vomiting (PONV) in adults for up to 24 hrs after surgery.
• Chemotherapy-induced nausea and vomiting:
  • prevention of acute nausea and vomiting due to initial and subsequent rounds of chemotherapy for cancer that is emetogenic (including extremely emetogenic chemotherapy) in young patients aged between one month and seventeen.
  • Prevention of immediate and delayed nausea and vomiting due to initial and subsequent courses in patients receiving adult cancer chemotherapy that has a moderate emetic risk.
  • prevention of acute nausea and vomiting brought on by the initial and subsequent rounds in patients receiving adult cancer chemotherapy that is extremely emetic.
  • Capsules (product from Canada): Adults' acute nausea and vomiting prevention following mildly emetogenic cancer chemotherapy.
• Limitations of use:
  • Routine prophylaxis for PONV is not advised in patients who have a low risk of experiencing nausea and/or vomiting, but it is advised in patients who need to avoid nausea and vomiting during the postoperative phase, even in cases where PONV incidence is low.

Palonosetron (Aloxi) Dose in Adults

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

Palonosetron is a medication used to prevent nausea and vomiting caused by chemotherapy. The dose depends on how likely the chemotherapy is to cause these side effects.

For chemotherapy that is likely to cause moderate or severe nausea and vomiting:

• If it's given through an IV, the dose is 0.25 mg about 30 minutes before starting chemotherapy.
• If it's in capsule form (specifically in Canada), the dose is 0.5 mg taken orally about 1 hour before starting chemotherapy.

For chemotherapy with a high risk of causing nausea and vomiting, like certain types combined with other drugs:

• For IV administration, the dose is 0.25 mg before chemotherapy starts.
• If taken orally (in Canada), the dose is 0.5 mg before chemotherapy starts.

For chemotherapy with a moderate risk of causing nausea and vomiting:

• The IV dose is 0.25 mg before starting chemotherapy.
• If taken orally (in Canada), the dose is 0.5 mg before starting chemotherapy.

For chemotherapy with a low risk of causing nausea and vomiting:

• The IV dose is 0.25 mg before starting chemotherapy.
• If taken orally (in Canada), the dose is 0.5 mg before starting chemotherapy.

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

• In preventing postoperative nausea and vomiting, the typical dose of palonosetron administered intravenously (IV) is 0.075 mg, given right before the induction of anesthesia.

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:

For the prevention of chemotherapy-induced nausea and vomiting:

For infants, children, and adolescents under 17 years old:

• The intravenous (IV) dose is 20 mcg per kilogram of body weight, given as a single dose about 30 minutes before starting chemotherapy. The maximum dose is 1,500 mcg (1.5 mg) per dose.

For adolescents aged 17 years and older:

• The IV dose is 0.25 mg, given as a single dose about 30 minutes before starting chemotherapy.
• If taken orally (specifically in Canada), limited data suggest a dose of 0.5 mg as a single dose before chemotherapy.

It's essential to follow specific protocols or guidelines provided by healthcare professionals, which may include using palonosetron alone or in combination with other medications such as dexamethasone and aprepitant, depending on factors like patient age, chemotherapy's potential to cause nausea and vomiting, and drug-interaction profiles.

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

In infants, children, and adolescents under 17 years old:

• Limited data are available, but based on a study, the intravenous (IV) dose is 1 mcg per kilogram of body weight, given as a single dose with a maximum of 75 mcg (0.075 mg) immediately before the induction of anesthesia. However, expert recommendations for PONV management in pediatric patients do not include palonosetron as a therapeutic option.

In adolescents aged 17 years and older:

• Limited data are available specifically for 17-year-olds, but the recommended IV dose is 0.075 mg, administered immediately before the induction of anesthesia.

It's important to note that while palonosetron has been studied for PONV prevention, expert recommendations currently do not include it as a therapeutic option for pediatric patients. Always consult with healthcare professionals for the most appropriate treatment options.

Pregnancy Risk Factor B

• Palonosetron has a pregnancy risk factor of B, which means that no adverse events have been observed in animal studies regarding its effects on pregnancy.
• However, it's advised to use it during pregnancy only if it's absolutely necessary and the benefits outweigh any potential risks.

Palonosetron use during breastfeeding:

• It's uncertain whether palonosetron is present in breast milk.
• Due to the possibility of adverse reactions in breastfed infants, the manufacturer advises making a decision on whether to stop breastfeeding or discontinue palonosetron, considering the importance of treatment for the mother's health.

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):

• If someone has a known hypersensitivity, which means a severe allergic reaction, to palonosetron or any component of the medication's formulation, they should not use it.
• It's crucial to avoid any substance that could trigger an allergic response to prevent potentially serious complications.

Warnings and precautions

ECG effects

• Selective 5-HT receptor antagonists, like palonosetron, can cause changes in ECG intervals such as PR, QRS duration, QT/QTc, and JT, which may increase with dosage.
• Studies have shown that palonosetron's effect on QT/QTc is below the level of regulatory concern.

Hypersensitivity reactions

• Some individuals may experience hypersensitivity reactions, including severe allergic reactions like anaphylaxis, even if they haven't had issues with other 5-HT receptor antagonists before.

Serotonin syndrome:

• Serotonin syndrome, a potentially serious condition, can occur when 5-HT receptor antagonists are used alongside other serotonergic agents like SSRIs, SNRIs, or MAOIs.
• Symptoms of serotonin syndrome include changes in mental status, autonomic instability, neuromuscular changes, gastrointestinal symptoms, and seizures.
• It's important to monitor patients for signs of serotonin syndrome and discontinue treatment with 5-HT receptor antagonists if it occurs, starting supportive management.

Palonosetron: Drug Interaction

Monitoring Parameters:

None mentioned.

How to administer Palonosetron (Aloxi)?

IV Administration:

• Flush the IV line with normal saline (NS) before and after administering the medication to ensure proper delivery.
• For preventing chemotherapy-induced nausea and vomiting, infuse the medication over 30 seconds, starting approximately 30 minutes before chemotherapy begins.
• For preventing postoperative nausea and vomiting, administer the medication over 10 seconds right before the induction of anesthesia.

Capsule Administration [Canadian Product]:

• The capsule form of the medication, available in Canada, can be taken with or without food.

These instructions ensure the appropriate administration of palonosetron for different purposes, either to prevent nausea and vomiting related to chemotherapy or postoperative recovery.

Mechanism of action of Palonosetron (Aloxi):

• Palonosetron is a medication that works by selectively blocking certain serotonin receptors, specifically the 5-HT receptors.
• It acts on serotonin not only in the peripheral nerves of the vagus nerve but also centrally in an area of the brain called the chemoreceptor trigger zone.
• By blocking serotonin in these areas, palonosetron helps prevent nausea and vomiting associated with chemotherapy or surgery.

Absorption:

• Palonosetron capsules available in Canada are well absorbed.

Distribution:

• In children aged 1 month to 17 years, the mean distribution volume ranges from 5.3 to 6.3 liters per kilogram of body weight.
• In adults, the distribution volume is approximately 8.3 liters per kilogram.

Protein Binding:

• Around 62% of palonosetron is bound to proteins in the blood.

Metabolism:

• About half of palonosetron is metabolized in the body, primarily by CYP enzymes, with contributions from enzymes like CYP1A2, 2D6, and 3A4.
• It is metabolized into relatively inactive forms, including N-oxide-palonosetron and 6-S-hydroxy-palonosetron.

Bioavailability:

• The bioavailability of palonosetron capsules in Canada is approximately 97%.

Half-life Elimination:

• For the intravenous (IV) administration, the half-life of elimination is around 29.5 hours in children aged 1 month to 17 years and approximately 40 hours in adults.

Time to Peak (Plasma):

• For palonosetron capsules, the time to reach peak plasma levels is about 5.1 ± 5.9 hours.

Excretion:

• Palonosetron is mainly excreted in urine, with approximately 80% excreted through this route, including 40% as unchanged drug.

Clearance:

• Clearance rates vary with age:
  • Infants and children under 2 years: 0.31 liters per hour per kilogram.
  • Children aged 2 to under 12 years: Mean clearance ranges from 0.19 to 0.23 liters per hour per kilogram.
  • Children aged 12 years and older, adolescents, and adults: Clearance is approximately 0.16 liters per hour per kilogram.

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