palonosetron

Action and Spectrum

Actions and Spectrum: 

palonosetron is a medication that belongs to a class of drugs known as serotonin 5-HT3 receptor antagonists. It is primarily used to prevent nausea and vomiting caused by chemotherapy or surgery. 

The action of palonosetron involves binding to and blocking serotonin receptors (specifically, the 5-HT3 receptors) in the brain and gastrointestinal tract. This prevents the transmission of signals that trigger the sensation of nausea and vomiting, thus helping to reduce these symptoms. 

palonosetron has a long half-life, meaning that it remains active in the body for an extended period. This makes it effective at preventing delayed nausea and vomiting that can occur after chemotherapy. 

In terms of spectrum, palonosetron is effective in preventing both acute and delayed nausea and vomiting associated with moderately and highly emetogenic chemotherapy, as well as preventing postoperative nausea and vomiting. It is generally well-tolerated and has a low risk of adverse effects, which makes it a preferred option for preventing chemotherapy-induced nausea and vomiting. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Anxiety 

Dizziness 

Headache 

Weakness 

Constipation 

Diarrhea 

Pruritus 

Hyperkalemia 

LFT’s increased 

<1% 

Atrioventricular block 

Frequency not defined 

Immune hypersensitivity 

Seizure 

Dyskinesia 

Pain at the infusion site 

Allergic dermatitis 

Black Box Warning

There is no black box warning for Palonosetron 

Contraindication / Caution

Contraindication/Caution: 

palonosetron is generally considered safe and well-tolerated, but there are some contraindications and precautions to keep in mind: 

• Hypersensitivity: palonosetron should not be used in patients with a known hypersensitivity or allergy to the drug. 
• Cardiac disorders: palonosetron may prolong the QT interval, which can lead to cardiac arrhythmias. It should be used with caution in patients with pre-existing cardiac disorders, electrolyte imbalances, or taking other medications that can prolong the QT interval. 
• Hepatic impairment: palonosetron is primarily metabolized by the liver, and its clearance may be reduced in patients with hepatic impairment. Therefore, it should be used with caution in patients with moderate to severe hepatic impairment. 
• Pregnancy and breastfeeding: The safety of palonosetron during pregnancy and breastfeeding is not well-established, and it should only be used if the benefits outweigh the potential risks. 
• Pediatrics: The safety and efficacy of palonosetron in pediatric patients under the age of 18 years have not been established, and it is not recommended for use in this population. 

Pregnancy / Lactation

Pregnancy consideration:  

No data available regarding the risk associated during pregnancy 

Breastfeeding warnings: palonosetron is not known for its excretion in breast milk; therefore, take it with caution 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no affirmation of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a product in humans; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits. The drug is not for pregnant women. 
• Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

palonosetron is a selective serotonin 5-HT3 receptor antagonist that is used to prevent nausea and vomiting caused by chemotherapy or surgery. It exerts its pharmacological effects by binding to and blocking the 5-HT3 receptors in the central nervous system and gastrointestinal tract, thereby inhibiting the transmission of signals that stimulate the vomiting center in the brain. 

palonosetron has a high affinity for the 5-HT3 receptor and a long half-life, which enables it to provide effective antiemetic activity for up to five days following a single dose. Unlike other 5-HT3 receptor antagonists, palonosetron also exhibits activity at other receptor sites, such as the dopamine D2 receptor and the neurokinin-1 receptor, which may contribute to its enhanced antiemetic activity. 

palonosetron is primarily metabolized by the liver via the cytochrome P450 (CYP) enzyme system, particularly CYP2D6 and CYP3A4. It is eliminated primarily via the feces, with a small percentage excreted in the urine. palonosetron does not appear to have any significant pharmacokinetic interactions with other commonly used medications. 

Pharmacodynamics: 

The pharmacodynamics of palonosetron involves its interaction with serotonin 5-HT3 receptors in the central nervous system and gastrointestinal tract. As a selective 5-HT3 receptor antagonist, palonosetron competitively binds to and blocks the 5-HT3 receptors, thereby inhibiting the transmission of signals that stimulate the vomiting centre in the brain. 

In addition to its antiemetic effects, palonosetron also exhibits activity at other receptor sites, such as the dopamine D2 receptor and the neurokinin-1 receptor. These additional actions may contribute to its enhanced antiemetic activity and may also be relevant in the management of other conditions, such as postoperative nausea and vomiting. 

palonosetron has a high affinity for the 5-HT3 receptor and a slow dissociation rate, which allows it to provide long-lasting antiemetic activity. Studies have shown that a single dose of palonosetron can provide effective control of acute and delayed chemotherapy-induced nausea and vomiting for up to five days. 

Pharmacokinetics: 

Absorption 

The half-life is 40 hours 

The peak plasma concentration is 5.6±5.5 ng/mL, proportional to the dose 

The area under the curve is 35.8±20.9 ng.hr/mL proportional to the dose 

Distribution 

The bound protein is 62% 

The volume of distribution is 8.3±2.5 L/kg 

Metabolism 

The drug is metabolized by CYP3A, CYP2D6 and CYP1A2 

The metabolites formed are N-oxide-palonosetron and 6-S-hydroxy-palonosetron 

Elimination and Excretion  

The drug is excreted 80-93% in urine and 5-8% in feces  

The total rate of clearance is 160±35 mL/hr/kg

Adminstartion

Administration: 

palonosetron is typically administered by injection into a vein (intravenous or IV) by a healthcare professional. The recommended dose for preventing chemotherapy-induced nausea and vomiting in adults is a single 0.25 mg dose administered over 30 seconds, either prior to the start of chemotherapy or within 30 minutes after the end of chemotherapy. 

For prevention of postoperative nausea and vomiting, the recommended dose is also a single 0.25 mg dose given by IV injection at least 30 minutes before the start of anesthesia. palonosetron should be administered as a single dose and should not be repeated within the same 24-hour period, as this may increase the risk of adverse effects. 

It is important to follow the instructions of the healthcare provider regarding the administration of palonosetron. palonosetron is usually administered in a hospital or clinic setting, and patients should remain under observation for at least 30 minutes following administration to monitor for any adverse reactions. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: palonosetron 

Pronounced: PAL-oh-NOE-se-tron 

Why do we use palonosetron? 

palonosetron is used primarily for the prevention of nausea and vomiting caused by chemotherapy or surgery. Chemotherapy-induced nausea and vomiting (CINV) are common side effects of many chemotherapy agents and can significantly impact the quality of life of cancer patients.

CINV can be classified as acute (within 24 hours after chemotherapy), delayed (more than 24 hours after chemotherapy), or anticipatory (before the next chemotherapy session). 

palonosetron is particularly effective at preventing delayed CINV, which can occur in up to 50% of patients treated with highly emetogenic chemotherapy regimens. It is also effective at preventing acute and delayed CINV in patients receiving moderately emetogenic chemotherapy. 

In addition to its use in CINV, palonosetron is also indicated for the prevention of postoperative nausea and vomiting (PONV), which is a common complication of surgery that can lead to prolonged hospitalization and increased healthcare costs.