Palonosetron is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is the most effective of the 5-HT3 antagonists in controlling delayed CINV nausea and vomiting that appear more than 24 hours after the first dose of a course of chemotherapy and is the only drug of its class approved for this use by the U.S. Food and Drug Administration. As of 2008, it is the most recent 5-HT3 antagonist to enter clinical uses
Mechanism of Action of Palonosetron
Palonosetron is a selective serotonin 5-HT3 receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors, in turn, inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone. Alternative mechanisms appear to be primarily responsible for delayed nausea and vomiting induced by emetogenic chemotherapy, since similar temporal relationships between serotonin and emesis beyond the first day after a dose have not been established, and 5-HT3 receptor antagonists generally have not appeared to be effective alone in preventing or ameliorating delayed effects. It has been hypothesized that palonosetron’s potency and long plasma half-life may contribute to its observed efficacy in preventing delayed nausea and vomiting caused by moderately emetogenic cancer chemotherapy.
Indications of Palonosetron
- Prophylaxis against postoperative nausea and vomiting
- Delayed chemotherapy-induced nausea and vomiting
- Prophylaxis of acute chemotherapy-induced nausea and vomiting
- Highly emetogenic cancer chemotherapy
- Palonosetron Hospira is indicated in adults for the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy, the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.
- Palonosetron Hospira is indicated in pediatric patients 1 month of age and older for the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy and prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.
- Palonosetron Accord is indicated in adults for the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy, the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.
- Palonosetron Accord is indicated in pediatric patients 1 month of age and older for.
- The prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy and prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.
- Palonosetron is indicated in adults for the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy, the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.
- Palonosetron is indicated in pediatric patients 1 month of age and older for the prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy and prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.
Contra Indications of Palonosetron
- Low amount of magnesium in the blood
- Low amount of potassium in the blood
- Neuroleptic Malignant Syndrome
- Serotonin syndrome – adverse drug interaction
- Heart Muscle Disease caused by the Medication Doxorubicin
- Complete Heart Block
- Very Rapid Heartbeat – Torsades de Pointes
- Slow Heartbeat
- Prolonged QT interval on EKG
- Chronic heart failure
- Abnormal EKG with QT changes from Birth
- kidney disease with a reduction in kidney function
- Allergies to Serotonin 5HT-3 Antagonists
Dosage of Palonosetron
Strengths: 0.25 mg/5 mL; 0.075 mg/1.5 mL
Chemotherapy Induce Nausea/Vomiting
- Oral: 0.5 mg orally administered approximately 1 hour prior to the start of chemotherapy
- Parenteral: 0.25 mg IV as a single dose 30 minutes before the start of chemotherapy
Postoperative Nausea/Vomiting
- Parenteral: 0.075 mg IV as a single dose immediately before induction of anesthesia
Chemotherapy Induce Nausea/Vomiting – Pediatric
- Parenteral: 20 mcg/kg IV (maximum 1.5 mg x 1) infused over 15 minutes beginning 30 minutes before the start of chemotherapy
Side Effects of Palonosetron
The most common
- Diarrhea
- muscle twitching
- weakness
- Any signs of infection, or a skin rash.
- Stomach pain, especially if it comes along with fever and diarrhea or constipation
- Yellowing of the skin or eyes
- Loss of appetite
- Constipation
- Chest pain or discomfort
- lightheadedness, dizziness, or fainting
- slow or irregular heartbeat
- unusual tiredness or weakness
- a decrease in the amount of urine
- fast, pounding, or irregular heartbeat or pulse
- false sense of well-being
- increased watering of mouth
- lightheadedness
- constipation;
- vision changes;
- breast swelling (in men or women); or
- decreased sex drive, impotence, or difficulty having an orgasm.
- blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- restless muscle movements in your eyes, tongue, jaw, or neck;
Common
- Drowsiness and lightheadedness the day after taking the medicine.
- Confusion.
- Numbed emotions.
- Visual disturbances such as blurred vision or double vision.
- Shaky movements and unsteady walk (ataxia).
- Muscle weakness.
- Dizziness.
- A headache.
- Skin rashes.
- Disturbances of the gut such as diarrhea, constipation, nausea, vomiting or abdominal pain.
- Changes in sex drive.
- Low blood pressure (hypotension).
- Blood disorders.
- Unexpected aggression, restlessness or irritability .
- Nightmares or hallucinations
Rare
- agitation
- anxiety
- behavioral changes, including aggressiveness, angry outbursts,
- confusion
- increased trouble sleeping
- muscle spasms
- shortness of breath
- difficult or labored breathing
- difficulty with swallowing
- dizziness, faintness, or lightheadedness
- frequent urination
- hallucinations
- bloating or swelling of the face, arms, hands, lower legs, or feet
- blurred vision
- hives or welts, itching, or skin rash
- the increased volume of pale, dilute urine
Drug Interactions of Palonosetron
Palonosetron may interact with following drugs, supplements, & may change the efficacy of drugs
- antipsychotics (e.g. haloperidol, ziprasidone)
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- beta-agonists (e.g., formoterol, salmeterol)
- cimetidine
- corticosteroids (high dose; e.g., hydrocortisone, methylprednisolone, prednisone)
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, indapamide)
- domperidone
- famotidine
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- other serotonin receptor antagonists (e.g., granisetron, ondansetron)
- quinolone antibiotics (e.g., ciprofloxacin, levofloxacin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine)
- sotalol
- tapentadol
- tramadol
- tricyclic antidepressants (e.g., amitriptyline, imipramine, nortriptyline)
- trimethoprim
- tyrosine kinase inhibitors (e.g., nilotinib, sunitinib)
Pregnancy & Lactation of Palonosetron
FDA pregnancy risk category B
Palonosetron is listed in FDA pregnancy risk category B. Animal-based teratology studies have not revealed evidence of impaired fertility or harm to the fetus due to palonosetron. There are, however, no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. The effects of palonosetron on labor and delivery are not known.
Lactation
It is not known if palonosetron is excreted in human milk. Many drugs are excreted in human milk and may increase the potential for serious adverse reactions in the breastfeeding infant. The manufacturer warns against the use of palonosetron in breast-feeding women due to the possible risks to the infant.
