Palonosetron hydrochloride
Palonosetron hydrochloride Uses, Dosage, Side Effects, Food Interaction and all others data.
Nausea and Vomiting is usually produced by chemotherapeutic agents by releasing serotonin from the enterochromaffin cells of the small intestine.The released serotonin (5-HT) then activates 5-HT3 receptors located on vagal afferents to initiate the vomiting reflex. Postoperative nausea and vomiting is influenced by multiple patient, surgical and anesthesia related factors and is triggered by release of serotonin (5-HT) in a cascade of neuronal events involving both the central nervous system and the gastrointestinal tract. The 5-HT3 receptor has been demonstrated to selectively participate in the emetic response. Palonosetron hydrochloride is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. So by binding with this receptor palonosetron inhibits binding of serotonine to this receptor and also inhibits vomiting reflux.
Palonosetron hydrochloride is an antinauseant and antiemetic agent indicated for the prevention of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and for the prevention of postoperative nausea and vomiting. Palonosetron hydrochloride is a highly specific and selective serotonin 5-HT3 receptor antagonist that is pharmacologically related to other 5-HT3 receptor antagonists, but differs structurally. Palonosetron hydrochloride has a high affinity for 5-HT3 receptors, but has little to no affinity for other receptors. The serontonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. It is suggested that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.
| Trade Name | Palonosetron hydrochloride |
| Availability | Prescription only |
| Generic | Palonosetron |
| Palonosetron Other Names | Palonosetron, Palonosétron, Palonosetrón, Palonosetronum |
| Related Drugs | lorazepam, ondansetron, Zofran, dexamethasone, Ativan, metoclopramide, Reglan, amisulpride, droperidol |
| Type | |
| Formula | C19H24N2O |
| Weight | Average: 296.414 Monoisotopic: 296.188863401 |
| Protein binding | 62% |
| Groups | Approved, Investigational |
| Therapeutic Class | Anti-emetic drugs |
| Manufacturer | |
| Available Country | Russia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Moderately emetogenic cancer chemotherapy- prevention of acute and delayed nausea and vomiting associated with initial and repeat courses
Highly emetogenic cancer chemotherapy- prevention of acute nausea and vomiting associated with initial and repeat courses
Prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated.
Palonosetron hydrochloride is also used to associated treatment for these conditions: Chemotherapy-Induced Nausea and Vomiting (CINV), Post Operative Nausea and Vomiting (PONV), Acute chemotherapy induced nausea and vomiting, Delayed chemotherapy induced nausea and vomiting
How Palonosetron hydrochloride works
Palonosetron hydrochloride 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 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.
Dosage
Palonosetron hydrochloride dosage
Chemotherapy-Induced Nausea and Vomiting: Dosage for Adults- a single 0.25 mg I.V. dose administered over 30 seconds. Dosing should occur 30 minutes before the start of chemotherapy. Alternatively 0.5 mg tablet approximately 1 hour before the start of chemotherapy.
Postoperative Nausea and Vomiting: Dosage for Adults- a single 0.075 mg I.V. dose administered over 10 seconds immediately before the induction of anesthesia. In case of 0.5 mg tablet, dose should be determined by the physician.
Instructions for I.V. Administration-
- It should not be mixed with other drugs
- Flush the infusion line with normal saline before and after administration
- Parenteral drug products should be inspected visually for particulate matter and discoloration before administration
Intravenous:
Nausea and vomiting associated with cancer chemotherapy: Physically and chemically stable at concentrations of 5 and 30 mcg/ml in glucose 5%, sodium chloride 0.9%, glucose 5% in lactated Ringer's for at least 48 hr at room temperature, exposed to light and for 14 days under refridgeration.
Side Effects
The most common adverse reactions of Palonosetron hydrochloride in chemotherapy-induced nausea and vomiting are headache and constipation. The most common adverse reactions of Palonosetron hydrochloride in postoperative nausea and vomiting are QT prolongation, bradycardia, headache and constipation.
Toxicity
A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse.
Precaution
- For IV administration only. Not for intradermal, subcutaneous, or IM administration.
- Do not administer if particulate matter, cloudiness, or discoloration is noted.
- Discard any unused solution. Do not save unused solution for later administration.
- Do not mix with other medications.
Interaction
In vitro studies indicated that Palonosetron hydrochloride is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6, or CYP3A4/5. Therefore, drug interactions with Palonosetron hydrochloride appears to be low. In controlled clinical trials, Palonosetron hydrochloride injection has been safely administered with corticosteroids, analgesics, antiemetics/ antinauseants, antispasmodics and anticholinergic drugs. Palonosetron hydrochloride did not inhibit the antitumor activity of the five chemotherapeutic agents tested (cisplatin, cytarabine, doxorubicin and mitomycin C) in murine tumor models.
Food Interaction
- Take with or without food.
Palonosetron hydrochloride Drug Interaction
Major: meperidine, fentanylModerate: doxorubicin, prochlorperazine, polyethylene glycol 3350, acetaminophen / hydrocodoneMinor: sulfamethoxazole / trimethoprimUnknown: diphenhydramine, pancrelipase, dexamethasone, dexamethasone, apixaban, aprepitant, omega-3 polyunsaturated fatty acids, pegfilgrastim, acetaminophen, cyanocobalamin, pyridoxine, ascorbic acid, cholecalciferol
Palonosetron hydrochloride Disease Interaction
Volume of Distribution
- 8.3 ± 2.5 L/kg
Elimination Route
Low oral bioavailability.
Half Life
Approximately 40 hours
Clearance
- 160 +/- 35 mL/h/kg
Elimination Route
After a single intravenous dose of 10 mcg/kg [14C]-palonosetron, approximately 80% of the dose was recovered within 144 hours in the urine
Pregnancy & Breastfeeding use
US FDA Pregnancy category B. It is not known whether Paloxiron is excreted in human milk.
Contraindication
Palonosetron hydrochloride is contraindicated in patients known to have hypersensitivity to the drug or any of its components. Hypersensitivity reactions may occur in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists.
Special Warning
Pediatric Use: Safety and effectiveness in patients below the age of 18 years have not been established. However different clinical trial shows Palonosetron hydrochloride is well tolerated and effective from one month of age.
Geriatric Use: Pharmacokinetics analysis did not reveal any differences in Palonosetron hydrochloride pharmacokinetics between patients ≥ 65 years of age and younger patients (18 to 64 years)
Renal Function Impairment: No dosage adjustments are needed with any degree of renal function impairment.
Hepatic Function Impairment: No dosage adjustments are needed with any degree of hepatic function impairment.
Elderly: No dosage adjustments or special monitoring are needed in elderly patients.
Storage Condition
Store at controlled temperature of 20-25°C (68°F-77°F). Protect from light and protect injectable from freezing.
Innovators Monograph
You find simplified version here Palonosetron hydrochloride
Palonosetron hydrochloride contains Palonosetron see full prescribing information from innovator Palonosetron hydrochloride Monograph, Palonosetron hydrochloride MSDS, Palonosetron hydrochloride FDA label
FAQ
What is Palonosetron hydrochloride used for?
Palonosetron hydrochloride is used to prevent nausea and vomiting that may occur within 24 hours after receiving cancer chemotherapy or surgery. It is also used to prevent delayed nausea and vomiting that may occur several days after receiving certain chemotherapy medications.
Is Palonosetron hydrochloride a chemo drug?
Palonosetron hydrochloride injection is used to prevent nausea and vomiting that is caused by cancer medicines (chemotherapy). It is also used to prevent nausea and vomiting that may occur after surgery. Palonosetron hydrochloride works by blocking the signals to the brain that cause nausea and vomiting.
What are the side effects of Palonosetron hydrochloride?
Pain, redness, or swelling at the injection site may occur. Headache, constipation, or diarrhea may also occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.
What is the mechanism of action of Palonosetron hydrochloride?
Palonosetron hydrochloride is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. Cancer chemotherapy may be associated with a high incidence of nausea and vomiting, particularly when certain agents, such as cisplatin, are used.
Is Palonosetron hydrochloride safe in pregnancy?
Many modern anti-nausea medications such as dolasetron, ondansetron, Palonosetron hydrochloride, and tropisetron are considered safe for use during pregnancy.
How is Palonosetron hydrochloride given?
Palonosetron hydrochloride is given as an infusion into a vein. A healthcare provider will give you this injection. Palonosetron hydrochloride is usually given 30 minutes before chemotherapy, or right before you are given anesthesia for surgery.
How often can I give Palonosetron hydrochloride?
Palonosetron hydrochloride is a long acting medication that has a duration of action of 3 to 5 days. In most instances, only one dose needs to be given to prevent nausea and vomiting from chemotherapy. However, in some cases where chemotherapy is given for more than three days in a row, a second dose of Palonosetron hydrochloride may be given.
What is the half life of Palonosetron hydrochloride?
Mean terminal elimination half life is approximately 40 hours. Efficacy of single-dose palonosetron injection in preventing nausea and vomiting induced by moderately and highly emetogenic chemotherapy was studied in a phase 2 dose-ranging trial and three phase 3 trials.
