Paloxiron0.5 mg

Paloxiron 0.5 mg indicated in- Acute and delayed nausea and vomiting Uncontrolled nausea and vomiting Chemotherapy-induced nausea and vomiting (CINV): Acute CINV resulting in on the day of treatment with certain types of chemotherapy Delayed CINV resulting in on days later with certain types of chemotherapy ... Read morePaloxiron 0.5 mg indicated in- Acute and delayed nausea and vomiting Uncontrolled nausea and vomiting Chemotherapy-induced nausea and vomiting (CINV): Acute CINV resulting in on the day of treatment with certain types of chemotherapy Delayed CINV resulting in on days later with certain types of chemotherapy Radiotherapy-induced nausea and vomiting (RINV) Post-operative & Post-discharge nausea and vomiting (PONV & PDNV).

Anti-emetic drugs

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. Paloxiron 0.5 mg 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 Paloxiron 0.5 mg inhibits binding of serotonine to this receptor and also inhibits vomiting reflux.

Usual dosage: Adult tablet dosage: 0.5 mg daily. Adult IV dosage: A single IV dose of 0.075 mg should be administered over 10 seconds.Chemotherapy-induced nausea and vomiting: Adult tablet dosage: 0.5 mg administered approximately 1 hour prior to the start of chemotherapy. Adult IV dosage: A single IV dose of 0.25 mg should be administered over 30 seconds approximately 30 minutes before the start of chemotherapy.Radiotherapy-induced nausea and vomiting: A single IV dose of 0.25 mg should be administered over 30 seconds approximately 30 minutes before each week of radiation fraction.Post-operative nausea and vomiting: A single IV dose of 0.075 mg should be administered over 10 seconds immediately before induction of anesthesia.Children dosage: (1 month to 17 years): A single IV dose at 20 mcg/kg body weight. Which maximum dose is 1.5 mg.

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

In controlled clinical trials, Paloxiron 0.5 mg injection has been safely administered with corticosteroids, analgesics, antiemetics/antinauseants, antispasmodics and anticholinergic agents. Paloxiron 0.5 mg did not inhibit the antitumor activity of cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C in murine tumor models. Concomitant administration of Paloxiron 0.5 mg and metoclopramide has no significant pharmacokinetic interactions. In vitro studies indicated that Paloxiron 0.5 mg is not inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 & CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6 or CYP3A4/5. Therefore, the potential for clinically significant drug interactions with Paloxiron 0.5 mg appears to be low.

Paloxiron 0.5 mg is contraindicated in patients known to have hypersensitivity to the drug or any of its components.

The most common adverse reactions are headaches and constipation.

US FDA Pregnancy category B. It is not known whether Paloxiron is excreted in human milk.

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.

There is no known antidote to Paloxiron 0.5 mg. Overdose should be managed with supportive care.

Store in a cool & dry place, protected from light.

Pediatric Use: Safety and effectiveness in patients below the age of 18 years have not been established. However different clinical trial shows Paloxiron 0.5 mg is well tolerated and effective from one month of age.Geriatric Use: Pharmacokinetics analysis did not reveal any differences in Paloxiron 0.5 mg 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.

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.

Anti-emetic drugs

Paloxiron 0.5 mg is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine and that the released serotonin then activates 5-HT3 receptors that are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema, to initiate the vomiting reflex. Postoperative nausea and vomiting is influenced by multiple patient, surgical and anesthesia related factorcs and is triggered by release of 5-HT3 in a cascade of neuronal event involving both the central nervous system and the gastrointestinal tract. The 5-HT3 receptor has been demonstrated to selectively participate in the emetic response. Paloxiron 0.5 mg works by blocking the actions of Serotonin, associated with nausea and vomiting, at 5-HTs receptor. It is likely that Paloxiron 0.5 mg works in the small intestine but it may also work in the brain.Pharmacokinetics: Paloxiron 0.5 mg exhibits linear dose-proportional pharmacokinetics over the doserange 1-90 pg/kg in healthy subjects and in patients with cancer. In cancer patients receiving single intravenous doses of Paloxiron 0.5 mg in this dose range, the mean maximum plasma concentration (Cmax) ranges from 0.89 to 336 ng/ml and the area under the plasma concentration-time curve from zero to infinity (AUCo-co) ranges from 13.8 to 957 ng.h/ml. Paloxiron 0.5 mg has a volume of distribution of approximately 6.9-7.9 L/kg, with approximately 62% bound to plasma proteins. Approximately 50% of Paloxiron 0.5 mg is metabolized into two inactive metabolites that exhibit <1% of the 5-HT3 receptor antagonist activity. Approximately 40% of the drug is metabolised via kidney, 50% by liver CYP2D6 (mainly), CYP3A4 and CYP1A2 isoenzymes. About 50% of the drug goes under metabolism. After a single intravenous dose, approximately 40% is excreted as unchanged drug in the urine after 144 hours. Total body clearance of Paloxiron 0.5 mg is 160±35 ml/h/kg, and renal clearance is 66.5±18.2 ml/h/kg in healthy subjects. Paloxiron 0.5 mg exhibits a longer half-life (40 hours) and has a greater 5-HT3 receptor binding affinity.

Pregnancy category 'B'. It is not known whether Paloxiron 0.5 mg is excreted in breast milk.

Use in elderly patients: No dosage adjustment is recommended in elderly patients >65 years of age.Use in Children: (1 month to 10 years): A single IV dose at 20 mcg/kg body weight. Which maximum dose is 1.5 mg.Use in patients with impaired renal and hepatic function: No dosage adjustment is recommended in patients with renal and hepatic dysfunction.