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Cureus Sep 2022Background Female gender, young age, first chemotherapy cycle, and low alcohol intake have all been linked to an increased risk of nausea and vomiting from chemotherapy....
The Effectiveness of an Oral Fixed-Dose Combination of Netupitant and Palonosetron (NEPA) in Patients With Multiple Risk Factors for Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Observational Indian Study.
Background Female gender, young age, first chemotherapy cycle, and low alcohol intake have all been linked to an increased risk of nausea and vomiting from chemotherapy. We intended to see if netupitant and palonosetron (NEPA) could prevent chemotherapy-induced nausea and vomiting (CINV) in patients with risk factors such as age, gender, chemotherapy cycle number, and alcohol consumption history. Methods In this retrospective study, chemotherapy-naïve patients who were prescribed netupitant (300 mg) and palonosetron (0.50 mg) (NEPA) before the first cycle of chemotherapy were analyzed for overall, acute, and delayed phases of complete response (CR), complete protection (CP), and control. Results In the acute phase (AP), delayed phase (DP), and overall phase (OP), complete response was 88.23%, 86.27%, and 86.27%, respectively; complete protection was 80.39%, 78.43%, and 76.47%, respectively; and complete control was 76.47%, 72.54%, and 70.58%, respectively, in the whole population (i.e., 51 patients). Complete response, protection, and control in the overall phase were achieved by 86.27%, 72.72%, and 68.18% of patients who received the highly emetogenic chemotherapy (HEC) regimen (i.e., 44 patients), respectively. Conclusion NEPA provided a consistent magnitude of benefit for patients who are at high risk, receiving HEC and moderately emetogenic chemotherapy (MEC), and having good control in the acute, delayed, and overall phases of CINV.
PubMed: 36259011
DOI: 10.7759/cureus.29094 -
Indian Journal of Anaesthesia Oct 2018Patients undergoing ovarian cancer surgery after chemotherapy and requiring opioid-based patient-controlled analgesia (PCA) are at high-risk of postoperative nausea and...
Comparison of palonosetron and dexamethasone with ondansetron and dexamethasone for postoperative nausea and vomiting in postchemotherapy ovarian cancer surgeries requiring opioid-based patient-controlled analgesia: A randomised, double-blind, active controlled study.
BACKGROUND AND AIMS
Patients undergoing ovarian cancer surgery after chemotherapy and requiring opioid-based patient-controlled analgesia (PCA) are at high-risk of postoperative nausea and vomiting (PONV). We aimed to assess the effect of palonosetron and dexamethasone combination for these patients for prevention of PONV.
METHODS
This study included 2 groups and 150 patients. At the time of wound closure, patients in group A received ondansetron 8 mg intravenous (IV) + dexamethasone 4 mg IV and group B received palonosetron 0.075 mg IV + dexamethasone 4 mg IV. Postoperatively for 48 hours, group A patients received ondansetron 4 mg 8 hourly IV, group B patients received normal saline 8 hourly IV in 2 cc syringe. The primary objective was the overall incidence of PONV. Independent -test, Chi-square test, and Fisher's exact test were used and multivariate regression analysis was done.
RESULTS
Vomiting was significantly higher in group A (37.3%) as compared with group B (21.3%) at 0-48 hours ( = 0.031). Significantly more patients in Group A had nausea as compared with group B at 90-120 minutes (30.66% vs 18.66%, = 0.043) and 6-24 hours (32.0% vs 22.66%, = 0.029). PCA opioid usage in microgram was significantly higher in group A at 0-24 hours (690.53 ± 332.57 vs 576.85 ± 250.79, = 0.024) and 0-48 hours (1126.10 ± 512.18 vs 952.13 ± 353.85, = 0.030).
CONCLUSION
Palonosetron with dexamethasone is more effective than ondasetron with dexamethasone for prevention of PONV in post-chemotherapy ovarian cancer surgeries receiving opioid-based patient controlled analgesia.
PubMed: 30443060
DOI: 10.4103/ija.IJA_437_18 -
Neuropharmacology Oct 2013Palonosetron is a potent 5-HT₃ receptor antagonist with a unique structure and some unusual properties. Here we explore the properties of palonosetron at...
Palonosetron is a potent 5-HT₃ receptor antagonist with a unique structure and some unusual properties. Here we explore the properties of palonosetron at heterologously expressed 5-HT₃A and 5-HT₃AB receptors. We used receptors expressed in HEK293 cells, and functionally analysed them using a membrane potential sensitive dye in a Flexstation, which revealed IC₅₀s of 0.24 nM and 0.18 nM for 5-HT₃A and 5-HT₃AB receptors respectively. Radioligand binding studies with [(3)H]palonosetron revealed similar Kds: 0.34 nM for 5-HT3A and 0.15 nM for 5-HT₃AB receptors. Kinetic studies showed palonosetron association and dissociation rates were slightly faster in 5-HT₃AB than 5-HT₃A receptors, and for both subtypes dissociation rates were ligand-dependent, with antagonists causing more rapid dissociation than agonists. Similar ligand effects were not observed for [(3)H]granisetron dissociation studies. These data support previous studies which show palonosetron has actions distinct to other 5-HT3 receptor antagonists, and the slow rates observed for agonist induced dissociation (t₁/₂ > 10 h) could at least partly explain the long duration of palonosetron effects in vivo.
Topics: Granisetron; HEK293 Cells; Humans; Inhibitory Concentration 50; Isoquinolines; Palonosetron; Protein Subunits; Quinuclidines; Radioligand Assay; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Agonists; Serotonin 5-HT3 Receptor Antagonists; Transfection; Tritium
PubMed: 23747573
DOI: 10.1016/j.neuropharm.2013.05.010 -
Oncology (Williston Park, N.Y.) Jul 2007
Topics: Administration, Oral; Anorexia; Antiemetics; Antineoplastic Agents; Aprepitant; Asthenia; Constipation; Diarrhea; Drug Interactions; Dyspepsia; Fatigue; Fever; Granisetron; Headache; Hiccup; Humans; Indoles; Injections, Intravenous; Isoquinolines; Morpholines; Nausea; Neoplasms; Ondansetron; Palonosetron; Quinolizines; Quinuclidines; Vomiting
PubMed: 17844897
DOI: No ID Found -
EClinicalMedicine Jul 2022Despite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) by using dexamethasone combined with palonosetron for patients who...
Aprepitant plus palonosetron versus dexamethasone plus palonosetron in preventing chemotherapy-induced nausea and vomiting in patients with moderate-emetogenic chemotherapy: A randomized, open-label, phase 3 trial.
BACKGROUND
Despite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) by using dexamethasone combined with palonosetron for patients who received moderate-emetogenic chemotherapy (MEC), some of these patients still suffer from CINV. We evaluated whether aprepitant combined with palonosetron can improve the efficacy in the prevention of CINV in patients receiving MEC.
METHODS
This was a single-centre, open-label, phase III, randomized controlled trial, which was done at the Sixth Affiliated Hospital of Sun Yat-sen University of China. The registered patients planned to receive mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) but had not received any chemotherapy previously. The patients were randomized in a 1:1 ratio to the aprepitant group (aprepitant 125 mg orally on day 1, 80 mg on day 2-3) and the dexamethasone group (dexamethasone 10 mg intravenously on day 1, 5 mg on days 2 and 3), both groups with palonosetron 0.25 mg intravenously on day 1. The primary endpoint was the proportion of patients who achieved a complete response (CR), defined as the absence of vomiting and no use of rescue medications in the overall phase (0-120 h). The primary outcome and safety were assessed in the modified intention-to-treat population, which excluded all patients who used estazolam within 24 h before registration and those who refused to keep a diary documenting the severity of nausea, frequency of vomiting, and the use of rescue therapy. This trial is registered with ClinicalTrials.gov, NCT02909478.
FINDINGS
Between Sep 1, 2017, and Oct 23, 2019, 320 patients were enrolled, and 315 patients were evaluated. The proportion of patients who achieved CR was significantly higher with aprepitant than that noted with dexamethasone in the overall phase (88.8% vs. 74.2%; = 0.0010; rate difference, RD 15%, 95% CI, 6% to 23%) and in the delayed phase (25-120 h), 90.6% vs. 75.5%, ( < 0.0001; RD 15%, 95%CI, 7% to 23%). No significant difference of CR rate was observed in the acute phase (0-24 h), 93.8% vs. 93.5%, ( = 0.94; RD 0%, 95% CI, -5% to 6%)). In the overall phase, the incidence of insomnia ( < 0.0010), dyspepsia ( = 0.038), and flushing ( = 0.0010) reported by the patients was significantly higher in the dexamethasone group than that in the aprepitant group.
INTERPRETATION
Aprepitant combined with palonosetron is superior to dexamethasone combined with palonosetron in patients who received the MEC regimen mFOLFOX6 in terms of preventing CINV.
FUNDING
The National Key R&D Program of China (2019YFC1316000) and the National Natural Science Foundation of China (81974369).
PubMed: 35747189
DOI: 10.1016/j.eclinm.2022.101480 -
Medicine Aug 2021Postoperative nausea and vomiting (PONV) is an undesirable complication in patients undergoing general anesthesia. Combination therapy via different mechanisms of action...
BACKGROUND
Postoperative nausea and vomiting (PONV) is an undesirable complication in patients undergoing general anesthesia. Combination therapy via different mechanisms of action for antiemetic prophylaxis has been warranted for effective treatment of PONV. This study was designed to compare the prophylactic antiemetic effect between midazolam combined with palonosetron (group MP) and palonosetron alone (group P) after laparoscopic cholecystectomy surgeries.
METHODS
A prospective randomized controlled trial was investigated in non-smoking female. Eighty-eight patients were randomly divided into 2 groups with 44 patients each. Group MP received 0.05 mg/kg of midazolam intravenously before induction of anesthesia whereas group P received the same volume of normal saline. Immediately after anesthetic induction, 0.075 mg of palonosetron was administered to both the groups. The incidence and severity of PONV were assessed during 2 time intervals (0-2 hours, 2-24 hours), postoperatively.
RESULTS
The incidence of PONV during 24 hours after surgery was lower in group MP as compared to group P. There was also a significant difference in the use of rescue antiemetics. The severity of nausea was significantly lower in group MP as compared to group P, in the initial 2 hours after surgery. The incidence of side effects was similar between the 2 groups.
CONCLUSION
In the prevention of PONV, midazolam combined with palonosetron, administered during induction of anesthesia was more effective as compared to palonosetron alone.
Topics: Adjuvants, Anesthesia; Adult; Antiemetics; Cholecystectomy, Laparoscopic; Female; Humans; Male; Midazolam; Middle Aged; Palonosetron; Postoperative Nausea and Vomiting; Prospective Studies; Republic of Korea
PubMed: 34414984
DOI: 10.1097/MD.0000000000026997 -
Current Therapeutic Research, Clinical... 2019Postoperative nausea and vomiting (PONV) are 2 of the most frequent adverse effects of anesthesia. PONV prolongs hospital stays and also delays the recovery of patients.
BACKGROUND
Postoperative nausea and vomiting (PONV) are 2 of the most frequent adverse effects of anesthesia. PONV prolongs hospital stays and also delays the recovery of patients.
OBJECTIVE
In this study, the effects of ondansetron, tropisetron, and palonosetron on PONV in patients who had undergone middle ear surgeries such as mastoidectomy or tympanoplasty were compared.
METHODS
The study included 165 American Society of Anesthesiologists grade 1 and 2 patients aged 18 to 65 years. Patients were randomized into 3 groups by a closed envelope method. Neither the patients nor the nurses administering the treatments knew which patient belonged to which group. The anesthetic technique was standardized for all groups. During skin closure, 0.075 mg palonosetron, 5 mg tropisetron, and 8 mg ondansetron were administered intravenously to the palonosetron, tropisetron, and ondansetron groups, respectively. After completion of the surgery, the patients were followed for 48 hours. Diclofenac sodium (100 mg IM) was administered to patients experiencing pain and metoclopramide chloride (10 mg IM) was administered to patients with nausea or vomiting. Potential side effects such as headache and constipation were recorded in the postanesthesia care unit and ear, nose, and throat clinic.
RESULTS
There was no significant difference in the effects of all 3 antiemetic agents on the severity of PONV ( = 0.081). At 48 hours postoperatively, the incidence of PONV was significantly lower in the palonosteron group (38.2%) than the ondansetron group (63.6%) and tropisetron group (61.8%) ( = 0.011). At 48 hours postoperatively, the incidence of postoperative nausea was significantly lower in the palonosetron group (32.7%) than in the ondansetron group (63.6%) and the tropisetron group (56.4%) ( = .003). The incidence of PONV between hours 12 and 24 postoperatively was significantly higher in the ondansetron group (27.3%) than in the palonosetron group (9.1%) ( = 0.013). The antiemetic requirement in the first hour after surgery was significantly higher in the tropisetron group (25.5%) than in the palonosetron group (7.3%) ( = .019).
CONCLUSIONS
The results of the current study support those of earlier studies that suggest that palonosetron was statistically more effective than the other 2 formulations in the prevention of PONV in patients who have undergone middle ear surgery. ( 2019; 80:XXXXXX).
PubMed: 31384338
DOI: 10.1016/j.curtheres.2019.06.002 -
Therapeutics and Clinical Risk... 2016As recommended by most recent antiemetic guidelines, the optimal prophylaxis of chemotherapy-induced nausea and vomiting (CINV) requires the combination of 5-HT3... (Review)
Review
As recommended by most recent antiemetic guidelines, the optimal prophylaxis of chemotherapy-induced nausea and vomiting (CINV) requires the combination of 5-HT3 receptor antagonist (RA) with an NK1-RA. Moreover, the major predictors of acute and delayed CINV include: young age, female sex, platinum- or anthracycline-based chemotherapy, nondrinker status, emesis in the earlier cycles of chemotherapy, and previous history of motion/morning sickness. Despite improved knowledge of the pathophysiology of CINV and advances in the availability of active antiemetics, an inconsistent compliance with their use has been reported, thereby resulting in suboptimal control of CINV in several cases. In this scenario, a new anti-emetic drug is now available, which seems to be able to guarantee better prophylaxis of CINV and improvement of adherence to guidelines. In fact, netupitant/palonosetron (NEPA) is a ready-to-use single oral capsule, combining an NK1-RA (netupitant) and a 5-HT3-RA (palonosetron), which is to be taken 1 hour before the administration of chemotherapy, ensuring the coverage from CINV for 5 days. We reviewed the role of NEPA in patients at high risk of CINV receiving highly emetogenic chemotherapy. In these patients, NEPA plus dexamethasone, as compared to standard treatments, achieved superior efficacy in all primary and secondary end points during the acute, delayed, and overall phases, including nausea assessment. Moreover, these results were also achieved in female patients receiving anthracycline plus cyclophosphamide-based chemotherapy. NEPA represents a real step forward in the prophylaxis of CINV.
PubMed: 27354807
DOI: 10.2147/TCRM.S89215 -
Annals of Oncology : Official Journal... Dec 2010The implications of chemotherapeutic drug-drug interactions can be serious and thus need to be addressed. This review concerns the potential interactions of the... (Review)
Review
The implications of chemotherapeutic drug-drug interactions can be serious and thus need to be addressed. This review concerns the potential interactions of the antiemetic aprepitant, a neurokinin-1 receptor antagonist indicated for use (in Europe) in highly emetogenic chemotherapy and moderately emetogenic chemotherapy (MEC) in combination with a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist and corticosteroids and (in the United States) in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy including high-dose cisplatin. When considering use of aprepitant for prevention of chemotherapy-induced nausea and vomiting, its potential drug-drug interaction profile as a moderate inhibitor of cytochrome P-450 isoenzyme 3A4 (CYP3A4) has been a source of concern for some physicians and other health care professionals. We explore in this paper how real those concerns are. Our conclusion is that either no interaction or no clinically relevant interaction exists with chemotherapeutic agents (intravenous cyclophosphamide, docetaxel, intravenous vinorelbine) or 5-HT3 antagonists (granisetron, ondansetron, palonosetron). For relevant interactions, appropriate measures, such as corticosteroid dose modifications and extended International Normalized Ratio monitoring of patients on warfarin therapy, can be taken to effectively manage them. Therefore, the concern of negative interactions remains largely theoretical but needs to be verified with new agents extensively metabolized through the 3A4 pathway.
Topics: Adrenal Cortex Hormones; Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Drug Combinations; Drug Interactions; Humans; Morpholines; Serotonin 5-HT3 Receptor Antagonists
PubMed: 20488873
DOI: 10.1093/annonc/mdq149