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Indian Journal of Otolaryngology and... Dec 2022We compared the use of palonosetron with combination of palonosetron and dexamethasone in prevention of PONV in patients undergoing middle ear surgery under general...
Comparison of Palonosetron with Combination of Palonosetron and Dexamethasone in the Prevention of Post Operative Nausea and Vomiting in Patients Undergoing Middle Ear Surgery: A Prospective Randomized Trial.
We compared the use of palonosetron with combination of palonosetron and dexamethasone in prevention of PONV in patients undergoing middle ear surgery under general anaesthesia. Prospective, randomized study was conducted including 90 adult patients who received either palonosetron (0.075 mg) (Group P) or combination of palonosetron (0.075 mg) and dexamethasone (8 mg) (Group PD). The primary outcome was incidence of nausea, vomiting and complete response. Secondary parameters were time to receive first rescue antiemetic, total dose required, patient's satisfaction, postoperative pain scores and total dose of rescue analgesic. The incidence of nausea was 15.5% and 8.8% ( = 0.522) and vomiting was 6.7% and 2.2% ( = 0.610) in group P and PD, respectively Complete response (CR) was observed in 84.4% patients in group P and 91% patients in group PD ( = 0.522). Combination of palonosetron and dexamethasone is not superior to use of palonosetron alone for PONV prevention.
PubMed: 36742568
DOI: 10.1007/s12070-020-01996-6 -
British Journal of Anaesthesia Jul 2023
Topics: Humans; Postoperative Nausea and Vomiting; Vomiting; Antiemetics; Dexamethasone; Quinuclidines
PubMed: 36737386
DOI: 10.1016/j.bja.2023.01.005 -
Scientific Reports Jan 2023We demonstrated the non-inferiority of a dexamethasone (DEX)-sparing (single-dose) regimen with NEPA, a netupitant/palonosetron fixed combination, for preventing... (Randomized Controlled Trial)
Randomized Controlled Trial
We demonstrated the non-inferiority of a dexamethasone (DEX)-sparing (single-dose) regimen with NEPA, a netupitant/palonosetron fixed combination, for preventing chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. This pre-planned exploratory analysis assessed the effect of the DEX-sparing regimen on a patient's food intake. Chemotherapy-naïve patients undergoing cisplatin (≥ 70 mg/m) were given NEPA and DEX (12 mg) on day 1 and randomized to receive either no further DEX (DEX1), or oral DEX (4 mg BID) on days 2-4 (DEX4). Patient-reported endpoint maintenance of usual daily food intake was assessed during the 5-days post-chemotherapy. The relationship between usual daily food intake and CINV control, pre-chemotherapy self-rated food intake and BMI-adjusted weight loss (WL) were evaluated. One-hundred fifty-two patients (76/group) were assessable. The proportion of patients reporting maintenance of usual daily food intake was similar in both groups: 69.7% (95% CI, 58.6-78.9) for DEX1 vs. 72.4% (95% CI, 61.4-81.2) for DEX4. Only CINV control was significantly associated with maintenance of usual daily food intake (P ≤ 0.001) during the overall phase. The DEX-sparing regimen does not adversely affect patient-reported daily food intake post-chemotherapy. The current analysis adds further insights into antiemetic efficacy of DEX sparing beyond day 1 in the challenging setting of cisplatin.Trial registration: The parent study was registered on ClinicalTrials.gov (NCT04201769).
Topics: Humans; Cisplatin; Palonosetron; Antiemetics; Vomiting; Nausea; Dexamethasone; Eating; Lung; Antineoplastic Agents
PubMed: 36690734
DOI: 10.1038/s41598-023-28464-9 -
Journal of Personalized Medicine Dec 2022This updated systematic review and meta-analysis with trial sequential analysis aimed to compare the efficacy of the perioperative administration of palonosetron with... (Review)
Review
Comparison of the Effectiveness of Palonosetron and Ramosetron in Preventing Postoperative Nausea and Vomiting: Updated Systematic Review and Meta-Analysis with Trial Sequential Analysis.
This updated systematic review and meta-analysis with trial sequential analysis aimed to compare the efficacy of the perioperative administration of palonosetron with that of ramosetron in preventing postoperative nausea and vomiting (PONV). A total of 17 randomized controlled trials comparing the efficacy of the perioperative administration of palonosetron to that of ramosetron for preventing PONV were included. The primary outcomes were the incidences of postoperative nausea (PON), postoperative vomiting (POV), and PONV, which were measured in early, late, and overall phases. Subgroup analysis was performed on the basis of the administration time of the 5-HT3 receptor antagonist and divided into two phases: early phase and the end of surgery. A total of 17 studies with 1823 patients were included in the final analysis. The incidence of retching (relative risk [RR] = 0.525; 95% confidence interval [CI] = 0.390 to 0.707) and late POV (RR = 0.604; 95% CI = 0.404 to 0.903) was significantly lower in the palonosetron group than in the ramosetron group. No significant differences were demonstrated in the incidence of PON, PONV, complete response, use of antiemetics, and adverse effects. Subgroup analysis showed that palonosetron was superior to ramosetron in terms of early PON, late PON, overall POV, and use of rescue antiemetics when they were administered early; in terms of retching, regardless of the timing of administration. Ramosetron was superior to palonosetron in terms of early PON when they were administered late. The prophylactic administration of palonosetron was more effective than that of ramosetron in preventing the development of retching and late POV. In this meta-analysis, no significant differences in PONV prevention between the two drugs were demonstrated. Further studies are required to validate the outcomes of our study.
PubMed: 36675743
DOI: 10.3390/jpm13010082 -
The Journal of Pharmacology and... Mar 2023Cancer treatments are frequently associated with nausea and vomiting despite greatly improved preventive medication. Administration of antinausea agents as eye drops...
Cancer treatments are frequently associated with nausea and vomiting despite greatly improved preventive medication. Administration of antinausea agents as eye drops might provide easy and rapid access to the systemic circulation for prevention of nausea and vomiting and for the treatment of breakthrough nausea, but the ocular administration route has rarely been evaluated. Palonosetron is a second-generation 5-hydroxytryptamine 3 receptor antagonist approved for prevention and treatment of chemotherapy-induced nausea and vomiting. We compared ocular administration of palonosetron to non-active vehicle eye drops and to intravenous palonosetron in the prevention of cisplatin-induced nausea and vomiting in beagle dogs. Palonosetron ocular drops at the dose of 30 g/kg reduced cumulative nausea over time as measured with the area under the visual analog scale curve by 98% compared with the vehicle and reduced nausea-associated dog behavior by 95%. Vomiting was completely prevented with repeated palonosetron ocular dosing. Hydroxypropyl--cyclodextrin (HP--CD) palonosetron formulation was well tolerated locally at the palonosetron concentration of 3 mg/ml. Absorption of palonosetron from eye drops was fast. Ten minutes after ocular administration, palonosetron plasma concentrations were similar compared with intravenous administration, and remained similar for six hours. We conclude that palonosetron is rapidly absorbed into the systemic circulation from eye drops. Ocularly administered palonosetron was well tolerated in the HP--CD formulation and was highly effective in the prevention of cisplatin-induced nausea and vomiting. Evaluation of the safety and efficacy of ocular administration of palonosetron is warranted in the prevention and treatment of chemotherapy-induced nausea and vomiting in clinical trials. SIGNIFICANCE STATEMENT: Palonosetron, an effective and well-tolerated antiemetic drug was rapidly absorbed into the systemic blood circulation when administered as eye drops. The achieved palonosetron blood concentrations prevented cisplatin-induced nausea and vomiting in beagle dogs. Palonosetron eye drops might provide an easy and quick method for administering palonosetron when parenteral administration is desired and intravenous administration is not feasible.
Topics: Animals; Dogs; Palonosetron; Cisplatin; 2-Hydroxypropyl-beta-cyclodextrin; Administration, Ophthalmic; Isoquinolines; Quinuclidines; Vomiting; Nausea; Antineoplastic Agents; Dexamethasone
PubMed: 36635086
DOI: 10.1124/jpet.122.001444 -
Future Oncology (London, England) Jan 2023Despite numerous available antiemetics, chemotherapy induced nausea and vomiting (CINV) still affects many patients, and CINV related hospitalizations and costs often...
Despite numerous available antiemetics, chemotherapy induced nausea and vomiting (CINV) still affects many patients, and CINV related hospitalizations and costs often result. PrecisionQ analyzed its database to evaluate CINV related hospitalizations and costs following antiemetics use including netupitant/fosnetupitant with palonosetron (NEPA), aprepitant/fosaprepitant with ondansetron (APON) or aprepitant/fosaprepitant with palonosetron (APPA) in patients receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy. Database analysis identified 15,583 patient records (807 NEPA, 2023 APON, 12,753 APPA) and mean CINV related hospitalization costs were lower across all patients receiving NEPA (US$301) compared with patients receiving APON ($1006, p < 0.0001) or APPA ($321, p < 0.0001). NEPA is associated with lower CINV related hospitalization costs compared with APON and APPA among patients receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy.
Topics: Humans; Antiemetics; Palonosetron; Aprepitant; Antineoplastic Agents; Nausea; Vomiting; Quinuclidines
PubMed: 36622264
DOI: 10.2217/fon-2022-0972 -
Molecules (Basel, Switzerland) Nov 2022Chemotherapeutic agent-induced nausea and vomiting are the severe adverse effects that are induced by their stimulations on the peripheral and/or central emetic nerve...
Chemotherapeutic agent-induced nausea and vomiting are the severe adverse effects that are induced by their stimulations on the peripheral and/or central emetic nerve pathways. Even though ginger has been widely used as an herbal medicine to treat emesis, mechanisms underlying its neuronal actions are still less clear. The present study aimed to determine the chemotherapeutic agent vincristine-induced effect on gastroesophageal vagal afferent nerve endings and the potential inhibitory role of ginger constituent 6-shogaol on such response. Two-photon neuron imaging studies were performed in ex vivo gastroesophageal-vagal preparations from Pirt-GCaMP6 transgenic mice. Vincristine was applied to the gastroesophageal vagal afferent nerve endings, and the evoked calcium influxes in their intact nodose ganglion neuron somas were recorded. The responsive nodose neuron population was first characterized, and the inhibitory effects of 5-HT3 antagonist palonosetron, TRPA1 antagonist HC-030031, and ginger constituent 6-shogaol were then determined. Vincristine application at gastroesophageal vagal afferent nerve endings elicited intensive calcium influxes in a sub-population of vagal ganglion neurons. These neurons were characterized by their positive responses to P2X receptor agonist α,β-methylene ATP and TRPA1 agonist cinnamaldehyde, suggesting their nociceptive placodal nodose C-fiber neuron lineages. Pretreatment with TRPA1 selective blocker HC-030031 inhibited vincristine-induced calcium influxes in gastroesophageal nodose C-fiber neurons, indicating that TRPA1 played a functional role in mediating vincristine-induced activation response. Such inhibitory effect was comparable to that from 5-HT3 receptor antagonist palonosetron. Alternatively, pretreatment with ginger constituent 6-shogaol significantly attenuated vincristine-induced activation response. The present study provides new evidence that chemotherapeutic agent vincristine directly activates vagal nodose nociceptive C-fiber neurons at their peripheral nerve endings in the upper gastrointestinal tract. This activation response requires both TRPA1 and 5-HT3 receptors and can be attenuated by ginger constituent 6-shogaol.
Topics: Mice; Animals; Zingiber officinale; Vincristine; Calcium; Palonosetron; Esophagus; Action Potentials; Mice, Transgenic
PubMed: 36364288
DOI: 10.3390/molecules27217465 -
Pharmacoepidemiology and Drug Safety Apr 2023We explored the adverse drug reaction signals of drug-induced neutropenia (DIN) and drug-induced agranulocytosis (DIA) in hospitalized patients and evaluated the novelty...
PURPOSE
We explored the adverse drug reaction signals of drug-induced neutropenia (DIN) and drug-induced agranulocytosis (DIA) in hospitalized patients and evaluated the novelty of these correlations.
METHOD
A two-step method was established to identify the relationship between drugs and DIN or DIA using 5-year electronic medical records (EMRs) obtained from 242 000 patients at Qilu Hospital of Shandong University. First, the drugs suspected to induce DIN or DIA were selected. The associations between suspected drugs and DIN or DIA were evaluated by a retrospective cohort study using unconditional logistic regression analysis and multiple linear regression model.
RESULTS
Twelve suspected drugs (vancomycin, meropenem, voriconazole, acyclovir, ganciclovir, fluconazole, oseltamivir, linezolid, compound borax solution, palonosetron, polyene phosphatidylcholine, and sulfamethoxazole) were associated with DIN, and six suspected drugs (vancomycin, voriconazole, acyclovir, ganciclovir, fluconazole, and oseltamivir) were associated with DIA. The multivariate linear regression model revealed that nine drugs (vancomycin, meropenem, voriconazole, ganciclovir, fluconazole, oseltamivir, compound borax solution, palonosetron, and polyene phosphatidylcholine) and four drugs (vancomycin, voriconazole, ganciclovir, and fluconazole) were found to be associated with DIN and DIA, respectively. While logistic regression analysis revealed that palonosetron and ganciclovir were associated with DIN and DIA, respectively.
CONCLUSION
Palonosetron and ganciclovir were found to be correlated with drug-induced granulocytopenia. The results of this study provide an early warning of drug safety signals for drug-induced granulocytopenia, facilitating a quick and appropriate response for clinicians.
Topics: Aged; Humans; Agranulocytosis; Electronic Health Records; Neutropenia; Thrombocytopenia; Vancomycin; Meropenem; Voriconazole; Acyclovir; Ganciclovir; Palonosetron
PubMed: 36305574
DOI: 10.1002/pds.5559 -
Clinical Pharmacology in Drug... Dec 2022Oral NEPA is the fixed-combination antiemetic comprising netupitant (neurokinin-1 receptor antagonist [NK RA]) and palonosetron (5-hydroxytryptamine-3 receptor... (Randomized Controlled Trial)
Randomized Controlled Trial
Challenges in the Development of Intravenous Neurokinin-1 Receptor Antagonists: Results of a Safety and Pharmacokinetics Dose-Finding, Phase 1 Study of Intravenous Fosnetupitant.
Oral NEPA is the fixed-combination antiemetic comprising netupitant (neurokinin-1 receptor antagonist [NK RA]) and palonosetron (5-hydroxytryptamine-3 receptor antagonist [5-HT RA]). Intravenous (IV) NEPA, containing fosnetupitant, a water-soluble N-phosphoryloxymethyl prodrug of netupitant, has been developed. Fosnetupitant does not require excipients or solubility enhancers often used to increase IV NK RA water solubility, preventing the occurrence of hypersensitivity and infusion-site reactions associated with these products. In this phase 1 study, subjects received a 30-minute placebo or fosnetupitant (17.6-353 mg) infusion and an oral NEPA or placebo capsule, with 2-sequence crossover treatment for fosnetupitant 118- to 353-mg dose cohorts. IV fosnetupitant safety and pharmacokinetics were evaluated, and its equivalence to an oral netupitant 300-mg dose was defined. Overall, 158 healthy volunteers were enrolled. All adverse events (AEs) were mild or moderate in intensity. Doppler-identified infusion-site asymptomatic thrombosis occurred in 5.4% (fosnetupitant) and 1.2% (oral NEPA) of subjects. The frequency or number of treatment-related AEs did not increase with ascending fosnetupitant doses. The most common treatment-related AEs were headache (fosnetupitant, 8.1%; oral NEPA, 12.7%) and constipation (fosnetupitant, 1.4%; oral NEPA, 7.5%). A fosnetupitant 235-mg dose was equivalent, in terms of netupitant exposure, to 300-mg oral netupitant. The safety profile of a single fosnetupitant 235-mg infusion was similar to that of single-dose oral NEPA.
Topics: Humans; Nausea; Neurokinin-1 Receptor Antagonists; Vomiting; Water
PubMed: 36263927
DOI: 10.1002/cpdd.1183 -
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