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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 -
Anesthesia, Essays and Researches 2022Postoperative nausea and vomiting (PONV) are one of the common distressing conditions after anesthesia. The PONV are related to several potential risk factors are...
Comparison of Palonosetron Versus Palonosetron and Dexamethasone for Prevention of Postoperative Nausea and Vomiting After Middle Ear Surgeries: A Randomized Controlled Study.
BACKGROUND
Postoperative nausea and vomiting (PONV) are one of the common distressing conditions after anesthesia. The PONV are related to several potential risk factors are patient related, anesthesia related, and surgery related. In surgery-related risk, middle ear surgery is associated with a high incidence of PONV.
AIMS
This study aimed to compare the efficiency of palonosetron versus palonosetron with dexamethasone in the prevention of PONV in middle ear surgeries.
SETTINGS AND DESIGN
This was a prospective, randomized, double-blind study.
STATISTICAL ANALYSIS
The data were presented as descriptive statistics for continuous variables and percentages for categorical variables and were subjected to Z-test/Chi-square test/Fisher's exact test. The value of < 0.05 was considered statistically significant.
RESULTS
Demographic parts in comparison to age, duration of surgery, and duration of anesthesia were similar in both the groups. Our study showed that the incidence of PONV during 0-6 h was 38% ( = 19) in Group A and 12% ( = 6) in Group B and the incidence during 6-12 h postoperatively was 14% ( = 7) in Group A and 8% ( = 4) in Group B. During 12-24 h, the incidence was 8% ( = 4) and 6% ( = 3) in Group A and B, respectively. Hence, the difference of total early PONV in Group A was 60% ( = 30) and in Group B, it was 26% ( = 13) which was statistically significant ( < 0.03).
CONCLUSIONS
The above result proves that palonosetron and dexamethasone group is superior in the prevention of PONV in middle ear surgery.
PubMed: 36249139
DOI: 10.4103/aer.aer_131_21 -
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 -
British Journal of Anaesthesia Aug 2023Approximately 25% of ambulatory surgery patients experience post-discharge nausea and vomiting (PDNV). We aimed to investigate whether palonosetron, a long-acting... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Approximately 25% of ambulatory surgery patients experience post-discharge nausea and vomiting (PDNV). We aimed to investigate whether palonosetron, a long-acting anti-emetic, decreases the incidence of PDNV in high-risk patients.
METHODS
In this prospective, randomised, double-blind, placebo-controlled trial, 170 male and female patients undergoing ambulatory surgery under general anaesthesia, with a high predicted risk for PDNV, were randomised to receive either palonosetron 75 μg i.v. (n=84) or normal saline (n=86) before discharge. During the first 3 postoperative days (PODs), we measured outcomes using a patient questionnaire. The primary outcome was the incidence of a complete response (no nausea, vomiting, or use of rescue medication) until POD 2. Secondary outcomes included the incidence of PDNV each day until POD 3.
RESULTS
The incidence of a complete response until POD 2 was 48% (n=32) in the palonosetron group and 36% (n=25) in the placebo group (odds ratio 1.69 [95% confidence interval: 0.85-3.37]; P=0.131). No significant difference in the incidence of PDNV was observed between the two groups on the day of surgery (47% vs 56%; P=0.31). Significant differences in the incidence of PDNV were found on POD 1 (18% vs 34%; P=0.033) and POD 2 (9% vs 27%; P=0.007). No differences were observed on POD 3 (15% vs 13%; P=0.700).
CONCLUSIONS
Compared with placebo, palonosetron did not reduce the overall incidence of post-discharge nausea and vomiting up to postoperative day 2. The lower incidence of post-discharge nausea and vomiting on poatoperative days 1 and 2 in the palonosetron group requires further investigation.
CLINICAL TRIAL REGISTRATION
EudraCT 2015-003956-32.
Topics: Humans; Male; Female; Palonosetron; Postoperative Nausea and Vomiting; Ambulatory Surgical Procedures; Prospective Studies; Patient Discharge; Aftercare; Antiemetics; Double-Blind Method
PubMed: 37246062
DOI: 10.1016/j.bja.2023.04.034 -
Journal of Pharmaceutical Health Care... Aug 2022Cisplatin (CDDP)-induced nephrotoxicity is the most important complication of CDDP treatment. 5-Hydroxytryptamine type 3 receptor antagonists (5-HTRAs) are widely used...
BACKGROUND
Cisplatin (CDDP)-induced nephrotoxicity is the most important complication of CDDP treatment. 5-Hydroxytryptamine type 3 receptor antagonists (5-HTRAs) are widely used to prevent chemotherapy-induced nausea and vomiting (CINV). However, in patients with the triple antiemetic (neurokinin-1 receptor antagonist, 5-HTRA, and dexamethasone) therapy, the advantage of palonosetron in comparison with other 5-HTRAs on CDDP-induced nephrotoxicity and CINV remains unclear. In the present study, we investigated the effect of palonosetron on CDDP-induced nephrotoxicity and CINV in patients with the triple antiemetic therapy by a retrospective cohort study and a pharmacovigilance analysis.
METHODS
We retrospectively analyzed the effect of 5-HTRAs on the development of nephrotoxicity and CINV in 110 patients who received CDDP, fluorouracil, and triple antiemetic therapy for the treatment of esophageal cancer. Moreover, the effect of 5-HTRAs on CDDP-induced nephrotoxicity was validated in patients with the triple antiemetic therapy using the Japanese Adverse Drug Event Report (JADER) database.
RESULTS
In a retrospective study, the incidence of nephrotoxicity (≥ grade 1) in patients receiving palonosetron (18%) was significantly lower than that in patients receiving ramosetron (another 5-HTRA) (36%, p = 0.044). Moreover, severe nephrotoxicity ≥ grade 3 was observed in one patient treated with ramosetron, whereas hematological toxicity was comparable between the two groups (p = 0.553). Furthermore, the incidence rate of CINV within 120 h following CDDP administration in patients treated with palonosetron (18%) was significantly lower than that in patients receiving ramosetron (39%, p = 0.026). JADER database analyses revealed that the reporting odds ratio of palonosetron for CDDP-induced acute kidney injury was 0.282 (95% confidence interval: 0.169-0.472).
CONCLUSIONS
The findings of the present study suggested a greater potential of palonosetron against CDDP-induced nephrotoxicity and CINV than other 5-HTRAs in patients with the triple antiemetic therapy.
PubMed: 35909131
DOI: 10.1186/s40780-022-00252-z -
Biological & Pharmaceutical Bulletin 2021Patients who undergo multiple-day chemotherapy sessions experience hard-to-treat nausea and vomiting. Currently, there is no effective standard treatment for this...
Patients who undergo multiple-day chemotherapy sessions experience hard-to-treat nausea and vomiting. Currently, there is no effective standard treatment for this condition. This study compared the preventive effect of first-generation 5-hydroxytryptamine 3 receptor antagonists (5-HT RAs) and second-generation 5-HT RAs palonosetron in multiple-day chemotherapy-induced nausea and vomiting. The design of this study was a retrospective case-control study of patients who received a five-day cisplatin-based chemotherapy and were treated with aprepitant, dexamethasone, granisetron, and ramosetron or palonosetron. The patients were divided into two groups: patients given granisetron and ramosetron (the first-generation group), and those given palonosetron (palonosetron group). The percentage of patients with a complete response or total control was assessed. They were divided into three phases: 0-216 h (overall phase), 0-120 h (remedial phase), and 120-216 h (after phase). The remedial phase was further divided into 0-24 h (early phase) and 24-120 h (later phase). Moreover, the nutritional status of each patient was assessed by noting the patients' total calorie-intake per day and total parenteral nutrition. First-generation 5-HT RAs and palonosetron were used for treatment in 18 and 28 patients, respectively. The complete response rate and caloric oral intake of the later phase were higher in the palonosetron group than in the first-generation group. We conclude that palonosetron treatment was more effective than first-generation 5-HT RAs in controlling multiple-day chemotherapy-induced nausea and vomiting.
Topics: Adult; Antiemetics; Antineoplastic Agents; Benzimidazoles; Bleomycin; Drug Therapy, Combination; Etoposide; Female; Granisetron; Humans; Male; Middle Aged; Nausea; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Palonosetron; Platinum Compounds; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Testicular Neoplasms; Vomiting
PubMed: 33790099
DOI: 10.1248/bpb.b20-00609 -
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 -
Best Practice & Research. Clinical... Dec 2020Postoperative nausea and vomiting (PONV) afflict approximately 30% of patients overall and up to 80% of high-risk patients after surgery. Optimal pharmacological... (Review)
Review
Postoperative nausea and vomiting (PONV) afflict approximately 30% of patients overall and up to 80% of high-risk patients after surgery. Optimal pharmacological prophylaxis of PONV is challenging as it necessitates the consideration of PONV risk, drug efficacy, and potential adverse effects. Despite significant advances in our understanding of the pathophysiology and risk factors of PONV, its incidence has remained largely unchanged. Newer antiemetics have been introduced that may have improved safety profiles, longer duration of action, and better efficacy. This review aims to summarize the recent developments pertaining to these new agents and their potential application toward the management of PONV.
Topics: Antiemetics; Aprepitant; Disease Management; Dopamine Antagonists; Drug Therapy, Combination; Humans; Neurokinin-1 Receptor Antagonists; Palonosetron; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists
PubMed: 33288125
DOI: 10.1016/j.bpa.2020.11.004 -
Biomedical Papers of the Medical... Jun 2023Postdischarge nausea and vomiting (PDNV) cause substantial pediatric morbidity with potentially serious postoperative complications. However, few studies have addressed... (Review)
Review
Postdischarge nausea and vomiting (PDNV) cause substantial pediatric morbidity with potentially serious postoperative complications. However, few studies have addressed PDNV prevention and treatment in pediatric patients. Here we searched the literature and processed it in a narrative review describing PDNV incidence, risk factors, and management in pediatric patients.. A successful strategy for reducing PDNV considers both the pharmacokinetics of the antiemetic agents and the principle of multimodal prophylaxis, utilizing agents of different pharmacologic classes. Since many highly effective antiemetic agents have relatively short half-lives, a different approach must be used to prevent PDNV. A combination of oral and intravenous medications with longer half-lives, such as palonosetron or aprepitant, can be used. In addition, we designed a prospective observational study with the primary objective of determining PDNV incidence. In our study group of 205 children, the overall PDNV incidence was 14.6% (30 of 205), including 21 children suffering from nausea and 9 suffering from vomiting.
Topics: Humans; Child; Antiemetics; Postoperative Nausea and Vomiting; Aftercare; Patient Discharge; Prospective Studies; Observational Studies as Topic
PubMed: 37222143
DOI: 10.5507/bp.2023.020