Palonosetron 250micrograms/5ml solution for injection vials

BACKGROUND: Despite guidelines for managing chemotherapy-induced nausea and vomiting (CINV), there remains a need to clarify the optimal use of neurokinin-1 (NK1) receptor antagonists. Comparing the effectiveness of NEPA (netupitant-palonosetron) plus dexamethasone with other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone is crucial for informed decision-making and improving patient outcomes. METHODS: We conducted a systematic review of the literature to assess randomized controlled trials (RCTs) comparing the efficacy, safety, and cost-effectiveness of NEPA plus dexamethasone and other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone. PubMed, Embase, and the Cochrane Library databases were systematically searched, with the latest update performed in December 2023. Data on patient demographics, chemotherapy regimen characteristics, and outcomes were extracted for meta-analysis using a random-effects model. RESULTS: Seven RCTs were analyzed. NEPA plus dexamethasone showed superior efficacy in achieving complete response in the overall (risk ratio [RR], 1.15; 95% CI, 1.02--1.30) and delayed phases (RR, 1.20; 95% CI, 1.03-1.41) of chemotherapy. It was more effective in controlling nausea (overall phase RR, 1.20; 95% CI, 1.05-1.36; delayed phase RR, 1.21; 95% CI, 1.05-1.40) and reducing rescue therapy use (overall phase RR, 1.45; 95% CI, 1.07-1.95; delayed phase RR, 1.75; 95% CI, 1.10-2.78). Adverse event rates were comparable (RR, 1.03; 95% CI, 0.96-1.10). Subgroup analysis indicated NEPA's particular efficacy in patients receiving moderately emetogenic chemotherapy (RR, 1.31; 95% CI, 1.07-1.60). CONCLUSION: NEPA plus dexamethasone regimens exhibit superior efficacy in preventing CINV, supporting their preferential inclusion in prophylactic treatment protocols. Its effective symptom control, safety profile, and cost-effectiveness endorse NEPA-based regimens as a beneficial option in CINV management.

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Purpose: Postoperative nausea and vomiting (PONV) is a prevalent and distressing complication, especially in laparoscopic surgeries. This review compares the efficacy and safety of palonosetron and ondansetron in preventing PONV after laparoscopic surgery. Methods: A systematic review was conducted in PubMed, Google Scholar, Semantic Scholar, and Cochrane Library to identify comparative studies that reported the efficacy (nausea and vomiting) at three postoperative time points T1 (0-2 hours), T2 (2-6 hours), T3 (6-24 hours) and safety (incidence of adverse effects). Meta-analysis of relative risk was performed using a random effect model and subgroup analysis based on factors such as antiemetic dose and timing of administration, type of surgery, and anesthetic agents. Results: Twenty-one randomized controlled trials were published between 2011 and 2022, involving 2,043 participants. Nineteen trials were included in the meta-analysis (efficacy, 17; safety, 11). The pooled risk ratio revealed that patients receiving palonosetron demonstrated significantly less likelihood of developing nausea and vomiting at various postoperative time points. Subgroup analysis indicated significantly less PONV when palonosetron was administered before intubation and in combination with isoflurane anesthesia. Headache, dizziness, constipation, and drowsiness were the most commonly reported. The safety profiles of palonosetron and ondansetron were comparable. Conclusion: Palonosetron exhibits superior efficacy within the first 24 hours postoperatively and requires less rescue antiemetic intervention compared to ondansetron in laparoscopic surgery patients. Both demonstrate nearly comparable safety profiles. Future trials focusing on cardiac safety (QT interval) and cost consideration are needed.

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<h2>ABSTRACT</h2><h3>Background</h3> Patients receiving moderately emetogenic chemotherapy (MEC) are commonly prescribed a 5-HT₃ receptor antagonist (RA) and dexamethasone (DEX) as standard of care (SOC) antiemetic prophylaxis. However, in patients with an elevated risk of chemotherapy-induced nausea and vomiting (CINV) due to individual risk factors, prophylaxis with an NK₁RA-containing regimen may optimise their antiemetic prevention. To address this unmet need for a more personalised antiemetic strategy, the MyRisk trial incorporated a predictive risk factor algorithm to select patients at increased risk of CINV who may benefit from enhanced antiemetic prophylaxis. <h3>Patients and Methods</h3> MyRisk was a phase IV, randomised, open-label, multicentre, multinational trial. Adult patients scheduled to receive 3 cycles of MEC with a high-risk CINV score were randomised to NEPA (a fixed combination of an NK₁RA, netupitant, and 5-HT₃RA, palonosetron) + DEX or SOC. The CINV risk score was calculated based on an algorithm that considered 7 risk factors. The primary endpoint was complete response (CR: no emesis/no rescue medication) during the overall phase (0-120h) across 3 consecutive cycles. <h3>Results</h3> Of 401 randomised patients, 388 were included in the efficacy analysis. The most common cancers were colorectal and lung; oxaliplatin and carboplatin were the most common MEC. Patients randomised to NEPA were significantly more likely to experience a CR compared to SOC (OR=1.67, 95%CI: 1.12 to 2.49; p=0.012). The NEPA group had a significantly higher probability of CR, no nausea, no emesis, and complete protection (81.0%, 63.7%, 95.4%, 71.8%, respectively) compared to the SOC arm (71.8%, 54.9%, 86.7%, 62.4, respectively) across 3 cycles of chemotherapy. <h3>Conclusions</h3> When individual risk factors are considered prior to MEC, a 3-drug regimen including NEPA provides superior CINV prevention across multiple cycles compared to the standard 2-drug approach. These findings underscore the value of personalised risk-adapted antiemetic strategies and have practice-changing potential for optimizing antiemetic control.

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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.

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BACKGROUND: Butorphanol has been used to reduce the incidence and severity of neuraxial morphine-induced pruritus. Palonosetron is a commonly used antiemetic for the prevention of postoperative nausea and vomiting. The aim of our study was to compare the effective dose in 50% of subjects (ED50) of intravenous butorphanol infusion with or without a single intravenous bolus of palonosetron for preventing pruritus induced by epidural administration of morphine. METHODS: A total of 120 parturients were randomly assigned to receive an intravenous bolus injection of palonosetron plus continuous infusion of butorphanol (Group P + B) or an intravenous bolus of saline plus continuous infusion of butorphanol (Group B) after epidural administration of morphine. The antipruritic effect was graded as satisfactory (numerical rating scale (NRS) of pruritus ≤3) or unsatisfactory (NRS >3) within 48 h after morphine treatment. The first patient in each group received butorphanol infusion at a rate of 4 µg/kg/h. The infusion dose for each subsequent patient in the corresponding group was increased by 0.2 µg/kg/h after an unsatisfactory response or decreased by 0.2 µg/kg/h after a satisfactory response. The ED50 was calculated for each group and compared using up-down sequential analysis. RESULTS: < 0.05). CONCLUSIONS: Under the conditions of the present study, a prophylactic use of 0.25 mg palonosetron reduced the ED50 of prophylactic infusion of butorphanol by approximately 8% to achieve a satisfactory antipruritic effect after epidural morphine for post-caesarean analgesia.

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Background: The incidence of postoperative nausea and vomiting (PONV) is quite high after laparoscopic surgeries. This study endeavors to compare the efficacy of the combination of palonosetron and dexamethasone with that of either drug alone in the prevention of PONV in patients undergoing laparoscopic surgeries. Methods: This randomized, parallel-group trial was done on ninety adults of American Society of Anesthesiologists Grade I and II patients aged 18–60 years undergoing laparoscopic surgeries under general anesthesia. The patients were randomly divided into three groups of thirty patients each. Group P ( n = 30) received palonosetron 0.075 mg intravenously (iv), Group D ( n = 30) received dexamethasone 8 mg iv and Group P + D ( n = 30) received palonosetron 0.075 mg and dexamethasone 8 mg iv. The primary outcome was incidence of PONV in 24 h, and the secondary outcome was a number of rescue antiemetics required. To compare the proportions in the groups, unpaired t -test, Mann–Whitney U -test, Chi-square test, or Fisher's exact test was applied. Results: We found that the overall incidence of PONV was 46.7% in Group P, 50% in Group D, and 43.3% in Group P + D during the first 24 h. Rescue antiemetic was required in 27% of the patients in Group P and Group D compared to 23% of the patients in Group P + D and twice in 3% of the patients in Group P, 7% of the patients in Group D, and none in Group P + D which were not significant. Conclusions: The combination therapy of palonosetron plus dexamethasone did not significantly reduce the incidence of PONV when compared with either drug alone.

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