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Drugs Jul 2021Netupitant/palonosetron (NEPA; Akynzeo), available in oral and intravenous (IV) formulations, is a fixed-dose combination of the neurokinin 1 (NK1) receptor antagonist... (Review)
Review
Netupitant/palonosetron (NEPA; Akynzeo), available in oral and intravenous (IV) formulations, is a fixed-dose combination of the neurokinin 1 (NK1) receptor antagonist netupitant (or the prodrug, fosnetupitant, in the IV formulation) and the second-generation serotonin 3 (5-HT) receptor antagonist palonosetron. Administered as a single dose, (fos)netupitant/palonosetron (in combination with dexamethasone) is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in adults. In clinical trials, (fos)netupitant/palonosetron plus dexamethasone was associated with high complete response rates (no emesis and no rescue medication) in the acute, delayed and overall phases in patients receiving highly or moderately emetogenic chemotherapy, with efficacy maintained over multiple cycles. Further, oral netupitant/palonosetron was found to be superior to palonosetron and non-inferior to aprepitant plus granisetron in preventing CINV in individual trials. Both the oral and IV formulations of the drug combination are well tolerated. The fixed-dose combination is concordant with guideline recommendations and provides a simple and convenient option for prophylaxis against acute and delayed CINV in patients receiving highly or moderately emetogenic chemotherapy.
Topics: Administration, Intravenous; Administration, Oral; Antiemetics; Antineoplastic Agents; Clinical Trials as Topic; Dexamethasone; Drug Combinations; Drug Interactions; Humans; Isoquinolines; Nausea; Pyridines; Quinuclidines; Vomiting
PubMed: 34292534
DOI: 10.1007/s40265-021-01558-2 -
British Journal of Anaesthesia Oct 2023Postoperative nausea and vomiting (PONV) is a major problem after surgery. Even with double prophylactic therapy including dexamethasone and a 5-hydroxytryptamine-3... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Postoperative nausea and vomiting (PONV) is a major problem after surgery. Even with double prophylactic therapy including dexamethasone and a 5-hydroxytryptamine-3 receptor antagonist, the incidence is still high in many at-risk patients. Fosaprepitant, a neurokinin-1 receptor antagonist, is an effective antiemetic, but its efficacy and safety in combination antiemetic therapy for preventing PONV remain unclear.
METHODS
In this randomised, controlled, double-blind trial, 1154 participants at high risk of PONV and undergoing laparoscopic gastrointestinal surgery were randomly assigned to either a fosaprepitant group (n=577) receiving fosaprepitant 150 mg i.v. dissolved in 0.9% saline 150 ml, or a placebo group (n=577) receiving 0.9% saline 150 ml before anaesthesia induction. Dexamethasone 5 mg i.v. and palonosetron 0.075 i.v. mg were each administered in both groups. The primary outcome was the incidence of PONV (defined as nausea, retching, or vomiting) during the first 24 postoperative hours.
RESULTS
The incidence of PONV during the first 24 postoperative hours was lower in the fosaprepitant group (32.4% vs 48.7%; adjusted risk difference -16.9% [95% confidence interval: -22.4 to -11.4%]; adjusted risk ratio 0.65 [95% CI: 0.57 to 0.76]; P<0.001). There were no differences in severe adverse events between groups, but the incidence of intraoperative hypotension was higher (38.0% vs 31.7%, P=0.026) and intraoperative hypertension (40.6% vs 49.2%, P=0.003) was lower in the fosaprepitant group.
CONCLUSIONS
Fosaprepitant added to dexamethasone and palonosetron reduced the incidence of PONV in patients at high risk of PONV undergoing laparoscopic gastrointestinal surgery. Notably, it increased the incidence of intraoperative hypotension.
CLINICAL TRIAL REGISTRATION
NCT04853147.
Topics: Humans; Postoperative Nausea and Vomiting; Antiemetics; Palonosetron; Digestive System Surgical Procedures; Saline Solution; Laparoscopy; Dexamethasone; Double-Blind Method
PubMed: 37423834
DOI: 10.1016/j.bja.2023.06.029 -
Chinese Clinical Oncology Apr 2020Review the clinical evidence of tropisetron or palonosetron, an old- and new-generation serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonist (RA),... (Review)
Review
Review the clinical evidence of tropisetron or palonosetron, an old- and new-generation serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonist (RA), respectively, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer, and evaluate any difference in efficacy trends. A literature search of the EMBASE and PubMed databases was performed to identify publications of intravenous (IV) tropisetron (generic forms or Navoban®) for the treatment of CINV in patients with various cancers. Data from the pivotal clinical studies evaluating the IV formulation of Aloxi® (palonosetron HCl) were also considered. The effectiveness and safety of each antiemetic was summarized. Sixteen papers for tropisetron fulfilled the inclusion criteria and were extracted for full analysis; publications from six pivotal palonosetron clinical trials were considered. No direct data comparisons could be made between the two drugs, due to the varying definitions of efficacy endpoints between studies. For tropisetron, the rates of no emesis were lower in patients receiving highly emetogenic chemotherapy (HEC) versus moderately emetogenic chemotherapy (MEC). For palonosetron, the rates of complete response (no emesis, no rescue medication) were comparable in the MEC and HEC settings, demonstrating the effectiveness of this agent in patients receiving HEC. Both antiemetics offered some protection against nausea, although lower rates of no nausea were achieved compared with rates of no emesis. Two trials that evaluated the efficacy of palonosetron and tropisetron within the same study reported that palonosetron was more effective than tropisetron in controlling delayed vomiting in the HEC and MEC settings, with significantly higher rates of no emesis observed (P≤0.01). Palonosetron was non-inferior or more efficacious in controlling CINV compared with other older 5-HT3RAs, such as dolasetron, ondansetron, and granisetron. Conversely, tropisetron was no more efficacious than ondansetron or granisetron. Both tropisetron and palonosetron were generally well tolerated, with adverse event profiles consistent with drugs of this class (e.g., headache, constipation, and diarrhea). These data suggest that palonosetron is a highly selective prophylactic agent that may have an improved therapeutic profile compared with tropisetron, and is a feasible treatment option for controlling CINV in patients with cancer.
Topics: Antineoplastic Agents; Female; Humans; Male; Nausea; Neoplasms; Palonosetron; Tropisetron; Vomiting
PubMed: 31865713
DOI: 10.21037/cco.2019.11.02 -
British Journal of Anaesthesia Jul 2023Postoperative nausea and vomiting (PONV) has been identified as a big (very frequently encountered) little (not linked to life-threatening outcomes) problem. Traditional...
Postoperative nausea and vomiting (PONV) has been identified as a big (very frequently encountered) little (not linked to life-threatening outcomes) problem. Traditional drugs (dexamethasone, droperidol or similar drugs, serotonin receptor antagonists) each have significant but limited effect, leading to an increasing use of combination therapies. High-risk patients, often identified through use of risk scoring systems, remain with a significant residual risk despite combining up to three traditional drugs. A recent correspondence in this Journal proposes the use of up to five anti-emetic drugs to further minimise the risk. This disruptive strategy was supported by favourable initial results, absence of side-effects and lower acquisition costs of the added new drugs (aprepitant and palonosetron) because of their recent loss of patent protection. These results are provocative and hypothesis generating, but need confirmation and do not warrant immediate changes in clinical practice. The next steps will also necessitate wider implementation of protocols protecting patients from PONV and a search for additional drugs and techniques aimed at treating established PONV.
Topics: Humans; Postoperative Nausea and Vomiting; Antiemetics; Droperidol; Serotonin Antagonists; Risk Factors; Vomiting; Dexamethasone; Drug Therapy, Combination
PubMed: 37179157
DOI: 10.1016/j.bja.2023.04.004 -
Current Cancer Drug Targets 2022Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with many anticancer therapies and can negatively impact patients' quality of life... (Review)
Review
Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with many anticancer therapies and can negatively impact patients' quality of life and potentially limit the effectiveness of chemotherapy. Currently, CINV can be prevented in most patients with guideline-recommended antiemetic regimens. However, clinicians do not always follow guidelines, and patients often face difficulties adhering to their prescribed treatments. Therefore, approaches to increase guideline adherence need to be implemented. NEPA is the first and only fixed combination antiemetic, composed of netupitant (oral)/fosnetupitant (intravenous) and palonosetron, which, together with dexamethasone, constitute a triple antiemetic combination recommended for the prevention of CINV for patients receiving highly emetogenic chemotherapy and for certain patients receiving moderately emetogenic chemotherapy. Thus, NEPA offers a convenient and straightforward antiemetic treatment that could improve adherence to guidelines. This review provides an overview of CINV, evaluates the accumulated evidence of NEPA's antiemetic activity and safety from clinical trials and real-world practice, and examines the preliminary evidence of antiemetic control with NEPA in daily clinical settings beyond those described in pivotal trials. Moreover, we review the utility of NEPA in controlling nausea and preserving patients' quality of life during chemotherapy, two major concerns in managing patients with cancer.
Topics: Antiemetics; Antineoplastic Agents; Benzeneacetamides; Dexamethasone; Humans; Nausea; Palonosetron; Piperazines; Pyridines; Quality of Life; Vomiting
PubMed: 35570542
DOI: 10.2174/1568009622666220513094352 -
Current Molecular Medicine 20235-HT receptor antagonists corresponding to ondansetron, granisetron, tropisetron, and palonosetron are clinically accustomed to treating nausea and emesis in... (Review)
Review
5-HT receptor antagonists corresponding to ondansetron, granisetron, tropisetron, and palonosetron are clinically accustomed to treating nausea and emesis in chemotherapy patients. However, current and previous studies reveal novel potentials of those ligands in other diseases involving the nervous system, such as addiction, pruritus, and neurological disorders, such as anxiety, psychosis, nociception, and cognitive function. This review gathers existing studies to support the role of 5-HT receptors in CIPN modulation. It has been reported that chemotherapy drugs increase the 5-HT content that binds with the 5-HT receptor, which later induces pain. As also shown in pre-clinical and clinical studies that various neuropathic pains could be blocked by the 5-HT receptor antagonists, we proposed that 5-HT receptor antagonists via 5- HT receptors may also inhibit neuropathic pain induced by chemotherapy. Our review suggests that future studies focus more on the 5-HT receptor antagonists and their modulation in CIPN to reduce the gap in the current pharmacotherapy for cancer-related pain.
Topics: Humans; Vomiting; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Antineoplastic Agents; Peripheral Nervous System Diseases
PubMed: 35549869
DOI: 10.2174/1566524022666220512122525 -
Medicine Oct 2023To investigate the efficacy and safety of dexamethasone + palonosetron in the prevention of post-embolization syndrome after drug-eluting beads transcatheter...
To investigate the efficacy and safety of dexamethasone + palonosetron in the prevention of post-embolization syndrome after drug-eluting beads transcatheter arterial chemoembolization (D-TACE). The data of 278 patients who received D-TACE from January 2018 to December 2021 were collected and divided into 2 groups: D-TACE group (N = 145) and D-TACE + dexamethasone + palonosetron group (N = 133). The incidence of post-embolization syndrome and infection after D-TACE was assessed in both groups. Incidence of abdominal pain: D-TACE group versus D-TACE + dexamethasone + palonosetron group, 56.6% versus 40.6%, P = .008; incidence of fever: D-TACE group versus D-TACE + dexamethasone + palonosetron group, 40.0% versus 14.3%, P = .000; incidence of nausea: D-TACE group versus D-TACE + dexamethasone + palonosetron group, 61.4% versus 39.8%, P = .001; incidence of vomiting: D-TACE group versus D-TACE + dexamethasone + palonosetron group, 48.3% versus 21.1%, P = .000; incidence of infection: D-TACE group versus D-TACE + dexamethasone + palonosetron group, 1.4% versus 1.5%, P = .931. The combined use of dexamethasone and palonosetron before D-TACE can effectively reduce the incidence of post-embolization syndrome and reduce the degree of side effects, but it will not increase the risk of infection.
Topics: Humans; Palonosetron; Antiemetics; Retrospective Studies; Dexamethasone; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; Vomiting
PubMed: 37800841
DOI: 10.1097/MD.0000000000035433 -
Current Medical Research and Opinion May 2021Postoperative nausea and vomiting (PONV) is a common complication following surgery, and may be one of the most distressing parts of the surgical journey. With... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Postoperative nausea and vomiting (PONV) is a common complication following surgery, and may be one of the most distressing parts of the surgical journey. With combination pharmacological therapy recommended for PONV prophylaxis, this systematic review and meta-analysis evaluates whether perioperative palonosetron and dexamethasone is more efficacious than palonosetron administered alone.
METHODS
We searched CENTRAL; EMBASE; CINAHL; Google Scholar; Web of Science citation index; the US clinical trials register; UK clinical trials register; Australia and New Zealand Clinical trials register; and conference abstracts for major anaesthesia conferences in the last three years.We included randomized controlled trials that compared adult patients undergoing surgery who received palonosetron and dexamethasone, against those who received palonosetron.
RESULTS
A total of 12 studies (1152 patients) were included. Medium-grade evidence showed that the palonosetron and dexamethasone combination significantly reduced 24-hour rescue anti-emetic requirement (RR: 0.59, 95% confidence interval (CI): 0.41-0.86). There was however no significant difference in the 6-hour (RR: 0.82, 95% CI: 0.61-1.09) and 24-hour PONV incidences (RR: 0.60, 95% CI: 0.33-1.10). Similarly, PONV incidences after 24 h did not differ between groups (RR:0.82, 95% CI: 0.59-1.14). Headache and dizziness were the most common side-effects reported.
CONCLUSIONS
Combination prophylaxis with palonosetron and dexamethasone reduces post-operative anti-emetic requirement, although is not associated with a significant difference in PONV. There was considerable heterogeneity in the studies, and trial sequential analysis indicates that further studies are needed to strengthen the clinical evidence.
Topics: Adult; Anesthesia; Antiemetics; Dexamethasone; Humans; Palonosetron; Postoperative Nausea and Vomiting
PubMed: 33617380
DOI: 10.1080/03007995.2021.1893677 -
Current Therapeutic Research, Clinical... 2022Spinal surgery is associated with severe pain within the first few days after surgery. Opioids are commonly used to control postoperative pain, but these can lead to... (Review)
Review
BACKGROUND
Spinal surgery is associated with severe pain within the first few days after surgery. Opioids are commonly used to control postoperative pain, but these can lead to postoperative nausea and vomiting (PONV). Therefore, use of more effective and better-tolerated agents would be beneficial for these patients. Serotonin receptor antagonists, such as ramosetron, have been used to reduce PONV in patients receiving anesthesia.
OBJECTIVE
We conducted a meta-analysis of published randomized controlled trials (RCTs) to compare the efficacy and tolerance of ramosetron to prevent PONV after spinal surgery.
METHODS
Medline, Embase, Cochrane Library, and Science Citation Index databases were systematically searched for relevant RCT articles published between January 1979 and November 2020. Full text articles restricted to English language that described RCTs comparing the use of ramosetron with other serotonin antagonists to treat PONV following spinal surgery in adult patients were considered for meta-analysis. Two reviewers independently performed study selection, quality assessment, and data extraction of all articles. Differences were resolved by a third reviewer.
RESULTS
The search identified 88 potentially relevant articles, of which only 3 met our selection criteria. Study drugs were administered at the end of spinal surgery in all 3 included articles. The meta-analysis revealed that ramosetron (0.3 mg) reduced the pain score (mean difference = -0.66; 95% CI -1.02 to -0.30), lowered the risk of PONV (risk ratio = 0.86; 95% CI, 0.76-0.97), and postoperative vomiting (risk ratio = 0.32; 95% CI, 0.17-0.60), and limited the use of rescue antiemetics (risk ratio = 0.66; 95% CI, 0.45-0.96) after spinal surgery. However, there were no significant differences in the incidence of postoperative nausea, the use of rescue pain medications, the number of rescue analgesics required, and the risk of discontinuation of patient-controlled analgesia between ramosetron and palonosetron (0.075 mg) or ondansetron (4 mg). There were no statistically significant differences in the risk of adverse events among the 3 medications.
CONCLUSIONS
This meta-analysis of 3 RCTs showed that ramosetron reduced the risk of PONV and POV, limited the use of rescue antiemetics, reduced the postoperative pain score, and did not increase the risk of discontinuing patient-controlled analgesia compared with palonosetron or ondansetron after spinal surgery in 3 RCTs. Therefore, this meta-analysis indicates that ramosetron is an effective and well tolerated antiemetic that can be used to prevent PONV following spinal surgery in adult patients. PROSPERO identifier: CRD42020223596 (. 2022; 83:XXX-XXX)© 2022 Elsevier HS Journals, Inc.
PubMed: 35464291
DOI: 10.1016/j.curtheres.2022.100666 -
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