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Therapeutics and Clinical Risk... 2015Nausea and vomiting are major adverse effects of chemotherapy and can greatly impact patients' quality of life. Although chemotherapy-induced nausea and vomiting (CINV)... (Review)
Review
PURPOSE
Nausea and vomiting are major adverse effects of chemotherapy and can greatly impact patients' quality of life. Although chemotherapy-induced nausea and vomiting (CINV) prevalence is high, treatment remains difficult. Palonosetron is a 5-hydroxytryptamine receptor antagonist (5-HT3RA) approved for treatment of CINV. The purpose of this review is to discuss existing and emerging therapeutic options, and examine studies focusing on palonosetron with regards to efficacy, pharmacology, tolerability, safety, and patient-derived outcomes.
METHODS
A literature search was conducted using Ovid MEDLINE and EMBASE to identify relevant studies using palonosetron alone or in combination with other antiemetics. Studies were extracted if they included complete response (CR), complete control (CC), no nausea, no vomiting, and no rescue medications as an endpoint. Studies were also included if safety endpoints were examined.
RESULTS
Palonosetron alone has been shown to improve CR and CC rates for patients receiving low, moderate, or high emetogenic chemotherapy. Rates were further improved with the addition of dexamethasone, a corticosteroid. Furthermore, the addition of neurokinin-1 receptor antagonists, such as netupitant markedly improved efficacy profiles compared to palonosetron alone. Aprepitant is an antiemetic that has exhibited positive results in combination with palonosetron. Recently, a new drug consisting of netupitant and palonosetron (NEPA) has demonstrated significantly more efficacious prevention of CINV. Regardless of the combination, palonosetron has been well tolerated. The most common adverse events were constipation, headache, fatigue, and dizziness, with the majority of patients describing them as only mild or moderate.
CONCLUSION
Palonosetron, alone or with other antiemetics, has improved CINV treatment due to its ability to significantly reduce delayed phases of CINV, compared to similar 5-HT3RAs. Palonosetron is both more effective than first generation 5-HT3RAs and safer, as it results in a smaller prolongation of the QTc interval, compared to other 5-HT3RAs.
PubMed: 25999723
DOI: 10.2147/TCRM.S68130 -
Anesthesia, Essays and Researches 2018Intrathecal morphine is commonly used for postcesarean analgesia. Its use is frequently associated with opioid-induced nausea, vomiting, and pruritus. Palonosetron...
Comparison of Palonosetron, Dexamethasone, and Palonosetron Plus Dexamethasone as Prophylactic Antiemetic and Antipruritic Drug in Patients Receiving Intrathecal Morphine for Lower Segment Cesarean Section.
BACKGROUND
Intrathecal morphine is commonly used for postcesarean analgesia. Its use is frequently associated with opioid-induced nausea, vomiting, and pruritus. Palonosetron (0.075 mg) combined with dexamethasone (8 mg) is postulated to have an additive effect over each drug alone. The study, therefore, compared the effect of intravenous (i.v.) palonosetron, dexamethasone, and palonosetron with dexamethasone combination in preventing intrathecal morphine-induced postoperative vomiting and pruritus in lower segment cesarean section (LSCS) patients.
SETTINGS AND DESIGN
Randomized, prospective, double-blinded, observational clinical study.
METHODS
Ninety pregnant women, American Society of Anesthesiologists physical status class I undergoing LSCS were included in the study. They were randomly assigned to three groups - Group received 0.075 mg palonosetron i.v., Group D received dexamethasone 8 mg i.v., and Group PD received palonosetron 0.075 mg along with dexamethasone 4 mg i.v., just after spinal anesthesia with bupivacaine 2.2 ml (12 mg) and 150 μg morphine. The incidence of pruritus, nausea, vomiting, and need for rescue drug were recorded for 24 h.
STATISTICAL ANALYSIS
Statistical analysis was performed using Student's -test for categorical variables and Chi-square test for noncategorical variables.
RESULTS
The incidence of nausea, vomiting was significantly more in Group D (40%) than Group (27%) and Group PD (20%) in 24 h. The incidence of pruritus was significantly more in Group D (6%) than Group and PD (3%). The need of rescue antiemetic was more in Group D (30%) than Group (6%) and Group PD (3%). No difference in three groups requiring rescue antipruritic drug.
CONCLUSION
Prevention of intrathecal morphine-induced vomiting and pruritus was more effective with palonosetron alone or with dexamethasone combination than dexamethasone alone. Combination of palonosetron and dexamethasone proved no better than palonosetron alone.
PubMed: 29962591
DOI: 10.4103/aer.AER_183_17 -
Drug Design, Development and Therapy 2015Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents,... (Review)
Review
Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists, appears to be the most effective agent in its class. Netupitant, is a new NK-1 receptor antagonist with a high binding affinity, a long half-life of 90 hours, is metabolized by CYP3A4, and is an inhibitor of CYP3A4. NEPA is an oral fixed-dose combination of netupitant and palonosetron which has recently been employed in Phase II and Phase III clinical trials for the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy (MEC and HEC). The clinical trials demonstrated that NEPA (300 mg of netupitant plus 0.50 mg of palonosetron) significantly improved the prevention of CINV compared to the use of palonosetron alone in patients receiving either HEC or MEC. The clinical efficacy was maintained over multiple cycles of chemotherapy. NEPA (Akynzeo(®)) has recently been approved by the Food and Drug Administration (FDA) to treat nausea and vomiting in patients undergoing cancer chemotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Isoquinolines; Molecular Structure; Nausea; Neoplasms; Palonosetron; Pyridines; Quinuclidines; Vomiting
PubMed: 25552904
DOI: 10.2147/DDDT.S76158 -
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 -
Advances in Therapy Jul 2023Chemotherapy-induced nausea and vomiting (CINV) is a recognized adverse outcome among patients with cancer. This retrospective study aimed to quantify the treatment...
INTRODUCTION
Chemotherapy-induced nausea and vomiting (CINV) is a recognized adverse outcome among patients with cancer. This retrospective study aimed to quantify the treatment outcomes, resource utilization, and costs associated with antiemetic use to prevent CINV in a broad US population who received cisplatin-based chemotherapy.
METHODS
Data from the STATinMED RWD Insights Database was collected from January 1, 2015 to December 31, 2020. Cohorts included any patients that had at least one claim for fosnetupitant + palonosetron (NEPA) or fosaprepitant + palonosetron (APPA) and evidence of initiating cisplatin-based chemotherapy. Logistic regression was used to evaluate nausea and vomiting visits within 14 days after chemotherapy, and generalized linear models were used to examine all-cause and CINV-related healthcare resource utilization (HCRU) and costs.
RESULTS
NEPA was associated with significantly lower rates of nausea and vomiting visits after chemotherapy (p = 0.0001), including 86% greater odds of nausea and vomiting events for APPA during the second week after chemotherapy (odds ratio [OR] = 1.86; p = 0.0003). The mean numbers of all-cause inpatient visits (p = 0.0195) and CINV-related inpatient and outpatient visits were lower among NEPA patients (p < 0.0001). These differences corresponded to 57% of NEPA patients and 67% of APPA patients having one or more inpatient visits (p = 0.0002). All-cause outpatient costs and CINV-related inpatient costs were also significantly lower for NEPA (p < 0.0001). The mean number of all-cause outpatient visits, all-cause inpatient costs, and CINV-related outpatient costs was not significantly different between groups (p > 0.05).
CONCLUSION
In this retrospective study based on claims data, NEPA was associated with lower rates of nausea and vomiting and lower CINV-related HCRU and costs compared to APPA following cisplatin-based chemotherapy. These results complement clinical trial data and published economic models supporting the use of NEPA as a safe, effective, and cost-saving antiemetic for patients undergoing chemotherapy.
Topics: Humans; Antiemetics; Cisplatin; Palonosetron; Retrospective Studies; Nausea; Vomiting; Neoplasms; Quinuclidines; Treatment Outcome; Gastrointestinal Agents; Delivery of Health Care; Antineoplastic Agents
PubMed: 37245189
DOI: 10.1007/s12325-023-02537-7 -
Annals of Palliative Medicine Apr 2018Chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy, can substantially impair a patient's quality of life, interfere with a patient's... (Comparative Study)
Comparative Study Review
Efficacy of the combination neurokinin-1 receptor antagonist, palonosetron, and dexamethasone compared to others for the prophylaxis of chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy, can substantially impair a patient's quality of life, interfere with a patient's compliance with anticancer therapy, and result in the manifestation of adverse events such as electrolyte imbalance, dehydration and malnutrition. The most recent guidelines published by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) recommend the combination of dexamethasone (DEX), a 5-hydroxytrypatmine-3 receptor antagonist (5-HT3RA), preferably palonosetron (PALO), and a neurokinin-1 receptor antagonist (NK1RA) for prophylactic treatment of CINV in patients receiving highly emetogenic chemotherapy (HEC). The aim of this review was to examine the efficacy of triple agent, as reported in randomized controlled trials (RCTs), compared to any other prophylactic treatments.
METHODS
A literature search was conducted in Ovid MEDLINE(R), Embase Classic & Embase, and the Cochrane Central Register of Controlled Trials. The primary endpoint was the proportion of patients achieving complete response (CR) in the acute, delayed and overall phase. Secondary endpoints included the percentage of patients who achieved complete control (CC), no nausea and no vomiting in the acute, delayed and overall phases.
RESULTS
A total of 17 RCTs were included in this review, of which 3,146 patients were randomized to receive NK1RA, PALO and DEX, and 2,987 patients to receive other antiemetic treatments. The combination was not superior to other treatments in five endpoints-CC and CR in the acute phase, nausea and emesis control in the delayed phase, and nausea in the overall phase-but was superior in the other 11 endpoints. When looking only at HEC and moderately emetogenic chemotherapy (MEC) studies, the combination was only superior to others in three endpoints (delayed and overall CC, and overall emesis control) in HEC setting, which is less than the nine identified endpoints (delayed and overall CR, delayed and overall CC, acute and overall nausea control, and acute, delayed and overall phases for emesis control) in the MEC setting.
CONCLUSIONS
The combination of NK1RA, PALO and DEX is superior in the majority of assessed endpoints of this meta-analysis. Further studies should investigate the efficacy and safety of the triple regimen compared to regimens lacking NK1RA, to add to the discussions about whether future CINV prophylaxis guidelines should include NK1RA as a first-line treatment in the MEC setting.
Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Dexamethasone; Drug Combinations; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Quinuclidines; Radiotherapy; Randomized Controlled Trials as Topic; Serotonin Antagonists; Vomiting
PubMed: 29764184
DOI: 10.21037/apm.2018.03.09 -
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 -
Anesthesia and Pain Medicine Jan 2020We compared the effects of palonosetron with ondansetron for preventing postoperative nausea and vomiting (PONV) during the first 24 h after surgery in women receiving...
BACKGROUND
We compared the effects of palonosetron with ondansetron for preventing postoperative nausea and vomiting (PONV) during the first 24 h after surgery in women receiving intravenous patient-controlled analgesia (IV-PCA) with fentanyl for pain control.
METHODS
In this prospective, randomized, double-blinded study, 204 healthy patients who were undergoing elective surgery with general anesthesia were enrolled. In the palonosetron group (n = 102), 0.075 mg bolus was given intravenously (i.v.) 30 min before the end of surgery and 8 ml saline was added to the IV-PCA. In the ondansetron group (n = 102), 8 mg bolus i.v. was given 30 min before the end of surgery and 16 mg of ondansetron was added to the IV-PCA. The incidence of PONV, severity of nausea, and use of rescue anti-emetics were evaluated 6 and 24 h after the operation.
RESULTS
The incidences of nausea (55.6%) and vomiting (14.1%) in the palonosetron group did not differ from those (58.3 and 19.8%) in the ondansetron group during the first 24 h after surgery (P > 0.05). No significant differences were observed in the severity of nausea and use of rescue anti-emetics between the two groups (P > 0.05).
CONCLUSIONS
The effects of palonosetron in preventing PONV were not different from those of ondansetron during the first 24 h postoperatively in women receiving IV-PCA with fentanyl.
PubMed: 33329786
DOI: 10.17085/apm.2020.15.1.28 -
Supportive Care in Cancer : Official... Nov 2022The aim of this study was to assess the cost-effectiveness of NEPA, a fixed-dose combination of oral netupitant (300 mg) and palonosetron (0.5 mg), compared to...
Cost-effectiveness analysis of NEPA, a fixed-dose combination of netupitant and palonosetron, for the prevention of highly emetogenic chemotherapy-induced nausea and vomiting: an international perspective.
PURPOSE
The aim of this study was to assess the cost-effectiveness of NEPA, a fixed-dose combination of oral netupitant (300 mg) and palonosetron (0.5 mg), compared to available treatments in Spain after aprepitant generic introduction in the market, and to discuss results in previously performed analyses in different wordwide settings.
METHODS
A Markov model including three health states, complete protection, complete response at best and incomplete response, was used to evaluate the cost-effectiveness of NEPA versus common treatment options in Spain during 5 days after chemotherapy. Incremental costs including treatment costs and treatment failure management cost as well as incremental effects including quality adjusted life days (QALDs) and emesis-free days were compared between NEPA and the comparator arms. The primary outcomes were cost per avoided emetic event and cost per QALDs gained.
RESULTS
NEPA was dominant (more effective and less costly) against aprepitant combined with palonosetron, and fosaprepitant combined with granisetron, while, compared to generic aprepitant plus ondansetron, NEPA showed an incremental cost per avoided emetic event of €33 and cost per QALD gained of €125.
CONCLUSION
By most evaluations, NEPA is a dominant or cost-effective treatment alternative to current antiemetic standards of care in Spain during the first 5 days of chemotherapy treatment in cancer patients, despite the introduction of generics. These results are in line with previously reported analyses throughout different international settings.
Topics: Humans; Palonosetron; Cost-Benefit Analysis; Aprepitant; Emetics; Vomiting; Antineoplastic Agents; Nausea; Antiemetics; Internationality; Quinuclidines
PubMed: 36074186
DOI: 10.1007/s00520-022-07339-1