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BMC Medicine Dec 2016Although serotonin (5-HT) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Although serotonin (5-HT) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy.
METHODS
We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted.
RESULTS
After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall.
CONCLUSIONS
Most 5-HT receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.
TRIAL REGISTRATION
This study was registered at PROSPERO: ( CRD42013003564 ).
Topics: Adult; Antiemetics; Antineoplastic Agents; Drug Therapy, Combination; Glucocorticoids; Humans; Nausea; Network Meta-Analysis; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 28007031
DOI: 10.1186/s12916-016-0761-9 -
World Journal of Clinical Oncology Aug 2020A new, oral fixed dose combination of highly selective neurokinin-1 receptor antagonist, netupitant with 5HT3 receptor antagonist, netupitant and palonosetron (NEPA) was...
BACKGROUND
A new, oral fixed dose combination of highly selective neurokinin-1 receptor antagonist, netupitant with 5HT3 receptor antagonist, netupitant and palonosetron (NEPA) was approved in India for prevention of chemotherapy induced nausea and vomiting (CINV).
AIM
To assess effectiveness of NEPA in real-world scenario.
METHODS
We retrospectively assessed the medical records and patient dairies of adult patients who received highly emetogenic or moderately emetogenic chemotherapy (HEC/MEC) and treated with NEPA (Netupitant 300 mg + Palanosetron 0.50 mg) for prevention of CINV. Complete response (CR) was defined as no emesis or no requirement of rescue medication in overall phase (0 to 5 d), acute phase (0-24 h) and delayed phase (2 to 5 d).
RESULTS
In 403 patients included in the analysis, mean age was 56.24 ± 11.11 years and 55.09% were females. Breast cancer (25.06%) was most common malignancy encountered. HEC and MEC were administered in 54.6% and 45.4% patients respectively. CR in overall phase was 93.79% whereas it was 98.01% in acute CINV and 93.79% in delayed CINV. Overall CR in HEC and MEC groups was 93.63% and 93.98% respectively. CR was more than 90% in different chemotherapy cycles except in group of patients of cycle 4 where CR was 88.88%.
CONCLUSION
NEPA is a novel combination that is effective in preventing CINV in up to 93% cases treated with highly emetogenic or moderately emetogenic chemotherapy. This study brings the first real-life evidence of its effectiveness in India population.
PubMed: 32879847
DOI: 10.5306/wjco.v11.i8.606 -
ELife Oct 2020Serotonin receptors (5-HTR) play a crucial role in regulating gut movement, and are the principal target of setrons, a class of high-affinity competitive antagonists,...
Serotonin receptors (5-HTR) play a crucial role in regulating gut movement, and are the principal target of setrons, a class of high-affinity competitive antagonists, used in the management of nausea and vomiting associated with radiation and chemotherapies. Structural insights into setron-binding poses and their inhibitory mechanisms are just beginning to emerge. Here, we present high-resolution cryo-EM structures of full-length 5-HTR in complex with palonosetron, ondansetron, and alosetron. Molecular dynamic simulations of these structures embedded in a fully-hydrated lipid environment assessed the stability of ligand-binding poses and drug-target interactions over time. Together with simulation results of apo- and serotonin-bound 5-HTR, the study reveals a distinct interaction fingerprint between the various setrons and binding-pocket residues that may underlie their diverse affinities. In addition, varying degrees of conformational change in the setron-5-HTR structures, throughout the channel and particularly along the channel activation pathway, suggests a novel mechanism of competitive inhibition.
Topics: Animals; Binding Sites; Binding, Competitive; Cryoelectron Microscopy; Female; Humans; Ligands; Mice; Molecular Dynamics Simulation; Oocytes; Protein Binding; Protein Conformation; Receptors, Serotonin, 5-HT3; Serotonin; Serotonin Antagonists; Xenopus laevis
PubMed: 33063666
DOI: 10.7554/eLife.57870 -
Frontiers in Pharmacology 2022To test the hypothesis that the single use of fosaprepitant is not inferior to the use of palonosetron as antiemetic prophylaxis in the first 48 h after surgery in...
Comparative Study Between Fosaprepitant and Palonosetron in the Prophylaxis of Postoperative Nausea and Vomiting in Women Undergoing Laparoscopic Cholecystectomy: Prospective, Randomized and Double-Blind Study.
To test the hypothesis that the single use of fosaprepitant is not inferior to the use of palonosetron as antiemetic prophylaxis in the first 48 h after surgery in women undergoing laparoscopic cholecystectomy. Eighty-eight nonsmoking women (American Society of Anesthesiologists physical status I or II) aged between 18 and 60 years who underwent laparoscopic cholecystectomy received 150 mg of fosaprepitant or 75 μg of palonosetron, administered intravenously after the induction of general anesthesia. In the fosaprepitant group and in the palonosetron group, 13.6 and 18.2% of the patients, respectively, vomited in the first 48 h after surgery ( = 0.560). There were no differences between groups in the total frequency and intensity of nausea, number of complete responders, need for rescue medication, time required for the first rescue medication dose or number of adverse events. The administration of a single dose of fosaprepitant after the induction of anesthesia was as effective as the administration of a single dose of palonosetron for the prophylaxis of vomiting in the first 48 h after surgery in women undergoing laparoscopic cholecystectomy.
PubMed: 35645797
DOI: 10.3389/fphar.2022.915347 -
Cureus Mar 2022Background Incidence of postoperative nausea and vomiting (PONV) in susceptible patients can be unacceptably high (70-80% reported incidence). This study was designed to...
Background Incidence of postoperative nausea and vomiting (PONV) in susceptible patients can be unacceptably high (70-80% reported incidence). This study was designed to evaluate the effect of palonosetron and ondansetron in preventing PONV in high-risk patients undergoing gynecological laparoscopic surgery. Methodology In this randomized, controlled, double-blind trial, non-smoking females aged 18-70 years, weighing 40-90 kg, and posted for elective laparoscopic gynecological surgeries were enrolled into ondansetron (Group A, n = 65) and palonosetron (Group B, n = 65) groups. Palonosetron (1 mcg/kg IV) or ondansetron (0.1 mg/kg IV) were administered just before induction. Postoperatively, the incidence of nausea, vomiting, PONV (scored on a scale of 0-3), need for rescue antiemetic, complete response, patient satisfaction, and adverse effects were evaluated up to 48 h following surgery. Normally distributed continuous variables were compared using Student's t-test. In addition, the Chi-squared test or Fisher's exact test were used to compare nominal categorical data as deemed appropriate. P-value <0.05 was observed as statistically significant. Results The overall PONV scores and postoperative nausea scores during 0-2 and 24-48 hours were comparable, but PONV scores (p = 0.023) and postoperative nausea scores (p = 0.010) during 2-24 hours were significantly lesser in Group B compared to Group A. There was no statistically significant difference in the postoperative vomiting score or retching during 0-48 hours. The amount of first-line rescue antiemetic used during 2-24 hours was significantly higher in Group A (56%) than in Group B (31%) (p = 0.012; p <0.05). A complete response to the drug during 2-24 hours was significantly higher (p = 0.023) in Group B (63%) compared to Group A (40%), whereas response was comparable during 0-2 and 24-48 hours. Both groups had a comparable incidence of adverse effects and patient satisfaction scores. Conclusion Palonosetron has a superior anti-nausea effect, less need for rescue antiemetics, and lesser incidence of total PONV compared to ondansetron during 2-24h and comparable effect to ondansetron during 0-2h and 24-48h postoperative period in high-risk patients undergoing gynecological laparoscopic surgery.
PubMed: 35505760
DOI: 10.7759/cureus.23615 -
Structure (London, England : 1993) Oct 2020Inaccurately perceived as niche drugs, antiemetics are key elements of cancer treatment alleviating the most dreaded side effect of chemotherapy. Serotonin 5-HT3...
Inaccurately perceived as niche drugs, antiemetics are key elements of cancer treatment alleviating the most dreaded side effect of chemotherapy. Serotonin 5-HT3 receptor antagonists are the most commonly prescribed class of drugs to control chemotherapy-induced nausea and vomiting. These antagonists have been clinically successful drugs since the 1980s, yet our understanding of how they operate at the molecular level has been hampered by the difficulty of obtaining structures of drug-receptor complexes. Here, we report the cryoelectron microscopy structure of the palonosetron-bound 5-HT3 receptor. We investigate the binding of palonosetron, granisetron, dolasetron, ondansetron, and cilansetron using molecular dynamics, covering the whole set of antagonists used in clinical practice. The structural and computational results yield detailed atomic insight into the binding modes of the drugs. In light of our data, we establish a comprehensive framework underlying the inhibition mechanism by the -setron drug family.
Topics: Animals; Antiemetics; Binding Sites; Cryoelectron Microscopy; Hydrogen Bonding; Mice; Molecular Dynamics Simulation; Palonosetron; Protein Conformation; Receptors, Serotonin, 5-HT3; Serotonin; Serotonin 5-HT3 Receptor Antagonists
PubMed: 32726573
DOI: 10.1016/j.str.2020.07.004 -
Supportive Care in Cancer : Official... Jul 2020There are several studies on premedication to prevent postembolization syndromes which occurs after transcatheter arterial chemoembolization (TACE), but the medication...
PURPOSE
There are several studies on premedication to prevent postembolization syndromes which occurs after transcatheter arterial chemoembolization (TACE), but the medication to be used is still not established. This study aimed to examine the effect of palonosetron and dexamethasone on the prevention of gastrointestinal symptoms induced by TACE.
METHODS
Patients with hepatocellular carcinoma who were treated with TACE with epirubicin were retrospectively evaluated. The complete response rate of antiemetic drugs and incidence and severity of gastrointestinal symptoms were compared between the antiemetic group (AE group), which includes 51 patients prophylactically administered with palonosetron 0.75 mg and dexamethasone 9.9 mg intravenously before TACE on day 1 and dexamethasone 6.6 mg intravenously on days 2 and 3, and control group with 101 patients without antiemetic premedication.
RESULTS
Complete response rate in the entire evaluation period was significantly higher in the AE group compared with that in the control group. In the acute phase, the incidence and severity of nausea, vomiting, and anorexia significantly decreased in the AE group, but only anorexia improved in the delay phase. Additionally, postembolization syndromes, such as abdominal pain and fever, were significantly attenuated in the AE group; however, constipation worsened in this group.
CONCLUSIONS
Premedication of palonosetron and dexamethasone significantly prevents the incidence and reduces the severity of gastrointestinal symptoms especially in the acute phase. Further studies will be needed to determine the most recommended 5-HT antagonist or dosage of dexamethasone in establishing the optimal antiemetic regimen.
Topics: Abdominal Pain; Adult; Aged; Antibiotics, Antineoplastic; Antiemetics; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Dexamethasone; Epirubicin; Female; Gastrointestinal Diseases; Humans; Liver Neoplasms; Male; Middle Aged; Nausea; Palonosetron; Retrospective Studies; Vomiting
PubMed: 31732854
DOI: 10.1007/s00520-019-05178-1 -
Annals of Palliative Medicine Apr 2018Palonosetron is an effective antiemetic in chemotherapy-induced nausea and vomiting (CINV), but has yet to be studied in the radiation setting. The purpose of the...
BACKGROUND
Palonosetron is an effective antiemetic in chemotherapy-induced nausea and vomiting (CINV), but has yet to be studied in the radiation setting. The purpose of the present study was to investigate the efficacy and safety of palonosetron in the prophylaxis of radiation-induced nausea and vomiting (RINV).
METHODS
Patients without existing nausea and vomiting undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg orally before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2-10 after treatment). The primary endpoint was control of vomiting. Complete control was defined as no use of rescue medication and no episodes of nausea or vomiting. Secondary endpoints included control of nausea and quality of life (QOL). QOL was assessed with the Functional Living Index-Emesis and the European Organisation for Research and Treatment of Cancer QOL Questionnaire-Core 15 Palliative (C15-PAL).
RESULTS
In all evaluable patients (n=75), complete control of vomiting was 93.3% in the acute phase and 93.2% in the delayed phase. Complete control of nausea was 74.7% in the acute phase and 74.0% in the delayed phase.
CONCLUSIONS
Results suggest improved control in RINV compared to historical reports with first generation serotonin receptor antagonists (RA). A randomized study will be needed to confirm this finding.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Pilot Projects; Quinuclidines; Radiotherapy; Serotonin Antagonists; Vomiting
PubMed: 29764183
DOI: 10.21037/apm.2018.03.12 -
Clinical and Translational Science Sep 2021Nausea, vomiting, and renal injury are the common adverse effects associated with cisplatin. Cisplatin is excreted via the multidrug and toxin release (MATE)...
Nausea, vomiting, and renal injury are the common adverse effects associated with cisplatin. Cisplatin is excreted via the multidrug and toxin release (MATE) transporter, and the involvement of the MATE transporter in cisplatin-induced kidney injury has been reported. The MATE transporter is also involved in the excretion of ondansetron, but the effects of 5-HT receptor antagonists used clinically for cisplatin-induced renal injury have not been elucidated. Therefore, the aim of this study was to investigate the effects of 5-HT receptor antagonists in a mouse model of cisplatin-induced kidney injury and to validate the results using medical big data analysis of more than 1.4 million reports and a survey of 3000 hospital medical records. The concomitant use of a first-generation 5-HT receptor antagonist (ondansetron, granisetron, or ramosetron) significantly increased cisplatin accumulation in the kidneys and worsened renal damage. Conversely, the concomitant use of palonosetron had no effect on renal function compared with the use of cisplatin alone. Furthermore, an analysis of data from the US Food and Drug Administration Adverse Event Reporting System and retrospective medical records revealed that the combination treatment of cisplatin and a first-generation 5-HT receptor antagonist significantly increased the number of reported renal adverse events compared with the combination treatment of cisplatin and a second-generation 5-HT receptor antagonist. These results suggest that compared with the first-generation antagonists, second-generation 5-HT receptor antagonists do not worsen cisplatin-induced acute kidney injury. The findings should be validated in a prospective controlled trial before implementation in clinical practice.
Topics: Acute Kidney Injury; Aged; Animals; Benzimidazoles; Cisplatin; Disease Models, Animal; Female; Granisetron; Humans; Kidney; Male; Mice; Middle Aged; Nausea; Ondansetron; Organic Cation Transport Proteins; Palonosetron; Renal Elimination; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 33982438
DOI: 10.1111/cts.13045 -
Frontiers in Surgery 2022The present study is designed to study the analgesic and sedative effect of different doses of dexmedetomidine combined with butorphanol in continuous analgesia after a...
OBJECTIVE
The present study is designed to study the analgesic and sedative effect of different doses of dexmedetomidine combined with butorphanol in continuous analgesia after a cesarean section.
METHODS
A total of 60 puerperae undergoing a cesarean section recruited from a single center were divided into three groups according to the postoperative continuous analgesia protocol: control group (100 mL of normal saline containing 10 µg/kg fentanyl and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h), DB1 group (100 mL of normal saline containing 1.0 µg/kg dexmedetomidine, 4 mg of butorphanol, 10 µg/kg fentanyl, and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h), and DB2 group (100 mL normal saline containing 2.0 µg/kg dexmedetomidine, 4 mg of butorphanol, 10 µg/kg fentanyl, and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h). We compared the blood pressure, heart rate, oxygen saturation, VAS score, Ramsay score, and adverse reactions of puerperae among the three groups after surgery.
RESULTS
The baseline data all have no significant difference in the three groups ( > 0.05). Compared with those in the control group, the systolic blood pressure, diastolic blood pressure, heart rate, and VAS score of the puerperae in the DB1 group and DB2 group were significantly decreased at 6, 24, and 48 h ( < 0.05), while the Ramsay scores of the puerperae in DB1 group and DB2 group were significantly increased at 6, 24, and 48 h ( < 0.05). At the same time, the systolic blood pressure, diastolic blood pressure, heart rate, and VAS score of the puerperae in the DB2 group were significantly lower than those in the DB1 group ( < 0.05), while the Ramsay scores of the puerperae in DB2 group were significantly higher than those in the DB1 group ( < 0.05). Also, there is no significant difference in oxygen saturation and adverse reactions of puerperae among the three groups after surgery ( > 0.05).
CONCLUSION
Dexmedetomidine combined with butorphanol can improve the analgesic and sedative effects in continuous analgesia after a cesarean section, and the analgesic and sedative effects of dexmedetomidine in the high-dose group are better than those in the low-dose group.
PubMed: 35599801
DOI: 10.3389/fsurg.2022.896536