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Medicine Nov 2018Microvascular decompression (MVD) is associated with a particularly high risk of postoperative nausea and vomiting (PONV) among craniotomy patients. However, there is no... (Observational Study)
Observational Study
Effect of prophylactic palonosetron and sugammadex on postoperative nausea and vomiting in patients undergoing microvascular decompression under propofol-maintained anesthesia: A retrospective observational study.
Microvascular decompression (MVD) is associated with a particularly high risk of postoperative nausea and vomiting (PONV) among craniotomy patients. However, there is no information regarding the effect of prophylactic palonosetron and sugammadex on PONV in patients undergoing MVD under propofol-maintained anesthesia.Medical records of 274 adults who had undergone MVD under propofol-maintained anesthesia were reviewed. Patients were classified into 4 groups, based on the reversal agent used (sugammadex/pyridostigmine) and whether or not prophylactic palonosetron was used. The PONV incidence and risk factors were analyzed according to the use of these agents.The overall incidence of PONV was 30.7% during the first 24 hours postoperatively. The incidence of PONV was lower in the group using combination of prophylactic palonosetron and sugammadex (19.3%) compared with the group not using both agents (37.2%). The combined use of the prophylactic palonosetron and sugammadex was identified as a factor affecting the occurrence of PONV in both univariable (OR = 0.40, 95% CI: 0.21-0.77, P = .006) and multivariable (OR = 0.38, 95% CI: 0.20-0.75, P = .005) logistic regression analyses. In multivariable logistic regression analysis, female sex was also significant independent risk factor in PONV (OR = 2.62, 95% CI: 1.35-5.08, P = .004).In this retrospective observational study, the combined use of prophylactic palonosetron before anesthetic induction and sugammadex as a reversal of neuromuscular blockade are associated with a reduction in the incidence of PONV in patients undergoing MVD under propofol-maintained anesthesia.
Topics: Aged; Anesthesia; Anesthetics, Intravenous; Antiemetics; Decompressive Craniectomy; Drug Therapy, Combination; Female; Humans; Incidence; Isoquinolines; Logistic Models; Male; Microvascular Decompression Surgery; Middle Aged; Palonosetron; Postoperative Nausea and Vomiting; Preoperative Period; Propofol; Quinuclidines; Retrospective Studies; Risk Factors; Sugammadex; Treatment Outcome; gamma-Cyclodextrins
PubMed: 30431604
DOI: 10.1097/MD.0000000000013237 -
National Journal of Maxillofacial... 2022The objective is to evaluate the efficacy of prophylactic single intravenous dose of palonosetron in the management of postoperative nausea and vomiting (PONV) following...
OBJECTIVE
The objective is to evaluate the efficacy of prophylactic single intravenous dose of palonosetron in the management of postoperative nausea and vomiting (PONV) following oral and maxillofacial surgical interventions performed through an intraoral approach under general anesthesia (GA).
MATERIALS AND METHODS
A prospective study was conducted on 100 subjects who underwent intraoral surgical procedures for the management of maxillofacial trauma, pathology, dentofacial anomalies, and deformities under GA. All subjects received a prophylactic single intravenous dose of 0.075 mg palonosetron along with premedication. Predisposing factors for PONV such as patient age, gender, Apfel risk score, history of motion sickness, smoking, type of procedure, and administration of postoperative opioids were taken into consideration. All the patients were monitored for PONV for the 1 24 h postoperatively (PO). First, at an interval of 30 min for 1 4 h and then at every 2 h interval for next 8 h followed by monitoring every 6 h interval till 24 h. Time and frequency of rescue medication were noted.
RESULTS
Seventy-nine percentage subjects did not have PONV. 15% subjects had a single episode of vomiting PO which could be attributed to multiple intra oral surgical sites performed as well as longer duration of exposure to anesthetic agents in addition to providing opioid analgesics for the management of postoperative pain. Only 6% subjects needed rescue antiemetic drug. Palonosetron did not show any significant changes in cardiac status and serum profile.
CONCLUSION
Palonosetron is effective in the management of PONV for maxillofacial surgical procedures performed through an intraoral approach under GA.
PubMed: 36051795
DOI: 10.4103/njms.NJMS_346_21 -
Advances in Therapy May 2023Chemotherapy-induced nausea and vomiting (CINV) is often ranked by patients as one of the most distressing and feared consequences of chemotherapy. The novel... (Review)
Review
Chemotherapy-induced nausea and vomiting (CINV) is often ranked by patients as one of the most distressing and feared consequences of chemotherapy. The novel neurokinin-1 (NK) receptor antagonist fosnetupitant, a phosphorylated prodrug formulation of netupitant, was approved in Japan in 2022. Fosnetupitant is one of the standard treatments for the prevention of CINV in patients who are receiving highly (any treatment where CINV occurs in more than 90% of patients) or moderately (where CINV occurs in 30-90% of patients) emetogenic chemotherapies. The aim of this commentary is to describe the mechanism of action, tolerability, and antiemetic efficacy of single-agent fosnetupitant in the prevention of CINV, and to discuss its clinical application, in order to aid optimal use.
Topics: Humans; Vomiting; Nausea; Antiemetics; Quinuclidines; Antineoplastic Agents
PubMed: 36884027
DOI: 10.1007/s12325-023-02474-5 -
European Review For Medical and... Aug 2021The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side...
NEPA (netupitant/palonosetron) for the antiemetic prophylaxis of nausea and vomiting induced by chemotherapy (CINV) with Folfirinox and Folfoxiri even during the COVID-19 pandemic: a real-life study.
OBJECTIVE
The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV.
PATIENTS AND METHODS
This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA).
RESULTS
During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox. During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox. There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox.
CONCLUSIONS
This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.
Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; COVID-19; Colorectal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Nausea; Oxaliplatin; Palonosetron; Pandemics; Prospective Studies; Pyridines; Vomiting
PubMed: 34486707
DOI: 10.26355/eurrev_202108_26552 -
Journal of Comparative Effectiveness... Jul 2019To evaluate real-world effectiveness of guideline-recommended palonosetron-containing antiemetic regimens in patients receiving highly (HEC) or moderately emetogenic...
To evaluate real-world effectiveness of guideline-recommended palonosetron-containing antiemetic regimens in patients receiving highly (HEC) or moderately emetogenic (MEC) chemotherapy. This retrospective analysis used records of adults receiving first-line chemotherapy and a three-drug palonosetron-containing antiemetic regimen for HEC or palonosetron-containing antiemetic regimen for MEC (carboplatin). A total of 1587 records were evaluated. For HEC and MEC, respectively, chemotherapy-induced nausea and vomiting (CINV) occurred in 40 versus 44% of patient cycles (p = 0.01), and unscheduled iv. antiemetics in 41 versus 35% (p < 0.05). A total of 48% of HEC patients versus 42% of MEC patients had CINV-related clinic visits (p = 0.05). Palonosetron-containing antiemetic regimens may provide insufficient CINV control. Alternative regimens may improve patient quality of life and reduce healthcare resource utilization.
Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Female; Humans; Insurance Claim Review; Longitudinal Studies; Male; Middle Aged; Nausea; Palonosetron; Quality of Life; Retrospective Studies; Vomiting
PubMed: 31070042
DOI: 10.2217/cer-2018-0104 -
International Journal of Molecular... Jun 2021The organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) mediate the renal secretion of drugs. Recent studies suggest that...
The organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) mediate the renal secretion of drugs. Recent studies suggest that ondansetron, a 5-HT antagonist drug used to prevent nausea and vomiting, can inhibit OCT2- and MATE1-mediated transport. The purpose of this study was to test the ability of five 5-HT antagonist drugs to inhibit the OCT2 and MATE1 transporters. The transport of the OCT2/MATE1 probe substrate ASP was assessed using two models: (1) HEK293 kidney cells overexpressing human OCT2 or MATE1, and (2) MDCK cells transfected with human OCT2 and MATE1. In HEK293 cells, the inhibition of ASP uptake by OCT2 listed in order of potency was palonosetron (IC: 2.6 μM) > ondansetron > granisetron > tropisetron > dolasetron (IC: 85.4 μM) and the inhibition of ASP uptake by MATE1 in order of potency was ondansetron (IC: 0.1 μM) > palonosetron = tropisetron > granisetron > dolasetron (IC: 27.4 μM). Ondansetron (0.5-20 μM) inhibited the basolateral-to-apical transcellular transport of ASP up to 64%. Higher concentrations (10 and 20 μM) of palonosetron, tropisetron, and dolasetron similarly reduced the transcellular transport of ASP. In double-transfected OCT2-MATE1 MDCK cells, ondansetron at concentrations of 0.5 and 2.5 μM caused significant intracellular accumulation of ASP. Taken together, these data suggest that 5-HT antagonist drugs may inhibit the renal secretion of cationic drugs by interfering with OCT2 and/or MATE1 function.
Topics: Animals; Antiemetics; Biological Transport; Cell Line; Cells, Cultured; Dogs; Gene Expression; HEK293 Cells; Humans; Kidney; Madin Darby Canine Kidney Cells; Molecular Structure; Organic Cation Transport Proteins; Organic Cation Transporter 2; Serotonin 5-HT3 Receptor Antagonists
PubMed: 34208557
DOI: 10.3390/ijms22126439 -
Frontiers in Pharmacology 2018Ghrelin has well-known activity to stimulate appetite and weight gain. Evidence suggests that ghrelin may also have effects in reducing chemotherapy-induced emesis via...
Anti-emetic Action of the Brain-Penetrating New Ghrelin Agonist, HM01, Alone and in Combination With the 5-HT Antagonist, Palonosetron and With the NK Antagonist, Netupitant, Against Cisplatin- and Motion-Induced Emesis in (House Musk Shrew).
UNLABELLED
Ghrelin has well-known activity to stimulate appetite and weight gain. Evidence suggests that ghrelin may also have effects in reducing chemotherapy-induced emesis via growth hormone secretagogue receptors (GHS-R1A) in the brain. However, it is not known whether the stimulation of GHS-R1A has broad inhibitory anti-emetic effects. In the present studies, we used to investigate the potential of the new and novel orally bioavailable brain-penetrating GHS-R1A mimetic, HM01 (1-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-3-methyl-3-[(4R)-1-Methyl-3,3-dimethyl-4-piperidyl]urea), to reduce emesis induced by a variety of emetic challenges. HM01 (1 to 30 mg/kg, p.o.) antagonized emesis induced by cisplatin (30 mg/kg, i.p.) and by motion (4 cm horizontal displacement, 1 Hz) but was ineffective against emesis induced by nicotine (5 mg/kg, s.c.) and copper sulfate (120 mg/kg by intragastric gavage). In other experiments, HM01 (3 mg/kg, p.o.) enhanced the anti-emetic control of a regimen of palonosetron (0.01 mg/kg, p.o.) alone and palonosetron (0.01 mg/kg p.o.) plus netupitant (1 mg/kg, p.o.). HM01 (10 mg/kg, p.o.) also had positive effects in increasing feeding and drinking in nicotine-treated animals, and it shortened the latency to drink in animals treated with cisplatin. These data indicate that brain-penetrating GHS-R1A agonists may have use alone and/or in combination with standard anti-emetic regimens for the treatment of chemotherapy-induced nausea and vomiting and motion sickness.
HIGHLIGHTS
- The novel orally bioavailable brain-penetrating GHS-R1A agonist, HM01 (1-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-3-methyl-3-[(4R)-1-Methyl-3,3-dimethyl-4-piperidyl]urea), antagonizes motion- and cisplatin-induced emesis.- HM01 did not reduce emesis induced by nicotine or by intragastric copper sulfate.- HM01 has positive effects on food consumption after treatment with nicotine.- HM01 has synergistic effects against cisplatin when combined with palonosetron and palonosetron/netupitant regimens.- It is suggested that GHS-R1A agonists may be protective against chemotherapy-induced nausea and vomiting in combination with traditional anti-emetics and against motion-induced emesis.
PubMed: 30127745
DOI: 10.3389/fphar.2018.00869 -
BMC Pharmacology & Toxicology Jan 2015Patients may experience nausea and vomiting when undergoing chemotherapy or surgery requiring anesthesia. Serotonin 5-hydroxytryptamine 3 (5-HT3) receptor antagonists... (Review)
Review
BACKGROUND
Patients may experience nausea and vomiting when undergoing chemotherapy or surgery requiring anesthesia. Serotonin 5-hydroxytryptamine 3 (5-HT3) receptor antagonists are effective antiemetics, yet may cause adverse cardiac events, such as arrhythmia. We aimed to identify interventions that mitigate the cardiac risk of 5-HT3 receptor antagonists.
METHODS
Electronic databases, trial registries, and references were searched. Studies on patients undergoing chemotherapy or surgery examining interventions to monitor cardiac risk of 5-HT3 receptor antagonists were included. Search results were screened and data from relevant studies were abstracted in duplicate. Risk of bias of included studies was assessed using the Cochrane Effective Practice and Organisation of Care (EPOC) group's risk-of-bias tool. Due to a dearth of included studies, meta-analysis was not conducted.
RESULTS
Two randomized clinical trials (RCT) and 1 non-randomized clinical trial (NRCT) were included after screening 7,637 titles and abstracts and 1,554 full-text articles. Intravenous administration of different dolasetron doses was examined in the NRCT, while dolasetron versus ondansetron and palonosetron versus ondansetron were examined in the RCT. Electrocardiogram (ECG) was the only intervention examined to mitigate cardiac harm. No differences in ECG evaluations were observed between dolasetron or palonosetron versus ondansetron after 15 minutes, 24 hours, and 1 week post-administration in the 2 RCTs. Four deaths were observed in one RCT, which were deemed unrelated to palonosetron or ondansetron administration. Minor increases in PR and QT intervals were observed in the NRCT for dolasetron dosages greater than 1.2 mg/kg 1-2 hours post-administration, but were deemed not clinically relevant.
CONCLUSIONS
ECG monitoring of chemotherapy patients administered with 5-HT3 receptor antagonists did not reveal clinically significant differences in arrhythmia between the medications at the examined time periods. The usefulness of ECG to monitor chemotherapy patients administered with 5-HT3 receptor antagonists remains unclear, as all patients received ECG monitoring.
TRIAL REGISTRATION
PROSPERO registry number: CRD42013003565.
Topics: Antiemetics; Antineoplastic Agents; Arrhythmias, Cardiac; Drug Therapy, Combination; Electrocardiography; Humans; Indoles; Isoquinolines; Ondansetron; Palonosetron; Quinolizines; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists
PubMed: 25623303
DOI: 10.1186/2050-6511-16-1 -
Scientific Reports Nov 2018This study aimed to compare the antiemetic efficacy and safety of a four-drug combination with those of a standard three-drug combination in Japanese patients with... (Comparative Study)
Comparative Study Observational Study
This study aimed to compare the antiemetic efficacy and safety of a four-drug combination with those of a standard three-drug combination in Japanese patients with breast cancer treated with anthracycline. We retrospectively analyzed data from Japanese patients with breast cancer, who had received their first cycle of anthracycline and were treated with aprepitant, palonosetron, and dexamethasone with or without olanzapine. This retrospective observational study was performed at Ehime University Hospital using the electronic medical records. Multivariable and propensity score-adjusted analyses were performed to compare the onset of complete response (CR) failure between the groups. One-hundred and thirty patients were included in this study and the four- and three-drug group had 22 and 108 patients, respectively. Similar to multivariable logistic regression analysis, propensity-adjusted logistic regression analysis revealed that the four-drug group was markedly associated with a decreased odds of CR failure in the overall, acute, and delayed phases (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.10-0.73; OR: 0.28, 95% CI: 0.10-0.76; and OR: 0.15, 95% CI: 0.04-0.57, respectively). Additionally, treatment-related adverse events were well tolerated in both the groups. These findings suggest that the antiemetic efficacy of the four-drug combination is superior to that of the standard three-drug combination.
Topics: Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Dexamethasone; Drug Therapy, Combination; Female; Humans; Incidence; Middle Aged; Nausea; Olanzapine; Palonosetron; Retrospective Studies; Sleep Initiation and Maintenance Disorders; Sleepiness; Treatment Outcome; Vomiting
PubMed: 30389996
DOI: 10.1038/s41598-018-34618-x