Increased Postoperative Opioid Consumption in the Presence of Coadministration of 5-Hydroxytryptamine Type 3 Antagonists with Acetaminophen: A Hospital Registry Study.

BACKGROUND: Acetaminophen and 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are administered as standard prophylaxes for postoperative pain, nausea, and vomiting. Preclinical studies, however, suggest that 5-HT3 antagonists may compromise acetaminophen's analgesic effect. This hospital registry study investigates whether 5-HT3 antagonists mitigate the analgesic effect of prophylactic acetaminophen in a perioperative setting. METHODS: This study included 55,016 adult patients undergoing general anesthesia for ambulatory procedures at a tertiary healthcare center in Massachusetts from 2015 to 2022. Using binary exposure variables and a comprehensive selection of preplanned patient- and procedure-related covariates for confounder control, the authors investigated whether intraoperative 5-HT3 antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in milligram oral morphine equivalents (OME) administered in the postanesthesia care unit. A multivariable, zero-inflated negative binomial regression model was applied. RESULTS: A total of 3,166 patients (5.8%) received only acetaminophen, 15,438 (28.1%) only 5-HT3 antagonists, 31,850 (57.9%) both drugs, and 4,562 (8.3%) neither drug. The median postanesthesia care unit opioid dose was 7.5 mg OME (interquartile range, 7.5 to 14.3 mg OME) among 16,640 of 55,016 (30.2%) patients who received opioids, and the mean opioid dose was 3.2 mg OME across all patients (maximum cumulative dose, 20.4 mg OME). Acetaminophen administration was associated with a -5.5% (95% CI, -9.6 to -1.4%; P = 0.009; adjusted absolute difference, -0.19 mg OME; 95% CI, -0.33 to -0.05; P = 0.009) reduction in opioid consumption among patients who did not receive a 5-HT3 antagonist, while there was no effect in patients who received a 5-HT3 antagonist (adjusted absolute difference, 0.00 mg OME; 95% CI, -0.06 to 0.05; P = 0.93; P for interaction = 0.013). CONCLUSIONS: A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT3 antagonists were coadministered, suggesting that physicians might consider reserving 5-HT3 antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis.

Commonly used antiemetics for prophylaxis of postoperative nausea and vomiting after Caesarean delivery with neuraxial morphine: a network meta-analysis.

BACKGROUND: Dopamine antagonists, 5-HT3 antagonists, and dexamethasone are frequently used in obstetrics to prevent postoperative nausea and vomiting (PONV). However, the superiority of any drug class is yet to be established. This network meta-analysis aimed to compare the efficacy of these antiemetics for PONV prophylaxis in women receiving neuraxial morphine for Caesarean delivery. METHODS: We searched PubMed, Embase, CENTRAL, Web of Science, and Wanfang Data for eligible randomised controlled trials. Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) within 24 h after surgery. We used a Bayesian random-effects model and calculated odds ratios with 95% credible intervals for dichotomous data. We performed sensitivity and subgroup analyses for primary outcomes. RESULTS: A total of 33 studies with 4238 women were included. In the primary analyses of all women, 5-HT3 antagonists, dopamine antagonists, dexamethasone, and 5-HT3 antagonists plus dexamethasone significantly reduced PON and POV compared with placebo, and 5-HT3 antagonists plus dexamethasone were more effective than monotherapy. In the subgroup analyses, similar results were seen in women receiving epidural morphine or intrathecal morphine alone but not in women receiving intrathecal morphine with fentanyl or sufentanil. However, most included studies had some concerns or a high risk of bias, and the overall certainty of the evidence was low or very low. CONCLUSIONS: Combined 5-HT3 antagonists plus dexamethasone are more effective than monotherapy in preventing PONV associated with neuraxial morphine after Caesarean delivery. Future studies are needed to determine the role of prophylactic antiemetics in women receiving intrathecal morphine and lipophilic opioids. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023454602.

Comparison of prophylaxis strategy for postoperative nausea and vomiting and its incidence before and after the implementation of 5-hydroxytryptamine 3 in surgical setting: a single-center, retrospective study.

PURPOSE: To investigate the association between adherence to guideline-recommended risk-based postoperative nausea and vomiting (PONV) prophylaxis, the antiemetics used for PONV prophylaxis, and the incidence of PONV in patients who were underwent general anesthesia before and after 5-HT3 receptor antagonists became available. METHODS: Patients (≥ 20 years old) who were extubated after scheduled surgery and returned to general wards between January 2021 and February 2022 and between June 2022 and July 2023 were included. Risk factors included age < 50, female, motion sickness, nonsmoker, surgical factors, and postoperative opioid use. Two and three or more prophylaxis were recommended for patients with one or two and three or more risk factors, respectively. The primary outcome was the number of patients who received adequate prophylaxis, and the secondary outcomes were antiemetic agents used during anesthesia and the incidence of PONV on postoperative days 0 and 1. PONV was defined as documented PONV or rescue antiemetic administration. RESULTS: From January 2021 to February 2022 and from June 2022 to July 2023, 2342 and 2682 patients were included, respectively. Before ondansetron became available, more D2 receptor antagonists were used (p < 0.001), and after ondansetron became available, both ondansetron (p < 0.001) and propofol (p < 0.001) were given more frequently. Before and after ondansetron became available, the number of patients with adequate prophylaxis was 3.7% and 9.2%, respectively (p < 0.001), and the incidence of PONV on postoperative days 0 and 1 was 44.6% and 44.0%, respectively (p = 0.67). CONCLUSION: The availability of ondansetron increased the number of patients with adequate PONV prophylaxis, but did not decrease the incidence of PONV.

Isopropyl alcohol inhalation versus 5-HT3 antagonists for treatment of nausea: a meta-analysis of randomised controlled trials.

PURPOSE: Nausea is a common and unpleasant sensation for which current therapies such as serotonin (5-HT3) antagonists are often ineffective, while also conferring a risk of potential adverse events. Isopropyl alcohol (IPA) has been proposed as a treatment for nausea. We aimed to compare IPA with 5-HT3 antagonists for the treatment of nausea across all clinical settings. METHODS: MEDLINE, EMBASE, PubMed, CENTRAL and CINAHL were searched from inception to 17 July 2023 for randomised controlled trials (RCTs) comparing inhaled IPA and a 5-HT3 antagonist for treatment of nausea. Severity and duration of nausea, rescue antiemetic use, adverse events and patient satisfaction were the outcomes sought. Risk of bias (RoB) was assessed using Cochrane RoB 2. Random-effects model was used for meta-analysis. Combination of meta-analyses and narrative review was used to synthesise findings. The evidence was appraised using GRADE. RESULTS: From 1242 records, 4 RCTs were included with 382 participants. Participants receiving IPA had a significantly lower mean time to 50% reduction in nausea (MD - 20.06; 95% CI - 26.26, - 13.85). Nausea score reduction at 30 min was significantly greater in the IPA group (MD 21.47; 95% CI 15.47, 27.47). IPA led to significantly reduced requirement for rescue antiemetics (OR 0.60; 95% CI 0.37, 0.95; p = 0.03). IPA led to no significant difference in patient satisfaction when compared with a 5-HT3 antagonist. The overall GRADE assessment of evidence quality ranged from very low to low. CONCLUSION: IPA may provide rapid, effective relief of nausea when compared with 5-HT3 antagonists.

Palonosetron for prevention of delayed chemotherapy-induced nausea and vomiting in pediatric patients: a meta-analysis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) are common adverse events in patients undergoing emetogenic chemotherapy. Palonosetron, a second-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), has demonstrated non-inferiority to first-generation 5-HT3 RAs for CINV in pediatric patients. Although palonosetron has a long half-life and prolonged antiemetic action, its efficacy against delayed CINV in pediatric patients is not well understood. Therefore, this meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy of palonosetron for delayed CINV in pediatric patients. METHODS: A literature search of MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science databases was performed. A meta-analysis was performed using forest plots, and risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A funnel plot was constructed to explore publication bias. RESULTS: The literature search retrieved 842 records, of which 23 full-text articles were assessed, including six RCTs. Meta-analysis of four RCTs that reported on the complete response (CR: defined as no emesis and no rescue medication) rate for delayed CINV revealed that palonosetron was statistically superior to first-generation 5-HT3 RAs (RR = 1.21 [95% CI 1.09-1.35]; p < 0.01). Although the number of studies included was small, no publication bias was observed in the funnel plots. In addition, the CR rate for overall and acute CINV was also significantly higher for palonosetron (RR = 1.25 [95% CI 1.01-1.54]; p = 0.04 and RR = 1.06 [95% CI 1.01-1.12]; p = 0.03, respectively). CONCLUSION: Palonosetron is effective in the prophylaxis of delayed CINV in pediatric patients.

Effects of adding a neurokinin-1 receptor antagonist to 5 mg olanzapine, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone for preventing carboplatin-induced nausea and vomiting: a propensity score-matched analysis.

BACKGROUND: Olanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK1RA) added to olanzapine, a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) has not been proven. This study aimed to assess the efficacy and safety of NK1RA, in combination with three-drug antiemetic regimens containing olanzapine, in preventing nausea and vomiting induced by carboplatin-based chemotherapy. METHODS: Data were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK1RA was estimated for each patient using a logistic regression model that included age, sex, and carboplatin dose. We analyzed a total of 62 patients, who were treated without NK1RA (non-NK1RA group: 31 patients) and with NK1RA (NK1RA group: 31 patients). The patients were selected using propensity score matching. RESULTS: The complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0-120 h post carboplatin administration) was 93.5% in the non-NK1RA group and 96.8% in the NK1RA group, with a difference of -3.2% (95% confidence interval, -18.7% to 10.9%; P = 1.000). In terms of safety, there was no significant difference between the groups in daytime sleepiness and concentration impairment, which are the most worrisome adverse events induced by olanzapine. CONCLUSIONS: The findings suggest that antiemetic regimens consisting of olanzapine, 5HT3RA, and DEX without NK1RA may be a treatment option for patients receiving carboplatin-based chemotherapy.

5-HT3 Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface.

5-HT3 receptor antagonists, first introduced to the market in the mid-1980s, are proven efficient agents to counteract chemotherapy-induced emesis. Nonetheless, recent investigations have shed light on unappreciated dimensions of this class of compounds in conditions with an immunoinflammatory component as well as in neurologic and psychiatric disorders. The promising findings from multiple studies have unveiled several beneficial effects of these compounds in multiple sclerosis, stroke, Alzheimer disease, and Parkinson disease. Reports continue to uncover important roles for 5-HT3 receptors in the physiopathology of neuropsychiatric disorders, including depression, anxiety, drug abuse, and schizophrenia. This review addresses the potential of 5-HT3 receptor antagonists in neurology- and neuropsychiatry-related disorders. The broad therapeutic window and high compliance observed with these agents position them as suitable prototypes for the development of novel pharmacotherapeutics with higher efficacy and fewer adverse effects.

5HT3 RA plus dexamethasone plus aprepitant for controlling delayed chemotherapy-induced nausea and vomiting in colorectal cancer.

Delayed chemotherapy-induced nausea and vomiting (CINV) is not well controlled in colorectal cancer (CRC) patients undergoing oxaliplatin (L-OHP)-based chemotherapy. Whether neurokinin-1 receptor antagonist addition to a first-generation 5HT3 antagonist (1st 5-HT3 RA) and dexamethasone (DEX) is beneficial to these patients remains controversial. Furthermore, whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV is unclear. We, therefore, investigated whether PALO+DEX or 1st 5-HT3 RA+DEX+APR was more effective in controlling delayed CINV, and the risk factors for delayed CINV, in CRC patients undergoing L-OHP-based chemotherapy. Data were pooled from two prospective observational Japanese studies and a phase III trial to compare CINV incidence between the PALO + DEX (PALO) and 5-HT3 RA+DEX+APR (APR) groups by propensity score-matched analysis. CINV risk factors were identified using logistic regression models. The CINV incidence was higher in the PALO group than in the APR group. Logistic regression analysis revealed alcohol consumption, motion sickness, and the PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and the PALO+DEX regimen as those for delayed vomiting. Compared with prophylactic PALO + DEX, 1st 5-HT3 RA+DEX+APR was more effective in controlling delayed CINV. Thus, CRC patients receiving L-OHP-based chemotherapy should be treated with three antiemetics, including APR.

Anterior resection syndrome: a randomized clinical trial of a 5-HT3 receptor antagonist (ramosetron) in male patients with rectal cancer.

BACKGROUND: No effective treatment exists for anterior resection syndrome (ARS) following sphincter-saving surgery for rectal cancer. This RCT assessed the safety and efficacy of a 5-HT3 receptor antagonist, ramosetron, for ARS. METHODS: A single-centre, randomized, controlled, open-label, parallel group trial was conducted. Male patients with ARS 1 month after rectal cancer surgery or ileostomy reversal were enrolled and randomly assigned (1 : 1) to 5 µg of ramosetron (Irribow®) daily or conservative treatment for 4 weeks. Low ARS (LARS) score was calculated after randomization and 4 weeks after treatment. The study was designed as a superiority test with a primary endpoint of the proportion of patients with major LARS between the groups. Primary outcome analysis was based on the modified intention-to-treat population. Safety was assessed by monitoring adverse events during the study. RESULTS: : A total of 100 patients were randomized to the ramosetron (49 patients) or conservative treatment group (51 patients). Two patients were excluded, and 48 and 50 patients were analysed in the ramosetron and control groups, respectively. The proportion of major LARS after 4 weeks was 58 per cent (28 of 48 patients) in the ramosetron group versus 82 per cent (41 of 50 patients) in the control group, with a difference of 23.7 per cent (95 per cent c.i. 5.58 to 39.98, P = 0.011). There were minor adverse events in five patients, which were hard stool, frequent stool or anal pain. These were not different between the two groups. There were no serious adverse events. CONCLUSION: : Ramosetron could be safe and feasible for male patients with ARS. TRIAL REGISTRATION NUMBER: NCT02869984 (http://www.clinicaltrials.gov).

Effectiveness of palonosetron versus granisetron in preventing chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) commonly occurs after chemotherapy, adversely affecting patients' quality of life. Recently, studies have shown inconsistent antiemetic effects of two common 5-hydroxytryptamine 3 receptor antagonists, namely, palonosetron and granisetron. Therefore, we conducted a meta-analysis to evaluate the effectiveness of palonosetron versus granisetron in preventing CINV. METHODS: Relevant studies were obtained from PubMed, Embase, and Cochrane databases. The primary outcome was the complete response (CR) rate. Secondary outcomes were headache and constipation events. RESULTS: In total, 12 randomized controlled trials and five retrospective studies were reviewed. Palonosetron was consistently statistically superior to granisetron in all phases in terms of the CR rate (acute phases: odds ratio [OR] = 1.28, 95% confidence interval [CI] = 1.06-1.54; delayed phases: OR = 1.38, 95% CI = 1.13-1.69; and overall phases: OR = 1.37, 95% CI = 1.17-1.60). Moreover, a non-significant difference was found between the two groups in terms of the headache event, but the occurrence of the constipation event was lower in the granisetron group than in the palonosetron group. CONCLUSION: Palonosetron showed a higher protective efficacy in all phases of CINV prevention, especially in delayed phases, and no relatively severe adverse effects were observed.

Mirtazapine, a dopamine receptor inhibitor, as a secondary prophylactic for delayed nausea and vomiting following highly emetogenic chemotherapy: an open label, randomized, multicenter phase III trial.

Background We examined the efficacy of mirtazapine in preventing delayed nausea and vomiting following highly emetogenic chemotherapy (HEC). Patients and methods Patients who had experienced delayed emesis and would be subsequently scheduled for at least three more cycles of the same chemotherapy were randomly assigned to either a mirtazapine (15 mg daily on days 2-4) or a control group. In addition, both groups received a standard triplet regimen comprising aprepitant, a 5-HT3 receptor antagonist, and dexamethasone (7.5 mg on days 2-4). The chemotherapy regimens were either an epirubicin plus cyclophosphamide regimen or cisplatin-containing regimens. The primary end point was a complete response (no emesis and no rescue treatment) to the delayed phase (25-120 h post-chemotherapy) during Cycle 1. The impact on quality of life (QOL) was assessed using the Functional Living Index-Emesis (FLIE) questionnaire. Results Of 95 enrolled patients, 46 were assigned to the mirtazapine group and 49 to the control group. The complete response rate in the delayed phase during Cycle 1 was significantly higher with mirtazapine than in the control group (78.3% versus 49.0%, P = 0.003). The main adverse effects of mirtazapine were mild to moderate somnolence and weight gain. Mean total FLIE scores were similar between the two arms. Conclusions This is the first randomized prospective study to show that adding mirtazapine has a substantial and statistically significant benefit with good tolerance in patients with breast cancer who have experienced delayed emesis following the same prior HEC. (Trial registration: ClinicalTrials.gov NCT02336750).

Tropisetron But Not Granisetron Ameliorates Spatial Memory Impairment Induced by Chronic Cerebral Hypoperfusion.

Tropisetron and Granisetorn are 5-HT3 antagonists with antiemetic effects. Tropisetron also has a partial agonistic effect on alpha-7 nicotinic acetylcholine receptors (α7 nAChRs). On the other hand, chronic cerebral hypoperfusion (CCH) attenuates cerebral blood flow and impairs cognitive functions. The goal of this study was to investigate the effect of Tropisetron and Granisetron on CCH-induced spatial memory impairment in rats. Forty-eight male Wistar rats were used in this study. 2-VO surgery was done to induce CCH and Radial Eight Arm Maz apparatus was used to evaluate spatial memory (working and reference memory). Tropisetron was injected intraperitoneally at the doses of 1 and 5 mg/kg, and Granisetron was injected intraperitoneally at the dose of 3 mg/kg. Dorsal hippocampal (CA1) neurons count, Interleukin 6 (IL-6) serum level, and serotonin-reuptake transporter (SERT) gene expression were also evaluated. The results showed, CCH impaired working and reference memory, increased IL-6 serum level, and decreased CA1 neurons and SERT expression. Tropisetron at the dose of 5 mg/kg restored all the effects of CCH. However, Granisetron did not restore CCH-induced memory impairment. Furthermore, Granisetron had no effect on IL-6. While, it increased SERT expression and CA1 neurons. In conclusion, Tropisetron but not Granisetron, ameliorated spatial memory impairment induced by CCH. We suggested conducting more detailed studies investigating the role of serotonergic system (5-HT3 receptors and serotonin transporters) and also α7 nAChRs in the effects of Tropisetron.

Evaluation of the Antiemetic Effect of Premedication Optimized by Pharmaceutical Support in Cisplatin Regimens.

Cisplatin is classified as a drug with high emetic risk; thus, the use of aprepitant or fosaprepitant in addition to a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist and dexamethasone is recommended for antiemetic therapy. Further, hydration is required to prevent renal dysfunction, and the use of magnesium has been proposed as a part of the hydration procedure. When fosaprepitant is chosen for antiemetic therapy because the patient has dysphagia, and magnesium is added to the hydration procedure, there may be an incompatibility between the two drugs that reduces the antiemetic effect. In our hospital, in a former regimen, these two drugs were administered concurrently as premedication for regimens containing cisplatin. We varied the conditions so that in a revised regimen the two drugs did not come into contact due to pharmaceutical support, and we conducted a retrospective study to determine the difference in the antiemetic effect. The observation period was 2 years (from October 2015 to September 2017) for the former regimen group (n = 89) and 2 years (from October 2017 to September 2019) for the revised regimen group (n = 177). Comparison of the former and revised regimen groups revealed sex (p = 0.012); anticancer drug dosage (p = 0.006); and variation of premedication condition (p = 0.043) as factors affected by the revised regimen. Optimization of the premedication regimen was a form of necessary pharmaceutical support to maintain the patient's QOL.

High-flow oxygen and pro-serotonin agents for non-interventional treatment of post-dural-puncture headache.

OBJECTIVE: Post dural puncture headache (PDPH) is a common complication in patients following diagnostic or therapeutic lumbar puncture, procedures requiring epidural access, and spinal surgery. Epidural blood patch (EBP), the gold standard for the treatment of this pathology requires training not provided to emergency physicians. In addition, the presence of concomitant pathology and abnormal laboratory values are contraindications to perform EBP. In presence of these limitations, we sought for a non-interventional management of PDPH utilizing high-flow oxygen and pro-serotonin agents. We reviewed the mechanism of action of this therapy METHODS: To illustrate our proposal, we report a series of twelve consecutive patients with PDPH treated with high-flow oxygen therapy at 12 L/min via a non-rebreathing mask and intravenous metoclopramide. RESULTS: All patients were treated with this conservative therapy, no adverse reactions were observed. After the intervention, the headache resolved without further indications for PDPH. CONCLUSION: Our series suggests that combining high-flow oxygen and pro-serotonin agents such metoclopramide in the ED might be a feasible option as effective as the invasive methods used in treating PDPH. This therapy appears to be efficient and to minimize risk, cost and side effects. It presents an easily accessible alternative that should be considered when PDPH is not a viable option.

Latest Update on Prevention of Acute Chemotherapy-Induced Nausea and Vomiting in Pediatric Cancer Patients.

PURPOSE OF REVIEW: Chemotherapy-induced nausea and vomiting (CINV) is a common cause of acute morbidity that impacts quality of life in children receiving cancer treatment. Here, we review the evolution of CINV prophylaxis guidelines in children, with an emphasis on the literature published in the last 5 years, to bring the reader up to date. RECENT FINDINGS: Recent studies have led to the adoption of the "triple therapy" regimen of antiemetic prophylaxis (a 5-HT3 antagonist, dexamethasone, and a neurokinin-1 antagonist) as the backbone of recommendations for the prevention of CINV in children. Areas of new data include the addition of aprepitant and inclusion of palonosetron as a non-inferior 5-HT3 antagonist. In addition, there are emerging pediatric data informing patient-derived risk factors associated with CINV risk and classification of antineoplastic drugs based on emetogenicity. Several recent pediatric studies have shaped published guidelines for CINV prophylaxis in children.

Hydration requirements in patients receiving highly emetogenic chemotherapy.

AIM: Chemotherapy-induced nausea and vomiting diminishes quality of life and increases healthcare resource use. This retrospective medical records analysis evaluated hydration requirements with emetogenic chemotherapy. PATIENTS & METHODS: Cancer patients received moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC), and antiemetics palonosetron or granisetron extended-release subcutaneous (GERSC), neurokinin 1 receptor antagonist and dexamethasone. Unscheduled hydration event rates were determined. RESULTS: For 186 patients (92 palonosetron, 94 GERSC) overall, mean hydration rate was significantly higher with palonosetron (0.6 vs 0.2; p = 0.0005). Proportion of patients with ≥1 hydration event was significantly higher with palonosetron overall (54 vs 33%; p = 0.0033) and in cycles 2-4 and the HEC subgroup. CONCLUSION: GERSC within a three-drug antiemetic regimen may reduce unscheduled hydration requirements with MEC or HEC.

Cost-effectiveness analysis of olanzapine-containing antiemetic therapy for managing highly emetogenic chemotherapy in Southeast Asia: a multinational study.

PURPOSE: Recent studies suggested that olanzapine, together with dexamethasone and serotonin-3 receptor antagonist (5HT3RA), is effective in preventing chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC). This regimen is particularly useful in Southeast Asia (SEA) countries where resources are limited. We aimed to evaluate the cost-effectiveness of incorporating olanzapine into standard antiemetic regimens for the prevention of CINV in patients receiving HEC among SEA countries. METHODS: Using a decision tree model, clinical and economic outcomes associated with olanzapine-containing regimen and standard antiemetic regimen (doublet antiemetic regimen: dexamethasone+first generation 5HT3RA) in most SEA countries except in Singapore (triplet antiemetic regimen: dexamethasone+first generation 5HT3RA + aprepitant) for CINV prevention following HEC were evaluated. This analysis was performed in Thailand, Malaysia, Indonesia, and Singapore, using societal perspective method with 5-day time horizon. Input parameters were derived from literature, network meta-analysis, government documents, and hospital databases. Outcomes were incremental cost-effectiveness ratio (ICER) in USD/quality-adjusted life year (QALY) gained. A series of sensitivity analyses including probabilistic sensitivity analysis were also performed. RESULTS: Compared to doublet antiemetic regimen, addition of olanzapine resulted in incremental QALY of 0.0022-0.0026 with cost saving of USD 2.98, USD 27.71, and USD 52.20 in Thailand, Malaysia, and Indonesia, respectively. Compared to triplet antiemetic regimen, switching aprepitant to olanzapine yields additional 0.0005 QALY with cost saving of USD 60.91 in Singapore. The probability of being cost-effective at a cost-effectiveness threshold of 1 GDP/capita varies from 14.7 to 85.2% across countries. CONCLUSION: The use of olanzapine as part of standard antiemetic regimen is cost-effective for the prevention of CINV in patients receiving HEC in multiple SEA countries.

One shot NEPA plus dexamethasone to prevent multiple-day chemotherapy in sarcoma patients.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared and disturbing adverse events of cancer treatment associated with decreased adherence to effective chemotherapy regimens. For high-risk soft tissue sarcoma patients, receiving multiple-day chemotherapy (MD-CT), antiemetic guidelines recommend a combination of an NK1 receptor antagonist (NK1-RA), a 5-HT3 receptor antagonist (5HT3-RA), and dexamethasone on each day of the antineoplastic treatment. NEPA is the first oral fixed-dose combination of a highly selective NK1-RA, netupitant, and second-generation 5HT3-RA, palonosetron. So far, no data has been published in literature about the efficacy of a single dose of NEPA in MD-CT. METHODS: We performed a prospective, non-comparative study to assess the efficacy of one shot of NEPA plus dexamethasone in sarcoma patients receiving MD-CT. The primary efficacy endpoint was a complete response (CR: no emesis, no rescue medication) during the overall phase (0-120 h) in cycle 1. The main secondary endpoints were CR during the overall phase of cycles 2 and 3. RESULTS: The primary endpoint was reached in 88.9% of patients. Cycles 2 and 3 overall CR rates were 88.9% and 82.4%, respectively. The antiemetic regimen was well tolerated. CONCLUSIONS: This pilot study showed the benefit of one shot of NEPA to prevent CINV in sarcoma patients receiving MD-chemotherapy.

Prophylactic use of antiemetics for prevention of opioid-induced nausea and vomiting: a survey about Italian physicians' practice.

PURPOSE: Antiemetics are being used both for the treatment and prophylaxis of opioid-induced nausea and vomiting (OINV) in clinical practice, despite the lack of evidence for the prophylactic benefit. Studies among Japanese physicians demonstrated over 80% prescribe antiemetics, with neuroleptic antipsychotics as the most commonly prescribed drugs. Our objective was to elucidate the current scenario of the prophylactic use of antiemetics for OINV among Italian physicians. METHODS: We conducted a web-based cross-sectional national survey. All the invited participants received an e-mail with an 11-item electronic questionnaire accessible through a direct link. Anonymity was guaranteed. According to the exploratory intent of the survey, we did not predefine any formal statistical hypothesis. Associations between variables were tested by the Pearson chi-square or the Fisher exact test. RESULTS: From January to March 2017, 112 completed the electronic questionnaire (112/256, overall response rate, 43.7%). Nearly half of the participants were oncologists (54; 48.2%). Sixty-one (54.4%) physicians worked in palliative care units. About 45% of the interviewed prescribed prophylactic antiemetics at the beginning of opioid prescription. The most commonly chosen drugs for this purpose were prokinetics such as metoclopramide and domperidone (84%), followed by 5-HT3 antagonists (8%), neuroleptic antipsychotics (6%), and corticosteroids (2%). Ninety-one physicians (81%) declared to prescribe antiemetics at the occurrence of OINV, mainly prokinetics (N = 70; 77%). CONCLUSION: Italian physicians do not commonly prescribe prophylactic antiemetics for OINV. Unlike previously reported data, dopamine antagonists resulted the most commonly prescribed drugs. Prospective clinical trials are necessary to evaluate the real efficacy of this practice.

Ramosetron for the treatment of irritable bowel syndrome with diarrhea: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Ramosetron is a potent and selective serotonin type 3 receptor antagonist. This meta-analysis aimed to analyze the efficacy and safety of ramosetron for irritable bowel syndrome with diarrhea (IBS-D). METHODS: Pubmed, MEDLINE, EMBASE and the Cochrane Library were searched for randomized controlled trials investigating the efficacy and safety of ramosetron for IBS-D. Risk of bias was assessed as described in the Cochrane handbook. A random effects model was used to calculate the effects of ramosetron vs placebo on symptomatic improvements, including relief of overall IBS symptoms, relief of abdominal discomfort/pain, improvement in abnormal bowel habits, and improvement in stool consistency, expressed as pooled relative risks (RRs) with 95% confidence interval (CI). Adverse events data were also summarized with RRs. RESULTS: Four randomized controlled trials involving 1623 participants were included. Compared with placebo, ramosetron could lead to relief of overall IBS symptoms (RR 1.70; 95%CI 1.48, 1.95), relief of abdominal discomfort/pain (RR 1.41; 95%CI, 1.24, 1.59), improvement in abnormal bowel habits (RR 1.72; 95%CI, 1.50, 1.98) and improvement in stool consistency (RR 1.71; 95%CI 1.40, 2.08). Ramosetron could lead to relief of overall IBS symptoms in both male and female patients (RR; 95%CI: 1.94; 1.58, 2.38 and 1.49; 1.25, 1.79). The RR (95%CI) for reported adverse events of ramosetron vs placebo was 1.10 (0.97, 1.26) across all studies. No serious adverse events (e.g., ischemic colitis) were reported. The incidences of hard stool and constipation were higher in ramosetron group compared with placebo group (RR; 95%CI: 4.74; 3.00, 7.51 and 2.53; 1.57, 4.10, respectively). CONCLUSIONS: Ramosetron had beneficial effects to both male and female IBS-D patients. Treatment with ramosetron could cause more hard stool and constipation, without severe adverse events.