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Background: The effectiveness of a dexamethasone-sparing strategy in the treatment of breast cancer with anthracycline-cyclophosphamide therapy when combined with first-generation 5-HT3 receptor antagonists (RAs) and neurokinin-1 RAs is unclear. This is attributable to a lack of evidence from direct comparison of multiple doses of DEX to a single dose of DEX in combination with first-generation 5-HT3 RAs in anthracycline-cyclophosphamide therapy. Our goal was to clarify the impact of dexamethasone-sparing strategies that involve both first-generation 5-HT3 RAs and palonosetron when combined with neurokinin-1 RAs, using a network meta-analysis. Materials and methods: A literature search was conducted on PubMed/Medline for articles published up to July 4, 2023. We included randomized controlled trials which assessed the efficacy of antiemetic regimens which combined 5-HT3 RAs and dexamethasone, with or without neurokinin-1 RAs, for the initial dose in anthracycline-cyclophosphamide therapy for patients with breast cancer. The primary outcome was the proportion of patients achieving a complete response during the delayed phase (CR-DP). Results: The difference in the proportion of patients achieving CR-DP between multiple and single doses of dexamethasone was 0.1% (95%CI: -12.4 to 12.5) with palonosetron and neurokinin-1 RAs, compared to 5.3% (95%CI: -13.4 to 23.0) with a single dose of a first-generation 5-HT3 receptor antagonist. Additionally, the difference was 12.7% (95% CI: -2.8 to 28.2) when comparing palonosetron against first-generation 5-HT3 RAs in combination with a single dose of dexamethasone and neurokinin-1 RAs. Conclusion: Palonosetron is recommended rather than a single dose of first-generation 5-HT3 RAs in dexamethasone-sparing strategies for anthracycline-cyclophosphamide therapy.

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PURPOSE: This review is an update of the MASCC/ESMO 2015 recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. METHODS: A systematic literature search was conducted using PubMed from June 1, 2015, through February 1, 2023. RESULTS: We identified 56 references (16 were duplications or invalid), leaving 40 manuscripts for this search. The panel classified level I evidence (three manuscripts) and level II evidence (14 manuscripts). High-dose chemotherapy and stem cell transplant were discussed in four of these manuscripts, and multiple-day chemotherapy treatment in 15. Some manuscripts covered both topics. Additionally, a search for breakthrough nausea and vomiting resulted in 12 "hits." No new relevant studies were identified. CONCLUSIONS: The recommendations for patients receiving high-dose chemotherapy with stem cell transplants and patients undergoing multiple-day cisplatin were updated. For patients receiving high-dose chemotherapy for stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant is recommended. Olanzapine could be considered part of the antiemetic regimen. Patients receiving multiple-day cisplatin should receive a 5-HT3 receptor antagonist plus dexamethasone plus aprepitant plus olanzapine. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests using a single dose of olanzapine daily for 3 days.

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BACKGROUND: Consensus guidelines recommend the use of multiple antiemetics as prophylaxis in patients at high risk of postoperative nausea and vomiting (PONV), but the evidence regarding combining acupuncture and antiemetics as a multimodal approach was of very low quality. OBJECTIVE: This study aimed to assess the effect of combinations of acupuncture with ondansetron versus ondansetron alone for PONV prophylaxis in women at a high risk. METHODS: This parallel, randomised controlled trial was conducted in a tertiary hospital in China. Patients who had three or four PONV risk factors on the Apfel simplified risk score, undergoing elective laparoscopic gynaecological surgery for benign pathology, were recruited. Patients in the combination group received two sessions of acupuncture treatment and 8 mg intravenous ondansetron, whereas those in the ondansetron group received ondansetron alone. The primary outcome was the incidence of PONV within 24 h postoperatively. Secondary outcomes included the incidence of postoperative nausea, postoperative vomiting, adverse events etc. RESULTS: Between January and July 2021, a total of 212 women were recruited, 91 patients in the combination group and 93 patients in the ondansetron group were included in the modified intention-to-treat analysis. In the first 24 h postoperatively, 44.0% of the patients in the combination group and 60.2% of the patients in the ondansetron group experienced nausea, vomiting, or both (difference, -16.3% [95% CI, -30.5 to -2.0]; risk ratio, 0.73 [95% CI, 0.55-0.97]; p = 0.03). However, the results of the secondary outcomes showed that compared to ondansetron alone, acupuncture together with ondansetron was only effective in reducing nausea but did not have a significant impact on vomiting. The incidence of adverse events was similar between the groups. CONCLUSION: Acupuncture combined with ondansetron as a multimodal prophylaxis approach is more effective than ondansetron alone in preventing postoperative nausea in high-risk patients.

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BACKGROUND: Postoperative nausea and vomiting (PONV) commonly occurs after spinal anesthesia; however, its incidence rate and predictors have been scarcely studied. Therefore, we aimed to investigate its incidence rate and potential predictors. METHODS: The electronic medical records of 6,610 consecutive patients undergoing orthopedic surgery under spinal anesthesia were reviewed between January 2016 and December 2020. The primary outcome was PONV incidence within 24 h after spinal anesthesia. Along with its incidence rate, we investigated its predictors using multivariable logistic regression analysis. RESULTS: Among the 5,691 patients included in the analysis, 1,298 (22.8%) experienced PONV within 24 h after spinal anesthesia. Female sex (odds ratio [OR]: 3.23, 95% CI [2.72, 3.83], P < 0.001), nonsmoker (OR: 2.12, 95% CI [1.46, 3.07], P < 0.001), history of PONV (OR: 1.52, 95% CI [1.26, 1.82], P < 0.001), prophylactic 5-hydroxytryptamine receptor antagonist use (OR: 0.35, 95% CI [0.24, 0.50], P < 0.001), prophylactic steroid use (OR: 0.53, 95% CI [0.44, 0.62], P < 0.001), baseline heart rate ≥ 60 beats/min (OR: 1.38, 95% CI [1.10, 1.72], P = 0.005), and postoperative opioid use (OR: 2.57, 95% CI [1.80, 3.67], P < 0.001), were significant predictors of the primary outcome. CONCLUSIONS: Our study showed the common incidence of PONV after spinal anesthesia and its significant predictors. A better understanding of its predictors may provide important information for its management.

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Background: In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was designed to assess the efficacy and safety of granisetron in patients with sepsis. Methods: Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome. Results: The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49-1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups. Conclusion: Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration.

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The frequency and severity of nausea and/or vomiting in patients receiving anticancer drugs are influenced by numerous factors, e.g., by the specific therapeutic agent, the dosage, the schedule and the form of administration. They are also influenced by individual factors of the patients, e.g., young age, female gender, previous cancer treatment, low or no alcohol consumption, morning sickness, travel sickness and states of anxiety. The emetogenicity of parenteral and oral medications is classified into high, moderate and minimal. For prophylaxis of highly emetogenic chemotherapy (HEC), neurokinin­1 receptor antagonists (NK1-RA), 5­hydroxytryptamine­3 receptor antagonists (5-HT3-RA), dexamethasone (DEX) and olanzapine (OLANZ) are used in combination. For moderate emetogenicity DEX and 5­HT3-RA are used together for prophylaxis of acute emesis and for low emetogenicity a monotherapy with 5­HT3-RA, DEX or metoclopramide is used. For minimal emetogenicity routine prophylaxis is not necessary. Standards are also prescribed for delayed emesis and oral anticancer medications. Guideline-conform prophylaxis is an indispensable component of medical oncological treatment.

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BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a troublesome side-effect of chemotherapy in pediatric patients undergoing osteosarcoma treatment. In this context, the role of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists needs to be explored. OBJECTIVES: To evaluate the superiority of single-dose palonosetron over granisetron in pediatric patients undergoing highly emetogenic chemotherapy (HEC) for osteosarcoma. MATERIAL AND METHODS: In this double-blind, randomized study, pediatric patients were assessed in terms of acute nausea and vomiting following HEC for osteosarcoma. These children were assigned to group 1 (palonosetron) and group 2 (granisetron) without any other antiemetic prophylaxis. The primary outcome variable was the children's segment with a complete response (CR) during the acute phase of the 1st on-study chemotherapy cycle. The risk factors associated with the emesis were analyzed. The patients were followed up for the first 24 h after chemotherapy. RESULTS: A total number of 200 children were evaluated in terms of the response, and other factors that might alter the response were assessed in the 2 groups. These 200 children underwent 604 blocks of chemotherapy. Complete responses were documented in 83% and 72% of children receiving palonosetron and granisetron, respectively, during the acute phase. Only dexamethasone, used as a rescue medication, was found to be a significant risk factor that predisposed to the response (p < 0.05). CONCLUSIONS: Single-dose palonosetron is an effective alternative to granisetron for preventing CINV in children receiving HEC for osteosarcoma.

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CONTEXT: No clinical trials have examined the effect of netupitant/palonosetron (NEPA) on chronic nausea in patients with cancer. OBJECTIVES: In this pilot randomized trial, we assessed the efficacy of NEPA and placebo on chronic nausea. METHODS: This double-blind, parallel, randomized trial enrolled patients with cancer and chronic nausea for at least 1 month, intensity ≥4/10 and not on moderately or highly emetogenic systemic therapies. Patients started with a placebo run-in period from days 1 to 5; those without a placebo response proceeded to the double-blinded phase between days 6 to 15 (NEPA: placebo 2:1 ratio). The primary outcome was within-group change in average nausea over the 24 hours on a 0-10 numeric rating scale between day 5 and 15. RESULTS: Among the 53 enrolled patients, 46 proceeded to placebo run-in and 33 had blinded treatment (22 NEPA and 11 placebo). We observed a statistically significant within-group improvement in nausea numeric rating scale between day 5 and 15 in the NEPA group (mean change, -2.0; 95% CI, -3.1 to -0.8) and the placebo group (mean change, -2.3; 95% CI, -3.9 to -0.7). A complete response was achieved in 8 (38%) patients in the NEPA group and 2 (20%) in the placebo group by day 15. No grade 3-4 toxicities were attributed to NEPA. There were no statistically significant between-group differences for the primary/secondary outcomes. CONCLUSIONS: NEPA and placebo were associated with similar magnitude of within-group improvement in chronic nausea without significant between-group differences (Clinicaltrials.gov NCT03040726).

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OBJECTIVE: Perioperative shivering (POS) is a common complication in patients undergoing spinal anaesthesia. The present study investigated the efficacy of 5-HT3 receptor antagonists in preventing POS following spinal anaesthesia. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Pubmed, Embase, the Web of Science and Cochrane Library were searched from database establishment on 31 July 2019. ELIGIBILITY CRITERIA: Randomised controlled trials that reported the effects of 5-HT3 receptor antagonists in the prevention of POS in patients after spinal anaesthesia. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data. The primary outcome of the present study was the incidence of POS. The risk of bias for the included studies was assessed according to the Cochrane Handbook. The quality of primary outcome was evaluated by Grading of Recommendations Assessment, Development and Evaluation. Trial sequential analysis for the primary outcome was performed to reduce the type 1 error caused by repeated meta-analysis and the required information size was calculated. RESULTS: A total of 13 randomised controlled trials consisting of 1139 patients were included. The overall incidence of POS was significantly lower in the 5-HT3 receptor antagonists group (risk ratio 0.31; 95% CI 0.26 to 0.38; p<0.01; I2=0%). Subgroup analysis for different types of 5-HT3 receptor antagonists and timing of administration produced similar results. Also, patients had a lower incidence of postoperative nausea and vomiting after administrating 5-HT3 receptor antagonists. No statistically significant differences in drug-related adverse effects were observed. Grading of Recommendations Assessment, Development and Evaluation revealed a high level of evidence. The cumulative z-curve crossed the trial sequential monitoring boundary. CONCLUSIONS: The present study revealed that prophylactic 5-HT3 receptor antagonists were an effective measure for reducing the incidence of POS in patients after spinal anaesthesia. However, further studies investigating the different types of surgeries are required. PROSPERO REGISTRATION NUMBER: CRD42019148191.

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BACKGROUND: Dexamethasone has many desirable pharmacologic properties for perioperative use. Its antiemetic potential has been a focus of many recent trials. METHODS: Trials comparing dexamethasone to 5-HT3-receptor antagonists (5HT3-RA) for 24 h postoperative vomiting incidences published till August 2017 were searched in the medical database. Comparisons for antiemetic efficiency variables (vomiting incidence, nausea incidence, rescue antiemetic need, and patients with complete response) during early (until 6 h) and late postoperative phase were made. Comparative analgesic requirements were also evaluated. RESULTS: Twenty randomized controlled double-blinded trials were included in the final analysis. Twenty-four-hour vomiting incidence was similar (Fixed-effects, P = 0.86, I2 = 2.94%). Trial sequential analysis (TSA) confirmed non-inferiority of dexamethasone for 24-h vomiting incidence. (α = 5%, ß = 20%, δ = 10%) with "information size" being 1619 (required > 573). Equivalence was also verified from early and delayed nausea rate as well using TSA. Pooled results did not demonstrate superiority/inferiority of 5-HT3-RAs over dexamethasone in all other antiemetic efficacy variables (early and delayed). Heterogeneity was found to be low in all of the comparisons. Linear-positive dose-response curve for dexamethasone 24-h vomiting and nausea incidence was seen (correlation coefficient being 0.21 and 0.28, respectively). Dexamethasone reduced the analgesic need (MH-odds of 0.64 (95% CI being 0.44 to 0.93) P = 0.02, I2 = 0)). Possibility of publication bias could not be ruled out (Egger's test, X-intercept = 1.41, P = 0.04). CONCLUSIONS: Dexamethasone demonstrates equal antiemetic efficacy compared to 5-HT3 receptor antagonists. The agents perform equally well both in early postoperative phase and up to 24 h after surgery. Use of dexamethasone replacing 5-HT3 RAs offers an additional advantage of lowering the opioid requirements during the perioperative period.

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Haloperidol is an antipsychotic with well-known antiemetic potential. It is underutilized for postoperative nausea vomiting due to reported corrected QT interval (QTc) prolongation. This meta-analysis evaluates its safety and efficacy as an antiemetic in the perioperative period. Trials comparing haloperidol to 5-HT3 -receptor antagonists (5-HT3 -RA) for 24 postoperative vomiting incidences published up to May 2017 were searched in the medical database. Comparisons were made for antiemetic efficiency variables (vomiting incidence, rescue antiemetic need, and patients with complete response) during early (until 6 hours) and late postoperative phases. Eight randomized controlled double-blinded trials were included in the final analysis. Twenty-four-hour vomiting incidence was similar in groups (fixed effects, P = 0.52, I2 = 0%). Trial-sequential analysis confirmed noninferiority of haloperidol over 5-HT3 -RAs (α = 5%, ß = 20%, δ = 10%), with "information size" being 859 (required > 812). Pooled results did not demonstrate superiority/inferiority of 5-HT3 -RAs over haloperidol in all other antiemetic efficacy variables (early and delayed). Negligible heterogeneity was found in all the comparisons made. Pooled Mantel Haenszel odds ratio for QTc prolongation was equivalent in both groups (fixed effects, P = 0.23, I2 = 0%). The mean dose of haloperidol used was 1.34 mg, and no trial reported extrapyramidal side effects. Trial-sequential analysis showed statistical equivalence (α = 5%, ß = 20%, δ = 10%), with information size being 745 (required > 591). Publication bias was unlikely (Egger test, X-intercept = 2.07, P = 0.10). We conclude that haloperidol is equivalent to the well-established 5-HT3 -RAs in preventing vomiting during the first day after surgery. The incidence of QTc prolongation with haloperidol is statistically equivalent to 5-HT3 -RAs and thus should not be the factor that discourages its use for treatment/prophylaxis of postoperative nausea vomiting.

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Fixed drug eruption (FDE) is a unique type of cutaneous drug reaction that typically recurs in the identical locations on re-exposure to the attributed drug. FDE is characterized by the appearance of a single or multiple sharply demarcated violaceous erythematous plaques which heal with residual hyperpigmentation. A 27-year-old woman presented with multiple dark patches over her eyelids, mouth, lips, and shoulders of 1 week's duration. These lesions followed multiple erythematous plaques over the same areas which appeared within 4 hours of the intake of an ondansetron tablet, 12 days previously. The case was diagnosed as post-inflammatory hyperpigmentation following ondansetron-induced FDE. There was an identical episode 1 year earlier due to the intake of the same drug. The causality assessment pointed toward a probable/likely association as per the Naranjo algorithm and the WHO-UMC scale. There have been only a few cases of FDE due to ondansetron in the reported literature.

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Drugs that prolong the electrocardiographic QT interval increase the risk of ventricular arrhythmias, particularly torsades de pointes. Ondansetron, a 5-hydroxytryptamine type 3 receptor antagonist antiemetic, is one such drug. We present the cases of 2 patients who were given intravenous ondansetron and subsequently developed torsades de pointes. Both had normal QT intervals at baseline but were discovered to have risk factors that predisposed them to drug-induced QT prolongation and ventricular arrhythmias. We briefly review the mechanisms for torsades de pointes caused by QT-prolonging medications, describe characteristics that increase patients' susceptibility to drug-induced QT prolongation, and call attention to the risk of ventricular arrhythmias in patients who are given ondansetron.

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INTRODUCTION: Chemotherapy Induced Nausea and Vomiting (CINV) is the most distressing side effect of cancer chemotherapy. It can seriously produce an impact on patient's quality of life. Prevention of CINV is far more effective than treatment of an established CINV. If the patient receives an optimal antiemetic regimen during the initial course of chemotherapy, the likelihood of developing emesis is greatly reduced. Although, all first generation 5HT3 antagonists demonstrate reasonable efficacy in preventing acute CINV, delayed CINV still remains a problem. AIM: To compare the effectiveness and safety of palonosetron versus ondansetron as an antiemetic agent in patients receiving cancer chemotherapy. MATERIALS AND METHODS: A prospective observational study was conducted in 106 patients in each treatment arm. Study duration was 12 months from January 2013 to January 2014. Consecutive patients diagnosed with cancer satisfying inclusion criteria, who were about to receive moderately or highly emetogenic chemotherapy were enrolled into the study after getting informed written consent. Each patient received either Intravenous (IV) palonosetron 0.25 mg or ondansetron 8 mg half an hour before chemotherapy as antiemetic. Patients were followed up for a period of five days following chemotherapy. Number of episodes, severity of vomiting and nausea and antiemetic rescue given if any were recorded. The data were graded using NCI-CTCAE (VERSION 3.0). Proportion of patients with nausea and vomiting during acute (0-24 hours), delayed (24-120 hours) and overall period (0-120 hours) in both the study groups were compared. Outcome was assessed in terms of symptom control and response. Data were analysed using SPSS-16.0 statistical software (IBM). Chi-square test was used to compare the difference in clinical response. RESULTS: Complete response during acute phase in ondansetron group was 80.2%, while for palonosetron it was 89.6%. During delayed phase, ondansetron and palonosetron produced complete response in 70.8% and 86.8% respectively. A total of 65.1% and 82.1% of subjects experienced complete response during the overall period in the ondansetron and palonosetron groups respectively. The difference in the response to antiemetic prophylaxis was statistically significant between the two groups for delayed (p-value = 0.006) and overall phase (p-value = 0.008). CONCLUSION: Palonosetron is clinically more efficacious than ondansetron in controlling CINV especially in delayed phase and overall period of emesis.

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Background Two pivotal Phase III trials compared the efficacy of palonosetron, ondansetron and granisetron, combined with dexamethasone, for the prevention of nausea and vomiting following highly emetogenic chemotherapy. However, an economic evaluation of these three regimens in the real-world setting of Chinese adult patients has not been determined. Objectives To estimate, from the perspective of the Chinese healthcare system, which of these frequently used strategies consisting of 0.25 mg palonosetron (0.25P), 16 mg ondansetron (Onda), and 3 mg granisetron (Gran), is the most cost-effective option in patients following highly emetogenic chemotherapy. Methods A Markov decision-analytic model was developed. The health and economic outcomes of the three strategies; 0.25P, Onda, and Gran were investigated. The clinical and utility data were taken from published studies. The cost data were calculated according to current local Chinese practices. Sensitivity analyses were performed to determine the impact of uncertainty regarding the results. Results The base-case analysis showed that the 0.25P strategy yielded maximum health benefits compared with the other two strategies. However, the probabilistic sensitivity analysis demonstrated that the Gran strategy was the most cost-effective approach when the willingness-to-pay threshold was not more than US$22,515/quality-adjusted life year. Moreover, palonosetron is not cost-effective in preventing 'overall' nausea and vomiting following highly emetogenic chemotherapy in Chinese patients. Conclusions Our analysis suggests that, compared with palonosetron and ondansetron, 3 mg granisetron may be a cost-effective treatment option in the current Chinese healthcare setting.

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The aim of this meta-analysis was to evaluate the preventive efficacy and safety of 5-HT3 receptor antagonists (5-HT3 RAs) on perioperative shivering. Relevant databases were searched to identify eligible randomized, controlled trials through January 2016. Primary outcome was the incidence of perioperative shivering, and secondary outcomes were the incidence of safety-related outcomes including postoperative nausea and vomiting (PONV), bradycardia, and hypotension. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous data. Trial sequential analysis was performed to assess the risk of random errors and calculate the required information size. Sixteen studies with a total of 1126 patients were included in the meta-analysis. Compared with the control group, 5-HT3 RAs administered intravenously could statistically significantly reduce the incidence of perioperative shivering (RR, 0.44; 95%CI, 0.35 to 0.56; P < .00001; heterogeneity: I2 = 30%) as well as PONV (RR, 0.52; 95%CI, 0.28 to 0.97; P = .04; heterogeneity: I2 = 0%). However, they did not show superiority in lowering the rate of bradycardia (RR, 0.75; 95%CI, 0.38 to 1.49; P = 0.42; heterogeneity: I2 = 0%) or hypotension (RR, 0.79; 95%CI, 0.44 to 1.43; P = .44; heterogeneity: I2 = 24%). Trial sequential analysis of primary outcome showed that the required information size was 2634 patients and that the trial sequential monitoring boundary was crossed. Thus, more high-quality randomized, controlled trials with larger sample sizes are still required to draw a definite conclusion about the preventive efficacy of 5-HT3 RAs on perioperative shivering prevention in the future.

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PURPOSE: An update of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy published after the last MASCC/ESMO antiemetic consensus conference in 2009 has been carried out. METHODS: A systematic literature search using PubMed from January 1, 2009 to January 6, 2015 with a restriction to papers in English was conducted. RESULTS: Overall, two randomized phase II and seven randomized phase III studies plus the results of three subgroup analysis of large phase III trials and those of a pilot study have been included. CONCLUSIONS: In carboplatin-treated patients, a moderate benefit from adding an NK1 receptor antagonist to dexamethasone and a 5-HT3 receptor antagonist has been shown. However, in oxaliplatin-treated patients, contrasting results about the role of NK1 receptor antagonists have been obtained. At present, it is not possible to suggest a specific 5-HT3 receptor antagonist to use for the prevention of acute emesis in these patients. No routine prophylaxis for delayed emesis is recommended but in patients receiving moderately emetogenic chemotherapy with known potential for delayed emesis (e.g., oxaliplatin, doxorubicin, cyclophosphamide) the use of dexamethasone for days 2-3 can be considered.

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OBJECTIVES: Patients can benefit from the coadministration of several medications because of the shorter infusion time and more rapid administration. The use of extemporaneously prepared admixtures of dexamethasone sodium phosphate (DSP) and 5-HT3 receptor antagonists (5-HT3RAs) must be supported by sufficient documentation of their compatibility. The objective of this study was to comprehensively investigate the compatibility of DSP with 5-HT3RAs in infusion solutions. METHODS: Admixtures of DSP with six different 5-HT3RAs (ondansetron hydrochloride, tropisetron hydrochloride, dolasetron mesylate, azasetron hydrochloride, palonosetron hydrochloride and ramosetron hydrochloride) were prepared in non-polyvinyl chloride (non-PVC) infusion bags filled with 5% glucose or 0.9% NaCl. Bags were stored at ambient temperature (25±2°C) without protection from light. Samples were taken immediately after preparation (0 hour) and at predetermined intervals (12, 24 and 48 hours after preparation). Particulate matter of admixtures was inspected visually and particles were counted with a particle counter. The pH of each sample was also determined. Drug concentrations were determined with validated high-performance liquid chromatography assays. RESULTS: No visible haze or particulate formation, colour change or gas evolution and no notable changes in pH were observed, and particulate matter was acceptable up to 48 hours. All preparations maintained more than 90.0% of the initial concentration over the study period. CONCLUSIONS: All the admixtures of DSP and the 5-HT3RAs studied were compatible and stable for at least 48 hours in a 5% glucose injection or a 0.9% NaCl injection stored in non-PVC infusion bags under ambient conditions.