Effective Antiemetic Agent Research Articles

Low-dose versus standard-dose olanzapine with triple antiemetic therapy for prevention of highly emetogenic chemotherapy-induced nausea and vomiting in patients with solid tumours: a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial

Olanzapine is an effective antiemetic agent but it results in substantial daytime somnolence when administered at the standard dose. Our aim was to compare the efficacy of low-dose versus standard-dose olanzapine after highly emetogenic chemotherapy in patients with solid tumours. This was a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial done in a tertiary care referral centre in India (Tata Memorial Centre, Homi Bhabha National Institute, Mumbai). Patients aged 13-75 years with an Eastern Cooperative Oncology Group performance status of 0-2, who were receiving doxorubicin-cyclophosphamide or high-dose cisplatin for a solid tumour were eligible. Patients were randomly assigned (1:1), with block randomisation (block sizes of 2 or 4) and stratified by sex, age (≥55 or <55 years), and chemotherapy regimen, to receive low-dose (2·5 mg) oral olanzapine or standard-dose (10·0 mg) oral olanzapine daily for 4 days, in combination with a triple antiemetic regimen. Study staff were masked to treatment allocation but patients were aware of their group assignment. The primary endpoint was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea in the overall phase (0-120 hours), assessed in the modified intention-to-treat (mITT) population (ie, all eligible patients who received protocol-specified treatment, excluding those who had eligibility violations and who withdrew consent after randomisation). Daytime somnolence was the safety endpoint of interest. Non-inferiority was shown if the upper limit of the one-sided 95% CI for the difference in the complete control proportions between the treatment groups excluded the non-inferiority margin of 10%. This study is registered with the Clinical Trial Registry India, CTRI/2021/01/030233, is closed to accrual, and this is the final data analysis. Between Feb 9, 2021, and May 30, 2023, 356 patients were pre-screened for eligibility, of whom 275 patients were enrolled and randomly assigned (134 to the 2·5 mg olanzapine group and 141 to the 10·0 mg olanzapine group). 267 patients (132 in the 2·5 mg group and 135 in the 10·0 mg group) were included in the mITT population, of whom 252 (94%) were female, 15 (6%) were male, and 242 (91%) had breast cancer. 59 (45%) of 132 patients in the 2·5 mg olanzapine group had complete control in the overall phase versus 59 (44%) of 135 in the 10·0 mg olanzapine group (difference -1·0% [one-sided 95% CI -100·0 to 9·0]; p=0·87). In the overall phase, there were significantly fewer patients in the 2·5 mg olanzapine group than in the 10·0 mg olanzapine group with daytime somnolence of any grade (86 [65%] of 132 vs 121 [90%] of 135; p<0·0001) and of severe grade on day 1 (six]5%] vs 54 [40%]; p<0·0001). Our findings suggest that olanzapine 2·5 mg is non-inferior to 10·0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care. Progressive Ladies Welfare Association.

Postdischarge nausea and vomiting (PDNV) in children: A review and observational study.

Postdischarge nausea and vomiting (PDNV) cause substantial pediatric morbidity with potentially serious postoperative complications. However, few studies have addressed PDNV prevention and treatment in pediatric patients. Here we searched the literature and processed it in a narrative review describing PDNV incidence, risk factors, and management in pediatric patients.. A successful strategy for reducing PDNV considers both the pharmacokinetics of the antiemetic agents and the principle of multimodal prophylaxis, utilizing agents of different pharmacologic classes. Since many highly effective antiemetic agents have relatively short half-lives, a different approach must be used to prevent PDNV. A combination of oral and intravenous medications with longer half-lives, such as palonosetron or aprepitant, can be used. In addition, we designed a prospective observational study with the primary objective of determining PDNV incidence. In our study group of 205 children, the overall PDNV incidence was 14.6% (30 of 205), including 21 children suffering from nausea and 9 suffering from vomiting.

Clinical interaction between dexamethasone and aprepitant in chemotherapy for lymphoma.

Aprepitant (Apr) is an effective antiemetic agent for chemotherapy-induced nausea and vomiting (CINV). Current CINV guidelines recommend the antiemetic combination of a 5-HT3 receptor antagonist, Apr, and dexamethasone (Dex) for highly emetogenic chemotherapies. Apr inhibits CYP3A4 dose-dependently. Since Dex is metabolized by CYP3A4, the combined use of Apr and Dex inhibits Dex metabolism. CINV guidelines therefore recommend dose-reduction of Dex when Apr and Dex are used together. However, there is some controversy over whether or not Dex should be reduced when administered as an antitumor agent for lymphoid malignancies. We retrospectively compared the antitumor effect of Dex-containing chemotherapy in which Dex is administered at the usual dose without Apr (group A) or administered at a half-dose in combination with Apr (group B). We analyzed 62 consecutive patients with refractory or relapsed CD20 + B cell lymphoma who received R-DHAP therapy in our hospital, including 29 and 33 cases in groups A and B, respectively. The response rate at the end of the first course of R-DHAP was 62.1% and 54.5%, respectively (P = 0.61). As another endpoint to evaluate the effect of Dex, group B tended to show greater suppression of the lymphocyte count (P = 0.05). Therefore, decreasing the dose of Dex by half appeared to be reasonable when combined with Apr.

Nausea and vomiting in end-of-life care: managing this debilitating symptom in the community.

Nausea and vomiting (N&V) are common, debilitating and distressing symptoms for patients with advanced cancer, precipitating admission to hospital for intravenous antiemetic and re-hydration (Glare et al, 2011). The causes of N&V in end-of-life care (EOLC) are multifaceted, with appropriate therapy guided by thorough assessment (Walsh et al, 2017; Watson et al, 2019). Cyclizine and levomepromazine can, depending on aetiology, be cited as effective antiemetic agents for patients with advanced cancer (Ingleton and Larkin, 2015; Watson et al, 2019). Conversely, careful consideration of the use of dexamethasone for the management of N&V in EOLC should be taken, due to known side effects (Ferrel and Paice, 2019). This case study will use a systematic approach to critically appraise the management of N&V, experienced by a community patient receiving EOLC from the district nurses.

Severity of constipation related to palonosetron during first-line chemotherapy: a retrospective observational study.

Palonosetron, a long-acting 5-HT3 receptor antagonist, is an effective antiemetic agent for chemotherapy-induced nausea and vomiting; however, it sometimes causes severe constipation. The aim of the present study was to evaluate the severity of palonosetron-related constipation. We retrospectively analyzed the incidence and severity of constipation after intravenous administration of 0.75-mg palonosetron in 150 chemotherapy-naïve patients who received first-line chemotherapy at Saga University Hospital. Constipation was classified into grades 1-5 according to the Common Terminology Criteria for Adverse Events version 5.0. Multiple logistic regression analysis was performed to identify factors associated with palonosetron-related worsening of constipation to grade 2 or higher. Palonosetron significantly increased the incidence and severity of constipation (incidence: before vs. after palonosetron, 35.4% vs. 74.0%, p < 0.0001, and severity: before vs. after palonosetron, 26.7% and 8.7% in grades 1 and 2, respectively, vs. 46.7%, 23.3%, and 4.0% in grades 1, 2, and 3, respectively, p < 0.0001). Despite the use of laxatives, 4.0% of patients had grade 3 constipation requiring manual evacuation. Combination treatment with aprepitant (odds ratio (OR), 10.9; 95% confidence interval (CI), 1.3-90.0; p = 0.026) and older age (OR, 1.25; 95% CI, 1.01-1.57; p = 0.039) were factors associated with the severity of constipation. Constipation was more severe in patients receiving combination treatment with aprepitant than in those treated with palonosetron alone. Older age was also associated with increased risk of severe palonosetron-related constipation. Identification of risk factors can help target risk-based laxative therapy.

Molecular mechanism of setron-mediated inhibition of full-length 5-HT3A receptor

Serotonin receptor (5-HT3AR) is the most common therapeutic target to manage the nausea and vomiting during cancer therapies and in the treatment of irritable bowel syndrome. Setrons, a class of competitive antagonists, cause functional inhibition of 5-HT3AR in the gastrointestinal tract and brainstem, acting as effective anti-emetic agents. Despite their prevalent use, the molecular mechanisms underlying setron binding and inhibition of 5-HT3AR are not fully understood. Here, we present the structure of granisetron-bound full-length 5-HT3AR solved by single-particle cryo-electron microscopy to 2.92 Å resolution. The reconstruction reveals the orientation of granisetron in the orthosteric site with unambiguous density for interacting sidechains. Molecular dynamics simulations and electrophysiology confirm the granisetron binding orientation and the residues central for ligand recognition. Comparison of granisetron-bound 5-HT3AR with the apo and serotonin-bound structures, reveals key insights into the mechanism underlying 5-HT3AR inhibition.

Incidence of nausea and vomiting in breast cancer patients treated with anthracycline plus cyclophosphamide-based chemotherapy regimens in Italy: NAVY observational study.

Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event with cancer chemotherapy, despite the availability of effective antiemetic agents. This is a prospective observational study of Italian breast cancer patients treated with anthracycline plus cyclophosphamide (AC), assessed CINV incidence, adherence to national antiemetic guidelines (AIOM 2012), and the relationship with CINV outcomes. Patients with breast cancer scheduled to receive their first cycle of an AC-based regimen were enrolled at 12 Italian centers and their clinical data prospectively recorded. CINV incidence was assessed from patient diaries after the first chemotherapy cycle. The relationship between guideline adherence and CINV outcomes was examined using multiple logistic regression. The overall incidence rates of nausea and vomiting among 246 evaluable patients were 63.0 and 25.4%, respectively. Most patients received a 5-HT3-RA agent and dexamethasone for acute phase CINV prophylaxis, whereas a triple combination including aprepitant (NK1-RA), consistent with national guidelines, was used in only 45.5% of cases. In the delayed phase, the guideline adherence was 48.8%, while the overall adherence was 43.5%. After adjusting for confounding factors, adherence to antiemetic prophylaxis guidelines was associated with a significant reduction in the odds of three endpoints, namely any nausea, "significant nausea," and vomiting (OR = 0.49, OR = 0.54, and OR = 0.48, respectively), and a 90% increase in the odds of overall complete protection (OR = 1.90). CINV is still a critical issue in AC-treated patients, despite antiemetic treatment. Non-adherence to antiemetic guidelines may lead to poorer outcomes and indicates the need for strategies to enhance the use of guidelines in clinical practice.

Prophylaxis of postoperative nausea and vomiting with combination of ondansetron and dexametasone in urology: Prophylaxis of postoperative nausea and vomiting

Introduction: Postoperative nausea and vomiting is an unpleasant, distressing and exhausting experience for patients. There are inconsistent findings concerning approach to the management of PONV and disagreement as to whether prophylaxis of PONV should be the standard of care. Antiemetic prophylaxis using the ondansetron (serotonin subtype 3 antagonist), that is primarily used in the therapy of chemotherapy-induced nausea and vomiting, alone results in a relative reduction rate of PONV of about 30%. It is also well known that dexamethasone, a corticosteroid, is an effective antiemetic agent with minimal side effect after single dose administration in prevention of PONV. Aim of this study was to evaluate the prophylactic effect of ondansetron combined with dexamethasone to prevent PONV in patients undergoing urological surgery. Methods: 60 patients scheduled for an elective surgery (nephrectomy) were involved in this study. Group one (n = 30) received dexamethasone at dose of 5 mg iv. after induction in general anesthesia and 4 mg iv. ondansetron 15 min before end of surgery. Group two (n = 30) was control group and they recieved only our standard antiemetic drug (metoclopramide) in case of PONV. The patients were observed for PONV symptoms during 24 hours after surgery. PONV in groups were evaluated by following parameters: incidence and intensity of PONV, frequency of emetic episodes, VAS pain and fatigue, rescue emetics, and stay in hospital. Results: There is statistical difference in occurring emetic episodes during first 8 hours postoperatively with no demographic influence on study results. Conclusion: Prophylactic dose ondansetron 4mg i.v. + dexamethason 5mg i.v. is effective combination that significantly reduces incidence of PONV in patients undergoing urological surgery.

Adherence to national guidelines for antiemesis prophylaxis in patients undergoing chemotherapy for lung cancer

Nausea and vomiting (N/V) during chemotherapy can have profound clinical and economic consequences. Effective antiemetic agents are available for prophylaxis, but barriers may prevent their use. For this population-based study, the authors assessed the rates of antiemetic prophylaxis use, and predictors of such use, among patients who were receiving platinum-based chemotherapy for lung cancer between 2001 and 2007. The authors searched the Texas Cancer Registry-Medicare-linked database for individuals aged >65 years who received platinum-based chemotherapy within 12 months after a first diagnosis of lung cancer from 2001 to 2007; and all patients had continuous Medicare Part A and Part B coverage for the same period. Adherence to recommended regimens for N/V prophylaxis (established by the National Comprehensive Cancer Network) was scored as a binary variable (adherent vs nonadherent) and was calculated as the percentages of treated patients receiving each recommended agent within 1 day of beginning chemotherapy. Logistic regression with stepwise selection was used to examine whether patient characteristics influenced adherence. Of 4566 selected patients, adherence rates for the receipt of serotonin antagonists (eg, ondansetron) with dexamethasone were 60% to 90% regardless of whether the chemotherapy agent was considered moderately or highly emetogenic. The receipt of substance-P antagonists was much less common (<10%) during any period. On multivariate logistic regression modeling, variables that predicted adherence were older age, white race, higher median income, and concurrent radiation therapy. Recommended use of antiemetics for prophylaxis, especially substance-P antagonists, during chemotherapy for lung cancer is suboptimal. Factors that were correlated with adherence suggest socioeconomic barriers in the community.

Evolving Treatment Paradigms for Chemotherapy-Induced Nausea and Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is one of the most debilitating toxicities associated with cancer treatment. Although effective antiemetic agents are available, their use in practice often is suboptimal. The author reviews the pathophysiology of CINV as well as the drug classes and cost considerations that should be incorporated into treatment planning. Several drug classes, including 5-hydroxytryptamine-3 receptor antagonists, neurokinin-1 receptor antagonists, and corticosteroids, are effective, especially when used in combination. Older antiemetic agents, such as prochlorperazine and metoclopramide, as well as olanzapine may provide reasonable alternatives in certain settings. Interventions for CINV should include standard-of-care antiemetics combined with corticosteroids. The cost of using older, less expensive antiemetics may be outweighed by the expenditures to rescue patients after suboptimal prophylaxis, as well as the indirect costs of missed work and lost productivity.

Aprepitant Pharmacokinetics and Assessing the Impact of Aprepitant on Cyclophosphamide Metabolism in Cancer Patients Undergoing Hematopoietic Stem Cell Transplantation

Aprepitant, a neurokinin antagonist, is an effective antiemetic agent in chemotherapy for delayed nausea and vomiting. The study objective was to evaluate the pharmacokinetics of aprepitant and concurrent cyclophosphamide (CY), often a component of hematopoietic stem cell transplant (HSCT) conditioning regimen, in cancer patients undergoing HSCT. Forty subjects were randomized to either aprepitant or placebo in addition to standard antiemetics. Aprepitant or placebo was started 1 hour before the first chemotherapy or radiation dose for HSCT conditioning and administered daily until 4 days after infusion of the hematopoietic cell graft (for a total of 10-12 days). Serial blood samples were collected for aprepitant and CY plus 2 important CY metabolites. The results indicate that aprepitant is well absorbed and does not auto-induce its metabolism. No significant drug interaction was observed with CY or its metabolites. A significant portion of the patients had subtherapeutic aprepitant concentrations; however, chemotherapy-induced nausea and vomiting were effectively managed. No dosage adjustment was necessary, and administration of aprepitant in HSCT at the prescribed dosage of 125 mg orally on day 1 and 80 mg orally on each consecutive day through day +4 after HSCT was well tolerated with no significant changes in CY pharmacokinetic parameters.

Prophylaxis of Postoperative Nausea and Vomiting in Adolescent Patients: A Review with Emphasis on Combination of Fixed-Dose Ondansetron and Transdermal Scopolamine

Postoperative nausea and vomiting (PONV) is a relatively common occurrence (20–30%) that delays discharge and, if persistent, can lead to serious complications. The incidence of PONV is a function of patient characteristics, the type and duration of surgery, the type of anesthesia, and the choice of pre-, intra-, and postoperative pharmacotherapy. There are no completely effective antiemetic agents for this condition, but recommendations for treatment strategies are separately available for pediatric and adult patients. Left unclear is whether adolescents should be guided by the pediatric or the adult recommendations. We review the developmental physiology of the relevant physiological factors (absorption, distribution, metabolism, and elimination). We also review the clinical evidence regarding the safety and efficacy of a fixed-dose combination of ondansetron (4 mg, i.v.) and transdermal scopolamine (1.5 mg).

Antiemetic activity of megestrol acetate in patients receiving chemotherapy

Several trials had independently noted that patients receiving megestrol acetate had less nausea and vomiting, but this antiemetic activity of megestrol acetate has not been reported separately in the literature. Our objective was to evaluate the antiemetic ability of megestrol acetate in patients receiving chemotherapy. Patients receiving chemotherapy were randomly assigned to receive either megestrol acetate 320 mg PO or placebo before the first day of chemotherapy, followed on days 1-4 by megestrol acetate 320 mg PO combined with granisetron 3 mg IV and metoclopramide 20 mg IM or only granisetron 3 mg IV combined with metoclopramide 20 mg IM in a crossover manner during two consecutive cycles. Rates of complete protection against both vomiting and moderate-to-severe nausea was the primary end point. One hundred patients were enrolled in the study. The antiemetic regimen containing megestrol acetate was superior in providing complete protection from nausea and vomiting (45% megestrol acetate regimen vs.17% no megestrol acetate regimen). Complete response of acute phase in both antiemetic regimens was different (85% megestrol acetate regimen vs. 72% no megestrol acetate regimen). Complete response of delayed emesis was also different (49% megestrol acetate regimen vs. 18% no megestrol acetate regimen). Adverse events were mostly mild to moderate. There were no serious drug-related adverse events between the two antiemetic regimens. Megestrol acetate was shown to be an effective antiemetic agent. Megestrol acetate might be a new antiemetic option for chemotherapy.

Fosaprepitant: a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a distressing and common adverse event associated with cancer treatment. Updated antiemetic guidelines were published in 2008 by the National Comprehensive Cancer Network and, in 2006, by the American Society of Clinical Oncology, which have included the use of the new and more effective antiemetic agents 5-hydroxytryptamine-3 (5-HT3) receptor antagonist and neurokinin (NK)-1 receptor antagonist. Aprepitant is a selective NK-1 receptor antagonist approved as part of combination therapy with a corticosteroid and a 5-HT3 receptor antagonist for the prevention of acute and delayed CINV in patients receiving moderately and highly emetogenic chemotherapy. Fosaprepitant (also known as MK-0517 and L-758,298) is a water-soluble phosphoryl prodrug for aprepitant, which, when administered intravenously, is converted to aprepitant within 30 min of intravenous administration via the action of ubiquitous phosphatases. Owing to the rapid conversion of fosaprepitant to the active form (aprepitant), fosaprepitant 115 mg provided the same aprepitant exposure in terms of AUC as aprepitant 12 mg orally, and fosaprepitant is expected to provide a correspondingly similar antiemetic effect as aprepitant. Clinical studies have suggested that fosaprepitant could be appropriate as an intravenous alternative to the aprepitant oral capsule. In a study in healthy subjects, fosaprepitant 115 mg was generally well tolerated at a final drug concentration of 1 mg/ml, and fosaprepitant 115 mg was AUC bioequivalent to aprepitant 125 mg. Fosaprepitant in the dose of 115 mg has been approved by the US FDA, the EU and the Australian authorities on day 1 of a 3-day oral aprepitant regimen, with oral aprepitant administered on days 2 and 3. Fosaprepitant may be a useful parenteral alternative to oral aprepitant. Further study is needed to clarify the utility of fosaprepitant in the prevention of CINV and to clarify optimal dosing regimens that may be appropriate substitutes for oral aprepitant.

Clinical Evaluation of Antiemetic Effects of 5-hydroxytryptamine Receptor type 3 (5HT&lt;sub&gt;3&lt;/sub&gt; Receptor) Antagonists Based on Changes in Eating Condition in Cancer Patients Receiving Chemotherapy

To evaluate the antiemetic effects of 5-HT(3) receptor antagonists, we investigated the relationship between condition of food intake and occurrence of nausea and vomiting. We collected data such as sex, age, disease, combination of steroids and central antiemetic agents, eating condition, and vomiting condition from medical records in 33 hematologic cancer patients receiving chemotherapy; combination with 5-HT(3) receptor antagonists. The conditions of food intake and nausea/vomiting were checked at 4 mealtime points (lunch, supper, breakfast, and next lunch) after chemotherapy, and were recorded as 1, 3, or 5 as each condition score. To calculate eating scores and nausea/vomiting scores, the sum of scores from 4 mealtime points was used. We found a significant negative correlation between eating scores and nausea/ vomiting scores (n=62, p<0.01). At eating points in which combination therapy with steroids and central antiemetic agents was not given, antiemetic effects of granisetron, azasetron and ramosetron were compared and revealed that azasetron was the most effective antiemetic agent. This result is in agreement with our previous study predicting antiemetic effects of 5-HT(3) receptor antagonists based on the receptor occupancy theory. This study suggests that eithes receptor occupancy or eating score is a useful indicator for assessment of the efficacy of 5-HT(3) receptor antagonists.

Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a distressing and common adverse event associated with cancer treatment. Updated anti-emetic guidelines were published in 2007 by the National Comprehensive Cancer Network and in 2006 by the American Society of Clinical Oncology, which have included the use of the new and more effective anti-emetic agents (5-hydroxytryptamine-3 [5-HT3] receptor antagonists and neurokinin-1 [NK-1] receptor antagonists). Aprepitant is a selective NK-1 receptor antagonist approved as part of combination therapy with a corticosteroid and a 5-HT3 receptor antagonist for the prevention of acute and delayed CINV. Fosaprepitant (also known as MK-0517 and L-758,298) is a water-soluble phosphoryl prodrug for aprepitant, which, when administered intravenously, is converted to aprepitant within 30 min after intravenous administration via the action of ubiquitous phosphatases. Because fosaprepitant is rapidly converted to the active form (aprepitant), it is expected to provide the same aprepitant exposure in terms of AUC, and a correspondingly similar anti-emetic effect. Clinical studies have suggested that fosaprepitant could be appropriate as an intravenous alternative to the aprepitant oral capsule. In a study in healthy subjects, fosaprepitant was well tolerated up to 150 mg (1 mg/ml), and fosaprepitant 115 mg was bioequivalent in its AUC to aprepitant 125 mg. Fosaprepitant 115 mg has been submitted for FDA approval as an alternative on day 1 of a 3-day oral aprepitant regimen, with oral aprepitant administered on days 2 and 3. Fosaprepitant may be a useful parenteral alternative to oral aprepitant. Further study is needed to clarify the use of fosaprepitant for the prevention of CINV, and to clarify optimal dosing regimens that may be appropriate substitutes for oral aprepitant.

Prophylaxis of Postoperative Nausea and Vomiting in Patients Scheduled for Breast Surgery

Breast surgery performed under general anaesthesia is associated with a high incidence of postoperative nausea and vomiting (PONV). Between 60% and 80% of patients undergoing mastectomy (with axillary dissection) experience PONV. Pharmacological approaches have been investigated to reduce PONV after breast surgery. Traditional antiemetics (droperidol and metoclopramide) are frequently used for the prevention of PONV during the first 24 hours after anaesthesia. The available non-traditional antiemetics that have been shown to be effective for prophylaxis against PONV are dexamethasone, clonidine, propofol and supplemental oxygen. Antiserotonins (ondansetron, granisetron, tropisetron, dolasetron and ramosetron) are highly effective for preventing PONV for 24 hours postoperatively, compared with traditional antiemetics. Ramosetron is effective for the long-term (up to 48 hours) prevention of PONV. Better results can be obtained by combining antiemetics, because they have different sites of action. Combination antiemetic therapy is often effective for preventing PONV after breast surgery. Combinations of an antiserotonin (granisetron or dolasetron) and droperidol or dexamethasone are more effective than monotherapy with antiserotonins. A non-pharmacological technique is acupuncture at the P6 (Nei-Kuan) point. Overall, these pharmacological and non-pharmacological approaches reduce the incidence of PONV following breast surgery. Most of the published trials indicate improved prophylaxis of PONV following breast surgery by avoiding risk factors, and by using effective antiemetic agents in women scheduled for mastectomy (with axillary dissection). The clinician must weigh the benefits of using pharmacological and non-pharmacological approaches for PONV against the risk of occurrence of adverse events.

Ondansetron Is Similar to Droperidol in Causing QT Prolongation

Data analyses that have been performed since the FDA’s controversial “black box” warning about droperidol in 2001 have strongly challenged the basis for the warning. Although the adverse cardiac events occurred at doses greatly exceeding those used for postoperative nausea and vomiting (PONV), the warning was issued in blanket fashion, and use of droperidol, an inexpensive and highly effective antiemetic and sedation agent, effectively ceased. In a prospective study from France, researchers evaluated the electrocardiographic effects of standardized doses of droperidol and ondansetron in 85 consecutive patients undergoing elective general anesthesia who experienced PONV in the recovery room. At the attending anesthesiologist’s discretion, patients …

A review of dolasetron as management of nausea and vomiting in cancer patients

Objective. To systematically review the literature about the pharmacology, pharmacokinetics, efficacy, dosing, and adverse effects of dolasetron, and to define its role in the management of chemotherapy-and radiation-induced nausea and vomiting. Data Synthesis. A MedLine search was conducted using 5-HT3-receptor antagonists, antiemetics, chemotherapy toxicity, dolasetron, emesis, nausea, and vomiting as search terms. Reference lists and bibliographies of pertinent articles were also identified and reviewed. Both preclinical and clinical literature were reviewed and analyzed. Data Synthesis. Dolasetron is a serotonin type 3 (5-HT3)-receptor antagonist with potent antiemetic effects in the management of nausea and vomiting. Following administration, dolasetron is rapidly converted to hydrodolasetron, which is believed to be responsible for the drug's antiemetic activity. Results of multiple studies have demonstrated the efficacy of this agent in the prevention of chemotherapy-induced emesis, including that induced by cisplatin. As a single agent, dolasetron produces a complete response rate (RR) in 44% to 57% of patients treated with cisplatin (≥70 mg/m2) and in 59% to 80% of patients treated with moderately emetogenic chemotherapy, such as cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy. When combined with dexamethasone, the RRs are increased. Dolasetron is well tolerated, with headache (24%) and diarrhea (12%) the most commonly reported adverse effects. The efficacy and safety of dolasetron are comparable to those observed with other 5-HT3-receptor antagonists. According to four recently published clinical practice guidelines for use of antiemetics, dolasetron is an appropriate first-line option for the prevention of nausea and vomiting due to moderately to highly emetogenic chemotherapy. Further clinical trials will determine the optimal dose and the role of this highly effective antiemetic agent for other purposes, such as treatment of delayed emesis and emesis resulting from radiation therapy and high-dose chemotherapy followed by bone marrow transplantation.

Prochlorperazine versus promethazine for uncomplicated nausea and vomiting in the emergency department: A randomized, double-blind clinical trial

Study Objective: Nausea and vomiting related to gastritis or gastroenteritis are common complaints in the emergency department. The most effective antiemetic agent is yet undetermined. This study was conducted to compare the efficacy of prochlorperazine versus promethazine for uncomplicated nausea and vomiting in the ED. Methods: The study was a randomized, double-blind comparison of prochlorperazine (Compazine) and promethazine (Phenergan) for acute ED treatment of gastritis or gastroenteritis. We studied patients 18 years or older with presumed uncomplicated gastritis or gastroenteritis who presented to 2 academic EDs. Patients were randomly assigned to receive either prochlorperazine, 10 mg intravenously, or promethazine, 25 mg intravenously. Visual analog scale readings of patient comfort were obtained at baseline and at 30- and 60-minute intervals. The primary endpoint was degree of relief at 30 and 60 minutes. Secondary endpoints were time to complete relief, need for further antiemetic medication (treatment failures), and side effects. Statistical analysis was performed using the Mann-Whitney U test for nonparametric analysis and repeated-measures analysis of variance (ANOVA). Results: Eighty-four patients were enrolled in the study; 42 received prochlorperazine and 42 received promethazine. There were no differences in demographics in the 2 groups. At baseline (time 0), there was no difference in symptoms (P =.23). At 30 and 60 minutes after receiving medication, prochlorperazine worked significantly better than promethazine (P =.004 and P <.001 using nonparametric analysis). Using repeated-measures ANOVA, there was a significant difference in symptoms over time for both groups (P <.001) and a significant difference in prochlorperazine versus promethazine (P =.002). Time to complete relief was significantly shorter with prochlorperazine (P =.021). There were significantly fewer treatment failures with prochlorperazine (P =.03, 9.5% versus 31%; difference 21%, 95% confidence interval 5 to 38). There was no difference in incidence of extrapyramidal effects. Prochlorperazine caused significantly fewer complaints of sleepiness (P =.002, 38% versus 71%; difference 33%, 95% confidence interval 13 to 53; P =.002). Conclusion: Prochlorperazine works significantly better than promethazine for relieving symptoms of nausea and vomiting more quickly and completely in ED patients with uncomplicated nausea and vomiting. [Ernst AA, Weiss SJ, Park S, Takakuwa KM, Diercks DB. Prochlorperazine versus promethazine for uncomplicated nausea and vomiting in the emergency department: a randomized, double-blind clinical trial. Ann Emerg Med. August 2000;36:89-94.]