Dolasetron 100mg/5ml solution for injection ampoules

BackgroundAlthough serotonin (5-HT3) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy.MethodsWe searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted.ResultsAfter screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall.ConclusionsMost 5-HT3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.Trial registrationThis study was registered at PROSPERO: ( CRD42013003564 ).

Abstract licence: CC BY

Review the clinical evidence of tropisetron or palonosetron, an old- and new-generation serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonist (RA), respectively, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer, and evaluate any difference in efficacy trends. A literature search of the EMBASE and PubMed databases was performed to identify publications of intravenous (IV) tropisetron (generic forms or Navoban®) for the treatment of CINV in patients with various cancers. Data from the pivotal clinical studies evaluating the IV formulation of Aloxi® (palonosetron HCl) were also considered. The effectiveness and safety of each antiemetic was summarized. Sixteen papers for tropisetron fulfilled the inclusion criteria and were extracted for full analysis; publications from six pivotal palonosetron clinical trials were considered. No direct data comparisons could be made between the two drugs, due to the varying definitions of efficacy endpoints between studies. For tropisetron, the rates of no emesis were lower in patients receiving highly emetogenic chemotherapy (HEC) versus moderately emetogenic chemotherapy (MEC). For palonosetron, the rates of complete response (no emesis, no rescue medication) were comparable in the MEC and HEC settings, demonstrating the effectiveness of this agent in patients receiving HEC. Both antiemetics offered some protection against nausea, although lower rates of no nausea were achieved compared with rates of no emesis. Two trials that evaluated the efficacy of palonosetron and tropisetron within the same study reported that palonosetron was more effective than tropisetron in controlling delayed vomiting in the HEC and MEC settings, with significantly higher rates of no emesis observed (P≤0.01). Palonosetron was non-inferior or more efficacious in controlling CINV compared with other older 5-HT3RAs, such as dolasetron, ondansetron, and granisetron. Conversely, tropisetron was no more efficacious than ondansetron or granisetron. Both tropisetron and palonosetron were generally well tolerated, with adverse event profiles consistent with drugs of this class (e.g., headache, constipation, and diarrhea). These data suggest that palonosetron is a highly selective prophylactic agent that may have an improved therapeutic profile compared with tropisetron, and is a feasible treatment option for controlling CINV in patients with cancer.

Abstract licence: CC BY-NC-ND