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Amphotericin formulations, indicated for invasive fungal infections (IFIs), vary in effectiveness, safety and costs. In Brazil, only the conventional formulation is provided by the Public Health System. The aim of this study was to perform a cost-effectiveness analysis comparing conventional amphotericin B (CAB), liposomal amphotericin B (LAB) and amphotericin B lipid complex (ABLC). Therefore, a decision tree was developed. The model began with high-risking patients on suspicion or confirmation of IFI. The analysis was conducted under the perspective of the Brazilian Public Health System. Model health states were defined according to medication use and clinical evolution. Clinical efficacy (cure) and transition probabilities were derived from the literature. Resource use was estimated from Brazilian data. Time horizon followed the maximum treatment time determined in the patient information leaflets (3 or 6 weeks). One-way and probabilistic-sensitivity analyses were conducted. The conventional formulation was the most cost-effective. No dominance was observed; however, high incremental cost-effectiveness ratios were obtained for LAB (USD 313 130) and ABLC (USD 1 711 280). Sensitivity analyses demonstrated the robustness of the results. CAB is the most cost-effective treatment, followed by LAB and ABLC. Although CAB presents critical safety aspects, the high acquisition costs of the other formulations prevent their large-scale use in Brazil., (© 2018 Blackwell Verlag GmbH.)

Objectives: Despite its broad spectrum, conventional amphotericin B (AB) is associated with serious adverse events. Lipid-based formulations may offer safer options. We aimed to synthesize the evidence of efficacy and safety of AB formulations., Methods: We performed a systematic review and network meta-analysis (NMA) to compare all available formulations: conventional AB; lipid complex or ABLC; colloidal dispersion or ABCD; liposomal or LAB; AB in Intralipid. Randomized controlled trials were searched in four databases. Cure, fever, chills, nephrotoxicity, death and drug discontinuation were assessed. NMA was based on Bayesian methods accounting for direct and indirect comparisons. Probability ranks estimating the best formulation were built for each outcome. The relative benefit-risk of formulations was assessed with stochastic multicriteria acceptability analyses (SMAA)., Key Findings: We identified 25 trials (n = 2996). No significant differences among drugs were observed for cure or death. All lipid-based formulations were safer than conventional AB for nephrotoxicity. AB-Intralipid was more tolerable than conventional AB and caused less chills than ABCD. AB-Intralipid was the best therapy (>60%) regarding nephrotoxicity, fever, chills and discontinuation. The scenario from SMAA favoured AB-Intralipid (81% acceptability). Conventional AB was secondary to all lipid-based formulations., Conclusions: Amphotericin B-Intralipid was identified as safer, cost-saving treatment in comparison with other formulations., (© 2017 Royal Pharmaceutical Society.)

What Is Known and Objective: Antifungal prophylaxis is an option to reduce the incidence of invasive fungal infection (IFI) in haematological patients. To date, no network meta-analysis (NMA) of high-quality evidence (double-blind randomized controlled trials) has been performed on this subject. This systematic review and NMA aimed to evaluate the safety and efficacy of different antifungal agents used for prophylaxis of IFI in patients with haematological disorders., Methods: A systematic review was performed according to PRISMA and Cochrane recommendations. The search for articles was conducted on PubMed, Scopus and the Web of Science. We searched for double-blind randomized clinical trials comparing antifungal agents for IFI prophylaxis head-to-head vs placebo in patients with any blood cancer. Network meta-analyses were conducted using Addis version 1.16.6. Evaluation of the quality of included RCTs was also performed., Results: Twenty-five trials were included in the qualitative and quantitative analyses. Posaconazole stood out as the best IFI prophylaxis option and for avoiding IFI-related mortality. For the incidence of candidiasis outcome, the azoles were superior to placebo. Voriconazole and posaconazole were, respectively, the first and second best options. For the incidence of aspergillosis outcome, the probability rank suggested that voriconazole followed by liposomal amphotericin B is, possibly, the best choice. The quality of studies was considered good, with a mean Jadad score of 4.0., What Is New and Conclusion: The results of our work support prophylaxis with antifungal agents as reducing the risk of IFI in haematological patients. Overall, the second-generation azoles were found to be the best option for preventing IFI in this population., (© 2017 John Wiley & Sons Ltd.)

Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional and lipid-based (liposomal, lipid complex, colloidal dispersion and Intralipid ® infusion). The aim of our study was to determine the efficacy and safety of conventional amphotericin B vs its lipid-based formulations. A systematic review followed by pairwise meta-analysis was performed, including randomised controlled trials (RCTs) that evaluated the use of lipid-based amphotericin B in patients with any degree of immunosuppression and susceptibility to invasive fungal infection. An electronic search was conducted using PubMed, Scopus, Web of Science and Scielo databases. Extracted outcomes were related to efficacy (cure) and safety (incidence of adverse events). Results were evaluated and meta-analyses were performed. Twenty-three RCTs were identified (n=2677 participants) for meta-analysis. No significant differences between conventional amphotericin B and any of the five formulations evaluated were observed, with regard to the efficacy analysis. With respect to the adverse events of nephrotoxicity, fever, chills and vomiting, all lipid formulations presented better profiles than the conventional formulation. The present systematic review and meta-analysis showed that conventional amphotericin B presents the same efficacy profile as lipid-based formulations, although the latter were associated with a safer profile., (© 2016 Blackwell Verlag GmbH.)