Drug interactions and adverse events associated with antimycotic drugs used for invasive aspergillosis in hematopoietic SCT

Abstract

The aim of this study was to assess the frequency of potential drug-drug interactions (pDDIs) and adverse drug events (ADEs) associated with antimycotics in hospitalized patients with hematopoietic SCT (HSCT). Of the 120 HSCT recipients evaluated, 36 received antimycotics. A total of 124 ADEs were recorded in 32 of the 36 patients treated, with 54 ADEs being possibly and 9 probably related to antimycotics. Of the treatments with amphotericin B, 93% were associated with one or more possible and 36% with probable ADEs. The corresponding figures for lipid-based amphotericin B were 100% and 7%, for voriconazole 68% and 11% and for caspofungin 70% and 0%. A total of 57 potentially severe DDIs associated with antimycotics were detected in 31 of the 36 patients. Of these, 14 DDIs were a possible cause of an ADE and 5 (4 times a combination of voriconazole with CYA and once a combination of CYA with conventional amphotericin B) were probably related. Although the prevalence of pDDIs and ADEs is high in HSCT patients, ADEs related with a high probability to treatment with antimycotics are rare. Regarding the high prevalence of pDDIs, our findings underscore the importance of close monitoring of laboratory and clinical parameters, as well as dose adjustment for critical drugs, in patients with HSCT.

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

“…26 Lipidbased formulations, such as AmBisome ® , AmhocilH ® , and Abelcet ® , have been developed and, despite improvements in the therapeutic index of these drugs, their uses still remain limited, mainly due to the high cost. 9 In this context, this study aims to use an in vivo model to validate a preparation based on engineered nanoparticles carrying AmpB, using BALB/c mice challenged with L. amazonensis.…”

“…8 Despite the improvement in the therapeutic index for its formulations, its use still remains limited due to the high cost. 9 Therefore, the development of other delivery systems by incorporating effective drugs to treat leishmaniasis, and aimed at reducing their side effects, as well as presenting an accessible cost, could be considered desirable. 10 Delivery systems using nanospheres, liposomes, or microspheres could result in a higher concentration and a slower distribution of drugs in organs, such as the spleen, liver, and kidneys.…”

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

“…This may explain, in part, the plethora of drug interactions between azoles and several other groups of drugs, many of which are clinically relevant to the HSCT recipient. 38 Fluconazole. Fluconazole is a triazole antifungal, with activity against Cryptococcus and many species of Candida, often with reduced activity against Candida glabrata and none against Candida krusei.…”

Drug interactions of anti-microbial agents used in hematopoietic stem cell transplantation

“…In this type of therapy, the receptor's marrow aplasia is first performed and then, previously treated hematopoietic tissue cells or those from a compatible donor, are intravenously infused to reestablish hematopoiesis (5) . Exposure of patients to complex therapeutic regimes consisting of a narrow therapeutic index, toxicity in various potentially interactive organ and antimicrobial systems, association with pharmacokinetics and pharmacodynamic variability, are some of the factors that increase the risk of DI in individuals undergoing HSCT (6)(7) .…”