Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients

Andes, David R.; Azie, Nkechi; Yang, Hongbo; Harrington, Rachel; Kelley, Caroline; Tan, Ruo-Ding; Wu, Eric Q.; Franks, Billy; Kristy, Rita M.; Lee, Edward; Khandelwal, Nikhil; Spalding, James

doi:10.1128/aac.00054-16

Cited by 49 publications

(27 citation statements)

References 25 publications

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“…In addition, intra‐patient variability in tacrolimus exposure is associated with an increased risk of acute rejection . In a recent retrospective database analysis of patients from 150 US hospitals between 2005 and 2013, tacrolimus was identified as one of the top 25 drugs for which interactions with both voriconazole and itraconazole were reported in hospitalized patients …”

Section: Introductionmentioning

confidence: 99%

“…26 In a recent retrospective database analysis of patients from 150 US hospitals between 2005 and 2013, tacrolimus was identified as one of the top 25 drugs for which interactions with both voriconazole and itraconazole were reported in hospitalized patients. 27 In this article, we review the inhibitory potential of CYP3A4 activity by the triazoles used to treat IA, as illustrated by their effects on the pharmacokinetics of midazolam, a pure CYP3A4 substrate. We then review the interaction profiles of these triazoles with cyclosporine, tacrolimus, and sirolimus as models for immunosuppressant drugs metabolized by CYP3A4 for which interactions with triazole antifungal agents have been best characterized.…”

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confidence: 99%

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Drug‐drug interactions between triazole antifungal agents used to treat invasive aspergillosis and immunosuppressants metabolized by cytochrome P450 3A4

Groll

Townsend

Desai

et al. 2017

Transplant Infectious Dis

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Patients undergoing treatment with immunosuppressant drugs following solid organ or hematopoietic stem cell transplantation are at particular risk for development of serious infections such as invasive aspergillosis. Four triazole antifungal drugs, voriconazole, posaconazole, itraconazole, and isavuconazole, are approved to treat invasive aspergillosis either as first-or second-line therapy. All of these agents are inhibitors of cytochrome P450 3A4, which plays a key role in metabolizing immunosuppressant drugs such as cyclosporine, tacrolimus, and sirolimus. Thus, co-administration of a triazole antifungal drug with these immunosuppressant drugs can potentially increase plasma concentrations of the immunosuppressant drugs, thereby resulting in toxicity, or upon discontinuation, inadvertently decrease the respective concentrations with increased risk of rejection or graft-versus-host disease. In this article, we review the evidence for the extent of inhibition of cytochrome P450 3A4 by each of these triazole antifungal drugs and assess their effects on cyclosporine, tacrolimus, and sirolimus. We also consider other factors affecting interactions of these two classes of drugs. Finally, we examine recommendations and strategies to evaluate and address those potential drug-drug interactions in these patients. Invasive aspergillosis (IA) is the most common IFD in HSCT recipients and has been reported to account for between 40% and 60% of cases. 4,5 In SOT recipients, IA is the second most common IFD overall, but the leading IFD in lung transplant recipients. 6 Mortality from IA is substantial in both patient populations. In prospective, multicenter, observational studies, the overall 6-week mortality rate among HSCT recipients with IA in North America was 22% 5 and 1-year mortality rate in the United States (US) was 75%. 4 In a separate prospective, multicenter, observational study, the 1-year mortality rate among SOT

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Drug‐drug interactions between triazole antifungal agents used to treat invasive aspergillosis and immunosuppressants metabolized by cytochrome P450 3A4

Groll

Townsend

Desai

et al. 2017

Transplant Infectious Dis

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“…Liposomal amphotericin B and azoles are both associated with a significant risk of hepatotoxicity (27%) [21,[33][34][35]. Moreover, liposomal amphotericin B has been associated with an increasing risk of nephrotoxicity and infusionrelated reactions [36], whereas azoles have a limited spectrum of antifungal activity and can cause severe drug-drug interactions [37]. Thus, the use of alternative antifungal drugs for the treatment of IFIs in patients with pre-existing liver disease is of particular clinical relevance.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Safety and Tolerance Profile of Micafungin with that of Other Echinocandins and Azoles in Patients with Pre-existing Child–Pugh B or C Liver Disease: A Case–Control Retrospective Study

et al. 2020

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Introduction: To assess the association between exposure to micafungin, other echinocandins, or azoles and the development of short-term liver injury (STLI) or long-term liver injury (LTLI) in patients with Child-Pugh B or C liver disease. Methods: Multicenter case-control study of patients with Child-Pugh B or C liver disease who received antifungals (AF) for C 72 h (May 2009-May 2015) in six Spanish and Italian hospitals. All micafungin patients were randomly matched with one patient who received another echinocandin and with one patient who received azole treatment. Primary outcome was development of STLI or LTLI (development of any type of liver tumor during the follow-up period). Results: Of 2335 patients with chronic liver disease admitted to the six centers, 20 (0.85%) were found to have Child-Pugh B or C liver disease and received micafungin for C 72 h. During AF treatment, the frequency of STLI was 10% in each group. Most cases of STLI were asymptomatic, and AFs had to be switched to another class of AF in only two patients (one micafungin and one azole). No patients developed acute liver insufficiency, were admitted to the ICU, or had to undergo transplantation. Follow-up data (median of 1.3 years) were Enhanced digital features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.11550816.

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“…No comprehensive indicator system has previously been created using the Delphi technique for evaluating the appropriate use of triazole antifungals. The evaluations performed in previous studies have mainly focused on only a subset of indicators such as therapeutic timing, duration of drug usage or drug dosage and have not included other indicators such as drug interactions, medication in specific populations and pharmaceutical care that are crucial in the treatment process due to their impacts on the safety and efficacy of drug therapy . In the initial secondary indicators, “drug interactions” comprises the two tertiary indicators of “drug interactions requiring attention” and “incompatible drugs.” “Medication in specific populations” comprises six tertiary indicators (pregnant women, patients with impaired liver function, patients with impaired renal function, children, elderly and patients with AIDS), and the third indicator for patients with AIDS was deleted after two rounds of Delphi consultation.…”

Section: Discussionmentioning

confidence: 99%

“…Triazoles including fluconazole, itraconazole, voriconazole and posaconazole are now widely used. The extensive use of triazoles has increased the frequency of drug interactions, fungi constantly evolving into resistant strains and an increasing medical expenses burden . The use of antifungal drugs poses a daily challenge for professionals in many different specialties in modern hospitals .…”

Section: What Is Known and Objectivementioning

confidence: 99%

Development of indicators for evaluating the appropriate use of triazoles for invasive fungal disease: A Delphi panel survey

Dong

Zhang

et al. 2017

J Clin Pharm Ther

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Contrasted with previous studies that have only focused on a subset of indicators, this research establishes comprehensive indicators for evaluating the use of triazoles for invasive fungal disease and which cover most of the medication process: indications, therapeutic timing, duration of drug usage, drug dosage, administration method, drug interactions, medication in specific populations and pharmaceutical care. The indicators can reflect the characteristic of triazoles throughout the process of clinical administration for an invasive fungal disease, and it will be helpful as references when hospital administrators are regulating the use of antifungals.

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Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients

Cited by 49 publications

References 25 publications

Drug‐drug interactions between triazole antifungal agents used to treat invasive aspergillosis and immunosuppressants metabolized by cytochrome P450 3A4

Drug‐drug interactions between triazole antifungal agents used to treat invasive aspergillosis and immunosuppressants metabolized by cytochrome P450 3A4

Comparison of the Safety and Tolerance Profile of Micafungin with that of Other Echinocandins and Azoles in Patients with Pre-existing Child–Pugh B or C Liver Disease: A Case–Control Retrospective Study

Development of indicators for evaluating the appropriate use of triazoles for invasive fungal disease: A Delphi panel survey

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