Voriconazole Autoinduction and Saturable Metabolism After Cessation of Rifampin in a Patient With Invasive Central Nervous System Aspergillus: Importance of Therapeutic Drug Monitoring

Farrokh, Salia; Avdic, Edina

doi:10.1177/0897190018760621

Cited by 8 publications

(7 citation statements)

References 27 publications

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“…Autoinduction of voriconazole has also been described in cases of low serum concentrations. ( 18 ) Although not attempted in our patients, the use of CYP2C19 inhibitors including cimetidine may be a potential strategy to maintain or increase voriconazole concentration, while reducing voriconazole daily dose (and associated fluoride metabolite) in patients with skeletal fluorosis.…”

Section: Discussionmentioning

confidence: 96%

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Voriconazole‐Associated Periostitis: New Insights into Pathophysiology and Management

et al. 2021

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Voriconazole‐associated periostitis (VAP) is an underrecognized and unpredictable side effect of long‐term voriconazole therapy. We report two cases of VAP occurring in the post‐transplant setting: a 68‐year‐old lung transplant recipient who required ongoing voriconazole therapy, in whom urinary alkalinization was used to promote fluoride excretion and minimize voriconazole‐related skeletal toxicity, and a 68‐year‐old stem‐cell transplant recipient with a high voriconazole dose requirement, identified on pharmacogenomic testing to be a CYP2C19 ultrarapid metabolizer, the dominant enzyme in voriconazole metabolism. This is the first reported case of pharmacogenomic profiling in VAP and may explain the variability in individual susceptibility to this uncommon adverse effect. Our findings provide new insights into both the management and underlying pathophysiology of VAP. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 96%

“…Posaconazole does not undergo significant CYP enzyme metabolism and is largely excreted unchanged in the feces, whereas isavuconazole is metabolized by CYP3A4/CYP3A5 to inactive metabolites. ( 3 , 17 , 18 , 19 )…”

Section: Discussionmentioning

confidence: 99%

Voriconazole‐Associated Periostitis: New Insights into Pathophysiology and Management

et al. 2021

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“…Therapeutic monitoring has been suggested in clinical practice to reduce adverse effects and increase the therapeutic efficacy and safety of VCZ [ 180 , 181 ]. Its unpredictable nonlinear pharmacokinetics, with wide variation in serum levels between individuals, makes therapeutic regimens difficult due to the polymorphisms associated with its primary metabolism, drug interactions, and oral bioavailability [ 135 , 182 ].…”

Section: Voriconazolementioning

confidence: 99%

Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections

et al. 2023

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Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections.

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“…AF TDM cases in real-life settings (pathogens, underlying diseases, 69,71–73,75,81 trends per year, 84,234,235,236,238,239,241,244,245,344–348 CNS 532–539 localization 541–566 ) 364,370,499,522,527–530 Trends are concerning a majority of mucomycosis and aspergillosis, in oncohematology and transplantation. VRZ, more recently PSZ tablets and ISZ are the most represented.…”

Section: Tdm For Af Drugsmentioning

confidence: 99%

“…Underexposure to VRZ was reported in a case of cerebral aspergillosis after rifampin treatment in a 32-year-old African American patient. Treatment failure occurred despite VRZ concentrations of 2–5 mg/L in plasma and 4 mg/L in CSF 71 being reached on day 106.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Antifungal Drugs TDM: Trends and Update

Kably

Launay

Derobertmasure

et al. 2022

Therapeutic Drug Monitoring

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The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM. Methods:We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-druginteraction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure.Results: More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available.Conclusions: TDM seems to be crucial for curative and/or longterm maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.

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Voriconazole Autoinduction and Saturable Metabolism After Cessation of Rifampin in a Patient With Invasive Central Nervous System Aspergillus: Importance of Therapeutic Drug Monitoring

Abstract: Our findings highlight the unpredictable PK of voriconazole and reinforce the importance of continuous therapeutic drug monitoring in critically ill patients.

Cited by 8 publications

References 27 publications

Voriconazole‐Associated Periostitis: New Insights into Pathophysiology and Management

Voriconazole‐Associated Periostitis: New Insights into Pathophysiology and Management

Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections

Antifungal Drugs TDM: Trends and Update

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