Therapeutic Drug Monitoring of Posaconazole: an Update

Dekkers, Bart G. J.; Bakker, M.; Elst, Kim C. M. van der; Sturkenboom, Marieke G G; Veringa, Anette; Span, Lambert F.R.; Alffenaar, Jan‐Willem C.

doi:10.1007/s12281-016-0255-4

Cited by 139 publications

(109 citation statements)

References 72 publications

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“…Indeed, drug exposure with POS‐OS will marginally cover the A fumigatus wild‐type population, let alone low‐level POS‐resistant isolates. Higher exposures can be achieved with the newer formulations . The pharmacodynamic‐pharmacokinetic (PK‐PD) relationships of POS have been studied in vivo .…”

Section: Discussionmentioning

confidence: 99%

High‐dose posaconazole for azole‐resistant aspergillosis and other difficult‐to‐treat mould infections

Schauwvlieghe

Buil

Verweij

et al. 2019

Mycoses

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Summary Background Oral follow‐up therapy is problematic in moulds with reduced azole‐susceptibility, such as azole‐resistant Aspergillus fumigatus infection. Currently, only intravenous liposomal amphotericin B (L‐AmB) is advocated by guidelines for the treatment of azole‐resistant aspergillosis infections. Preclinical research indicates that high‐dose posaconazole (HD‐POS) might be a feasible option provided that high drug exposure (ie POS serum through levels >3 mg/L) can be achieved and is safe. Objectives To describe our experience with the use of oral HD‐POS as treatment strategies for patients infected with pathogens with a POS MIC close to the clinical breakpoint. Patients/Methods We review evidence supporting the use of HD‐POS and describe our experience on safety and efficacy in 16 patients. In addition, we describe the adverse events (AE) observed in 25 patients with POS concentrations at the higher end of the population distribution during treatment with the licensed dose. Results Sixteen patients were treated intentionally with HD‐POS for voriconazole‐resistant invasive aspergillosis (7/16), mucormycosis (4/16), salvage therapy for IA (4/16) and IA at a sanctuary site (spondylodiscitis) in 1. Grade 3‐4 AEs were observed in 6, and all of them were considered at least possibly related. Grade 3‐4 AEs were observed in 5 of the 25 patients with spontaneous high POS serum through levels considered at least possibly related using Naranjo scale. Conclusions High‐dose posaconazole is a treatment option if strict monitoring for both exposure and for AE is possible.

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Section: Discussionmentioning

confidence: 99%

High‐dose posaconazole for azole‐resistant aspergillosis and other difficult‐to‐treat mould infections

Schauwvlieghe

Buil

Verweij

et al. 2019

Mycoses

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“…Since the 2009 guidelines were written, evidence supporting the case for TDM in patients receiving posaconazole has increased and routine TDM is now recommended, especially in patients receiving oral suspension . However, our institution switched to the delayed‐release tablet form of posaconazole in 2015, which is less affected by concomitant PPI administration, reducing the need for routine TDM . We currently only perform TDM in patients where drug interactions are anticipated.…”

Section: Discussionmentioning

confidence: 99%

Antifungal prophylaxis in newly diagnosed AML patients–Adherence to guidelines and feasibility in a real life setting

Berking¹,

Doedens²,

Horns³

et al. 2017

Mycoses

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Antifungal posaconazole prophylaxis for AML patients receiving induction chemotherapy has been routine at our centre since 2009. This retrospective study examined the feasibility and practicability of our prophylaxis guidelines in clinical practice. Data sets of 90 patients undergoing induction-chemotherapy for AML between 2011 and 2014 were evaluated regarding adherence to local guidelines for the administration of antifungal prophylaxis with posaconazole. 75.5% of the 90 patients received posaconazole prophylaxis. All but eight patients received the recommended dosage. A total of 77.95% on prophylaxis had serum galactomannan measured twice weekly. Contradicting our guidelines, 89.70% of patients received concomitant therapy with PPI. Overall, 16.17% of patients had prophylaxis discontinued and started empirical antifungal treatment in the absence of diagnostic criteria for IFI. The breakthrough IFI rate was 36.76% (proven, probable and possible) with 7.35% of infections being classified as proven or probable. Although limited by a small sample size, our study demonstrates the feasibility of local guidelines in a real life setting and outlines areas for improvement in both guidelines and clinical practice. We also highlight the importance of ensuring awareness of guidelines and raise questions about a uniform approach to antifungal prophylaxis in AML patients.

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“…A therapeutic range, however, is described for this drug (area under the concentration-time curve [AUC]/MIC > 100; 400 AUC mg·h/L; trough > 10-15 mg/L) [59]. A therapeutic range for voriconazole (trough 1-5 mg/L, both prophylaxis and treatment) and posaconazole is defined for prophylaxis and treatment (trough concentration > 0.7 and > 1.25 mg/L, respectively) [56,59,61,62]. Figure 2 illustrates when TDM should be considered.…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

Strategies to Improve Medication Adherence in Older Persons: Consensus Statement from the Senior Italia Federanziani Advisory Board

et al. 2016

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Candida infections in the elderly are an important and expanding clinical problem, with significantly higher mortality in this group than in younger patients. The increasing problem of invasive Candida infections may be related to higher prevalence of immunocompromised older people and the emergence of treatment resistance. Older people, especially the frail and critically ill, are at higher risk of medication-related harmful effects due to changes in pharmacokinetics and pharmacodynamics, which may be further complicated by organ dysfunction, diminished homeostatic control, co-morbidities and polypharmacy. Here, we review the available options for the treatment of Candida infections and provide insights into the challenges surrounding the optimal use of antifungal drugs in the elderly. Key PointsCandida infections are a growing problem in elderly patients, with significant mortality in this group.Treatment in the elderly requires careful consideration of benefit and harm in the selection of both the drug and dose regimen.Therapeutic drug monitoring can be recommended for selected antifungal agents.

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Therapeutic Drug Monitoring of Posaconazole: an Update

Cited by 139 publications

References 72 publications

High‐dose posaconazole for azole‐resistant aspergillosis and other difficult‐to‐treat mould infections

High‐dose posaconazole for azole‐resistant aspergillosis and other difficult‐to‐treat mould infections

Antifungal prophylaxis in newly diagnosed AML patients–Adherence to guidelines and feasibility in a real life setting

Strategies to Improve Medication Adherence in Older Persons: Consensus Statement from the Senior Italia Federanziani Advisory Board

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