Therapeutic drug monitoring and adverse events of delayed-release posaconazole tablet in patients with chronic pulmonary aspergillosis

Chris Kosmidis*, Isabel Rodriguez-Goncer, Riina Rautemaa-Richardson , Malcolm Richardson, Caroline Moore, D W Denning

*Corresponding author for this work

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Abstract

Background: Posaconazole delayed-release tablet offers better bioavailability than the liquid suspension, but no post-marketing data are available in immunocompetent hosts such as those with chronic pulmonary aspergillosis (CPA).

Objectives: To explore the pharmacokinetics and adverse event (AE) profile of posaconazole tablet in patients with CPA.

Methods: Patients started on posaconazole tablet at the National Aspergillosis Centre, Manchester, between February 2014 and October 2015 were identified from Centre database and analysed retrospectively. The medical records were reviewed for factors which could impact on posaconazole serum levels and developing AE.

Results: Seventy-two patients were included; 50 (69%) were male and mean age was 48.5±12 years. Therapeutic levels (>1mg/L) were achieved in 90% of cases on 200mg versus 90% of cases on 300mg (p, NS). On multivariate analysis, female sex (p=0.041), 100mg daily dose (p<0.001), asthma (p=0.01) and bronchiectasis (p=0.001) were associated with sub-therapeutic levels. Forty-nine (68%) patients developed AE, mainly fatigue (37%), breathlessness (18%) and nausea (12%). AEs were present on 115/196 (59%) occasions on 300mg and on 45/115 (39%) occasions on 200mg a day, (p<0.01). Mean level was 1.81±0.96mg/L for patients reporting no AE, and 1.90±1.11 mg/L for those reporting AEs (p, NS). Factors associated with AE of Grade 2 or higher were: dose of 300mg versus 200mg (p=0.001) and asthma (p=0.008).Conclusions: A lower than recommended posaconazole tablet dose achieved therapeutic levels in most patients and was better tolerated. Males were more likely to achieve a therapeutic level. Underlying conditions affected the levels and AE frequency.
Original languageEnglish
Pages (from-to)1056-1061
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume74
Issue number4
Early online date26 Dec 2018
DOIs
Publication statusPublished - 1 Apr 2019

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