PMID- 30590533 OWN - NLM STAT- MEDLINE DCOM- 20200625 LR - 20200625 IS - 1460-2091 (Electronic) IS - 0305-7453 (Linking) VI - 74 IP - 4 DP - 2019 Apr 1 TI - Therapeutic drug monitoring and adverse events of delayed-release posaconazole tablets in patients with chronic pulmonary aspergillosis. PG - 1056-1061 LID - 10.1093/jac/dky539 [doi] AB - BACKGROUND: Posaconazole delayed-release tablets offer 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 tablets in patients with CPA. METHODS: Patients started on posaconazole tablets at the National Aspergillosis Centre (NAC), Manchester, UK between February 2014 and October 2015 were identified from the NAC database and analysed retrospectively. The medical records were reviewed for factors that could affect posaconazole serum levels and the development of AEs. RESULTS: Seventy-two patients were included; 50 (69%) were male and the mean age was 48.5 +/- 12 years. Therapeutic levels (>/=1 mg/L) were achieved in 90% of cases on 200 mg versus 90% of cases on 300 mg daily (P = not significant). Based on multivariate analysis, female sex (P = 0.041), a 100 mg daily dose (P < 0.001), asthma (P = 0.01) and bronchiectasis (P = 0.001) were associated with subtherapeutic levels. Forty-nine (68%) patients developed AEs, mainly fatigue (37%), dyspnoea (18%) and nausea (12%). AEs were present on 115/196 (59%) occasions on 300 mg/day and on 45/115 (39%) occasions on 200 mg/day (P < 0.01). The mean level was 1.81 +/- 0.96 mg/L for patients reporting no AEs and 1.90 +/- 1.11 mg/L for those reporting AEs (P = not significant). Factors associated with AEs of grade >/=2 were a daily dose of 300 versus 200 mg (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 degree and frequency of AEs. CI - (c) The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Kosmidis, Chris AU - Kosmidis C AD - Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. AD - National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Southmoor Road, Manchester, UK. FAU - Rodriguez-Goncer, Isabel AU - Rodriguez-Goncer I AD - National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Southmoor Road, Manchester, UK. FAU - Rautemaa-Richardson, Riina AU - Rautemaa-Richardson R AD - Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. AD - National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Southmoor Road, Manchester, UK. AD - Mycology Reference Centre Manchester, ECMM Centre of Excellence, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, UK. FAU - Richardson, Malcolm D AU - Richardson MD AD - Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. AD - Mycology Reference Centre Manchester, ECMM Centre of Excellence, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, UK. FAU - Moore, Caroline B AU - Moore CB AD - Mycology Reference Centre Manchester, ECMM Centre of Excellence, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, UK. FAU - Denning, David W AU - Denning DW AD - Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. AD - National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Southmoor Road, Manchester, UK. LA - eng PT - Journal Article PL - England TA - J Antimicrob Chemother JT - The Journal of antimicrobial chemotherapy JID - 7513617 RN - 0 (Antifungal Agents) RN - 0 (Delayed-Action Preparations) RN - 0 (Tablets) RN - 0 (Triazoles) RN - 6TK1G07BHZ (posaconazole) SB - IM MH - Administration, Oral MH - Adult MH - Aged MH - Antifungal Agents/*administration & dosage/*pharmacokinetics MH - Chronic Disease MH - Delayed-Action Preparations MH - Drug Monitoring MH - Female MH - Humans MH - Male MH - Middle Aged MH - Pulmonary Aspergillosis/*drug therapy/*microbiology MH - Tablets MH - Treatment Outcome MH - Triazoles/*administration & dosage/*pharmacokinetics EDAT- 2018/12/28 06:00 MHDA- 2020/06/26 06:00 CRDT- 2018/12/28 06:00 PHST- 2018/08/21 00:00 [received] PHST- 2018/10/12 00:00 [revised] PHST- 2018/11/24 00:00 [accepted] PHST- 2018/12/28 06:00 [pubmed] PHST- 2020/06/26 06:00 [medline] PHST- 2018/12/28 06:00 [entrez] AID - 5262264 [pii] AID - 10.1093/jac/dky539 [doi] PST - ppublish SO - J Antimicrob Chemother. 2019 Apr 1;74(4):1056-1061. doi: 10.1093/jac/dky539.