Posaconazole liquid vs tablet formulation in lung transplant recipients

被引:27
作者
Stelzer, D. [1 ,2 ,3 ,4 ]
Weber, A. [4 ]
Ihle, F. [1 ,2 ,3 ]
Matthes, S. [1 ,2 ,3 ]
Ceelen, F. [1 ,2 ,3 ]
Zimmermann, G. [1 ,2 ,3 ]
Kneidinger, N. [1 ,2 ,3 ]
Schramm, R. [5 ]
Winter, H. [6 ]
Zoller, M. [7 ]
Vogeser, M. [8 ]
Behr, J. [1 ,2 ,3 ]
Neurohr, C. [1 ,2 ,3 ]
机构
[1] Ludwig Maximilians Univ Munchen, Dept Internal Med 5, Munich, Germany
[2] Comprehens Pneumol Ctr, Munich, Germany
[3] German Ctr Lung Res DZL, Munich, Germany
[4] Ludwig Maximilians Univ Munchen, Hosp Pharm, Munich, Germany
[5] Ludwig Maximilians Univ Munchen, Dept Cardiac Surg, Munich, Germany
[6] Ludwig Maximilians Univ Munchen, Dept Thorac Surg, Munich, Germany
[7] Ludwig Maximilians Univ Munchen, Dept Anesthesiol, Munich, Germany
[8] Ludwig Maximilians Univ Munchen, Inst Lab Med, Munich, Germany
关键词
antifungal agents; dosage form; invasive fungal infection; lung transplantation; posaconazole; therapeutic drug monitoring; INVASIVE FUNGAL-INFECTIONS; MYCOSES STUDY-GROUP; ORAL SUSPENSION; INTERNATIONAL SOCIETY; EUROPEAN-ORGANIZATION; SERUM CONCENTRATIONS; ANTIFUNGAL THERAPY; PHARMACOKINETICS; DISEASE; SAFETY;
D O I
10.1111/myc.12724
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Posaconazole is an extended-spectrum triazole antifungal used in the treatment and prophylaxis of Aspergillus infections. It is available as oral suspension (POS-Liq) and delayed-release tablets (POS-Tab). The aim of this longitudinal, retrospective study was to compare the clinical effectiveness, toxicity and pharmacokinetics of POS-Liq vs POS-Tab in lung transplant recipients (LTx-recipients), who were treated with both formulations subsequently. Twenty-four consecutive LTx-recipients with 191 documented posaconazole trough levels (PTLs) for POS-Liq or POS-Tab were included. The administered daily doses were 300mg for POS-Tab and 600mg (prophylaxis) or 800mg (therapy) for POS-Liq. Target PTLs were 700ng/mL (prophylaxis) and 1250ng/mL (therapy). The overall prophylactic and therapeutic response rates were 78% and 67%, respectively. No cases of hepatotoxicity or QT-prolongation were observed with either formulation. The achieved target PTLs were tripled under POS-Tab compared to POS-Liq with fewer risk factors for sub-therapeutic PTLs. Concomitant administration of POS-Tab significantly reduced the tacrolimus concentration-to-dose ratio (P=.001). We suggest the use of POS-Tab is appropriate for prophylaxis and therapy of Aspergillus infections in LTx-recipients, since POS-Tab displayed more reliable PTLs with no added adverse events. However, we recommend regular drug monitoring for POS-Liq and for therapy with POS-Tab and that immunosuppressant levels are monitored closely when the posaconazole formulation is switched.
引用
收藏
页码:186 / 194
页数:9
相关论文
共 44 条
[1]   Omeprazole Significantly Reduces Posaconazole Serum Trough Level [J].
Alffenaar, Jan-Willem C. ;
van Assen, Sander ;
van der Werf, Tjip S. ;
Kosterink, Jos G. W. ;
Uges, Donald R. A. .
CLINICAL INFECTIOUS DISEASES, 2009, 48 (06) :839-839
[2]  
Certican<(R)>, 2016, TABL PRESCR INF
[3]   The Registry of the International Society for Heart and Lung Transplantation: 29th Adult Lung and Heart-Lung Transplant Report-2012 [J].
Christie, Jason D. ;
Edwards, Leah B. ;
Kucheryavaya, Anna Y. ;
Benden, Christian ;
Dipchand, Anne I. ;
Dobbels, Fabienne ;
Kirk, Richard ;
Rahmel, Axel O. ;
Stehlik, Josef ;
Hertz, Marshall I. .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2012, 31 (10) :1073-1086
[4]   Phase 3 pharmacokinetics and safety study of a posaconazole tablet formulation in patients at risk for invasive fungal disease [J].
Cornely, Oliver A. ;
Duarte, Rafael F. ;
Haider, Shariq ;
Chandrasekar, Pranatharthi ;
Helfgott, David ;
Lopez Jimenez, Javier ;
Candoni, Anna ;
Raad, Issam ;
Laverdiere, Michel ;
Langston, Amelia ;
Kartsonis, Nicholas ;
Van Iersel, Marlou ;
Connelly, Nancy ;
Waskin, Hetty .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2016, 71 (03) :718-726
[5]   Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults [J].
Courtney, R ;
Wexler, D ;
Radwanski, E ;
Lim, J ;
Laughlin, M .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2004, 57 (02) :218-222
[6]   Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies [J].
Cumpston, Aaron ;
Caddell, Ryan ;
Shillingburg, Alexandra ;
Lu, Xiaoxiao ;
Wen, Sijin ;
Hamadani, Mehdi ;
Craig, Michael ;
Kanate, Abraham S. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2015, 59 (08) :4424-4428
[7]   Inhibition of antifungal therapy by gastric acid suppressants [J].
Daniell, Harry W. .
INTENSIVE CARE MEDICINE, 2015, 41 (03) :565-566
[8]   Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group [J].
De Pauw, Ben ;
Walsh, Thomas J. ;
Donnelly, J. Peter ;
Stevens, David A. ;
Edwards, John E. ;
Calandra, Thierry ;
Pappas, Peter G. ;
Maertens, Johan ;
Lortholary, Olivier ;
Kauffman, Carol A. ;
Denning, David W. ;
Patterson, Thomas F. ;
Maschmeyer, Georg ;
Bille, Jacques ;
Dismukes, William E. ;
Herbrecht, Raoul ;
Hope, William W. ;
Kibbler, Christopher C. ;
Kullberg, Bart Jan ;
Marr, Kieren A. ;
Munoz, Patricia ;
Odds, Frank C. ;
Perfect, John R. ;
Restrepo, Angela ;
Ruhnke, Markus ;
Segal, Brahm H. ;
Sobel, Jack D. ;
Sorrell, Tania C. ;
Viscoli, Claudio ;
Wingard, John R. ;
Zaoutis, Theoklis ;
Bennett, John E. .
CLINICAL INFECTIOUS DISEASES, 2008, 46 (12) :1813-1821
[9]   Multicenter Study of Posaconazole Therapeutic Drug Monitoring: Exposure-Response Relationship and Factors Affecting Concentration [J].
Dolton, Michael J. ;
Ray, John E. ;
Chen, Sharon C. -A. ;
Ng, Kingsley ;
Pont, Lisa ;
McLachlan, Andrew J. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2012, 56 (11) :5503-5510
[10]   Phase 1b Study of New Posaconazole Tablet for Prevention of Invasive Fungal Infections in High-Risk Patients with Neutropenia [J].
Duarte, Rafael F. ;
Lopez-Jimenez, Javier ;
Cornely, Oliver A. ;
Laverdiere, Michel ;
Helfgott, David ;
Haider, Shariq ;
Chandrasekar, Pranatharthi ;
Langston, Amelia ;
Perfect, John ;
Ma, Lei ;
van Iersel, Marlou L. P. S. ;
Connelly, Nancy ;
Kartsonis, Nicholas ;
Waskin, Hetty .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2014, 58 (10) :5758-5765