Elise J Smolders1, Floor Ac Berden2, Clara Tmm de Kanter3, Wietske Kievit4, Joost Ph Drenth2, David M Burger1. 1. Department of Pharmacy, Radboud university medical center, Nijmegen, The Netherlands. 2. Department of Gastroenterology and Hepatology, Radboud university medical center, Nijmegen, The Netherlands. 3. Department of Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands. 4. Department for Health Evidence, Radboud university medical center, Nijmegen, The Netherlands.
Abstract
BACKGROUND: Direct-acting antivirals have improved treatment of chronic hepatitis C virus infection significantly. Direct-acting antivirals inhibit/induce and can also be substrates of drug-metabolising enzymes and transporters. This increases the risk for drug-drug interactions. OBJECTIVE: The purpose of this study was to predict drug-drug interactions with co-medication used by hepatitis C virus-infected patients. METHODS: We assembled a nationwide cohort of hepatitis C patients and collected cross-sectional data on co-medication use. We compiled a list of currently available direct-acting antiviral regimens and cross-checked for potential drug-drug interactions with used co-medication. RESULTS: The cohort included 461 patients of which 77% used co-medication. We identified 260 drugs used as co-medication. Antidepressants (7.4%), proton pump inhibitors (7.1%) and benzodiazepines (7.1%) were most frequently used. Of the patients, 60% were at risk for a clinically relevant drug-drug interaction with at least one of the direct-acting antiviral regimens. Interactions were most common with paritaprevir/ritonavir/ombitasvir/dasabuvir and least interactions were predicted with grazoprevir/elbasvir. CONCLUSION: Co-medication use is rich in frequency and diversity in chronic hepatitis C patients. The majority of patients are at risk for drug-drug interactions which may affect efficacy or toxicity of direct-acting antivirals or co-medication. The most recently introduced direct-acting antivirals are associated with a lower risk of drug-drug interactions.
BACKGROUND: Direct-acting antivirals have improved treatment of chronic hepatitis C virus infection significantly. Direct-acting antivirals inhibit/induce and can also be substrates of drug-metabolising enzymes and transporters. This increases the risk for drug-drug interactions. OBJECTIVE: The purpose of this study was to predict drug-drug interactions with co-medication used by hepatitis C virus-infectedpatients. METHODS: We assembled a nationwide cohort of hepatitis C patients and collected cross-sectional data on co-medication use. We compiled a list of currently available direct-acting antiviral regimens and cross-checked for potential drug-drug interactions with used co-medication. RESULTS: The cohort included 461 patients of which 77% used co-medication. We identified 260 drugs used as co-medication. Antidepressants (7.4%), proton pump inhibitors (7.1%) and benzodiazepines (7.1%) were most frequently used. Of the patients, 60% were at risk for a clinically relevant drug-drug interaction with at least one of the direct-acting antiviral regimens. Interactions were most common with paritaprevir/ritonavir/ombitasvir/dasabuvir and least interactions were predicted with grazoprevir/elbasvir. CONCLUSION: Co-medication use is rich in frequency and diversity in chronic hepatitis Cpatients. The majority of patients are at risk for drug-drug interactions which may affect efficacy or toxicity of direct-acting antivirals or co-medication. The most recently introduced direct-acting antivirals are associated with a lower risk of drug-drug interactions.
Authors: Hélène Fontaine; Arnaud Lazarus; Stanislas Pol; Caroline Pecriaux; François Bagate; Philippe Sultanik; Estelle Boueyre; Marion Corouge; Vincent Mallet; Anaïs Vallet-Pichard; Philippe Sogni; Denis Duboc Journal: N Engl J Med Date: 2015-11-05 Impact factor: 91.245
Authors: B Maasoumy; K Port; B Calle Serrano; A A Markova; L Sollik; M P Manns; M Cornberg; H Wedemeyer Journal: Aliment Pharmacol Ther Date: 2013-10-16 Impact factor: 8.171
Authors: Floor A C Berden; Inke M J M van Zwietering; Raoel Maan; Robert J de Knegt; Wietske Kievit; Joost P H Drenth Journal: J Gastrointestin Liver Dis Date: 2016-06 Impact factor: 2.008
Authors: Christoph Höner Zu Siederdissen; Benjamin Maasoumy; Fiona Marra; Katja Deterding; Kerstin Port; Michael P Manns; Markus Cornberg; David Back; Heiner Wedemeyer Journal: Clin Infect Dis Date: 2015-11-26 Impact factor: 9.079
Authors: J Vermehren; K-H Peiffer; C Welsch; G Grammatikos; M-W Welker; N Weiler; S Zeuzem; T M Welzel; C Sarrazin Journal: Aliment Pharmacol Ther Date: 2016-08-23 Impact factor: 8.171
Authors: Minou van Seyen; Angela Colbers; Evertine J Abbink; Joost P H Drenth; David M Burger Journal: Clin Pharmacol Ther Date: 2019-08-18 Impact factor: 6.875