title: Clinical management of drug-drug interactions in HCV therapy: challenges and solutions.
abstract: Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals telaprevir and boceprevir, which are both substrates and inhibitors of the cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug-drug interactions have become a cornerstone in the evaluation of patients starting and continuing HCV combination therapy. In our opinion, an overview of conducted drug-drug interaction studies and a list of contraindicated medications is not enough for the clinical management of these drug-drug interactions. Knowledge of pharmacokinetic profiles and concentration-effect relationships is key for the interpretation of these data, and insight into how to manage these interactions (e.g., dose adjustments, safe alternatives and therapeutic drug monitoring) is of equal importance. This review provides a practical overview of the safe and effective management of these clinical challenges.
authors.affiliation: Department of Pharmacy, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. D.Burger@akf.umcn.nl
authors.forename: David
authors.initials: D
authors.lastname: Burger
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: Peter
authors.initials: P
authors.lastname: Buggisch
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxí
authors.forename: Graham
authors.initials: G
authors.lastname: Foster
authors.forename: Hartwig
authors.initials: H
authors.lastname: Klinker
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
authors.forename: Igor
authors.initials: I
authors.lastname: Nikitin
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gómez
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D002047:Buprenorphine / Q000008:administration & dosage / Q000009:adverse effects; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects; D058850:Opiate Substitution Treatment / Q000009:adverse effects
chemical_list: D000890:Anti-Infective Agents; D000928:Antidepressive Agents; D000998:Antiviral Agents; D002317:Cardiovascular Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006993:Hypnotics and Sedatives; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D002047:Buprenorphine; D008691:Methadone