Potential P-glycoprotein Pharmacokinetic Interaction of Telaprevir With Morphine or Methadone

Jeffrey FudinJeffrey Fudin, BS, PharmD, FCCP, is a clinical pharmacy specialist at the Stratton VA Medical Center, Albany, New York, USA, and Adjunct Associate Professor, Albany College of Pharmacy and Health Sciences, Albany, New York USA and Adjunct Assistant Professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Connecticut USA. Dania Vanesta Fontenelle, PharmD is a pharmacy resident at the APR Regional Medical Center, Hazard, Kentucky, USA. Hannah Rebecca Fudin, PharmD, is a pharmacy practice resident at Virtua Memorial, Mt. Holly, New Jersey, USA. Cynthia Carlyn, MD, is Chief of Infectious Disease at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College, Albany, New York, USA. Debra Ann Hinden, PA-C, is the Liver Transplant Coordinator at the Stratton VA Medical Center. Christopher C. Ashley, MD, is Chief of Gastroenterology at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College.Correspondence[email protected]

Dania Vanesta FontenelleJeffrey Fudin, BS, PharmD, FCCP, is a clinical pharmacy specialist at the Stratton VA Medical Center, Albany, New York, USA, and Adjunct Associate Professor, Albany College of Pharmacy and Health Sciences, Albany, New York USA and Adjunct Assistant Professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Connecticut USA. Dania Vanesta Fontenelle, PharmD is a pharmacy resident at the APR Regional Medical Center, Hazard, Kentucky, USA. Hannah Rebecca Fudin, PharmD, is a pharmacy practice resident at Virtua Memorial, Mt. Holly, New Jersey, USA. Cynthia Carlyn, MD, is Chief of Infectious Disease at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College, Albany, New York, USA. Debra Ann Hinden, PA-C, is the Liver Transplant Coordinator at the Stratton VA Medical Center. Christopher C. Ashley, MD, is Chief of Gastroenterology at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College.

Hannah Rebecca FudinJeffrey Fudin, BS, PharmD, FCCP, is a clinical pharmacy specialist at the Stratton VA Medical Center, Albany, New York, USA, and Adjunct Associate Professor, Albany College of Pharmacy and Health Sciences, Albany, New York USA and Adjunct Assistant Professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Connecticut USA. Dania Vanesta Fontenelle, PharmD is a pharmacy resident at the APR Regional Medical Center, Hazard, Kentucky, USA. Hannah Rebecca Fudin, PharmD, is a pharmacy practice resident at Virtua Memorial, Mt. Holly, New Jersey, USA. Cynthia Carlyn, MD, is Chief of Infectious Disease at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College, Albany, New York, USA. Debra Ann Hinden, PA-C, is the Liver Transplant Coordinator at the Stratton VA Medical Center. Christopher C. Ashley, MD, is Chief of Gastroenterology at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College.

Cynthia CarlynJeffrey Fudin, BS, PharmD, FCCP, is a clinical pharmacy specialist at the Stratton VA Medical Center, Albany, New York, USA, and Adjunct Associate Professor, Albany College of Pharmacy and Health Sciences, Albany, New York USA and Adjunct Assistant Professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Connecticut USA. Dania Vanesta Fontenelle, PharmD is a pharmacy resident at the APR Regional Medical Center, Hazard, Kentucky, USA. Hannah Rebecca Fudin, PharmD, is a pharmacy practice resident at Virtua Memorial, Mt. Holly, New Jersey, USA. Cynthia Carlyn, MD, is Chief of Infectious Disease at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College, Albany, New York, USA. Debra Ann Hinden, PA-C, is the Liver Transplant Coordinator at the Stratton VA Medical Center. Christopher C. Ashley, MD, is Chief of Gastroenterology at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College.

Debra Ann HindenJeffrey Fudin, BS, PharmD, FCCP, is a clinical pharmacy specialist at the Stratton VA Medical Center, Albany, New York, USA, and Adjunct Associate Professor, Albany College of Pharmacy and Health Sciences, Albany, New York USA and Adjunct Assistant Professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Connecticut USA. Dania Vanesta Fontenelle, PharmD is a pharmacy resident at the APR Regional Medical Center, Hazard, Kentucky, USA. Hannah Rebecca Fudin, PharmD, is a pharmacy practice resident at Virtua Memorial, Mt. Holly, New Jersey, USA. Cynthia Carlyn, MD, is Chief of Infectious Disease at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College, Albany, New York, USA. Debra Ann Hinden, PA-C, is the Liver Transplant Coordinator at the Stratton VA Medical Center. Christopher C. Ashley, MD, is Chief of Gastroenterology at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College.

Christopher C. AshleyJeffrey Fudin, BS, PharmD, FCCP, is a clinical pharmacy specialist at the Stratton VA Medical Center, Albany, New York, USA, and Adjunct Associate Professor, Albany College of Pharmacy and Health Sciences, Albany, New York USA and Adjunct Assistant Professor of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Connecticut USA. Dania Vanesta Fontenelle, PharmD is a pharmacy resident at the APR Regional Medical Center, Hazard, Kentucky, USA. Hannah Rebecca Fudin, PharmD, is a pharmacy practice resident at Virtua Memorial, Mt. Holly, New Jersey, USA. Cynthia Carlyn, MD, is Chief of Infectious Disease at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College, Albany, New York, USA. Debra Ann Hinden, PA-C, is the Liver Transplant Coordinator at the Stratton VA Medical Center. Christopher C. Ashley, MD, is Chief of Gastroenterology at the Stratton VA Medical Center and Assistant Professor of Medicine, Albany Medical College.

ABSTRACT

Telaprevir (TVR) effects on P-glycloprotein and cytochrome P450 (CYP) may significantly elevate serum levels of morphine and methadone. Recent literature points to major interactions when combining TVR with warfarin or rifampin. Opioid interactions are especially dangerous in hepatitis C patients, as coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) occurs in 50–90% of HIV-infected drug users that are prescribed opioids for chronic pain and/or methadone for maintenance. TVR has been shown to significantly inhibit the active transport enzyme pGP and may therefore increase intestinal morphine absorption. TVR also inhibits hepatic CYP3A4 that are responsible for metabolizing methadone. Patients requiring opioid analgesics must be carefully monitored because of potential for elevated opioid levels and overdose risk. Current recommendations minimize potential drug interactions between telaprevir and opioids, especially methadone, based on a single 7-day trial. We outline the various pharmacokinetic mechanisms involved when combining TVR with methadone or morphine and recommend that current data are not sufficiently robust to minimize the potentially significant interaction with opioids, especially methadone. Clinicians must be mindful of these understated interactions, know that the opioid dose may need to be significantly increased or reduced, and use caution during upward titration of opioids affected by these enzyme systems.

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Potential P-glycoprotein Pharmacokinetic Interaction of Telaprevir With Morphine or Methadone

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