Pharmacokinetic interaction between HCV protease inhibitor boceprevir and methadone or buprenorphine in subjects on stable maintenance therapy

Hulskotte, Ellen; Bruce, R. Douglas; Feng, Hwa‐Ping; Webster, Lynn R.; Xuan, F.; Lin, Wen Hsing; O’Mara, Edward; Wagner, John A.; Butterton, Joan R.

doi:10.1007/s00228-014-1789-4

Cited by 23 publications

(24 citation statements)

References 23 publications

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“…Boceprevir was studied in 11 buprenorphine/naloxone patients and demonstrated an increase in the AUC of buprenorphine and naloxone of 19% and 33%, respectively, which was not statistically significant. Norbuprenorphine was significantly reduced by 65% with the addition of boceprevir [194]. The increase in buprenorphine and the reduction in norbuprenorphine are reminiscent of the tipranavir/ritonavir inhibition of 3A4 and the shunting of buprenorphine metabolism away from norbuprenorphine.…”

Section: Interactions Between Hepatitis C Antivirals and Methadone Ormentioning

confidence: 99%

A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice

Bruce

Moody

Altice

et al. 2013

Expert Review of Clinical Pharmacology

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Global access to opioid agonist therapy and HIV/HCV treatment is expanding but when used concurrently, problematic pharmacokinetic and pharmacodynamic interactions may occur. Review of articles from 1966 into 2012 in Medline using the following keywords: HIV, AIDS, HIV therapy, HCV, HCV therapy, antiretroviral therapy, HAART, drug interactions, methadone, and buprenorphine. Additionally, abstracts from national and international meetings and a review of conference proceedings were conducted; selected reports were reviewed as well. The metabolism of both opioid and antiretroviral therapies, description of their known interactions, and clinical implications and management of these interactions are reviewed. Important pharmacokinetic and pharmacodynamic drug interactions affecting either methadone or HIV medications have been demonstrated within each class of antiretroviral agents. Drug interactions between methadone, buprenorphine and HIV medications are known and may have important clinical consequences. Clinicians must be alert to these interactions and have a basic knowledge regarding their management.

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Section: Interactions Between Hepatitis C Antivirals and Methadone Ormentioning

confidence: 99%

A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice

Bruce

Moody

Altice

et al. 2013

Expert Review of Clinical Pharmacology

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“…No free methadone concentrations were performed. Boceprevir was also associated with an increase of naloxone and buprenorphine exposure by 19 and 33% respectively, which is considered to be clinically non-significant [88]. …”

Section: Resultsmentioning

confidence: 99%

Psychiatric treatment considerations with direct acting antivirals in hepatitis C

et al. 2013

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BackgroundDespite recent advances in hepatitis C (HCV) treatment, specifically the addition of direct acting antivirals (DAAs), pegylated interferon-alpha remains the backbone of HCV therapy. Therefore, the impact of DAAs on the management of co-morbid psychiatric illness and neuropsychiatric sequalae remains an ongoing concern during HCV therapy. This paper provides a review of the neuropsychiatric adverse effects of DAAs and drug-drug interactions (DDIs) between DAAs and psychiatric medications.MethodsWe conducted a Pubmed search using relevant search terms and hand searched reference lists of related review articles. In addition, we searched abstracts for major hepatology conferences and contacted respective pharmaceutical companies for additional studies.ResultsLimited data is available on the neuropsychiatric adverse effects of DAAs; however, data from major clinical trials suggest that DAAs have minimal neuropsychiatric risk. DAAs can potentially interact with a variety of psychotropic agents via cytochrome P450 and p-glycoprotein interactions. Triazolam, oral midazolam, St. John’s Wort, carbamazepine and pimozide, are contraindicated with DAAs. DDIs between DAAs and antidepressants, anxiolytics, hypnotics, mood stabilizers, antipsychotics and treatments for opioid dependence are summarized.ConclusionsAlthough DAAs do not add significant neuropsychiatric risk, the potential for DDIs is high. Consideration of DDIs is paramount to improving medication adherence and mitigating adverse effects during HCV therapy.

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“…Naloxone, coformulated with buprenorphine, is primarily metabolized by conjugation with glucuronic acid but may also be metabolized by CYP3A4, as shown in vitro [38,39]. In an open-label, fixed-sequence study in 11 adult volunteers receiving stable buprenorphine/naloxone maintenance therapy, boceprevir (800 mg every 7-9 h) increased the AUC s and C max of buprenorphine by 19 and 18 %, respectively, and of naloxone by 33 and 9 %, respectively ( Table 2) [35]. The increase in buprenorphine concentrations was accompanied by a corresponding reduction in norbuprenorphine concentrations, and is consistent with boceprevir-mediated inhibition of buprenorphine metabolism via CYP3A4.…”

Section: Buprenorphine/naloxonementioning

confidence: 92%

“…The increase in buprenorphine concentrations was accompanied by a corresponding reduction in norbuprenorphine concentrations, and is consistent with boceprevir-mediated inhibition of buprenorphine metabolism via CYP3A4. Based on the assessment of patients with OOWS, SOWS, and OOAS, the observed changes in buprenorphine exposure did not result in clinically relevant changes in opioid withdrawal or opioid excess data on file, Merck & Co., Inc. A clinically significant difference in boceprevir exposure was similar to that of historical controls in the presence of buprenorphine/naloxone (Table 3) [35].…”

Section: Buprenorphine/naloxonementioning

confidence: 96%

“…In an open-label, fixed-sequence study in ten adult volunteers who were receiving stable methadone maintenance therapy, boceprevir (800 mg every 7-9 h) added to stable methadone therapy reduced the AUC s and C max of R-methadone (active enantiomer) by 15 and 22 %, respectively, and of S-methadone by 22 and 17 %, respectively (Table 2) [35]. A significant clinical difference was not seen in boceprevir exposure from that of historical controls (Table 3) [35,36]. During this study, patients were also assessed using the Objective Opioid Withdrawal Scale (OOWS), the Subjective Opioid Withdrawal Scale (SOWS), and the Opioid Overdose Assessment Scale (OOAS).…”

Section: Methadonementioning

confidence: 96%

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Clinical Pharmacology Profile of Boceprevir, a Hepatitis C Virus NS3 Protease Inhibitor: Focus on Drug–Drug Interactions

et al. 2015

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Boceprevir is a potent, orally administered ketoamide inhibitor that targets the active site of the hepatitis C virus (HCV) non-structural (NS) 3 protease. The addition of boceprevir to peginterferon plus ribavirin resulted in higher rates of sustained virologic response (SVR) than for peginterferon plus ribavirin alone in phase III studies in both previously treated and untreated patients with HCV infection. Because boceprevir is metabolized by metabolic routes common to many other drugs, and is an inhibitor of cytochrome P450 (CYP) 3A4/5, there is a high potential for drug-drug interactions when boceprevir is administered with other therapies, particularly when treating patients with chronic HCV infection who are often receiving other medications concomitantly. Boceprevir is no longer widely used in the US or EU due to the introduction of second-generation treatments for HCV infection. However, in many other geographic regions, first-generation protease inhibitors such as boceprevir continue to form an important treatment option for patients with HCV infection. This review summarizes the interactions between boceprevir and other therapeutic agents commonly used in this patient population, indicating dose adjustment requirements where needed. Most drug interactions do not affect boceprevir plasma concentrations to a clinically meaningful extent, and thus efficacy is likely to be maintained when boceprevir is coadministered with the majority of other therapeutics. Overall, the drug-drug interaction profile of boceprevir suggests that this agent is suitable for use in a wide range of HCV-infected patients receiving concomitant therapies.

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Pharmacokinetic interaction between HCV protease inhibitor boceprevir and methadone or buprenorphine in subjects on stable maintenance therapy

Cited by 23 publications

References 23 publications

A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice

A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice

Psychiatric treatment considerations with direct acting antivirals in hepatitis C

Clinical Pharmacology Profile of Boceprevir, a Hepatitis C Virus NS3 Protease Inhibitor: Focus on Drug–Drug Interactions

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