Drug interactions between buprenorphine, methadone and hepatitis C therapeutics

ABSTRACT

Introduction: People who inject drugs (PWID) and other individuals with opioid use disorders have a dramatically higher prevalence of hepatitis C virus (HCV) infection than the general population. The availability of novel direct acting antivirals (DAAs) for the treatment of HCV infection with very high efficacy, improved tolerability and shortened treatment durations have led to global efforts to ramp up treatment for all HCV-infected individuals to prevent or delay complications of the disease. Individuals with opioid use disorders, including those on medication-assisted therapy such as methadone or buprenorphine, are a key demographic group that can benefit from HCV treatment given their high HCV prevalence; however, pharmacokinetic and pharmacodynamic drug interactions could blunt their utility.

Areas covered: We performed a comprehensive literature review of published and unpublished data from PubMed database, relevant conference abstracts/proceedings and FDA approved drug package inserts, to review the pharmacokinetic (PK) profile and drug interactions between currently approved HCV DAAs and methadone and buprenorphine.

Expert opinion: The paper highlights specific drug combinations which result in altered opioid drug levels including telaprevir/methadone, daclatasvir/buprenorphine, and Abbvie 3D combination regimen (paritaprevir, ritonavir, ombitasvir and dasabuvir)/buprenorphine. However, concurrent pharmacodynamics assessments did not reveal significant signs and symptoms of opioid withdrawal or toxicity that would preclude concurrent administration.

KEYWORDS:

• Chronic pain
• direct-acting antiviral agent
• hepatitis C virus
• opioid use disorder
• opioids

Article highlights

• Sofosbuvir and ledipasvir are not metabolized by hepatic CYP 450 enzymes, therefore can be co-administered with medications that induce or inhibit the enzymes without concern for interactions.

• Telaprevir reduces the Cmax and AUC of R-methadone by 29% and reduces the Cmin by 31%. S-methadone Cmax, AUC and Cmin, while R-methadone is reduced by 35%, 36% and 40%, respectively.

• Daclatasvir increases buprenorphine Cmax, AUC and Cmin by 30%, 37% and 17%. Norbuprenorphine Cmax, AUC, and Cmin are increased by 65%, 62%, and 46% respectively.

• Paritaprevir/ritonavir/ombitasvir and dasabuvir results in significant increase in buprenorphine exposure when they are co-administered. Buprenorphine Cmax, AUC, and Cmin increased by 218%, 207%, and Cmin 312%. Norbuprenorphine Cmax, AUC, and Cmin increased by 207%, 184%, and 210%.

• No significant pharmacodynamic effects were reported in the interaction studies reported between approved DAAs and buprenorphine or methadone and dose adjustments are not recommended. It remains prudent to exercise careful education and observation of patients regarding side effects when these medications are co-administered.

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Declaration of interests

O Ogbuagu has served on an advisory board for Gilead Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.