The investigators suggested that GZR may be coadministered with buprenorphine/ naloxone without dose adjustment. However, monitor the patient closely as PK parameters of GZR were variably affected when coadministered with buprenorphine/naloxone.
Grazoprevir vs opioid maintenance agents
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Study Design
In single-center, open-label, fixed sequence, and multiple dose study, 24 HCV-negative adults with ages 18-55 years on stable opiate maintenance therapy with methadone (20-150 mg daily) received grazoprevir (GZR; formerly known as MK-5172) 200 mg once daily for 10 days.
Study Results
Coadministration of GZR (200 mg daily) for 10 days did not significantly impact exposures of buprenorphine (2% decrease AUC) or naloxone (10% increase AUC). Geometric mean ratios (GMRs; GZR + buprenorphine/naloxone / buprenorphine/naloxone) [90% CIs] of AUC and Cmax for buprenorphine were 0.98 [0.81, 1.20] and 0.90 [0.76, 1.07], respectively, while those for metabolite norbuprenorphine were 1.13 [0.97, 1.32] and 1.10 [0.97, 1.25], respectively. GMRs (GZR + buprenorphine/naloxone / buprenorphine/naloxone) [90% CIs] of AUC and Cmax for naloxone were 1.10 [0.82, 1.46] and 1.00 [0.80, 1.27], respectively.Coadministration of these agents modestly decreased GZR AUC by 16% and Cmax by 21%, but [90% CI] were wide; [0.53, 1.33] for AUC and [0.39, 1.59] for Cmax.No symptoms of opiate toxicity or withdrawal were noted.
References
Fraser IP, W Yeh, C Reitmann, et al. Lack of pk interaction between the hcv protease inhibitor mk-5172 and methadone or buprenorphine/naloxone in subjects on opiate maintenance therapy [abstract o_16_pk]. 8th International Workshop On Clinical Pharmacology Of Hepatitis Therapy. Cambridge, USA. ; 2013.
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