No Clinically Relevant Drug-Drug Interactions Between Methadone or Buprenorphine/Naloxone and Anti-Viral Combination Glecaprevir and Pibrentasvir [PublishAheadOfPrint]

The combination of glecaprevir (formerly ABT-493), a nonstructural (NS) protein 3/4A protease inhibitor, and pibrentasvir (formerly ABT-530), a NS5A protein inhibitor, is being developed as treatment for HCV genotype 1-6 infection. The pharmacokinetics, pharmacodynamics, safety, and tolerability of methadone or buprenorphine/naloxone when coadministered with the glecaprevir and pibrentasvir combination in HCV-negative subjects on stable opioid maintenance therapy were investigated in a Phase 1, single-center, two-arm, multiple-dose, open-label sequential study. Subjects received methadone (Arm 1) or buprenorphine/naloxone (Arm 2) once daily (QD) as per their existing individual prescriptions alone (days 1-9) and then in combination with glecaprevir 300 mg QD and pibrentasvir120 mg QD (days 10-16) each morning. Dose-normalized exposures were similar with and without glecaprevir and pibrentasvir for R- and S- methadone (≤ 5% difference) and for buprenorphine and naloxone (≤ 24% difference); norbuprenorphine area under the curve was 30% higher, consistent with maximum and trough plasma concentrations that increased by 21% to 25%. No changes in pupil response, short opiate withdrawal scale, or desire for drugs questionnaire were observed when glecaprevir and pibrentasvir were added to methadone or buprenorphine/naloxone therapy. No dose adjustment is required when glecaprevir and pibrentasvir are coadministered with methadone or buprenorphine/naloxone.

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