The aim of this study was to determine the clinical and pharmacological compatibility of methadone with modern direct antiviral agents (DAAs) in the treatment of chronic viral hepatitis in patients with opioid dependence. Methadone maintenance therapy is an effective approach to reducing the prevalence of HIV/AIDS; however, the risk of hepatitis virus infection among drug-dependent individuals exceeds 80 %, necessitating combined treatment. Bibliosemantic, analytical, statistical, and graphical methods were used, along with certified protocols from DrugBank and Hep Drug Interactions databases. It was established that entecavir, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) do not interact with the CYP450 system and are compatible with methadone, ensuring safe therapy of hepatitis B virus (HBV). Direct-acting antivirals against hepatitis C virus (HCV) — sofosbuvir/velpatasvir, glecaprevir/ pibrentasvir — likewise do not affect methadone pharmacokinetics and can be administered within opioid substitution programs. In contrast, peginterferons α-2a and α-2b increase serum methadone concentrations by 10—15 %, and in rare cases up to 100 %, leading to potential toxicity and cardiac complications (QT prolongation, torsades de pointes). Ursodeoxycholic acid may theoretically induce CYP3A4 and alter methadone absorption, although the clinical relevance remains uncertain. Thus, most current DAAs can be safely co-administered with methadone, while interferon-based therapy requires careful monitoring and possible dose adjustmen