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People who inject drugs (PWID) are often affected by physical and psychological diseases and prone to co-medication. In Germany, about 50% of PWID are on opioid substitution therapy (OST). Comprehensive data on pharmacotherapy in these patients may help to select antiviral therapy against hepatitis C virus (HCV) infections and avoid drug–drug interactions (DDIs). We compared co-medication profiles based on statutory health insurance prescriptions (IQVIA database) of PWID (n = 16,693), OST (n = 95,023) and treated HCV patients (n = 7886). Potential DDIs with the most widely used HCV direct-acting agents (Sofosbuvir/Velpatasvir, Glecaprevir/Pibrentasvir and Elbasvir/Grazoprevir) were evaluated based on the Liverpool DDI database. Co-medication was present in 57% of PWID, 57% of OST, 44% of patients on HCV therapy and 46% in a subgroup receiving OST+HCV therapy (n = 747 of 1613). For all groups, co-medication belonging to ATC-class N (nervous system) was most commonly prescribed (in 75%, 68%, 41% and 62% of patients, respectively). Contraindications (i.e., DDIs precluding HCV therapy) were infrequent (0.4–2.5% of co-medications); potential DDIs with HCV therapies were shown for 13–19% of co-medications, namely for specific substances including some analgesics, antipsychotics, anticoagulants, lipid lowering drugs and steroids. In conclusion, concomitant pharmacotherapy is common and clinically relevant when treating HCV infection in PWID.

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