Hepatitis C therapy with pangenotypic direct-acting antivirals: Drug-drug interactions in drug-using HCV patients and antipsychotic-treated HCV patients.

People who use drugs (PWUD) are at high risk of hepatitis C virus (HCV) infection, and HCV patients often have psychiatric disorders requiring nervous system drugs, including antipsychotics. These medicines can interact with HCV treatment-related metabolic pathways producing DDIs (drug-drug interactions). This analysis focused on potential DDIs between direct-acting antivirals (DAAs) and concomitant medications used in PWUD/antipsychotics-treated HCV patients, alongside associated adverse events (AEs) and clinical interventions in Spain. Electronic medical records (BIG-PAC® database) were used to analyse adult HCV patients treated with glecaprevir/pibrentasvir (GLE/PIB) or sofosbuvir/velpatasvir (SOF/VEL) between 2017-2020. The study included 1,620 HCV patients, 985 identified as PWUD and 187 as antipsychotic users, 75% of whom were also PWUD. In the PWUD cohort, cardiovascular (CV) comorbidities were the most frequent; 22.7% patients were at risk of DDIs with CV, with the risk being higher in GLE/PIB-treated (36.8%) versus SOF/VEL (13.7%) (p<0.001). Cardiovascular AEs were more common in the GLE/PIB group. In the antipsychotic cohort, quetiapine was the most prescribed antipsychotic comedication (26.2%), followed by paliperidone (17.6%) and olanzapine (17.1%). Fifty-one per cent of those on GLE/PIB were at risk of DDIs versus 23% on SOF/VEL (p<0.001). Two AEs were reported in the GLE/PIB group (n=37): one patient on quetiapine at a dose <300mg/day experienced extrapyramidal symptoms, leading to DAA discontinuation, and another paliperidone-treated experienced sedation, necessitating a dose reduction. The findings highlight DDIs risks in HCV patients on antipsychotics or with substance addiction, particularly with GLE/PIB. Comprehensive clinical follow-up is essential to optimise treatment and improve patient safety. Electronic medical records (BIG-PAC® database) were used to analyse adult HCV patients treated with glecaprevir/pibrentasvir (GLE/PIB) or sofosbuvir/velpatasvir (SOF/VEL) between 2017-2020. The study included 1,620 HCV patients, 985 identified as PWUD and 187 as antipsychotic users, 75% of which were also PWUD. In the PWUD cohort, cardiovascular (CV) comorbidities were the most frequent; 22.7% patients were at risk of DDIs with CV, being the risk higher in GLE/PIB-treated (36.8%) versus SOF/VEL (13.7%) (p<0.001). Cardiovascular AEs were more common in the GLE/PIB group. In the antipsychotic cohort, quetiapine was the most prescribed antipsychotic comedication (26.2%), followed by paliperidone (17.6%) and olanzapine (17.1%). Fifty-one per cent of those on GLE/PIB were at risk of DDIs versus 23% on SOF/VEL (p<0.001). Two AEs were reported in the GLE/PIB group (n=37): one patient on quetiapine at a dose <300mg/day experienced extrapyramidal symptoms, leading to DAA discontinuation, and another paliperidone-treated experienced sedation, necessitating a dose reduction. The findings highlight DDIs risks in HCV patients on antipsychotics or with substance addiction, particularly with GLE/PIB. Comprehensive clinical follow-up is essential to optimise treatment and improve patient safety.