Reported safety of HCV direct-acting antivirals with opioids: 2017 to 2021

ABSTRACT

Background and aims: As a result of disengagement in addiction care during the COVID-19 pandemic, there has been a record increase in mortality associated with opioid overdoses (primarily fentanyl), particularly in North America. In the USA there were over 100, 000 overdose deaths in 2021, while over 2000 were recorded in the province of British Columbia. As we attempt to develop novel ways to increase HCV treatment following ≥30% declines during the pandemic, we evaluated publicly available adverse events (AEs) reports for opioids and DAAs to assess whether safety concerns from potential drug interactions arewarranted, particularly amongst those using fentanyl. Method: Data were downloaded from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) Public Dashboard. AEswith the DAAs glecaprevir/pibrentasvir (G/P), sofosbuvir/ velpatasvir (SOF/VEL), ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/ velpatasvir/voxilaprevir (SOF/VEL/VOX), andelbasvir/grazoprevir (EBR/ GZR) listed as the suspect product were analyzed with an initial received date from July 28, 2017-December 31, 2021, as were opioidassociated AEs for all 2017–2021. Subsequently, AEs were counted based on listed concomitant use of opioids (fentanyl, oxycodone, hydrocodone), or overdose outcomes irrespective of concomitant opioid use. Data are descriptivewithout any statistical analyses. Results: In the reporting period, 40 total AEs were recorded with concomitant DAA and fentanyl use, 14 resulting in death (G/p = 3, SOF/VEL = 11;Table 1);626 total AEs were recorded with concomitant DAA and oxycodone or hydrocodone use, 28 resulting in death. Separately, overdose events were reported 196 times, 32 resulting in death. The number of overdoses declined each year from 2018 (N = 56) to 2021 (N = 29). Fentanyl AEs showed no trend year to year. Table 1 FAERs AEs and deaths with opioids and with concomitant HCV DAAs. (Table Presented) *N represents the sum of fentanyl, oxycodone, and hydrocodone overdose AEs and deaths, whereas n’s for DAA overdose AEs and deaths are irrespective of concomitant opioids. Conclusion: With the limitations of FAERS data (under or duplicate reporting, inability to establish causation or incidence), these data showthat among ~58, 000 fentanyl, ~189, 000 oxycodone, and ~100, 000 hydrocodone AEs reported to FAERS since 2017, a small proportion (0.19%) have been reported in association with concomitant DAA therapy, with no association between recorded events and a specific DAA regimen. This should reassure HCV treaters on a lack of safety signal for concomitant opioid and DAA use.