(B-093) Preliminary results from a European post authorization study to assess the safety of Paxlovid among patients with moderate or severe hepatic or renal impairment

Background: Paxlovid is an oral antiviral licensed in January 2022 in Europe to treat COVID‑19 in patients who do not require supplemental oxygen and who are at increased risk for progression to severe COVID‑19. Here, we describe preliminary results from a PASS to assess the safety of Paxlovid in populations with hepatic or renal impairment not studied in clinical trials.

Objectives: To assess the safety of Paxlovid in persons with moderate or severe hepatic or renal impairment and adverse events resulting from drug overexposure potentially related to hepatic or renal impairment.

Methods: This ongoing cohort study used data from SIDIAP (Spain), CPRD Aurum (UK), and SNDS (France) from January 2022 until December 2023/January 2024. In SIDIAP and CPRD, the ConcePTION common data model and common analytics were used. In France, user counts from the general population were obtained via Open Medic.
The study included users of Paxlovid who had moderate or severe hepatic or renal impairment, ≥12 months of enrollment, and prior COVID-19 diagnosis. Follow-up started the date of first use ever and ended at the earliest of the following: 30 days after time zero, outcome, death, disenrollment, or end of study period.
Primary outcomes were (1) hepatic transaminase elevations, clinical hepatitis, or jaundice; (2) severe nausea, vomiting, diarrhea, or abdominal pain; (3) dysgeusia; (4) headache; (5) hypertension; (6) anaphylactic reactions; and (7) data-driven outcomes (identified based on conditions recorded within 30 days after exposure to Paxlovid).

Results: In SIDIAP, of the 35 Paxlovid users with hepatic impairment, 1 (2.9%) had hepatic transaminase elevations postexposure. Similarly, of the 560 users with renal impairment, 4 (0.7%) had headaches and 23 (7.6%) had hypertension postexposure. In CPRD, there were 0 Paxlovid users with hepatic impairment. However, of the 37 Paxlovid users with renal impairment in CPRD, 1≤n≤4 had severe abdominal pain and 1≤n≤4 had a headache postexposure. In both SIDIAP and CPRD, data-driven outcomes were mostly related to COVID-19, such as respiratory infections and symptoms. In France, < 206,069 subjects in the general population had ≥1 Paxlovid dispensing; use among patients with hepatic or renal impairment will be assessed in future analysis.

Conclusions: The small number of Paxlovid-exposed patients with moderate or severe hepatic or renal impairment was expected given the short observation period and the low prevalence of Paxlovid use in these populations, in alignment with recommendations from the EU and UK summary of product characteristics. Overall, the observed number of outcomes was low, and the high frequency of hypertension in SIDIAP in patients with renal impairment was likely driven by the inclusion of prevalent hypertension events.