(040) Bleeding related adverse events associated with antiviral treatment in influenza patients: a disproportionality analysis using FDA adverse event reporting system (FAERS)

Publication Number: 1036

Background: The US Centers for Disease Control and Prevention (CDC) guideline suggests antiviral (AV) therapy for individuals with confirmed diagnosis or symptoms of influenza, especially for those who are at high risk of disease complications. A number of case studies have reported bleeding events among AV users and the prescribing information notes postmarketing reports of gastrointestinal bleeding.

Objectives: To compare reports of gastrointestinal (GI) and intracranial (IC) bleeding associated with AVs (oseltamivir, zanamivir, peramivir, and baloxavir marboxil) indicated for influenza to antibiotics and all other medications.

Methods: We queried the FAERS database using OpenVigil 2.1 to find GI and IC bleeding events reported between 2004Q1 to 2022Q3. Bleeding events were identified using “narrow Standardized MedDRA Query (SMQ)” terms. AVs were identified using ATC codes and generic drug names, whereas antibiotics (AB) were identified using only ATC codes. We estimated the Reporting Odds Ratio (ROR) and 95% confidence interval comparing the occurrence of GI and IC bleeding events in reports where influenza AVs were suspected to those with (1) all other medications and (2) antibiotics. We also estimated RORs comparing the different AVs.

Results: We identified 135,658 and 157,241 case reports of GI and IC bleeds respectively. Among these, AVs were the suspect drug for 256 GI bleed and 78 IC bleed events. Most of these bleeds were associated with either oseltamivir (199 GI and 65 IC bleeds) or baloxavir (43 GI and 5 IC bleeds). Antibiotics were the suspect for 7,122 GI and 4,071 IC bleeds. The ROR for GI bleeds when AVs were compared to all other medications was 1.26 (95% CI 1.12, 1.43). The ROR for IC bleeds when AVs were compared to all other medications was 0.33 (95% CI 0.26, 0.80). When AVs were specifically compared to ABs, the ROR for GI bleed was 0.99 (95% CI 0.87, 1.11) and for IC bleed was 0.52 (95% CI 0.42, 0.65). Compared to oseltamivir, the ROR for baloxavir marboxil and GI bleed was 2.13 (95% CI 1.72,2.65); for IC bleed the ROR was 0.74 (95% CI 0.52, 1.06).

Conclusions: We observed a signal for GI bleeds for AV therapy in comparison to all other medications; however, it was not present when compared to ABs. In contrast, we did not find any AV therapy related signals for IC bleeding. Among the AVs, baloxavir exhibited noteworthy signals of GI bleeding signals compared to oseltamivir. These results should be interpreted with caution as findings from disproportionality analysis do not indicate causal relationships, but may warrant future research.