Comparison of the incidence of bleeding between baloxavir marboxil and other anti‐influenza drugs among outpatients with influenza virus infection: A retrospective cohort study using an employment‐based health insurance claims database in Japan

Abstract

Purpose: Alerts for bleeding events are included in the Japanese package inserts of some anti-influenza drugs, including baloxavir marboxil and oseltamivir. However, there are few reports on the incidence of bleeding events during treatment with antiinfluenza drugs. This large-scale quantitative assessment compared the incidence of bleeding events in influenza patients treated with baloxavir and other anti-influenza drugs and in untreated patients.Methods: This retrospective cohort study used a large-scale Japanese employmentbased health insurance claims database provided by JMDC Inc. and included outpatients diagnosed with influenza between October 1, 2018 and April 11, 2019. Bleeding events were identified by International Classification of Diseases 10th revision codes. Incidences were compared between patients treated with baloxavir or neuraminidase inhibitors and untreated patients.Odds ratios were calculated after exact matching to adjust for potential confounders.

Antiviral influenza treatments and hemorrhage‐related adverse events in the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database

“…Results from our study differ from these findings. 5 The primary difference lies in the aim and design of the two studies. 5 The prior observational study focused on comparing the risk of bleeding in baloxavir-treated patients with those treated with other drugs or untreated patients.…”

“…5 The primary difference lies in the aim and design of the two studies. 5 The prior observational study focused on comparing the risk of bleeding in baloxavir-treated patients with those treated with other drugs or untreated patients. 5 In contrast, the aim of our study was to identify It is imperative to approach the interpretation of these findings with due caution.…”

“…3,4 However, concerns have been raised regarding potential adverse effects associated with the use of these antivirals, including the risks of gastrointestinal (GI) hemorrhage and intracranial (IC) hemorrhage. 5,6 Bleeding events are reported as potential adverse reactions in package inserts of oseltamivir and baloxavir marboxil. 7,8 A recent study explored the risk of bleeding events in patients treated with influenza antivirals, providing valuable insights.…”

“…7,8 A recent study explored the risk of bleeding events in patients treated with influenza antivirals, providing valuable insights. 5 However, this study focused only on Japanese individuals from a employment-based health insurance database and was limited in scope, necessitating further investigation into this association. 5 Our study aims to build on these findings by employing a more inclusive approach to capture a comprehensive view of potential adverse effects associated with influenza antivirals across diverse demographics and treatment scenarios.…”

Antiviral drugs

“…In a retrospective cohort study based on a large-scale Japanese employment-based health insurance claims database, 498 237 patients (271 997 males and 226 240 females) were treated with anti-influenza drugs, with which 207 630 patients (207 630 males and 91 796 females) received baloxavir marboxil. In the baloxavir group, 397 bleeding events occurred (19%), which was similar to oseltamivir, zanamivir, and laninamivir ( Hara et al, 2021 ) [MC]. Patients receiving antiviral medications for influenze should be monitored for signs and symptoms of bleeding.…”