Tamiflu Linked to More Adverse Events than Xofluza for Treating Flu

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A recent study of FDA Adverse Event Reporting System (FAERS) data drew attention to the potentially toxic effect of oseltamivir (Tamiflu) on the liver when used to treat the flu, and the potential use of baloxavir marboxil (Xofluza) as a safer alternative in patients with liver diseases.

A study conducted using real-world data to investigate the post-market safety of both popular flu medicines outlined notable adverse event (AE) categories to provide clinicians and patients with insight into preferred treatment options for influenza from a safety perspective.

“To our knowledge, we are the first study where the AEs of oseltamivir and baloxavir marboxil were comprehensively evaluated and compared using a vast real-world AE reporting database,” investigators wrote.

According to the US Centers for Disease Control and Prevention (CDC), the effects of flu vary but generally pose a substantial health burden, resulting in an estimated 9.3 to 41 million illnesses, 100,000 to 710,000 hospitalizations and 4,900 to 51,000 deaths annually between 2010 and 2023.

Although it is preventable with annual vaccination, for those who are infected and at an increased risk of influenza-related complications, antiviral treatment is recommended. However, real-world data comparing the safety of these medications are limited.

To investigate post-market safety profiles and real-world safety data of two FDA-approved influenza antiviral treatments, oseltamivir and baloxavir marboxil, investigators sourced data from the FAERS from the first quarter of 2004 through the fourth quarter of 2022. However, investigators noted adverse reaction data for baloxavir marboxil were only available from the first quarter of 2018 to the fourth quarter of 2022.

After duplicate records were removed, investigators included analyses involving at least three reports and recorded AEs using preferred terms from the Medical Dictionary for Drug Regulatory Activities.

The final analysis included 15,104 Tamiflu cases and 1594 Xofluza cases. Within the 2753 different types of AE reports for Tamiflu, totaling 43,675 reports, 242 AEs displayed significant safety signals. In the 536 different types of AE reports for Xofluza, comprising 3315 reports, 55 AEs exhibited significant safety signals.

Investigators performed differential analyses of SOC signal strength for age groups younger than 18 years versus 18 to 64 years and age groups older than 64 years versus 18 to 64 years for both medication groups.

For Tamiflu, in the age group younger than 18 years compared to 18 to 64 years, a significant safety signal was observed in nervous system disorders, whereas in the age group older than 64 years compared to 18 to 64 years, more significant safety signals were observed in renal and urinary disorders, metabolism and nutrition disorders, and cardiac disorders.

For Xofluza, in the age group younger than 18 years compared to 18 to 64 years, a more significant safety signal was observed in general disorders and administration site reactions, whereas in the age group older 64 years compared to 18 to 64 years, more significant safety signals were observed in metabolism and nutrition disorders, cardiac disorders, musculoskeletal and connective tissue disorders, and blood and lymphatic system disorders.

Investigators noted Tamiflu had 221 specific AEs, whereas Xofluza had 34. Wain analysis revealed 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains.

Significant AEs for Tamiflu included appendicolith, acne infantile, acute macular neuroretinopathy, proctitis and Purpura senile. Designated adverse events (DMEs) associated with Tamiflu included fulminant hepatitis, ventricular fibrillation, and toxic epidermal necrolysis.

Significant AEs for Xofluza included melena, cystitis hemorrhagic, ileus paralytic, and hemorrhagic diathesis. DMEs associated with Xofluza included rhabdomyolysis.

Investigators pointed out multiple limitations to these findings, including the inability to confirm any causal relationships, the potential influence of lost data, disease complications, comorbidities, and drug interactions on safety signal data, the large difference in sample size between the drugs, and the fact that the FAERS database only accounts for reported cases rather than all cases.

“This study offers crucial safety insights for guiding drug selection in seasonal influenza therapy. Key findings highlight the need for vigilant monitoring of fulminant hepatitis during oseltamivir treatment, especially in patients with liver-related diseases,” investigators concluded. “Baloxavir marboxil, with lower hepatic toxicity, emerges as a promising alternative for patients with liver diseases."

This article was originally published on sister site HCPLive.