Pharmacovigilance analysis of drug-induced hypofibrinogenemia using the FDA Adverse Event Reporting System.

Background: Drug-induced hypofibrinogenemia has received increasing scrutiny; however, the specific drugs involved remain poorly characterized. Hypofibrinogenemia can have significant clinical implications, including increased bleeding risks.

Aim: This study aimed to utilize the FDA Adverse Event Reporting System (FAERS) to identify and analyze drugs frequently implicated in drug-induced hypofibrinogenemia.

Method: A disproportionality analysis was conducted using FAERS data from January 2004 to March 2024. Various statistical tools were used, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio, Medicines and Healthcare Products Regulatory Agency metrics, and Bayesian confidence propagation neural network.

Results: The analysis included 17,627,340 cases involving 52,373,206 adverse events, with 1,661 cases identified as hypofibrinogenemia. The top five drugs associated with hypofibrinogenemia by case number were methotrexate (124 cases), tigecycline (119 cases), tocilizumab (100 cases), pegaspargase (83 cases), and alteplase (57 cases). The drugs ranked by signal strength based on ROR included eravacycline (ROR 2173.84, 95% CI 1208.80-3909.30), tigecycline (ROR 747.34, 95% CI 619.03-902.24), crotalidae polyvalent immune Fab (ROR 407.67, 95% CI 291.07-570.99), pegaspargase (ROR 216.06, 95% CI 173.15-269.61), and asparaginase (ROR 184.93, 95% CI 132.18-258.72).

Conclusion: This analysis of FAERS data identified 52 drugs associated with hypofibrinogenemia, most (88.5%) of which do not mention this risk in their prescribing information. These findings demonstrate the need for the monitoring of blood fibrinogen and may serve as a reference for the explore of the characteristics and underlying mechanism of drug-induced hypofibrinogenemia in the real world.