Safety Evaluation of the Combination with Dexrazoxane and Anthracyclines: A Disproportionality Analysis Based on the Food and Drug Administration Adverse Event Reporting System Database

Abstract

Objectives: As one of the important interventions to alleviate anthracycline-related cardiotoxicity (ARC), the safety assessment of dexrazoxane in clinical practice is particularly important. This study aims to evaluate the actual efficacy and potential adverse effects of dexrazoxane in clinical practice by analyzing the reports of adverse events (AEs) related to the combination with dexrazoxane and anthracyclines. Methods: We utilized four disproportionality analysis methods to analyze AE reports of the combination with dexrazoxane and anthracyclines in the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the third quarter of 2014 to the first quarter of 2024. Results: Under the three backgrounds, a large number of preferred terms (PTs) such as cardiac failure disappeared in the combined group, and the PTs with significant signal values were mainly concentrated in infections and infestations. For patients under 18, some PTs associated with infections and infestations disappeared after the combination of the two drugs. Conclusions: Dexrazoxane can effectively alleviate ARC, but it may also increase the risk of infection. For infections and infestations, children under 18 years old are more likely to benefit from the combination therapy. More attention should be paid to infectious AEs in the clinical use of dexrazoxane, though disproportionality analysis is a hypothesis-generating approach.

Keywords: anthracyclines; cardiotoxicity; children; dexrazoxane; disproportionality analysis; infection.

Figure 1

Comparison of AE signal detection results for the three groups under the background of all datasets. #: PT in anthracyclines labels; *: PT in dexrazoxane labels.

Figure 2

Comparison of AE signal detection results for the three groups under three backgrounds. #: PT in anthracyclines labels; *: PT in dexrazoxane labels.

Figure 3

Comparison of AE signal detection results for the two groups with cardiac disorders under the background of all datasets. #: PT in anthracyclines labels; *: PT in dexrazoxane labels.

Figure 4

Comparison of AE signal detection results for age subgroups under the background of all datasets. #: PT in anthracyclines labels; *: PT in dexrazoxane labels.