Concomitant use of low molecular weight heparin mitigates bortezomib-induced peripheral Neuropathy: Analysis of the...

The concurrent use of bortezomib and anticoagulants, including heparin and low molecular weight heparin (LMWH), is increasingly common in the standard clinical management of multiple myeloma. Peripheral neuropathy (PN) is a common and significant toxicity associated with bortezomib. This study aimed to identify and characterize interaction signals for the concomitant use of bortezomib with heparin/LMWH, resulting in PN, using data mining of the FDA Adverse Event Reporting System (FAERS). Adverse event (AE) reports to FAERS were analyzed. We conducted disproportionality analysis to detect PN signals associated with the combined use of bortezomib and heparin/LMWH by estimating reporting odds ratio (ROR) with 95 % confidence interval (CI). Adjusted odds ratios (ORs) were calculated using logistic regression analysis (adjusting for age, sex, and reporting year), and the Ω shrinkage measure method was used to further confirm the findings. Subset data analysis was performed based on the use of heparin and LMWH as a specific drug. From 84,428 AE reports, including 2805 PN reports, the combined use of bortezomib and heparin/LMWH was associated with a lower PN reporting (OR = 1.852, 95 % CI, 1.098-3.126) compared to bortezomib monotherapy (OR = 3.809, 95 % CI, 3.435-4.224), indicating a significant interaction signal. The results remained significant according to the Ω shrinkage measure method. In the subset analyses, an interaction signal was identified for enoxaparin but not for heparin. FAERS data suggest that combining bortezomib and LMWH, specifically enoxaparin, is associated with a reduced risk of PN reporting. No significant interaction was found between bortezomib and heparin.