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Bumex (Bumetanide) & Nitrosamine Impurity

    Basic Details
    Status
    Complete
    Last Updated
    Tuesday, September 24, 2024
    Original Posting Date
    Health Outcome(s)
    nitrosamine impurity
    Purpose
    Drug and Outcome Analysis
    Meets requirements of FD&C Act Sec 505(o) prior to requiring a PMR
    No
    Study Summary

    The U.S. Food and Drug Administration (FDA) initiated this study in the Sentinel System to assess whether there is a signal of carcinogenicity for bumetanide due to nitrosamine-related impurity using epidemiological data. N-Nitroso bumetanide can form as a degradation impurity in some formulations of bumetanide during shelf-life. Due to its structural similarity to other nitrosamine genotoxic impurities, it is potentially genotoxic.

    This study explored whether bumetanide is associated with an increased risk of cancer compared to other loop diuretics and the background population.

    Results from Sentinel analyses did not demonstrate an increased risk of four biologically plausible cancer outcomes (liver, colorectal, bladder and esophageal cancers) among bumetanide users compared to users of other loop diuretics. Similarly, a dose-response signal was not suggested by the findings.

    Results from this study were shared with FDA’s nitrosamine task force as part of their efforts to address nitrosamine-related impurities in human drug products.