Postdoctoral Fellow, Clinical Pharmacogenomics University of Colorado Anschutz Medical Campus Denver, Colorado, United States
Background: Sex differences in drug-dosing and clinical outcomes have been described in the literature for decades, but are not routinely utilized in clinical practice. We sought to characterize available sex-specific data, compare occurrences of adverse drug events (ADEs) between women and men, and identify specific medications which may warrant sex-specific approaches to clinical practice. Methods: Using a list of the top 50 drugs prescribed in the U.S. in 2019, we evaluated drug information resources (FDA labels, clinical practice guidelines, and tertiary medication resources) for clinical data regarding sex-specific considerations. We used the FDA Adverse Event Reporting System (FAERS) Public Dashboard to investigate sex-specific differences in ADEs for nine drugs with plausible evidence. Descriptive and comparative statistics were used to characterize the findings. Results: Fifty drugs were included in this analysis, 28 (56.0%) of which had sex-specific data in their FDA label, 19 (38.0%) from tertiary medication resources, and 6 (12.0%) from clinical guidelines. Thirteen (26.0%) had sex-specific data from at least one resource regarding pharmacokinetic (PK) differences, eight (16%) for clinical outcome differences, and eight (16%) for safety differences. Only zolpidem had sex-specific dosing recommendations in its drug label. Preliminary FAERS analyses showed a significant association with an increased risk of lisinopril-induced cough in women vs. men (modified PRR 2.46, Χ2 1529.1; p < 0.0001). Conclusion: Data exist supporting sex-specific differences in drug PK, clinical outcomes, and safety measures; associated educational efforts can help mitigate sex-related inequalities in healthcare. Further research is warranted to better define how biological sex affects medication response and clinical outcomes.
