Identifying Sex Differences in Adverse Events Reported on Opioid Drugs in the FDA’s Adverse Event Reporting System (FAERS)

Purpose: Opioids are widely used for pain management but are associated with adverse events that may differ between women and men. However, post-marketing safety data are rarely examined at the individual level to characterize these sex differences. This study aimed to identify sex disparities in opioid-associated adverse events using the FDA Adverse Event Reporting System (FAERS) to inform safer opioid selection for women. Methods: Opioid drugs were identified using the FDA’s Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) list and official drug labeling. Relevant FAERS reports were extracted, and adverse events were classified into 27 System Organ Classes (SOCs) based on the Medical Dictionary for Regulatory Activities (MedDRA). Sex-specific signals of disproportionate reporting were evaluated using proportional reporting ratios and reporting odds ratios for drug–SOC pairs. Results: Across most opioid drugs and SOCs, adverse events were reported more frequently in women than in men. The largest sex disparities were observed for codeine, fentanyl, tapentadol, hydrocodone, and sufentanil, with significantly higher disproportionate reporting rates among women. These findings indicate pronounced sex-specific differences in the post-marketing safety profiles of several commonly used opioids. Conclusions: Women demonstrate higher disproportionate reporting of adverse events for certain opioid medications, particularly codeine and fentanyl. These results suggest the need for increased awareness of sex-specific safety differences and support sex-informed prescribing and monitoring strategies to improve opioid safety in women. Since pharmacists are medication experts and play a key role in promoting rational and safe use, our findings may further support pharmacists counseling patients and monitoring for opioid-related adverse events.