Drug-Associated Alcohol Intolerance: A Real-World Disproportionality Analysis Study

Background: Alcohol intolerance, characterized by adverse reactions following alcohol consumption, can occur due to interactions between alcohol and certain medications. Despite its clinical significance, evidence for alcohol intolerance induced by commonly prescribed drugs remains limited. This study aimed to identify signals for drug-associated alcohol intolerance using the United States Food and Drug Administration (USFDA) Adverse Event Reporting System (AERS). Methods: A disproportionality analysis was conducted on the USFDA AERS spanning the first quarter of 2004 to the second quarter of 2024. Cases were identified using the Preferred Term "alcohol intolerance". Duplicate reports were excluded, and only drugs classified as primary suspects were analyzed. The key disproportionality measures included frequentists (reporting odds ratio [ROR]) and Bayesian methods. Top 10 drugs associated with alcohol intolerance were identified using volcano plot. Subgroup analyses by age and gender were performed, and clinical outcomes were evaluated. Results: Among 29 153 222 reports, 406 cases of drug-associated alcohol intolerance were identified, predominantly in adults aged 18 to 65 years. Multiple drug classes demonstrated significant signals including antimicrobials (metronidazole [ROR: 27.4], cefoperazone [ROR: 290.6]), and ketoconazole [ROR: 27.6]), respiratory medications (salmeterol [ROR: 6], mometasone [ROR: 6], and dupilumab [ROR: 6.1]), and psychoanaleptics (bupropion [ROR: 8.1] and several selective serotonin reuptake inhibitors). The Volcano plot analysis highlighted 10 drugs with particularly strong associations, including cefoperazone, spiramycin, metronidazole, and dupilumab. Outcomes included hospitalization (16%), disability (6.4%), and death (1.7%). Conclusion: This study highlights significant associations between several medications and alcohol intolerance, emphasizing the need for further research to confirm these findings and inform clinical guidelines to optimize patient safety.