Risk Factors for Drug-Induced Severe Cutaneous Adverse Reactions: A Real-World Pharmacovigilance Analysis

Drug-induced severe cutaneous adverse reactions (SCARs) are rare but potentially life-threatening drug-induced hypersensitivity reactions. Current understanding of the drug risks associated with SCARs is limited, emphasizing the need for more research to identify and understand medications that may trigger these reactions. This study aimed to identify risk factors and suspect drugs associated with SCARs. Disproportionality analysis was conducted through the case-control design using the FDA Adverse Event Reporting System (FAERS) database of drug-induced SCARs. The reporting odds ratios (ROR) were used to analyze reports of drug-induced SCARs from January 1, 2004, to March 31, 2025. Least absolute shrinkage and selection operator (LASSO), and multivariable regression analyses were conducted to identify risk factors associated with SCARs. Bonferroni correction was applied to adjust for multiple comparisons. A total of 103 337 drug-induced SCARs cases were identified. The median patient age was 57.00 years (IQR 37.00-70.00), with a nearly equal sex distribution (49.26% female, 40.57% male). Disproportionality analysis identified 415 drugs with positive signals for drug-induced SCARs. Logistic regression identified older age, male sex, and 114 drugs as independent risk factors for drug-induced SCARs, including amlodipine (adjusted ROR = 2.89), bisoprolol (adjusted ROR = 3.52), and losartan (adjusted ROR = 2.77). In the non-Asian population, the strongest signals were observed for allopurinol (adjusted ROR = 98.52), cefotaxime (adjusted ROR = 68.52), and lamotrigine (adjusted ROR = 38.59), whereas apalutamide (adjusted ROR = 14.57), ipilimumab (adjusted ROR = 3.24), and acetylsalicylic acid (adjusted ROR = 2.85) were detected only in Asians. The median time to onset (TTO) of drug-induced SCARs was 14 days (IQR 4-47). The Asian population had a significantly shorter TTO compared to the non-Asian population (p < 0.001). This study uses FAERS data to analyze risk factors for drug-induced SCARs, emphasizing early identification and discontinuation of suspected drugs to enhance patient safety.