Medication Associations With Severe Cutaneous Adverse Reactions: A Case/Non-Case Analysis Using the FDA Adverse Event Reporting System.

ABSTRACT

BACKGROUND: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) are potentially life-threatening severe cutaneous adverse reactions (SCARs). Although the classical causal agents of SCARs (antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs, and allopurinol) are well characterized, there has been little update to this list to account for newly marketed medications. OBJECTIVE: To provide an updated and stratified list of medications with significant reporting odds ratios (RORs) of SCARs. METHODS: A case/non-case analysis using the United States FDA Adverse Event Reporting System was performed. RESULTS: As expected, the prototypical medication classes made up the majority of reported cases of SJS, TEN, AGEP, and DRESS (77%, 64%, 75%, and 72%, respectively). In addition, several infrequently or previously undescribed classes/medications implicated in SCARs were identified to have significant ROR signals, including acetylcysteine, anticoagulants, diuretics, immunotherapies, proton pump inhibitors, antivirals, and antifungals. Among these reported for SJS were acetylcysteine (ROR 64.38) and fluconazole (ROR 17.13). For TEN, we identified furosemide (ROR 26.32), spironolactone (ROR 14.45), fluconazole (ROR 30.21), amphotericin B (39.06), and acetylcysteine (ROR 93.12). For AGEP, we identified acyclovir (ROR 61.72), valacyclovir (ROR 30.76), and enoxaparin (ROR 27.37). For DRESS, we identified vemurafenib (ROR 17.35), acyclovir (ROR 30.63), abacavir (ROR 26.62), raltegravir (ROR 23.27), and valacyclovir (ROR 21.77) to have strong reporting odds. CONCLUSION: Our analysis provides an updated tool for physicians to reference when identifying suspected SCARs and a basis for future studies to investigate atypical medication causality.