Abstract
Acute generalized exanthematous pustulosis (AGEP) is a rare skin adverse drug reaction. The pathophysiology and causative drugs associated with AGEP are poorly understood, with the majority of studies in AGEP focusing on a single-drug-outcome association. We therefore aimed to explore and characterize frequently reported drug combinations associated with AGEP using the WHO pharmacovigilance database VigiBase. In this explorative cross-sectional study of a pharmacovigilance database using a data-driven approach, we assessed individual case safety reports (ICSR) with two or more drugs reported to VigiBase. A total of 2649 ICSRs reported two or more drugs. Cardiovascular drugs, including antithrombotics and beta-blockers, were frequently reported in combination with other drugs, particularly antibiotics. The drug pair of amoxicillin and furosemide was reported in 57 ICSRs (2.2%), with an O/E ratio of 1.3, and the combination of bisoprolol and furosemide was recorded 44 times (1.7%), with an O/E ratio of 5.5. The network analysis identified 10 different communities of varying sizes. The largest cluster primarily consisted of cardiovascular drugs. This data-driven and exploratory study provides the largest real-world assessment of drugs associated with AGEP to date. The results identify a high frequency of cardiovascular drugs, particularly used in combination with antibiotics.
Highlights
Acute generalized exanthematous pustulosis (AGEP) is a rare but severe skin adverse drug reaction (ADR) [1]
We extracted all individual case safety reports (ICSRs) with AGEP recorded as the suspected ADR according to the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term version 22.1 from VigiBase via VigiLyze (https://vigilyze.who-umc.org/)
We extracted 5983 ICSRs with AGEP reported to the World Health Organization (WHO) VigiBase
Summary
Acute generalized exanthematous pustulosis (AGEP) is a rare but severe skin adverse drug reaction (ADR) [1]. This reaction is described as a neutrophilic hypersensitivity reaction (type IVd) [2], and it is characterized by the sudden presence of several miniscule nonfollicular pustules over an edematous erythema [1,3]. In addition to the skin reaction, high fever and high neutrophil counts are frequent [4]. Regulatory authorities have included warnings and watchlists for multiple individual drugs. In the US, the Food and Drug Administration (FDA) added aripiprazole [16], vancomycin [17], hydroxyzine pamoate, levocetirizine, cetirizine, and 13 different proton-pump inhibitors to a watchlist for AGEP [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
