(178) Drugs-Associated with Red Man Syndrome: An Integrative Approach Using Disproportionality Analysis and PHARMIP

Publication Number: 509

Background: Red Man Syndrome (RMS) is a non-IgE mediated anaphylactoid adverse event frequently witnessed after a rapid infusion of vancomycin. However, dearth in literature pertinent to the genetic mutations underlying pathogenesis of RMS and the potential association of other drugs in triggering RMS have been incompletely investigated.

Objectives: This study aims to unravel drugs and associated off-label targets (OLTs) which induce RMS by exploiting FDA Adverse Event Reporting System (FAERS) and Pharmacovigilance/Pharmacogenomics In silico Pipeline (PHARMIP).

Methods: The case/non-case retrospective observational study design was used for data retrieval and analysis from the FDA database. Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) data mining algorithms were used to evaluate the strength of the signal. A value of ROR-1.96SE>1 (SE-standard error), PRR≥2 are considered as positive signals. The OLTs of the drugs were obtained using online servers by applying a similarity ensemble approach and a reverse pharmacophore database, which were further validated by molecular docking studies.

Results: Oritavancin exhibited a strong positive signal (PRR:1185.20 and ROR:1256), which suggests a higher risk for causing RMS. Exploring enormous literature revealed the involvement of the MRGPRX2 gene in the development of RMS, while the PHARMIP study unearthed Carbonic anhydrase II (CA2) as the common OLT amongst the drugs causing RMS. The results obtained from molecular docking studies reinforced the aforementioned findings, wherein the highest docking score was disinterred for oritavancin (-9.4 for MRGPRX2 and -8.7 for CA2).

Conclusions: Many antibiotics and other classes of medications have been discovered in the quest for drugs that may induce RMS, although a causal relationship could not be established. The implication of MRGPX2 and CA2 in the initial stages of pathogenesis necessitates the development of inhibitors that could be used as potential therapeutic agents against RMS.