Drugs‐associated with red man syndrome: An integrative approach using disproportionality analysis and Pharmip

Abstract

What is known and objective Red man syndrome (RMS) is a non‐IgE‐mediated anaphylactoid adverse event frequently witnessed after a rapid infusion of vancomycin. This study aims to unravel drugs and associated off‐label targets that induce RMS by exploiting FDA Adverse Event Reporting System (FAERS) and Pharmacovigilance/Pharmacogenomics Insilico Pipeline (PHARMIP). Methods The case/non‐case retrospective observational study was conducted in the FAERS database. Reporting odds ratio (ROR) and proportional reporting ratio (PRR) data mining algorithms were used to evaluate the strength of the signal. The off‐label targets of the drugs with potential signals were obtained using online servers by applying a similarity ensemble approach and a reverse pharmacophore database, which was further validated by molecular docking studies. Results and discussion Oritavancin exhibited a strong positive signal (PRR:1185.20 and ROR:1256), which suggests a higher risk for causing RMS. The literature search revealed the involvement of the MRGPRX2 gene in the development of RMS. PHARMIP study unearthed Carbonic anhydrase II (CA2) as the common off‐label target among the drugs causing RMS. The results obtained from molecular docking studies reinforced the findings as mentioned earlier, wherein the highest docking score was disinterred for oritavancin (−9.4 for MRGPRX2 and − 8.7 for CA2). What is new and conclusion 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.

Pharmacovigilance Strategies to Address Resistance to Antibiotics and Inappropriate Use—A Narrative Review

“…Data from spontaneous reports are key sources for the identification of safety signals related to the use of medicines after they have been approved and commercialized, i.e., their use in real life [38][39][40]. One of the features of spontaneous reporting is the use of internationally standardized terminologies, allowing for better evaluation and comparison between different countries/regions [38,41].…”

“…Data from spontaneous reports are key sources for the identification of safety signals related to the use of medicines after they have been approved and commercialized, i.e., their use in real life [38][39][40]. One of the features of spontaneous reporting is the use of internationally standardized terminologies, allowing for better evaluation and comparison between different countries/regions [38,41]. In addition to the adverse effect itself, the information collected in the standard and simple report form lets us recognise the reason for using the medicine, medicines taken concomitantly, and the underlying diseases of patients affected by an ADR.…”

“…These studies aimed to identify the main substances related to a given event, or the reverse, the main events related to an AB, the frequency of observation of an AE/AB pair, and the evaluation of rare events or drug-drug interactions involving an AB, in addition to the identification of populations at risk. Supplementary Table S1 lists recent studies that exemplify the recognized goals of PV [38][39][40].…”

Pharmacovigilance Strategies to Address Resistance to Antibiotics and Inappropriate Use—A Narrative Review

“…This same information allows the evaluation of the use of the involved medicines in different situations, an insight into the behavioural/epidemiological changes that populations are experiencing, and the indirect evaluation of the observed risks and benefits [26,39]. Data from spontaneous reports are key sources for the identification of safety signals related to the use of medicines after they have been approved and marketed, i.e., their use in real life [40][41][42].…”

“…One feature of spontaneous reporting is the use of internationally standardised terminologies, which allows for better evaluation and comparison between different countries/regions [40,43]. In addition to the adverse effect itself, the information collected in the standard and simple report form lets us recognise the reason for using the medicine, medicines taken concomitantly, and the underlying diseases of patients affected by an ADR.…”