Pharmacovigilance‐based drug repurposing: The search for inverse signals via OpenVigil identifies putative drugs against viral respiratory infections

Abstract

Pharmacovigilance data are primarily used to identify adverse drug reactions by screening for disproportionate reporting, i.e. more reports of certain combinations of adverse events and drugs than expected. However, scanning for associations of drugs and adverse events that occur less frequently than expected provides hypotheses for drug repurposing, i.e. a known drug could be therapeutically beneficial for a new indication such as the coronavirus disease (COVID-19). As coronavirus-related adverse events are scarce in pharmacovigilance data prior to 2020, we searched for drugs suitable against similar viral diseases.Methods: In this observational, retrospective, pharmacovigilance study, drugs associated with viral respiratory tract infections and/or diseases caused by RNA-viruses, which are phylogenetically similar to SARS-CoV-2, were extracted from the US FAERS pharmacovigilance data 2004Q1 to 2020Q2 using OpenVigil 2.1-MedDRA17, filtered for significant inverse associations (reporting odds ratio <1 and adjusted P < .05), checked for implausibility (e.g. only topically) or clinical infeasibility (e.g. strong cytotoxic effects), and categorised by their World Health Organization Anatomical Therapeutic Chemical classification code.Results: A total of 126 drugs were identified. Anatomical Therapeutic Chemical clustering of the manually curated list of 112 candidate drugs revealed female sex hormones, antidiabetics, neuropharmacological sigma-receptor modulators, peptidase inhibitors, antiviral drugs, nicotinic acetylcholine receptor agonists and tyrosine kinase inhibitors as putatively antiviral. Conclusion:Scanning for inverse signals in pharmacovigilance data provides new hypotheses for drug repurposing, theoretically for all indications. Concerning the treatment of viral respiratory infections, there are affirmative data for some candidate drugs; the remaining proposed candidate drugs without already known antiviral mechanism of action should stimulate further exploration.

Myelodysplastic Syndrome/Acute Myeloid Leukemia Following the Use of Poly-ADP Ribose Polymerase (PARP) Inhibitors: A Real-World Analysis of Postmarketing Surveillance Data

“…Data were retrieved from the public release of FAERS and EV database between 1 October 2014 (considering the FDA approved the first PARP inhibitors, olaparib on 19 December 2014) and the 30 September 2021. OpenVigil FDA, a pharmacovigilance tool, is a web-based user interface to the FAERS database for extraction and analysis of adverse event safety reports which has been successful verified by FDA( Bohm et al, 2021 ). For the present study, we used the OpenVigil FDA to analysis the data from FAERS.…”

Analysis of pharmacovigilance databases for spontaneous reports of adverse drug reactions related to substandard and falsified medical products: A descriptive study

“…We used the previously selected preferred terms. The program is presenting an ADR as putative whenever the followings are true: report count >3, PRR >2, and χ2 >4 ( Böhm et al, 2021 ; Chiappini et al, 2022 ).…”

Peripheral Neuropathy During Concomitant Administration of Proteasome Inhibitors and Factor Xa Inhibitors: Identifying the Likelihood of Drug-Drug Interactions

“…OpenVigil FDA is a novel web-based pharmacovigilance analysis tool that uses the openFDA online interface to access the drug-event dataset from FAERS ( Böhm et al, 2012 ; Böhm et al, 2016 ). It is widely utilized in pharmacovigilance research ( Huang et al, 2020a ; Huang et al, 2020b ; Böhm et al, 2021 ). OpenVigil only operates on cleaned data by eliminating duplicates or reports with missing data ( Oshima et al, 2018 ).…”