Association of antiviral drugs and their possible mechanisms with DRESS syndrome using data mining algorithms

Abstract

Antiviral drugs are not known for drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. The current study aims is to find out the association of antiviral drugs and their possible mechanism with DRESS. Data mining algorithms such as proportional reporting ratio that is, PRR (≥2) with associated χ 2 value (>4), reporting odds ratio that is, ROR (≥2) with 95% confidence interval and case count (≥3) were calculated to identify a possible signal. Further, molecular docking studies were conducted to check the interaction of selected antiviral drugs with possible targets. The potential signal of DRESS was found to be associated with abacavir, acyclovir, ganciclovir, lamivudine, lopinavir, nevirapine, ribavirin, ritonavir, and zidovudine among all selected antiviral drugs. Further, subgroup analysis has also shown a potential signal in different age groups and gender. The sensitivity analysis results have shown a decrease in the strength of the signal, however, there was no significant impact on the outcome except for acyclovir. The docking results have indicated the possible involvement of human leukocyte antigen (HLA)*B1502 and HLA*B5801. The positive signal of DRESS was found with selected antiviral drugs except for acyclovir.antiviral drugs, data mining algorithms, docking study, DRESS | INTRODUCTIONVarious unexpected adverse drug reactions (ADRs) are observed in the postmarketing phase of drugs which are important for patient safety. Therefore, signal analysis plays an important role which is defined by World Health Organization (WHO) as "Reported information on a possible causal relationship between an adverse event and a drug, the relationship being previously unknown or incompletely documented. 1 Signals of disproportionate reporting (SDRs) are defined as the statistical association of drugs and ADRs which is also known as drug-event pairs. 2 Data mining algorithms (DMAs) such as proportionality reporting ratio (PRR) with associated χ 2 value, and reporting odds ratio (ROR) with 95% confidence interval are used to generate a hypothesis for SDRs using global databases such as Food and Drug Administration (FDA) adverse event reporting system (FAERS). 3,4 FAERS is a web-based tool for the public that contains human adverse events data reported to FDA by healthcare providers, consumers, and pharmaceutical industries. 5 OpenVigil is a tool used to extract clean data from the FAERS database. 6 Various classes of antiviral drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and so forth are widely used in the treatment of various types of viral infections. 7 Most common ADRs associated with the use of these drugs are upset stomach, vomiting, diarrhea, and dizziness with antiherpes drugs (acyclovir, famciclovir, ganciclovir, etc.), headache, nausea, insomnia, bronchitis, hypersensitivity reactions with antiinfluenza virus drugs (oseltamivir, zanamivir, peramivir), pharyngitis, anemia, neutropenia,

Safety profile of vascular endothelial growth factor receptor tyrosine-kinase inhibitors in pediatrics: a pharmacovigilance disproportionality analysis

“…The FDA adverse event reporting system (FAERS) is a well-known AE spontaneous reporting system that documents numerous drug AE reports and medication errors and contains the largest and most normative data ( Sakaeda et al, 2013 ). Disproportionality analysis in data mining algorithms (DMAs) such as proportionality reporting ratio (PRR) with associated χ 2 value and reporting odds ratio (ROR) with 95% confidence interval (CI) are used to generate a hypothesis for risk signals using FAERS database ( Sharma et al, 2023 ). We sought to explore the safety of VEGFR-TKI via FAERS while focusing on potential AEs associated with using these drugs in pediatric patients.…”

Relevance of Human Herpesvirus 6 Reactivation in Drug Rash With Eosinophilia and Systemic Symptoms—Reply

“…We think that a critical and complex aspect is the distinction between virus-induced complications/manifestations and nonpathogenic reactivations of dormant viral infections. This is particularly important since caution is warranted when introducing new medications for patients with DRESS due to the risk of a new sensitization …”

Antiviral therapy in DRESS

“…Ganciclovir, a nucleotide analogue with antiviral activity against HHV-6, was included as part of Sharma et al's study to assess antiviral culprits in DRESS. 1 Although the association between DRESS and ganciclovir was significant, only 10 cases of ganciclovir-associated DRESS were identified. 1 There are numerous cases of HHV-6-associated DRESS where treatment with ganciclovir resulted in significant improvement and control of symptoms.…”

“…1 Although the association between DRESS and ganciclovir was significant, only 10 cases of ganciclovir-associated DRESS were identified. 1 There are numerous cases of HHV-6-associated DRESS where treatment with ganciclovir resulted in significant improvement and control of symptoms. For example, colitis that developed after corticosteroid treatment acutely resolved with ganciclovir.…”

“…The authors also discussed the possibility of viral reactivation contributing to DRESS pathogenesis. 1 Given the morbidity and mortality associated with DRESS, we believe that assessing the role of viral reactivation as a potential exacerbator of disease is important. We hope to extend the discussion regarding viral reactivation and its implications for DRESS treatment.…”