PMID- 35935872
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230426
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Detecting drug-drug interactions between therapies for COVID-19 and concomitant 
      medications through the FDA adverse event reporting system.
PG  - 938552
LID - 10.3389/fphar.2022.938552 [doi]
LID - 938552
AB  - Background: COVID-19 patients with underlying medical conditions are vulnerable 
      to drug-drug interactions (DDI) due to the use of multiple medications. We 
      conducted a discovery-driven data analysis to identify potential DDIs and 
      associated adverse events (AEs) in COVID-19 patients from the FDA Adverse Event 
      Reporting System (FAERS), a source of post-market drug safety. Materials and 
      Methods: We investigated 18,589 COVID-19 AEs reported in the FAERS database 
      between 2020 and 2021. We applied multivariate logistic regression to account for 
      potential confounding factors, including age, gender, and the number of unique 
      drug exposures. The significance of the DDIs was determined using both additive 
      and multiplicative measures of interaction. We compared our findings with the 
      Liverpool database and conducted a Monte Carlo simulation to validate the 
      identified DDIs. Results: Out of 11,337 COVID-19 drug-Co-medication-AE 
      combinations investigated, our methods identified 424 signals statistically 
      significant, covering 176 drug-drug pairs, composed of 13 COVID-19 drugs and 60 
      co-medications. Out of the 176 drug-drug pairs, 20 were found to exist in the 
      Liverpool database. The empirical p-value obtained based on 1,000 Monte Carlo 
      simulations was less than 0.001. Remdesivir was discovered to interact with the 
      largest number of concomitant drugs (41). Hydroxychloroquine was detected to be 
      associated with most AEs (39). Furthermore, we identified 323 gender- and 254 
      age-specific DDI signals. Conclusion: The results, particularly those not found 
      in the Liverpool database, suggest a subsequent need for further 
      pharmacoepidemiology and/or pharmacology studies.
CI  - Copyright (c) 2022 Jeong, Nelson, Su, Malin, Li and Chen.
FAU - Jeong, Eugene
AU  - Jeong E
AD  - Department of Biomedical Informatics, School of Medicine, Vanderbilt University 
      Medical Center, Nashville, TN, United States.
FAU - Nelson, Scott D
AU  - Nelson SD
AD  - Department of Biomedical Informatics, School of Medicine, Vanderbilt University 
      Medical Center, Nashville, TN, United States.
FAU - Su, Yu
AU  - Su Y
AD  - Department of Computer Science and Engineering, College of Engineering, the Ohio 
      State University, Columbus, OH, United States.
FAU - Malin, Bradley
AU  - Malin B
AD  - Department of Biomedical Informatics, School of Medicine, Vanderbilt University 
      Medical Center, Nashville, TN, United States.
AD  - Department of Biostatistics, School of Medicine, Vanderbilt University Medical 
      Center, Nashville, TN, United States.
AD  - Department of Computer Science, School of Engineering, Vanderbilt University, 
      Nashville, TN, United States.
FAU - Li, Lang
AU  - Li L
AD  - Department of Biomedical Informatics, College of Medicine, the Ohio State 
      University, Columbus, OH, United States.
FAU - Chen, You
AU  - Chen Y
AD  - Department of Biomedical Informatics, School of Medicine, Vanderbilt University 
      Medical Center, Nashville, TN, United States.
AD  - Department of Computer Science, School of Engineering, Vanderbilt University, 
      Nashville, TN, United States.
LA  - eng
GR  - T15 LM007450/LM/NLM NIH HHS/United States
PT  - Journal Article
DEP - 20220722
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9353301
OTO - NOTNLM
OT  - COVID-19
OT  - FAERS
OT  - additive interaction
OT  - discovery-driven
OT  - drug-drug interactions
OT  - hypothesis generation
OT  - logistic regresion
OT  - multiplicative interaction
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/09 06:00
MHDA- 2022/08/09 06:01
PMCR- 2022/07/22
CRDT- 2022/08/08 03:40
PHST- 2022/05/07 00:00 [received]
PHST- 2022/07/01 00:00 [accepted]
PHST- 2022/08/08 03:40 [entrez]
PHST- 2022/08/09 06:00 [pubmed]
PHST- 2022/08/09 06:01 [medline]
PHST- 2022/07/22 00:00 [pmc-release]
AID - 938552 [pii]
AID - 10.3389/fphar.2022.938552 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Jul 22;13:938552. doi: 10.3389/fphar.2022.938552. 
      eCollection 2022.