Drug Interaction Checkers Could Have Prevented Pandemic Adverse Events

In the push early in the COVID_19 pandemic to find drugs – any drugs, even repurposed ones __ to care for very sick patients, the use of drug interaction checkers could have helped avoid some adverse events, according to a new Italian pharmacy study. Find out which drugs were most likely to cause those events and what checkers the authors used to reach their conclusions.

BARONISSI, ITALY — Repositioning drugs has been common during the COVID_19 pandemic, especially in urgent situations. A new study raises concerns that some of the drugs not only have been proven ineffective but have caused adverse events related to drug_drug interactions (DDIs).

A study in JAMA Network Open sought to identify DDIs that led to adverse clinical outcomes and/or adverse drug reactions in patients with COVID_19. Italian researchers from the University of Salerno systematically reviewed the literature and assessed the value of drug interaction checkers in identifying such events.


After identifying drugs used during the COVID_19 pandemic, the study team employed the following drug interaction checkers __ Drugs.com, COVID_19 Drug Interactions, LexiComp, Medscape, and WebMD __ to analyze theoretical DDI_associated adverse events in patients with COVID_19 from March 1, 2020, through Feb. 28, 2022.

Researchers also performed a systematic literature review, searching the databases PubMed, Scopus, and Cochrane for articles published from March 1, 2020, through Feb. 28, 2022, to retrieve articles describing actual adverse events associated with DDIs. They again consulted the drug interaction checkers to evaluate their potential to assess such events.

The authors report that the DDIs identified in the reviewed articles involved 46 different drugs.” In total, 575 DDIs for 58 drug pairs (305 associated with at least 1 adverse drug reaction) were reported,” they write. “The drugs most involved in DDIs were lopinavir and ritonavir. Of the 6917 identified studies, 20 met the inclusion criteria. These studies, which enrolled 1297 patients overall, reported 115 DDI_related adverse events: 15 (26%) were identifiable by all tools analyzed, 29 (50%) were identifiable by at least 1 of them, and 14 (24%) remained nonidentifiable.”

A key conclusion from the systematic review was that the use of drug interaction checkers could have identified several DDI_associated adverse drug reactions before they occurred, including severe and life_threatening events. “Both the interactions between the drugs used to treat COVID_19 and between the COVID_19 drugs and those already used by the patients should be evaluated,” they advise.

Background information in the article recounted the chaos that occurred early in the COVID_19 pandemic, noting that clinicians were “faced with the challenge of caring for infected patients in the absence of consolidated scientific evidence and guidelines. As a consequence, they have used drugs already approved for other diseases, referred to as repositioned drugs. Especially at the beginning of the pandemic, the potential efficacy of these repositioned drugs against SARS_CoV_2 was often based on in vitro or in vivo evidence.3 Some of these drugs have been used without considering their potential to cause adverse outcomes associated with drug_drug interactions (DDIs).”

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