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ABSTRACT
Introduction
Since COVID-19 patients are often polytreated, monitoring drug–drug interaction (DDIs) is necessary. We evaluated whether drugs used after the second COVID-19 pandemic wave were associated with DDI-related adverse events and the role of drug interaction checkers in identifying them.
Methods
The study (PROSPERO-ID: CRD42024507634) included: 1) consulting the drug interaction checkers Drugs.com, Liverpool COVID-19 Interactions, LexiComp, Medscape, and Micromedex; 2) systematic review; 3) reviewed studies analysis; 4) evaluating drug interaction checkers potential to anticipate DDI-related adverse events.
The systematic review was performed searching PubMed, Scopus, ScienceDirect, and Cochrane databases from 1 March 2022 to 11 November 2023. Observational studies, and clinical trials were included. Article without reporting direct association between DDIs and adverse events were excluded. The risk of bias was assessed by Newcastle-Ottawa scale.
Results
The most frequent DDIs involved nirmatrelvir/ritonavir (N/R) and fluvoxamine. Fifteen studies, including 150 patients and 35 DDI-related outcomes, were analyzed. The most frequent DDIs involved tacrolimus with N/R, resulting in creatinine increase.
Eighty percent of reported DDI-related adverse events would have been identified by all drug-interaction checkers, while the remaining 20% by at least 2 of them.
Conclusions
Drug interaction checkers are useful but show inconsistencies. Multiple sources are needed to tailor treatment in the context of COVID-19.
Article highlights
Patients with COVID-19 often suffer from several comorbidities that require multiple treatments.
Even in the post-pandemic era, DDI-related adverse outcomes in COVID-19 patients remain a concern.
Use of multiple drugs in patients with COVID-19 increases the risk of DDI-related adverse events.
It may be necessary to perform clinical monitoring and therapeutic drug monitoring to improve the risk/benefit ratio taking into account potential DDIs between the drugs used against COVID-19 and between them and co-administered drugs.
Drug interaction checkers are useful for predicting and managing DDIs, but show important differences and inconsistencies.
Multiple sources are needed to tailor drug therapy in the context of COVID-19.
Abbreviations
| AIFA | = | Italian Medicine Agency (Agenzia Italiana del Farmaco) |
| FDA | = | Food and Drug Administration |
| EMA | = | European Medicines Agency |
| PK | = | pharmacokinetics |
| PD | = | pharmacodynamics |
| DDI | = | drug-drug interaction |
| MESH | = | MEdical Subject Heading |
| MOOSE | = | Meta-analysis of Observational Studies in Epidemiology |
| ADRs | = | Adverse Drug Reactions |
| N/R | = | nirmaltrevir/ritonavir |
| SOTRs | = | solid organ transplant recipients |
| TDM | = | therapeutic drug monitoring |
| SmPC | = | Summary of Product Characteristics |
| OATP1B1 | = | organic anion transporting polypeptide 1B1 |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Author Contributions
Conceptualization, V Conti, P Pagliano, and A Filippelli; methodology N Bertini, R Ricciardi, E De Bellis, and B Stefanelli; software, G Corbi, F Sabbatino, M Cascella, and V Conti; data curation, F Sabbatino, P Pagliano, G Corbi, A Filippelli, and V Conti; writing – original draft preparation, V Conti, C Sellitto, A Filippelli, E De Bellis, B Stefanelli, and R Ricciardi; writing – review and editing, G Corbi, P Pagliano, and N Bertini; supervision, V Conti, P Pagliano, and A Filippelli. All authors have read and agreed to the published version of the manuscript.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Data availability statement
All the studies used for the systematic review were freely available.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/17425255.2024.2339397