Background: Direct oral anticoagulants (DOACs), as substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, are susceptible to drug–drug interactions (DDIs). Hepatitis C direct-acting antiviral agents (DAAs), via P-glycoprotein or CYP3A4 inhibition, may increase DOAC exposure with relevant bleeding risk. We performed a systematic review on DDIs between DOACs and DAAs. Methods: Two reviewers independently identified studies through electronic databases, until 7 July 2020, supplementing the search by reviewing conference abstracts and the ClinicalTrials.gov website. Results: Of 1386 identified references, four articles were finally included after applying the exclusion criteria. Three phase I clinical studies in healthy volunteers assessed interactions between dabigatran and glecaprevir/pibrentasvir, odalasvir/simeprevir, or sofosbuvir/velpatasvir/voxilaprevir, showing an increase in the dabigatran area under the concentration–time curve (AUC) by 138%, 103%, and 161%, respectively. Conclusions: DOACs and DAAs are under-investigated for DDI risk. Real-world studies are needed to assess the clinical relevance of the pharmacokinetic interactions with dabigatran and describe the actual spectrum of possible DDIs between DAAs and other DOACs.

Drug–Drug Interactions between Direct Oral Anticoagulants and Hepatitis C Direct-Acting Antiviral Agents: Looking for Evidence Through a Systematic Review

Bellesini M.;Donadini M. P.;Squizzato A.
2020

Abstract

Background: Direct oral anticoagulants (DOACs), as substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, are susceptible to drug–drug interactions (DDIs). Hepatitis C direct-acting antiviral agents (DAAs), via P-glycoprotein or CYP3A4 inhibition, may increase DOAC exposure with relevant bleeding risk. We performed a systematic review on DDIs between DOACs and DAAs. Methods: Two reviewers independently identified studies through electronic databases, until 7 July 2020, supplementing the search by reviewing conference abstracts and the ClinicalTrials.gov website. Results: Of 1386 identified references, four articles were finally included after applying the exclusion criteria. Three phase I clinical studies in healthy volunteers assessed interactions between dabigatran and glecaprevir/pibrentasvir, odalasvir/simeprevir, or sofosbuvir/velpatasvir/voxilaprevir, showing an increase in the dabigatran area under the concentration–time curve (AUC) by 138%, 103%, and 161%, respectively. Conclusions: DOACs and DAAs are under-investigated for DDI risk. Real-world studies are needed to assess the clinical relevance of the pharmacokinetic interactions with dabigatran and describe the actual spectrum of possible DDIs between DAAs and other DOACs.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/2102714
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