Journal
CLINICAL DRUG INVESTIGATION
Volume 40, Issue 11, Pages 1001-1008Publisher
ADIS INT LTD
DOI: 10.1007/s40261-020-00962-y
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Funding
- Alma Mater Studiorum - Universita di Bologna within the CRUI-CARE Agreement
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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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