Alberta pharmacists develop DOAC drug interactions management resource

A new drug interactions management resource for direct oral anticoagulants (DOACs) has been developed by pharmacists in Alberta. Although DOACs (apixaban, dabigatran, edoxaban, rivaroxaban) have fewer drug-drug interactions compared to warfarin, an increase in their use in clinical practice necessitates more knowledge about clinically significant interactions, to enable healthcare providers to make timely clinical decisions. Rivaroxaban and apixaban are substrates for P-glycoprotein (P-gp) and are metabolized (in part) by CYP3A4. Clinicians should ensure that a patient is not on two concomitant drugs that affect CYP3A4 and P-gp separately, as these combined drug-drug interactions could cause significant changes in DOAC concentrations. Dabigatran and edoxaban are affected only by strong inhibitors/inducers of P-gp within the gastrointestinal tract. To minimize P-gp drug-drug interactions, dabigatran or edoxaban may be administered two hours before the interacting agent. Front-line clinicians continue to manage more complex clinical scenarios with DOAC use, with little to none or conflicting information on drug interactions with these agents. Read: QUIZ: Test your knowledge of health anxiety To assist clinicians, a tool was developed to differentiate drug-drug interactions among the four marketed DOACs, with a description of available supporting data. The resulting table summarizes published data as of July 2021. It provides recommendations for concomitant use of drugs with a DOAC, with recommendations classified into five categories: Dark green: No interaction or clinically nonsignificant interaction—no effect on pharmacokinetics Green/yellow (lighter green): Use together with caution; limited data suggest either increased major bleeding or altered drug concentrations Yellow: Use with caution because of a theoretical/documented interaction that would affect DOAC concentration; a product monograph recommendation to use with caution; or for edoxaban, recommendation to reduce dose (signified with ↓ dose) Yellow/red (orange): Concomitant use is not recommended; limited data may support use Red: Avoid combination, may use only if DOAC concentrations are assessed, due to a theoretical/documented interaction that affects DOAC concentration, or a product monograph recommendation to avoid or contraindicate implies expected drug concentrations exceed the observed and acceptable variability. The authors caution that not all actual or potential interactions with DOACs are included in the tool. The tool was developed for use by practitioners within an anticoagulation clinic in thrombosis/cardiology-based practice. Therefore, the tool does not include DOAC interactions with herbal supplements or drugs not commonly encountered in a thrombosis/cardiology-based practice (e.g., hormonal agents, monoclonal antibodies, tyrosine kinase inhibitors, antimitotic agents). To effectively manage a potential or actual drug interaction with a DOAC, healthcare providers must consider various patient factors such as the risk of clotting vs bleeding, other drugs that may increase bleeding risk (e.g., concomitant antiplatelet therapy) and renal function, while using clinical judgement to gauge the overall impact of the interaction on DOAC concentrations. Reference 1. Chadha A, Guirguis M, Bungard TJ. DOAC drug interactions management resource. CPJ/RPC 2022; published online September 20, 2022. (accessed October 4, 2022).

Alberta pharmacists develop DOAC drug interactions management resource

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