PS-042 Potential interactions in patients treated with dabigatran, prevalence and therapeutic approach

Abstract

BackgroundThe thrombin inhibitor dabigatran (D) is the first new oral anticoagulant approved in Europe for the prevention of non-valvular atrial fibrillation; its advantage is that it has less interactions that antagonists of vitamin K.PurposeThe aim of the study was to determine the prevalence and type of potential drug interactions (PDI) in the treatment of patients with D in a health area, and to analyse the possible clinical relevance of these.Material and methodsThe study was performed in a health area serving 194 737 inhabitants for 6 months (July–December 2014). We included all patients treated with D and recorded demographic data and the full treatment prescribed for each patient to identify PDI, which were obtained from programs prescribing and dispensing primary care (ADN and Agoraplus) and managing medication dispensed in hospital (SAVAC). We considered PDI as those described in the technical data and classified according to the mechanism and recommendation indicated. Finally, we estimated the potential clinical relevance of the presence of PDI based on: visits to the emergency department (per patients and average/patient), hospitalisations and diagnoses in emergencies related to an adverse effect to D.ResultsWe included 206 patients treated with D (56% women, mean age 76.8 ± 8.6 years). 128 PDI were recorded in 50.5% of patients, with an average per patient of 1.24 ± 0.53 (75.3% for 1 interaction, 18.6% for 2, 6.2% for >2). 25.8% were pharmacokinetic and 74.2% were pharmacodynamics. In 11 interactions (8.6%), co-administration was contraindicated, in 86 (67.2%) it was necessary to monitor and in 31 (24.2%) the dosage was reduced and track performed. The drug groups involved in the PDI were: 7.8% NSAIDs; 25.8% inhibitors of P-glycoprotein (IGP-P), dronedarone, amiodarone, verapamil, etc; 30.5% antiplatelet drugs; 28,9% SSRI/SNRI; and 7.1% anticoagulants. We did not find significant differences in any of the relevant clinical variables studied between patients with and without PDI.ConclusionA considerable proportion of patients (50.5%) presented PDI in treatment, but without apparent clinical relevance to serious adverse events.The majority of PDI were pharmacodynamic and could be sought to improve the therapeutic effect. However, the significant percentage of PDI with SSRIs suggests that they may be unknown by some prescribers; there is a need to monitor their use along with inhibitors of IGP-P which are often prescribed to these patients.References and/or AcknowledgementsThanks to the documentation department.No conflict of interest.

Potential drug–drug interactions with direct oral anticoagulants in elderly hospitalized patients

“…No patients in the study took contraindicated interacting medications with DOACs. This is pleasing considering that Candel and colleagues 28 and Trujillano and colleagues 31 found 8.6% and 8.2% of patients in their respective studies took contraindicated drugs. Importantly, there were eight patients in the study who had greater than one potential DDI.…”

“…Thirty-seven percent of patients had potential interactions, which is just below the lower limit of the range collated from other studies with DOACs in clinical settings (40-88%). [28][29][30][31][32][33][34] Twice as many patients had potential PD-DDIs with DOACs compared with PK-DDIs, driven predominantly by concomitant use of SSRIs/SNRIs [ Figure 1(a, b)].…”

“…Third, apixaban, rivaroxaban and dabigatran were studied here, whereas most of the comparator studies included only dabigatran. [28][29][30][31][32][33][34] The prevalence difference could be explained because PPIs were classified as interacting drugs in several of the previous dabigatran studies, in which up to 64% of patients were taking dabigatran and PPIs together. 32 The rationale for this classification is that the bioavailability of dabigatran is dependent on an acidic gastric environment, and pantoprazole decreased dabigatran absorption by 30% in a phase I healthy volunteer study and by an average of 12.5% in RE-LY.…”

“…Indeed, when PPIs were included as perpetrators, this increased the overall prevalence of patients with potential interactions to 42%, consistent with the range of previous work (40-88%). [28][29][30][31][32][33][34] However, the consensus now is that interactions between dabigatran and PPIs are not clinically important. 5 Therefore, PPIs were excluded from the list of clinically relevant perpetrators (Table 2) and the final prevalence calculations.…”

“…have at least one potential DDI with DOACs. [28][29][30][31][32][33][34] For example, one study showed that nearly 80% of hospitalized patients on dabigatran had potential PK-DDIs, 32 whereas another showed that concomitant use of dabigatran with P-gp inhibitors occurred in 45% of patients. 33 Likewise, in a study of rivaroxaban after major orthopaedic surgery, there was a high prevalence of potential PD-DDIs, particularly with NSAIDs (52% of patients), although concomitant use of CYP3A or P-gp inhibitors or inducers was very low (<5% of patients).…”