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New oral anticoagulants: relevance of P-glycoprotein in stroke prevention with Apixaban, Dabigatran and Rivaroxaban


The new oral anticoagulants ( NOACs ) Dabigatran etexilate ( Pradaxa ), Rivaroxaban ( Xarelto ), and Apixaban ( Eliquis ) show similar efficacy for stroke prevention in patients with atrial fibrillation as the vitamin K antagonist Warfarin ( Coumadin ).
Absorption of new oral anticoagulants is dependent on the intestinal P-glycoprotein ( P-gp ) system and P-gp activity is modulated by a variety of drugs and food components.

The aim of a review was to give an overview of P-gp-associated drug-drug and drug-food interactions with new oral anticoagulants in patients with atrial fibrillation.

A literature search was carried out.

Concomitant medication with proton pump inhibitors, Amiodarone, Clarithromycin, and Verapamil increased bioavailability whereas Rifampicin decreased the bioavailability of Dabigatran.

Coadministration of Erythromycin, Clarithromycin, Fluconazole, Ketoconazole, and Ritonavir increased Rivaroxaban plasma concentrations.

No data were found on Apixaban and P-gp-modulating drugs or on new oral anticoagulants and food components modulating P-gp.

The clinical relevance of interactions between new oral anticoagulants and P-gp-modulating drugs or food components is largely unknown as bleeding complications under new oral anticoagulants and P-gp-inhibiting drugs are mainly reported from patients with concomitant renal failure.

There is an urgent need to investigate the role of P-gp-modulating substances as potential sources of drug-drug and drug-food interactions.
A thorough analysis of the data accumulated in the three large new oral anticoagulant trials regarding the role of P-gp-modulating drugs in bleeding and embolic events is desirable.
Pharmacological studies should investigate the influence of P-gp-modulating drugs and food on new oral anticoagulant plasma concentrations and coagulation parameters.

When prescribing new oral anticoagulants, patients should be informed about the potential interactions with drugs and herbal drugs.
Patients who develop bleeding or embolic events under treatment with new oral anticoagulants should be investigated for co-medications as well as for over-the-counter drugs and dietary habits. ( Xagena )

Stöllberger C1, Finsterer J, Herz 2015;40(Supplement 2):140-145

XagenaMedicine_2015



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