Below is a summary of relevant drug interactions taken from the prescribing information for each agent:

Dabigatran (Pradaxa; Boehringer Ingelheim)

  • Antagonized by P-gp inducers (eg, rifampin); avoid.
  • Increased dabigatran levels with P-gp inhibitors (eg, dronedarone, ketoconazole, verapamil, amiodarone, quinidine, clarithromycin).
  • Concomitant NSAIDs, platelet inhibitors, heparin, fibrinolytic therapy: increased risk of bleeding. 

Rivaroxaban (Xarelto; Janssen)

  • Increased risk of bleeding with concomitant aspirin, P2Y12 platelet inhibitors, other antithrombotic agents, fibrinolytic therapy, NSAIDs, clopidogrel; avoid.
  • Avoid with concomitant combined P-gp and strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, conivaptan).
  • Avoid with concomitant combined P-gp and strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s wort).
  • May be potentiated with concomitant renal impairment and combined P-gp and weak or moderate CYP3A4 inhibitors (eg, erythromycin, azithromycin, diltiazem, verapamil, quinidine, ranolazine, dronedarone, amiodarone, felodipine).

Apixaban (Eliquis; Bristol-Myers Squibb & Pfizer)

  • Concomitant strong dual inhibitors of CYP3A4 and P-gp (eg, ketoconazole, itraconazole, ritonavir, clarithromycin): 2.5mg twice daily; if already on 2.5mg twice daily, coadministration should be avoided.
  • Potentiated by dual inhibitors of CYP3A4 and P-gp.
  • Antagonized by concomitant strong dual inducers of CYP3A4 and P-gp (eg, rifampin, carbamazepine, phenytoin, St. John’s wort); avoid.
  • Increased risk of bleeding with concomitant aspirin, antiplatelet agents, fibrinolytics, other anticoagulants, heparin, thrombolytic agents, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, NSAIDs.


All physicians, including cardiologists, need to become more familiar with potential DDIs between commonly used agents. Zhou et al posit that one of the drivers of DDIs is lack of coordination among healthcare providers and suggest a model of “integrated care, in a dynamic continuum.”

RELATED: Drug Interactions Checker


1. Hakkarainen KM, Hedna K, Petzold M, Hägg S. Percentage of patients with preventable adverse drug reactions and preventability of adverse drug reactions–a meta-analysis. PLoS One. 2012;7(3):e33236.

2. Iyer SV, Lependu P, Harpaz R, et al. Learning signals of adverse drug-drug interactions from the unstructured text of electronic health records. AMIA Summits Transl Sci Proc. 2013;18:83-87.

3. Gurwitz JH, Field TS, Harrold LR, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA. 2003;289(9):1107-1116.

4. Jyrkkä J, Vartiainen L, Hartikainen S, et al. Increasing use of medicines in elderly persons: a five-year follow-up of the Kuopio 75+ Study. Eur J Clin Pharmacol. 2006; 62(2):151-158. 

5. Patel VK, Acharya LD, Rajakannan T, et al. Potential drug interactions in patients admitted to cardiology wards of a South Indian teaching hospital. Australas Med J. 2011;4(1):9-14

6. Straubhaar B, Krähenbühl S, Schlienger RG. The prevalence of potential drug-drug interactions in patients with heart failure at hospital discharge. Drug Saf. 2006;29(1):79-90.

7. Zhou YT, Yu LS, Zeng S, et al. Pharmacokinetic drug-drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management. Ther Clin Risk Manag. 2014;10:17-26. Epub 2013 Dec 20.

8. Hobl EL, Stimpfl T, Ebner J, et al. Morphine decreases clopidogrel concentrations and effects: A randomized, double blind, placebo-controlled trial. J Am Coll Cardiol. 2013 Nov 21. [Epub ahead of print]

9. Hellwig T, Gulseth M. Pharmacokinetic and pharmacodynamic drug interactions with new oral anticoagulants: what do they mean for patients with atrial fibrillation? Ann Pharmacother. 2013;47(11):1478-1487.