Oral anticoagulants

Last updated: December 1, 2021

Summarytoggle arrow icon

Anticoagulants are used for treating and preventing embolic events. The most common oral anticoagulatory agents are vitamin K antagonists such as warfarin and phenprocoumon. Non-vitamin K antagonist oral anticoagulants (NOACs) like dabigatran and rivaroxaban have also gained popularity in recent years. Vitamin K antagonists inhibit the enzyme vitamin K epoxide reductase, thereby blocking hepatic synthesis of the active, reduced form of vitamin K (needed for carboxylation of coagulation factors II, VII, IX, and X, protein C, protein S). This effect can last for several days, which complicates exact dosing and makes regular monitoring necessary. Vitamin K antagonists are also metabolized by C-P450 (CYP) enzymes and therefore interact with a broad range of foods and drugs. NOACs act selectively via inhibition of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban). Because of their comparatively short half-life and fewer interactions, NOACs are easier to control and administer than warfarin and do not require regular monitoring to ensure their efficacy and safety. For all substances, it is important to consider the dose-dependent risk of bleeding, especially when combining different substances that affect hemostasis (e.g., aspirin, clopidogrel, ticagrelor).

Overviewtoggle arrow icon

Overview of commonly used oral anticoagulants

Overview of commonly used oral anticoagulants
Mechanism of action Advantages Disadvantages
Vitamin K antagonists (coumarins)


Warfarin [1][2]

Direct oral anticoagulants
Direct oral thrombin inhibitors Dabigatran [3]
  • Costly
  • Limited clinical experience with these drugs
  • Not recommended, and partially contraindicated, in patients with artificial cardiac valves
  • Not suited for patients with valvular atrial fibrillation
Direct oral factor Xa inhibitors




  • Selective and direct inhibition of factor Xa

General notes regarding oral anticoagulation

The most important side effect of all oral anticoagulants is a dose-dependent increase in bleeding risk.

DRAW: Dabigatran, Rivaroxaban, Apixaban, and Warfarin are the most important oral anticoagulants.

RivaroXaban, apiXaban, and edoXaban are factor Xa inhibitors.

WARsaw is an EXTRaordinary Place To check out: WARfarin affects the EXTRinsic pathway; therefore, PT should be regularly checked.

WEPT: Warfarin Extrinsic pathway PT

Comparison of heparin and warfarin

Heparin vs. warfarin
Anticoagulant Route of administratIon Mechanism of action Monitoring Reversal agents
  • Intravenous
  • Subcutaneous
  • Activates antithrombin↓ action of factors IIa and Xa
  • Site of action: blood
  • Rapid onset of action
  • Shorter half time: duration of action is several hours
  • PTT (affects intrinsic pathway)
  • Oral
  • PT or INR (affects extrinsic pathway)

Adverse effectstoggle arrow icon


Individuals with protein C deficiency are at a higher risk of developing warfarin necrosis.

Direct factor Xa inhibitors and direct thrombin inhibitors

RivaroXaban and apiXaban can be reversed with andeXanet alfa.


We list the most important adverse effects. The selection is not exhaustive.

Indicationstoggle arrow icon

Overview of indications of oral anticoagulants [9]
Drugs Indications



Direct thrombin inhibitors


Direct factor Xa inhibitors




Contraindicationstoggle arrow icon

Warfarin crosses the placenta and is teratogenic, in contrast to heparin, which does not cross the placenta.


We list the most important contraindications. The selection is not exhaustive.

Interactionstoggle arrow icon

Warfarin interactions

Warfarin is metabolized by cytochrome P450 (CYP) enzymes. Its effects can be significantly impacted by a variety of interactions; for this reason, warfarin serum levels should be monitored regularly.

Chronic alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs): Chronic alcohol use, St. John's wort, Phenytoin, Phenobarbital, Nevirapine, Rifampin, Griseofulvin, and Carbamazepine are P450 inducers (warfarin levels).

“ group”: Sulfonamides, Isoniazid, Cimetidine, Ketoconazole, Fluconazole, Alcohol (binge drinking), Ciprofloxacin, Erythromycin, Sodium valproate, Chloramphenicol, Omeprazole, Metronidazole, and Grapefruit juice are P450 inhibitors.

Additional considerationstoggle arrow icon


Referencestoggle arrow icon

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  2. $Warfarin reversal Guideline.
  3. Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013; 369 (13): p.1206-1214.doi: 10.1056/NEJMoa1300615 . | Open in Read by QxMD
  4. Antidote to Dabigatran Is Approved. Updated: February 21, 2017. Accessed: February 21, 2017.
  5. Warfarin Reversal. Updated: February 21, 2017. Accessed: February 21, 2017.
  6. Warfarin-induced skin necrosis. Updated: February 1, 2016. Accessed: February 21, 2017.
  7. Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016; 41 (1): p.206-232.doi: 10.1007/s11239-015-1310-7 . | Open in Read by QxMD
  8. Kakagia DD, Papanas N, Karadimas E, Polychronidis A. Warfarin-induced skin necrosis. Ann Dermatol. 2014; 26 (1): p.96.doi: 10.5021/ad.2014.26.1.96 . | Open in Read by QxMD
  9. Falck-ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141 (Suppl 2): p.e278S-325S.doi: 10.1378/chest.11-2404 . | Open in Read by QxMD
  10. Weitz JI. Expanding use of new oral anticoagulants. F1000Prime Rep. 2014; 6: p.93.doi: 10.12703/P6-93 . | Open in Read by QxMD
  11. Ginsberg JS, Crowther MA. Direct oral anticoagulants (DOACs) and pregnancy: A plea for better information. Thromb Haemost. 2016; 116 (4): p.590-591.doi: 10.1160/TH16-08-0602 . | Open in Read by QxMD
  12. Juurlink DN. Drug interactions with warfarin: what clinicians need to know. Can Med Assoc J. 2007; 177 (4): p.369-371.doi: 10.1503/cmaj.070946 . | Open in Read by QxMD
  13. Investigators TBS. Bridging anticoagulation: is it needed when warfarin is interrupted around the time of a surgery or procedure?. Circulation. 2012; 125 (12): p.e496-e498.doi: 10.1161/CIRCULATIONAHA.111.084517 . | Open in Read by QxMD

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