New oral anticoagulants apixaban (Eliquis▼), dabigatran (Pradaxa) and rivaroxaban (Xarelto▼)

Risk of serious haemorrhage—clarified contraindications apply to all 3 medicines.

Article update September 2016:

In November 2015, idarucizumab (Praxbind▼) was granted a European licence as a specific reversal agent for dabigatran. Idarucizumab is indicated for adults treated with dabigatran when rapid reversal of its anticoagulant effects is required for emergency surgery/urgent procedures, or in life-threatening or uncontrolled bleeding. Further information about this medicine is available on the website of the European Medicines Agency

Article date: October 2013

Dabigatran (Pradaxa) is a potent, orally active, direct inhibitor of free thrombin, fibrin-bound thrombin and thrombin-induced platelet aggregation.

Apixaban (Eliquis ▼) and rivaroxaban (Xarelto ▼) are direct, highly selective, orally active inhibitors of activated factor X (factor Xa).  

All 3 new oral anticoagulants are licensed for:

  • prevention of venous thromboembolic events in adults who have had elective total hip-replacement or knee-replacement surgery
  • prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation and one or more cardiovascular risk factors

Rivaroxaban is additionally licensed for:

  • treatment of deep-vein thrombosis and pulmonary embolism, and prevention of their recurrence, in adults

Risk of haemorrhage

Haemorrhage is a common adverse effect of all anticoagulants. Although these three new oral anticoagulants have some differing contraindications due to their different properties, the contraindications in patients with conditions putting them at significant risk of major bleeding, and those relating to use with other concomitant anticoagulants, now apply to all 3 of the medicines. This is the result of a European review.  

Updated advice on contraindications and warnings

The following contraindications now apply to all 3 new oral anticoagulants, for all doses and indications:

  • a lesion or condition, if considered a significant risk factor for major bleeding. This may include:
    • current or recent gastrointestinal ulceration
    • presence of malignant neoplasm at high risk of bleeding
    • recent brain or spinal injury
    • recent brain, spinal, or ophthalmic surgery
    • recent intracranial haemorrhage
    • known or suspected oesophageal varices
    • arteriovenous malformation
    • vascular aneurysms, or major intraspinal or intracerebral vascular abnormalities
  • concomitant treatment with any other anticoagulant agent—eg:
    • unfractionated heparin
    • low molecular weight heparin (such as enoxaparin or dalteparin)
    • heparin derivatives (such as fondaparinux)
    • oral anticoagulants (such as warfarin).

Exceptions are switching of therapy to or from the medicine, or when unfractionated heparin is given at doses necessary to maintain an open central venous or arterial catheter.

Additional advice and information for healthcare professionals:

  • special care should be taken when deciding to prescribe these anticoagulant medicines to patients with other conditions, procedures, and concomitant treatments (eg, non-steroidal anti-inflammatory drugs, antiplatelets), which may increase the risk of major bleeding 
  • attention should be paid to renal function - impaired renal function may constitute a contraindication or recommendation not to use the anticoagulant medicine, or may require a dose reduction; recommendations differ for the 3 medicines
  • the contraindications, posology, and warnings and precautions for use specific to each medicine, together with the individual’s risk factors for bleeding (eg, renal function), should be considered before prescribing these medicines

There is no specific antidote available for any of these 3 new oral anticoagulants. Please consult the product information for advice on treatment in the event of bleeding complications, or overdose.

A full list of contraindications, warnings and information on posology can be found in the individual summaries of product characteristics for apixaban, dabigatran, and rivaroxaban.

Further information

Letter for healthcare professionals sent 29 September 2013

Drug Safety Update articles from July 2012 and December 2011

Article citation: Drug Safety Update volume 7 issue 3, October 2013: A1.

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