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PI documents for DOACs in Australia are being updated to include new information about increased risk of recurrent thrombotic events in a specific group of patients

Pharmacists are advised that Product Information (PI) documents for direct acting oral anticoagulants (DOACs) registered in Australia are being updated to include new information about increased risk of recurrent thrombotic events in patients diagnosed with antiphospholipid syndrome (APS).

The DOACs marketed in Australia are apixaban (Eliquis), dabigatran etexilate (Pradaxa) and rivaroxaban (Xarelto).

DOACs are indicated in adults for: the prevention of venous thromboembolic events (VTE) in patients who have undergone elective total hip or total knee replacement surgery;  prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and at least one additional risk factor for stroke; and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and for the prevention of recurrent DVT and PE.

Additionally, rivaroxaban in combination with aspirin is indicated for the prevention of major cardiovascular events such as stroke, myocardial infarction and cardiovascular death in patients with coronary artery disease and/or peripheral artery disease.

A clinical trial (TRAPS study) has shown an increase in the risk of recurrent thrombotic events with rivaroxaban compared to warfarin in patients with APS, a history of thrombosis and a high risk of recurrent thrombotic events (patients who are triple positive for lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I antibodies).

While there are currently no completed controlled trials relating to this issue for the other two DOACs marketed in Australia, these medicines may be associated with a similar risk.

The final results from an investigator-led randomised controlled trial comparing apixaban and warfarin for secondary prevention of thromboembolism in patients with APS (ASTRO-APS), recently closed due to lack of enrolment, are not yet available.

A review by the European Medicines Agency found that the use of DOACs in patients with APS could be associated with increased rates of recurrent thrombotic events compared with treatment with a vitamin K antagonist.

The level of evidence for increased risk of recurrent thrombotic events in patients differs between agents, but there is insufficient evidence that any DOAC offers sufficient protection in patients with APS, particularly high-risk patients, such as those who are triple positive for lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I antibodies.

The TGA has investigated this safety issue and is working with sponsors to update the PI documents for apixaban, dabigatran etexilate and rivaroxaban to reflect current evidence.

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