Populations potentially at higher risk of bleeding^1,2

• Unfractionated heparin (UFH), low molecular weight heparins (e.g. enoxaparin, dalteparin), heparin derivatives (e.g. fondaparinux)
• Oral anticoagulants (e.g. warfarin, rivaroxaban, dabigatran)

Due to an increased bleeding risk, concomitant treatment with apixaban and any other anticoagulant agent is contraindicated, except under specific circumstances of switching anticoagulant therapy, when UFH is given at doses necessary to maintain an open central venous or arterial catheter, or when UFH is given during catheter ablation for atrial fibrillation.

The concomitant use of apixaban with antiplatelet agents increases the risk of bleeding.

Apixaban should be used with caution when coadministered with selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs), non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA) and/or P2Y12 inhibitors (e.g. clopidogrel).

There is limited experience of co-administration with other platelet aggregation inhibitors (such as GPIIb/ IIIa receptor antagonists, dipyridamole, dextran or sulfinpyrazone) or thrombolytic agents. As such agents increase the bleeding risk, co-administration of these medicinal products with apixaban is not recommended.

See sections on patients with renal impairment under dosing recommendations for each separate indication

• Use is not recommended in patients with CrCl <15 ml/min or patients undergoing dialysis
• No dose adjustment is required in patients with mild or moderate renal impairment

Patients with NVAF

• Patients with severe renal impairment (CrCl 15–29 ml/min) should receive the lower dose of apixaban 2.5 mg twice daily
• Patients with serum creatinine ≥1.5 mg/dL (133 µmol/L) associated with age ≥80 years or body weight ≤60 kg should receive the lower dose of apixaban 2.5 mg twice daily

No dose adjustment required

Patients with NVAF

No dose adjustment required except in combination with other factors

No dose adjustment required

Patients with NVAF

No dose adjustment required except in combination with other factors

Apixaban is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp, such as azole-antimycotics (e.g. ketoconazole, itraconazole, voriconazole and posaconazole) and HIV protease inhibitors (e.g. ritonavir).

No dose adjustment for apixaban is required when coadministered with, for example, amiodarone, clarithromycin, diltiazem, fluconazole, naproxen, quinidine and verapamil.

The concomitant use of apixaban with strong inducers of both CYP3A4 and P-gp (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital or St. John’s Wort) may lead to a ~50% reduction in apixaban exposure and should be used with caution.

Treatment of DVT or PE

Apixaban is not recommended