Apixaban is a novel oral anticoagulant (NOAC) that was approved by the US Food and Drug Administration (FDA) in 2012 for use in patients with non-valvular atrial fibrillation to reduce the risk of stroke and blood clots. [1][2][3]  Later, in 2014, it was approved for the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). In 2014, it was also approved for use to reduce the risk of blood clots (DVT and PE) in patients following knee and hip replacement surgery.[4][5]

The clotting cascade is a complex process involving multiple factors acting in 3 defined phases: initiation, propagation, and fibrin formation. 

Initiation

This occurs when the vascular endothelium and the clotting factors are disturbed.

Propagation

This involves the production of large amounts of thrombin at the site of injury.

Fibrin Formation

Thrombin acts on fibrinogen to form fibrin. 

The coagulation proteins form the basic components of the coagulation system. They lead to a complex interplay of reactions resulting in the conversion of plasma soluble fibrinogen to insoluble fibrin strands. There are 2 main pathways to the clotting cascade: the intrinsic pathway and the extrinsic pathway. External trauma activates the extrinsic pathway and causes blood loss from the vascular system. It is faster than the intrinsic pathway and involves factor VII. Trauma inside the vascular system activates platelets via exposed endothelium, chemicals, or collagen which can initiate the intrinsic pathway. It involves factors XII, XI, IX, and VIII. Both pathways share a common ending where they activate factor X to Xa, which activates prothrombin (II) to thrombin (IIa), thereby forming a stable clot. Apixaban is a direct factor Xa inhibitor, blocking the propagation phase of the coagulation cascade. Other direct factor Xa inhibitors include rivaroxaban and edoxaban.

Apixaban is available in the oral formulation as 2.5 mg and 5 mg tablets. Dosing depends on the indication for treatment, the age of the patient, serum creatinine, and body weight.

Patients with deep vein thrombosis and pulmonary embolism are required to take 10 mg twice daily for 7 days, followed by 5 mg twice daily. For patients with non-valvular atrial fibrillation, the recommended dose is 5 mg twice daily. As a prophylactic agent post hip and knee replacement surgery, a dose of 2.5 mg twice daily starting 12 to 24 hours postoperatively for a total duration of 35 and 12 days respectively is recommended.

In patients with 2 out of 3 of the following, the dose of 5 mg should be reduced to 2.5 mg daily.

• Age 80 years or older
• Serum creatinine greater than or equal to 1.5 mg/dl
• Bodyweight less than or equal to 60 kg

It can be administered without regard to the meal. Its elimination occurs via urine and feces. Biliary and direct intestinal excretion contributes to its elimination in the feces. Usually, 27% of the drug is cleared by the renal route.

Dosing in Renal Impairment

As mentioned above, the recommended dose for patients with at least 2 of the following, the dose of 5 mg should be reduced to 2.5 mg daily.

• Age 80 years or older
• Serum creatinine greater than or equal to 1.5 mg/dl
• Bodyweight less than or equal to 60 kg

Clinical efficacy and safety studies with apixaban did not include patients with end-stage renal disease (ESRD) on dialysis. It is thereby not recommended in the drug label as a proven anticoagulant of choice in patients with ESRD. An alternate anticoagulant like warfarin should be considered in patients with ESRD.

Dosing in Hepatic Impairment

Mild hepatic impairment (Child-Pugh class A): No dose adjustment required.

Moderate hepatic impairment (Child-Pugh class B): Limited clinical experience in patients with moderate hepatic impairment, hence, dosing adjustment cannot be provided.

Severe hepatic impairment (Child-Pugh class C): Apixaban is not recommended.

Being an anticoagulant, the most common adverse effect of apixaban is bleeding (1% to 10%). The risk of major bleeding is 3% or less, and clinically relevant nonmajor bleeding is 2% to 4%. Other less common adverse effects include nausea (3%), gingival hemorrhage (1% or less), hematuria (2% or less), hypermenorrhea (1%), anemia (3%), bruise (1% to 2%), hematoma (1% to 2%), postprocedural hemorrhage (1% or less), rectal hemorrhage (1% or less), increased serum transaminases (1% or less), epistaxis (4% or less), hemoptysis (1% or less). Rarely (less than 1%), it can cause a hypersensitivity reaction.

Active pathological bleeding and severe hypersensitivity reaction to apixaban, for example, an anaphylactic reaction, are the contraindications to the use of apixaban.