Apixaban is an oral, reversible, and selective active site inhibitor of Factor Xa. It does not require antithrombin III for antithrombotic activity. The drug is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. The drug is contraindicated in patients with active pathological bleeding or severe hypersensitivity to the drug.
Apixaban displays prolonged absorption. Thus, despite a short clearance half-life of about 6 hours, the apparent half-life during repeat dosing is about 12 hours, which allows twice-daily dosing to provide effective anticoagulation, but it also means that when the drug is stopped for surgery, anticoagulation persists for at least a day. The absolute bioavailability of apixaban is approximately 50% for doses up to 10 mg. Food does not affect the bioavailability of apixaban. Maximum concentrations (Cmax) of apixaban appear 3 to 4 hours after oral administration. The drug is eliminated in both urine and feces. Renal excretion accounts for about 27% of total clearance. Biliary and direct intestinal excretion contributes to elimination of apixaban in the feces.
Apixaban carries a Boxed Warning. Discontinuing of the drug places patients at an increased risk of thrombotic events. An increased rate of stroke was observed following discontinuation of apixaban in clinical trials in patients with nonvalvular atrial fibrillation. If anticoagulation with apixaban must be discontinued for a reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered. The drug is listed in Pregnancy category B. There are no well controlled studies in pregnant women. Nursing mothers should either discontinue the drug or discontinue breast feeding.
The study that was reviewed by the FDA to bring apixaban to market was the ARISTOTLE trial. This study revealed a clinically significant decrease in overall bleeding when compared to warfarin (p<0.0001). It also revealed a significant decrease in the incidence of stroke or systemic embolism (p=0.01) when compared to warfarin.
Apixaban is dosed at 5 mg BID. In patients with at least 2 of the following characteristics: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥ 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily.
- Apixaban: official website
- Wikipedia entry on Apixaban
- Oral Apixaban for the Treatment of Acute Venous Thromboembolism, Giancarlo Agnelli, M.D., Harry R. Buller, M.D., Ph.D. et al NEJM July 1st 2013