Betrixaban for Prophylaxis of Venous Thromboembolism

June 4, 2018
Gianna Casal, PharmD
Gianna Casal, PharmD

,
Matthew Davis, PharmD
Matthew Davis, PharmD

,
Lisa Holle, PharmD, BCOP, FHOPA
Lisa Holle, PharmD, BCOP, FHOPA

Betrixaban has been approved by the FDA for patients at risk for thromboembolisms. 

The FDA has approved betrixaban (Bevyxxa) to prevent venous thromboembolism (VTE) in inpatients at risk for thromboembolic events due to immobility or clinical contributing factors.1 Current standard of therapy includes subcutaneous heparin or enoxaparin, which may require multiple doses per day.

As the only direct oral anticoagulant (DOAC) approved for inpatient VTE prophylaxis, a once-daily oral option avoids the difficulty and inconvenience of giving a dose by injection and can help promote adherence. Betrixaban binds to the active site of factor Xa and inhibits its activity. It inhibits both free factor Xa and prothrombinase activity, which leads to decreased thrombin generation. Betrixaban has no effect on platelet aggregation activity.2

Efficacy

Approval of betrixaban was based on data collected from the APEX trial, a randomized double blind multinational study that compared extended duration betrixaban with standard duration enoxaparin in the prevention of VTE in acutely ill hospitalized patients with VTE risk factors.1 The trial consisted of 7,513 patients who were randomized to receive betrixaban 160 mg orally on day 1 followed by 80 mg once daily for 35 to 42 days or enoxaparin 40 mg subcutaneously once daily for 6 to 14 days.1,3

The efficacy of the trial was measured by a composite score comprised of either occurrence of asymptomatic or symptomatic proximal deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death. Betrixaban was associated with fewer events (4.4%) than enoxaparin (6%) (relative risk 0.75, 95% CI: 0.61, 0.91).1,3

Safety

In the APEX trial, 54% of patients in the betrixaban group experienced at least one adverse effect compared with 52% of those receiving enoxaparin. The most frequent reason for treatment discontinuation was bleeding, with an incidence rate of 2.4% in the betrixaban group and 1.2% in the enoxaparin group. Severe bleeding occurred in 0.7% of the betrixaban group and 0.6% in the enoxaparin group. Only two cases of intracranial bleeding occurred in the betrixaban group compared with seven cases in the enoxaparin group; and only one major bleeding event that lead to death occurred in both arms. Fewer stroke events occurred in the betrixaban group (0.6%) than the enoxaparin group (1.1%) (relative risk 0.59; 95% CI, 0.35 to 0.97; P=0.03).3

Monitoring for signs of bleeding and for concomitant medications that alter hemostasis is important. Therapy should be discontinued in the event of an active hemorrhage. No reversal agent exists for this medication.This medication has a black box warning for spinal or epidural hematomas, which may occur in patients receiving neuraxial anesthesia or undergoing spinal puncture. Other adverse effects from betrixaban are minimal. Side effects include hypertension, headache, hypokalemia, constipation, nausea, and diarrhea.4

Dosing and Cost

Recommended dosing for betrixaban is 160 mg orally once daily on day 1, then 80 mg once daily for 35 to 42 days. All doses should be taken with food. There should be a 50% dose reduction for patients with a creatinine clearance of 15 to 30 ml/min or if the patient takes p-glycoprotein inhibitors. This drug should not be used in patients with hepatic impairment. If a dose is missed, the dose should be taken as soon as possible on the same day and then continue the normal schedule on the next day.4 The estimated out-of-pocket price for a 42-day supply of 44 tablets is about $683.5

References
1. FDA approved betrixaban (Bevyxxa, Portola) for the prophylaxis of venous thromboembolism (VTE) in adult patients. U.S. Food and Drug Administration. https://bit.ly/2I1DN3n Accessed April 9, 2018.
2. Bevyxxa (betrixaban). CenterWatch.  https://bit.ly/2Ia4Be2. Accessed April 9, 2018.
3. Chi G. Extended-duration betrixaban reduces the risk of rehospitalization associated with venous thromboembolism among acutely ill hospitalized medical patients. Circulation. 2017;137(1):91-94.
4. Bevyxxa (betrixaban). Lexi-Comp, Inc. https://bit.ly/2G0cTmH.  Accessed April 9, 2018.
5. Byvexxa prices and Byvexxa coupons. GoodRx Web site. https://bit.ly/2Iv4wVx. Accessed April 9, 2018.