CMSA Announcement Newsletter

Once-daily oral Bevyxxa^® (betrixaban) capsules

One Capsule,* Two Settings...

VTE protection in-hospital to home

The first and only oral anticoagulant indicated for the prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe restricted

*Initial day 1 dose is 160 mg, or two 80-mg capsules.

SELECT IMPORTANT SAFETY INFORMATION

WARNING: SPINAL/EPIDURAL HEMATOMA
EPIDURAL OR SPINAL HEMATOMAS MAY OCCUR IN PATIENTS TREATED WITH BEVYXXA WHO ARE RECEIVING NEURAXIAL ANESTHESIA OR UNDERGOING SPINAL PUNCTURE. THE RISK OF THESE EVENTS MAY BE INCREASED BY THE USE OF IN-DWELLING EPIDURAL CATHETERS OR THE CONCOMITANT USE OF MEDICAL PRODUCTS AFFECTING HEMOSTASIS. THESE HEMATOMAS MAY RESULT IN LONG-TERM OR PERMANENT PARALYSIS. CONSIDER THESE RISKS WHEN SCHEDULING PATIENTS FOR SPINAL PROCEDURES.

LIMITATIONS OF USE

The safety and effectiveness of Bevyxxa have not been established in patients with prosthetic heart valves because this population has not been studied.

For 35 to 42 days starting from hospital admission...

Reduce VTE risk by 32%, with no increase in major bleeding
(80-mg dose)¹

ARR=absolute risk reduction; CI=confidence interval; NNT=number needed to treat.

Bevyxxa 80-mg and 40-mg doses reduced the composite inicidence of VTE by 25% vs enoxaparin + placebo: 4.4% vs 6.0%, 95% Cl: 0.61, 0.91¹

Patients who were randomized to receive Bevyxxa 40 mg due to severe renal impairment or because they were taking a concomitant P-gp inhibitor had VTE event rates similar to those in the enoxaparin arm¹

Bevyxxa increases the risk of bleeding and can cause serious and potentially fatal bleeding. Concomitant use of drugs affecting hemostasis increases the risk of bleeding.¹

See More Data

For 35 to 42 days starting from hospital admission...

No significant increase in major bleeding (80-mg dose)¹

ARR=absolute risk reduction; CI=confidence interval; NNT=number needed to treat.

No significant increase in major bleeding with Bevyxxa 80-mg and 40-mg doses vs enoxaparin + placebo: 0.67% vs 0.57%, P=0.554¹

Patients with severe renal impairment or on concomitant P-gp inhibitors taking Bevyxxa may have an increased risk of bleeding. Avoid use of Bevyxxa in patients with severe renal impairment receiving concomitant P-gp inhibitors¹

Clinically relevent non-major bleeding increased vs enoxaparin + placebo¹:

- 2.21% vs 1.10%, 95% Cl: 1.32, 3.03 (80-mg dose)

- 2.45% vs 1.02%, P<0.001 (80-mg and 40-mg doses)

See More Data

Once-daily oral dosing and clinically important pharmacologic properties¹

	Rapid onset of action¹
Initial day 1 dose is 160 mg Peak concentrations occur within 3 to 4 hours after daily 80-mg dose - Maximum inhibition of thrombin generation coincides with the time of peak concentrations
	Low renal excretion, with 11% excreted in urine—the lowest of all approved direct oral anticoagulants¹
Initial day 1 dose is 160 mg Peak concentrations occur within 3 to 4 hours after daily 80-mg dose - Maximum inhibition of thrombin generation coincides with the time of peak concentrations
	Metabolism is independent of CYP enzymes¹
<1% of minor metabolites could be formed via metabolism by CYP enzymes
	No injections¹

	Once-daily oral dosing¹
Effective half-life of 19 to 27 hours¹ Low peak-to-trough concentration ratio²

About Dosing

INDICATION

Bevyxxa is indicated for the prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe restricted mobility and other risk factors for VTE.

LIMITATIONS OF USE

The safety and effectiveness of Bevyxxa have not been established in patients with prosthetic heart valves because this population has not been studied.

SELECT IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

●	Occlusive for absorption with a cream-like feel
●	Fewer prescriptions and patient refills

WARNINGS AND PRECAUTIONS
Risk of Bleeding

●	Bevyxxa increases the risk of bleeding and can cause serious and potentially fatal bleeding
●	Concomitant use of drugs affecting hemostasis increases the risk of bleeding. These include aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs)
●	Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room
●	Promptly evaluate any signs or symptoms of blood loss and consider the need for blood replacement
●	Discontinue Bevyxxa in patients with active pathological bleeding
●	There is no established way to reverse the anticoagulant effect of Bevyxxa, which can be expected to persist for at least 72 hours after the last dose
●	It is unknown whether hemodialysis removes Bevyxxa
●	Protamine sulfate, vitamin K, and tranexamic acid are not expected to reverse the anticoagulant activity of Bevyxxa

Spinal/Epidural Anesthesia or Puncture

●	When neuraxial anesthesia (spinal/epidural anesthesia) or spinal/epidural puncture is employed, patients treated with antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis
●	Do not remove an epidural catheter earlier than 72 hours after the last administration of Bevyxxa. The next Bevyxxa dose is not to be administered earlier than 5 hours after the removal of the catheter. If traumatic puncture occurs, delay the administration of Bevyxxa for 72 hours
●	Monitor patients frequently for signs and symptoms of neurological impairment (e.g., numbness or weakness of the legs, bowel or bladder dysfunction). If neurological compromise is noted, urgent diagnosis and treatment is necessary
●	Prior to neuraxial intervention, consider the potential benefit versus the risk in anticoagulated patients or in patients to be anticoagulated for thromboprophylaxis

Use in Patients with Severe Renal Impairment

●	Patients with severe renal impairment (CrCl = 15 to < 30 mL/min computed by Cockcroft-Gault) taking Bevyxxa may have an increased risk of bleeding events
●	Reduce dose of Bevyxxa, monitor patients closely, and promptly evaluate any signs or symptoms of blood loss in these patients

Use in Patients on Concomitant P-glycoprotein (P-gp) Inhibitors

●	Patients on concomitant P-gp inhibitors with Bevyxxa may have an increased risk of bleeding
●	Reduce dose of Bevyxxa in patients receiving or starting concomitatnt P-gp inhibitors, monitor patients closely, and promptly evaluate any signs or symptoms of blood loss in these patients
●	Avoid use of Bevyxxa in patients with severe renal impairment receiving concomitant P-gp inhibitors

ADVERSE REACTIONS

●	The most common adverse reactions with Bevyxxa were related to bleeding (> 5%)

USE IN SPECIFIC POPULATIONS
Hepatic Impairment

●	Bevyxxa has not been evaluated in patients with hepatic impairment, because these patients may have intrinsic coagulation abnormalities
●	Bevyxxa is not recommended in patients with hepatic impairment

Please see full Prescribing Information, including Boxed Warning.

References: 1. Bevyxxa ® (betrixaban) Prescribing Information. South San Francisco, CA: Portola Pharmaceuticals, Inc; 2017. 2. Chan NC, Bhagirath V, Eikelboom JW. Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag. 2015;11:343-351.

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