Skip to Content

Bevyxxa

Generic Name: Betrixaban Maleate
Class: Direct Factor Xa Inhibitors
Chemical Name: N-(5-chloropyridin-2-yl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide
Molecular Formula: C23H22ClN5O3
CAS Number: 330942-05-7

Warning(s)

Warning: Spinal/epidural hematoma.1

See full prescribing information for complete boxed warning.1

Epidural or spinal hematomas may occur in patients treated with betrixaban 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.1

Introduction

Betrixaban maleate is a direct factor Xa inhibitor.1

Uses for Bevyxxa

Betrixaban maleate has the following uses:

Betrixaban maleate is a factor Xa (FXa) inhibitor 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.1

Limitations of use:

Safety and efficacy of betrixaban maleate have not been established in patients with prosthetic heart valves because this population has not been studied.1

Bevyxxa Dosage and Administration

General

Betrixaban maleate is available in the following dosage form(s) and strength(s):

Capsules: 40 mg and 80 mg.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

The recommended dose of betrixaban maleate is an initial single dose of 160 mg, followed by 80 mg once daily, taken at the same time each day with food. The recommended duration of treatment is 35 to 42 days.1

  • Reduce dose for patients with severe renal impairment (CrCl ≥ 15 to < 30 mL/min, computed by Cockcroft-Gault using actual body weight).1 In such patients, the recommended dose of betrixaban maleate is an initial single dose of 80 mg, followed by 40 mg once daily. The recommended duration of treatment is 35 to 42 days.1

  • Reduce dose for patients on P-glycoprotein (P-gp) inhibitors.1 For patients receiving or starting concomitant P-gp inhibitors, the recommended dose of betrixaban maleate is an initial single dose of 80 mg, followed by 40 mg once daily. The recommended duration of treatment is 35 to 42 days.1

Cautions for Bevyxxa

Contraindications

  • Active pathological bleeding.1

  • Severe hypersensitivity reaction to betrixaban.1

Warnings/Precautions

Risk of Bleeding

Betrixaban maleate increases the risk of bleeding and can cause serious and potentially fatal bleeding. Promptly evaluate any signs or symptoms of blood loss.1

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).1

Advise patients of signs and symptoms of blood loss and to report them immediately and seek emergency care. Promptly evaluate any signs or symptoms of blood loss and consider the need for blood replacement. Discontinue betrixaban maleate in patients with active pathological bleeding.1

There is no established way to reverse the anticoagulant effect of betrixaban maleate, which can be expected to persist for at least 72 hours after the last dose. It is unknown whether hemodialysis removes betrixaban maleate. Protamine sulfate, vitamin K, and tranexamic acid are not expected to reverse the anticoagulant activity of betrixaban maleate.1

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.1

Do not remove an epidural catheter earlier than 72 hours after the last administration of betrixaban maleate. Do not administer the next betrixaban maleate dose earlier than 5 hours after the removal of the catheter. If traumatic puncture occurs, delay the administration of betrixaban maleate for 72 hours.1

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.1

Use in Patients with Severe Renal Impairment

Patients with severe renal impairment (CrCl ≥ 15 to < 30 mL/min computed by Cockcroft-Gault using actual body weight) taking betrixaban maleate may have an increased risk of bleeding events. Reduce dose of betrixaban maleate, monitor patients closely, and promptly evaluate any signs or symptoms of blood loss in these patients.1

Use in Patients on Concomitant P-gp Inhibitors

Patients on concomitant P-gp inhibitors with betrixaban maleate may have an increased risk of bleeding. Reduce dose of betrixaban maleate in patients receiving or starting P-gp inhibitors. Monitor patients closely and promptly evaluate any signs or symptoms of blood loss in these patients. 1

Avoid use of betrixaban maleate in patients with severe renal impairment receiving concomitant P-gp inhibitors.1

Specific Populations

Pregnancy

There are no data with the use of betrixaban maleate in pregnant women, but treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. Betrixaban was studied in reproductive and developmental toxicology studies in rats and rabbits during the period of organogenesis at exposures up to 44 times the recommended clinical dose of 80 mg daily. Although betrixaban was not associated with adverse developmental fetal outcomes in animals, maternal toxicity (i.e., hemorrhage) was identified in these studies. Betrixaban maleate should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.1

Embryo-fetal development studies were conducted in pregnant rats and rabbits during the period of organogenesis. In rats, no adverse embryofetal or teratogenic effects were seen when betrixaban was administered orally at doses up to 200 mg/kg/day, or 44 times the human dose of 80 mg/day when based on AUC. In rabbits, no adverse embryofetal or teratogenic effects were seen at doses up to 45 mg/kg/day, or 35 times the human exposure at a dose of 80 mg/day when based on AUC. Pregnant rabbits administered the highest dose of 150 mg/kg/day were terminated prematurely due to excessive maternal toxicities. Upon post-mortem examination, early and/or late resorptions and fetal deaths were observed at the 150 mg/kg dose, which may be linked to hemorrhage observed in various organs including the reproductive tract. In a rat pre- and post-natal developmental study, betrixaban was administered orally during the period of organogenesis and through lactation day 20 at doses up to 200 mg/kg/day. Maternal toxicities (including decreased body weight gain and food consumption and red/brown perivaginal substance) were observed at 200 mg/kg/day, which is approximately 44 times the human exposure when based on AUC. At a maternal dose up to 200 mg/kg/day, betrixaban did not have adverse effects on sexual maturation, reproductive performance, or behavioral development of the F1 generation.1

Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. Consider the risks of bleeding and of stroke in using betrixaban maleate in this setting.1

Lactation

No data are available regarding the presence of betrixaban or its metabolites in human milk, the effects of the drug on the breast-fed infant, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for betrixaban maleate and any potential adverse effects on the breast-fed child from betrixaban maleate or from the underlying maternal condition.1

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.1

Geriatric Use

Of the total number of patients in the APEX clinical study, 90% were 65 years and over, while 68.6% were 75 years and over. No clinically significant differences in safety or effectiveness were observed between older and younger patients.1

Renal Impairment

Patients with severe renal impairment (CrCl ≥ 15 to < 30 mL/min computed by Cockcroft-Gault using actual body weight) may have an increased risk of bleeding events. Reduce the betrixaban maleate dose for patients with severe renal impairment. Monitor patients closely and promptly evaluate any signs or symptoms of blood loss in these patients. No dose adjustment is needed for mild or moderate renal impairment (CrCl > 30 mL/min, computed by Cockcroft-Gault using actual body weight). 1

Hepatic Impairment

Betrixaban maleate has not been evaluated in patients with hepatic impairment because these patients may have intrinsic coagulation abnormalities. Therefore, the use of betrixaban maleate is not recommended in patients with hepatic impairment.1

Common Adverse Effects

Most common adverse reaction (incidence > 5%) is bleeding.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

  • P-gp inhibitors increase the blood levels of betrixaban. Reduce betrixaban maleate dose.1

  • Anticoagulants: Avoid concomitant use.1

Actions

Mechanism of Action

Betrixaban is an oral FXa inhibitor that selectively blocks the active site of FXa and does not require a cofactor (such as antithrombin III) for activity. Betrixaban inhibits free FXa and prothrombinase activity. By directly inhibiting FXa, betrixaban decreases thrombin generation. Betrixaban has no direct effect on platelet aggregation.1

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Medication Guide).1

Risk of Bleeding

Advise patients that it might take longer than usual for bleeding to stop, and that they may bruise or bleed more easily when treated with betrixaban maleate. Instruct patients to report any unusual bleeding to their physician. 1

Instruct patients to tell their physicians and dentists that they are taking betrixaban maleate, and/or any other products known to affect bleeding (including nonprescription products, such as aspirin or NSAIDs), before any surgery or medical or dental procedure is scheduled and before any new drug is taken.1

Use in Patients with Severe Renal Impairment

Advise patients that the risk of bleeding is higher in people who have severe kidney problems (severe renal impairment).1

Spinal/Epidural Hematoma

Advise patients having neuraxial anesthesia or spinal puncture to watch for signs and symptoms of spinal or epidural hematomas, such as numbness or weakness of the legs, or bowel or bladder dysfunction. Instruct patients to contact their physician immediately if any of these symptoms occur.1

Pregnancy and Lactation

Advise female patients to inform their physicians if they are pregnant or plan to become pregnant or are breastfeeding or intend to breastfeed during treatment with betrixaban maleate.1

How to Take Betrixaban Maleate

Instruct patients to take betrixaban maleate with food, and instruct patients on what to do if a dose is missed.1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Betrixaban Maleate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsule, Gelatin Coated

40 mg

Bevyxxa

Portola Pharmaceuticals Inc.

80 mg

Bevyxxa

Portola Pharmaceuticals Inc.

AHFS Drug Information. © Copyright 2017, Selected Revisions July 17, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Portola Pharmaceuticals, Inc.. Bevyxxa (betrixaban) oral prescribing information. South San Francisco, CA; 2017 Jul.

Hide