Betrixaban

Approved Indications:

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

Off-label / Clinically Accepted Uses:

• Currently, there are no widely accepted off-label uses for Betrixaban. Its use is focused on extended-duration VTE prophylaxis in acute medically ill patients.

Adult Dosage:

• Initial Dose: 160 mg orally once on Day 1.
• Maintenance Dose: 80 mg orally once daily for 35–42 days.

With Renal Impairment (CrCl ≥15 to <30 mL/min):

• Initial Dose: 80 mg orally once.
• Maintenance Dose: 40 mg orally once daily for 35–42 days.

Administration Instructions:

• Administer with food to enhance absorption.
• Capsules should be swallowed whole, not chewed or opened.

Pediatric Use:

• Safety and efficacy in pediatric patients have not been established.

Elderly Patients:

• No dosage adjustment required; monitor renal function closely.

Betrixaban is an oral, direct, and selective inhibitor of activated Factor Xa (FXa). By inhibiting FXa, Betrixaban interrupts the intrinsic and extrinsic pathways of the blood coagulation cascade, thus reducing thrombin generation and thrombus development. Unlike vitamin K antagonists, it does not require a cofactor (e.g., antithrombin III) for its activity, and it does not affect platelet aggregation. This targeted inhibition leads to effective anticoagulation with predictable pharmacodynamics.

• Absorption: Oral bioavailability is approximately 34–50%. Peak plasma concentration (Tmax) occurs at 3–4 hours post-dose.
• Distribution: Highly protein-bound (~60%); volume of distribution is ~32 L.
• Metabolism: Minimally metabolized; CYP-independent metabolism (minor involvement of CYP3A4).
• Elimination: Primarily eliminated unchanged in the feces (85%); ~11% excreted via the kidneys.
• Half-life: Terminal half-life ranges from 19 to 27 hours.
• Steady State: Achieved within 3–5 days of once-daily dosing.

• Pregnancy: No FDA pregnancy category assigned (FDA has phased out the A/B/C/D/X system). Use in pregnancy is not recommended unless clearly needed due to limited human data and potential risk of bleeding.
• Lactation: It is unknown whether Betrixaban is excreted in human breast milk. Animal studies suggest excretion into milk. Due to potential for serious adverse reactions in nursing infants, a decision should be made to discontinue breastfeeding or discontinue the drug.

• Primary Class: Oral Anticoagulant
• Subclass: Direct Factor Xa Inhibitor (DOAC – Direct Oral Anticoagulant)

• Known hypersensitivity to Betrixaban or any component of the formulation
• Active pathological bleeding
• Severe hepatic impairment
• Use with other anticoagulants (except during transitions)
• Severe renal impairment with concomitant use of P-glycoprotein inhibitors

• Bleeding Risk: Increases risk of bleeding; use cautiously in patients with recent surgery, trauma, or known bleeding disorders.
• Spinal/Epidural Hematoma: Risk of hematomas and paralysis with neuraxial anesthesia or spinal puncture.
• Hepatic Impairment: Not recommended in severe hepatic impairment due to increased bleeding risk.
• Renal Monitoring: Assess renal function before initiation and periodically thereafter.
• Drug Discontinuation: Premature discontinuation increases risk of thrombotic events.

Common Side Effects:

• Gastrointestinal: Constipation, nausea, diarrhea
• General: Fatigue, dizziness

Serious Side Effects:

• Hemorrhagic Events: Major bleeding, gastrointestinal bleeding, intracranial hemorrhage
• Hypersensitivity Reactions: Rash, pruritus, anaphylaxis (rare)

Rare Side Effects:

• Hepatic dysfunction (elevated liver enzymes)
• Thrombocytopenia

Major Drug-Drug Interactions:

• P-glycoprotein (P-gp) Inhibitors: Concomitant use with strong P-gp inhibitors (e.g., amiodarone, verapamil, ketoconazole) increases Betrixaban plasma levels. Dose adjustment is necessary.
• Other Anticoagulants/Antiplatelets: Increased risk of bleeding when used concurrently with heparin, warfarin, aspirin, or NSAIDs.

Drug-Food Interactions:

• Must be taken with food to ensure adequate absorption.

Enzyme Systems:

• Minimal interaction with CYP450 enzymes (not a major CYP substrate, inducer, or inhibitor).

• FDA Update: Betrixaban (Bevyxxa) was voluntarily withdrawn from the U.S. market in 2020 due to business reasons, not safety concerns.
• Guideline Note: Betrixaban remains referenced in anticoagulation guidelines for extended VTE prophylaxis in specific high-risk patients. However, other DOACs have taken precedence in clinical use.
• NICE/EMA: Currently not recommended for new initiation due to lack of commercial availability in many regions.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C (59°F–86°F).
• Light & Moisture: Store in a dry place, away from light and moisture.
• Handling Precautions: Keep in original container; protect from excessive heat and humidity.
• No Reconstitution Required: Oral formulation; do not crush or chew capsules.