Betrixaban

• It is used to thin the blood so that clots will not form.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time betrixaban is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take betrixaban or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to betrixaban. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Inhibits fibrin clot formation via direct and selective inhibition of factor Xa (FXa). FXa, as part of the prothrombinase complex consisting also of factor Va, calcium ions, and phospholipid, catalyzes the conversion of prothrombin to thrombin. Thrombin both activates platelets and catalyzes the conversion of fibrinogen to fibrin.

Absorption

Cmax and AUC reduced by ~70% and 61% for low-fat and 50% and 48% for high-fat meal, respectively; effect of food observed for up to 6 hours.

Distribution

Vd: 32 L/kg

Metabolism

Minimal via CYP-independent hydrolysis to 2 major metabolites (inactive, accounting for 15% to 18% of parent compound); <1% of minor metabolites formed via CYP 1A1, 1A2, 2B6, 2C9, 2C19, 2D6, and 3A4; substrate of P-glycoprotein (P-gp).

Excretion

Feces (~85%); urine (11%)

VTE (prophylaxis): Prophylaxis of VTE in adults 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: Safety and effectiveness have not been established in patients with prosthetic heart valves (has not been studied).

Administer with food at the same time each day.

Store at 20°C to 25°C (68°F to 77°F).

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Many other drugs (including some over-the-counter medicines) can increase your risk of bleeding, or your risk of developing blood clots around the brain or spinal cord during a spinal tap or epidural. It is very important to tell your doctor about all medicines you have recently used, especially:

• ketoconazole;
• an antibiotic--azithromycin, clarithromycin, erythromycin;
• heart medication--amiodarone, quinidine, verapamil;
• an antidepressant, such as citalopram, duloxetine, escitalopram, fluoxetine (Prozac), fluvoxamine, paroxetine, sertraline (Zoloft), trazodone, venlafaxine, or vilazodone;
• an NSAID, such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib (Celebrex), diclofenac, indomethacin, or meloxicam; or
• other medicines to treat or prevent blood clots, such as dabigatran, dalteparin, enoxaparin, fondaparinux, heparin, or warfarin (Coumadin, Jantoven).

This list is not complete and many other drugs can interact with betrixaban. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Betrixaban is usually taken once per day for up to 42 days. Follow your doctor's dosing instructions very carefully.

Take with food.

Because betrixaban keeps your blood from coagulating (clotting) to prevent unwanted blood clots, this medicine can also make it easier for you to bleed. Contact your doctor or seek emergency medical attention if you have unusual bruising, or any bleeding that will not stop.

If you need surgery or dental work, tell the doctor or dentist ahead of time that you take betrixaban. You may need to stop taking the medicine for a short time before you have surgery or other medical procedures.

Do not stop taking betrixaban unless your doctor tells you to. Stopping suddenly can increase your risk of blood clot or stroke.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose may cause excessive bleeding.

Take the missed dose on the same day you remember it. Take your next dose at the regular time and stay on your once-daily schedule. Do not take extra medicine to make up the missed dose.

Dosage Forms & Strengths

capsule

• 40mg
• 80mg

Venous Thromboembolism Prevention

Indicated for prophylaxis of venous thromboembolism (VTE) in adults hospitalized for acute medical illness who are at risk for thromboembolic complications owing to moderate or severe restricted mobility and other risk factors for VTE

Initial single dose: 160 mg PO, THEN 80 mg PO qDay

Recommended duration of treatment: 35-42 days

Dosage Modifications

Coadministration with P-gp inhibitors

• Initial single dose of 80 mg, then 40 mg PO qDay x35-42 days
• Patients taking P-gp inhibitor who also have severe renal impairment: Not recommended

Renal impairment

• Mild-to-moderate (CrCl >30 mL/min): No dose adjustment needed
• Severe (CrCl ≥15 to <30 mL/min): Initial single dose of 80 mg, then 40 mg PO qDay x35-42 days

Hepatic impairment

• Not recommended; drug was not evaluated in hepatic impairment, because these patients may have intrinsic coagulation abnormalities

Dosing Considerations

Limitations of use

• Safety and efficacy not established for patients with prosthetic heart valves (not studied)

Safety and efficacy not established

1-10%

Clinically relevant nonmajor bleeding (2.45%)

Epistaxis (2%)

Hematuria (2%)

<1%

Bleeding

• Major bleeding (0.67%)
• GI bleeding (0.51%)
• Intracranial hemorrhage (0.05%)
• Fatal bleeding (0.03%)

Pregnancy

No data exist with use in pregnant women, but treatment is likely to increase risk of hemorrhage during pregnancy and delivery

Use during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus

Animal studies

• Although betrixaban has not been associated with adverse developmental fetal outcomes in animals, maternal toxicity (ie, hemorrhage) was identified in these studies

Lactation

Unknown if distributed in human breast milk

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.