Factor Xa inhibitors: Uses, common brands, and safety info

An arrhythmia is a problem with the heartbeat’s rate or rhythm—the heart can beat too quickly, too slowly, or in an irregular pattern. A faster than normal heartbeat is called tachycardia. A slower than normal heartbeat is called bradycardia. Atrial fibrillation, or AFib, is the most common type of heart arrhythmia. AFib causes an irregular and fast heartbeat. 

AFib increases the risk for stroke—and strokes caused by AFib complications are usually more serious than strokes from other causes. AFib is the most common cause of stroke. Anticoagulants, or blood thinners, used in people with AFib, can help lower the risk of complications, including stroke. 

Factor Xa inhibitors (FXa inhibitors) are a group of anticoagulant drugs that work by blocking factor Xa, which produces thrombin from prothrombin. Thrombin is a necessary ingredient in blood clot production. By blocking factor Xa, these medications decrease clot production. Factor Xa inhibitors are also known as NOACs (novel oral anticoagulants, or new oral anticoagulants) or DOAC (direct oral anticoagulants) and do not require routine monitoring.

This article will discuss uses, common brand names, and safety information of factor Xa inhibitors. 

Other factor Xa inhibitors

Bevyxxa (betrixaban)—This drug is a factor Xa inhibitor that is no longer available. It was taken off the market in 2020. 

What are factor Xa inhibitors?

Factor Xa inhibitors are a group of newer anticoagulants or blood thinners. All of the drugs in this class are available by prescription and are approved by the U.S. Food and Drug Administration (FDA).  

How do factor Xa inhibitors work?

Factor Xa inhibitors have an anticoagulant effect (blood-thinning effect) by blocking factor Xa. Factor Xa makes thrombin, which helps make clots. Blocking factor Xa interrupts the blood coagulation cascade, inhibiting thrombin formation and the development of clots. 

What are factor Xa inhibitors used for?

Factor Xa inhibitors are used to prevent and treat clotting events. More specifically, Eliquis and Xarelto are approved to:

• Prevent stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AFib that is not caused by a heart valve issue)

• Treat deep vein thrombosis (DVT) and pulmonary embolism (PE)

• Prevent the recurrence of DVT and PE 

• Prevent venous thromboembolism after knee replacement or hip replacement surgery

Additionally, Xarelto is approved to:

• Prevent venous thromboembolism in acutely ill medical patients at risk for thromboembolic complications, who are not at high risk of bleeding.

• Lower the risk of major cardiovascular events in patients with coronary artery disease (CAD), used in combination with aspirin

• Lower the risk of major thrombotic vascular events in patients with peripheral artery disease, used in combination with aspirin

Arixtra is approved to:

• Prevent DVT and PE in patients undergoing knee or hip replacement surgery, or hip fracture surgery. It can also be used in patients undergoing abdominal surgery who are at risk for clotting complications.

• Treat acute DVT or PE (when given with warfarin).

Savaysa is approved to: 

• Lower the risk of stroke and systemic embolism in patients with nonvalvular AFib. 

• Treat DVT and PE by oral route, after 5-10 days of initial treatment with a parenteral anticoagulant. 

Types of factor Xa inhibitors 

Direct factor Xa inhibitors

Eliquis, Savaysa, and Xarelto are direct oral factor Xa inhibitors. They directly work on the factor Xa molecule. These drugs are taken orally (by mouth). 

Indirect factor Xa inhibitor

Arixtra is an indirect factor Xa inhibitor. It does not work directly on the factor Xa molecule. Arixtra is administered by subcutaneous (under the skin) injection. 

Who can take factor Xa inhibitors?

Before taking a factor Xa inhibitor, consult your healthcare professional for medical advice. Tell your doctor about your medical history, medical conditions, allergies to medications, and all of the medications you take. This includes prescription and OTC medicines, vitamins, and supplements.

Men

Men can take a factor Xa inhibitor, provided that it is needed for an approved indication, and that there are no contraindications for its use (see below section for more information about contraindications). 

Women who are not pregnant or breastfeeding

Women who are not pregnant or breastfeeding can take a factor Xa inhibitor, if it is needed for an approved indication, and if there are no contraindications for use (see below section for more information about contraindications).

Women who are pregnant or breastfeeding

• Eliquis, Savaysa, and Xarelto should not be used in pregnant women. 

• In some cases, such as when there is a severe allergy to heparin (another blood thinner), Arixtra may be used with caution in pregnancy. 

• Women who are breastfeeding should consult their healthcare provider, as factor Xa inhibitors are generally not used in breastfeeding women due to lack of human data.

Children

Factor Xa inhibitors are not approved for use in children under the age of 18 years old. They have not been studied for safety and efficacy in this age group. 

Seniors

Older adults should consult with their healthcare provider for medical guidance. Provided that the factor Xa inhibitor is needed for an approved indication and that there are no contraindications for use, see below information:

• Arixtra: In clinical trials, serious side effects increased with age. Arixtra is largely processed by the kidney, and older adults are more likely to have kidney (renal) problems. Kidney function should be evaluated before taking Arixtra. Patients older than 75 years old eliminate Arixtra more slowly from the body.

• Eliquis: Older adults (ages 65 years and older) can take Eliquis.

• Savaysa: Older adults can take Savaysa.

• Xarelto: In clinical studies, both clotting events and bleeding events were higher in older adults.

Are factor Xa inhibitors safe?

Recalls

• Eliquis recall (February 7, 2018, February 8, 2018)

Restrictions

Factor Xa inhibitors are not safe for some people. This means the drug is contraindicated. Each drug has a specific set of contraindications and warnings, so it is important to ask your doctor about the specific drug you are taking. The list below is a general list of contraindications and warnings. Your doctor can provide you with more specific information.

Factor Xa inhibitors are contraindicated in people who are/who have: 

• Allergic to any drug in the class 

• Experiencing active bleeding (from a surgery, injury, or other cause)

• Pregnant

• Child-Pugh Class C liver impairment

• Antiphospholipid syndrome

• Acute pulmonary embolism 

All factor Xa inhibitors have a black box warning for premature discontinuation and spinal/epidural hematoma. The risk for clotting events increases when a factor Xa inhibitor is discontinued prematurely without another blood thinner in place. There is also a risk of developing spinal/epidural hematoma when a factor Xa inhibitor is used in patients who are undergoing a spinal procedure.

In some cases, benefits and risks will be evaluated and if the healthcare provider determines a factor Xa inhibitor is safe to take, the patient will be prescribed the medication with caution, and the patient will be closely monitored. The criteria vary slightly for each group,  so the prescribing information should be consulted. Some of these groups include patients who are/who have:

• Women of reproductive age

• Risk of bleeding

• Kidney problems 

• Uncontrolled high blood pressure

• Diabetic retinopathy

• Recent surgery or trauma

Are factor Xa inhibitors controlled substances?

No, factor Xa inhibitors are not controlled substances.

Common factor Xa inhibitors side effects

The most common side effects of factor Xa inhibitors are related to bleeding. Bleeding can even be severe or life-threatening. Bleeding is more likely to occur in patients who take other medications that interfere with hemostasis (the body’s normal response of stopping bleeding to prevent major blood loss). These drugs include but are not limited to, SSRI antidepressants, nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen, platelet inhibitors such as clopidogrel, and other anticoagulants such as dabigatran. Notify your doctor right away if you have signs of bleeding (whether minor bleeding or major bleeding), such as:

• Easy bruising

• Unusual bleeding

• Unexpected pain or swelling

• Weakness or dizziness

• Bleeding gums

• Nosebleeds 

• Heavy menstrual bleeding

• Blood in the urine or stools

If you are coughing up blood or vomit that looks like coffee grounds or have any bleeding that will not stop, call your doctor right away or get emergency medical help. 

Other common side effects of factor Xa inhibitors include: 

• Anemia (low red blood cell counts)

• Nausea

• Back and stomach pain

• Itching

• Dizziness 

• Changes in liver function tests

Additionally, patients who take Arixtra may experience bleeding, pain, and/or rash at the injection site. 

Serious side effects are possible as well. In addition to the bleeding which can be serious, some people experience a hypersensitivity reaction to a factor Xa inhibitor. Symptoms such as hives, difficulty breathing, or swelling around the face, lips, tongue, or throat, require emergency medical attention. Symptoms of a severe skin reaction, including fever, sore throat, burning eyes, red or purple rash, and/or blistering or peeling skin require emergency medical attention. Symptoms of a spinal cord blood clot, such as numbness, tingling, or muscle weakness, especially in the legs, and feet, also require emergency medical help.

Other serious side effects can include:

• Epidural or spinal hematoma

• Low platelet counts

• Fainting 

• Liver problems (symptoms can include fatigue, stomach pain, dark urine, clay-colored stools, and yellowing of the skin or whites of the eyes)

Also, stopping the medication too soon can cause a blood clot or stroke. Do not stop taking the medication unless your doctor tells you to do so. 

This is not a full list of side effects. Other side effects may occur. Talk to your doctor about what side effects to expect and how to address them. 

How to stay safe while taking a blood thinner

Because taking a blood thinner can make you more likely to bleed, it’s important to take steps to prevent bleeds. Here are a few tips:

• If you need a medical procedure/surgery or dental work, tell your healthcare provider ahead of time that you take a blood thinner.

• Seek emergency medical help immediately if you fall or hit your head. Even if you do not see blood, you may be bleeding under the skin or in the skull. 

• Use sharp objects like knives, scissors, and razors carefully. Choose an electric razor if possible. 

• When taking care of your teeth, use a soft toothbrush and waxed floss. Avoid the use of toothpicks.

• Avoid activities that may cause injury. Talk with your doctor about what type of exercise is safe for you, such as swimming or walking. 

• If you ride a bike, wear a helmet. 

• Always wear a medical alert ID that says you take a blood thinner.

• When inside, wear shoes or non-slip slippers. When outside, always wear shoes.

• Be careful when cutting toenails. Do not try to trim your own calluses—go to a podiatrist instead.  

• When you work outside, wear appropriate gloves.

How much do factor Xa inhibitors cost?

The price of factor Xa inhibitors varies, depending on insurance coverage. The best way to find out how much you will pay for a factor Xa inhibitor is to contact your insurance or Medicare prescription plan for up-to-date coverage information. You can always use a free SingleCare coupon to save money on your factor Xa inhibitor prescription. Customers can save up to 80% on medications by using a SingleCare coupon at participating pharmacies.