Products
Direct factor Xa inhibitors are commercially available in the form of film-coated tablets and capsules. In 2008, rivaroxaban (Xarelto) was the first agent in this group to be approved in many countries and in the EU. Today, there are other drugs on the market, which are listed below. Like thrombin inhibitors, these active ingredients belong to the so-called DOAKs (direct oral anticoagulants) and NOAKs (new oral anticoagulants), respectively. The names of the active ingredients contain the abbreviation Xa, e.g., edoxaban.
Structure and properties
Factor Xa inhibitors are small-molecule compounds and not biologics. They are designed to bind in an L-shape to the active site of the drug target factor Xa.
Effects
Factor Xa inhibitors (ATC B01AF) have antithrombotic properties. The effects are based on direct, reversible, and selective inhibition of factor Xa. This coagulation factor plays an important role in the blood clotting cascade. It is a serine protease formed from factor X in both the intrinsic and extrinsic pathways and catalyzes the formation of thrombin from prothrombin. Thrombin converts fibrinogen to fibrin, promoting the formation of the fibrin plug. Factor Xa inhibitors additionally have an indirect effect on platelet aggregation. Unlike low-molecular-weight heparins, factor Xa inhibitors do not have to be injected under the skin but can be taken perorally. Compared with vitamin K antagonists such as phenprocoumon, they have predictable and linear pharmacokinetics and a rapid onset of action. Dosing is simple (fixed) and no therapy monitoring is required.
Indications
- For the prevention of thrombosis during major orthopedic surgery of the lower extremities such as hip and knee replacements (joint replacements).
- For the treatment of deep vein thrombosis and pulmonary embolism.
- For the prevention of recurrent deep vein thrombosis and pulmonary embolism.
- For the prevention of stroke and for the prevention of systemic embolism in non-valvular atrial fibrillation.
Dosage
According to the professional information. The drugs are usually taken once a day. This is with the exception of apixaban (Eliquis), which must be administered twice daily, in the morning and evening.
Active ingredients
Direct factor Xa inhibitors:
- Apixaban (Eliquis)
- Betrixaban (Bevyxxa, currently not approved in many countries).
- Edoxaban (Lixiana)
- Rivaroxaban (Xarelto)
Contraindications
Contraindications include (selection, depending on the active ingredient):
- Hypersensitivity
- Clinically significant active bleeding
- Acute gastric or intestinal ulceration
- Severe liver and kidney disease
- Pregnancy and lactation
Full precautions can be found in the drug label.
Interactions
Factor Xa inhibitors are substrates of CYP450 isozymes and may cause corresponding interactions. Caution is advised when combining them with drugs that affect blood clotting. These include, for example, nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, platelet aggregation inhibitors, and vitamin K antagonists.
Adverse effects
The most common potential adverse effects include bleeding in various organs, such as the eye, gums, skin, gastrointestinal tract, and nose. Severe to life-threatening bleeding may rarely occur. As a universal antidote, Andexanet alfa was developed, a recombinant, modified and enzymatically inactive factor Xa, which binds the active substances and thus inactivates them.