Products
Rivaroxaban is commercially available in the form of film-coated tablets (Xarelto, Xarelto vascular). It was approved in 2008 as the first agent in the direct factor Xa inhibitor group. Low-dose Xarelto vascular, 2.5 mg, was registered in many countries in 2019.
Structure and properties
Rivaroxaban (C19H18ClN3O5S, Mr = 435.9 g/mol) is a pure -enantiomer and exists as an odorless, non-hygroscopic, white to yellowish powder that is practically insoluble in water. It is an oxazolidinone derivative closely related to the antibiotic linezolid. Rivaroxaban contains a chlorthiophene ring and a morpholinone ring.
Effects
Rivaroxaban (ATC B01AF01) has antithrombotic properties. The effects are due to direct, reversible, and selective inhibition of factor Xa (hence the brand name Xarelto). This blood clotting 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. It additionally has an influence on platelet aggregation. Unlike the heparins, rivaroxaban does not have to be injected under the skin, but can be taken as a tablet. It has predictable pharmacokinetics, rapid onset of action, and a medium-length half-life between 5 to 13 hours, unlike phenprocoumon.
Indications
- For thrombosis prophylaxis during major orthopedic surgery of the lower extremities. For example, in hip and knee joint replacements, such as after osteoarthritis surgery.
- For the treatment of deep vein thrombosis.
- For the treatment of pulmonary embolism.
- To prevent recurrent deep vein thrombosis or pulmonary embolism.
- For prevention of stroke and prevention of systemic embolism in non-valvular atrial fibrillation.
Deep-dose tablets (Xarelto vascular):
- In combination with acetylsalicylic acid for the prevention of serious atherothrombotic events (stroke, myocardial infarction, cardiovascular death) in patients with coronary artery disease or manifest peripheral arterial vascular disease and a high risk of ischemic events.
Dosage
According to the professional information. The tablets of 2.5 mg and 10 mg are taken independently of meals. The 15 mg and 20 mg tablets, on the other hand, are administered with food because this increases bioavailability. The tablets are taken once or twice daily, depending on the indication.
Contraindications
For complete precautions, see the drug label.
Interactions
Rivaroxaban is metabolized by CYP3A4, CYP2J2, and CYP-independent mechanisms and is a substrate of P-glycoprotein and BCRP. CYP inhibitors may increase the risk of bleeding and CYP inducers may reduce the effect. Combination with other antithrombotics/anticoagulants also increases bleeding risk.
Adverse effects
The most common potential adverse effects include bleeding in various organs. The following side effects are also common:
- Fever, peripheral water retention, weakness, fatigue.
- Gastrointestinal symptoms such as nausea, diarrhea, abdominal pain, constipation.
- Skin rash, itching
- Pain in the extremities
- Dizziness, headache
- Anemia
- Increase in transaminases
Bleeding can rarely be fatal.
Antidote
Andexanet alfa is available as an antidote. It is an inactive factor Xa that binds rivaroxaban and abolishes the anticoagulant effects.
