Direct factor Xa inhibitors

Direct factor Xa inhibitors (xabans) are anticoagulants (blood thinning drugs), used to both treat and prevent blood clots in veins, and prevent stroke and embolism in people with atrial fibrillation (AF).

Direct factor Xa inhibitors include rivaroxaban, apixaban and edoxaban, and are types of direct oral anticoagulant (DOAC), which are blood thinning drugs, one of the classes of antithrombotic drugs. They are commonly prescribed to treat and prevent blood clots in veins, prevent stroke and embolism in people with non-valvular atrial fibrillation (AF) who have other risk factors, and prevent blood clots after routine knee and hip replacement surgery.

Direct factor Xa inhibitors can be considered as an alternative to warfarin, particularly if a person is on several other medications that interact with warfarin, or if attending medical appointments and laboratory monitoring becomes difficult. Factors considered before deciding on whether warfarin or a DOAC or which direct factor Xa inhibitor is used, include: the presence or absence of valvular heart disease, state of kidney function, the risk of stroke and the risk of bleeding.

Direct Xa inhibitors are contraindicated in people who are actively bleeding or who are at high risk of bleeding. The effects on a fetus or neonate are unknown, hence these drugs are not prescribed in pregnancy or breast feeding mothers.

Side effects may include bleeding, most commonly from the nose, gastrointestinal tract (GI) or genitourinary system. Compared to the risk of bleeding with warfarin use, direct factor Xa inhibitors have a higher risk of GI bleeding, but lower risk of bleeding in the brain. Other side effects may include stomach upset, dizziness, anemia or increased blood levels of liver enzymes.

A specialist may request a quantitative factor Xa assay in a situation of overdose. Andexanet alfa, a specific antidote to reverse the anticoagulant activity of direct Xa inhibitors in the event of major bleeding, was approved by the FDA in 2018. It is also available in the UK.

The risk of bleeding is increased if used at the same time as other blood thinning drugs such as nonsteroidal anti-inflammatory drugs, antiplatelet drugs and heparin. The blood thinning effects can be reduced if used at the same time as rifampicin and phenytoin, and increased with fluconazole. Compared to warfarin they have fewer interactions with other medications.

Direct factor Xa inhibitors block the enzyme called factor Xa, preventing the conversion of prothrombin to thrombin in the final common pathway of clot formation in veins and the heart.