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).^[2][3]

Medical use

Direct factor Xa inhibitors include

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.[2]

Adverse effects

Side effects may include

A specialist may request a quantitative factor Xa assay in a situation of overdose.[2] 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.^[9] It is also available in the UK.^[10]

Drug interactions

The risk of bleeding is increased if used at the same time as other blood thinning drugs such as

Direct factor Xa inhibitors block the enzyme called

They have a rapid onset and offset of action. This means it is often possible to pause them 12 to 48 hours before surgery and resume them shortly after the surgery. By contrast, warfarin and phenprocoumon are often paused up to a week before surgery, and low-molecular-weight heparins are used to "bridge" the therapy gap, typically for several weeks.^[12][13]

Also in contrast to warfarin and phenprocoumon, direct factor Xa inhibitors do not require frequent monitoring of the prothrombin time (also called the INR) and dose adjustments.^[12]

History

Prior to the introduction of direct factor Xa inhibitors,

A naturally occurring inhibitor of factor Xa was reported in 1971 by Spellman et al. from the dog hookworm.[15] In 1987, Tuszynski et al. discovered antistasin, which was isolated from the extracts of the Mexican leech, Haementeria officinalis.^[16][17] Later, another naturally occurring inhibitor, tick anticoagulant peptide (TAP) was isolated from the extract of tick Ornithodoros moubata.^[18] Trials subsequently demonstrated efficacy and safety against warfarin for stroke prevention in AF and against LMWH for treatment and prevention of VTE including in people undergoing hip or knee replacement.^[19]

Society and culture

Economics

The cost of direct Xa inhibitors can reach more than 50 times that of warfarin, although this difference may be offset by lower monitoring costs.^[2][5]

Brand names

Brands include

Xabans that never reached the market include darexaban (YM150) from Astellas,^[22][23] otamixaban from Sanofi,^[24] letaxaban (TAK-442) from Takeda,^[25] and eribaxaban (PD0348292) from Pfizer.^[26]

References