Edoxaban


Edoxaban, sold under the brand name Lixiana among others, is an anticoagulant medication and a direct factor Xa inhibitor. It is taken by mouth.
Compared with warfarin it has fewer drug interactions.
It was developed by Daiichi Sankyo and approved in July 2011 in Japan for prevention of venous thromboembolisms following lower-limb orthopedic surgery. It was also approved in the United States by the Food and Drug Administration in January 2015, for the prevention of stroke and non–central-nervous-system systemic embolism. It was approved for use in the European Union in June 2015.

Medical uses

In the US, edoxaban is approved for treating deep vein thrombosis and pulmonary embolism following 5 to 10 days of initial therapy with a parenteral anticoagulant. It is also approved for reducing the risk of blood clots in patients with nonvalvular atrial fibrillation.
In the EU, edoxaban is approved for preventing blood clots in patients with nonvalvular atrial fibrillation who also have at least one risk factor, such as having had a previous stroke, high blood pressure, diabetes mellitus, heart failure or being 75 years old or over. It is also used to treat deep vein thrombosis and pulmonary embolism and to prevent either of these from reoccurring.
Doses are often taken regularly and with or without food. Typical doses for clot prevention are 60 milligrams once a day for adults, but 30 mg doses may be used in people who weigh less than 60 kilograms or have moderate kidney failure. 15 mg daily doses may be used when transitioning between edoxaban and some other anticoagulant.

Contraindications and notes

Edoxaban is often contraindicated in people :
Edoxaban :
May affect up to 1 in 10 people:
May affect up to 1 in 100 people:
May affect up to 1 in 1000 people: bleeding in the muscles, joints, abdomen, heart or inside the skull.

Overdose

Edoxaban overdose can cause serious bleeding. No FDA or EMA approved antidotes for edoxaban overdose exist. Hemodialysis does not significantly contribute to edoxaban clearance. Andexanet alfa has been studied as an antidote for edoxaban overdose, but has only been approved for reversing rivaroxaban and apixaban effects by the FDA and the EMA as of 2019.

Mechanism of action

Edoxaban is a direct, selective, reversible and competitive inhibitor of human factor Xa, with an inhibitory constant value of 0.561 nM. In coagulation, uninhibited factor Xa forms a prothrombinase complex with factor Va on platelet surfaces. Prothrombinases turn prothrombins to thrombins. Thrombins turn blood-soluble fibrinogens to insoluble fibrins, which are the main components of blood clots.

Pharmacokinetics

In human, 15–150 mg oral doses of edoxaban reach their maximum concentrations in blood 1–2 hours after ingestion. With 60 mg doses of isotope labeled edoxaban, 97% of the total radiation was detected after oral administration, with 62% from feces and 35% from urine. 49% of the total radiation from the feces and 24% from the urine were from edoxaban, the rest from its metabolites.
Metabolism occurs mostly via CES1, CYP3A4, CYP3A5 and enzymatic hydrolysis. CES1 oxidizes the tertiary amide carbonyl carbons of edoxabans to carboxylic acid groups. CYP3A4 and CYP3A5 oxidize edoxabans via hydroxylation or demethylation. In hydrolysis, 2-amino-5-chloropyridine moiety of edoxaban is removed. Glucuronidation occurs to a lesser extend via glucuronosyltransferases.