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 (FDA) 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. It is  on the World Health Organization's List of Essential Medicines. Medical uses. In the United States, edoxaban is indicated to treat deep vein thrombosis and pulmonary embolism following five to ten days of initial therapy with a parenteral anticoagulant. It is also indicated to reduce the risk of blood clots in people with nonvalvular atrial fibrillation. In the European Union, edoxaban is indicated for preventing blood clots in people with nonvalvular atrial fibrillation who also have at least one risk factor, such as having had a previous stroke, high blood pressure (hypertension), diabetes mellitus, congestive heart failure or being 75  years of age or older. It is also used to treat deep vein thrombosis and pulmonary embolism and to prevent either of these from reoccurring. Contraindications and notes. Edoxaban is often contraindicated in people (incomplete list): Edoxaban (incomplete list): Adverse effects. 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 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 (K) 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.