Edoxaban

Structural formula
General
Non-proprietary name	Edoxaban
other names	N - (5-chloro-2-pyridinyl) -N '- [(1 S , 2 R , 4 S ) -4- (dimethylcarbamoyl) -2 - {[(5-methyl-4,5,6,7- tetrahydro [1,3] thiazolo [5,4-c] pyridin-2-yl) carbonyl] amino} cyclohexyl] ethanediamide ( IUPAC )
Molecular formula	C 24 H 30 ClN 7 O 4 S
External identifiers / databases
CAS number 480449-70-5 480449-71-6 (tosylate) PubChem 10280735 ChemSpider 8456212 DrugBank DB09075 Wikidata Q21011234
Drug information
ATC code	B01 AF03
properties
Molar mass	548.06 g mol −1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS hazard labeling no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Edoxaban (trade name Lixiana , in some countries Savaysa ) is a drug belonging to the class of anticoagulants (anticoagulants). It was approved for use in preventing blood clotting in Japan in 2011 and in Europe in 2015 . The substance is a direct factor Xa inhibitor and thus belongs to the group of direct oral anticoagulants (DOAC), which are also known as new oral anticoagulants (NOAC).

The word Edoxaban is composed of the old name Edo for Tokyo , the seat of the manufacturer Daiichi Sankyo , from Xa as an abbreviation for the inhibition of the coagulation factor Xa and from the suffix - (b) an for the group of DOAKs.

indication

Edoxaban is like the other new oral anticoagulants in connection with non-valvular atrial fibrillation for prevention of an embolism or a stroke prescribed. Another approved application is the therapy of deep vein thrombosis or pulmonary embolism .

effect

Edoxaban, like rivaroxaban and apixaban, directly inhibits activated blood coagulation factor Xa. As a result, less thrombin is produced, which causes the last step in blood clotting , namely the formation of fibrin from fibrinogen. Blood clotting is therefore delayed or not at all. It works through a different mechanism than warfarin or phenprocoumon .

The conventional coagulation tests such as INR or PTT do not reliably indicate the effect of edoxaban. The direct determination of factor Xa for the detection of a therapy with edoxaban or another factor Xa antagonist is only possible in special laboratories . A routine control of the effect is not necessary. The standard dose is 60 mg once a day. The half-life of edoxaban is 9 to 11 hours.

Studies

For approval, the manufacturer conducted the ENGAGE AF-TIMI 48 study in 46 countries worldwide at 1,393 clinics with more than 21,000 patients with atrial fibrillation. Inclusion criterion was a CHADS2 score of 2 or higher with an indication for the drug prevention of a stroke.

This study showed a slightly better effect of edoxaban in preventing strokes and, in addition, a significantly lower risk of undesirable bleeding complications, which is typical of the new oral anticoagulants. According to a meta-analysis published in 2019, the likelihood of bleeding inside the eye (intraocular) was lower than with other NOACs and than with warfarin.

Contraindications

Before surgery, especially those with elevated or not portable risk of bleeding, as well as before neuraxial regional anesthesia long (two to five should Edoxaban enough half-lives ) will be paused when this is justifiable. No approval for stage V renal insufficiency with a glomerular filtration rate below 15 ml / min. Prohibited during pregnancy and breastfeeding .

The dose should be reduced in the case of impaired kidney function (with a creatinine clearance of 15 to 50 ml / min), in case of low body weight (≤ 60 kg) and / or while taking P-gp inhibitors (dronedarone, erythromycin , ketoconazole, Ciclosporin).

Early benefit assessment

In Germany, since 2011, newly approved drugs with new active ingredients must be subjected to an " early benefit assessment " by the Federal Joint Committee (G-BA) in accordance with Section 35a SGB ​​V if the pharmaceutical manufacturer wants to achieve a higher sales price than just the fixed amount . Only if there is an additional benefit can the pharmaceutical manufacturer negotiate a price with the umbrella association of statutory health insurance companies. The dossier evaluations, on the basis of which the G-BA makes its decisions, are created by the Institute for Quality and Efficiency in Health Care (IQWiG) .

In 2015, edoxaban was evaluated in two indications in such a procedure: firstly, for the prophylaxis of strokes and systemic embolisms in adult patients with non-valvular atrial fibrillation and at least one risk factor such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic Attack (TIA) in the anamnesis and secondly for the treatment of deep vein thrombosis and pulmonary embolism as well as for the prophylaxis of corresponding recurrences in adults. According to the G-BA decision, there is an indication of a minor additional benefit compared to vitamin K antagonists as an appropriate comparator therapy for the first-named patient group. For the second group named, an added benefit compared to the same ACT is not proven.

Individual evidence

1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
2. ^ Atrial fibrillation: Edoxaban new alternative to warfarin . In: aerzteblatt.de , November 20, 2013.
3. ↑ Henri Bounameaux, A. John Camm: Edoxaban: An Update on the New Oral Direct Factor Xa inhibitor. In: Drugs. 74, 2014, p. 1209, doi: 10.1007 / s40265-014-0261-1 .
4. ↑ ^{a b} Anticoagulation: edoxaban inhibits factor Xa . Pharmaceutical newspaper online; accessed on February 24, 2017
5. ↑ The New England Journal of Medicine: Edoxaban versus Warfarin in Patients with Atrial Fibrillation , doi: 10.1056 / NEJMoa1310907 .
6. ↑ Phan K et al .: intraocular bleeding in patients managed with novel oral anticoagulation and traditional anticoagulation: a network meta-analysis and systematic review. Br J Ophthalmol 2019; 103: 641-647.
7. ↑ A15-29 Edoxaban - Benefit assessment according to Section 35a SGB V (dossier assessment). iqwig.de; accessed on April 20, 2020.
8. ↑ Benefit assessment procedure for the active ingredient edoxaban (prophylaxis of thromboembolic events). g-ba.de; accessed on April 20, 2020.

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