Edoxaban

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Edoxaban
Names
Trade namesSavaysa, Lixiana, Roteas, others
Other namesDU-176b
  • N'-(5-chloropyridin-2-yl)-N-[(1S,2R,4S)-4-(dimethylcarbamoyl)-2-[(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-2-carbonyl)amino]cyclohexyl]oxamide
Clinical data
Pregnancy
category
  • US: N (Not classified yet)[1]
Routes of
use		By mouth
External links
AHFS/Drugs.comMonograph
MedlinePlusa614055
Legal
License data
Legal status
Pharmacokinetics
Bioavailability62%; Tmax 1–2 hours[5]
Protein binding55%[5]
Metabolismminimal CES1, CYP3A4/5, hydrolysis, glucuronidation[5]
Elimination half-life10–14 hours[5]
Excretion62% feces, 35% urine (97% of 60 mg)[5]
Chemical and physical data
FormulaC24H30ClN7O4S
Molar mass548.06 g·mol−1
3D model (JSmol)
  • CN1CCC2=C(C1)SC(=N2)C(=O)N[C@@H]3C[C@H](CC[C@@H]3NC(=O)C(=O)NC4=NC=C(C=C4)Cl)C(=O)N(C)C
  • InChI=1S/C24H30ClN7O4S/c1-31(2)24(36)13-4-6-15(27-20(33)21(34)30-19-7-5-14(25)11-26-19)17(10-13)28-22(35)23-29-16-8-9-32(3)12-18(16)37-23/h5,7,11,13,15,17H,4,6,8-10,12H2,1-3H3,(H,27,33)(H,28,35)(H,26,30,34)/t13-,15-,17+/m0/s1 ☒N
  • Key:HGVDHZBSSITLCT-JLJPHGGASA-N ☒N

Edoxaban, sold under the brand-name Lixiana among others, is a anticoagulant (blood thinner) used to prevent and treat blood clots.[6] It is not clear if it is safe with prosthetic heart valves.[6] It is taken by mouth once a day; either 30mg or 60mg depending on body weight and kidney function.[6]

Common side effects include nose bleeds, blood in the urine, and anemia.[7] Other side effects may include nausea, skin rash, and brain bleeding.[6] Compared with warfarin it has fewer interactions.[5] It is in the direct factor Xa inhibitors family of medications.[6]

Edoxaban was developed by Daiichi Sankyo and approved for medical use in Japan in 2011.[8] Approval in the United States and Europe occurred in 2015.[9][7] It is on the World Health Organization's List of Essential Medicines as an alternative to dabigatran.[10] In the UK, a month supply costs the NHS around £50 as of 2021, more than 50 times that of warfarin, although this difference may be offset by lower monitoring costs.[6][11] This amount in the United States costs about 390USD.[12]

Medical uses

Edoxaban is used to treat deep vein thrombosis and pulmonary embolism following 5-10 days of initial therapy with an injectable anticoagulant.[4][13] It is also used to prevent deep vein thrombosis and pulmonary embolism.[2]

It is also used for reducing the risk of blood clots in people with nonvalvular atrial fibrillation.[14][4] Specifically it is used 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, diabetes mellitus, heart failure or being 75 years old or over.[2]

Dose

The defined daily dose is 60mg/day.[15] For people who weigh less than 61kg or who have severe kidney problems, the dose is reduced to 30mg/day.[13] The dose is once daily and it can be taken with or without food.[16]

Contraindications

Edoxaban is contraindicated in people who have abnormal active bleeding or a known allergy to edoxaban.[13]

Other contraindications include:

Side effects

May affect up to 1 in 10 people:[17]

  • stomach ache
  • abnormal results of blood tests that measure liver function
  • anemia
  • bleeding from the skin, nose, vagina, bowel, mouth, throat or stomach
  • rash
  • bloody urine
  • dizziness
  • feeling sick
  • headache
  • itching

May affect up to 1 in 100 people:[17]

  • bleeding in the eyes, brain, after a surgical operation or other types of bleeding
  • blood in the spit when coughing
  • reduced number of platelets in blood
  • allergic reaction
  • hives

May affect up to 1 in 1000 people: bleeding in the muscles, joints, abdomen, heart or inside the skull.[17]

Overdose

Edoxaban overdose can cause serious bleeding.[medical citation needed] No approved antidotes for edoxaban overdose exist.[6] Hemodialysis does not significantly contribute to edoxaban clearance.[4][17] 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.[18][19]

Interactions

Edoxaban:

Mechanism of action

Edoxaban is a direct, selective, reversible and competitive inhibitor of human factor Xa, with an inhibitory constant (Ki) 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.[5]

It has a half-life of around 10-14 hours, and can sustain a blood thinning effect for 24 hours.[16]

Pharmacology

In human, 15–150 mg oral doses of edoxaban reach their maximum concentrations in blood 1–2 hours after ingestion.[16] 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.[5]

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.[5]

More than two-thirds of edoxaban is eliminated unchanged.[16]

Society and culture

Cost

In the UK, a month supply of edoxaban costs the NHS around £50, more than 50 times that of warfarin, although this difference may be offset by lower monitoring costs.[11][6]

Brand names

It is sold under the brand names Savaysa and Lixiana.[4][7]

References

  1. ↑ "Edoxaban (Savaysa) Use During Pregnancy". Drugs.com. 17 June 2020. Archived from the original on 18 May 2021. Retrieved 18 May 2021.
  2. ↑ 2.0 2.1 2.2 "Lixiana EPAR". European Medicines Agency (EMA). Archived from the original on 24 October 2020. Retrieved 23 July 2020.
  3. ↑ "Roteas EPAR". European Medicines Agency (EMA). Archived from the original on 25 November 2020. Retrieved 25 September 2020.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 "Savaysa- edoxaban tosylate tablet, film coated". DailyMed. 24 April 2020. Archived from the original on 23 July 2020. Retrieved 23 July 2020.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Parasrampuria DA, Truitt KE (June 2016). "Pharmacokinetics and Pharmacodynamics of Edoxaban, a Non-Vitamin K Antagonist Oral Anticoagulant that Inhibits Clotting FactorXa". Clinical Pharmacokinetics. 55 (6): 641–55. doi:10.1007/s40262-015-0342-7. PMC 4875962. PMID 26620048.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 135-136. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
  7. ↑ 7.0 7.1 7.2 "Lixiana 60mg Film-Coated Tablets - Summary of Product Characteristics (SmPC) - (emc)". www.medicines.org.uk. Archived from the original on 5 March 2021. Retrieved 18 May 2021.
  8. ↑ "First market approval in Japan for Lixiana (Edoxaban)". Daiichi Sankyo Europe GmbH (Press release). 2011-04-22. Archived from the original on 2013-11-06.
  9. ↑ "Edoxaban Tosylate Monograph for Professionals". Drugs.com. Archived from the original on 4 March 2021. Retrieved 14 July 2021.
  10. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  11. ↑ 11.0 11.1 Hitchings, Andrew; Lonsdale, Dagan; Burrage, Daniel; Baker, Emma (2019). The Top 100 Drugs: Clinical Pharmacology and Practical Prescribing (2nd ed.). Elsevier. pp. 118–119. ISBN 978-0-7020-7442-4. Archived from the original on 2021-05-22. Retrieved 2021-11-09.
  12. ↑ "Edoxaban Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 14 July 2021.
  13. ↑ 13.0 13.1 13.2 "Edoxaban". 2019 Nurse's Drug Handbook (18th ed.). Jones & Bartlett Learning. 2019. p. 391. ISBN 978-1-284-14489-5. Archived from the original on 2021-08-28. Retrieved 2021-05-19.
  14. ↑ Lowenstern A, Al-Khatib SM, Sharan L, Chatterjee R, Allen LaPointe NM, Shah B, et al. (December 2018). "Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation: A Systematic Review". Annals of Internal Medicine. 169 (11): 774–787. doi:10.7326/M18-1523. PMC 6825839. PMID 30383133. Archived from the original on 2021-08-28. Retrieved 2022-03-14.
  15. ↑ "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 19 May 2021. Retrieved 19 May 2021.
  16. ↑ 16.0 16.1 16.2 16.3 Dobesh, Paul P.; Stacy, Zachary A. (2019). "2. Pharmacology of oral anticoagulants". In Greg Flaker (ed.). Stroke Prevention in Atrial Fibrillation. St. Louis, Missouri: Elsevier. pp. 28–29. ISBN 978-0-323-55429-9. Archived from the original on 2021-08-28. Retrieved 2021-05-19.
  17. ↑ 17.0 17.1 17.2 17.3 17.4 17.5 17.6 17.7 17.8 17.9 "Lixiana, INN-edoxaban" (PDF). Archived (PDF) from the original on 2019-11-06. Retrieved 2019-11-06.
  18. ↑ Ovanesov M (2017-08-03). "Summary basis for regulatory action - ANDEXXA". Archived from the original on 2020-12-06. Retrieved 2019-11-06.
  19. ↑ "Ondexxya". European Medicines Agency. 2019-02-27. Archived from the original on 2019-10-16. Retrieved 2019-11-06.

External links

External sites:
Identifiers:
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