Ximelagatran

Jump to navigation Jump to search
Ximelagatran
Clinical data
Pregnancy
category
  • uncategorised
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • Rx only/POM
Pharmacokinetic data
Bioavailability20%
MetabolismNone
Elimination half-life3-5h
ExcretionRenal (80%)
Identifiers
CAS Number
PubChem CID
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC24H35N5O5
Molar mass474 (429 after conversion)

WikiDoc Resources for Ximelagatran

Articles

Most recent articles on Ximelagatran

Most cited articles on Ximelagatran

Review articles on Ximelagatran

Articles on Ximelagatran in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Ximelagatran

Images of Ximelagatran

Photos of Ximelagatran

Podcasts & MP3s on Ximelagatran

Videos on Ximelagatran

Evidence Based Medicine

Cochrane Collaboration on Ximelagatran

Bandolier on Ximelagatran

TRIP on Ximelagatran

Clinical Trials

Ongoing Trials on Ximelagatran at Clinical Trials.gov

Trial results on Ximelagatran

Clinical Trials on Ximelagatran at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Ximelagatran

NICE Guidance on Ximelagatran

NHS PRODIGY Guidance

FDA on Ximelagatran

CDC on Ximelagatran

Books

Books on Ximelagatran

News

Ximelagatran in the news

Be alerted to news on Ximelagatran

News trends on Ximelagatran

Commentary

Blogs on Ximelagatran

Definitions

Definitions of Ximelagatran

Patient Resources / Community

Patient resources on Ximelagatran

Discussion groups on Ximelagatran

Patient Handouts on Ximelagatran

Directions to Hospitals Treating Ximelagatran

Risk calculators and risk factors for Ximelagatran

Healthcare Provider Resources

Symptoms of Ximelagatran

Causes & Risk Factors for Ximelagatran

Diagnostic studies for Ximelagatran

Treatment of Ximelagatran

Continuing Medical Education (CME)

CME Programs on Ximelagatran

International

Ximelagatran en Espanol

Ximelagatran en Francais

Business

Ximelagatran in the Marketplace

Patents on Ximelagatran

Experimental / Informatics

List of terms related to Ximelagatran

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Ximelagatran (Exanta® or Exarta®, H 376/95) is an anticoagulant that has been investigated extensively as a replacement for warfarin that would overcome the problematic dietary, drug interaction, and monitoring issues associated with warfarin therapy. In 2006, its manufacturer AstraZeneca announced that it would not attempt to market ximelagatran after reports of hepatotoxicity (liver damage) during trials, and to discontinue its distribution in countries where the drug had been approved.

Method of action

Ximelagatran was the first member of the drug class of direct thrombin inhibitors that can be taken orally. It acts solely by inhibiting the actions of thrombin. It is taken orally twice daily, and rapidly absorbed by the small intestine. Ximelagatran is a prodrug, being converted in vivo to the active agent melagatran. This conversion takes place in the liver and many other tissues through dealkylation and dehydroxylation (replacing the ethyl and hydroxyl groups with hydrogen).

Uses

Ximelagatran was expected to replace warfarin and sometimes aspirin and heparin in many therapeutic settings, including deep venous thrombosis, prevention of secondary venous thromboembolism and complications of atrial fibrillation such as stroke. The efficacy of ximelagatran for these indications had been well-documented (Eriksson et al 2003, Frances et al 2004, Schulman et al 2004).

An advantage, according to early reports by its manufacturer, was that it could be taken orally without any monitoring of its anticoagulant properties. This would have set it apart from warfarin and heparin, which require monitoring of the international normalized ratio (INR) and the partial thromboplastin time (PTT), respectively. A disadvantage recognised early was the absence of an antidote in case acute bleeding develops, while warfarin can be antagonised by vitamin K and heparin by protamine sulfate.

Side-effects

Ximelagatran was generally well tolerated in the trial populations, but a small proportion (5-6%) developed elevated liver enzyme levels, which prompted the FDA to reject an initial application for approval in 2004. The further development was discontinued in 2006 after it turned out hepatic damage could develop in the period subsequent to withdrawal of the drug. According to AstraZeneca, a chemically different but pharmacologically similar substance, AZD0837, is undergoing testing for similar indications (AstraZeneca press release 2006).

References

  • "AstraZeneca Decides to Withdraw Exanta" (Press release). AstraZeneca. February 14, 2006.
  • Eriksson, H (2003). "A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I". Journal of Thrombosis and Haemostasis. 1: 41&ndash, 47. PMID 12871538. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  • Francis, CW (2003). "Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement". New England Journal of Medicine. 349 (18): 1703&ndash, 1712. PMID 14585938. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  • Schulman, S (2003). "Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran". New England Journal of Medicine. 349 (18): 1713&ndash, 1721. PMID 14585939. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  • Weitz, JI (2004). "New anticoagulants for treatment of venous thromboembolism". Circulation. 110 (Suppl 1): 19&ndash, 26. PMID 15339877. Unknown parameter |month= ignored (help)