Ancrod

Identification

Summary

Ancrod is an anticoagulant purified from the venom of the Malayan pit viper that functions by inactivating circulating plasma fibrinogen. Not currently approved for use or marketed in any country.

Generic Name
Ancrod
DrugBank Accession Number
DB05099
Background

Ancrod, marketed as Viprinex, is a defibrinogenating agent derived from Malayan pit viper venom. The defribrinogenation of blood results in an anticoagulant effect. Currently, Viprinex®/ancrod is not approved or marketed in any country, but is being investigated as a stroke treatment in worldwide clinical trials. In January 2005, the U.S. FDA granted a 'fast-track status' for investigation of ancrod use in patients suffering from acute ischemic stroke, a life threatening condition caused by the blockage of blood vessels supplying blood and oxygen to portions of the brain, for which phase III trials are currently being conducted.

Type
Biotech
Groups
Approved, Investigational
Synonyms
  • Ancrod

Pharmacology

Indication

Ancrod is indicated for the treatment of deep vein thrombosis (DVT), central retinal branch vein thrombosis, pripaism, pulmonary hypertension of embolic origin, embolism after insertion of prosthetic cardiac valves, rethrombosis after thrombolytic therapy, rethrombosis after vascular surgery, and prevention of DVT after repair of a fractured neck of a femur.

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

The decreased viscosity is directly attributable to lowered fibrinogen levels and leads to important improvements in blood flow and perfusion of the microcirculation. Ancrod decreases the blood viscosity in affected arteries, leads to less intense pain, improves physical limb mobility, facilitates physical and ergo therapy, and decreases the likelihood of local thrombotic events.

Mechanism of action

Ancrod's anticoagulant effects are through the rapid removal of fibrinogen from the blood within hours following ancrod administration. Ancrod specifically cleaves only the alpha chain of fibrinogen, producing the characteristic fibrinopeptides A, AP and AY, not the B-fibrinopeptide. The resulting fibrin polymers are imperfectly formed and much smaller in size (1 to 2 µm long) than the fibrin polymers produced by the action of thrombin. These ancrod-induced microthrombi are friable, unstable, urea-soluble and have significantly degraded a-chains. They do not cross-link to form thrombi. They are markedly susceptible to digestion by plasmin and are rapidly removed from circulation by either reticuloendothelial phagocytosis or normal fibrinolysis, or both. Blood viscosity is reduced by 30-40%. Ancrod does not activate plagminogen and does not degrade preformed, fully cross-linked thrombin fibrin. Consequently, unlike fibrinolytic agents, ancrod can be used postoperatively. Ancrod does not activate Factor XIII, produce platelet aggregation, or release ADP, ATP, potassium, or serotonin from platelets.

TargetActionsOrganism
UFibrinogen alpha chainNot AvailableHumans
Absorption

100% after i.v. dosing

Volume of distribution

Not Available

Protein binding

95% bound to erythrocytes

Metabolism
Not Available
Route of elimination

Not Available

Half-life

3 to 5 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Currently, a new dosing strategy is being investigated in two international phase III trials as part of the 'Ancrod Stroke Program (ASP).' Each of these studies will enroll 650 patients and assess whether a brief, relatively rapid ancrod infusion with no maintenance dosing will be both effective and safe.

Ancrod is contraindicated in patients with known bleeding disorders, unexplained excessive bleeding in the past, platelet counts <100,000 except for Heparin-induced thrombocytopenia, planned surgery, active GIT ulcerations, malignant disease, renal stones, uncontrolled arterial hypertension, active pulmonary tuberculosis, impaired fibrinolysis, severe liver disease, shock, or impending shock. Ancrod should not be given shortly before delivery or via the intramuscular route.

Ancrod has been listed as pregnancy category X by the FDA. Ancrod should not be used in pregnancy as it may interfere with implantation. It is not teratogenic in animal studies but there were some fetal deaths from placental hemorrhage.

Side effects may include hypersensitivity reactions and pain at the injection site.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Ancrod.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Ancrod.
AcemetacinThe risk or severity of bleeding and hemorrhage can be increased when Acemetacin is combined with Ancrod.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Ancrod.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Ancrod.
Albutrepenonacog alfaThe therapeutic efficacy of Albutrepenonacog alfa can be decreased when used in combination with Ancrod.
AlclofenacThe risk or severity of bleeding and hemorrhage can be increased when Alclofenac is combined with Ancrod.
AldesleukinThe risk or severity of bleeding can be increased when Ancrod is combined with Aldesleukin.
AlemtuzumabThe risk or severity of bleeding can be increased when Ancrod is combined with Alemtuzumab.
AlteplaseThe risk or severity of bleeding can be increased when Ancrod is combined with Alteplase.
Interactions
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Food Interactions
  • Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Products

Products
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ViprinexLiquid70 unit / mLIntravenous; SubcutaneousAbbott1986-12-312007-07-31Canada flag

Categories

ATC Codes
B01AD09 — Ancrod
Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
EL55307L15
CAS number
9046-56-4

References

General References
  1. Hennerici MG, Kay R, Bogousslavsky J, Lenzi GL, Verstraete M, Orgogozo JM: Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial. Lancet. 2006 Nov 25;368(9550):1871-8. [Article]
  2. Kelton JG, Smith JW, Moffatt D, Santos A, Horsewood P: The interaction of ancrod with human platelets. Platelets. 1999;10(1):24-9. [Article]
KEGG Drug
D02938
PubChem Substance
347909946
RxNav
772
Wikipedia
Ancrod

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedNot AvailableInfarction, Brain / Ischemia, Cerebral / Stroke, Acute1
3TerminatedTreatmentInfarction, Brain / Ischemia, Cerebral / Stroke2
1, 2CompletedTreatmentDeafness / Ear Diseases / Hearing Disorders / Hearing loss or impairment / Hearing Loss, Sensorineural1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
LiquidIntravenous; Subcutaneous70 unit / mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Structural molecule activity
Specific Function
Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function ...
Gene Name
FGA
Uniprot ID
P02671
Uniprot Name
Fibrinogen alpha chain
Molecular Weight
94972.455 Da

Drug created on October 21, 2007 22:23 / Updated on February 21, 2021 18:51