Ancrod

Ancrod

Clinical data
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Ancrod (current brand name: Viprinex) is a

As of 2017 ancrod was not marketed for any medical use.[2]

Pregnancy

Category X : Ancrod was not found to be

• Known
  bleeding disorders
  of any origin or any unexplained excessive bleedings in the past.
• Platelet counts
  of less than 100,000 (even if asymptomatic), exemption : HIT (Heparin- induced thrombocytopenia).
• Planned surgery or short before delivery.
• Active
  ulcerations
  of the GIT.
• Any kind of
  malignant
  disease.
• Renal stones
  (increased likelihood of significant urological bleeding).
• Severe and uncontrolled
  arterial hypertension
  .
• Active
  pulmonary tuberculosis
  .
• Impaired fibrinolysis.
• Severe liver disease.
• Manifest or impending shock.
• I.M.-Injection : Ancrod should not be injected i.m., because of rapid induction of neutralizing
  antibodies and thus drug resistance
  .

• Hypersensitivity reactions : Local or generalized
  antibodies
  to ancrod with partial or total loss of ancrod activity (drug resistance).
• Sometimes pain at injection site (normally mild). This side effect may be, if necessary, treated with local or oral
  antihistaminic drugs (e.g., clemastine, or diphenhydramine). Bleeding at injection site, thrombophlebitis
  at local veins, and (paradoxical) arterial thrombotic events.
• Occasionally deposition of cleaved fibrinogen derivates in the spleen resulting in splenomegaly; rupture is possible, if the spleen is palpated too strongly (life-threatening bleeding and need of splenectomy may result).
• Specific side effects are local and systemic bleeding events. Local bleeding events may be treated with local pressure or
  surgical dressings
  , if necessary. Compared with other anticoagulants the risk of systemic bleeding is relatively low. If systemic bleeding is severe enough to warrant fast reversal of ancrod action, fibrinogen should be substituted (please refer to section 'special antidotes').
• Occasionally, increased headache has been found in patients with known migraine.
• Also, chills and fever may occur infrequently.

Thrombocytopenia as side effect has never been noticed with ancrod in contrast to heparin.

It was not found to be of much use in the clinical trials. In vitro experiments show that it may actually clot blood.^[4]

Pharmacology

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Ancrod has a triple mode of action. It was found that ancrod's actions are

The

Due to its special mode of action (see below) and its price, Arwin has never been used as 'normal' anticoagulant such as heparin, but only for the symptomatic treatment of moderate to severe forms of peripheral arterial circulatory disorders such as those resulting from years of heavy smoking and/or arteriosclerosis.

The substance is intended for

Ancrod decreases the blood viscosity in affected arteries, leads to less intense pain, improves physical limb mobility, and facilitates physical and ergo therapy. Finally, ancrod decreases the likelihood of local thrombotic events. These mechanisms also account for ancrod's activity in other diseases.

Effects on other

Ancrod was originally isolated from the venom of the Malayan pit viper (Calloselasma rhodostoma, formerly Agkistrodon rhodostoma) and is a serine protease.^[5] It is one of the Venombin A enzymes. Two genes encoding for such enzymes have been found in the viper genome.^[6][7]

The form used in clinical trials was not made recombinantly, but was purified from harvested venom.^[8][9]

History

Under the brand name Arwin, ancrod was marketed for several decades in

In 2001 Knoll was acquired by Abbott Laboratories, and in 2002 Abbott licensed the rights to ancrod to Empire Pharmaceuticals, a startup that included a Knoll employee who had worked on ancrod.^{[10][11] : 5} In 2004 Empire was acquired by Neurobiological Technologies.^[12] NTI also acquired a lot of unpurified venom in the acquisition, and had that purified for use in its clinical trials.^[8][9]

The failure of ancrod in the 6-hour window for ischemic stroke trial in 2008 led to cuts in staff, an effort to sell off the company's assets, and finally to the dissolution of NTI in August 2009.^[13][14]

Society and culture

Viprinex is not currently approved or available.

Research

For the treatment of established

For the treatment of moderate and severe chronic circulatory disorders of peripheral arteries (e.g.,

Ancrod has been shown to be useful for maintaining anticoagulation in the presence of Heparin-induced thrombocytopenia (HIT) and thrombosis.

A small study compared to ancrod to

References

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