General Information

ATryn is a recombinant antithrombin produced by recombinant DNA.

ATryn is indicated for the pevention of peri-operative and peri-partum thromboembolic events in hereditary antithrombin-deficient patients.

ATryn is supplied as a powder for reconstitution designed for intravenous administration. The dosage of ATryn is to be individualized based on the patient’s pretreatment functional antithrombin activity level (expressed in percent of normal) and body weight (expressed in kilograms) and using therapeutic drug monitoring. The goal of treatment is to restore and maintain functional AT activity levels between 80% and 120% of normal (0.8 to 1.2 IU/mL). Treatment should be initiated prior to delivery or approximately 24 hours prior to surgery. Administer loading dose as a 15-minute intravenous infusion, immediately followed by a continuous infusion of the maintenance dose.

Mechanism of Action

ATryn is a recombinant antithrombin produced by recombinant DNA technology using genetically engineered goats into which the DNA coding sequence for human antithrombin (AT) has been introduced, along with a mammary gland-specific DNA sequence, which directs the expression of AT into the milk. The amino acid sequence of recombinant AT is identical to that of human plasma-derived AT, which plays a central role in the regulation of hemostasis. AT is the principal inhibitor of thrombin and Factor Xa5, the serine proteases that play pivotal roles in blood coagulation. AT neutralizes the activity of thrombin and Factor Xa by forming a complex that is rapidly removed from circulation.

Side Effects

Adverse events associated with the use of ATryn may include, but are not limited to, the following:

• Intra-abdominal hemorrhage
• Application-site pruritus
• Feeling hot
• Noncardiac chest pain
• Hepatic enzyme abnormality
• Hemarthrosis/hematuria
• Hematoma

Clinical Results

FDA approval of ATryn was based on the results of two clinical studies. These single-arm, open-label studies were conducted in 31 hereditary AT-deficient patients and 35 human plasma-derived AT-treated hereditary AT-deficient patients. The endpoint was noninferiority in the reduction in the incidence of the occurrence of venous thromboembolic events between the two treatment arms. ATryn was administered as a continuous infusion for at least three days, starting one day prior to the surgery or delivery. Plasma AT was administered for at least two days as single bolus infusions. The efficacy was assessed during treatment with AT and up to seven days after stopping AT treatment. In the human plasma-derived AT group, there were zero incidences of thromboembolic events and in the ATryn-treated arm, there was one confirmed diagnosis of an acute deep vein thrombosis.