Generic Name: Antithrombin [Recombinant]
Date of Approval: February 6, 2009
Company: GTC Biotherapeutics
Treatment for: Prevention of Peri-Operative and Peri-Partum Thromboembolic Events in Hereditary Antithrombin Deficient Patients
FDA Approves ATryn
The U.S. Food and Drug Administration (FDA) has approved ATryn (Antithrombin [Recombinant]) for the prevention of peri-operative and peri-partum thromboembolic events in hereditary antithrombin deficient patients. It is not indicated for treatment of thromboembolic events in hereditary antithrombin deficient patients.
ATryn is the first ever transgenically produced therapeutic protein and the first recombinant antithrombin approved in the U.S.
People with hereditary antithrombin deficiency are at increased risk for venous thromboembolic events, including pulmonary embolism and deep vein thrombosis, which can be life-threatening, particularly in high risk situations. Antithrombin is a natural anticoagulant that plays an important role in controlling the formation of blood clots. Purified recombinant antithrombin has the same amino acid sequence as antithrombin derived from human plasma.
The safety and efficacy of ATryn was established in clinical studies conducted in hereditary antithrombin deficient patients with a history of thromboembolic events in the U.S., Europe and Canada. During these studies, ATryn was shown to prevent the formation of clinically overt thromboembolic events. Post-marketing studies will be performed to assess safety and immunogenicity after repeat dosing.
ATryn is the first recombinant antithrombin product approved in the world and the first antithrombin product that has been approved through the centralized procedure in the European Union. It is now also the first recombinant antithrombin product approved by the FDA.
Important Safety Information
ATryn is contraindicated in patients with known hypersensitivity to goat and goat milk proteins. Allergic-type hypersensitivity reactions, including anaphylaxis are possible. If these reactions occur during administration, treatment must be discontinued immediately and emergency treatment should be administered.
The anticoagulant effect of drugs that use antithrombin to exert their anticoagulation may be altered when ATryn is added or withdrawn. To avoid excessive or insufficient anticoagulation, coagulation tests suitable for the anticoagulant used (e.g., aPTT and anti-Factor Xa activity) are to be performed regularly, at close intervals, and in particular in the first hours following the start or withdrawal of ATryn. Additionally, patients must be monitored for the occurrence of bleeding or thrombosis in such situations.
The serious adverse reaction that has been reported in clinical studies is hemorrhage (intra-abdominal, hemarthrosis and post procedural). The most common adverse events reported in clinical trials at a frequency of = 5% are hemorrhage and infusion site reaction.
Highlights of Prescribing Information
These highlights do not include all the information needed to use ATryn safely and effectively. See full prescribing information for ATryn.
Indications and Usage
ATryn is a recombinant antithrombin indicated for the prevention of peri-operative and peri-partum thromboembolic events in hereditary antithrombin deficient patients. It is not indicated for treatment of thromboembolic events in hereditary antithrombin deficient patients.
Dosage and Administration
- For intravenous use only after reconstitution
- The dosage of ATryn is individualized for each patient. Treatment goal is to restore and maintain functional antithrombin (AT) activity levels between 80% - 120% (0.8 - 1.2 IU/mL) of normal.
- Administer loading dose as a 15-minute intravenous infusion immediately followed by continuous infusion of the maintenance dose.
- AT activity monitoring is required for proper treatment. Check AT activity once or twice per day and adjust dose accordingly.
- Continue administration of ATryn until adequate follow-on anticoagulation has been established.
- Store at 2-8°C (36-46°F). Discard any unused portion.
Dosage Forms and Strengths
- ATryn is a sterile lyophilized powder for reconstitution. Each single dose vial of ATryn contains the potency as stated on the label, which is approximately 1750 IU.
- Known hypersensitivity to goat and goat milk proteins.
Warnings and Precautions
- Anaphylaxis and severe hypersensitivity reactions are possible. Should symptoms occur, treatment with the product should be discontinued, and emergency treatment should be administered.
- The anticoagulant effect of drugs that use antithrombin to exert their anticoagulation may be altered when ATryn is added or withdrawn. To avoid excessive or insufficient anticoagulation, regularly perform coagulation tests suitable for the anticoagulant used, at close intervals, especially in the first hours following the start or withdrawal of ATryn and monitor patients for bleeding or thrombosis.
ATryn Side Effects
Most common adverse reactions reported in clinical trials at a frequency of = 5% were hemorrhage and infusion site reaction.
To report suspected adverse reactions, contact Ovation Pharmaceuticals at 1-800-455-1141 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
- ATryn enhances anticoagulant effect of heparin and low molecular weight heparin.
- The half-life of ATryn may be altered by concomitant treatment with anticoagulants that use antithrombin to exert their anticoagulant effect.
Use in Specific Populations
- Pregnancy Category C. Studies in pregnant women have not shown that ATryn increases the risk of fetal abnormalities if administered during the third trimester of pregnancy. No data is available for use of ATryn in earlier stages of pregnancy.
- Labor and Delivery: ATryn is used in the treatment of peri-partum women with hereditary antithrombin deficiency.
- Nursing Mothers: ATryn administered by infusion will be present in breast milk at estimated concentrations 1/50 to 1/100 that of concentration in blood. Use only if clearly needed.
See also: Side effects (in more detail)
Patient Counseling Information for ATryn
Inform patients that allergic-type hypersensitivity reactions are possible and instruct them to inform their physicians about any past or present known hypersensitivity to goats or goat milk proteins prior to treatment with ATryn. Inform patients of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis and to notify their health care provider immediately if these events develop.
Inform patients about the risk of bleeding when ATryn is administered with other anticoagulants and instruct them to notify their physicians of any bleeding events while on treatment with ATryn.