What ATryn contains
- The active substance is antithrombin alfa
- The other ingredients are: glycine, sodium chloride, sodium citrate
What ATryn looks like and contents of the pack
Powder for solution for infusion.
White to off-white powder.
Package size: 1, 10 or 25 vials per carton. Each vial of ATryn contains a nominal value of 1750 IU of recombinant antithrombin alfa. The powder will be dissolved before it can be infused.
Marketing Authorisation Holder and Manufacturer
Marketing authorisation Holder
GTC Biotherapeutics UK Limited, 10 Norwich Street, London EC4A 1BD, United Kingdom.
Manufacturer authorisation holder responsible for batch release
LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.
This leaflet was last approved in
This medicinal product has been authorized under ?Exceptional Circumstances?. This means that due to the rarity of the disease, it has not been possible to obtain complete information on this medicinal product.
The European Medicines Agency (EMEA) will review any new information which may become available every year and this leaflet will be updated as necessary.
Detailed information is available on the European Medicines Agency (EMEA) web site: http://www.emea.europa.eu
--------------------------------------------------------------------------------------------------------------------- The following information is intended for medical or healthcare professionals only:
Each vial of ATryn contains a lyophilised powder of 1750 IU antithrombin alfa and is intended for single use only. Vials should be brought to room temperature prior to reconstitution and kept no longer than 3 hours. The powder should be reconstituted with 10 ml of Sterile Water for Injection (WFI) injected along the side wall of the vial and gently swirled (not shaken) to prevent foaming. The reconstituted product should be inspected visually for particulate matter and discolouration prior to administration. The solution should be clear or slightly opalescent. Do not use solutions that are cloudy or have deposits. Upon complete dissolution, the reconstituted product may be drawn up into a sterile disposable syringe. The reconstituted product should be administered by intravenous infusion using a sterile disposable syringe or an infusion bag with an in-line filter e.g. a methylcellulose filter with a 0.2 micron pore size. Normal sodium chloride solution 9 mg/ml (0.9%) may be added to dilute to a concentration convenient for administration. The contents of infusion syringes on diluted solution prepared in infusion bags should be administered within 8 hours of preparation. Compatibility with PVC infusion lines with in-line filters has been established.
Any unused product or waste material should be disposed of in accordance with local requirements.
The therapeutic goal of treatment with ATryn is to increase to, and maintain antithrombin activity between 80 ? 120% (0.8 ? 1.2 IU/ml) for the duration of treatment.
Initial treatment starts with a loading dose of ATryn targeting an antithrombin activity level of 100%. This initial loading dose is based on body weight and on the pretreatment antithrombin activity level.
The required loading dose is determined using the following formula:
Loading Dose (IU) = [(100 ? patient?s pre-treatment AT activity level in %) /2.28] x Body Weight in kg
The usual loading dose in surgical patients (baseline AT activity 50%, bodyweight 75 kg) with congenital antithrombin deficiency in clinical risk situations is 20-25 IU/kg bodyweight. The loading dose should be given as a 15 minute infusion immediately followed by initiation of the maintenance infusion.
The required maintenance dose for surgical patients is given as a continuous infusion and is determined using the following formula:
Maintenance Dose (IU/hour) = [(100 ? patient?s pre-treatment AT activity level in %) /10.22] x Body Weight in kg
The usual maintenance dose in surgical patients with congenital antithrombin deficiency in clinical risk situations is 4-5 IU/kg/h. During consumptive states (e.g. major surgery, concomitant use of heparin) the actual dose may be higher. See therapeutic monitoring and dose adjustment recommendations below.
Therapeutic Monitoring and Dose Adjustment
The dosage should be adjusted on the basis of laboratory measurements of antithrombin activity. Response to ATryn may vary in individual patients, achieving different levels of in vivo recovery and different half-lives. Frequent antithrombin activity assessments and dosing adjustments may be necessary when starting treatment and just after surgery.After the start of the maintenance dose infusion, blood for AT activity levels should be drawn at 45 minutes after the start of the loading dose infusion. In case the AT activity level is between 80% and 120% (0.8- 1.2 IU/ml), no dose adjustment is needed. In case the AT activity level is less than 80%, increase the maintenance infusion rate by 50%. In case the AT activity level is greater than 120% decrease the infusion rate by 30%. Check AT activity level 30 minutes after any change in infusion rate, or four hours after a value within the target range. Subsequently, antithrombin activity should be checked 1-2 times a day and dose adjustments made accordingly. The antithrombin activity level should be maintained above 80% for the duration of the treatment, unless clinical particulars would indicate a different effective level.
It is possible that the surgical procedure will influence AT activity levels. Therefore, an additional check of the AT activity level should be done after the surgery. In case the activity level is below 80% a 15 minutes bolus infusion of AT can be given to quickly restore the AT activity level. The dose can be calculated utilizing the post-surgical AT activity in the loading dose formula above.
There is no experience in children.