ATryn 1750 IU powder for solution for infusion

ATryn is an anti-clotting agent and contains antithrombin alfa which is similar to human antithrombin. Antithrombin alfa is produced by recombinant DNA technology from the milk of goats. If you have congenital antithrombin deficiency, your blood level of antithrombin is lower than normal, which may result in a reduced anti-clotting capacity of your blood. If your anti-clotting capacity is reduced, there is an increased risk of the formation of clots in the vessels of your legs (deep vein thrombosis) or in other vessels of your body (thromboembolism) during major surgery. Therefore, it is important that your antithrombin blood level be maintained at sufficient levels in these situations.

Do not use ATryn
If you are allergic (hypersensitive) to antithrombin alfa or any of the other ingredients of ATryn.

Take special care with ATryn

If you are allergic to goat products, please tell your treating physician since you should not use ATryn. As with any intravenous protein product, allergic reactions are possible. If you experience hives, itchy welts or wheals all over the skin, tightness of the chest, wheezing (difficulty breathing), you should immediately contact your physician since these might be symptoms of a severe allergic reaction. To test for the occurrence of an allergic reaction, blood will be collected and tested before and some time after you have been treated with ATryn.

Using other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
When ATryn is used together with heparin (an anti-clotting drug), or some other anti-clotting drugs, this may increase the risk of bleeding. Therefore your doctor will carefully monitor the use of ATryn when administered together with these anti-clotting drugs.

Using ATryn with food and drink

No special precautions should be taken while eating or drinking.

Pregnancy

ATryn is not indicated for use in pregnant patients.

Breast-feeding

It is unknown whether ATryn is present in breast milk. Therefore it is not recommended to breastfeed whilst being treated with ATryn.

Driving and using machines
Not relevant.

Important information about some of the ingredients of ATryn

Not relevant.

Your health care provider will prepare a solution of ATryn to be administered through an infusion directly into a blood vessel. Blood levels of antithrombin will be regularly checked in the blood and a change of dose may be necessary.

If you use more ATryn than you should

The doctor will treat you, as appropriate, if you have any particular ill effects.

If you stop using ATryn

Please discuss possibility of stopping the treatment with your doctor.
If you have any further questions on the use of this product, ask your doctor.

Like all medicines, ATryn may cause side effects, although not everybody gets them. Some side effects such as bleeding, bruises, redness, or pain at the site of injection, nausea, headache, feeling hot, dizziness, bruising and increased bleeding may occur during treatment with ATryn.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

Keep out of the reach and sight of children.

Unopened vials:
Store in a refrigerator (2°C ? 8°C).
Do not use ATryn after the expiry date stated on the labelling after the letters EXP.

Diluted solutions:
The product should be used immediately.

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.