ATryn
antithrombin alfa
antithrombin alfa (rDNA)
This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor.
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.
What ATryn is and what it is used for
What you need to know before you use ATryn
How to use ATryn
Possible side effects
How to store ATryn
Medicinal product no longer authorised
Contents of the pack and other information
ATryn contains antithrombin alfa which is similar to the naturally occurring human antithrombin. In the body, antithrombin blocks thrombin, a substance that plays a central role in the process of blood clotting.
If you have an inborn deficiency of antithrombin, your blood level of antithrombin is lower than normal. This may result in a higher tendency to form clots in your blood vessels. This may be in the vessels of your legs (deep vein thrombosis) or in other vessels of your body (thromboembolism). Around major surgical procedures this tendency to clot is even more increased. Therefore, it is important that your antithrombin blood level be maintained at sufficient levels in these situations.
This medicine is used in patients who have ‘congenital antithrombin deficiency’ (inherited low levels of the protein antithrombin). It is used when the patients are having surgery, to prevent problems due to the formation of blood clots in the vessels. It is normally given in association with heparin or low molecular weight heparin (another medicine that helps to prevent blood clots).
if you are allergic to antithrombin alfa or any of the other ingredients of this medicine (listed in section
6).
if you are allergic to goat products as antithrombin alfa is produced in the milk of transgenic goats by recombinant DNA technology (rDNA).
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 whether you developed an allergic reaction, blood may be collected and tested before and some time after you have been treated with ATryn.
No information on the use of ATryn in patients less than 18 years is available. This medicine should therefore not be used if you are less than18 years.
Tell your doctor if you are taking, have recently taken or might take any other medicines.
When ATryn is used together with heparin (an anti-clotting medicine), or some other anti-clotting medicines, this may increase the risk of bleeding. Therefore your doctor will carefully monitor the use of this medicine when administered together with these anti-clotting medicines.
ATryn is not indicated for use in pregnant women. It is unknown whether it is present in breast milk. Therefore it is not recommended to breastfeed whilst being treated with this medicine.
This medicinal product contains 1.65 mmol (or 37.9 mg) sodium per vial. To be taken into consideration by patients on a controlled sodium diet.
Medicinal product no longer authorised
Your treatment will be initiated under the supervision of a physician experienced in the care of patients with an inborn deficiency of antithrombin.
Your health care provider will prepare a solution of antithrombin alfa to be administered to you through your
vein. To protect you from developing blood clots the medicine will continue to be administered to you until your doctor determines it safe to stop treatment.
The doctor will treat you, as appropriate, if you have any particular side effects.
Please discuss possibility of stopping the treatment with your doctor.
If you have any further questions on the use of this medicine, ask your doctor.
Like all medicines, this medicine can cause side effects, although not everybody gets them. 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.
In studies with ATryn the following side effects were reported: Common side effects (may affect up to 1 in 10 people) are:
itching at the site of infusion
dizziness
headache
bleeding (at site of infusion or after surgery)
nausea
Uncommon side effects (may affect up to 1 in 100 people) are:
feeling hot
infusion site reactions such as pain, bruising and redness
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Keep out of the sight and reach of children. Unopenedvials:
Store in a refrigerator (2°C – 8°C).
Do not use this medicine after the expiry date stated which is stated on the carton and vial label after EXP. The expiry date refers to the last date of that month.
Reconstituted/dilutedsolutions:
After reconstitution, from a microbiological pointy of view, this medicinal product should be used
immediately. However, chemical and physical stability has been demonstrated for 3 hours after reconstitution and 8 hours after dilution at a temperature not above 25°C.
Medicinal product no longer authorised
The active substance is antithrombin alfa*: 1750 IU. After reconstitution, 1 ml of solution contains 175 IU antithrombin alfa.
The specific activity of ATryn is approximately 7 IU/mg protein.
* recombinant human antithrombin produced in the milk of transgenic goats by recombinant DNA technology (rDNA).
The other ingredients are: glycine, sodium chloride, sodium citrate
ATryn is supplied as a powder for solution for infusion (1750 IU powder in vial). The powder is white to off-white.
Pack sizes of 1, 10 or 25 vials.
Laboratoire Français du Fractionnement et des Biotechnologies, 3 Avenue des Tropiques, ZA de
Courtaboeuf, 91940 Les Ulis, France
LFB-BIOTECHNOLOGIES, 3 Avenue des Tropiques, ZA de Courtaboeuf, 91940 Les Ulis, France
MedImmunePharmaBVLagelandseweg786545CGNijmegen,TheNetherlands.
This medicine has been authorised under ‘exceptional circumstances’. This means that because of the rarity of this disease it has been impossible to get complete information on this medicine.
The European Medicines Agency will review any new information on this medicine every year and this
leaflet will be updated as necessary.
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The following information is intended for healthcare professionals only: This medicine is intended for single use only.
Reconstitution/dilution
Vials should be brought at temperature not above 25°C prior to reconstitution. The powder should be reconstituted with 10 ml of water for injections (WFI) injected along the side wall of the vial and gently swirled (not shaken) to prevent foaming.
The reconstituted solution should be inspected visually for particulate matter and/or discolouration prior to administration. The solution should be slightly yellow, clear to slightly opalescent. Do not use solutions that are cloudy or have deposits.
Medicinal product no longer authorised
The vials should be used immediately and no longer than 3 hours after reconstitution.
Normal sodium chloride solution 9 mg/ml (0.9%) may be added to dilute to a concentration convenient for administration.
Administration
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 a 0.22 micron pore size in-line filter. The contents of the syringes should be administered immediately and no longer than 3 hours after reconstitution. If diluted, the solution prepared in infusion bags should be administered immediately and no longer than 8 hours after dilution. Compatibility with PVC infusion lines with in-line filters has been established.
Disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
The therapeutic goal of treatment with antithrombin alfa 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 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. Treatment should be continued until the risk for venous thromboembolisms is reduced and/or when effective follow-on anticoagulation has been established.
Therapeutic Monitoring and Dose Adjustment
The dose should be adjusted on the basis of laboratory measurements of antithrombin activity. Response 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
Medicinal product no longer authorised
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.
Paediatric population
The safety and efficacy of ATryn in children and adolescents (<18 years) have not been established. No data are available. Paediatric antithrombin levels may be different from adult levels, particularly in neonates.
Method of administration
For intravenous use.
The loading dose should be given as a 15 minute infusion immediately followed by initiation of the maintenance infusion.