Atenativ

Package Leaflet: Information for the User

ATENATIV, 50 IU/ml, powder and solvent for solution for infusion
Human antithrombin III

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Atenativ and what is it used for
• 2. Important information before using Atenativ
• 3. How to use Atenativ
• 4. Possible side effects
• 5. How to store Atenativ
• 6. Contents of the pack and other information

1. What is Atenativ and what is it used for

Atenativ is an anticoagulant (blood thinner) medicine that contains antithrombin isolated from human plasma. Antithrombin is a normal component of human plasma and an important inhibitor of blood clotting.
Atenativ is used to treat hereditary antithrombin deficiency, particularly to prevent the formation and development of blood clots in deep veins and pulmonary embolism in clinical risk situations (e.g., during surgery or childbirth) in adults. Atenativ is also used to treat acquired antithrombin deficiency.

2. Important information before using Atenativ

When not to use Atenativ

• if you are allergic to human antithrombin III or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

You should discuss any concomitant diseases with your doctor.
Before starting treatment with Atenativ, you should discuss it with your doctor.

Viral safety

For medicines derived from human blood or plasma, measures are taken to prevent the transmission of infectious diseases. These measures include careful selection of blood and plasma donors to exclude carriers of infectious diseases, testing each donated blood and plasma pool for the presence of viruses/infections, and using virus inactivation or removal procedures in the blood or plasma processing. Despite these measures, when administering medicines derived from human blood or plasma, it is not possible to completely eliminate the risk of transmitting infectious diseases. This includes unknown or emerging viruses or other types of infections.
Observance of safety measures prevents the transmission of enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B and C viruses, and non-enveloped hepatitis A virus. The safety measures taken may have limited applicability for non-enveloped viruses, such as parvovirus B19. Parvovirus B19 infection can be serious in pregnant women (fetal infection) and individuals with immune disorders or certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).
It is strongly recommended that each time Atenativ is administered, the name and batch number of the product should be recorded in order to maintain information on the batches used.
In the case of regular/repeated administration of antithrombin products derived from human plasma, consideration should be given to vaccination against hepatitis A and B.

Children and adolescents

There are no data on the use of Atenativ in children.

Atenativ and other medicines

You should inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Treatment with Atenativ enhances the anticoagulant effect of heparin and may increase the risk of bleeding. In the case of increased bleeding risk, concomitant administration of heparin should be carefully considered. If the doctor decides that concomitant administration of heparin is necessary, the patient should remain under close laboratory monitoring.

Atenativ with food and drink

No effect has been observed.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before using this medicine.
Only limited data are available on the safety of Atenativ during pregnancy or breastfeeding. Atenativ should be used during pregnancy and breastfeeding only when necessary due to increased risk of thromboembolic disorders in patients with hereditary antithrombin deficiency.

Driving and using machines

No effect on the ability to drive or use machines has been observed. The patient decides whether they are able to drive a vehicle or perform tasks that require greater concentration.

Atenativ contains sodium

This medicine contains 36 mg (Atenativ, 500 IU) or 72 mg (Atenativ, 1000 IU) of sodium (main component of table salt) per vial. This corresponds to 1.8% or 3.6% of the recommended maximum daily intake of sodium for an adult.

3. How to use Atenativ

The need to use and the dose of Atenativ are determined by a doctor. Atenativ is administered by infusion by medical personnel. During treatment, the patient remains under necessary laboratory monitoring.

Overdose of Atenativ

No symptoms of overdose with Atenativ have been reported.

Missed dose of Atenativ

The doctor is responsible for supervising the administration of the medicine and monitoring laboratory results and maintaining them within the normal range.

Stopping treatment with Atenativ

The decision to stop treatment with Atenativ is made by a doctor based on laboratory results and risk factor assessment. If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Atenativ can cause side effects, although not everybody gets them.
The use of medicines derived from plasma may – although rarely – cause allergic reactions (e.g., eye, face, or tongue swelling, burning sensation and prickling at the infusion site, skin inflammation, fever, chills, urticaria, nausea, vomiting, shortness of breath, headache, dizziness, shortness of breath, wheezing, changes in blood pressure, rapid heartbeat, drowsiness, restlessness, back pain, sweating, flushing, tingling, or even anaphylactic shock).
Additionally, anxiety, bleeding, abdominal pain, diarrhea (unknown frequency).
In case of suspected allergy or hypersensitivity reactions with the above-mentioned side effects, administration of the medicine should be stopped immediately. The doctor should follow the applicable guidelines for the treatment of anaphylactic shock.

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, please inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Aleje Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Atenativ

Keep the medicine out of the sight and reach of children.
Store in a refrigerator (2°C – 8°C). Vials should be stored in the outer packaging to protect from light.
Do not use this medicine after the expiry date stated on the label and carton after: EXP.
The expiry date refers to the last day of the month.
Within the shelf-life period, the product can be stored at room temperature (25°C) for one month without being returned to the refrigerator. If the product is not used within this time, it should be discarded.
After reconstitution, use the product as soon as possible. If the medicine is not used immediately after reconstitution or within 12 hours if stored at 15-25°C, the responsibility for the storage time and conditions before administration lies with the user. If the reconstitution process is carried out under controlled aseptic conditions, the product can be stored at 2-8°C for a maximum of 24 hours. Unused solution should be discarded.
Do not use Atenativ if the solution is cloudy or contains sediment.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Atenativ contains

• The active substance is human antithrombin III (50 IU/ml).
• The other ingredients are: Powder: sodium chloride, human albumin, N-acetyltryptophan, and caprylic acid. Solvent: water for injections.

What Atenativ looks like and contents of the pack

Powder and solvent for solution for infusion.
Atenativ is a white or yellowish powder or a hard, brittle mass.
The solvent is water for injections, which is a clear and colorless liquid.
Powder in a vial (type II glass) with a stopper (bromobutyl rubber) and solvent in a vial (type I glass) with a stopper (bromobutyl rubber)
Atenativ, 500 IU: 1 vial of powder (500 IU) and 1 vial of water for injections (10 ml)
Atenativ, 1000 IU: 1 vial of powder (1000 IU) and 1 vial of water for injections (20 ml)

Marketing authorization holder and manufacturer

Octapharma (IP) SPRL
Allée de la Recherche 65
1070 Anderlecht
Belgium

Manufacturer

Octapharma AB
Lars Forssells gata 23
SE-112 75 Stockholm
Sweden

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Austria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Spain, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden: Atenativ

Date of last revision of the package leaflet: 23.03.2022

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Information intended for healthcare professionals only:
Antithrombin should be administered under the supervision of a doctor specializing in coagulation disorders.
Dosage
In hereditary deficiency, the dose of the medicine should be determined individually for each patient, taking into account family history of thromboembolic events, current clinical risk factors, and laboratory results.
The dosage and duration of substitution therapy in acquired deficiency depend on the antithrombin level in plasma, signs of increased consumption, underlying disease, and severity of the clinical condition. The dose and frequency of administration should always be adjusted according to clinical efficacy and laboratory results in individual cases.
The number of antithrombin units administered is expressed in international units (IU), which are related to the current WHO standard for antithrombin. Antithrombin activity in plasma is expressed as a percentage (relative to normal human plasma) or in international units (related to the international standard for antithrombin in plasma).
One international unit (IU) of antithrombin activity is equivalent to the amount of antithrombin in one ml of normal human plasma. The calculation of the required dose of antithrombin is based on the observation that 1 international unit (IU) of antithrombin per kilogram of body weight increases antithrombin activity in plasma by approximately 1% (correction factor).
The initial dose is determined according to the following formula:

Required units = body weight (kg) x (target concentration – actual antithrombin activity [%])

The initial target antithrombin activity depends on the clinical situation. When substitution of antithrombin is indicated, the dose should be sufficient to achieve the target antithrombin activity and maintain effective levels. The dose should be determined and monitored based on laboratory measurements of antithrombin activity, which should be performed at least twice a day until the patient's condition stabilizes, and then once a day, preferably immediately before the next infusion. Dose adjustment should take into account both signs of increased antithrombin consumption determined by laboratory results and clinical course.
During treatment, antithrombin activity should be maintained above 80%, unless clinical conditions indicate the use of a different effective concentration.
Typically, the initial dose in hereditary deficiency is 30-50 IU/kg body weight.
Subsequent dosing and frequency, as well as duration of treatment, should be adjusted according to biological data and clinical situation.
Method of administration
The product should be administered intravenously.
The infusion rate for adult patients should not exceed 300 IU/min.
The lyophilized powder is reconstituted in sterile water for injections.
After reconstitution, Atenativ can be mixed with isotonic sodium chloride solution (9 mg/ml) and isotonic glucose solution (50 mg/ml) in glass infusion bottles and plastic containers.
The medicinal product Atenativ should not be used after the expiry date stated on the packaging.
In a typical situation, the solution is clear or slightly opalescent. Cloudy solutions or solutions with sediment should not be used.
The reconstitution time is up to 5 minutes. After preparation of the solution, the product should be used as soon as possible and no later than within 12 hours if stored at 15-25°C. Unused solution should be discarded.
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.