ATENATIV 1000 IU POWDER AND SOLVENT FOR SOLUTION FOR INFUSION

Introduction

ATENATIV 500 UI, powder and solvent for solution for infusion.

Antithrombin III derived from human plasma

ATENATIV 1000 UI, powder and solvent for solution for infusion.

Antithrombin III derived from human plasma

Read the entire leaflet carefully before starting to use this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience side effects, ask your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the leaflet:

1. What Atenativ is and what it is used for
2. What you need to know before taking Atenativ
3. How to take Atenativ
4. Possible side effects
5. Storage of Atenativ
6. Package contents and additional information

1. What Atenativ is and what it is used for

Atenativ is a medicine called an antithrombotic (anticoagulant) that contains antithrombin isolated from human plasma. Antithrombin is a normal constituent of human plasma and an important inhibitor of blood coagulation.

Atenativ is used to treat patients with congenital deficiency (present at birth) of antithrombin, in particular, to prevent the formation and development of blood clots in deep veins (deep vein thrombosis) and embolisms (thromboembolism) in situations of clinical risk (e.g., during surgery or childbirth) and in association with heparin if necessary.

2. What you need to know before taking Atenativ

Do not use Atenativ:

If you are allergic to antithrombin III or any of the components of this medicine (listed in section 6).

Warnings and precautions:

Tell your doctor if you have any other illness.

Ask your doctor, pharmacist, or nurse before starting to use Atenativ.

Viral safety

When medicines are manufactured from blood or human plasma, certain measures are implemented to prevent the transmission of infections to patients. This includes careful selection of blood and plasma donors to ensure that those at risk of carrying infections are excluded, analysis of each donation and plasma pools for signs of viruses/infections, and inclusion of steps in the processing of blood or plasma that can inactivate or eliminate viruses. Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of transmitting infections cannot be entirely excluded. This also applies to unknown or emerging viruses or other types of infections.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and against the non-enveloped hepatitis A virus. The measures taken may have limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection can be severe for pregnant women (fetal infection) and for individuals with a weakened immune system or with anemia (e.g., sickle cell disease or hemolytic anemia).

It is strongly recommended that each time you receive a dose of Atenativ, you record the name and batch number of the medicine to keep a record of the batch used.

• You may be advised by your doctor to consider getting vaccinated against hepatitis A and B if you regularly/repeatedly receive antithrombin products derived from human plasma.

Other medicines and Atenativ:

Tell your doctor or pharmacist if you are using, have recently used, or may need to use another medicine, including those obtained without a prescription.

The anticoagulant effect of heparin increases with Atenativ treatment, and the risk of bleeding may increase. If you have a higher risk of bleeding, concomitant administration of heparin should be carefully evaluated. If your doctor decides that you should receive heparin, you will be closely monitored through laboratory tests.

Atenativ with food and drinks:

No effects have been observed.

Pregnancy, breastfeeding, and fertility:

Ask your doctor or pharmacist before using this medicine if you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant.

There is only limited information on the safety of using Atenativ during pregnancy or breastfeeding. Atenativ should only be used during pregnancy and breastfeeding if it is considered necessary due to the high risk of thromboembolism in patients with congenital antithrombin deficiency.

Driving and using machines:

No effects have been observed on the ability to drive vehicles or operate machinery. You are responsible for deciding whether you are fit to drive a motor vehicle or perform other tasks that require increased concentration.

Important information about some of the components of Atenativ

This medicine contains 36 mg (Atenativ 500) or 72 mg (Atenativ 1000) of sodium (main component of table/cooking salt) in each vial. This is equivalent to 1.8% or 3.6% of the maximum recommended daily intake of sodium for an adult.

3. How to take Atenativ

Treatment should be started under the supervision of a doctor specializing in the treatment of patients with antithrombin deficiency.

Your doctor will decide if you need Atenativ and at what dose. The dose will be individualized for each patient, taking into account the family history related to thromboembolic episodes, real clinical risk factors, and laboratory tests. You will be monitored with necessary laboratory tests during treatment.

Atenativ is administered as an infusion by healthcare personnel.

If you use more Atenativ than you should:

No symptoms of overdose have been reported in relation to Atenativ.

If you forget to use Atenativ:

Your doctor is responsible for supervising the optimal administration and keeping your laboratory values within the specified ranges.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The use of plasma derivatives can cause allergic reactions or hypersensitivity (e.g., swelling of the eyes, face, burning, and itching at the infusion site, fever, chills, urticaria (hives), nausea, vomiting, dyspnea, headache, dizziness, vertigo, difficulty breathing, wheezing, changes in blood pressure, palpitations, lethargy, restlessness, back pain, sweating, flushing, tingling, or even shock).

In case of suspected allergy or hypersensitivity reaction with the above symptoms, administration should be stopped immediately. Your doctor will follow the applicable guidelines for the treatment of shock.

Reporting side effects

If you experience any side effects, ask your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the Spanish Medicines and Healthcare Products Agency: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

For information on viral safety, see section 2.

5. Storage of Atenativ

Keep this medicine out of the sight and reach of children.

Store in a refrigerator (between 2°C and 8°C). Keep the vials in the outer packaging to protect them from light.

Do not freeze.

Do not use this medicine after the expiration date stated on the packaging. The expiration date is the last day of the month indicated.

Do not use Atenativ if you notice that the solution is cloudy or contains any residue.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package contents and additional information

Composition of Atenativ:

The active substance is antithrombin III derived from human plasma (50 UI/ml).

The other components are:

• Powder: sodium chloride, human albumin, acetryptophan, capric acid.
• Solvent: water for injectable preparations.

Appearance of the product and package contents

Atenativ is a powder and solvent for solution for infusion. The packaging contains a lyophilized powder in a vial (type II glass) and a solvent (water for injectable preparations) in a vial (type I glass) used for reconstitution of the powder. Normally, the solution obtained is clear or slightly opalescent. The reconstituted solution contains 50 UI of human antithrombin III/ml of infusion solution.

Atenativ is available in two sizes: 500 UI or 1000 UI.

Marketing authorization holder

OCTAPHARMA S.A.

Avda. Castilla, 2. (P.E. San Fernando) Ed. Dublín, 2ª Planta

28830 San Fernando de Henares Madrid

Manufacturer

OCTAPHARMA AB.

Lars Forssells gata 23

SE-112 75 Stockholm

Sweden

Date of the last revision of this leaflet: February 2020

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS)http://www.aemps.gob.es/

----------------------------------------------------------------------------------------------------------

This information is intended only for healthcare professionals:

INSTRUCTIONS FOR HEALTHCARE PERSONNEL:

Dosage:

In congenital deficiency, the dose should be individualized for each patient, taking into account the family history related to thromboembolic episodes, real clinical risk factors, and laboratory tests.

The number of antithrombin units administered is expressed in International Units (UI), which are related to the current WHO standard for antithrombin. Antithrombin activity in plasma is expressed as a percentage (in relation to normal human plasma) or in International Units (in relation to the International Standard for antithrombin in plasma).

One International Unit of antithrombin III is equivalent to the amount of antithrombin III present in 1 ml of normal human plasma. This concentration corresponds to 100%. The administration of 1 UI of Atenativ 1000 UI per kilogram of body weight increases the antithrombin III activity by approximately 1%.

The initial dose is determined using the following formula:

Units required (UI) = body weight (kg) x [desired level (%) - actual antithrombin III level (%)]

The antithrombin activity to be achieved initially depends on the clinical situation. When antithrombin substitution is indicated, the dose should be sufficient to achieve the desired antithrombin activity and to maintain an effective level. The dose should be determined and monitored according to the analytical data of antithrombin activity, which should be performed at least twice a day until the patient is stabilized, and then once a day, preferably immediately before the next infusion. The dose correction should take into account both the signs of increased antithrombin turnover according to laboratory tests and the clinical evolution. Antithrombin activity should be maintained above 80% throughout the treatment period, unless clinical data indicate a different level of efficacy.

The usual initial dose in congenital deficiencyis 30-50 UI/kg.

Subsequently, the dose and frequency, as well as the duration of treatment, should be adjusted according to the biological data and clinical situation.

There is insufficient data to recommend the administration of this product in children under 6 years of age.

Instructions for the correct administration of the preparation.

• The lyophilized powder should be reconstituted with the recommended solvent (water for injectables).

• Atenativ is compatible and can also be reconstituted with an isotonic sodium chloride solution (9 mg/ml) and with an isotonic glucose solution (50 mg/ml), in glass bottles for infusion, as well as in plastic containers.

• The maximum reconstitution time is 5 minutes. Once the preparation is reconstituted, it should be used as soon as possible and always within 12 hours.

• Any remaining solution that is not used should be discarded.

• Do not use cloudy solutions or those that contain any residue.

• The Atenativ solution is reconstituted as indicated above and injected or infused slowly intravenously (maximum 300 UI/minute)