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

Human plasma-derived antithrombin III

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

Human plasma-derived antithrombin III

Atenativ is a medication called an antithrombotic (anticoagulant) that contains isolated antithrombin 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 (birth) deficiency of antithrombin, particularly to prevent the formation and development of blood clots in deep veins (deep vein thrombosis) and embolisms (thromboembolism) in clinical risk situations (for example, during surgeries or births) and in association with heparin if necessary,

No use Atenativ:

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

Warnings and precautions:

Inform your doctor if you have any other medical condition.

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

Viral safety:

When medications are manufactured from blood or human plasma, certain measures are taken to prevent the transmission of infections to patients. This includes a careful selection of blood and plasma donors to ensure that those at risk of carrying infections are excluded, analysis of each donation and plasma mixtures to detect signs of viruses/infections, and the inclusion of steps in the blood or plasma processing that may inactivate or eliminate viruses. Despite these measures, when administering medications prepared from human blood or plasma, the possibility of transmission of infections cannot be entirely ruled out. This also applies to unknown or emerging viruses or other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and for 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 people with a weakened immune system or 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 medication to maintain a record of the batch used.

• Your doctor may recommend that you consider vaccinating against hepatitis A and B if you regularly/repeatedly receive human plasma-derived antithrombin products.

Other medications and Atenativ:

Inform your doctor or pharmacist if you are using, or have recently used or may need to use another medication, even 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, the concomitant administration of heparin should be carefully evaluated. If your doctor decides that you should receive heparin, it will be closely monitored through laboratory tests.

Atenativ with food and beverages:

No effects have been observed.

Pregnancy, breastfeeding, and fertility:

Consult your doctor or pharmacist before using this medication if you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant.

There is limited information available 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 operating machinery:

No effects have been observed on the ability to drive vehicles or operate machinery. Only you are responsible for deciding if you are in good condition to drive a motor vehicle or perform other tasks that require greater concentration.

Important information about some of the components of Atenativ:

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

The treatment must be initiated under the supervision of a specialized doctor in the treatment of patients with antithrombin deficiency.Your doctor will decide if you need Atenativ and at what dose.

Your doctor will individualize the dose for each patient, taking into account family history related to thromboembolic episodes, real clinical risk factors, and laboratory tests.Laboratory tests necessary during treatment will be monitored.

Atenativ is administered as an infusion by healthcare personnel.

If you use more Atenativ than you should:

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

If you forgot to use Atenativ:

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

Like all medications, this medication may produce adverse effects, although not all people will experience them.

The use of plasma derivatives may cause allergic or hypersensitivity reactions (for example, 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, redness, tingling, or even shock).

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

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist or nurse, even if it is about possible adverse effects not listed in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

For information on viral safety, see section 2

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

Store in refrigerator (between2°Cand8°C). Store the vials in the outer packaging to protect them from light.

Do not freeze.

Do not usethis medicationafter the expiration date that appears on the packaging. The expiration date is the last day of the month indicated.

Do not useAtenativif you observe that the solution is cloudy or has any residue.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. By doing so, you will help protect the environment.

Atenativ Composition:

The active principle is human plasma-derived antithrombin III (50 UI/ml).

The other components are:

• Sodium chloride, human albumin acetiltriptophan, caprylic acid powder.
• Injectable preparation water as a solvent.

Product appearance and packaging content

Atenativ is a powder and solvent for perfusion solution. The packaging contains a lyophilized powder in a vial (type II glass) and a solvent (injectable preparation water) in a vial (type I glass) used for reconstituting the powder. Normally, the solution obtained is clear or slightly opalescent.The reconstituted solution contains 50 UI of human antithrombin III/ml of perfusion 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. Dublin, 2nd Floor

28830 San Fernando de Henares Madrid

Responsible for manufacturing:

OCTAPHARMA AB.

Lars Forssells gata 23

SE-112 75 Stockholm

Sweden

Last review date of this leaflet:February 2020

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

INSTRUCTIONS FOR HEALTHCARE PERSONNEL:

Dosage:

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

The number of antithrombin units administered is expressed in International Units (UI), which are related to the current standard pattern of the WHO for antithrombin. Antithrombin activity in plasma is expressed either as a percentage (in relation to normal human plasma) or in International Units (in relation to the International pattern 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 antithrombin III activity by approximately 1%.

The initial dose is determined by the following formula:

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

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

The initial dose is usually 30-50 UI/kg incongenital deficiency.

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

There are not enough data to recommend the administration of this product in children under 6 years old.

Instructions for correct administration of the preparation.

• The lyophilized powder must be reconstituted with the recommended solvent (injectable preparation water).

• Atenativ is compatible and can also be reconstituted with a 9 mg/ml isotonic sodium chloride solution and with a 50 mg/ml isotonic glucose solution, in glass vials for perfusion, 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 before 12 hours.

• Any remaining solution should be discarded.

• Do not use turbid or residue-containing solutions.

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