ATENATIV 500 IU POWDER AND SOLVENT FOR SOLUTION FOR INFUSION

2. What you need to know before using Atenativ

Do not use Atenativ:

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

Warnings and precautions:

Tell your doctor if you have any other illness.

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

Viral safety

When medicines are manufactured from blood or plasma, certain measures are put in place 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 remove viruses. Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of transmitting infections cannot be totally 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, the name and batch number of the medicine should be recorded to keep a record of the batch used.

• Your doctor may recommend that you 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 might use any other medicines, including those obtained without a prescription.

The anticoagulant effect of heparin is increased 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 be given heparin, you will be closely monitored with laboratory tests.

Atenativ with food and drinks:

No effects have been observed.

Pregnancy, breastfeeding, and fertility:

Consult 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 attention.

Important information about some of the ingredients of Atenativ

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

3. How to use 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, current 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-mentioned symptoms, administration should be stopped immediately. Your doctor will follow the applicable guidelines for the treatment of shock.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this package leaflet. You can also report side effects directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) website: 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 expiry date stated on the packaging. The expiry date is the last day of the month stated.

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 medicines no longer required. This will help protect the environment.

6. Package contents and further information

Composition of Atenativ:

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

The other ingredients are:

• Powder: sodium chloride, human albumin, acetriptophan, capric acid.
• Solvent: water for injections.

Appearance of the product and package contents

Atenativ is a powder and solvent for solution for infusion. The package contains a lyophilized powder in a vial (type II glass) and a solvent (water for injections) in a vial (type I glass) used for reconstitution of the powder. The solution obtained is usually 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 Estocolmo

Suecia

Date of last revision of this package 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/

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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, current 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 either 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%. 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 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 analytical data on 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. Dose adjustment should take into account both signs of increased antithrombin turnover according to laboratory tests and 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 biological data and the clinical situation.

There is not enough 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 injections).

• 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 by intravenous route (maximum 300 UI/minute).