Antithrombin iii nf takeda

Package leaflet: Information for the user

Antithrombin III NF Takeda, 50 IU/mL, powder and solvent for solution for infusion
Human antithrombin III derived from plasma
Please read all of this leaflet carefully before this medicine is given, because it contains important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any further questions, please ask your doctor or pharmacist.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Antithrombin III NF Takeda is and what it is used for
2. What you need to know before being given Antithrombin III NF Takeda
3. How Antithrombin III NF Takeda is given
4. Possible side effects
5. How to store Antithrombin III NF Takeda
6. Contents of the pack and other information

1. What Antithrombin III NF Takeda is and what it is used for

Antithrombin III NF Takeda is supplied as a fine, pale yellow to pale greenish powder with a solvent for preparing a solution for infusion.
Antithrombin III NF Takeda is available in packs containing:

• 500 IU antithrombin III and 10 mL solvent or
• 1000 IU antithrombin III and 20 mL solvent

Antithrombin III NF Takeda belongs to a pharmacotherapeutic group called antithrombotic agents.
Antithrombin III NF Takeda is used in the treatment of congenital or acquired antithrombin III deficiency, where acquired deficiency may occur in the course of various clinical conditions.

2. Important information before using Antithrombin III NF Takeda

When not to use Antithrombin III NF Takeda

• if the patient is allergic to antithrombin III or to any of the other components of this medicine (listed in section 6)
• in patients with a history of heparin-induced thrombocytopenia (i.e. reduced platelet count)

Warnings and precautions
Traceability
To improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly documented.

• Inform your treating physician immediately if the first signs of an allergic reaction occur (e.g. urticaria, including generalized urticaria, chest tightness, wheezing, hypotension, and anaphylactic shock). Severe symptoms may require emergency treatment.
• Inform your doctor if the patient is currently taking or has recently taken heparin-containing medications (e.g. for the treatment of thrombosis), as the activity of antithrombin is significantly enhanced by heparin.
• Antithrombin III NF Takeda is manufactured from human plasma. When administering medicinal products derived from human blood or plasma, the possibility of transmitting infectious agents cannot be completely ruled out. This includes pathogens currently unknown. However, the risk of transmission of infectious agents is reduced by careful selection of donors and plasma, testing of plasma pools, and by virus inactivation/removal procedures.

Children
Do not use this medicine in children under 6 years of age, as safety and efficacy have not yet been established in this age group.

Antithrombin III NF Takeda and other medicines
Tell your doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Inform your doctor about any current or recent treatment with heparin-containing medicines (e.g. for the treatment of thrombosis), as the activity of antithrombin is significantly enhanced by heparin.

Pregnancy, breastfeeding and fertility
Tell your doctor if the patient is pregnant or breastfeeding. The doctor will decide whether Antithrombin III NF Takeda can be used during pregnancy or breastfeeding.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Driving and operating machinery
Although no effect on the ability to drive or operate machinery has been observed, such an effect cannot be excluded. Therefore, it is recommended that patients do not drive or operate machinery without prior consultation with their doctor.

Antithrombin III NF Takeda contains sodium
500 IU/10 ml
The medicine contains 37.7 mg of sodium (the main component of table salt) per vial. This corresponds to 1.9% of the WHO recommended maximum daily intake of 2 g of sodium for adults.
1000 IU/20 ml
The medicine contains 75.5 mg of sodium (the main component of table salt) per vial. This corresponds to 3.8% of the WHO recommended maximum daily intake of 2 g of sodium for adults.

3. How to use Antithrombin III NF Takeda

Antithrombin III NF Takeda will be administered exclusively under medical supervision. The dose will depend on body weight and the individual patient's requirements. Your physician will determine the dose to be administered. Antithrombin III NF Takeda will be given by intravenous infusion.
Use of a higher than recommended dose of Antithrombin III NF Takeda
Symptoms of antithrombin overdose have not been reported.
Missed dose of Antithrombin III NF Takeda
Not applicable.
Discontinuation of Antithrombin III NF Takeda
Not applicable.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Adverse reactions observed after Antithrombin III NF Takeda was placed on the market include hypersensitivity, anaphylactic reaction, tremor, and hot flushes.

• Hypersensitivity or allergic reactions such as angioedema, burning and stinging at the infusion site, chills, hot flushes, generalized urticaria, headache, itchy rash, hypotension, somnolence, nausea, restlessness, tachycardia, chest tightness, paresthesia, vomiting, and wheezing have been observed rarely, but may in some cases progress to severe anaphylactic reaction (including shock).
• Fever has been observed rarely.
• Thrombocytopenia (i.e. decreased platelet count), mediated by heparin-induced antibodies, may occur rarely. A decrease in platelet count below 100,000/µL or a reduction in platelet count by 50% has been observed.

If any of the adverse reactions worsen or if any adverse reactions not listed in this leaflet occur, inform a doctor.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 4921301
Fax: +48 22 4921309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the Marketing Authorization Holder.
Reporting adverse reactions contributes to enhancing the safety of the medicine by providing additional information.

5. How to store Antithrombin III NF Takeda

Keep this medicine out of sight and reach of children.
Store in a refrigerator (2°C to 8°C). Do not freeze.
Store in the original packaging to protect from light.
Do not use this medicine after the expiry date stated on the label and carton following EXP. The expiry date refers to the last day of the stated month.
Do not use this medicine if the solution is cloudy or contains particles.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Antithrombin III NF Takeda contains

• The active substance is human antithrombin III derived from plasma
• The other components are glucose, sodium chloride, disodium citrate dihydrate and tris(hydroxymethyl)aminomethane

What Antithrombin III NF Takeda looks like and contents of the pack
Antithrombin III NF Takeda is a lyophilized powder for solution for infusion, containing nominally 500 IU (or 1000 IU) of antithrombin derived from human plasma per vial, together with solvent.
500 IU/10 ml
After reconstitution with 10 ml of sterile water for injections, the medicinal product contains approximately 50 IU/ml (500 IU/10 ml) of human antithrombin III from plasma.
1000 IU/20 ml
After reconstitution with 20 ml of sterile water for injections, the medicinal product contains approximately 50 IU/ml (1000 IU/20 ml) of human antithrombin III from plasma.
Antithrombin III NF Takeda is a pale yellow or pale greenish, friable mass or powder.
Each pack also contains:

• 1 transfer needle
• 1 filter needle
• 1 venting needle
• 1 single-use needle
• 1 infusion set

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warsaw, Poland
Manufacturer
Takeda Manufacturing Austria AG
Industriestrasse 67
1221 Vienna, Austria

Information intended exclusively for healthcare professionals:

Dosage and administration
Treatment should be supervised by a physician experienced in managing patients with antithrombin deficiency.

Dosage
In congenital antithrombin deficiency, the dose should be individually adjusted for each patient, taking into account family history of thromboembolic events, current risk factors, and laboratory test results.

The dosage and duration of replacement therapy in acquired deficiency depend on plasma antithrombin levels, presence of symptoms indicating increased consumption, the underlying cause of the disorder, and the clinical severity of the patient's condition. In all cases, the dose size and frequency of administration must be determined based on laboratory results and clinical assessment of the patient's condition and response to treatment.

The number of administered antithrombin units is expressed in International Units (IU), corresponding to the current WHO standard for antithrombin. Plasma antithrombin activity is expressed as a percentage (relative to normal human plasma) or in International Units (referring to the International Standard for antithrombin in plasma).

The activity of one International Unit (IU) of antithrombin corresponds to the amount of antithrombin present in one ml of normal human plasma. The calculation of the required antithrombin dose is based on empirical data showing that administration of 1 IU of antithrombin per kilogram of body weight increases plasma antithrombin activity by approximately 2%.

The initial dose is calculated using the following formula:
Required number of units = body weight (kg) × (Target level – current antithrombin activity [%]) × 0.5

The initial target plasma antithrombin activity depends on the clinical assessment of the patient. Once replacement therapy is indicated, a single dose should achieve the target antithrombin activity in plasma and subsequently maintain it within the desired range. The administered dose should be determined and monitored based on measurements of antithrombin activity, which should be performed at least twice daily until the patient's condition stabilizes, and thereafter once daily, preferably just before the next infusion. Dose adjustments should take into account both increased antithrombin consumption and laboratory results along with clinical symptoms. During treatment, antithrombin activity should be maintained above 80%, unless clinical considerations require a different, effective level.

The average initial dose in congenital deficiency is 30–50 IU/kg body weight.
Subsequently, the dose, frequency of administration, and duration of treatment should be adjusted according to laboratory results and the patient's clinical condition.

Children and adolescents
The safety and efficacy of Antithrombin III NF Takeda in children under 6 years of age have not been established. Therefore, use of the medicinal product is not recommended in this patient group.

Administration
Administer intravenously. The maximum infusion rate is 5 ml/min.

Special precautions for removal and preparation of the medicinal product for administration
Antithrombin III NF Takeda should be reconstituted immediately before use, as the product does not contain preservatives.

Only the provided infusion set should be used. Aseptic techniques must be followed during solution preparation. The prepared solution should be used immediately after reconstitution.

Before administration, check that the reconstituted medicinal product does not contain insoluble particles and has not discolored. The solution should be clear or slightly opalescent. Do not use solutions that are cloudy or contain precipitates.

Do not store in the refrigerator after reconstitution.

Preparation of the solution:

1. Bring the vial containing the solvent (water for injections) to room temperature (maximum 37°C).
2. Remove protective caps from both the powder vial and the solvent vial (Fig. A) and disinfect the rubber stoppers of both vials.
3. Remove the protective cap from one end of the transfer needle by twisting and pulling (Fig. B). Insert the exposed end of the needle into the rubber stopper of the solvent vial (Fig. C).
4. Remove the protective cap from the other end of the transfer needle, taking care not to touch the exposed part.
5. Invert the solvent vial and insert the free end of the transfer needle into the stopper of the powder vial (Fig. D). The solvent will be drawn into the powder vial by vacuum.
6. Disconnect the two vials by removing the needle from the powder vial (Fig. E). Gently swirl the vial to accelerate dissolution.
7. After complete dissolution of the powder, insert the provided venting needle (Fig. F) until the foam subsides. Remove the venting needle.

Administration:

8. Remove the protective cover from the provided filter needle by twisting and pulling, and attach it to a sterile single-use syringe. Draw the solution into the syringe (Fig. G).
9. Detach the filter needle from the syringe and, after attaching the provided single-use needle (or provided infusion set), slowly administer the solution intravenously (maximum administration rate: 5 ml/min).

If the medicinal product was not filtered during reconstitution, a single-use infusion set with an appropriate filter should be used (maximum infusion rate: 5 ml/min).

Fig. A Fig. B Fig. C Fig. D Fig. E Fig. F Fig. G
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.

Pharmaceutical incompatibilities
The medicinal product must not be mixed with other medicinal products.

Special warnings and precautions for use
As with other protein-containing medicinal products administered by intravenous infusion, administration of Antithrombin III NF Takeda may cause allergic-type hypersensitivity reactions.

Hypersensitivity and anaphylactic reactions have been reported post-marketing for Antithrombin III NF Takeda. In some cases, these may progress to severe anaphylactic reactions (including anaphylactic shock).

Patients must be closely monitored and carefully observed for any signs of adverse reactions during infusion. Patients should be informed about early signs of hypersensitivity reactions, such as itchy rash, generalized urticaria, chest tightness, wheezing, hypotension, and anaphylactic shock. If these symptoms occur after administration of the medicinal product, the patient should contact their treating physician.

In the event of shock, standard treatment should be initiated.

Takeda is a registered trademark of Takeda Pharmaceutical Company Limited.