Atked

Package leaflet: Information for the user

ATKED 500 UI/10 ml Powder and solvent for solution for infusion, 1000 UI/20 ml Powder and solvent for solution for infusion

Human Antithrombin
Please read all of this leaflet carefully before you start using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ATKED is and what it is used for

ATKED is a solution of Antithrombin derived from human plasma. Antithrombin is a plasma glycoprotein (a normal constituent of human plasma) with anticoagulant activity (inhibitor of blood coagulation).
ATKED is used in the following treatments:
In patients with congenital or acquired Antithrombin deficiency:
a) for prophylaxis (prevention) of deep vein thrombosis (blockage of a vein by a blood clot) and thromboembolism (abnormal formation of blood clots) in clinical risk situations (especially during surgical procedures or during childbirth), in combination with heparin when indicated;
b) for prevention of progression of deep vein thrombosis and thromboembolism in combination with heparin, when indicated.

2. What you need to know before using ATKED

Do not use ATKED

• if you are allergic to ATKED or to any of the other ingredients of this medicine (listed in section 6).
• if you have previously experienced heparin-induced thrombocytopenia (low platelet count).

Warnings and precautions
Talk to your doctor before using ATKED.
Your doctor or another healthcare professional will closely monitor and carefully observe you throughout the entire infusion period with ATKED to ensure that no reactions occur.
As with any intravenous protein product, allergic-type hypersensitivity reactions are possible.
If during administration you notice any of the symptoms listed below, you must inform the attending doctor immediately, as these symptoms could be the first signs of an allergic reaction. The doctor will decide whether to reduce the rate of administration or to stop the infusion.
Furthermore, the doctor will determine the necessary treatment based on the nature and severity of the side effect.
The first signs of hypersensitivity reactions include:

• urticaria,
• generalized urticaria,
• chest tightness (feeling of chest constriction),
• wheezing (breathing difficulty),
• hypotension and anaphylaxis (severe and rapid allergic reaction). If these symptoms occur after administration, contact your doctor.

In case of shock, the doctor must follow the standard treatment for this condition.
If antithrombin is administered together with heparin:
to adjust the heparin dosage and to avoid excessive hypocoagulability (poor blood clotting), clinical tests will be performed at close intervals, particularly during the first minutes/hours following the start of antithrombin administration, to monitor the extent of anticoagulation;
to adjust the individual dose, antithrombin levels will be monitored daily through clinical tests due to the risk of decreasing antithrombin levels associated with prolonged treatment with unfractionated heparin.

Viral safety
Medicines prepared from human blood or plasma are subject to a number of safety measures designed to prevent transmission of infections to patients. These measures include careful selection of blood or plasma donors to ensure that potentially infected donors are excluded, and testing of each donation and plasma pool to detect possible presence of viruses. In addition, manufacturers of these medicines incorporate into the manufacturing process several steps capable of inactivating or removing pathogens. Despite these measures, when administering medicines derived from human blood or plasma, the possibility of transmitting an infection cannot be completely ruled out. This also applies to emerging or unknown viruses or other types of infectious agents.
The measures taken are considered effective against lipid-enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and the non-lipid-enveloped hepatitis A virus (HAV).
The measures adopted have limited effectiveness against non-lipid-enveloped viruses such as parvovirus B19.
Parvovirus B19 infection can be severe during pregnancy (fetal infection) and in individuals with weakened immune systems or those with certain types of anemia (e.g. hemolytic anemia).
Appropriate vaccination (hepatitis A and B) is recommended for patients who regularly receive plasma-derived antithrombin concentrates.

Other medicines and ATKED
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Antithrombin replacement therapy during administration of therapeutic doses of heparin increases the risk of bleeding.
The effect of antithrombin is strongly enhanced by heparin.
Concomitant administration of heparin and antithrombin in patients with increased risk of bleeding must be clinically and biologically monitored.
ATKED must not be mixed with other medicinal products.
For infusion, only authorized commercially available devices should be used, as treatment may become ineffective due to adsorption of human antithrombin onto the inner surfaces of certain injection/infusion devices.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
Experience regarding the safety of using human antithrombin-containing products during human pregnancy is limited.
ATKED should be administered during pregnancy and breastfeeding to women with antithrombin deficiency under medical supervision, considering that these patients have an increased risk of thromboembolic events during pregnancy.

Driving and using machines
No effects on the ability to drive or operate machinery have been observed.

ATKED contains sodium
This medicine contains up to 92 mg of sodium (a main component of table salt) per vial in the 1000 IU presentation and up to 46 mg of sodium per vial in the 500 IU presentation.
This corresponds to 4.6% and 2.3% respectively of the maximum recommended daily dietary intake of sodium for an adult.

3. How to use ATKED

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor.
ATKED may only be used in hospitals or clinics and healthcare facilities by medical professionals or other healthcare providers.
For instructions on correct use and dosage, refer to the section "The following information is intended exclusively for doctors or healthcare professionals".
Treatment must be initiated under the supervision of a physician experienced in the treatment of patients with antithrombin deficiency.
The dose and treatment regimen depend on the indication; your doctor will determine the appropriate dose and treatment schedule for you.
For patient safety, whenever ATKED is administered, it is recommended to record the product's brand name and the production batch number, in order to maintain traceability between the patient and the product batch.
Use in children
There are insufficient data to recommend the use of ATKED in children under 6 years of age.
If you use more ATKED than you should
Symptoms of antithrombin overdose are not known.

4. Possible side effects

Like all medicines, ATKED can cause side effects, although not everyone experiences them.
Rarely, hypersensitivity or allergic reactions have been observed, which may include angioedema (localized swelling), burning and stinging sensation at the infusion site, chills, flushing, generalized urticaria, headache, urticaria, hypotension, lethargy (drowsiness), nausea, restlessness, tachycardia, chest tightness (feeling of chest constriction), paresthesia (altered sensation in limbs), vomiting, wheezing (difficulty breathing), which in some cases may lead to acute anaphylaxis including shock (severe and rapid allergic reaction).
Fever has been observed in rare cases.
For information on viral safety, see the section “Viral safety”.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor. You may also report side effects directly via the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ATKED

Keep this medicine out of the sight and reach of children.
See the expiry date stated on the packaging.
The expiry date refers to the product in its original, unopened packaging, correctly stored.
Do not use this medicine after the expiry date stated on the label and on the carton. The expiry date refers to the last day of that month.
Store in the refrigerator (2°C - 8°C). Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
Do not use this medicine if you notice cloudy solutions or deposits.
The product should be used within 8 hours after reconstitution. It is, however, advisable, whenever possible, to administer the solution immediately after reconstitution with the solvent provided.
The reconstituted product can be stored for up to 8 hours at a temperature not exceeding 30°C, or in the refrigerator (2°C - 8°C).
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What ATKED contains
The active substance is antithrombin derived from human plasma.

The activity (IU) is determined using the chromogenic method of the European Pharmacopoeia.
The specific activity of ATKED is approximately 5.0 IU/mg of protein.
The other components in the powder vial are: Monosodium phosphate, Sodium chloride, Glycine.
The solvent vial contains water for injections.
Description of the appearance of ATKED and contents of the pack
Powder and solvent for solution for infusion.
The medicine is presented as a hygroscopic powder or friable mass, white or almost white.
After reconstitution with the solvent, the solution is clear or slightly opalescent.
Before administration, the dissolved products must be visually inspected for the presence of
suspended particles or abnormal discoloration.
Do not use solutions that are cloudy or show deposits.
The ATKED pack contains one vial of powder, one vial of solvent for preparing the solution to be administered, and a sterile, pyrogen-free, single-use set consisting of a reconstitution device, an injection syringe, and a butterfly needle with PVC tubing.
Pack
ATKED 500 IU/10 ml powder and solvent for solution for infusion. Contains: 1 powder vial + 1 solvent vial 10 ml + reconstitution and administration set.
ATKED 1000 IU/20 ml powder and solvent for solution for infusion. Contains: 1 powder vial + 1 solvent vial 20 ml + reconstitution and administration set.
MARKETING AUTHORISATION HOLDER
Kedrion S.p.A. – Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca).
MANUFACTURER
Kedrion S.p.A. – 55027 Bolognana, Gallicano (Lucca).

The following information is intended exclusively for healthcare professionals:

Dosage recommendations:
In congenital deficiencies, the dosage must be individualized for each patient, taking into account
family history—particularly with regard to thromboembolic events—existing clinical risk factors, and
laboratory assessments.
The dosage and duration of replacement therapy in acquired deficiencies depend on the plasma
antithrombin level, the presence of signs indicating increased turnover, the underlying disease, and the severity of the
clinical condition. The amount to be administered and the frequency of administration must always be
based, on a case-by-case basis, on clinical efficacy and laboratory assessments.
The quantity of antithrombin administered is expressed in International Units (IU), which are
referenced to the current WHO standard for antithrombin. Antithrombin activity in plasma is
expressed both as a percentage (relative to normal human plasma) and as International Units (relative
to the international standard for plasma antithrombin).
One International Unit (IU) of antithrombin activity is equivalent to the amount of antithrombin present
in one milliliter of normal human plasma. The calculation of the required antithrombin dose is based on
the empirical observation that one International Unit (IU) of antithrombin per kg of body weight increases
plasma antithrombin activity by approximately 1.5%.
The initial dose is determined using the following formula:
Units required = body weight (kg) × (desired level – actual antithrombin activity [%]) ×
correction factor
The initial antithrombin activity level to be achieved depends on the clinical situation. When antithrombin
replacement is indicated, the dosage must be sufficient to reach the desired antithrombin activity level and to
maintain an effective level. The dosage must be individualized and monitored based on laboratory
measurements of antithrombin activity, which should be performed at least twice daily until the patient is stabilized, and then once daily, preferably immediately before the next infusion. Dosage adjustments must take into account both signs of increased antithrombin turnover, as indicated by laboratory monitoring, and the clinical course. Antithrombin activity should be maintained above 80% throughout the treatment period, unless clinical characteristics suggest a different effective level.
The usual initial dose in congenital deficiencies is 30–50 IU/kg.
Subsequently, the dose, frequency, and duration of treatment must be adjusted based on biological data and clinical status.

Method of administration
Reconstitute the lyophilized powder as described in the following section Instructions for correct use.
The product must be administered intravenously.
The infusion should be completed within a maximum of two hours.

Instructions for correct use
Reconstitution of the powder with the solvent:

1. bring the vial of powder and the solvent vial to room temperature;
2. maintain this temperature throughout the entire reconstitution process (maximum 10 minutes);
3. remove the protective caps from the powder and solvent vials;
4. clean the stoppers of both vials with alcohol;
5. open the device package by removing the top part; take care not to touch the inside (fig. A);
6. do not remove the device from the packaging;
7. turn the device package upside down and insert the plastic spike through the stopper of the solvent vial so that the blue part of the device is connected to the solvent vial (fig. B);
8. grasp the edge of the device package and pull it off to release the device without touching it (fig. C);
9. ensure that the vial containing the powder is placed on a stable surface; invert the system so that the solvent vial comes above the device; push the transparent/white adapter onto the stopper of the vial containing the powder so that the plastic spike pierces the stopper of the powder vial. The solvent will be automatically drawn into the powder vial (fig. D);
10. after the transfer of solvent, unscrew the blue part of the transfer system with the attached solvent vial and remove it (fig. E);
11. gently rotate the vial until the powder is completely dissolved. Do not shake vigorously to avoid foam formation (fig. F);

Ensure that the powder is completely dissolved; otherwise, there will be a loss of product activity.

Administration of the solution
The reconstituted medicinal product must be visually inspected before administration for the presence of
particles or color changes. The solution should be clear or slightly opalescent.
Do not use cloudy solutions or those containing deposits.

1. Fill the syringe with air by pulling back the plunger, attach it to the device, and inject the air into the vial containing the reconstituted solution (fig. G);
2. while holding the plunger steady, invert the system so that the vial containing the reconstituted solution comes above the device, and draw the concentrate into the syringe by slowly pulling back the plunger (fig. H);
3. disconnect the syringe by rotating it counterclockwise;
4. visually inspect the solution in the syringe, which should appear clear or slightly opalescent and free of particles;
5. attach the butterfly needle to the syringe and infuse or inject slowly intravenously.

Once the vials have been opened, the contents must be used immediately.
The reconstituted solution transferred into the syringe must be administered immediately.
The vial contents must be used for a single administration only.
Do not use after the expiry date stated on the label.
Unused medicinal product and waste materials derived from this medicinal product must be disposed of in accordance with local regulations.

Warnings and precautions
Patients must be closely monitored and carefully observed for any symptoms during the infusion period.
The half-life of antithrombin may be considerably reduced by concomitant heparin therapy due to accelerated antithrombin turnover. Therefore, the simultaneous administration of heparin and antithrombin to a patient with an increased risk of bleeding must be clinically and biologically monitored.

Package leaflet: Information for the user

ATKED 2000 UI/40 ml Powder and solvent for solution for infusion

Human antithrombin
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ATKED is and what it is used for

ATKED is a solution of Antithrombin derived from human plasma. Antithrombin is a plasma glycoprotein (a normal constituent of human plasma) with anticoagulant activity (inhibitor of blood coagulation).
ATKED is used in the following therapies:
In patients with congenital or acquired Antithrombin deficiency:
a) for prophylaxis (prevention) of deep vein thrombosis (obstruction of a vein by a blood clot) and thromboembolism (abnormal formation of blood clots) in clinical risk situations (especially during surgical procedures or during childbirth), in association with heparin when indicated;
b) for prevention of progression of deep vein thrombosis and thromboembolism, in combination with heparin, when indicated.

2. What you need to know before using ATKED

Do not use ATKED

• if you are allergic to ATKED or to any of the other ingredients of this medicine (listed in section 6).
• if you have previously experienced heparin-induced thrombocytopenia (low platelet count)

Warnings and precautions
Talk to your doctor before using ATKED.
Your doctor or another healthcare professional will closely monitor and carefully observe you throughout
the entire infusion period with ATKED to ensure that no reactions occur.
As with any intravenous protein product, allergic-type hypersensitivity reactions are possible.
If during administration you notice any of the symptoms listed below, inform the attending doctor immediately,
as these symptoms could be the first signs of an allergic reaction. The doctor will decide whether to reduce
the infusion rate or to stop the infusion.
Furthermore, the doctor will determine the necessary treatment based on the nature and severity of the
side effect.
The first signs of hypersensitivity reactions include:

• urticaria,
• generalized urticaria,
• chest tightness (feeling of chest constriction),
• wheezing (breathing difficulty),
• hypotension and anaphylaxis (severe and rapid allergic reaction). If these symptoms occur after administration, contact your doctor.

In case of shock, the doctor must follow the standard treatment for this condition.
If antithrombin is administered together with heparin:
to adjust the heparin dosage and to avoid excessive hypocoagulability (poor blood clotting), clinical tests
will be performed at close intervals, especially during the first minutes/hours after the start of antithrombin
administration, to monitor the extent of anticoagulation;
to adjust the individual dose, antithrombin levels will be monitored daily through clinical tests due to the
risk of decreased antithrombin levels associated with prolonged treatment with unfractionated heparin.
Viral safety
Medicines prepared from human blood or plasma are subject to a number of safety measures to prevent
the transmission of infections to patients. These measures include careful selection of blood or plasma
donors to ensure that potentially infected donors are excluded, and testing of each donation and plasma
pool to detect possible presence of viruses. In addition, manufacturers of these medicines include in the
processing of blood or plasma certain steps capable of inactivating or removing pathogens. Despite these
measures, when administering medicinal products prepared from human blood or plasma, the possibility
of transmitting an infection cannot be completely ruled out. This also applies to emerging or unknown
viruses or other types of infectious agents.
The measures taken are considered effective against enveloped viruses such as human immunodeficiency
virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and the non-enveloped hepatitis A virus (HAV).
The measures adopted have limited effectiveness against non-enveloped viruses such as parvovirus B19.
Infection with parvovirus B19 may be severe during pregnancy (fetal infection) and in individuals with
depressed immune systems or with certain types of anemia (e.g., hemolytic anemia).
Appropriate vaccination (hepatitis A and B) is recommended for patients who regularly receive antithrombin
concentrates derived from plasma.
Other medicines and ATKED
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Antithrombin replacement therapy during administration of therapeutic doses of heparin increases the
risk of bleeding.
The effect of antithrombin is strongly enhanced by heparin.
Concomitant administration of heparin and antithrombin in a patient with increased risk of bleeding must
be clinically and biologically monitored.
ATKED must not be mixed with other medicinal products.
For infusion, only authorized commercially available devices should be used, as treatment may be
ineffective due to adsorption of human antithrombin onto the inner surfaces of certain injection/infusion
devices.
Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult
your doctor or pharmacist before using this medicine.
Experience regarding the safety of antithrombin human-based products during human pregnancy is limited.
ATKED should be administered during pregnancy and breastfeeding to women with antithrombin deficiency
under medical supervision, considering that in these patients, the risk of thromboembolic events increases
during pregnancy.
Driving and using machines
No effects on the ability to drive or operate machinery have been observed.
ATKED contains sodium
This medicine contains up to 184 mg of sodium (a main component of table salt) per vial.
This corresponds to 9.2% of the maximum daily recommended dietary intake for an adult.

3. How to use ATKED

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.
ATKED may only be used in hospitals or clinics and healthcare facilities by medical professionals or other healthcare providers.
For instructions on correct use and dosage, refer to the section "The following information is intended exclusively for doctors or healthcare professionals."
Treatment must be initiated under the supervision of a physician experienced in the treatment of patients with antithrombin deficiency.
The dose and treatment regimen depend on the indication; your doctor will determine the appropriate dose and treatment schedule for you.
For patient safety, whenever ATKED is administered, it is recommended to record the brand name of the product and the production batch number to ensure traceability between the patient and the product batch.
Use in children
There are insufficient data to recommend the use of ATKED in children under 6 years of age.
If you use more ATKED than you should
Symptoms of antithrombin overdose are not known.

4. Possible side effects

Like all medicines, ATKED can cause side effects, although not everyone experiences them.
Hypersensitivity or allergic reactions have rarely been observed, which may include angioedema (localized swelling), burning and stinging sensation at the infusion site, chills, flushing, generalized urticaria, headache, urticaria, hypotension, lethargy (drowsiness), nausea, restlessness, tachycardia, chest tightness (feeling of chest constriction), paresthesia (altered sensation in the limbs), vomiting, wheezing (breathing difficulty), which in some cases may lead to acute anaphylaxis including shock (severe and rapid allergic reaction).
Fever has been observed in rare cases.
For information on viral safety, see section “Viral safety”.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor. You may also report side effects directly through the national adverse reaction reporting system.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ATKED

Keep this medicine out of the sight and reach of children.
See the expiry date stated on the packaging.
The expiry date refers to the product in its original packaging, when properly stored.
Do not use this medicine after the expiry date stated on the label and on the carton. The expiry date refers to the last day of that month.
Store in the refrigerator (2°C - 8°C). Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
Do not use this medicine if you notice cloudy solutions or particles present.
The product should be used within 8 hours after reconstitution. Immediate administration of the solution reconstituted with the supplied solvent is recommended, whenever possible.
The reconstituted product may be stored for up to 8 hours at a temperature not exceeding 30°C, or in the refrigerator (2°C - 8°C).
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What ATKED contains
The active substance is antithrombin derived from human plasma.

The activity (IU) is determined using the chromogenic method of the European Pharmacopoeia.
The specific activity of ATKED is approximately 5.0 IU/mg of protein.
The other components of the powder vial are Monobasic sodium phosphate, Sodium chloride, Glycine.
The solvent vial contains Water for injections.
Description of the appearance of ATKED and contents of the pack
Powder and solvent for solution for infusion.
The medicinal product is presented as a hygroscopic powder or friable mass, white or almost white.
After reconstitution with the solvent, the solution is clear or slightly opalescent.
Before administration, the dissolved products must be visually inspected for the presence of suspended particles or abnormal discoloration.
Do not use cloudy solutions or those showing deposits.
The ATKED pack contains one vial of powder, one vial of solvent for the preparation of the solution to be administered, and a sterile, pyrogen-free, single-use kit consisting of a double needle, a filter needle, a butterfly needle, a medicated plaster, and an infusion set for the 2000 IU/40 ml pack.
Pack
ATKED 2000 IU/40 ml powder and solvent for solution for infusion, 1 vial of powder + 1 vial of solvent 40 ml + infusion set.
MARKETING AUTHORISATION HOLDER
Kedrion S.p.A. – Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca).
MANUFACTURER
Kedrion S.p.A. – 55027 Bolognana, Gallicano (Lucca).

The following information is intended exclusively for healthcare professionals:

Dosage recommendations:
In congenital deficiencies, the dosage must be individualized for each patient, taking into account the
family history, particularly with regard to thromboembolic events, the actual clinical risk factors, and
laboratory assessments.
The dosage and duration of replacement therapy in acquired deficiencies depend on the plasma level of
antithrombin, the presence of signs indicating increased turnover, the underlying disease, and the severity of the
clinical condition. The amount to be administered and the frequency of administration must always be based,
on a case-by-case basis, on clinical efficacy and laboratory assessments.
The quantity of antithrombin administered is expressed in International Units (IU), which are related to the
current WHO standard for antithrombin. Antithrombin activity in plasma is expressed both as a percentage
(relative to normal human plasma) and as International Units (relative to the international standard for plasma
antithrombin).
One International Unit (IU) of antithrombin activity is equivalent to the amount of antithrombin present in one
milliliter of normal human plasma. The calculation of the required antithrombin dose is based on the empirical
observation that one International Unit (IU) of antithrombin per kg of body weight increases plasma antithrombin
activity by approximately 1.5%.
The initial dose is determined using the following formula:
Units required = body weight (kg) x (desired level – actual antithrombin activity [%]) x
correction factor
The initial antithrombin activity level to be achieved depends on the clinical situation. When antithrombin
replacement is indicated, the dosage should be sufficient to reach the desired antithrombin activity and to
maintain an effective level. The dosage must be individualized and monitored based on laboratory determinations
of antithrombin activity, which should be performed at least twice daily until the patient is stabilized, and then
once daily, preferably immediately before the next infusion. Dose adjustments should take into account both
signs of increased antithrombin turnover, as indicated by laboratory monitoring, and the clinical course.
Antithrombin activity should be maintained above 80% throughout the duration of treatment, unless clinical
characteristics indicate a different effective level.
The usual initial dose in congenital deficiencies is 30–50 IU/kg.
Subsequently, the dose, frequency, and duration of treatment must be adjusted based on biological data and
clinical status.

Method of administration
Reconstitute the lyophilized powder as described in the following section Instructions for correct use.
The product must be administered intravenously.
The infusion should be completed within a maximum of two hours.

Instructions for correct use
Reconstitution of the powder with the solvent:

1. Remove the protective caps from the vials of lyophilized powder and solvent;
2. Clean the stoppers of both vials with alcohol;
3. Insert the double-ended needle, from the corrugated side, into the vial containing the solvent;
4. Remove the needle cover from the other end of the double-ended needle;
5. Be careful not to touch the second needle;
6. Invert the solvent vial with the double-ended needle and insert the other end of the needle into the lyophilized powder vial; at the moment the stopper of the lyophilized powder vial is punctured, the tip of the needle in the solvent vial must be in contact with the liquid and not with the air;
7. Gently swirl slowly at room temperature until complete dissolution is achieved;
8. Remove together the solvent vial with the double-ended needle;
9. Attach the infusion set and administer intravenously.

Maximum reconstitution time: 10 minutes.

Administration of the solution
Reconstituted products must be visually inspected for the presence of suspended particles or abnormal
discoloration prior to administration.
The solution should be clear or slightly opalescent.
Do not use solutions that are cloudy or contain deposits.
Any unused medicinal product and waste material derived from this medicinal product must be disposed of in
accordance with local applicable regulations.

Warnings and precautions
Patients must be closely monitored and carefully observed for any symptoms during the infusion period.
The half-life of antithrombin may be considerably reduced by concomitant heparin therapy due to
accelerated antithrombin turnover. Therefore, the simultaneous administration of heparin and
antithrombin to a patient with an increased risk of bleeding must be clinically and biologically monitored.