ATKED 500 UI/10 ML Powder and solvent for intravenous infusion solution

Зміст інструкції

1. ATKED 500 IU/ 10 ml Powder and solvent for infusion solution, 1000 IU/ 20 ml Powder and solvent for infusion solution
   1. What is ATKED and what is it 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. Content of the pack and other information
2. ATKED 2000 IU/ 40 ml Powder and solvent for infusion solution
   1. What is ATKED and what is it 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

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

Human antithrombin

Read this leaflet carefully before you use 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 their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell 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 you use 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 is ATKED and what is it 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 action (inhibitor of blood coagulation).
ATKED is used in the following therapies:
In patients with congenital or acquired Antithrombin deficiency:
a) for the prophylaxis (prevention) of deep vein thrombosis (obstruction of a vein by a blood clot) and thromboembolism (abnormal production of blood clots) in situations of clinical risk (especially in case of surgical interventions or during the postpartum period), in association with heparin when indicated;
b) for the prevention of the progression of deep vein thrombosis and thromboembolism in association 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
Consult your doctor before using ATKED.
The doctor or another healthcare professional will monitor you closely and observe you carefully during
the entire period of the infusion with ATKED to verify that there are no reactions.
As with any intravenous protein product, hypersensitivity reactions of an allergic type are possible.

If you notice any of the following symptoms during the administration of the product, you must
immediately inform the doctor present, because these symptoms may be the first signs of
an allergic reaction. The doctor will decide whether to reduce the administration rate or to stop
the infusion.
In addition, the doctor will decide the necessary treatment based on the nature and the side effect.
The first signs of hypersensitivity reactions are:

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

In case of shock, the doctor must follow the standard treatment for this condition.
If you are given antithrombin together with heparin:
to adjust the dosage of heparin and to avoid excessive hypocoagulability (poor coagulation),
you will undergo clinical tests to check the extent of anticoagulation, at close intervals and particularly in the first minutes/hours following the start of antithrombin administration;
to adjust the individual dose, antithrombin levels will be checked daily with clinical tests, due to the risk of decreased antithrombin levels due to prolonged treatment with
unfractionated heparin.
Viral safety
Medicines prepared from human blood or plasma undergo 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 any presence of viruses. Manufacturers of
these medicines also introduce some steps into the processing of blood or plasma that are capable of
inactivating or removing pathogens. Despite these measures, when administering medicines prepared
from human blood or plasma, the possibility of transmitting an infection cannot be completely
excluded. This also applies to viruses, or other types of infectious agents, emerging or unknown.
The measures taken are considered effective for enveloped viruses such as the human immunodeficiency virus (HIV), the hepatitis B virus (HBV), the hepatitis C virus (HCV) and the non-enveloped virus of hepatitis A (HAV).
The measures adopted have limited value against non-enveloped viruses such as parvovirus B19.
Infection with parvovirus B19 can be severe in pregnancy (fetal infection) and in individuals whose immune system is depressed or who have some type of anemia (e.g. hemolytic anemia).
Appropriate vaccination (hepatitis A and B) is recommended for patients receiving antithrombin concentrates regularly derived from plasma.

Other medicines and ATKED
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicine.
Replacement therapy with antithrombin during the administration of therapeutic doses of heparin increases
the risk of bleeding.
The effect of antithrombin is strongly potentiated by heparin.
The simultaneous administration of heparin and antithrombin to a patient with an increased risk of
bleeding must be monitored clinically and biologically.
ATKED must not be mixed with other medicinal products.
Only commercially available devices authorized for infusion should be used, as treatment
may be ineffective due to absorption of human antithrombin to the inner walls of some
injection/infusion devices.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
Experience regarding the safety of the use of human antithrombin-based products during human pregnancy
is limited.
ATKED should be administered during pregnancy and breastfeeding to women with antithrombin deficiency under medical supervision, bearing in mind that these patients have an
increased risk of thromboembolic events during pregnancy.

Driving and operating machinery
No effects on the ability to drive and operate machinery have been observed.

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

3. How to use ATKED

Use this medicine following the instructions of your doctor exactly. If you have any doubts, consult your doctor.
ATKED can only be used in hospitals or clinics and nursing homes by medical professionals
or other healthcare operators.
For instructions on correct use and Dosage, refer to the section “The following information is
intended exclusively for doctors or healthcare operators”.
Treatment must begin under the supervision of a doctor experienced in treating patients with
antithrombin deficiency.
The dose and treatment regimen depend on the indication; the doctor will determine the dose and regimen
suitable for you.
In the interest of patients, whenever ATKED is administered to them, it is recommended to record the
trade name of the product and the production batch number, in order to maintain
traceability between the patient and the product batch.

Use in children
There is 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 may cause side effects, although not everybody gets 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
(hives), headache, urticaria, hypotension, lethargy (drowsiness), nausea, restlessness,
tachycardia, chest tightness (feeling of chest constriction), paresthesia (altered sensation of the
limbs), vomiting, wheezing (difficulty breathing), which can lead in some cases to acute anaphylaxis including
shock (severe and rapid allergic reaction).
Fever has been observed in rare cases.
For information on viral safety see the “Viral safety” section.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor. You can also report side effects directly through the national system of
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 printed on the packaging.
The expiry date refers to the product in intact packaging, correctly stored.
Do not use this medicine after the expiry date that is reported on the label and on the box. The expiry
date refers to the last day of that month.

Store in a 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 those that contain deposits.
The product must be used within 8 hours of reconstitution. However, it is recommended, when possible,
to administer the reconstituted solution with the included solvent immediately.
The reconstituted product can be stored for 8 hours at a temperature not exceeding 30°C, or in
a refrigerator (2°C -8°C).
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What ATKED contains
The active ingredient 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 medicine presents as a hygroscopic powder or friable mass, white to almost white.
After reconstitution with the solvent, the solution appears clear or slightly opalescent.
Before administration, the dissolved products must be visually checked for the presence of
particles in suspension, or abnormal coloration.
Do not use turbid solutions or those with deposits.
The ATKED pack contains a vial of powder, a vial of solvent with which the solution is prepared for
administration, and a sterile and apyrogenic, single-use set consisting of a reconstitution device, a
syringe for injections and a butterfly needle with a PVC tube.

Pack
ATKED 500 IU/10 ml powder and solvent for solution for infusion. Contains: 1 vial powder + 1
solvent vial 10 ml + set for reconstitution and administration.
ATKED 1000 IU/20 ml powder and solvent for solution for infusion. Contains: 1 vial powder + 1
solvent vial 20 ml + set for reconstitution and administration.

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:

Recommendations for dosage:
In congenital deficiencies, the dosage must be individualized for each patient, taking into account the
family history with particular regard to thromboembolic events, actual clinical risk factors and
laboratory tests.
The dosage and duration of replacement therapy in acquired deficiencies depend on the plasma level of
antithrombin, the presence of signs of increased turnover, the underlying disease and the severity of the
clinical condition. The amount to be administered and the frequency of administrations must always be
based for each individual case on clinical efficacy and laboratory tests.
The amount of antithrombin units administered is expressed in International Units (IU), which are
correlated with the current WHO standard for antithrombin. The activity of antithrombin 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 dose of antithrombin 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 to be achieved depends on the clinical situation. When there is
an indication for antithrombin replacement, the dosage must be sufficient to reach the desired antithrombin
activity and to maintain an effective level. The dosage must be determined and monitored based on
determinations of antithrombin activity in the laboratory; determinations that must be performed at least
twice a day until the patient has stabilized, and then once a day, preferably immediately before the next
infusion. Dosage correction must take into consideration both signs of increased antithrombin turnover,
in accordance with laboratory tests, and the clinical course. Antithrombin activity must be maintained
above 80% for the entire duration of treatment, unless clinical characteristics indicate a different effective
level. The usual initial dose in congenital deficiencies is 30-50 IU/kg.
Then, the dose and frequency, as well as the duration of treatment, must be adjusted based on
biological data and the clinical situation.

Route of administration
Dissolve the lyophilized powder as described in the following paragraph Instructions for correct use.
The medicine must be administered intravenously.
The infusion must be completed within a maximum of two hours.

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

• 1. Bring the powder and solvent vial to room temperature;
• 2. This temperature must be maintained throughout the entire reconstitution process (maximum 10 minutes);
• 3. Remove the protective caps from the powder and solvent vials;
• 4. Clean the surfaces of the vial caps with alcohol;
• 5. Open the package of the device by removing the top part; be careful not to touch the inside (fig. A);
• 6. Do not remove the device from the package;
• 7. Turn the device box over and insert the plastic tip through the cap of the solvent vial so that the blue part of the device is connected to the solvent vial (fig. B);
• 8. Grab the edge of the device box and pull it off, freeing the device without touching it (fig. C);
• 9. Make sure that the vial containing the powder is positioned on a secure support, turn the system over so that the solvent vial is above the device; push the transparent adapter onto the cap of the vial containing the powder so that the plastic tip passes through the cap of the powder vial. The solvent will be automatically drawn into the powder vial (fig. D);

• 10. After transferring the solvent, unscrew the blue part of the transfer system with the solvent vial attached and remove it (fig. E);
• 11. Gently rotate the vial until all the powder is completely dissolved. Do not shake the vial vigorously to avoid foaming (fig. F);

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

fig. A	c fig. B a m r a
fig. C n	F fig. D l e d a
a i fig. E l a t I a	fig. F

Administration of the solution
The reconstituted medicine must be visually inspected before administration to
identify particles or color changes. The solution should be clear or slightly
opalescent.
Do not use turbid solutions or those with 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. Holding the plunger steady, turn the system over so that the vial containing the powder with the reconstituted solution is 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 be clear or slightly opalescent, free of particles;
• 5. Connect the butterfly needle to the syringe and infuse or inject slowly intravenously.

fig. G a i

l fig. H e d a n

Pharmaceutical Service, Inc.
Once the vials have been opened, the contents must be used immediately.
The reconstituted solution and transferred to the syringe must be administered immediately.
The contents of the vial must be used in a single administration.
Do not use after the expiry date stated on the label.
Unused medicine and waste derived from such medicine must be disposed of in accordance with
current 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 treatment with
heparin due to an accelerated turnover of antithrombin. Therefore, the simultaneous administration of
heparin and antithrombin to a patient with an increased risk of bleeding must be monitored
clinically and biologically.

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

Human antithrombin

Read this leaflet carefully before you use 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 their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell 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 you use 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 is ATKED and what is it 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 action (inhibitor of blood coagulation).
ATKED is used in the following therapies:
In patients with congenital or acquired Antithrombin deficiency:
b) for the prophylaxis (prevention) of deep vein thrombosis (obstruction of a vein by a blood clot) and thromboembolism (abnormal production of blood clots) in situations of clinical risk (especially in case of surgical interventions or during the postpartum period), in association with heparin when indicated;
b) for the prevention of the progression of deep vein thrombosis and thromboembolism in association 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
Consult your doctor before using ATKED.
The doctor or another healthcare professional will monitor you closely and observe you carefully during
the entire period of the infusion with ATKED to verify that there are no reactions.
As with any intravenous protein product, hypersensitivity reactions of an allergic type are possible.

If you notice any of the symptoms listed below during the administration of the product, you must
immediately inform the doctor present, because these symptoms may be the first signs of
an allergic reaction. The doctor will decide whether to reduce the administration rate or to stop
the infusion.
The doctor will also decide on the necessary treatment based on the nature and the side effect.
The first signs of hypersensitivity reactions are:

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

In case of shock, the doctor must follow the standard treatment for this condition.
If you are given antithrombin together with heparin:
to adjust the heparin dosage and to avoid excessive hypocoagulability (poor coagulation),
you will be subjected to clinical tests to check the extent of anticoagulation, at close intervals and in particular in the first minutes/hours following the start of administration of
antithrombin;
to adjust the individual dose, antithrombin levels will be checked daily with clinical tests, due to the risk of a decrease in antithrombin levels due to prolonged treatment with
unfractionated heparin.
Viral safety
Medicines prepared from human blood or plasma are subjected 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 any presence of viruses. Manufacturers of
these medicines also introduce some steps into the processing of blood or plasma that are capable of
inactivating or removing pathogens. Despite these measures, when administering medicinal specialties
prepared from human blood or plasma, the possibility of transmitting an infection cannot be completely
excluded. This also applies to viruses, or other types of infectious agents, emerging or unknown.
The measures taken are considered effective for enveloped viruses such as the human immunodeficiency virus (HIV), the hepatitis B virus (HBV), the hepatitis C virus (HCV) and the non-enveloped hepatitis A virus (HAV).
The measures adopted have limited value against non-enveloped viruses such as parvovirus
B19.
Infection with parvovirus B19 can be severe in pregnancy (fetal infection) and in individuals whose immune system is depressed or who have some type 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
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicines.
Replacement therapy with antithrombin during the administration of therapeutic doses of heparin increases
the risk of bleeding.
The effect of antithrombin is strongly potentiated by heparin.
The simultaneous administration of heparin and antithrombin to a patient with an increased risk of
bleeding must be monitored clinically and biologically.
ATKED must not be mixed with other medicinal products.
Only commercially available devices authorized for infusion should be used, as the treatment
may be ineffective due to the absorption of human antithrombin to the inner walls of some
injection/infusion devices.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding with breast
milk, ask your doctor or pharmacist for advice before using this medicine.
Experience regarding the safety of use of human antithrombin-based products during human pregnancy
is limited.
ATKED should be administered during pregnancy and breastfeeding to women with antithrombin deficiency under medical supervision, bearing in mind that these patients have an
increased risk of thromboembolic events during pregnancy.

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

ATKED contains sodium
This medicine contains up to 184 mg of sodium (the main component of table salt) per
vial.
This is equivalent to 9.2% of the recommended maximum daily intake with the diet of an adult.

3. How to use ATKED

Use this medicine following the doctor's instructions exactly. If you have any doubts, consult your doctor.
ATKED can only be used in hospitals or clinics and nursing homes by medical professionals
or other healthcare operators.
For Instructions on correct Use and Dosage, refer to the section “The following information is
intended exclusively for doctors or healthcare operators”
Treatment must begin under the supervision of a doctor experienced in the treatment of patients with
antithrombin deficiency.
The dose and treatment regimen depend on the indication; the doctor will establish the dose and regimen of
treatment suitable for you.
In the interest of patients, whenever ATKED is administered to them, it is recommended to record the
trade name of the product and the production batch number, in order to maintain
traceability between the patient and the product batch.

Use in children
There is not enough data to recommend the use of ATKED in children under 6 years of age.

If you use more ATKED than you should
No symptoms of antithrombin overdose are known.

4. Possible side effects

Like all medicines, ATKED can cause side effects, although not everybody gets them.
Rarely, hypersensitivity or allergic reactions have been observed, which may include angioedema
(localized swelling), burning and stinging sensation at the infusion site, chills, redness, urticaria
generalized, headache, hives, hypotension, lethargy (drowsiness), nausea, restlessness,
tachycardia, chest tightness (feeling of chest constriction), paresthesia (altered sensation of the
limbs), vomiting, wheezing (difficulty breathing), which can lead in some cases to acute anaphylaxis including
shock (severe and rapid allergic reaction).
In rare cases, fever has been observed.
For information on viral safety see the section “Viral safety”.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor. You can also report side effects directly through the national reporting system
for adverse reactions.
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 intact packaging, correctly stored.
Do not use this medicine after the expiry date that is stated on the label and on the box. The expiry
date refers to the last day of that month.

Store in a 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 turbid solutions or those with deposits.
The product must be used within 8 hours of reconstitution. However, it is recommended, when possible,
to administer the reconstituted solution with the included solvent immediately.
The reconstituted product can be stored for 8 hours at a temperature not exceeding 30°C, or in
a refrigerator (2°C -8°C).
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What ATKED contains
The active ingredient 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 medicine presents as a hygroscopic powder or friable mass, white or almost white.
After reconstitution with the solvent, the solution appears clear or slightly opalescent.
Before administration, dissolved products must be visually checked for the presence of
particles in suspension, or abnormal coloration.
Do not use turbid solutions or those containing deposits.
The ATKED pack contains one vial of powder, one vial of solvent with which the solution is prepared for administration, and a sterile and apyrogenic, single-use set consisting of a double needle, a filter needle, a butterfly needle, an adhesive bandage and an infusion set for the 2000 IU/40ml pack.

Pack
ATKED 2000 IU/40 ml powder and solvent for solution for infusion, 1 powder vial + 1 solvent vial 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:

Recommendations for dosage:
In congenital deficiencies, the dosage must be individualized for each patient, taking into account family history with particular regard to thromboembolic events, actual clinical risk factors and laboratory tests.
The dosage and duration of replacement therapy in acquired deficiencies depend on the plasma level of
antithrombin, the presence of signs of increased turnover, the underlying pathology and the severity of the
clinical condition. The amount to be administered and the frequency of administrations must always be based for each individual case on clinical efficacy and laboratory tests.
The amount of antithrombin units administered is expressed in International Units (IU), which are
correlated to the current WHO standard for antithrombin. The activity of antithrombin 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 millilitre 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 to be achieved depends on the clinical situation. When there is
an indication for antithrombin replacement, the dosage must be sufficient to reach the desired antithrombin activity and to maintain an effective level. The dosage must be determined and controlled on the basis of determinations of antithrombin activity in the laboratory; determinations that
must be performed at least twice a day until the patient has stabilized, and then once a day, preferably immediately before the next infusion. Adjustment of the dosage
must take into consideration both signs of increased antithrombin turnover, in accordance with laboratory tests, and the clinical course. Antithrombin activity must be maintained above 80% for the entire
duration of treatment, unless clinical characteristics indicate a different effective level.
The usual initial dose in congenital deficiencies is 30-50 IU/kg.
Then, the dose and frequency, as well as the duration of treatment, must be adjusted on the basis of
biological data and the clinical situation.

Route of administration
Dissolve the lyophilized powder as described in the following paragraph Instructions for correct use.
The product must be administered intravenously.
The infusion must 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 surfaces of the stoppers of the two vials with alcohol;
• 3. insert the double needle, from the corrugated part, into the vial containing the solvent;
• 4. remove the cap covering the needle from the other side of the double needle;
• 5. be careful not to touch the second needle;
• 6. invert the solvent vial with the double needle inserted and insert the other needle into the lyophilized powder vial; when piercing the stopper of the vial containing the lyophilized powder, the end of the needle in the solvent vial must be in contact with the liquid and not with the air;
• 7. shake very slowly at room temperature until completely dissolved;
• 8. remove the solvent vial with the double needle together;
• 9. apply the infusion set and infuse intravenously.

Maximum reconstitution time 10 minutes.

Administration of the solution
Reconstituted products must be visually checked for the presence of particles in suspension or abnormal
coloration before administration.
The solution must be clear or slightly opalescent.
Do not use turbid solutions containing deposits.
Unused medicine and waste derived from such medicine must be disposed of in accordance with
current 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 treatment
with heparin due to accelerated antithrombin turnover. Therefore, the simultaneous
administration of heparin and antithrombin to a patient with increased risk of bleeding
must be monitored clinically and biologically.