UMAN 500 U.I./20 ML Порошок и раствор для раствора для внутривенного введения

Содержание инструкции

1. UMAN COMPLEX 500 UI/20 ml Powder and solvent for infusion solution
   1. What is UMAN COMPLEX and what is it used for
   2. What you need to know before using UMAN COMPLEX
   3. How to use UMAN COMPLEX
   4. Possible side effects
   5. How to store UMAN COMPLEX
   6. Contents of the pack and other information

UMAN COMPLEX 500 UI/20 ml Powder and solvent for infusion solution

Factor IX + Factor II + Factor X of human plasma coagulation
Read this leaflet carefully before using this medicine as it contains important
information for you.

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

Contents of this leaflet:

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

1. What is UMAN COMPLEX and what is it used for

UMAN COMPLEX is a solution of coagulation factors IX, II and X derived from human plasma.
The blood coagulation factors IX, II and X are proteins that have an antihemorrhagic effect.
UMAN COMPLEX is used in the following therapies:

• Treatment and perioperative prophylaxis of bleeding (medical procedure in the period before or immediately after surgery to prevent bleeding) in acquired deficiency of prothrombin complex coagulation factors, such as deficiency caused by treatment with vitamin K antagonists, or in case of overdose of vitamin K antagonists, when a rapid correction of the deficiency is required.
• Treatment and perioperative prophylaxis of bleeding (medical procedure in the period before or immediately after surgery to prevent bleeding) in deficiency

congenital of some of the vitamin K-dependent coagulation factors, when the purified product
of the specific coagulation factor is not available.

2. What you need to know before using UMAN COMPLEX

Do not use UMAN COMPLEX
if you are allergic to any of the proteins in the prothrombin complex (Factor IX, Factor II and Factor X) or to
any of the other ingredients of this medicine (listed in section 6);
if you have previously experienced thrombocytopenia (low platelet count) induced by heparin;
if you have previously experienced allergic reactions induced by heparin.

Warnings and precautions
Consult a doctor specializing in the treatment of coagulation disorders before using UMAN
COMPLEX.
The doctor or another healthcare professional will monitor you closely and observe you carefully during
the entire period of the infusion with UMAN COMPLEX 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 reaction during the administration of the product, you must immediately inform the
doctor present, because you may experience 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 on the necessary treatment based on the nature and the side effect.
If these symptoms occur after administration, contact your doctor.
In case of shock, the doctor must follow the standard treatment for this condition.

Viral safety
Medicines prepared from human blood or plasma undergo a number of safety measures implemented 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 highlight any presence of
infections/viruses. Manufacturers of these medicines also introduce some steps into the processing of blood and
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
totally 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 taken may have a limited effect against non-enveloped viruses such as parvovirus
B19. Infection with parvovirus B19 can be severe during pregnancy (fetal infection) and in individuals whose
immune system is depressed or who have some type of anemia (e.g. sickle cell anemia or hemolytic anemia).
Appropriate vaccination (hepatitis A and B) is recommended for patients receiving human prothrombin complex regularly.

Children
No data are available regarding the use of UMAN COMPLEX in case of bleeding in the perinatal period due to
vitamin K deficiency in the newborn.
The safety and efficacy of UMAN COMPLEX in children have not yet been established. No data are currently available.

Other medicines and UMAN COMPLEX
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
Human prothrombin complex (UMAN COMPLEX) neutralizes the effect of treatment with
vitamin K antagonists. No interactions with other medicines are known.
UMAN COMPLEX must not be mixed with other medicines.
Only the devices included in the package must be used for infusion, as ineffective treatment may occur due to absorption of coagulation factors on the inner walls of some infusion devices.
Interference with biological tests
When coagulation tests sensitive to heparin are performed in patients receiving high doses of human prothrombin complex, the heparin contained in the administered product must be taken into consideration.

Pregnancy and breastfeeding
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.
The safety of the plasma prothrombin complex concentrate during pregnancy has not been established by controlled clinical studies.
Animal studies are insufficient to support safety with regard to reproduction, embryo and fetal development, the course of gestation and peri- and postnatal development.
Therefore, human prothrombin complex may be used during pregnancy and breastfeeding only if a documented need exists.

Driving and using machines
No effects on the ability to drive and use machines are known.

UMAN COMPLEX contains sodium
This medicine contains up to a maximum of 92 mg of sodium (the main component of table salt)
per 20 ml vial.
This is equivalent to 4.6% of the recommended daily intake of salt for an adult.

3. How to use UMAN COMPLEX

For Instructions on correct use and Dosage, refer to the section “The following information is
intended exclusively for doctors or healthcare professionals”
Treatment must begin under the supervision of a physician experienced in the treatment of coagulation disorders. The dosage and duration of replacement therapy depend on the severity of the hemostatic function disorder, the location and extent of the bleeding, and the patient's clinical condition; the dose to
be administered and the frequency of applications will always be calculated based on the individual
response.
Therapeutic ranges must be adapted to the different half-lives of the various coagulation factors
of the prothrombin complex.
The doctor will determine the dose and treatment regimen suitable for you based on clinical examinations.
If you have any doubts about the use of UMAN COMPLEX, consult your doctor.
It is strongly recommended that, each time you receive a dose of UMAN COMPLEX, both the name and the
batch number of the product are recorded, in order to maintain traceability of the batch used.

4. Possible side effects

Like all medicines, UMAN COMPLEX can cause side effects, although not everybody gets them.
manifest.

• Adverse reactions known to be associated with the administration of human prothrombin complex can also occur with UMAN COMPLEX and include: rare cases of allergic or anaphylactic reactions due to hypersensitivity to the infused proteins.
• Insufficient clinical response following the formation of circulating antibodies that inhibit one or more factors of the prothrombin complex.
• Potential risk of thromboembolic events such as embolism and thrombosis (complications due to abnormal production of blood clots), disseminated intravascular coagulation (DIC acquired thrombo-hemorrhagic syndrome) and myocardial infarction.
• In rare cases, pyrexia (fever) has been observed.

For information on viral safety see section 2 “What you need to know before you use UMAN
COMPLEX”.
Reporting of side effects
If you get any side effects, even if 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 UMAN COMPLEX

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 UMAN COMPLEX after the expiry date which is reported on the label and on the box.
The expiry date refers to the last day of the month.
Store in a refrigerator (2  C - 8  C). Do not freeze.
Keep the vial in the box, to protect the medicine from light.
Once the infusion container has been opened, the contents must be used immediately. The
contents of the vial must be used in a single administration.
Do not use UMAN COMPLEX if you notice that the solution is cloudy or has deposits.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to eliminate
medicines that you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What UMAN COMPLEX contains
UMAN COMPLEX is presented as powder and solvent for infusion solution containing human prothrombin complex.
The active substances are contained in the powder vial and are:

• Human plasma coagulation Factor IX (Christmas factor).
• Human plasma coagulation Factor II (prothrombin).
• Human plasma coagulation Factor X (Stuart-Prower factor).

The other components of the powder vial are: sodium chloride, sodium citrate, glycine, heparin,
antithrombin III.
The solvent vial contains water for injections.
The product nominally contains the IU of human coagulation factors as shown in the following
table:

Factor IX titrated according to the International standard.
The total protein content in the vial is  300 mg. The specific activity of the product is greater than 0.6
IU of factor IX/mg of protein.
The powder vial contains factor IX, factor II, factor X of human plasma coagulation, sodium
chloride, sodium citrate, glycine, heparin, antithrombin III.

Description of the appearance of UMAN COMPLEX and contents of the pack
The medicine is presented as a very hygroscopic powder (powder capable of absorbing moisture) or friable
solid, white or slightly colored.
The reconstituted solution is clear or slightly opalescent.
Before administration, the reconstituted solution must be visually checked for the presence of
particles in suspension, or abnormal coloration. Do not use turbid solutions or those with deposits.
The pack of UMAN COMPLEX contains a vial of powder of 500 IU of prothrombin complex, a vial of
solvent of 20 ml with which the solution to be administered is prepared, and a sterile and apyrogenic,
single-use set consisting of a reconstitution device, a syringe for injection and a butterfly needle with
PVC tubing.

MARKETING AUTHORISATION HOLDER
Kedrion S.p.A. - Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca).

MANUFACTURER:
Kedrion S.p.A. - 55027 Bolognana, Gallicano (Lucca).
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The following information is intended exclusively for healthcare professionals:

Warnings and Precautions.
In patients with acquired deficiency of vitamin K-dependent coagulation factors (e.g. if induced
by treatments with vitamin K antagonists), UMAN COMPLEX should be used only when a rapid
correction of prothrombin complex levels is necessary, such as in major bleeding or in emergency
surgery. In other cases, reducing the dose of the vitamin K antagonist and/or administering vitamin K are
usually sufficient.
Patients receiving vitamin K antagonists may have an underlying state of hypercoagulability and
infusion of human prothrombin complex may exacerbate this situation.
In congenital deficiencies of a vitamin K-dependent factor, the specific product should be used if
available.
If hypersensitivity or anaphylactic (allergic) reactions occur, the infusion must be stopped
immediately.
It has been reported that the use of plasma prothrombin complex concentrate is associated with an
increased risk of disseminated intravascular coagulation (DIC acquired thrombo-hemorrhagic syndrome),
thromboembolic complications (abnormal production of blood clots) and myocardial infarction.
Patients receiving plasma prothrombin complex concentrate should be carefully observed for signs or
symptoms of disseminated intravascular coagulation (DIC acquired thrombo-hemorrhagic syndrome) or
thrombosis (abnormal formation of blood clots within the vessels).
Due to the potential risk of thrombotic complications (complications due to abnormal production of blood
clots), clinical surveillance to identify early signs of thrombotic and consumption coagulopathies must be
initiated with appropriate biological tests when this product is administered to patients with a positive
history for coronary artery disease (anatomical or functional alterations of the coronary arteries) or
myocardial infarction, patients with liver disease, post-operative patients, newborns or patients at risk for
thromboembolic phenomena (abnormal production of blood clots) or disseminated intravascular
coagulation (DIC acquired thrombo-hemorrhagic syndrome). In each of these conditions, the potential
benefit of treatment with UMAN COMPLEX must be assessed against the risk of these
complications.

Recommendations for dosage:
Therapeutic ranges must be adapted to the different half-life of the various coagulation factors
of the prothrombin complex. The individual doses required can only be identified on the basis of
regular determinations of individual plasma levels of the coagulation factors involved or on global
analyses of the prothrombin complex levels (prothrombin time, INR), and on continuous monitoring
of the patient's clinical condition.
In the case of major surgery, it is essential to carefully monitor replacement therapy by means of
coagulation analysis (specific coagulation factor dosage and/or global tests for prothrombin complex
levels).
Bleeding and perioperative prophylaxis of bleeding during treatment with vitamin K antagonists:
The dose will depend on the INR before treatment and the INR to be reached. The correction of
hemostasis impairment induced by the vitamin K antagonist persists for approximately 6-8 hours. However,
the effects of vitamin K, if administered simultaneously, are usually achieved within 4-6 hours. Therefore,
repeated treatment with human prothrombin complex is usually not required when vitamin K has
been administered.
Since these recommendations are empirical and recovery and duration of effect may vary, it is
mandatory to monitor the INR during treatment.
Bleeding and perioperative prophylaxis of bleeding in congenital deficiency of some vitamin K-dependent
coagulation factor when the specific coagulation factor product is not
available:
The calculation of the therapeutic dose required is based on the empirical observation that approximately 1 IU
of factor IX per Kg of body weight increases the plasma factor IX activity by 0.01 IU/ml; 1 IU of
factor II or factor X per Kg of body weight increases the activity of factor II or factor X plasma
respectively by 0.02 and 0.017 IU/ml.
The administered dose of a specific factor is expressed in International Units (IU), which are related to
the current standard of the WHO for each factor. The activity of a specific coagulation factor in plasma is
expressed either as a percentage (relative to normal human plasma) or in International Units (relative to an
international standard for the specific coagulation factor).
The activity of one International Unit (IU) of a coagulation factor is equivalent to that of the
amount of factor contained in one milliliter of normal human plasma.
For example, the calculation of the factor X dose required is based on the empirical observation that 1 International
Unit (IU) of factor X per Kg of body weight increases the plasma factor X activity by
0.017 IU/ml.
The necessary dose is determined using the following formula:

Units required = body weight (Kg) x desired increase of factor X (IU/ml) x 60
where 60 (ml/Kg) is the reciprocal of the observed recovery for factor X.
If individual recovery is known, that value must be used for the calculation.

Route of administration
Dissolve the lyophilized powder as described in the following paragraph Instructions for correct use.
The product must be administered intravenously.

Instructions for correct use
It is recommended not to administer doses greater than 100 IU/Kg of body weight per day.
Only injection/infusion devices included in the package must be used. Others may also be
used if they are authorized for use with prothrombin complex-based medicines. Failure of treatment may occur
with unapproved devices because some of the prothrombin complex may remain on the walls of the device.
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 of the powder and solvent vials;
• 4. clean the surfaces of the caps of the two vials with alcohol;
• 5. open the device packaging by removing the top part; be careful not to touch the inside (fig. A);
• 6. do not remove the device from the packaging;
• 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. grasp the edge of the device box and pull it off, freeing the device without touching it (fig. C);
• 9. make sure that the powder vial is positioned on a secure support surface; turn the system over so that the solvent vial is above the device; push the transparent/white 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 foam formation (fig. F).

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

Administration of the solution
The reconstituted medicine must be visually inspected before administration for corpuscles or chromatic
alterations. The solution must 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, connect it to the device and inject the air into the powder vial containing the reconstituted solution (fig. G);
• 2. holding the plunger steady, turn the system over so that the powder vial 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 and free of corpuscles;
• 5. connect 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 and transferred solution into the syringe must be administered immediately.
Unused medicine and waste derived from such medicine 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.

If more UMAN COMPLEX than intended has been administered
The use of high doses of plasma prothrombin complex concentrate has been associated with cases of
myocardial infarction, disseminated intravascular coagulation, venous thrombosis and pulmonary embolism.
Therefore, in
case of overdose, the risk of developing thromboembolic complications or disseminated intravascular
coagulation is increased.
If an accidental overdose of UMAN COMPLEX is administered, immediately warn
the doctor.