Uman Complex D.i. (Lyophilisate) Instructions for Use

ATC Code

B02BD (Blood coagulation factors)

Active Substance

Human prothrombin complex (Ph.Eur. European Pharmacopoeia)

Clinical-Pharmacological Group

Blood clotting factors (II, IX, X) preparation

Pharmacotherapeutic Group

Hemostatic agent

Pharmacological Action

Uman Complex D.I. replenishes the deficiency of coagulation factor IX and corrects hypocoagulation in patients with its deficiency.

The drug is converted into activated factor IXa in the human body and, in combination with factor VIII, activates blood coagulation factor X (Xa), which causes the conversion of prothrombin to thrombin and promotes the formation of a fibrin clot.

The drug increases the level of vitamin K-dependent blood coagulation factors (II, VII, IX, X) in the plasma.

When the level of blood coagulation factor IX falls below 5%, the risk of spontaneous bleeding increases sharply; a blood coagulation factor IX level above 20% provides satisfactory hemostasis.

Immediately after IV administration of the drug, about 30-40% of blood coagulation factor IX is detected in the blood serum, then the hemostatic activity gradually decreases.

Indications

• Treatment and prevention of bleeding in patients with single or multiple deficiency of blood coagulation factor IX (hemophilia B, Christmas disease), blood coagulation factor II (prothrombin deficiency), or X (Stuart-Prower deficiency).
• Treatment and prevention of bleeding in patients with single or multiple acquired deficiency of the prothrombin complex.

ICD codes

Dosage Regimen

Lyophilisate

The doses and duration of replacement therapy depend on the severity of the hemostatic function impairment, the location and volume of bleeding, and the clinical condition of the patient.

The calculation of the required dose is based on empirical data: 1 IU of blood coagulation factor IX per kg of body weight increases the activity of blood coagulation factor IX in the plasma by 0.8%, and 1 IU of blood coagulation factor II increases the activity of factor II or X by 1.5%, respectively.

The required dose is determined by the following formula:

Initial dose = body weight (kg) × required increase in factor IX (%) × 1.2

Special attention should be paid to the fact that in each individual case, when determining the required amount and frequency of administration of the drug, clinical effectiveness should always be taken into account.

In case of bleeding, the activity of blood coagulation factor IX in the corresponding period should not be below the level of activity of the corresponding factor in the blood plasma indicated in the table (% of normal).

In acquired deficiency of prothrombin complex factors, the dose and duration of replacement therapy depend on the severity of the hemostatic function impairment, the location and severity of bleeding, and the clinical condition.

The dosage regimen also depends on the T_1/2 in vivo of the required factor and the patient’s body weight.

To ensure complete control of therapy, as far as possible, blood coagulability should be monitored using coagulation tests.

In case of massive bleeding and before surgeries associated with a high risk of bleeding, it is necessary to administer the prothrombin complex preparation until normal prothrombin time values are obtained.

Preparation and administration of the infusion solution

The solution of Uman Complex D.I. should be prepared immediately before administration. The solution should not be used if it contains flaky or other mechanical inclusions.

The drug is administered intravenously over 3-5 minutes under control of the patient’s pulse.

To prepare the solution, add the solvent to the vial with the lyophilisate through a double-ended needle and rotate the vial until completely dissolved.

The lyophilisate may dissolve faster if the solvent is heated in a water bath to a temperature not exceeding 37°C (98.6°F).

If the drug is not completely dissolved, difficulty may be observed when filtering the drug through the filter needle.

To avoid foaming, the solvent must be slowly poured onto the wall of the vial with the lyophilisate.

After preparing the solution, it must be drawn into a syringe using the supplied filter needle and administered intravenously using the supplied kit.

Adverse Reactions

In rare cases, anaphylactic and allergic reactions to the drug have been observed. Increased body temperature. Formation of antibodies to one or more coagulation factors included in the drug.

Contraindications

• High risk of thrombosis or disseminated intravascular coagulation;
• Hypersensitivity to the components of the drug.

Use with caution in patients with coronary artery disease or a history of myocardial infarction, liver disease, in the postoperative period, in newborns.

Use in Pregnancy and Lactation

Clinical studies on the use of the drug during pregnancy have not established complications. Experimental animal studies are insufficient to assess the effect on reproductive function, embryonic or fetal development, the course of pregnancy, peri- and postnatal development of the child. In this regard, the drug can only be used if the expected benefit for the woman outweighs the possible risk to the fetus and child.

Use in Hepatic Impairment

The drug should be used with caution in liver diseases.

Pediatric Use

The drug should be used with caution in newborns.

Special Precautions

Patients who require a course of treatment with Uman Complex D.I. longer than 3-5 days should be under close observation for the timely detection of symptoms of DIC syndrome.

Experience in the treatment of hereditary deficiency of coagulation factors II and X is limited. Under certain conditions, quantities greater than calculated may be required, especially in the initial dose. In particular, in the case of extensive surgical interventions, it is necessary to establish monitoring of replacement therapy using coagulation tests. For long-term prevention of bleeding in patients with severe hemophilia B, initial doses may be 10-20 IU of coagulation factor IX per 1 kg of body weight.

Uman Complex D.I. is made from human plasma. When using plasma or products made from human plasma, the transmission of infectious agents, including those still unknown, cannot be completely excluded. To reduce the risk of transmission, careful selection of donors and harvested plasma is carried out through special testing (control of each plasma unit used for the production of the drug for the absence of HIV type 1 and 2, HbsAg, antibodies to hepatitis C virus and ALT activity; in addition, each plasma pool is tested by polymerase chain reaction for the detection of hepatitis C virus genome). In addition to testing, the production process includes measures for double virus inactivation (solvent-detergent method and heat treatment at 100°C (212°F) for 30 minutes).

If necessary, in the absence of a concentrate of blood coagulation factor IX, Uman Complex D.I. can be administered to patients with hemophilia B.

If anaphylactic reactions occur, the administration of the drug must be stopped immediately.

It is necessary to carefully monitor the patient’s condition to identify symptoms of disseminated intravascular coagulation.

Overdose

The use of high doses of human prothrombin complex concentrate can lead to myocardial infarction, DIC syndrome, venous thrombosis and pulmonary embolism. The risk group consists of patients predisposed to the listed diseases.

Drug Interactions

Uman Complex D.I. should not be mixed with other drugs.

Only approved equipment should be used for the administration of the drug, as the use of other equipment may lead to a decrease in the effectiveness of therapy due to the deposition of the drug on the internal surfaces of some medical devices for intravenous administration.

Storage Conditions

List B. The drug should be stored at a temperature of 2°-8°C (35.6°-46.4°F) in a place protected from light. Do not freeze. Do not use after the expiration date. After preparation, the solution must be used immediately. Keep out of reach of children.

Shelf Life

The shelf life is 2 years if all storage conditions are met in undamaged packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.