Tranexamic acid-zdorovya

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TRANEXAMIC ACID-ZDOROVYE (TRANEXAMIC ACID-ZDOROVYE)

Composition:

active substance: tranexamic acid;

1 ml of the preparation contains 50 mg of tranexamic acid;

excipient: water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless or almost colorless solution.

Pharmacotherapeutic group. Antihemorrhagic agents. Fibrinolysis inhibitors. Amino acids. ATC code B02A A02.

Pharmacological Properties.

Pharmacodynamics.

Tranexamic acid exerts an antihemorrhagic effect by inhibiting the fibrinolytic activity of plasmin.

Tranexamic acid forms a complex with plasminogen; it binds to plasminogen during its conversion to plasmin.

The activity of the tranexamic acid–plasmin complex toward fibrin is lower than that of free plasmin.

High doses of tranexamic acid have been shown to reduce complement activity.

Children from 1 year of age. Data are available showing reduced blood loss and decreased need for blood products in pediatric cardiac surgery with cardiopulmonary bypass, where there is a high risk of bleeding, especially in cyanotic patients or those undergoing repeat surgical procedures. The following dosing regimen has been found to be most appropriate:

• Initial bolus dose of 10 mg/kg after induction of anesthesia and before skin incision;
• Continuous infusion of 10 mg/kg/hour or injection into the cardiopulmonary bypass circuit priming fluid at a dose corresponding to the cardiopulmonary bypass procedure or according to patient body weight at 10 mg/kg, or according to the priming volume of the cardiopulmonary bypass circuit, with the final dose of 10 mg/kg administered at the end of the cardiopulmonary bypass procedure.

Limited data suggest that continuous administration is the most suitable approach, as it maintains a therapeutic plasma concentration throughout the entire surgical procedure.

No specific dose-dependent studies have been conducted in children.

Pharmacokinetics.

Absorption. Maximum plasma concentration of tranexamic acid is rapidly achieved after short intravenous administration, after which it declines in a multiexponential manner.

Distribution. Plasma protein binding of tranexamic acid at therapeutic plasma levels is approximately 3%, likely due to its binding to plasminogen. Tranexamic acid does not bind to serum albumin. The initial volume of distribution is approximately 9–12 liters.

Tranexamic acid crosses the placental barrier. After intravenous administration at a dose of 10 mg/kg to pregnant women, serum concentrations ranged from 10–53 μg/mL and cord blood concentrations ranged from 4–31 μg/mL. Tranexamic acid rapidly penetrates into synovial fluid and synovial membrane. After intravenous administration of 10 mg/kg in patients undergoing knee surgery, the concentration in synovial fluid was similar to that observed in corresponding serum samples. Tranexamic acid concentrations in other tissues as a fraction of blood concentration are as follows: in breast milk — approximately 1/100, in cerebrospinal fluid — approximately 1/10, in intraocular fluid — approximately 1/10. Tranexamic acid has been detected in seminal fluid, where it inhibits fibrinolytic activity without affecting spermatozoa migration.

Elimination. It is primarily excreted unchanged in urine. Renal excretion via glomerular filtration is the main elimination pathway. Renal clearance equals plasma clearance (110–116 mL/min). Approximately 90% of tranexamic acid is excreted in urine within the first 24 hours after intravenous administration of a 10 mg/kg body weight dose. The elimination half-life of tranexamic acid is approximately 3 hours.

Special populations. Plasma concentration increases in patients with renal impairment.
Pharmacokinetic studies in children have not been conducted separately.

Clinical characteristics.

Indications.

Prevention and treatment of bleeding caused by generalized or local fibrinolysis in adults and children aged 1 year and older, including:

• menorrhagia and metrorrhagia;
• gastrointestinal bleeding;
• bleeding from urinary tract disorders, following prostate surgery or surgical procedures on the urinary tract;
• surgery on ENT organs (adenoidectomy, tonsillectomy, tooth extraction);
• gynecological surgery or complications in obstetric practice;
• surgery on the organs of the thoracic and abdominal cavities and other major surgical interventions, including cardiovascular surgery;
• hemorrhagic complications of fibrinolytic therapy.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Acute venous or arterial thrombosis.

Fibrinolytic states as a result of coagulopathy, except for cases with predominant activation of the fibrinolytic system during acute severe bleeding.

Severe renal insufficiency (risk of accumulation).

History of seizures.

Intrathecal and intraventricular injection of the drug, intracerebral administration (risk of cerebral edema and seizures).

Interaction with other medicinal products and other types of interactions.

Interaction studies have not been conducted. Concomitant use with anticoagulants should be performed under strict supervision of a physician experienced in this field. Medicinal products affecting hemostasis should be prescribed cautiously to patients receiving tranexamic acid. There is a theoretical risk of increased thrombotic potential when used with estrogens. The antifibrinolytic effect of the drug may be inhibited by thrombolytics.

Tranexamic acid can be mixed with most infusion solutions, such as electrolyte solutions, carbohydrates, amino acids, and dextrans. Heparin can be added to the injectable solution of tranexamic acid.

Special precautions for use.

The following recommendations should be strictly observed:

• Intravenous injections should be administered very slowly;
• Tranexamic acid must not be administered intramuscularly.

Seizures
Seizures have been reported in association with tranexamic acid treatment. Most of these cases were reported after intravenous administration of high-dose tranexamic acid during coronary artery bypass graft surgery. When recommended low doses of tranexamic acid are used, the incidence of postoperative seizures is similar to that in patients not receiving tranexamic acid.

Visual disturbances

Visual disorders, including decreased visual acuity, blurred vision, and color vision disturbances, may occur during treatment with this drug. If such symptoms occur, treatment should be discontinued. Regular ophthalmological examinations (including assessment of visual acuity, color vision, fundus, and visual fields) are recommended during continuous long-term use of tranexamic acid injection solution. If pathological ophthalmological changes are present, especially retinal disorders, the physician should determine the necessity of continued long-term use of tranexamic acid injection solution on an individual basis after consultation with a specialist.

Hematuria
In cases of hematuria originating from the upper urinary tract, there is a risk of urethral obstruction.

Thromboembolic complications

Before administering tranexamic acid, risk factors for thromboembolic complications should be considered. Tranexamic acid injection solution should be prescribed to patients with a history of thromboembolic disorders or with increased familial incidence (patients at high risk of thrombophilia) only when there is a strict medical indication, after consultation with a specialist in hemostasis, and under strict medical supervision (see section "Contraindications").

Due to the increased risk of thrombosis, the drug should be prescribed with caution to patients taking oral contraceptives (see section "Interaction with other medicinal products and other forms of interaction").

Disseminated intravascular coagulation (DIC)

Patients with DIC generally should not receive this drug. The use of tranexamic acid should be limited to patients with predominant activation of the fibrinolytic system in cases of acute severe hemorrhage.

Typically, the hematological profile is characterized as follows: shortened euglobulin fibrinolysis time; prolonged prothrombin time; decreased plasma levels of fibrinogen, factors V and VIII, plasminogen, fibrinolysin, and α2-macroglobulin; normal plasma levels of P and P-complex, i.e., factors II (prothrombin), VIII, and X; elevated plasma levels of fibrinogen degradation products; normal platelet count. The above assumes that the underlying pathological condition does not alter the various parameters of this profile. In such acute cases, a single dose of 1 g of tranexamic acid is usually sufficient to stop bleeding. The use of tranexamic acid in DIC should be considered only if hematological laboratory facilities and expertise are available.

Use during pregnancy or breastfeeding.

Women of reproductive age should use a reliable method of contraception during treatment.

There are insufficient clinical data on the use of tranexamic acid in pregnant women.
Although animal studies do not indicate teratogenic effects, the drug is not recommended during the first trimester of pregnancy.

Limited clinical data on the use of tranexamic acid in various clinical hemorrhagic conditions during the second and third trimesters have not demonstrated harmful effects on the fetus. Tranexamic acid should be used during pregnancy only when the expected benefit to the mother outweighs the potential risk to the fetus.

Tranexamic acid passes into breast milk; therefore, breastfeeding is not recommended.

Ability to affect reaction speed when driving or operating machinery.

Studies on the effect on the ability to drive or operate machinery have not been conducted.

Administration and Dosage

The route of administration is strictly limited to slow intravenous injection.

Adults.
Unless otherwise indicated, the following doses are recommended:

Standard treatment for local fibrinolysis:

0.5 g (2 vials) to 1 g (4 vials) of tranexamic acid administered by slow intravenous injection (= 1 mL/min) two or three times daily.

Standard treatment for generalized fibrinolysis:

1 g (4 vials) of tranexamic acid administered by slow intravenous injection (= 1 mL/min) every 6–8 hours, equivalent to 15 mg/kg body weight.

Renal impairment.

The use of tranexamic acid is contraindicated in patients with severe renal impairment (see section "Contraindications"). For patients with mild or moderate renal impairment, the dosage of tranexamic acid should be reduced according to serum creatinine levels:

Hepatic impairment.

Dose adjustment is not required in patients with hepatic impairment.

Elderly patients.

Dose reduction is not necessary in the absence of renal impairment.

Children.

For children aged 1 year and older, the dose is 20 mg/kg/day. Data on efficacy, dosing, and safety are limited.

The efficacy, dosing, and safety of tranexamic acid in children who have undergone cardiac surgery have not been fully established.

Overdose.

No cases of overdose have been reported.

Signs and symptoms may include dizziness, headache, arterial hypotension, and seizures. Seizures usually occur more frequently with increasing doses.

In case of overdose, supportive therapy should be administered.

Adverse reactions.

The adverse reactions are listed in the table below according to system organ class and frequency of occurrence. Within each frequency group, adverse reactions are presented in order of decreasing severity.

Reporting of adverse reactions following the registration of the medicinal product is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of effectiveness of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze. Keep out of reach and sight of children.

Incompatibility.

This medicinal product must not be added to blood for transfusion or to injectable solutions of penicillin.

Packaging.

5 ml in a vial; 5 or 10 vials per carton; 5 vials in a blister, 1 or 2 blisters of 5 vials per carton.

Prescription status. Prescription only.

Manufacturer.

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Location of manufacturer and address of its place of business.

22 Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.