Instructions Sterksamic solution for injection 100 mg/ml ampoule 5 ml No. 5
Composition
active ingredient: tranexamic acid;
1 ml of solution contains 100 mg of tranexamic acid;
excipients: water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent colorless solution.
Pharmacotherapeutic group
Antihemorrhagic agents, antifibrinolytic amino acids. Fibrinolysis inhibitors.
ATX code B02A A02.
Pharmacological properties
Pharmacodynamics.
Tranexamic acid exerts its antihemorrhagic effect by inhibiting the fibrinolytic properties of plasmin. A complex is formed between tranexamic acid and plasminogen; tranexamic acid binds to plasminogen during conversion with the participation of plasmin. The effect of the complex of tranexamic acid and plasmin on fibrin activity is lower than the effect of plasmin alone. In vitro studies have shown that high doses of tranexamic acid reduced the activity of this complex.
Pediatric population
Children aged 1 year and older. The scientific literature describes 12 efficacy studies in pediatric cardiac surgery involving 1073 children; of these, 631 patients received tranexamic acid. The condition of most of them was evaluated in comparison with the placebo control group. The study population was heterogeneous in terms of age, type of surgery, dosage. The results of the study of the use of tranexamic acid indicate a decrease in blood loss and a decrease in the need for the use of blood products in pediatric cardiac surgery using artificial circulation (AC) (cardiopulmonary arterial circulation), in operations with a high risk of bleeding, especially in patients with cyanosis (with significant circulatory impairment) or patients undergoing re-operation. It has been found that the most adapted dosage regimen may be as follows:
- first administration (loading dose) - bolus infusion of 10 mg/kg, administered in the period after the initial anesthesia and before the skin incision;
- continuous infusion of 10 mg/kg/h or injection into the SC pump adapter at a dose adjusted for the procedure of the indicated surgical intervention, or at a dose calculated according to the patients' body weight - 10 mg/kg, or into the SC pump adapter and a final injection of 10 mg/kg at the end of the SC surgery.
Some data suggest that continuous infusion is preferable as it will maintain therapeutic plasma concentrations throughout surgery. No specific dose-response studies have been conducted in children.
Pharmacokinetics
Absorption: Peak plasma concentrations of tranexamic acid are reached rapidly after short-term intravenous infusion, after which plasma concentrations begin to decline multiexponentially.
Distribution: At therapeutic plasma levels, the plasma protein binding of tranexamic acid is approximately 3%; the binding is thought to be entirely due to binding to plasminogen. Tranexamic acid does not bind to serum albumin. The initial volume of distribution is approximately 9 to 12 liters.
Tranexamic acid crosses the placental barrier. After intravenous injection of 10 mg/kg in pregnant women, serum concentrations of tranexamic acid range from 10 to 53 μg/ml, while those in cord blood range from 4 to 31 μg/ml. Tranexamic acid rapidly penetrates into synovial fluid and synovial tissue. After intravenous injection of 10 mg/kg in 17 patients undergoing knee surgery, synovial fluid concentrations were similar to those in serum. The values are comparable to those observed in blood (in breast milk about 1/100, in cerebrospinal fluid about 1/10, in intraocular fluid about 1/10). Tranexamic acid has been found in semen, where it inhibits fibrinolytic activity but has little effect on sperm migration (motility).
Excretion. The drug is excreted mainly in the urine as unchanged compound. Urinary excretion via glomerular filtration is the major route of elimination. Renal clearance is approximately equivalent to plasma clearance (110 mL/min to 116 mL/min). Approximately 90% of tranexamic acid is excreted within the first 24 hours after intravenous administration of a dose of 10 mg/kg body weight. The half-life of tranexamic acid is approximately 3 hours.
Special patient groups: Plasma concentrations are increased in patients with renal insufficiency.
No specific pharmacokinetic studies have been conducted in children.
Indication
For the prevention and treatment of bleeding caused by generalized or local fibrinolysis in adults and children aged 1 year and older.
Specific indications include:
- bleeding caused by increased general or local fibrinolysis, such as:
o menorrhagia and metrorrhagia;
o gastrointestinal bleeding;
- use during operations on ENT organs (adenoidectomy, tonsillectomy, dental interventions);
- use during gynecological surgeries or complications in obstetric practice;
- use during thoracic, abdominal and other major surgical interventions, for example in cardiovascular surgery;
- use to control bleeding associated with the administration of a fibrinolytic drug.
Contraindication
Hypersensitivity to the active substance or to any of the excipients.
Acute venous or arterial thrombosis (see section "Special warnings and precautions for use").
Fibrinolytic conditions due to consumption coagulopathy, with the exception of excessive activation of the fibrinolytic system in acute severe bleeding (see section "Special warnings and precautions for use").
Severe renal failure (risk of accumulation).
History of seizures.
Intrathecal and intraventricular injection, intracerebral administration (risk of brain edema with subsequent development of seizures) of the drug are contraindicated.
Interaction with other medicinal products and other types of interactions
Interaction studies have not been conducted.
Concomitant administration with anticoagulants should be carried out under the strict supervision of a physician with appropriate experience.
Patients receiving tranexamic acid should be prescribed drugs that affect hemostasis with caution.
When used concomitantly with estrogens, there is an increased potential for blood clot formation.
The antifibrinolytic effect of tranexamic acid may be inhibited by thrombolytic drugs.
Application features
The indicated indications and the following recommendations should be strictly adhered to:
- intravenous administration should be very slow (maximum 1 ml per minute);
- Tranexamic acid should not be administered intramuscularly.
Convulsions
Cases of convulsions have been reported in association with tranexamic acid treatment. Most of these cases were reported after intravenous administration of high doses of tranexamic acid during coronary artery bypass grafting (CABG). At the recommended low doses of tranexamic acid, the incidence of postoperative convulsions was similar to that in patients not receiving tranexamic acid.
Vision impairment
During treatment with tranexamic acid, attention should be paid to possible visual disturbances, including decreased visual acuity, blurred vision, and color vision impairment. Treatment may need to be discontinued. With continuous long-term use of tranexamic acid, regular ophthalmological examinations should be performed (eye examination, including visual acuity, color vision, fundus examination, and visual field examination). If pathological ophthalmological changes are detected, especially retinal lesions, the doctor, after consultation with a specialist, should decide in each individual case on the need for long-term use of tranexamic acid.
Hematuria
In case of bleeding from the upper urinary tract, there is a risk of urethral obstruction.
Thromboembolic complications
Before using tranexamic acid, risk factors for thromboembolic diseases should be assessed. In patients with a history of thromboembolic diseases or with an increased frequency in the family history (patients at high risk of thrombophilia), tranexamic acid should be used only if there is an absolute medical indication, after consultation with a specialist experienced in hemostasis and under strict medical supervision (see section "Contraindications").
Tranexamic acid should be administered with caution to patients receiving oral contraceptives due to the increased risk of thrombosis (see section "Interaction with other medicinal products and other types of interactions").
Disseminated intravascular coagulation (DIC)
Tranexamic acid is not recommended in most cases for patients with disseminated intravascular coagulation (DIC). The use of tranexamic acid should be restricted to patients with predominantly activated fibrinolytic systems in acute severe bleeding.
Typically, the characteristic hematological profile in these conditions is similar to the following: shortened fibrinolysis time; prolonged prothrombin time; decreased plasma levels of fibrinogen, factors V and VIII, plasminogen fibrinolysin, and alpha-2-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 possibility of using tranexamic acid in DIC should be considered only if there is an adequate hematological laboratory base and accumulated clinical experience.
Use during pregnancy or breastfeeding
Women of reproductive age should use reliable methods of contraception during treatment.
Pregnancy
Although animal studies do not indicate teratogenic effects, the use of tranexamic acid is not recommended during the first trimester of pregnancy.
Limited clinical data on the use of tranexamic acid in various clinical hemorrhagic conditions in the second and third trimesters of pregnancy do not indicate a harmful effect on the fetus.
Tranexamic acid should be used during pregnancy only if the expected benefit to the mother outweighs the potential risks to the mother and fetus.
Lactation
Tranexamic acid passes into breast milk. Breastfeeding is not recommended while using tranexamic acid.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies to assess the effect on the ability to drive or operate other mechanisms have not been conducted.
Method of administration and doses
The use of the drug is strictly limited to slow intravenous administration (injection or infusion).
Adults
Unless otherwise stated, the following doses are recommended.
Standard treatment for local fibrinolysis:
1 g (2 ampoules of 5 ml) of tranexamic acid by slow intravenous injection (approximately 1 ml/min) 2–3 times a day.
Standard treatment for generalized fibrinolysis:
1 g (2 ampoules of 5 ml) of tranexamic acid, equivalent to 15 mg/kg body weight, by slow intravenous injection (approximately 1 ml/min) every 6–8 hours.
Patients with renal impairment
In severe renal impairment, which leads to a risk of accumulation, the use of tranexamic acid is contraindicated (see section "Contraindications"). For patients with mild to moderate renal impairment, the dose of tranexamic acid should be reduced according to the serum creatinine level:
| Serum creatinine | Intravenous dose | Introduction | |
| µmol/l | mg/10 ml | | |
| 120–249 | 1.35–2.82 | 10 mg/kg body weight | Every 12 hours |
| 250–500 | 2.82–5.65 | 10 mg/kg body weight | Every 24 hours |
| > 500 | > 5.65 | 5 mg/kg body weight | Every 24 hours |
Patients with liver dysfunction
No dose adjustment is required for patients with impaired liver function.
Elderly patients
If there are no renal impairment, dose adjustment is not required.
Method of application
The administration has strict restrictions - slow intravenous administration (injection or infusion), no more than 1 ml/min.
The drug can be mixed with electrolyte solutions, amino acids, carbohydrates and dextran solutions.
Heparin can be added to the medicine.
Diluted solutions should be used immediately after dilution.
Tranexamic acid should not be administered intramuscularly.
Intravenous injection. The drug should be administered as a slow bolus over at least 5 minutes.
Intravenous infusion. The drug should be mixed with the following solutions for injection/infusion: sodium chloride 0.9%, Ringer's solution, dextrose solution 5%; dextran-40 in dextrose solution (5%); dextran-40 in 0.9% sodium chloride solution, amino acid solution.
Children
For children aged 1 year and older, the dose is 20 mg/kg/day when used according to the approved indications. However, data on efficacy, safety, and dosing for these indications are limited.
The efficacy, safety and dosage of tranexamic acid in children undergoing cardiac surgery have not been fully established. The limited data available are presented in the Pharmacodynamics section.
Overdose
No cases of overdose have been observed. Signs and symptoms may include dizziness, headache, hypotension and convulsions. Convulsions tend to occur more frequently with increasing dose.
In case of overdose, provide supportive therapy.
Adverse reactions
The table below lists adverse reactions that occurred during clinical trials and in the post-marketing period.
The frequency of adverse reactions is classified as follows: very common (≥ 1/10); common (≥ 1/100, ≥ 1/1000, ≥ 1/10000, ≥ 1/100000,
| Organ systems | Frequency | Adverse reactions |
| Immune system | Frequency unknown | Hypersensitivity reactions, including anaphylaxis |
| Nervous system | Frequency unknown | Convulsions, especially if used incorrectly |
| Organs of vision | Frequency unknown | Visual disturbances, including color vision impairment |
| Vessels | Frequency unknown | General malaise with or without hypotension, loss of consciousness (especially after rapid intravenous administration, in exceptional cases after oral administration) Arterial or venous thromboembolism of any location |
| Gastrointestinal tract | Often | Nausea, vomiting, diarrhea |
| Skin and subcutaneous tissue | Infrequently | Allergic dermatitis |
Reporting adverse reactions after registration of a medicinal product is of great importance. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of a medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ° C. Do not freeze. Keep out of the reach of children.
Incompatibility.
The drug cannot be added to blood for transfusion or to injection solutions containing penicillin drugs.
Packaging
5 ml in an ampoule; 5 ampoules in a blister pack, 1 blister pack in a cardboard box.
Vacation category
According to the recipe.
Producer
Steryl-Jen Life Sciences (P) Ltd.
Location of the manufacturer and address of its place of business.
No. 45, Mangalam Main Road, Villianur Commune, Puducherry, 605110, India.
