Instructions Tranexamic acid-Zdorovye solution for injection 100 mg/ml ampoule 5 ml No. 5
Composition
active ingredient: tranexamic acid;
1 ml of the drug contains tranexamic acid 100 mg;
excipient: water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent colorless or almost 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 tranexamic acid-plasmin complex on fibrin activity is lower than the effect of plasmin alone.
In vitro research data showed that high doses of tranexamic acid reduced the activity of the indicated complex.
Pediatric population: Children aged 1 year and over
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 a placebo control group. The study population was heterogeneous in terms of age, type of surgery and dosage. The results of the study of tranexamic acid indicate a decrease in blood loss and a decrease in the need for blood products in pediatric cardiac surgery using artificial blood circulation (AC) (cardiopulmonary AC) during operations with a high risk of bleeding, especially in patients with cyanosis or patients undergoing reoperation. It was 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 initial anesthesia and before 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 patient's body weight – 10 mg/kg, or injection into the SC pump adapter and a final injection at a dose 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: The maximum plasma concentration of tranexamic acid (Cmax) is 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 synovial fluid and synovial tissue. After intravenous injection of 10 mg/kg in patients undergoing knee surgery, synovial fluid concentrations were similar to those in serum. Tranexamic acid concentrations in some other tissues and fluids are comparable to those observed in blood (breast milk approximately 1/100, cerebrospinal fluid approximately 1/10, and intraocular fluid approximately 1/10). Tranexamic acid has been found in seminal fluid, 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 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
Prevention and treatment of bleeding due to 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:
· menorrhagia and metrorrhagia;
· hemorrhagic disorders of the urinary tract that have arisen in connection with surgical intervention on the prostate gland or as a result of surgical intervention or procedures on the urinary tract;
– operations in the area of ENT organs (adenoidectomy, tonsillectomy, tooth extraction);
− gynecological surgeries or complications in obstetric practice;
− thoracic, abdominal and other major surgical interventions, such as cardiovascular surgery;
− control of hemorrhages associated with the administration of fibrinolytic drugs.
Contraindication
– Hypersensitivity to the active substance or to any of the excipients of the medicinal product;
– acute venous or arterial thrombosis (see section “Special warnings and precautions for use”);
– fibrinolytic states after coagulopathy due to exhaustion, with the exception of excessive activation of the fibrinolytic system in acute severe bleeding (see section “Special instructions for use”);
– severe renal failure (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 administration with anticoagulants should be carried out under the strict supervision of a physician experienced in this field.
Drugs that affect hemostasis should be administered with caution 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.
Application features
The following recommendations should be strictly followed:
• intravenous injections should be given very slowly;
• Tranexamic acid should not be administered intramuscularly.
Convulsions Convulsions have been reported in association with tranexamic acid treatment. Most of these cases were reported following intravenous injection of high doses of tranexamic acid during coronary artery bypass grafting (CABG). The incidence of postoperative seizures was similar to that in patients not receiving tranexamic acid at the recommended low doses.
Vision impairment
When using the drug, visual disturbances are possible, including decreased visual acuity, blurred vision, and color vision impairment. If necessary, treatment should be discontinued. With continuous long-term use of tranexamic acid injection solution, regular ophthalmological examinations are recommended (eye examination, including visual acuity, color vision, fundus examination, and visual field). In the presence of pathological ophthalmological changes, especially in retinal lesions, the doctor, after consultation with a specialist, should determine the need for long-term use of tranexamic acid injection solution in each individual case.
Hematuria In case of hematuria from the upper urinary tract, there is a risk of urethral obstruction.
Thromboembolic complications
Before using tranexamic acid, it is necessary to consider the risk factors for thromboembolic complications. In patients with a history of thromboembolic diseases or with an increased frequency in the family history (patients with high risk of thrombophilia), tranexamic acid solution for injection should be prescribed only when there is a strict medical indication, after consultation with a specialist experienced 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 using oral contraceptives (see section "Interaction with other medicinal products and other types of interactions").
Disseminated intravascular coagulation
Patients with disseminated intravascular coagulation (DIC) should not use the drug in most cases (see section "Contraindications"). The use of tranexamic acid should be limited in patients with predominant activation of the fibrinolytic system in acute severe bleeding.
Typically, the hematological profile approximates the following: 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.
This assumes that the underlying pathological condition does not alter the various parameters of this profile. In such acute cases, a single dose of tranexamic acid 1 g is usually sufficient to stop the bleeding. The use of tranexamic acid in DIC should only be considered if haematological laboratory facilities and expertise are available.
Use during pregnancy or breastfeeding
Women of reproductive age
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 a teratogenic effect, the drug is not recommended for use 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 any harmful effects on the fetus. Tranexamic acid should be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.
Breastfeeding period
Tranexamic acid passes into breast milk, so breastfeeding is not recommended.
Fertility
There are no clinical data on the effect of tranexamic acid on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effect on the ability to drive vehicles and other mechanisms have not been conducted.
Method of administration and doses
The method of administration is strictly limited to slow intravenous injection or infusion.
Adults: Unless otherwise prescribed, the following doses are recommended:
Standard treatment for local fibrinolysis:
0.5 g to 1 g of tranexamic acid should be administered by slow intravenous injection or infusion (= 1 ml/min) 2 or 3 times daily.
Standard treatment for generalized fibrinolysis:
1 g of tranexamic acid should be administered by slow intravenous injection or infusion (= 1 ml/min) every 6–8 hours, equivalent to 15 mg/kg body weight.
Kidney failure.
Tranexamic acid is contraindicated in patients with severe renal impairment (see Contraindications). For patients with mild or moderate renal impairment, the dosage of tranexamic acid should be reduced according to serum creatinine levels:
| 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 |
Liver failure.
No dose adjustment is required for patients with hepatic impairment.
Elderly patients.
Dose reduction is not necessary in the absence of renal insufficiency.
Children.
For children aged 1 year and older, use according to the currently approved therapeutic indications as described in the Indications section is recommended, with a dosage of approximately 20 mg/kg/day. Data on efficacy, dosage and safety are limited.
The efficacy, dosage, and safety of tranexamic acid in children undergoing cardiac surgery have not been fully established.
Overdose
No cases of overdose have been reported.
Signs and symptoms may include dizziness, headache, hypotension, and convulsions. Convulsions usually occur more frequently with increasing dose.
In case of overdose, supportive therapy is provided.
Adverse reactions
Adverse reactions are listed in the table below by system organ class and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
| Classification by organ systems | often (> 1/100, | infrequently (> 1/1000, | frequency unknown (cannot be estimated from the available data) |
| On the part of the immune system | Hypersensitivity reactions, including anaphylaxis | | |
| From the nervous system | Convulsions, especially in cases of misuse | | |
| From the organs of vision | Visual disturbances, including color vision impairment | | |
| Cardiovascular system | Malaise caused by hypotension with or without loss of consciousness (usually after too rapid intravenous injection, exclusively after oral administration); arterial or venous thromboembolism of any location | | |
| From the digestive system | Diarrhea, vomiting, nausea | | |
| Skin and subcutaneous tissue disorders | Allergic dermatitis | | |
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.
This medicine should not be added to blood for transfusion or to injectable penicillin solutions.
Packaging
5 ml in ampoules No. 5 (5×1), No. 10 (5×2) in blisters in a cardboard box, No. 5, No. 10 in a cardboard box.
Vacation category
According to the recipe.
Producer
Limited Liability Company "Pharmaceutical Company "Zdorovya".
Address
Ukraine, 61013, Kharkiv region, Kharkiv city, Shevchenko street, building 22.
