Instructions Hemotran solution for injection 100 mg/ml ampoule 10 ml No. 5
Composition
active ingredient: tranexamic acid;
1 ml of solution contains tranexamic acid, calculated as 100% dry matter, 50 mg or 100 mg;
excipient: water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent colorless or light brown solution.
Pharmacotherapeutic group
Antihemorrhagic agents. 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 blood products in pediatric cardiac surgery when using artificial circulation (AC) (cardiopulmonary artificial circulation) during operations with a high risk of bleeding, especially in “cyanotic” (with significant circulatory disorders) patients 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 pump adapter of the artificial circulation system 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 pump adapter of the artificial circulation system and a final injection at a dose of 10 mg/kg at the end of the surgical intervention using SC.
Some data suggest that continuous infusion is preferable as it will maintain therapeutic plasma concentrations throughout surgery. No specific dose-response or pharmacokinetic 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 placenta. 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 patients undergoing knee surgery, synovial fluid concentrations were similar to those in serum. Tranexamic acid concentrations in a number of other tissues and fluids are comparable to those observed in blood (one hundredth of one in breast milk, one tenth in cerebrospinal fluid, and one tenth in aqueous humor). 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 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
Bleeding or risk of bleeding with increased fibrinolysis, both generalized and local, in adults and children aged 1 year and over.
- menorrhagia and metrorrhagia;
- gastrointestinal bleeding;
- 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;
- otolaryngological (adenoid removal, tonsillectomy) and dental (tooth extraction) surgical interventions;
- gynecological surgeries or complications in obstetric practice;
- thoracic, abdominal and other major surgical interventions, such as cardiovascular surgery;
- control of bleeding associated with the administration of a fibrinolytic drug.
Contraindication
Hypersensitivity to the active substance or to any of the components of the drug. Acute venous or arterial thrombosis. Fibrinolytic conditions due to consumption coagulopathy, except for conditions with excessive activation of the fibrinolytic system in acute severe bleeding. Severe renal failure (there is a risk of drug accumulation). History of seizures. Intrathecal and intraventricular injection, intracerebral administration (risk of brain edema with subsequent development of seizures).
Interaction with other medicinal products and other types of interactions
Drug interaction studies have not been conducted. Concomitant (simultaneous) administration of anticoagulants should be under the strict supervision of a physician experienced in this area of therapy. Drugs that affect hemostasis should be used with caution in patients treated with tranexamic acid. In such cases, there is a risk of thrombosis, for example, when estrogens are used. In addition, the antifibrinolytic effect of the drug may be antagonized by thrombolytics. Heparins may be added to intravenous drip administration.
Application features
The following indications and method of application should be strictly adhered to:
- intravenous injections should be given very slowly;
- Tranexamic acid should not be administered intramuscularly.
Convulsions: Convulsions have been reported in patients treated with tranexamic acid. In coronary artery bypass grafting (CABG) surgery, most of these cases were reported after high-dose intravenous tranexamic acid. When using the recommended low doses of tranexamic acid, the incidence of postoperative seizures was similar to that in patients not treated with this drug.
Visual impairment: attention should be paid to possible ophthalmological complications, including visual impairment, visual impairment, color vision impairment. In these cases, treatment should be discontinued. With continuous long-term use of tranexamic acid (injection), regular ophthalmological examinations should be prescribed (including checking visual acuity, color vision, fundus, visual field, etc.). In the presence and occurrence of pathological ophthalmological changes associated in particular with retinal diseases, after appropriate specialist consultation, the doctor should decide on the need and possibility of long-term use of tranexamic acid (injection) in each individual case individually.
Hematuria: In the case of hematuria involving the upper urinary tract, there may be a risk of urethral obstruction.
Thromboembolic complications: Before prescribing tranexamic acid, risk factors for thromboembolic complications should be considered. In patients with a history of thromboembolic diseases and patients with a family history of thromboembolic complications (patients with high risk of thrombophilia), tranexamic acid (solution for injection) should be administered only in cases where there are direct vital indications, and treatment should be initiated after consultation with a specialist experienced in hemostasis and carried out under strict medical supervision.
Disseminated intravascular coagulation syndrome (DIC): Patients with DIC should not normally be treated with tranexamic acid. If tranexamic acid is required, it should be used only in the presence of predominant activation of the fibrinolytic system with acute severe bleeding. The characteristic haematological profile in these conditions has been shown to be approximately the following: euglobulin clot lysis time is reduced; prothrombin time is prolonged; plasma levels of fibrinogen, factors V and VIII, plasminogen, fibrinolysin and alpha-2 macroglobulin are reduced; plasma levels of P and P-complex are normal; i.e. factors II (prothrombin), VIII and X are increased; plasma levels of fibrinogen breakdown products are increased; platelet count is normal. This suggests that the presence of an underlying disease state does not necessarily alter the various elements of this profile. In such acute cases, a single dose of 1 g of tranexamic acid is often sufficient to stop bleeding. The use of tranexamic acid in a patient with DIC should only be considered when an adequate hematological laboratory basis and accumulated clinical experience are available.
Use during pregnancy or breastfeeding
Women of childbearing potential should use effective contraception during treatment.
There are insufficient clinical data on the use of tranexamic acid in pregnant women.
During the first trimester of pregnancy, the administration of tranexamic acid is not recommended as a precautionary measure.
There are only limited clinical data on the use of tranexamic acid in various clinical hemorrhagic conditions during the second and third trimesters of pregnancy, from which it is not possible to identify a harmful effect on the fetus. Tranexamic acid should be used during pregnancy only if the expected therapeutic benefit justifies the potential risk.
Tranexamic acid is excreted in breast milk. Therefore, breastfeeding is not recommended.
There are no clinical data on the effect of tranexamic acid on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
There are no studies assessing the effect on the ability to drive vehicles or other mechanisms.
Method of administration and doses
Hemotran® should be administered intravenously (drip, jet).
Adults.
For local fibrinolysis, it is recommended to use the drug starting at a dose of 500 mg to 1 g intravenously slowly (approximately 1 ml/min) 2–3 times a day.
In case of generalized fibrinolysis, tranexamic acid should be administered intravenously, slowly, at a dose of 1 g or 15 mg/kg of body weight every 6–8 hours, at a rate of 1 ml/min.
Dosage for patients with renal impairment. In renal failure, the use of tranexamic acid is contraindicated in patients with severe renal failure. For patients with mild or moderate renal failure, the dosage of tranexamic acid should be reduced according to serum creatinine levels:
Table 1
| Serum creatinine | Dose (intravenous) | Introduction |
| µmol/l | mg/10 ml |
| 120 – 249 | 1.35 – 2.82 | 10 mg/kg | Every 12 hours |
| 250 – 500 | 2.82 – 5.65 | 10 mg/kg | Every 24 hours |
| > 500 | > 5.65 | 5 mg/kg | Every 24 hours |
Dosage for patients with hepatic impairment: No dosage adjustment is required for patients with hepatic impairment.
Application to children.
For children over 1 year of age, use as indicated (see section "Indications"), dosage - about 20 mg/kg/day. However, data on efficacy, safety, and dosage characteristics when used in children for these indications are limited.
The efficacy, dosage, and safety aspects of tranexamic acid in children undergoing heart surgery have not been fully studied.
Use in elderly patients: Usually, dose adjustment is not required unless there is evidence of renal insufficiency.
Method of application
The administration has a strictly limited regimen – slow intravenous administration (injection/infusion).
Children.
The maximum single dose for children over 1 year of age is 10 mg/kg body weight. The maximum daily dose is 20 mg/kg body weight.
Overdose
No cases of overdose were observed.
Symptoms of overdose may include dizziness, headache, hypotension, and seizures (convulsions). It has also been shown that seizures tend to occur more frequently with increasing doses.
Treatment of overdose is symptomatic.
Adverse reactions
Adverse reactions are listed below, classified according to MedDRA system organ class (main organ system classes). Within each system organ class, adverse reactions are ranked by frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency has been defined as follows: very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1000 to < 1/100), not known (cannot be estimated from the available data).
Table 2
MedDRA class
(systems and organs)
Frequency | Undesirable effects |
| On the part of the immune system | Unknown | Hypersensitivity reactions, including anaphylactic-type reactions |
| From the nervous system | Unknown | Convulsions, particularly if used incorrectly |
| From the organs of vision | Unknown | Visual impairment, including color vision impairment |
| Blood and lymphatic system disorders | Unknown | Malaise caused by hypotension, with or without loss of consciousness (usually after too rapid intravenous injection, as an exception - after oral administration). Arterial or venous thromboembolism of any location |
| From the digestive system | Often | Diarrhea, vomiting, nausea |
| Skin and subcutaneous tissue diseases | Infrequently | Allergic dermatitis |
Expiration date
2 years.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Incompatibility.
Tranexamic acid for injection should not be added to blood for transfusion or to injectable solutions containing penicillin drugs.
Packaging
For dosage 50 mg/ml: 5 ml or 10 ml in an ampoule; 5 ampoules in a blister; 1 or 2 blisters in a pack.
For dosage 100 mg/ml: 5 ml or 10 ml in an ampoule; 5 ampoules in a blister; 1 or 2 blisters in a pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Location of the manufacturer and its business address.
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
