Identified the need to bring instructions for use in accordance with the following requirements:
1. bring the section "Indications for use" in the following edition:
"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 after surgical interventions on the prostate and urinary tract;
- bleeding during surgical interventions in the nasal cavity, mouth and pharynx (adenoidectomy, tonsillectomy, tooth extraction);
- bleeding with thoracic, abdominal and other extensive surgical interventions (including cardiosurgery operations);
- obstetric-gynecological bleeding (including bleeding during gynecological operations);
- bleeding caused by the use of fibrinolytic drugs ";
2. to bring the section "Contraindications" in the following edition:
- Hypersensitivity to tranexamic acid or other components of the drug;
- Severe chronic renal failure (glomerular filtration rate [GFR] less than 30 mg / ml / 1.73 m2) due to the risk of cumulation;
- Venous or arterial thrombosis at present or in the anamnesis (thrombosis of deep veins of legs, pulmonary embolism, thrombosis of intracranial vessels, etc.) with the impossibility of simultaneous therapy with anticoagulants;
- Fibrinolysis due to consumption coagulopathy (hypocoagulation stage of disseminated intravascular coagulation syndrome [DVS-syndrome]);
- Seizures in the anamnesis;
- Acquired violation of color vision;
- Subarachnoid hemorrhage (due to the risk of developing cerebral edema, ischemia and cerebral infarction);
- Treatment of menorrhagia in patients under the age of 16 years (no experience of use);
- Children under 1 year of age (no experience of use) ";
3. bring the section "With caution" in the following edition:
"Tranexamic acid should be used with caution in the following situations:
- Hematuria caused by diseases of the kidney parenchyma, and bleeding from the upper urinary tract (risk of secondary mechanical obstruction of the urinary tract with a clot of blood with the development of anuria) (See section "Special instructions");
- Patients with a high risk of thrombosis (history of thromboembolic events or family history of thromboembolic disease, verified diagnosis of thrombophilia);
- Syndrome of disseminated intravascular coagulation [DVS-syndrome]);
- The presence of blood in the cavities, for example, in the pleural cavity, cavities of the joints and urinary tract;
- Patients receiving anticoagulant therapy (limited experience);
- Simultaneous use of preparations of coagulation factors II, VII, IX and X in combination [prothrombin complex] or anti-inhibitory coagulant complex (See section "Interaction with other drugs");
- Patients taking combined oral contraceptives (due to an increased risk of venous thromboembolic complications and arterial thrombosis) (See section "Interaction with Other Drugs");
4. to bring the section "Application during pregnancy and during breast-feeding" in the following edition:
"In preclinical studies tranexamic acid had no teratogenic effect. Adequate and strictly controlled studies of the efficacy and safety of the use of tranexamic acid preparations in pregnant women have not been conducted. Tranexamic acid penetrates the placenta and can be contained in cord blood in a concentration close to the mother's.
Because studies of reproductive function in animals do not always allow predicting reactions in humans, tranexamic acid should be used during pregnancy only in case of emergency.
Tranexamic acid penetrates into breast milk (the concentration of the drug in milk is about 1% of the concentration in the blood plasma of the mother). The development of antifibrinolytic effect in an infant is unlikely. Nevertheless, caution should be exercised when using tranexamic acid in nursing mothers. ";
5. Give the section "Method of administration and dose" in the following edition: "Intravenous drip or jet slowly, rate of administration of 1 ml / min (50 mg / min).You should avoid rapid intravenous injection!
Adult patients:
- Menorrhagia and metrorrhagia, gastrointestinal bleeding: 500 mg (1
ampulla 5.0 ml) 2-3 times a day from the moment of development of bleeding to its stop;
- Treatment of bleeding after surgical interventions on the prostate and urinary tract: 1000 mg (2 ampoules 5.0 ml) 3 times a day from the moment of development of bleeding to its stop;
- Prevention and treatment of bleeding during surgery in the nasal cavity, mouth and pharynx: 10-15 mg / kg body weight every 6-8 hours until bleeding stops.
- Prevention and treatment of bleeding during thoracic, abdominal and other large surgical interventions: 15 mg / kg body weight every 6-8 hours until bleeding stops.
- Prophylaxis and treatment of bleeding during cardiosurgery operations: a loading dose of 15 mg / kg after the induction of anesthesia prior to the onset of surgery, then intravenous infusion at a rate of 4.5 mg / kg / hour throughout the operation; it is recommended to administer tranexamic acid in a dose of 0.6 mg / kg in an artificial circulation device.
- Treatment of obstetric-gynecological bleeding (including bleeding during gynecological operations). 15 mg / kg body weight every 6-8 hours from the time of bleeding to its stop;
- Treatment of bleeding caused by the use of fibrinolytic drugs: 10 mg / kg body weight every 6-8 hours from the time of bleeding to its stop.
In case of long (more than 48 hours) long-term haemostatic therapy, the use of tranexamic acid preparations in the tablet dosage form is recommended.
Children over 1 year old:
The experience of using tranexamic acid drugs in children is limited. The recommended dose of the drug for treatment of bleeding caused by local and generalized fibrinolysis is 20 mg / kg / day.
Use of the drug in specific patient groups
Impaired renal function
In patients with mild and moderate impairment of the excretory function of the kidneys
it is necessary to correct the dose and the frequency of administration of tranexamic acid:
| Concentration of serum creatinine | Glomerular filtration rate (GFR) | The dose of tranexamic acid | Multiplicity admission |
| 120-249 μmol / L (1.36-2.82 mg / dl) | 60 - 89 ml / min / 1.73 m2 | 15 mg / kg body weight | 2 times a day |
| 250-500 μmol / L (2.83-5.66 mg / dl) | 30 - 59 ml / min / 1.73 m2 | 15 mg / kg body weight | 1 time per day |
Impaired liver function
In patients with impaired liver function, dose adjustment is not required.
Elderly age
In elderly patients, in the absence of renal failure, dose adjustment is not required ";
6. bring the section "Side effect" in the following edition:
"The incidence of adverse drug reactions is determined according to the WHO classification: very often (> 1/10), often (> 1/100, ≤ 1/10), infrequently (> 1/1000, ≤ 1/100), rarely > 1/10000, ≤ 1/1000), very rarely (less than 1/10000), the frequency is unknown (can not be determined from available data).
Disorders from the gastrointestinal tract: often - nausea, vomiting, diarrhea (symptoms go away with a decrease in dose);
Disturbances from the skin and subcutaneous tissues: rarely - skin allergic reactions, incl. allergic dermatitis.
Disturbances on the part of the organ of sight: rarely - visual impairment, incl. violation of color perception, thrombosis of the retina.
Vascular disorders: rarely - thromboembolic complications, marked decrease in blood pressure (usually due to excessively rapid intravenous administration); very rarely - arterial and venous thrombosis of different localization;
frequency is unknown - acute myocardial infarction, cerebral artery thrombosis, carotid thrombosis, stroke, deep vein thrombosis of the legs, pulmonary embolism, renal artery thrombosis with cortical necrosis and acute renal failure, coronary artery bypass graft occlusion, central artery thrombosis and retinal veins).
Immune system disorders: very rarely - hypersensitivity reactions, incl. anaphylactic shock.
Disturbances from the nervous system: rarely - dizziness; convulsions (usually with intravenous administration). "
7. bring the section "Overdose" in the following edition:
"There are limited data on cases of overdose. one case of overdose (ingestion of 37 g of tranexamic acid).
Symptoms: dizziness, headache, nausea, vomiting, diarrhea, orthostatic symptoms (including, dizziness when passing from horizontal to vertical position), orthostatic arterial hypotension. In predisposed patients, the risk of thrombosis increases.
Treatment: antidote is unknown. If you suspect an overdose tranexamic acid, hospitalization is necessary. When providing care, you should induce vomiting, then rinse the stomach. Activated carbon reduces the absorption of tranexamic acid when ingested during the first 1 to 2 hours after an overdose. If the patient is unconscious or if swallowing is impaired Activated carbon can be administered through a nasogastric tube. It is recommended ingestion or parenteral administration of a large amount of fluid to enhance renal excretion, forced diuresis, control of the amount of urine released. In some cases, the use of anticoagulants may be justified. ";
8. to bring the section "Interaction with other medicinal products" in the following edition:
"Special clinical studies on the interaction of tranexamic acid with other drugs have not been conducted.
Tranexamic acid prevents the development of the pharmacological effect of fibrinolytic (thrombolytic) drugs.
Combined oral contraceptives increase the risk of venous thromboembolic complications and arterial thrombosis (in particular, ischemic stroke and myocardial infarction).The experience of using tranexamic acid in women taking combined oral contraceptives is not available. Because the tranexamic acid has antifibrinolytic effect, simultaneous application with combined oral contraceptives may lead to an additional increase in the risk of thrombotic complications.
Simultaneous use of tranexamic acid with preparations of coagulation factors II, VII, IX and X in combination [prothrombin complex] or anti-inhibitory coagulant complex increases the risk of thrombosis.
Possible increased risk of thrombotic complications (in particular, myocardial infarction) with the simultaneous use of tranexamic acid with hydrochlorothiazide, desmopressin, ampicillin-sulbactam, ranitidine and nitroglycerin.
When combined with hemostatic drugs, activation of thrombosis is possible.
Simultaneous administration of tranexamic acid with anticoagulants should be carried out under the strict supervision of a physician (experience of use is limited).
Pharmaceutical drug interactions
Tranexamic acid solution is compatible with most infusion solutions (0.9% sodium chloride solution, Ringer's solution, 5% dextrose solution, solutions of amino acids, dextrans). The tranexamic acid solution is compatible with unfractionated heparin.
A solution of tranexamic acid is pharmaceutically incompatible with urokinase, norepinephrine, dipyridamole, diazepam.
A solution of tranexamic acid should not be mixed with solutions of antibiotics (penicillins, tetracyclines) and blood preparations. "
9. Give the section "Special instructions" in the following edition:
"Before and during the treatment with tranexamic acid preparations, it is necessary to consult an ophthalmologist (determining visual acuity, color vision, and the condition of the fundus) .If visual impairment occurs with treatment with tranexamic acid, the drug must be discontinued.
Tranexamic acid preparations should be used with caution in hematuria caused by kidney parenchyma diseases, since intravascular precipitation of fibrin is often observed in these conditions, which can exacerbate kidney damage.In addition, in cases of massive bleeding of any etiology from the upper urinary tract, antifibrinolytic therapy increases the risk of blood clots in the renal pelvis and / or ureter and, accordingly, secondary mechanical obstruction of the urinary tract and the development of anuria.
Although clinical studies have not revealed a significant increase in the incidence of thrombosis, the risk of thrombotic complications can not be completely ruled out. The cases of development of venous and arterial thrombosis and thromboembolism in patients receiving tranexamic acid are described. In addition, cases of occlusion of the central artery of the retina and the central vein of the retina have been reported. Several patients developed intracranial thrombosis during treatment with tranexamic acid. Accordingly, in patients with a high risk of thrombosis (thromboembolic complications in the anamnesis, cases of thromboembolism in relatives, verified diagnosis of thrombophilia), tranexamic acid should be used only in case of emergency and under strict medical supervision.Before the application of tranexamic acid, a check should be carried out to determine the risk factors for thromboembolic complications.
The presence of blood in the cavities, for example, in the pleural cavity, joint cavities and urinary tracts (including in the renal pelvis and in the bladder) can lead to the formation of an "insoluble clot" in them due to extravascular coagulation, which can be resistant to physiological fibrinolysis.
Patients with irregular menstrual bleeding should not be prescribed tranexamic acid until the cause of dysmenorrhea is established. If the amount of menstrual bleeding is inadequately reduced with treatment with tranexamic acid, alternative treatment should be considered.
The efficacy and safety of tranexamic acid preparations for the treatment of menorrhagia in patients younger than 16 years of age have not been established.
Caution should be used traneksamovuyu acid in women, while taking combined oral contraceptives, in communication with an increased risk of thrombosis (See section "Interaction with other drugs").
In patients with DIC syndrome who need treatment with tranexamic acid, therapy should be performed under the close supervision of a physician with experience in the treatment of this disease.
Due to the lack of adequate clinical studies, the simultaneous use of tranexamic acid with anticoagulants should be carried out under the close supervision of a specialist with experience in the treatment of blood clotting disorders.
If treneksamova acid is noted for visual impairment, it is necessary to stop taking the drug and consult a doctor. ";
10. bring the section "Impact on the ability to drive vehicles, mechanisms" in the following edition:
"The ability of tranexamic acid to influence the speed of psychomotor reactions and the ability to control transport or other mechanical means has not been studied. Tranexamic acid may cause dizziness and visual impairment, and, accordingly, may affect the ability to engage in potentially hazardous activities requiring increased concentration and speed of psychomotor reactions. ";
11. bring the section "Conditions of Leave" in the following edition:
"Let go of the prescription."