Traneksam - instructions for use, doses, side effects, contraindications

Tranexamic acid is a competitive (at high concentrations - noncompetitive) inhibitor of the activation of profibrinolysin (plasminogen) and its conversion into fibrinolysin (plasmin). Antifibrinolytic activity of tranexamic acid in vitro about 10 times the activity of aminocaproic acid, which is due to a stronger bond with the receptor molecule of plasminogen. Tranexamic acid has a local and systemic hemostatic effect in bleeding associated with increased fibrinolysis. By suppressing the formation of kinins and other active peptides involved in allergic and inflammatory reactions, tranexamic acid has also anti-inflammatory and anti-allergic effect.

Tranexamic acid in a concentration of 1 mg / ml does not affect the aggregation of platelets in vitro, in a concentration of up to 10 mg / ml of blood does not affect the number of platelets, clotting time and various coagulation factors in whole blood or citrated blood of a healthy person. In the same time, tranexamic acid both at a concentration of 1 mg / ml and 10 mg / ml blood elongates thrombin time.

The experiment confirms the own analgesic activity of tranexamic acid, as well as the over-lunar potentiating effect on the analgesic activity of opiates. Pre-clinical data indicate that tranexamic acid has anti-carcinogenic and anti-angiogenic properties.

Pharmacokinetics:

Distributed in the tissues relatively evenly (except - spinal fluid, where the concentration is 1/10 of the plasma). It penetrates through the placental and blood-brain barrier into the breast milk (about 1% of the concentration in the mother's plasma). It is found in seminal fluid, where it reduces fibrinolytic activity, but does not affect the migration of spermatozoa. Tranexamic acid quickly diffuses into the joint fluid and through the synovial membranes, in the joint fluid is found at the same concentration as in the blood. The half-life of the joint fluid is about 3 hours.

The initial volume of distribution is 9-12 liters. The connection with plasma proteins is about 3% (due to binding to plasminogen). Tranexamic acid does not bind to albumin. Antifibrinolytic concentration in various tissues persists for 17 hours, in plasma - up to 7-8 hours.

Metabolized to a small extent. Two metabolites of tranexamic acid have been identified: N-acetylated and deaminated derivative.

Area under the curve "concentration-time" (AUC) has a three-phase form with a half-life in the terminal phase - 3 hours. The total renal clearance is equal to the plasma clearance (110-116 ml / min).

It is excreted by the kidneys (the main way is glomerular filtration), more than 95% unchanged during the first 12 hours. After intravenous administration at a dose of 10 mg / kg for 24 hours by glomerular filtration, about 90% of tranexamic acid is excreted.

In patients with impaired renal function there is an increase in the concentration of tranexamic acid in the blood plasma and there is a risk of cumulation of the drug.

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 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 large surgical interventions (including cardiosurgery operations);

- obstetric-gynecological bleeding (including bleeding during gynecological surgeries);

- bleeding caused by the use of fibrinolytic drugs.

Contraindications:

- 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 (deep vein thrombosis of the legs, pulmonary embolism, thrombosis of the 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 younger than 16 years of age (no experience of use);

- Age younger than 1 year (no experience of use).

Carefully:

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);

- Patients with a high risk of thrombosis (history of thromboembolic events or family history of thromboembolic disease, verified diagnosis of thrombophilia);

- Patients taking combined oral contraceptives (in connection with increased risk of venous thromboembolic complications and arterial thrombosis);

- Simultaneous use of preparations of coagulation factors II, VII, IX and X in combination [prothrombin complex] or anti-inhibitory coagulant complex;

- Patients receiving anticoagulant therapy (limited experience).

Pregnancy and lactation:

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.

Dosing and Administration:

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 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 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 throat. 10-15 mg / kg body weight every 6-8 hours until bleeding stops.

- Prevention and treatment of bleeding with thoracic, abdominal and other large surgical interventions: 15 mg / kg body weight every 6-8 hours before stop bleeding.

- 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 surgeries): 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 medicines: 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, correction of the dose and the frequency of administration of tranexamic acid is necessary:

Concentration of serum creatinine	Glomerular filtration rate (GFR)	The dose of tranexamic acid	Multiplicity of the introduction
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.

Side effects:

The incidence of adverse events was determined in accordance with the WHO classifications: very often (> 1/10), often (> 1/100, ≤1 / 10) infrequently (> 1/1000, 1/100 ≤), rare (> 1/10000, ≤ 1/1000), very rarely (less than 1/10000), the frequency is unknown (can not be determined from available data).

Disorders from the organs of the gastrointestinal tract: often - nausea, vomiting, diarrhea (symptoms go away with a lower dose).

Disturbances from the skin and subcutaneous tissues: rarely - skin allergic reactions, including allergic dermatitis.

Disorders from the side of the organ of vision: rarely - visual impairment, including a 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; the frequency is unknown - acute myocardial infarction, thrombosis, cerebral arterial thrombosis, carotid arteries, stroke, deep vein thrombosis of the legs, pulmonary embolism, thrombosis, renal artery with the development of cortical necrosis and acute renal failure, occlusion of coronary artery bypass,central artery thrombosis and retinal veins.

Immune system disorders: very rarely - hypersensitivity reactions, including anaphylactic shock.

Disturbances from the nervous system: rarely - dizziness, convulsions.

Overdose:

There are limited data on overdose cases.

Symptoms may include nausea, vomiting, diarrhea, dizziness, headache, lowering blood pressure (including orthostatic hypotension). In predisposed patients, the risk of thrombosis increases.

Treatment: symptomatic; forced diuresis. In some cases, the use of anticoagulants may be justified.

Interaction:

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 I, 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.

Pharmaceutical drug interactions

A solution of tranexamic acid is compatible with most infusion solutions (0.9% sodium chloride solution, Ringer's solution, 5% dextrose solution, amino acid solutions, 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.

Special instructions:

A solution of tranexamic acid is introduced intravenously very slowly; tranexamic acid can not be administered intramuscularly.

Convulsions

Cases of seizures that are associated with the use of tranexamic acid are described. In patients undergoing aortocoronary bypass surgery, seizures, in most cases, developed with the use of tranexamic acid in high doses. When the drug is used in recommended doses, the frequency of seizures after

operation was the same as in patients who did not receive tranexamic acid.

Visual impairment

With the use of tranexamic acid, it is possible to develop visual disturbances, including a violation of color perception. Before and during the long-term treatment with tranexamic acid, an examination of the ophthalmologist (visual acuity, color vision,ocular fundus). When there are visual impairments against the background of treatment, it is necessary to cancel the drug.

Hematuria

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.

Thromboembolic events

Prior to the use of tranexamic acid, possible risk factors for the development of thromboembolic events should be considered. Patients with a history of thromboembolic disease, or patients with an increased incidence of thromboembolic events in the family history (patients with a high risk of thrombophilia) tranexamic acid in the form of a solution for injection should be prescribed only under strict medical conditions after consultation with a specialist in hemostasis.The use of the drug in such patients should be carried out under close medical supervision.

Tranexamic acid should be used with caution in patients receiving oral contraceptives, due to an increased risk of thrombosis.

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.

The syndrome of disseminated intravascular coagulation (DVS-syndrome)

The use of tranexamic acid in patients with DIC syndrome is contraindicated in most cases. Tranexamic acid can be prescribed to such patients only if the patient has symptoms of a predominance of fibrinolytic system activation with acute severe bleeding. In such acute cases of a single administration of tranexamic acid at a dose of 1 g, it is often sufficient to stop bleeding. The administration of tranexamic acid in DIC syndrome should be performed only when availability of appropriate laboratory test data and after evaluating these data by a specialist.

Due to the lack of adequate clinical studies,The simultaneous use of tranexamic acid preparations with anticoagulants should be carried out under the close supervision of a specialist with experience in the treatment of blood clotting disorders.

Effect on the ability to drive transp. cf. and fur:

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 can cause dizziness and visual disturbances, and. accordingly, can affect the ability to engage in potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous administration, 100 mg / ml.

Packaging:

5 ml in neutral glass ampoules of grade НС-3 or imported.

5 ampoules per contour cell pack of polyvinylchloride film or in contour cell packaging made of polyvinyl chloride film and foil of aluminum printed varnished.

For 1 or 2 contour packs with instructions for use in a pack of cardboard. In the pack invest scarifiers or knives ampoule.When packing ampoules with incisions, rings and break points, scarifiers or ampoule knives do not.

Packing for hospitals

For 20, 50 or 100 cell-packed, foil-coated packaging units, together with 20, 50 and 100 instructions for use, with scarifiers or knives, ampoule into carton boxes or in crimped corrugated cardboard boxes.

When packing ampoules with incisions, rings and break points, scarifiers or ampoule knives do not.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004676

Date of registration:26.01.2018

Expiration Date:26.01.2023

The owner of the registration certificate:NIZHFARM, JSC NIZHFARM, JSC Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Information update date: & nbsp26.03.2018

Illustrated instructions

Instructions

Tranexam® (Tranexam®)