GEMTRANIX - instructions for use, dose, side effects, contraindications

Composition per one ampoule	50 mg / ml	100 mg / ml
Active substance:
tranexamic acid (in terms of dry matter)	250 mg	500 mg
Excipient: water for injections	up to 5 ml	up to 5 ml

Description:A clear, colorless solution.

Pharmacotherapeutic group:Hemostatic agent

ATX: & nbsp

B.02.A.A Amino acids

B.02.A.A.02 Tranexamic acid

Pharmacodynamics:Tranexamic acid is an antifibrinolytic agent that specifically inhibits the activation of the profibrinolysin (plasminogen) and its conversion to fibrinolysin (plasmin). Has a local and systemic hemostatic effect in bleeding associated with increased fibrinolysis. In studies in vitro tranexamic acid at high concentrations decreased complement activity.

Pharmacokinetics:

Absorption

The peak concentration in plasma after intravenous administration (500 mg) is achieved immediately and then the concentration gradually decreases.

Distribution

The connection with plasma proteins (plasminogen) of tranexamic acid is about 3%. The initial volume of distribution is approximately 9-12 liters.

Tranexamic acid passes through the placenta. After intravenous injection of 10 mg / kg to pregnant women, the concentration of tranexamic acid in the serum is in the range of 10-53 μg / ml, while in the cord blood - in the range of 4-31 μg / ml. Tranexamic acid quickly penetrates into the joint fluid and synovial membranes, with a delay - into the cerebrospinal fluid.After intravenous injection of 10 mg / kg in patients who underwent knee joint surgery, the concentrations in synovial fluids were the same as in the corresponding serum samples. The concentration of tranexamic acid in breast milk is one hundredth of that observed in the blood and a tenth of the spinal and intraocular fluids. Tranexamic acid was found in sperm, where it inhibits fibrinolytic activity, but does not affect the migration of spermatozoa.

Excretion

Tranexamic acid is excreted in the urine by glomerular filtration in unchanged form. The total renal clearance is equal to the total clearance from plasma (110-116 ml / min). The excretion of tranexamic acid is about 90% within the first 24 hours after intravenous administration of 10 mg / kg body weight. The half-life (T1 / 2) is about 3 hours.

Special Groups

In patients with renal insufficiency, plasma concentrations of tranexamic acid are increased.

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 extensive 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;

- chronic severe 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 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]);

- convulsions in the anamnesis;

- acquired color vision disorder;

- 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);

- syndrome of disseminated intravascular coagulation [DVS-syndrome];

- the presence of blood in the cavities, for example, in the pleural cavity, joint cavities and urinary tracts;

- patients taking combined oral contraceptives (due to an increased risk of venous thromboembolic complications and arterial thrombosis);

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

- patients receiving anticoagulant therapy (experience of use is limited).

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

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

Prevention and treatment of bleeding during cardiac surgery: a loading dose of 15 mg / kg after the induction of anesthesia before 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 drugs: 10 mg / kg body weight every 6-8 hours from the time the bleeding develops 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	The dose of tranexamic acid	Multiplicity of reception
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 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 is established according to 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.

Disturbances on the part of the organ of sight: 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 intravenousintroduction); very rarely - arterial and venous thrombosis of different localization; frequency 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 occlusion, central artery vein and retinal veins .

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

Impaired nervous system: rarely - dizziness; convulsions.

Overdose:

There are limited data on overdose cases. One case of overdose (ingestion of 37 g of tranexamic acid) is reported.

Symptoms: dizziness, headache, nausea, vomiting, diarrhea, orthostatic symptoms (including dizziness when moving from horizontal to vertical position), orthostatic arterial hypotension. In predisposed patients, the risk of thrombosis increases.

Treatment: antidote is unknown. If suspected overdose of 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 for the first 1-2 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.

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 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

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

The drug should be used strictly according to the indications and in accordance with the indicated method of administration:

- the solution is administered intravenously very slowly;

- Tranexamic acid can not be administered intramuscularly.

Before and during the treatment with tranexamic acid preparations, an ophthalmologist should be consulted (visual acuity, color vision, eye fundus condition). If visual disturbances occur against the background of treatment with tranexamic acid, the drug should be discarded.

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. Besides,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, e.g., in pleural cavities, the cavities of the joints and the urinary tract (in t. H. In the renal pelvis and urinary bladder) may lead to the formation of these "insoluble clot" due to extravascular blood coagulation, which may 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.

It should be used with caution tranexamic acid in women, at the same time taking combined oral contraceptives, in connection with an increased risk of thrombosis.

In patients with DIC syndrome who need treatment with tranexamic acid,Therapy should be carried out under the close supervision of a doctor who has experience in the treatment of this disease. 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. Such patients, in general, are characterized by such hematological profile: shortening the lysis time of the euglobulin clot. prolongation of prothrombin time, decrease in plasma fibrinogen concentration, factors V and VIII, plasminogen and its activators, alpha-2 macroglobulin; normal concentrations in the plasma of factor II (prothrombin), factors VIII and X; increased plasma concentrations of fibrin degradation products; normal number of platelets. It is assumed that the underlying disease does not modify the individual hematological profile. In such acute cases of a single administration of tranexamic acid at a dose of 1000 mg often enough to stop bleeding. The administration of tranexamic acid in the DIC of the blood should be performed only if there are appropriate laboratory test data and after the expertise of these data by a specialist.

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.

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. 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 50 mg / ml and 100 mg / ml.

Packaging:

5 ml in ampoules of colorless neutral glass type I with a color fracture ring or with a colored dot and a notch. Ampoules are additionally applied with one, two or three color rings and / or a two-dimensional bar code,and / or alphanumeric encoding or without additional color rings, a two-dimensional barcode, alphanumeric encoding.

By 5 ampoules in a contour cell box from a polyvinyl chloride film and a polymer film or without a film.

1 or 2 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

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

Terms of leave from pharmacies:On prescription

Registration number:LP-004408

Date of registration:14.08.2017

Expiration Date:14.08.2022

The owner of the registration certificate:FarmSirma Soteks, ZAO FarmSirma Soteks, ZAO Russia

Manufacturer: & nbsp

FarmSirma Soteks, ZAO Russia

Information update date: & nbsp06.09.2017

Illustrated instructions

Instructions

GEMTRANIKS (Hemtranix)