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

Pharmacodynamics:Antifibrinolytic agent, is a competitive (at high concentrations-uncompetitive) inhibitor of plasminogen activation and its conversion into plasmin. Has local and systemic hemostatic effect in bleeding associated with increased fibripolysis (platelet pathology, menorrhagia). By suppressing the formation of kinins and other active peptides involved in allergic and inflammatory reactions. has anti-allergic, anti-inflammatory, anti-infective and antitumor effect. In experimental studies, the own analgesic activity of tranexamic acid has been confirmed, as well as a potentiating effect on the analgesic activity of opioid analgesics.

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

Pharmacokinetics:

It is distributed in tissues relatively evenly (with the exception of cerebrospinal fluid, where the concentration is 1/10 of the plasma one). Penetrates through the placental barrier (the concentration in the cord blood after administration to a woman at a dose of 10 mg / kg can be quite high, about 30 μg / ml fetal serum) and the blood-brain barrier (BBB). is excreted in breast milk (reaching approximately 1% of the concentration in the mother 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 serum. The biological half-life of the joint fluid is about 3 hours. The initial volume of distribution (V_d) - 9-12 liters.Binding to plasma proteins (profibrinolysin) is less than 3%.

In blood, about 3% is associated with a protein (plasminogen). The total renal clearance is equal to the plasma clearance.

Antifibrinolytic concentration in various tissues persists for 17 hours in plasma - up to 7-8 hours.

Metabolized to a small extent. Area under the curve "concentration / time" (AUC) has a three-phase form with a half-life (T_1/2) in the terminal phase - 2 hours. The total renal clearance is equal to the plasma clearance (7 l / h). 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. Two metabolites of tranexamic acid have been identified: N-acetylated and deaminated derivatives.

Pharmacokinetics in special clinical cases:

If there is a violation of kidney function, there is a risk of cumulation of tranexamic acid.

Indications:

Prevention and treatment of bleeding caused by generalized or local fibrinolysis in adults and children aged 1 year and older. Tranexamic acid preparations are used in the following situations:

- Treatment of bleeding caused by generalized or local fibrinolysis.such as: menorrhagia and metrorrhagia. gastrointestinal bleeding, bleeding after surgical interventions on the prostate and bladder;

- Prevention and treatment of bleeding during surgical interventions in the nasal cavity, mouth and pharynx (adenoidectomy, tonsillectomy, tooth extraction), with thoracic, abdominal and other large surgical interventions (including cardiosurgery operations), with gynecological surgeries:

- Treatment of obstetric-gynecological bleeding;

- Treatment of bleeding caused by the use of fibrinolytic drugs.

Contraindications:

Hypersensitivity to tranexamic acid or other components of the drug. Patients with an anamnesis and a risk of developing thrombosis with the impossibility of simultaneous treatment with anticoagulants, active thromboembolic disease, incl. deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acquired color vision disorder, subarachnoid hemorrhage (risk of edema and cerebral infarction), hematuria,caused by diseases of the renal parenchyma and bleeding from the upper urinary tract (the risk of secondary mechanical obstruction of the urinary tract with a clot of blood with the development of anuria). Simultaneous use of preparations of coagulation factors II, VII. IX and X in combination [prothrombin complex], or anti-inhibitory coagulant complex.

Severe chronic renal failure (glomerular filtration rate [GFR] less than 30 mg / ml / 1.73 m²) due to the risk of cumulation. Fibrinolysis due to coagulopanand consumption (hypocoagulation stage of the syndrome of disseminated intravascular coagulation [DVS-syndrome]).

Cramps in the anamnesis. Treatment of menorrhagia in patients under the age of 16 years (no experience is available).

Children under 2 years of age (limited experience in clinical use).

Carefully:

Patients with a high risk of thrombosis (history of thromboembolic events or a family history of thromboembolism).

Patients taking combined oral contraceptives (due to an increased risk of venous thromboembolic complications and arterial thrombosis).

Patients receiving anticoagulant therapy (limited experience).

Pregnancy and lactation:

Animal studies have shown that there is no effect of tranexamic acid on the embryonic or neonatal development of the offspring. Adequate and strictly controlled studies in pregnant women are absent. Tranexamic acid penetrates the placental barrier and is found in cord blood in concentrations close to the maternal.

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 (reaching approximately 1% of the concentration in the mother's plasma). When prescribing tranexamic acid, breastfeeding should be abolished.

Dosing and Administration:

Intravenous (drip, jet). With the infusion method of administration, the drug should be diluted in 0.9% sodium chloride solution.

In generalized fibrinolysis, 15 mg / kg body weight every 6-8 hours at a rate of 1 ml / min.

When used in cardiac surgery, in operations under extracorporeal circulation, tranexamic acid is used during the induction of anesthesia before sternotomy at a dose of 15 mg / kg, then intraoperatively at a dose of 4.5 mg / kg. of which 0.6 mg / kg is introduced into the primary volume of filling of the artificial circulation apparatus (AIC).

With local fibrinolysis, 250-500 mg 2-3 times a day.

When prostatectomy or bladder surgery - 1 g during the operation, then 1 g every 8 hours for 3 days, then go to the reception inside the tablet form until the disappearance of the macrohematuria.

Treatment of obstetric-gynecological bleeding: 15 mg / kg of 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.

Patients with coagulopathies, before extraction of the tooth are administered in a dose of K) mg / kg. after extraction of the tooth, they switch to ingestion into a tablet form.

Correction of dosing regimens in case of impaired renal function

Concentration of creatinine		Glomerular filtration rate, ml / min / 1.73 m²	Single dose, mg / kg	Multiplicity of administration, once a day
μmol / l	mg / dL	Glomerular filtration rate, ml / min / 1.73 m²	Single dose, mg / kg	Multiplicity of administration, once a day
120-250	1.36-2.82	60 - 89	10	2
250-500	2,83 - 5.66	30 - 59	10	1

Dysfunction of the liver: In patients with impaired liver function, dose adjustment is not required.

Elderly: In elderly patients in the absence of renal failure, dose adjustment is not required.

Side effects:

The frequency of adverse reactions is distributed in the following order:

often (>1/100. <1/10): infrequently (>1/1000. <1/100); rarely (>1/10000. <1/1000): very rarely (<1/10000). including reports of isolated cases.

From the digestive system: often (> 1/100) - Anorexia, nausea, vomiting, heartburn, diarrhea.

From the central nervous system: rarely - convulsions; rarely - dizziness, weakness, drowsiness.

From the coagulation system of the blood: rarely - thrombosis, thromboembolism.

From the side of the cardiovascular system: rarely - thromboembolic complications, marked decrease in blood pressure (usually due to excessively rapid intravenous administration);

rarely - arterial and venous thrombosis of different localization; frequency unknown - Acute myocardial infarction, cerebral thrombosis, carotid thrombosis, stroke, deep vein thrombosis of the legs.thromboembolism of the pulmonary artery, thrombosis of the renal artery with the development of cortical necrosis and acute renal failure, occlusion of the aorto-coronary shunt.

Allergic reactions: rarely rash, itching, hives.

From the side immune systems: rarely - hypersensitivity reactions, incl. anaphylactic shock.

From the skin and subcutaneous tissues: rarely - skin allergic reactions, incl. allergic dermatitis.

From the side of the organ of vision: rarely - visual impairment, incl. violation of color perception, thrombosis of the vessels of the retina.

Overdose:

Symptoms: nausea, vomiting, diarrhea; orthostatic hypotension; arterial or venous thromboembolism; impaired vision; change in mental status; myoclonus, rash.

Treatment: The antidote is unknown. If suspected overdose of tranexamic acid, hospitalization is necessary. 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:

Tranexamic acid is pharmaceutically incompatible with urokinase, hypertensive drugs (norepinephrine), dipyridamole, diazepam.

May interfere with the development of the thrombolytic effect of fibrinolytic drugs.

With the combined use of tranexamic acid with haemostatic drugs, activation of thrombus formation is possible.

Combined oral contraceptives increase the risk of venous thromboembolic complications and arterial thrombosis (in particular, ischemic stroke and myocardial infarction). Experience with the use of traieksamic acid in women taking combined oral contraceptives is not available. Because the tranexamic acid has an antifibrinolytic effect, simultaneous use with combined oral contraceptives can 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 [protrombnnovym complex] or anti-inhibitory coagulant complex increases the risk of thrombosis.

Special clinical studies on the interaction of tranexamic acid with other drugs have not been conducted. Tranexamic acid solution 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 should not be mixed with solutions of antibiotics (penicillins, tetracyclines) and blood preparations.

Special instructions:

Before and during the treatment with the drug Stagemin, an examination of the ophthalmologist (visual acuity, color vision, eye fundus) is necessary.

With hematuria from the upper parts of the urinary tract, in rare cases, there may be a risk of mechanical anuria due to the formation of a clot in the urethra.

In patients with renal insufficiency, the concentration of tranexamic acid in the blood rises, so in such cases it is recommended to reduce the dose of the drug (see section "Method of administration and dose").

Patients with DIC syndrome who need treatment with tranexamic acid should be under the strict supervision of a physician with experience in the treatment of this disease.

In patients with a high risk of developing thrombosis (thromboembolic complications in history, 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 cavity and urinary tract (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 stable 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.

Due to the lack of adequate clinical studies, the simultaneous use of tranexamic acid with anticoagulants should be performed 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:During the treatment period, one should refrain from driving vehicles, and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Solution for intravenous administration 50 mg / ml. 5 ml into neutral glass ampoules.

Packaging:For 10 ampoules with instructions for use and a vial for opening ampoules or a scarifier ampoule is placed in a box of cardboard for consumer packaging. 5 or 10 ampoules are placed in a contoured cell pack of a polyvinylchloride film or polyethylene terephthalate tape and aluminum foil or paper with a polyethylene coating or without a foil, or without paper. 1, 2 or 10 contour cells (5 ampoules each) or 1. 2 or 5 contour cells (10 ampoules each) with instructions for use and a vial or ampoule ampoule with a knife are placed in a pack of cardboard.
When you pack the ampoules with a break ring or break point, the ampoule opener or ampoule scapper is not put in.

Storage conditions:

At a temperature of 2 C to 25 ° C.

Keep out of the reach of children.

Shelf life:

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

Terms of leave from pharmacies:On prescription

Registration number:LP-003061

Date of registration:25.06.2015

The owner of the registration certificate:NOVOSIBHIMFARM, OJSC NOVOSIBHIMFARM, OJSC Russia

Manufacturer: & nbsp

NOVOSIBHIMFARM, OJSC Russia

Information update date: & nbsp19.09.2015

Illustrated instructions

Instructions

Stagemine (Stagemin)