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

An antifibrinolytic agent specifically inhibiting the activation of profibrinolysin (plasminogen) and its conversion to fibrinolysin (plasmin). Has local and systemic hemostatic effect in bleeding associated with increased fibrinolysis, as well as anti-inflammatory and anti-allergic action due to inhibition of the formation of kinins and other active peptides involved in allergic and inflammatory reactions.

Pharmacokinetics:

Suction

The maximum concentration (C_m_Oh) tranexamic acid is observed immediately after intravenous administration (500 mg), then C_m_Oh decreases for about 6 hours.

Distribution

It is distributed in tissues relatively evenly (with the exception of cerebrospinal fluid, where the concentration is 1/10 of the concentration in the blood plasma). Penetrates through the placental and blood-brain barrier, excreted in breast milk (reaching approximately 1% of the concentration in the blood plasma of the mother).It is found in seminal fluid, where it reduces fibrinolytic activity, but does not affect the migration of spermatozoa.

Linkage to blood plasma proteins (fibrinolysin) is about 3%. Tranexamic acid does not bind to serum albumin.

The initial volume of distribution is 9-12 liters. Antifibrinolytic concentration in various tissues persists for 17 hours, in plasma of blood - up to 7-8 hours.

Metabolism

Metabolized to a small extent. Two metabolites of tranexamic acid - N-acetylated and deaminated derivatives.

Excretion

Curve AUC (the area under the concentration-time curve) has a three-phase form with a half-life T_1/2in the final phase - 3 hours. The total renal clearance is equal to the plasma clearance (7 l / h). More than 95% is excreted by the kidneys unchanged during the first 12 hours (the main way is glomerular filtration).

Pharmacokinetics in special clinical cases

With impaired renal 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:

with surgical interventions in the nasal cavity, mouth and pharynx (adenoidectomy, tonsillectomy, tooth extraction);
with thoracic, abdominal and other large surgical interventions (including cardiosurgery operations);
at gynecological operations;

- 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;

- chronic renal failure of severe degree (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 diseases, verified diagnosis of thrombophilia);

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

- 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). Development antifibrinolytic effect in an infant is unlikely. Nevertheless, caution should be exercised when using tranexamic acid in nursingmothers.

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:

- Treatment of bleeding due to generalized fibrinolysis: 15 mg / kg body weight every 6-8 hours from the time of bleeding to its stop;

- Treatment of bleeding due to local fibrinolysis: 500 mg (1 ampoule 5.0 ml) 2-3 times a day from the moment of development of bleeding to its stop;

- Prevention and treatment of bleeding:

with surgical interventions in the nasal cavity, mouth and pharynx: 10-15 mg / mg of body weight every 6-8 hours before stopping bleeding;
with thoracic, abdominal and other large surgical interventions: 15 mg / kg of body weight every 6-8 hours until bleeding stops;
for cardiosurgery: a loading dose of 15 mg / kg after the induction of anesthesia before 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 the device of artificial circulation;
with gynecological surgeries: 10-15 mg / kg of body weight every 6-8 hours before stopping bleeding.

- Treatment of obstetric-gynecological bleeding: 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.

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 introduction of

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 determined from available data).

Disturbances from the organs of the gastrointestinal tract: often - nausea, vomiting, diarrhea (symptoms go with decreasing 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 unknown - acute myocardial infarction, cerebral artery thrombosis, carotid thrombosis, stroke,thrombosis of the deep veins 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, central artery thrombosis and retinal veins.

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

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

Overdose:

Cases of overdose of a solution of tranexamic acid have not been described. There are limited data on overdose of tablets of tranexamic acid (one case of ingestion of 37 g of tranexamic acid is reported).

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

Treatment: antidote is unknown. If there is a suspicion of overdose with 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:

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.

Pharmaceutical drug interactions:

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

Before and during the treatment with tranexamic acid preparations, an ophthalmologist should be consulted (visual acuity, color vision, eye fundus conditions).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. 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 exercised with tranexamic acid in women taking concomitant oral contraceptives concurrently with an increased risk of thrombosis (see "Interactions 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.

In connection with the lack of adequate clinical studies, 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.

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 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.

Form release / dosage:

Solution for intravenous administration, 100 mg / ml.

Packaging:

For 5 ml of the drug in ampoules of colorless transparent neutral glass type I.

For 5 ampoules in a plastic pallet of PVC, together with the instruction for use, is placed in a cardboard pack.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003698

Date of registration:22.06.2016

Expiration Date:22.06.2021

The owner of the registration certificate:Novator Pharma, LLCNovator Pharma, LLC United Kingdom

Manufacturer: & nbsp

Bioindustria Laboratorio Italiano Medicinali S.p.A. Italy

Representation: & nbspNOVATOR PHARMA, LLCNOVATOR PHARMA, LLCRussia

Information update date: & nbsp17.08.2016

Illustrated instructions

Instructions

Tramzon (Tramestone)