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

Antifibrinolytic agent, is a competitive (at high concentrations - non-competitive) inhibitor of plasminogen activation and its transformation into plasmin. It has local and systemic hemostatic as well as anti-allergic and anti-inflammatory effects due to inhibition of the formation of kinins and other active peptides involved in allergic and inflammatory reactions.

Has a local and systemic hemostatic effect in bleeding associated with increased fibrinolysis (platelet pathology, menorrhagia).

Also tranexamic acid by suppressing the formation of kinins and other active peptides involved in allergic and inflammatory reactions, has anti-allergic and anti-inflammatory effects.

Tranexamic acid at a concentration of 1 mg / ml does not aggregate platelets in vitro, in a concentration of up to 10 mg / ml blood does not affect the number of platelets, clotting time 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 umbilical cord 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 (GEB), excreted in breast milk (reaching about 1% from 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 rapidly diffuses into the joint fluid and through the synovial membranes, and 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.

Initial volume of distribution Vd - 9-12 liters.

The connection with 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.The area under the concentration-time curve (AUC) has a three-phase form with a half-life in the terminal phase - 2 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). After intravenous administration at a dose of 10 mg / kg for 24 hours, approximately 90% of tranexamic acid is released by glomerular filtration. Two metabolites of tranexamic acid have been identified: N-acetylated and deaminated derivatives.

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, 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 or other large surgical interventions (incl.at cardiosurgical operations);

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

- 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 and arterial thrombosis at present or in the anamnesis (thrombosis of deep veins 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]);

- 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);

- 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; injection rate 1 ml / min.

You should avoid rapid intravenous injection!

Adult patients:

- menorrhagia and metrorrhagia, gastrointestinal bleeding: 500 mg (1 ampoule of the drug at a dosage of 100 mg / ml or 2 ampoules of the drug at a dosage of 50 mg / 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 of the drug at a dosage of 100 mg / ml or 4 ampoules of the drug at a dosage of 50 mg / ml) 3 times a day from the moment 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 until bleeding stops;

- prevention and treatment of bleeding during cardiac surgery: 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 the device of artificial circulation;

- 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 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 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, 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 - reactions hypersensitivity, incl. anaphylactic shock.

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

Overdose:

In predisposed patients with an overdose of the drug, the risk of thrombosis increases.

Overdose Symptoms: dizziness, headache, nausea, vomiting, diarrhea, orthostatic symptoms and lowering blood pressure.

Treatment. The antidote is unknown. If you suspect an overdose, hospitalization is necessary. With the aim of providing relief, symptomatic therapy, gastric lavage, Activated carbon within 1-2 hours after an overdose; Also, oral administration or parenteral administration of a large amount of fluid to enhance renal excretion, forced diuresis, control of the amount of urine released is also recommended. 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 interferes with the development of pharmacological effect 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 ghydrochlorothiazide, desmopressin, ampicillin-sulbactam, ranitidine and nitroglycerin.

When combined with hemostatic drugs activation of thrombosis is possible.

Pharmaceutical drug interactions:

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

A solution of tranexamic acid is compatible with unfractionated heparin.

Tranexamic acid solution pharmaceutically incompatible from urokinase, norepinephrine, dipyridamole, diazepam.

A solution of tranexamic acid should not be mixed with solutions of antibiotics (penicillins, tetracyclines) and blood products.

Special instructions:

Before and during the treatment it is necessary to conduct an examination of the oculist for visual acuity, color perception, and the condition of the fundus. When there are visual impairments against the background of treatment, it is necessary to cancel the drug.

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, consequently, secondary mechanical obstruction of the urinary tract and the development of anuria.

Although the clinical data do not show a significant increase in the incidence of thrombosis, a possible risk of thrombotic complications can not be completely ruled out. There have been reports of cases of venous and arterial thrombosis and thromboembolism in patients receiving tranexamic acid. 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, but further studies are needed to assess the significance of this potential risk.

There are no data on the use of tranexamic acid in women taking concurrent oral contraceptives. Caution should be used traneksamovuyu acid in women, while taking combined oral contraceptives,in connection with an increased risk of thrombosis (see "Interaction with other drugs").

In patients with a high risk of developing thrombosis (history of thromboembolic events, history of thromboembolism in a family history), tranexamic acid should be used only in case of emergency and under strict medical supervision. The presence of blood in the body cavities, for example, the pleural cavity, articular cavity and urinary tract (including the kidneys, small pelvis, bladder) can lead to the formation of an "insoluble clot" due to extravascular coagulation, which can be resistant to physiological fibrinolysis.

Patients with irregular menstrual bleeding should be administered tranexamic acid only after establishing the cause. 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.

Clinical experience in children younger than 1 year is limited, so tranexamic acid It should be used in this category of patients only if the potential benefit exceeds the risk. The use of antifibrinolytic drugs in newborns and children younger than 1 year remains controversial, since bleeding in this category of patients is largely due to the immaturity of the clotting system than fibrinolysis.

The published data on the efficacy and safety of tranexamic acid administration do not allow us to draw a definitive conclusion about the benefits of using tranexamic acid in newborns, children under 1 year. In connection with the physiological characteristics of newborns and infants (immaturity of the blood-brain barrier and renal function), there is a potential risk of seizures when tranexamic acid is used.

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.

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.

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, 50 mg / ml and 100 mg / ml.

Packaging:

For 5 ml of the drug in a vial of colorless clear glass (US Pharm. Type I) with a fault line at the top. On the ampoule glue a label from paper label or writing or from polymer materials, self-adhesive.

5 ampoules per contour cell packaging made of polyvinyl chloride film.

1 pack together with instructions for use in a cardboard box.

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 the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003593

Date of registration:26.04.2016

Expiration Date:26.04.2021

The owner of the registration certificate:SP.INKOMED, LLC SP.INKOMED, LLC Russia

Manufacturer: & nbsp

SANJIVANI PARANTERAL, Limited India

Representation: & nbspSP.INKOMED LLCSP.INKOMED LLC

Information update date: & nbsp08.07.2016

Illustrated instructions

Instructions

Sanssamik (Sanssamik)