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

Excipients: microcrystalline cellulose 45.05 mg or 90.10 mg, pregelatinized starch 4.85 mg or 9.70 mg, sodium carboxymethyl starch 6.20 mg or 12.40 mg, talc 7.99 mg or 15.98 mg , silicon dioxide colloid - 6,01 mg or 12,02 mg, sodium stearyl fumarate - 9.90 mg or 19.80 mg.

Sheath: VIVACOAT® PA-1P-000 [hypromellose 6 cps (hydroxypropylmethylcellulose 6 cps) 3.51 mg or 7.02 mg titanium dioxide 2.70 mg or 5.40 mg polydextrose (E1200) 1.35 mg or 2, 70 mg, talc 0.90 mg or 1.80 mg, polyethylene glycol 3350 0.54 mg or 1.08 mg] 9.00 mg or 18.00 mg.

Description:

Dosage of 250 mg: tablets, covered with a film shell of white or almost white color, round, biconcave. On the cut is white or almost white.

Dosage 500 mg: tablets, covered with a film coating of white or almost white color, oblong, biconcave. On the cut is white or almost white.

Pharmacotherapeutic group:Hemostatic agent

ATX: & nbsp

B.02.A.A Amino acids

B.02.A.A.02 Tranexamic acid

Pharmacodynamics:

Antifibrinolytic agent. Tranexamic acid specifically inhibits the activation of profibrinolysin (plasminogen) and its transformation into fibrinolysin (plasmin). The antifibrinolytic activity of tranexamic acid is about 10 times higher than the activity of epsilon-aminocaproic acid.

Tranexamic acid has a local and systemic hemostatic effect in bleeding associated with increased fibrinolysis. Besides, tranexamic acid has analgesic, anti-allergic and anti-inflammatory effects by suppressing the formation of kinins and other active peptides involved in allergic and inflammatory reactions.

Pharmacokinetics:

Absorption at oral intake of doses in the range of 0.5-2 g is 30-50%. Time to reach the maximum concentration with oral administration 0.5; 1 and 2 g of tranexamic acid is 3 hours, the maximum concentration is 5, 8 and 15 μg / ml, respectively. The intake of food does not affect the absorption of tranexamic acid in the gastrointestinal tract.

The connection with plasma proteins (profibrinolysin) is less than 3%. Tranexamic acid does not bind to albumin. The therapeutic concentration of tranexamic acid in the blood plasma is 5-10 mg / l.

It is distributed relatively evenly in the tissues (the exception is the cerebrospinal fluid, where the concentration is 1/10 of the plasma one); penetrates the placental barrier, into breast milk (about 1% of the concentration in the mother's plasma), through the blood-brain barrier, into the intra-articular fluid and the synovial membranes. The initial volume of distribution is 9-12 liters. Antifibrinolytic concentration in various tissues persists for 17 hours, in plasma - up to 7-8 hours.

Metabolized to a small extent.The pharmacokinetic curve has a three-phase form with a half-life in the final phase - 3 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 % in unmodified form during the first 12 hours.

Two metabolites of tranexamic acid have been identified: N-acetylated and deaminated derivative.

After taking tranexamic acid, 1%, 7%, 39% and 79% of the dose taken are taken internally at a dose of 10-15 mg / kg during the first hour, 3 hours, 24 hours and 48 hours, respectively.

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

Indications:

Short-term treatment of bleeding associated with increased fibrinolysis, with the following pathological conditions:

- Prostatectomy; operative interventions on the bladder;

- Menorrhagia;

- Nose bleed;

- Conization of the cervix;

- Traumatic hyphema (hemorrhage in the anterior chamber of the eye).

- Prevention and treatment of hemorrhage in patients with hemophilia, who undergo a small surgical intervention (including extraction of the tooth).

- Hereditary angioedema (prevention of exacerbations of the disease).

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);

- Children up to 3 years of age (solid dosage form).

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 parts of the urinary tract (risk of secondary mechanical obstruction of the urinary tract with a clot of blood with the development of anuria).section "Special instructions");

- 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, cavities of the joints and urinary tract;

- Patients receiving anticoagulant therapy (limited experience);

- Simultaneous use of preparations of clotting factors II, VII, IX and X in combination [prothrombin complex] or anti-inhibitory coagulant complex (See section "Interaction with other drugs");

- Patients taking combined oral contraceptives (due to an increased risk of venous thromboembolic complications and arterial thrombosis) (See section "Interaction with Other Drugs").

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:

Inside, regardless of food intake.

- Short-term treatment of bleeding, caused by increased fibrinolysis: the recommended standard dose of tranexamic acid is 15-25 mg / kg body weight, an average of 1000-1500 mg 2-3 times a day.

- With prostatectomy and surgical interventions on the bladder: 1000 mg for 6 hours before the operation, then 1000 mg 3-4 times a day until the disappearance of the macrohematuria. Do not use the drug for more than 2 weeks after surgery.

- With menorrhagia: the recommended daily dose is 1000 mg 3 times a day until the termination of menorrhagia, but no more than 4 days. With profuse bleeding, the dose of the drug can be increased, while the total daily dose should not exceed 4000 mg. Treatment with tranexamic acid should not be started before menstrual bleeding occurs. In clinical trials tranexamic acid not used more three menstrual cycles in a row.

- With recurrent nasal bleeding: 1000 mg 3 times a day for 7 days.

- After the operation of conization of the cervix: 1500 mg 3 times a day for 12 days after the operation.

- In case of traumatic hyphema: 1000-1500 mg 3 times a day (a target dose of 25 mg / kg body weight) for 7 days.

- Patients with hemophilia: the drug is administered orally at a dose of 25 mg / kg body weight 2 hours before the extraction of the tooth, and then 1000-1500 mg 3 times a day for 6-8 days. It is necessary to simultaneously prescribe preparations of coagulation factors VIII or IX.

- With hereditary angioedema: 1000-1500 mg 2-3 times a day. If the patient can foresee an exacerbation of the disease, the drug can be taken intermittently, depending on the presence of prodromal symptoms.In other cases, the drug should be taken continuously.

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, dose adjustment and the frequency of administration of tranexamic acid are necessary:

Concentration of serum creatinine

Glomerular filtration rate (GFR)

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.

Childhood

Data on the efficacy and safety of tranexamic acid drugs in children are limited.

Children tranexamic acid is prescribed at the rate of 25 mg / kg body weight 2-3 times a day.

Actions when missing the next dose

If you miss a dose, you need to take the next dose of the drug at the set time.Do not take twice the dose after skipping the next dose.

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).

Disorders from 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, incl. allergic dermatitis.

Disorders from the side of the organ of vision: 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, in exceptional cases - after ingestion); very rarely - arterial and venous thrombosis of different localization; frequency unknown - acute myocardial infarction, cerebral thrombosis, carotid thrombosis, stroke, deep vein thrombosis of the legs, pulmonary embolism,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.

Impaired nervous system: rarely - dizziness; convulsions (usually with intravenous administration).

Overdose:

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

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 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).

Special instructions:

In patients with hereditary angioedema, the ophthalmologist should be consulted prior to starting treatment (determination of visual acuity, color vision, eye fundus condition). In the process of treatment, a regular ophthalmological examination is necessary (including assessment of visual acuity and color perception, examination of the fundus by a slit lamp, measurement of intraocular pressure, evaluation of visual fields).If visual disturbances occur against the background of treatment with tranexamic acid, the drug should be discarded.

Patients with hereditary angioedema, who have been receiving tranexamic acid for a long time, need regular laboratory monitoring of liver function.

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 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 blood, which can be resistant to physiological fibrinolysis.

Patients with irregular menstrual bleeding should not be prescribed grannexamic 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.

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

Form release / dosage:

Film-coated tablets, 250 mg or 500 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

1, 2, 3 or 6 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004304

Date of registration:22.05.2017

Expiration Date:22.05.2022

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

Manufacturer: & nbsp

PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Information update date: & nbsp22.06.2017

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