Cyclogemal, 250 mg 30 pcs

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

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

Pharmacokinetics

The absorption with oral doses in the range of 0.5-2 g is 30-50%. Time to reach maximum concentration when oral administration of 0.5; 1 and 2 g tranexamic acid is 3 h, maximum concentration is 5.8 and 15 mcg/ml, respectively. Food intake has no effect on the absorption of tranexamic acid in the gastrointestinal tract.

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

The distribution in tissues is relatively uniform (the exception is cerebrospinal fluid, where the concentration is 1/10 of the plasma concentration); it penetrates through the placental barrier, into breast milk (about 1% of the concentration in maternal plasma), through the blood-brain barrier, into the intraarticular fluid and synovial membranes. The initial volume of distribution is 9-12 liters. Antifibrinolytic concentration in various tissues lasts for 17 hours, in plasma – up to 7-8 hours.

It is metabolized to a small extent. Pharmacokinetic curve has a three-phase shape with a half-life of 3 hours in the final phase. Total renal clearance is equal to plasma clearance (7 l/h). It is excreted by the kidneys (main route is glomerular filtration) – more than 95% unchanged during the first 12 hours.

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

After oral administration of tranexamic acid at a dose of 10-15 mg/kg within the first hour, 3 h, 24 h, and 48 h, 1%, 7%,39%, and 79% of the administered dose, respectively, are eliminated.

There is a risk of cumulation of tranexamic acid if renal function is impaired.

Indications

Nasal bleeding, Bleeding

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

– Prostatectomy; bladder surgery;

– Menorrhagia;

– Nasal bleeding;

– Uterine conization;

– Traumatic hyphema (bleeding into the anterior chamber of the eye).

The prevention and treatment of bleeding in patients with hemophilia who undergo minor surgical intervention (including tooth extraction).

Hereditary angioedema (prevention of exacerbations of the disease).

Bleeding during pregnancy.

Active ingredient

Tranexamic acid

Composition

The active ingredient:

tranexamic acid – 250 mg or 500 mg.

Auxiliary substances: Microcrystalline cellulose – 45.05 mg or90.10 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, colloidal silica – 6.01 mg or 12.02 mg, sodium stearyl fumarate – 9.90 mg or 19.80 mg.

Shell:VIVACOAT^®.PA-1P-000 [hypromellose 6 cPs (hydroxypropyl methylcellulose 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.

How to take, the dosage

Ingestion, regardless of meals.

The short-term treatment of bleeding due to increased fibrinolysis: the recommended standard dose of tranexamic acid is 15-25 mg/kg body weight, on average 1000-1500 mg 2-3 times a day.

In prostatectomy and surgical interventions on the bladder:1000 mg 6 hours before surgery, then 1000 mg 3-4 times a day until macrohematuria disappears. It is not recommended to use the drug more than 2 weeks after surgical intervention.

In case of menorrhagia:Recommended daily dose is 1000 mg 3 times a day until cessation of menorrhagia, but not more than 4 days. In case of profuse bleeding, the dose of the drug may be increased, and the total daily dose should not exceed 4000 mg. Treatment with tranexamic acid should not be started before menstrual bleeding. In clinical trials tranexamic acid has not been used for more than three consecutive menstrual cycles.

In recurrent nasal bleeding: 1000 mg 3 times daily for 7 days.

After cervical conization surgery: 1,500 mg 3 times daily for 12 days after surgery.

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

Patients with hemophilia: the drug is administered orally in a dose of 25 mg/kg body weight 2 hours before tooth extraction and then 1000-1500 mg 3 times daily for 6-8 days. Preparations of blood clotting factors VIII or IX should be administered simultaneously.

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

Bleeding during pregnancy: 250-500 mg 3-4 times a day until the bleeding completely stops. The average duration of the treatment course is 7 days.

Interaction

Special clinical studies on interactions of tranexamic acid with other drugs have not been conducted.

Tranexamic acid interferes with the pharmacological effect of fibrinolytic (thrombolytic) drugs.

The combined oral contraceptives increase the risk of venous thromboembolic complications and arterial thrombosis (particularly ischemic stroke and myocardial infarction).

Tranexamic acid has no experience in women taking combined oral contraceptives. Since tranexamic acid has an antifibrinolytic effect, concomitant use with combined oral contraceptives may lead to an additional increased risk of thrombotic complications.

The concomitant use of tranexamic acid with preparations of clotting factors II, VII, IX and X in combination [prothrombin complex] or anti-inhibitorcoagulant complex increases the risk of thrombosis.

The risk of thrombotic complications (particularly myocardial infarction) may be increased when tranexamic acid is used simultaneously with hydrochlorothiazide, desmopressin, ampicillin-sulbactam, ranitidine and nitroglycerin.

When used concomitantly with hemostatic drugs, activation of thrombosis is possible.

The concomitant use 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 a consultation with an ophthalmologist (determination of visual acuity, color vision, ocular fundus condition) is necessary before the start of treatment. Regular ophthalmologic examinations (including evaluation of visual acuity and color perception, examination of fundus with slit lamp, intraocular pressure measurement, assessment of visual fields) are necessary during treatment. If visual disturbances occur during treatment with tranexamic acid, the drug should be discontinued.

In patients with hereditary angioedema receiving tranexamic acid preparations for a long time, regular laboratory monitoring of liver function is necessary.

Tranexamic acid preparations should be used with caution in hematuria caused by renal parenchymal disease because intravascular fibrin deposition is often observed under these conditions, which may aggravate renal damage. In addition, in cases of massive bleeding of any etiology from the upper urinary tract, antifibrinolytic therapy increases the risk of blood clot formation in the renal pelvis and/or ureter and, accordingly, secondary mechanical obstruction of the urinary tract and development of anuria.

While clinical studies have shown no significant increase in the incidence of thrombosis, however, the risk of thrombotic complications cannot be completely excluded. Cases of venous and arterial thrombosis and thromboembolism have been described in patients treated with tranexamic acid. In addition, cases of central retinal artery occlusion and central retinal vein occlusion have been reported. Several patients developed intracranial thrombosis during treatment with tranexamic acid. Accordingly, in patients with a high risk of thrombosis (history of thromboembolic complications, cases of thromboembolism in relatives, verified diagnosis of thrombophilia) tranexamic acid should be used only if absolutely necessary and under strict medical supervision. Prior to the use of tranexamic acid, an examination should be performed to identify risk factors for thromboembolic complications.

The presence of blood in cavities such as the pleural cavity, joint cavities, and urinary tract (including renal pelvis and bladder) can lead to the formation of an “insoluble clot” due to extravascular clotting, which may be resistant to physiological fibrinolysis.

Patients with irregular menstrual bleeding should not be prescribed tranexamic acid until the cause of dysmenorrhea has been determined. If menstrual bleeding volume is inadequately reduced by tranexamic acid treatment, alternative treatment should be considered.

The efficacy and safety of tranexamic acid preparations in the treatment of menorrhagia in patients younger than 16 years of age have not been established.

Tranexamic acid should be used with caution in women concomitantly taking combined oral contraceptives because of the increased risk of thrombosis (See section “Interaction with other medicinal products”).

In patients with DICT who require treatment with tranexamic acid, therapy should be performed under the close supervision of a physician experienced in the treatment of this disease.

In the absence of adequate clinical studies, concomitant use of tranexamic acid with anticoagulants should be under the close supervision of a specialist experienced in the treatment of blood clotting disorders.

If visual impairment occurs while taking tranexamic acid, it is necessary to stop taking the drug and consult a physician.

The effect on the ability to drive vehicles, mechanisms

The ability of tranexamic acid to affect the speed of psychomotor reactions and the ability to operate vehicles or other mechanical devices has not been studied. Tranexamic acid may cause dizziness and visual impairment, and, accordingly, may affect the ability to engage in potentially dangerous activities requiring increased concentration and rapid psychomotor reactions.

Synopsis

Dosage 250 mg: film-coated tablets, white or almost white, round, biconvex.

Contraindications

• Hypersensitivity to tranexamic acid or other drug components;

• Chronic renal failure of severe degree (glomerular filtration rate [GFR] less than 30mg/mL/1.73 m

  sup>2) due to the risk of cumulation;

• Present or past venous or arterial thrombosis (deep leg vein thrombosis, pulmonary thromboembolism, intracranial thrombosis, etc).) when concomitant therapy with anticoagulants is not possible;

• Fibrinolysis due to consumption coagulopathy (hypocoagulable stage of disseminated intravascular coagulation syndrome [DIC]);

• A history of seizures;

• Acquired color vision impairment;

• Subarachnoid hemorrhage (due to risk of cerebral edema, ischemia, and cerebral infarction);

• Children under 3 years of age (solid dosage form).

With caution

• Tranexamic acid should be used with caution in the following situations:

• Hematuria due to renal parenchymal disease and upper urinary tract bleeding (risk of secondary mechanical obstruction of the urinary tract by a blood clot with development of anuria) (See

• Patients at high risk of thrombosis (history of thromboembolic events or family history of thromboembolic disease, verified diagnosis of thrombophilia);

• Disseminated intravascular coagulation syndrome [DIC];

• Presence of blood in cavities, such as pleural cavity, joint cavities, and urinary tract;

• Patients receiving anticoagulant therapy (experience limited);

• Patients receiving clotting factor II, VII, IX, and X drugs in combination with [prothrombin complex] or an anti-inhibitor-coagulant complex (See “Interaction with other blood clotting factors. Interactions with other medications);

• Treatment of menorrhagia in patients younger than 15 years of age (limited experience);

• Patients taking combined oral contraceptives (due to increased risk of venous thromboembolic complications and arterial thrombosis) (See “Interaction with other drugs”). Patients taking combined oral contraceptives (due to increased risk of venous thromboembolic complications and arterial thrombosis).
  

Side effects

The incidence of adverse drug reactions is defined according to the WHO classification: very common (> 1/10), common (> 1/100, ≤ 1/10), infrequent (> 1/1000, ≤ 1/100), rare (> 1/10000,≤ 1/1000), very rare (less than 1/10000), frequency unknown (cannot be established from available data).

Gastrointestinal disorders: frequent – nausea, vomiting, diarrhea (symptoms subside with dose reduction).

Skin and subcutaneous tissue disorders: rare – skin allergic reactions, including allergic dermatitis.

Visual disorders: rare – visual disturbances, including color perception disorders, retinal vascular thrombosis.

Vascular disorders: rare – thromboembolic complications, marked BP decrease (usually due to excessively rapid intravenous administration, in exceptional cases – after oral administration); very rare – arterial and venous thrombosis of various localization; incidence unknown – acute myocardial infarction, cerebral artery thrombosis, carotid artery thrombosis, stroke, deep vein thrombosis in legs, pulmonary embolism, renal artery thrombosis with development of cortical necrosis and acute renal failure, coronary artery occlusion, central artery and retinal vein thrombosis.

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

Nervous system disorders: rarely – dizziness; convulsions (usually when administered intravenously).

Overdose

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

Symptoms: dizziness, headache, nausea, vomiting, diarrhea, orthostatic symptoms (including dizziness when moving from horizontal to vertical position), orthostatic arterial hypotension. Predisposed patients have an increased risk of thrombosis.

Treatment: the antidote is unknown. In case of suspected tranexamic acid overdose, hospitalization is required.When assisted, vomiting should be induced, then gastric lavage should be performed. Activated charcoal reduces absorption of tranexamic acid when taken orally during the first 1-2 hours after overdose.

If the patient is unconscious or if swallowing is impaired, activated charcoal may be administered via a nasogastric tube. Oral or parenteral administration of a large amount of fluid is recommended to enhance renal excretion, increase diuresis, and control the amount of urine secreted. The use of anticoagulants may be justified in some cases.

Pregnancy use

In preclinical studies tranexamic acid had no teratogenic effects. Adequate and strictly controlled studies of efficacy and safety of tranexamic acid in pregnant women have not been conducted. Tranexamic acid penetrates the placenta and may be present in umbilical cord blood at maternal concentrations.

Because reproductive studies in animals cannot always predict reactions in humans, tranexamic acid should only be used during pregnancy if absolutely necessary.

Tranexamic acid penetrates into breast milk (the drug concentration in milk is about 1% of the concentration in maternal blood plasma). The development of antifibrinolytic effect in the infant is unlikely. Nevertheless, caution should be exercised when using tranexamic acid in nursing mothers.

Similarities

Tranexam