Cyclogemal^® (Tablets) Instructions for Use

Marketing Authorization Holder

Otisipharm, JSC (Russia)

Manufactured By

Pharmstandard-UfaVITA OJSC (Russia)

ATC Code

B02AA02 (Tranexamic acid)

Active Substance

Tranexamic acid (Rec.INN registered by WHO)

Dosage Form

Cyclogemal®

Film-coated tablets, 250 mg: 10, 20, 30, 50, or 60 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex; the cross-section is white or almost white.

Excipients: microcrystalline cellulose – 45.05 mg, pregelatinized starch – 4.85 mg, sodium carboxymethyl starch – 6.2 mg, talc – 7.99 mg, colloidal silicon dioxide – 6.01 mg, sodium stearyl fumarate – 9.9 mg.

Shell composition VIVACOAT^® PA-1P-000 [hypromellose 6 cPz (hydroxypropyl methylcellulose 6 cPz) – 3.51 mg, titanium dioxide – 2.7 mg, polydextrose (E1200) – 1.35 mg, talc – 0.9 mg, polyethylene glycol-3350 – 0.54 mg] – 9 mg.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.

Clinical-Pharmacological Group

Hemostatic agent. Fibrinolysis inhibitor – inhibitor of plasminogen to plasmin conversion

Pharmacotherapeutic Group

Hemostatic agents; antifibrinolytic agents; amino acids

Pharmacological Action

Tranexamic acid specifically inhibits the activation of profibrinolysin (plasminogen) and its conversion to fibrinolysin (plasmin).

It 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 an anti-allergic and anti-inflammatory effect.

Pharmacokinetics

Absorption after oral administration of doses in the range of 0.5-2 g is 30-50%. Time to reach C_max after oral administration of 0.5, 1, and 2 g is 3 hours, C_max is 5, 8, and 15 µg/ml, respectively. Binding to plasma proteins (profibrinolysin) is less than 3%. It is distributed relatively evenly in tissues (exception – cerebrospinal fluid, where the concentration is 1/10 of the plasma concentration); penetrates the placental barrier, into breast milk (about 1% of the concentration in maternal plasma). It is found in seminal fluid, where it reduces fibrinolytic activity but does not affect sperm migration. Initial V_d is 9-12 L. The antifibrinolytic concentration in various tissues persists for 17 hours, in plasma – up to 7-8 hours. A small part is metabolized. The concentration-time curve has a three-phase shape with T_1/2 in the terminal phase of 3 hours. Total renal clearance is equal to plasma clearance (7 L/h). It is excreted by the kidneys (the main route is glomerular filtration) – more than 95% unchanged within the first 12 hours. Two metabolites of tranexamic acid have been identified: N-acetylated and deaminated derivative.

Indications

Short-term treatment of bleeding associated with increased fibrinolysis in the following pathological conditions: prostatectomy; surgical interventions on the bladder; abnormal uterine bleeding (AUB); nosebleed; cervical conization; traumatic hyphema (hemorrhage into the anterior chamber of the eye).

Prevention and treatment of bleeding in patients with hemophilia undergoing minor surgery (including tooth extraction).

Hereditary angioedema (prevention of disease exacerbations).

Bleeding during pregnancy.

ICD codes

Dosage Regimen

Administer orally with water.

For adults, the typical single dose is 250 mg to 1500 mg.

For children, calculate the daily dose at 25 mg per kg of body weight.

Divide the total daily dose for children into 2 or 3 separate administrations.

For abnormal uterine bleeding, administer 1000-1500 mg three to four times daily for the duration of menses.

For hereditary angioedema prophylaxis, use a dose of 1000-1500 mg two to three times daily.

For bleeding associated with tooth extraction in hemophilia, administer 1500 mg three to four times daily for 2 to 8 days.

Adjust the frequency and duration of therapy based on the specific indication and clinical response.

In patients with mild to moderate renal impairment (GFR 30-89 ml/min/1.73 m²), reduce the dose by 25%.

In patients with moderate to severe renal impairment (GFR 10-29 ml/min/1.73 m²), reduce the dose by 50%.

Do not exceed a maximum daily dose of 4000 mg (4 grams) in adults without explicit medical direction.

Discontinue use immediately if visual disturbances occur and seek medical attention.

Adverse Reactions

From the immune system very rarely – hypersensitivity reaction, including anaphylactic shock.

From the nervous system rarely – dizziness, convulsions.

From the organ of vision rarely – visual disturbances, including impaired color perception, retinal vascular thrombosis.

From the vascular system rarely – thromboembolic complications, marked decrease in blood pressure (usually due to excessively rapid IV administration); very rarely – arterial and venous thromboses of various locations; frequency unknown – acute myocardial infarction, cerebral artery thrombosis, carotid artery thrombosis, stroke, deep vein thrombosis of the legs, pulmonary embolism, renal artery thrombosis with the development of cortical necrosis and acute renal failure, aortocoronary bypass occlusion, central retinal artery and vein thrombosis.

From the digestive system often – nausea, vomiting, diarrhea (symptoms disappear when the dose is reduced).

From the skin and subcutaneous tissues rarely – skin allergic reactions, including allergic dermatitis.

Contraindications

Hypersensitivity to tranexamic acid; severe chronic renal failure (GFR less than 30 ml/min/1.73 m²) due to the risk of accumulation; current or history of venous or arterial thrombosis (including deep vein thrombosis of the legs, pulmonary embolism, intracranial vascular thrombosis) if simultaneous anticoagulant therapy is not possible; fibrinolysis due to consumption coagulopathy (hypocoagulation stage of DIC syndrome); history of seizures; acquired color vision impairment; subarachnoid hemorrhage (due to the risk of cerebral edema, cerebral ischemia and infarction); children under 3 years of age.

With caution

Hematuria caused by renal parenchymal diseases, and bleeding from the upper urinary tract (risk of secondary mechanical obstruction of the urinary tract by a blood clot with the development of anuria); patients at high risk of thrombosis (history of thromboembolic events or family history of thromboembolic diseases, verified diagnosis of thrombophilia); DIC syndrome; presence of blood in cavities, for example, in the pleural cavity, joint cavities and urinary tract; patients receiving anticoagulant therapy (experience of use is limited); simultaneous use of blood coagulation factors II, VII, IX and X in combination (prothrombin complex) or anti-inhibitor coagulant complex; treatment of abnormal uterine bleeding in patients under 15 years of age (experience of use is limited); women taking combined oral contraceptives (due to an increased risk of venous thromboembolic complications and arterial thromboses).

Use in Pregnancy and Lactation

Tranexamic acid should be used during pregnancy only in case of extreme necessity.

Use with caution during breastfeeding.

Use in Hepatic Impairment

In patients with impaired liver function, dose adjustment is not required.

Use in Renal Impairment

Contraindication: severe chronic renal failure (GFR less than 30 ml/min/1.73 m²).

In mild to moderate renal failure, adjustment of the dosage regimen is required.

Pediatric Use

Contraindicated in children under 3 years of age.

Use with caution in patients under 15 years of age.

Geriatric Use

In elderly patients without renal failure, dose adjustment is not required.

Special Precautions

In patients with hereditary angioedema, consultation with an ophthalmologist is necessary before starting treatment (determination of visual acuity, color vision, fundus condition). During treatment, regular ophthalmological examination is necessary (including assessment of visual acuity and color perception, fundus examination with a slit lamp, measurement of intraocular pressure, assessment of visual fields). If visual disturbances occur during treatment with tranexamic acid, the use should be discontinued. If visual impairment is noted while taking tranexamic acid, the patient should stop taking the drug and consult a doctor.

In patients with hereditary angioedema who are 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 diseases, since intravascular fibrin deposition is often observed under these conditions, which may worsen kidney 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 the development of anuria.

Although conducted clinical studies have not revealed a significant increase in the frequency of thrombosis, the risk of thrombotic complications cannot be completely excluded. Cases of venous and arterial thrombosis and thromboembolism have been described in patients receiving tranexamic acid. In addition, cases of occlusion of the central retinal artery and central retinal vein have been reported. Several patients developed intracranial thrombosis during treatment with tranexamic acid. Accordingly, in patients at high risk of thrombosis (history of thromboembolic complications, cases of thromboembolism in relatives, verified diagnosis of thrombophilia), tranexamic acid should be used only in case of extreme necessity and under strict medical supervision.

Before using tranexamic acid, an examination aimed at identifying risk factors for thromboembolic complications should be performed.

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

Women with irregular menstrual bleeding should not be prescribed tranexamic acid preparations until the cause of dysmenorrhea is established. If the volume of menstrual bleeding does not adequately decrease during treatment with tranexamic acid, the possibility of alternative treatment should be considered.

Data on the efficacy and safety of tranexamic acid in the treatment of menorrhagia in patients under 15 years of age are insufficient, so caution is necessary when using it.

Tranexamic acid should be used with caution in women simultaneously taking combined oral contraceptives due to an increased risk of thrombosis.

In patients with DIC syndrome who require treatment with tranexamic acid, therapy should be carried out under the careful supervision of a physician experienced in the treatment of this disease.

Due to the lack of adequate clinical studies, simultaneous use of tranexamic acid with anticoagulants should be carried out under careful supervision by a specialist experienced in the treatment of coagulation disorders.

Effect on ability to drive vehicles and mechanisms

Tranexamic acid may cause dizziness and visual disturbances, and, accordingly, may affect the ability to engage in potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

Drug Interactions

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 thromboses (in particular, ischemic stroke and myocardial infarction). Experience with the use of tranexamic acid in women taking combined oral contraceptives is lacking. Since Tranexamic acid has an antifibrinolytic effect, simultaneous use with combined oral contraceptives may lead to an additional increase in the risk of thrombotic complications.

Simultaneous use of tranexamic acid with blood coagulation factors II, VII, IX and X in combination [prothrombin complex] or anti-inhibitor coagulant complex increases the risk of thrombosis.

An increase in the risk of thrombotic complications (in particular, myocardial infarction) is possible with the simultaneous use of tranexamic acid with hydrochlorothiazide, desmopressin, ampicillin-sulbactam, ranitidine and nitroglycerin.

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

Simultaneous administration of tranexamic acid with anticoagulants should be carried out under strict medical supervision (experience of use is limited).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.