Tranexamic acid-zdorovya

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT TRANEXAMIC ACID-ZDOROVYE (TRANEXAMIC ACID-ZDOROVYE)

Composition:

Active ingredient: tranexamic acid;

1 tablet contains 500 mg of tranexamic acid;

Excipients: microcrystalline cellulose, povidone, colloidal anhydrous silicon dioxide, talc, magnesium stearate, crospovidone, dry mixture "Opadry white" containing titanium dioxide (E 171), hypromellose, triacetin.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets, white or almost white, oval-shaped, with a score line on one side.

Pharmacotherapeutic group. Antihemorrhagic agents, antifibrinolytic amino acids. Fibrinolysis inhibitors. ATC code B02A A02.

Pharmacological properties.

Pharmacodynamics.

An antifibrinolytic agent. Tranexamic acid specifically inhibits the activation of plasminogen (profibrinolysin) and its conversion into plasmin (fibrinolysin). It exerts local and systemic hemostatic action in bleeding associated with increased fibrinolysis (platelet disorders, menorrhagia). Additionally, tranexamic acid, by suppressing the formation of kinins and other active peptides involved in allergic and inflammatory reactions, exhibits antiallergic and anti-inflammatory effects.

Pharmacokinetics.

Oral absorption of doses in the range of 0.5–2 g is 30–50 %. Tmax after oral administration of 0.5 g, 1 g, and 2 g is 3 hours; Cmax is 5, 8, and 15 µg/mL, respectively. Plasma protein binding (to plasminogen) is not less than 3 %.

Distributed relatively uniformly in tissues (except cerebrospinal fluid, where concentration is 1/10 of plasma concentration); crosses the placental barrier and is excreted into breast milk (approximately 1 % of maternal plasma concentration). Detected in seminal fluid, where it reduces fibrinolytic activity but does not affect spermatozoa migration. Initial volume of distribution is 9–12 L. Antifibrinolytic concentrations in various tissues are maintained for 17 hours, in plasma – up to 7–8 hours.

A minor portion undergoes metabolism. The AUC curve has a triphasic profile with a terminal T1/2 of 3 hours. Total renal clearance equals plasma clearance (7 L/h). Excreted by the kidneys (main pathway – glomerular filtration), approximately 95 % unchanged within the first 12 hours.

Two metabolites of tranexamic acid have been identified: N-acetylated and deaminated derivatives. In renal impairment, there is a risk of accumulation of tranexamic acid.

Clinical characteristics.

Indications.

Bleeding or risk of bleeding due to enhanced fibrinolysis, either generalized (bleeding during prostate surgery and in the postoperative period, hemorrhagic complications of fibrinolytic therapy) or local (uterine, gastrointestinal, nasal bleeding, post-traumatic hyphema, bleeding after prostatectomy or urinary bladder interventions, tonsillectomy, cervical conization, dental extraction in patients with hemophilia).

Hereditary angioedema.

Contraindications.

Hypersensitivity to tranexamic acid or to any of the excipients, severe renal insufficiency (due to risk of accumulation), macroscopic hematuria, acute thromboembolic disorders, acute venous or arterial thrombosis, thrombophlebitis, history of arterial or venous thrombosis, high risk of thrombosis, myocardial infarction, subarachnoid hemorrhage, history of seizures; fibrinolytic states due to consumption coagulopathy, except in cases of excessive activation of the fibrinolytic system during acute severe bleeding; color vision disturbances.

Interaction with other medicinal products and other forms of interaction.

Tranexamic acid is incompatible with urokinase, norepinephrine bitartrate, desoxyephedrine hydrochloride, metharamine bitartrate, dipyridamole, and diazepam. Highly active prothrombin complexes and antifibrinolytic agents, as well as anti-inhibitor coagulation complexes, should not be administered simultaneously with tranexamic acid. The combination of chlorpromazine and tranexamic acid should be avoided in patients with subarachnoid hemorrhage, as it may lead to cerebral vasospasm and cerebral ischemia, possibly resulting in reduced cerebral blood flow; the pharmacological properties of both agents may contribute to the development of vasospasm and cerebral ischemia in these patients. Tranexamic acid should be used with caution in patients taking oral contraceptives, as this increases the risk of thrombosis.

Special precautions.

In renal insufficiency (depending on the degree of serum creatinine elevation), the dose and frequency of administration must be reduced.

In cases of renal origin hematuria (especially in hemophilia), the risk of mechanical anuria due to blood clot formation in the urinary tract increases.

Cases of central retinal artery and central retinal vein occlusion have been reported. Patients receiving the drug for more than several days should undergo an ophthalmological examination, including assessment of visual acuity, color perception, fundus, visual fields, and liver function evaluation.

Treatment must be discontinued in patients experiencing visual disturbances.

This medicinal product should not be used until the cause of menstrual cycle disturbances has been established. If menstrual bleeding cannot be controlled with tranexamic acid, alternative treatment should be considered.

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

Cases of venous and arterial thrombosis or thromboembolism have been reported in patients receiving tranexamic acid. Patients with previous thromboembolic complications or a family history of thromboembolic disorders (patients with thrombophilia) should use the drug only when clearly indicated and under strict medical supervision.

The use of tranexamic acid is not recommended in cases of increased fibrinolysis due to disseminated intravascular coagulation.

Patients with disseminated intravascular coagulation requiring treatment with tranexamic acid should be managed under the supervision of a physician experienced in treating such conditions.

There is no clinical experience with the use of tranexamic acid in children under 15 years of age with menorrhagia; therefore, the drug should not be used in this patient population.

Tranexamic acid should not be administered concomitantly with Factor IX complex or anti-inhibitor coagulation factor complexes, as this may increase the risk of thrombosis.

Tranexamic acid has been detected in semen at fibrinolytic concentrations, but it did not affect sperm motility. Clinical studies have not revealed any effect on fertility.

Seizures have been reported during the use of tranexamic acid. Most of these cases occurred after intravenous administration of high doses during coronary artery bypass grafting (CABG). When recommended low doses of tranexamic acid are used, the incidence of postoperative seizures is similar to that in patients not receiving tranexamic acid.

Use during pregnancy or breastfeeding.

Tranexamic acid crosses the placenta and is excreted in breast milk. Safety studies of the drug use during pregnancy have not been conducted; therefore, the drug should be prescribed to pregnant women only when the expected benefit to the mother outweighs the potential risk to the fetus.

If use of the drug is necessary, the decision should be made whether to discontinue breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

During treatment with the drug, patients should refrain from driving or operating complex machinery.

Dosage and Administration

The medication should be administered orally. The drug can be taken regardless of food intake.

Adult patients with normal renal function.

Dosage recommendations should follow the guidelines below for adult patients with normal renal function, in whom creatinine clearance is over 50 mL/min.

Elderly patients.

Dose adjustment is not required in the absence of impaired renal excretory function.

Children.

To be administered to children aged 12 years and older at a dose of 20–25 mg/kg. The duration of treatment is usually 2–8 days.

Patients with renal impairment.

Dose adjustment is necessary according to plasma creatinine levels.

Children. Do not use in children under 12 years of age.

There is no clinical experience with the use of tranexamic acid in children under 15 years of age with menorrhagia; therefore, this medicinal product should not be used in this patient population.

Overdose.

Symptoms: nausea, vomiting, abdominal pain, orthostatic hypotension, arterial hypotension, dizziness, headache, seizures, or exacerbation of other adverse reactions, including thrombosis risk.

Treatment: induce vomiting, gastric lavage, administration of activated charcoal. It is necessary to consume large amounts of fluid to promote renal excretion. Provide symptomatic treatment and, if necessary, anticoagulant therapy.

Side effects.

Immune system: hypersensitivity reactions, including anaphylaxis.

Gastrointestinal system: nausea, vomiting, heartburn, diarrhea, abdominal pain, decreased appetite.

Skin and subcutaneous tissue: rash, pruritus, allergic skin reactions.

Nervous system: drowsiness, dizziness, seizures.

Eye disorders: visual disturbances, color vision abnormalities, retinal artery occlusion, stasis retinopathy.

Vascular disorders: thromboembolic complications, arterial or venous thrombosis at any site, arterial hypotension.

Renal disorders: acute cortical necrosis of the kidneys.

Shelf life. 2 years.

Storage conditions. Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. Tablets No. 20 (10×2) in blisters in a box.

Prescription category. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Manufacturer's address and place of business.

22 Shevchenka Street, Kharkiv, Kharkiv region, 61013, Ukraine.