Tranexa 500

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TRENAXA 250 TRENAXA 500

Composition:

Active substance: tranexamic acid;

1 tablet contains 250 mg or 500 mg of tranexamic acid;

Excipients: microcrystalline cellulose, povidone, sodium croscarmellose, colloidal anhydrous silicon dioxide, talc, magnesium stearate, titanium dioxide (E 171), hypromellose, propylene glycol, diethyl phthalate.

Pharmaceutical form. Coated tablets.

Main physicochemical properties:

250 mg tablets: white or almost white, round, biconvex, coated tablets, smooth on both sides;

500 mg tablets: white or almost white, round, biconvex, coated tablets, smooth on one side and with a score line on the other.

Pharmacotherapeutic group.

Antihemorrhagic agents. 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 effects in bleeding associated with increased fibrinolysis (thrombocyte pathology, menorrhagia). In addition, tranexamic acid exerts antiallergic and anti-inflammatory effects by suppressing the formation of kinins and other active peptides involved in allergic and inflammatory reactions.

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 blood plasma – up to 7–8 hours.

A minor portion undergoes metabolism. The AUC curve has a triphasic pattern with a terminal half-life (T_1/2) of 3 hours. Total renal clearance equals plasma clearance (7 L/h). Excreted by the kidneys (main route – 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 tranexamic acid accumulation.

Clinical characteristics.

Indications.

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

Hereditary angioneurotic edema.

Contraindications.

Hypersensitivity to the drug or to other components of the drug, severe renal insufficiency, macroscopic hematuria, high risk of thrombosis, thrombophlebitis; active thromboembolic disease, history of venous or arterial thrombosis; myocardial infarction, subarachnoid hemorrhage, acute venous or arterial thrombosis; fibrinolytic states following coagulopathy due to exhaustion, except excessive activation of the fibrinolytic system in acute severe bleeding; history of seizures; color vision disturbances.

Interaction with other medicinal products and other types of interactions.

Tranexamic acid is incompatible with urokinase, noradrenaline bitartrate, desoxyepinephrine hydrochloride, metharamine bitartrate, dipyridamole, diazepam. Highly active prothrombin complex concentrates and antifibrinolytic agents, antithrombin inhibitor coagulation complexes should not be used simultaneously with tranexamic acid. The combination of chlorpromazine and tranexamic acid should be avoided in patients with subarachnoid hemorrhage; this may lead to cerebral vasospasm and cerebral ischemia, and possibly to reduced cerebral blood flow; the pharmacological properties of both drugs may contribute to the development of vascular spasm 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 for use.

In renal impairment (depending on the degree of serum creatinine elevation), reduce the dose and frequency of administration. Patients with impaired renal function have increased plasma concentrations of the drug. Therefore, these patients should receive a reduced dose. Cases of urinary obstruction due to clot formation originating from bleeding sites in the upper urinary tract have been reported in patients receiving the drug. Cases of venous and arterial thrombosis or thromboembolism have been reported in patients treated with tranexamic acid. In addition, cases of central retinal artery occlusion and central retinal vein occlusion have been reported. Patients receiving the drug for longer than several days should undergo ophthalmological examination, including assessment of visual acuity, color vision, fundus examination, visual field testing, and liver function monitoring.

Patients experiencing visual disturbances must discontinue treatment.

Patients with thromboembolic disease may be at increased risk of venous or arterial thrombosis.

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

The drug should not be administered to patients with disseminated intravascular coagulation (DIC).

Tranexamic acid should not be administered to patients with hyperfibrinolysis resulting from disseminated intravascular coagulation.

Tranexamic acid has been detected in semen at fibrinolytic concentrations, but it does 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-dose tranexamic acid 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.

Women with irregular menstrual bleeding should not use tranexamic acid until the underlying cause of bleeding has been established. If tranexamic acid does not reduce the intensity of menstrual bleeding, alternative treatment options should be considered.

The drug should be administered to patients with a history of thromboembolic events or those with a family history of thromboembolic disorders (patients with thrombophilia) only under strict medical indications and under close physician supervision.

There is no clinical experience with the use of tranexamic acid for the treatment of menorrhagia in children under 15 years of age.

Cases of seizures have been reported in association with tranexamic acid treatment. In cardiac surgery, most of these cases were reported after intravenous administration of high-dose 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 administered during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus or infant. If use of the drug is necessary during lactation, a decision should be made whether to discontinue breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Patients should refrain from driving or operating complex machinery during treatment with the drug.

Dosage and Administration

Administer the drug orally to adults regardless of food intake.

Local fibrinolysis: The recommended dose is 1–1.5 g 2–3 times daily.

Prostatectomy: For prevention and treatment of hemorrhage in patients at increased risk before or after surgery, administer tranexamic acid by injection initially, followed by tablets 1 g (2 tablets of 500 mg) 3–4 times daily until macroscopic hematuria resolves.

Menorrhagia: The recommended dose is 1 g 3 times daily for no more than 4 days. In cases of prolonged menstrual bleeding, the dose may be increased but should not exceed the maximum daily dose of 4 g (8 tablets of 500 mg). Treatment should not be initiated before the onset of menstrual bleeding.

Epistaxis: 1 g 3 times daily for 7 days.

Cervical conization: 500 mg 3 times daily for up to 12 days.

Post-traumatic hematoma: The recommended dose is 1 g 3 times daily orally.

Hereditary angioedema: Some patients, who are aware of the pattern of disease exacerbations, usually require 1–1.5 g 2–3 times daily for several days. Other patients should take the drug at the same dosage over a prolonged period depending on the course of the disease.

Tooth extraction in patients with hemophilia: The recommended dose is 25 mg/kg of tranexamic acid administered orally every 8 hours, starting 1 day before surgery and continuing for 2–8 days afterward.

Patients with renal impairment.

Dosage adjustment is required for patients with mild to moderate renal insufficiency according to plasma creatinine levels.

Elderly patients.

In the absence of renal excretory function impairment, dose adjustment is not required.

For patients aged 15 years and older, the recommended dose is 25 mg/kg body weight.

The duration of treatment is usually 2–8 days.

Children.

Clinical experience with the use of tranexamic acid in children and adolescents under 15 years of age is lacking.

However, data on dosing, efficacy, and safety under these conditions are limited.

Overdose.

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

Treatment: induce emesis, followed by gastric lavage and administration of activated charcoal. Maintain high fluid intake to promote renal elimination of the drug. In patients predisposed to thrombosis, there is a risk of developing thrombotic events. Anticoagulant therapy should be considered.

Adverse Reactions.

Gastrointestinal system: nausea, vomiting, heartburn, diarrhea, which resolve upon dose reduction, decreased appetite, abdominal pain.

Skin and subcutaneous tissue: rash, pruritus, urticaria.

Nervous system: drowsiness, dizziness, seizures, especially with improper use.

Eyes: color vision disturbances, visual disturbances, seizures, retinal venous stasis, retinal vein/artery occlusion.

Immune system: hypersensitivity reactions, including anaphylaxis.

Vascular system: arterial or venous thrombosis, thromboembolism, arterial hypotension.

Renal system: acute cortical necrosis of the kidneys.

Shelf life.

3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

6 tablets per strip, 2 strips per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Macleods Pharmaceuticals Limited.

Manufacturer's address and place of business.

Phase II, Plot No. 12,15, 21, 23, 24, 25, 26, 27, 28, and 30, Survey No. 366, Premier Industrial Estate, Kachigam, Daman – 396210, India.