Tughina-500

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT TUGYNA-500 (TUGYNA-500)

Composition:

Active substance: tranexamic acid;

1 tablet contains 500 mg of tranexamic acid;

Excipients: microcrystalline cellulose, corn starch, sodium croscarmellose, stearic acid, colloidal silicon dioxide anhydrous, magnesium stearate, film coating Opadry White YS-1R-7003 (titanium dioxide (E 171)), isopropyl alcohol, dichloromethane.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white or almost white, capsule-shaped, biconvex film-coated tablets with a break line on one side and engraved "500" on the other side.

Pharmacotherapeutic group.

Antihemorrhagic agents. Fibrinolysis inhibitors. Amino acids. Tranexamic acid.

ATC code B02A A02.

Pharmacological properties

Pharmacodynamics

An antifibrinolytic agent. Tranexamic acid specifically inhibits activation of plasminogen and its conversion into plasmin. It exerts local and systemic hemostatic effects in bleeding associated with increased fibrinolysis (thrombocyte disorders, 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 μg/mL, 8 μg/mL, 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 levels); 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 sperm motility. 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 (mainly via 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 on the prostate gland and in the postoperative period, hemorrhagic complications of fibrinolytic therapy), or localized (uterine, nasal bleeding, post-traumatic hyphema, bleeding after prostatectomy or bladder interventions, cervical conization, tooth extraction in patients with hemophilia). Hereditary angioneurotic edema.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients; severe renal insufficiency due to the risk of drug accumulation; active thromboembolic disorders; history of venous or arterial thrombosis; fibrinolytic states following coagulopathy due to exhaustion; history of seizures.

Interaction with other medicinal products and other forms of interaction.

Tranexamic acid counteracts the thrombolytic effect of fibrinolytic agents.

Special precautions for use.

In cases of renal origin hematuria (especially in hemophilia), there is a risk of mechanical anuria due to clot formation in the ureters.

During long-term therapy, patients with hereditary angioedema should undergo regular eye examinations (e.g., visual acuity, visual fields, intraocular pressure, fundoscopy) and liver function tests.

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

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

Patients with a history of thromboembolic disease or a family history of thromboembolic disorders (patients with thrombophilia) should use tranexamic acid only when there is a clear medical indication and under strict medical supervision.

In patients with impaired renal function, plasma concentrations of the drug are increased; therefore, dose reduction is recommended in such patients.

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

If visual disturbances occur, treatment must be discontinued.

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

Seizures have been reported during treatment with tranexamic acid. Most of these cases occurred after intravenous administration of high doses of tranexamic acid during coronary artery bypass grafting.

Use during pregnancy or breastfeeding.

Pregnancy

Although preclinical studies have not shown teratogenic effects of tranexamic acid on fetal development, general recommendations for the use of medicinal products during pregnancy should be followed.

Tranexamic acid crosses the placenta.

Breastfeeding period

Tranexamic acid is excreted in breast milk at concentrations approximately 100 times lower than those in maternal blood. An antifibrinolytic effect in infants is unlikely.

Ability to influence reaction rate while driving or operating machinery.

The medicinal product has no effect or has negligible effect on the ability to drive or operate machinery.

Method of Administration and Dosage

Local fibrinolysis: The recommended standard dose is 15−25 mg/kg body weight (i.e. 2−3 tablets) 2−3 times daily. For the indications listed below, the following dosage regimens may be used:

Prostatectomy: For prevention and treatment of hemorrhages in patients at increased risk, tranexamic acid is initially administered by injection, followed by oral administration of 1 g (2 tablets of 500 mg) 3–4 times daily until macroscopic hematuria disappears.

Menorrhagia: The recommended dose is 2 tablets (1 g) 3 times daily for no more than 4 days. In cases of prolonged menstrual bleeding, the dose may be increased, but must not exceed the maximum daily dose (8 tablets of 500 mg per day). Treatment should not be initiated before the onset of menstrual bleeding.

Epistaxis (nosebleeds): For recurrent episodes, administer 2 tablets of 500 mg 3 times daily for 7 days.

Cervical conization: 3 tablets of 500 mg 3 times daily.

Post-traumatic hyphema: 2–3 tablets of 500 mg 3 times daily. The dose is 25 mg/kg 3 times daily.

Hereditary angioedema: Some patients familiar with the pattern of their disease episodes may require only 2–3 tablets of 500 mg 2–3 times daily for several days. Others 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: 2–3 tablets orally every 8 hours. The dose is 25 mg/kg.

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

Patients with renal impairment: Dose adjustment is necessary for patients with mild to moderate renal impairment, based on plasma creatinine levels.

Children.

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.

The recommended dose for children is 25 mg/kg. Data on the efficacy, dosing, and safety of tranexamic acid in pediatric patients are limited.

Overdose.

Symptoms: nausea, vomiting, orthostatic symptoms and/or arterial hypotension, dizziness, headache, seizures.

Treatment: induce vomiting, gastric lavage, administration of activated charcoal. It is necessary to drink large amounts of fluid to promote renal excretion. In individuals predisposed to thrombosis, there is a risk of developing thrombotic events. Anticoagulant therapy should be considered.

Adverse Reactions

The adverse reactions listed below are categorized by organ system classes and frequency of occurrence. Frequencies are defined as follows: very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from available data).

Immune system disorders: very rare – hypersensitivity reactions, including anaphylaxis.

Gastrointestinal disorders: very rare – nausea, vomiting, diarrhea, which resolve upon dose reduction.

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

Nervous system disorders: frequency not known – seizures, particularly in cases of improper use (see sections "Contraindications" and "Special Warnings and Precautions for Use").

Eye disorders: rare – colour vision disorders, retinal vein/artery occlusion.

Vascular disorders: rare – thromboembolic complications; very rare – arterial or venous thrombosis at any site.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicinal product registration is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report any suspected adverse reactions and lack of efficacy through the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

Store in the original packaging, protected from light, in a place inaccessible to children, at a temperature not exceeding 25 °C.

Packaging

10 tablets per blister; 1 blister per cardboard pack.

Prescription status

Prescription only.

Manufacturer

Tulip Lab Pvt. Ltd.

Tulip Lab Pvt. Ltd.

Manufacturer's address and location of operation

F-20/21, Ranjangaon MIDC, Tal. Shirur, Dist. Pune, India

F-20/21, Ranjangaon MIDC, Tal. Shirur, Dist - Pune, India