Texacaind

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TЕXAKIND (TEXAKIND)

Composition:

Active substance: tranexamic acid;

1 ml of solution contains 100 mg of tranexamic acid;

Excipient: water for injections.

Pharmaceutical form. Solution for injection.

Main physico-chemical properties: clear, colorless solution.

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

Pharmacological Properties

Pharmacodynamics

Tranexamic acid exerts an antihemorrhagic effect by inhibiting the fibrinolytic activity of plasmin.

Tranexamic acid forms a complex with plasminogen; tranexamic acid binds to plasminogen during its conversion into plasmin.

The activity of the tranexamic acid–plasmin complex against fibrin is lower than that of free plasmin.

In vitro studies have shown that high doses of tranexamic acid reduce complement activity.

Children

Children aged 1 year and older

Literature data identified 12 studies on efficacy in pediatric cardiac surgery involving 1073 children, of whom 631 received tranexamic acid. Most of these studies were placebo-controlled. The study population was heterogeneous in terms of age, types of surgery, and dosing regimens. Results from studies using tranexamic acid indicate reduced blood loss and decreased need for blood products in pediatric cardiac surgery with cardiopulmonary bypass, where there is a high risk of bleeding, especially in cyanotic patients or those undergoing reoperation.

The most commonly used dosing regimen:

• Initial bolus dose of 10 mg/kg body weight administered after induction of anesthesia and before skin incision;
• Continuous infusion at 10 mg/kg body weight/hour or administration into the cardiopulmonary bypass circuit at a dose adjusted to the cardiopulmonary bypass procedure, or according to patient body weight at 10 mg/kg body weight, or according to the priming volume of the cardiopulmonary bypass circuit, with the final dose administered at 10 mg/kg body weight at the end of cardiopulmonary bypass use.

Although studies have been limited in number, available data suggest that continuous infusion is preferable, as it maintains therapeutic plasma concentrations throughout the entire surgical procedure.

No specific dose-effect or pharmacokinetic studies have been conducted in children.

Pharmacokinetics

Absorption

Peak plasma concentrations of tranexamic acid are rapidly achieved following short intravenous infusion, after which plasma concentrations decline multi-exponentially.

Distribution

Plasma protein binding of tranexamic acid is approximately 3% at therapeutic plasma levels and is likely entirely explained by its binding to plasminogen. Tranexamic acid does not bind to serum albumin. The initial volume of distribution is approximately 9 to 12 liters.

Tranexamic acid crosses the placenta. After intravenous injection at a dose of 10 mg/kg body weight in 12 pregnant women, serum concentration of tranexamic acid ranged from 10 to 53 μg/mL, while in umbilical cord blood it ranged from 4 to 31 μg/mL. Tranexamic acid rapidly penetrates into joint fluid and synovial membrane. After intravenous injection at a dose of 10 mg/kg body weight in 17 patients undergoing knee surgery, concentrations in joint fluid were similar to those in corresponding serum samples. Concentrations of tranexamic acid in other tissues are a fraction of those observed in blood (breast milk, 0.01; cerebrospinal fluid, 0.1; intraocular fluid, 0.1). Tranexamic acid has been detected in semen, where it inhibits fibrinolytic activity but does not affect sperm migration.

Elimination

Tranexamic acid is primarily excreted unchanged in urine. Glomerular filtration is the main route of elimination. Renal clearance equals plasma clearance (110–116 mL/min). Excretion of tranexamic acid is approximately 90% within the first 24 hours after intravenous administration of a 10 mg/kg body weight dose. The elimination half-life of tranexamic acid is approximately 3 hours.

Other special population groups

Plasma concentrations increase in patients with renal impairment.

No specific pharmacokinetic studies have been conducted in children.

Preclinical safety data

Preclinical data reveal no special hazard to humans based on conventional studies of safety pharmacology, repeat-dose toxicity, genotoxicity, carcinogenic potential, reproductive and developmental toxicity. Epileptogenic activity was observed in animals following intraperitoneal administration of tranexamic acid.

Clinical characteristics.

Indications.

Tranexamic acid is indicated in adults and children aged 1 year and older for the prevention and treatment of hemorrhage due to systemic or local fibrinolysis.

Specific indications include:

• bleeding due to systemic or local fibrinolysis, such as:
  • menorrhagia and metrorrhagia;
  • gastrointestinal bleeding;
  • hemorrhagic disorders of urination, in addition to prostate surgery or surgical procedures affecting the urinary tract;
• ear, nose, and throat surgery (adenoidectomy, tonsillectomy, dental interventions);
• gynecological surgery or obstetric complications;
• thoracic and abdominal surgery and other major surgical procedures, such as cardiovascular surgery;
• control of bleeding following administration of a fibrinolytic agent.

Contraindications.

Hypersensitivity to the active substance of the medicinal product.

Acute venous or arterial thrombosis (see section "Special precautions").

Fibrinolytic states following consumption coagulopathy, except those with predominant activation of the fibrinolytic system associated with acute severe bleeding (see section "Special precautions").

Severe renal function impairment (risk of accumulation).

History of seizures.

Intracerebral and intraventricular administration, intracerebral administration (risk of cerebral edema and seizures).

Special safety precautions.

The medicinal product is intended for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Interaction with other medicinal products and other forms of interaction.

No interaction studies have been conducted. Concomitant treatment with anticoagulants should be performed under strict supervision of a physician experienced in this field. Medicinal products affecting hemostasis should be used with caution in patients who have received tranexamic acid. There is a risk of increased thrombotic potential, for example with estrogens. Alternatively, the antifibrinolytic effect of the drug may be antagonized by thrombolytic agents.

Special precautions for use.

When using the medicinal product, indications and method of administration must be strictly observed:

• intravenous injections or infusions should be administered very slowly (maximum 1 mL/min);
• tranexamic acid must not be administered intramuscularly.

Seizures

Cases of seizures have been reported during the use of tranexamic acid. In coronary artery surgery, most cases of seizures were reported after intravenous administration of high doses of tranexamic acid. When recommended lower doses of tranexamic acid are used, the frequency of postoperative seizures is the same as in untreated patients.

Visual disturbances

Possible visual disturbances, including impaired vision, blurred vision, and impaired color vision, should be taken into account; if such disturbances occur, treatment should be discontinued. During prolonged continuous use of tranexamic acid, regular ophthalmological examinations should be scheduled (eye examination including visual acuity, color vision, fundus examination, and visual field testing). When prescribing tranexamic acid to patients with pre-existing ophthalmological pathology, especially retinal disorders, the physician should decide, in consultation with a specialist, on the duration of treatment in each individual case.

Hematuria

In hematuria originating from the upper urinary tract, there is a risk of urethral obstruction.

Thromboembolic disorders

Risk factors for thromboembolic disease should be considered before administering tranexamic acid. Tranexamic acid should be administered only under strict medical indications, after consultation with a physician experienced in hemostasis, and under close medical supervision to patients with a history of thromboembolic disorders or those with a family history of increased incidence of thromboembolic disorders (patients at high risk of thrombophilia) (see section "Contraindications").

Tranexamic acid should be used with caution in patients taking oral contraceptives due to an increased risk of thrombosis (see section "Interaction with other medicinal products and other forms of interaction").

Disseminated intravascular coagulation

Patients with disseminated intravascular coagulation (DIC) should generally not be treated with tranexamic acid (see section "Contraindications"). If tranexamic acid is used, it should be restricted only to patients in whom activation of the fibrinolytic system predominates during acute, severe bleeding. Typically, the hematological profile includes the following: shortened euglobulin clot lysis time; prolonged prothrombin time; decreased plasma levels of fibrinogen, factors V and VIII, plasminogen, and alpha-2-macroglobulin; normal levels of plasma factors P and P-complex, i.e., factors II (prothrombin), VIII, and X; elevated levels of fibrinogen degradation products in plasma; and normal platelet count. The above findings suggest that the underlying disease state itself does not modify the various components of this profile. In such acute cases, administration of a single dose of 1 g of tranexamic acid is often sufficient to control bleeding. The use of tranexamic acid in DIC syndrome should be considered only when appropriate hematological laboratory facilities are available and under expert supervision.

Use during pregnancy or breastfeeding.

Women of childbearing potential.

Women of childbearing potential should use effective contraception during treatment.

Pregnancy

There is limited data on the use of tranexamic acid in pregnant women. Although animal studies do not indicate teratogenic effects, as a precautionary measure, tranexamic acid is not recommended during the first trimester of pregnancy.

Limited clinical data on the use of tranexamic acid in various hemorrhagic conditions during the second and third trimesters of pregnancy have not shown any harmful effects on the fetus. Tranexamic acid should be used during pregnancy only if the expected benefit outweighs the potential risk.

Breastfeeding period

Tranexamic acid is excreted in breast milk; therefore, breastfeeding should be discontinued during treatment with this medicinal product.

Fertility

There are no clinical data on the effect of tranexamic acid on fertility.

Ability to influence reaction speed when driving or operating machinery.

Studies on the ability to drive or operate machinery have not been conducted.

Method of administration and dosage.

Dosage

Adults

Unless otherwise indicated, the following doses are recommended:

1. Standard treatment of local fibrinolysis:

0.5 g (1 vial of 5 ml) to 1 g (2 vials of 5 ml) of tranexamic acid should be administered slowly intravenously as an injection or infusion (approximately 1 ml/min) 2–3 times daily.

2. Standard treatment of general fibrinolysis:

1 g (2 vials of 5 ml) of tranexamic acid should be administered slowly intravenously as an injection or infusion (approximately 1 ml/min) every 6–8 hours, equivalent to 15 mg/kg body weight.

Renal impairment

In renal insufficiency leading to a risk of accumulation, the use of tranexamic acid is contraindicated in patients with severe renal function impairment (see section "Contraindications"). For patients with mild to moderate renal function impairment, the dosage of tranexamic acid should be reduced according to serum creatinine levels:

Hepatic impairment

Dose adjustment is not required in patients with hepatic impairment.

Children

For children aged 1 year and older, use as indicated (see section "Indications"), with a dosage of approximately 20 mg/kg/day. However, data on efficacy, safety, and dosing specifics when used in children for the indicated conditions are limited.

The efficacy, dosing specifics, and safety of tranexamic acid in children following cardiac surgery have not been fully investigated.

Elderly patients

Dose reduction is not necessary in the absence of evidence of renal impairment.

Administration method

Administration is strictly limited to slow intravenous injection or infusion (see section "Special precautions for safety") at a rate not exceeding 1 mL/min.

The medicinal product may be mixed with most infusion solutions, such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and dextran solutions. Heparin may be added to the preparation.

Children

The maximum single dose for children aged 1 year and older is 10 mg/kg body weight. The maximum daily dose is 20 mg/kg body weight.

Overdose

No cases of overdose have been reported.

Signs and symptoms may include dizziness, headache, hypotension, and seizures. Seizures have been shown to occur more frequently with increasing doses.

Treatment of overdose should be supportive.

Adverse reactions.

Adverse reactions reported in clinical trials and post-marketing experience are listed below by system organ class. Within each organ system, adverse reactions are categorized by frequency. Within each frequency group, adverse reactions are presented in order of decreasing severity. Adverse reactions are classified by frequency of occurrence as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), frequency not known (frequency cannot be estimated from available data).

Immune system disorders.

Frequency not known: hypersensitivity reactions, including anaphylaxis.

Nervous system disorders.

Frequency not known: convulsions, particularly with incorrect use (see sections "Contraindications" and "Special warnings and precautions for use").

Eye disorders.

Frequency not known: visual disturbances, including color vision disturbances.

Cardiovascular system disorders.

Frequency not known: feeling of general malaise with hypotension, with or without loss of consciousness (usually after too rapid intravenous injection; exception – after oral administration). Arterial or venous thrombosis at any site.

Gastrointestinal disorders.

Common: diarrhea, vomiting, nausea.

Skin and subcutaneous tissue disorders.

Uncommon: allergic dermatitis.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging, protected from light, at a temperature not exceeding 30 °C. Keep out of reach of children.

Incompatibilities.

The medicinal product should not be mixed with blood for transfusion or with solutions containing penicillin.

Packaging. 5 ml in vials, 4 vials in a blister pack, 1 blister pack in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Mankind Pharma Limited.

Manufacturer's address and location of business activity.

Village Kishanpura, P.O. Jamniwala, Tehsil Paonta Sahib, District Sirmaur 173025, Himachal Pradesh, India.