Pauz-EM (Solution) Instructions for Use

Marketing Authorization Holder

Emcure Pharmaceuticals, Ltd. (India)

Manufactured By

Samrudh Pharmaceuticals, Pvt. Ltd. (India)

ATC Code

B02AA02 (Tranexamic acid)

Active Substance

Tranexamic acid (Rec.INN registered by WHO)

Dosage Form

Pauz-EM

Solution for intravenous administration 100 mg/ml: amp. 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous administration transparent colorless.

Excipients : water for injections.

5 ml – ampoules (5) – cardboard packs with an insert.

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 is a competitive (at high concentrations – non-competitive) inhibitor of the activation of profibrinolysin (plasminogen) and its conversion to fibrinolysin (plasmin). The antifibrinolytic activity of tranexamic acid in vitro is approximately 10 times greater than that of aminocaproic acid, which is due to a stronger binding to the receptor of the plasminogen molecule. Tranexamic acid has local and systemic hemostatic effects in bleeding associated with increased fibrinolysis. By suppressing the formation of kinins and other active peptides involved in allergic and inflammatory reactions, Tranexamic acid also has anti-inflammatory and anti-allergic effects.

Tranexamic acid at a concentration of 1 mg/ml does not affect platelet aggregation in vitro, at concentrations up to 10 mg/ml of blood it does not affect platelet count, blood clotting time or various blood clotting factors in whole blood or citrated blood of a healthy person. At the same time, Tranexamic acid, both at a concentration of 1 mg/ml and 10 mg/ml of blood, prolongs thrombin time.

The experiment confirmed the intrinsic analgesic activity of tranexamic acid, as well as a supra-summative potentiating effect on the analgesic activity of opiates.

Preclinical study data indicate that tranexamic acid has anti-carcinogenic and anti-angiogenic properties.

Pharmacokinetics

It is distributed in tissues relatively evenly (exception – cerebrospinal fluid, where the concentration is 1/10 of the plasma concentration). Penetrates the blood-brain barrier and placental barrier, excreted in 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. Tranexamic acid rapidly diffuses into the synovial fluid and through the synovial membranes, and is found in the synovial fluid at the same concentration as in the blood. T_1/2 from the synovial fluid is about 3 hours. Initial V_d – 9-12 L. Binding to plasma proteins – less than 3% (due to binding to plasminogen). Tranexamic acid does not bind to albumin. The antifibrinolytic concentration in various tissues is maintained for 17 hours, in plasma – up to 7-8 hours. It is metabolized to a small extent. Two metabolites of tranexamic acid have been identified: N-acetylated and deaminated derivatives. The AUC has a triphasic form with T_1/2 in the terminal phase – 3 hours. Total renal clearance is equal to plasma clearance (110-116 ml/min). It is excreted by the kidneys (the main route is glomerular filtration), more than 95% unchanged within the first 12 hours. After IV administration at a dose of 10 mg/kg, about 90% of tranexamic acid is excreted by glomerular filtration within 24 hours.

Indications

Prevention and treatment of bleeding in systemic and local fibrinolysis disorders, including: menorrhagia and metrorrhagia; gastrointestinal bleeding; bleeding after surgical interventions on the prostate gland and urinary tract; bleeding during surgical interventions in the nasal cavity, mouth and pharynx (adenoidectomy, tonsillectomy, tooth extraction); bleeding during thoracic, abdominal and other extensive surgical interventions (including cardiac surgery); obstetric and gynecological bleeding (including bleeding during gynecological surgical interventions); bleeding caused by the use of fibrinolytic drugs.

ICD codes

Dosage Regimen

Administer by intravenous drip or slow intravenous bolus at a rate not exceeding 50 mg per minute.

Do not administer intramuscularly.

Determine the dose individually based on body weight and the specific clinical indication for treatment.

For the treatment of bleeding, administer a dose of 10-15 mg/kg body weight every 6-8 hours.

For the prevention of bleeding during surgical procedures, administer a dose of 10 mg/kg body weight immediately before the operation.

In cases of generalized hyperfibrinolysis, administer a loading dose of 1 gram (10 ml) by slow IV injection, followed by a maintenance infusion.

For the maintenance infusion, mix 1-2 grams (10-20 ml) with a large-volume parenteral fluid and administer by IV drip at a rate of 25-50 mg per hour.

In patients with mild to moderate renal impairment (GFR 30-89 mL/min/1.73 m²), reduce the dose by 25-50%.

Contraindicated in patients with severe renal impairment (GFR less than 30 mL/min/1.73 m²).

For pediatric patients over 1 year of age, a typical dose for bleeding is 20 mg/kg/day, divided into multiple administrations.

Adjust the dosage and frequency based on clinical response and laboratory parameters of hemostasis.

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 vessel thrombosis.

From the vessels rarely – thromboembolic complications, pronounced decrease in BP (usually due to excessively rapid IV administration); very rarely – arterial and venous thromboses of various localization; 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, occlusion of aortocoronary bypass, thrombosis of the central retinal artery and vein.

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; chronic renal failure of severe degree (GFR less than 30 mg/ml/1.73 m²) due to the risk of accumulation; venous or arterial thrombosis currently or in history (including deep vein thrombosis of the legs, pulmonary embolism, intracranial vessel thrombosis) in the absence of the possibility of simultaneous therapy with anticoagulants; fibrinolysis due to consumption coagulopathy (hypocoagulation stage of DIC syndrome); history of convulsions; acquired color vision impairment; subarachnoid hemorrhage (due to the risk of developing cerebral edema, cerebral ischemia and infarction); treatment of menorrhagia in patients under 16 years of age; age under 1 year.

With caution

Hematuria caused by renal parenchyma 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 with a 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; female patients taking combined oral contraceptives (due to an increased risk of venous thromboembolic complications and arterial thromboses); simultaneous use of blood coagulation factors II, VII, IX and X in combination (prothrombin complex) or anti-inhibitor coagulant complex; patients receiving anticoagulant therapy.

Use in Pregnancy and Lactation

Use during pregnancy is possible only in cases of extreme necessity.

Tranexamic acid penetrates into breast milk (the concentration of the drug in milk is about 1% of the concentration in the mother’s blood plasma). The development of an antifibrinolytic effect in the infant is unlikely. Use with caution during breastfeeding.

Use in Renal Impairment

Contraindication: chronic renal failure of severe degree (GFR less than 30 mg/ml/1.73 m²) due to the risk of accumulation

In patients with mild and moderate impairment of renal excretory function, correction of the dosage regimen is required.

Pediatric Use

Contraindications: age under 1 year; treatment of menorrhagia in patients under 16 years of age.

Experience with the use of tranexamic acid preparations in children over 1 year of age is limited. The recommended dose for the treatment of bleeding due to local and generalized fibrinolysis is 20 mg/kg/day.

Geriatric Use

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

Special Precautions

In patients who underwent coronary artery bypass graft surgery, convulsions, in most cases, developed with the use of tranexamic acid in high doses.

Before starting and during long-term treatment with tranexamic acid, an examination by an ophthalmologist is necessary (visual acuity, color vision, fundus). If visual disturbances occur during treatment, tranexamic acid should be discontinued.

Tranexamic acid preparations should be used with caution in hematuria caused by renal parenchyma diseases, since under these conditions intravascular deposition of fibrin is often observed, 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.

Before starting the use of tranexamic acid, possible risk factors for the development of thromboembolic events should be taken into account. Patients with a history of thromboembolic diseases or patients with an increased frequency of thromboembolic events in the family history (patients at high risk of thrombophilia) should receive intravenous tranexamic acid only for strict medical reasons after consultation with a hemostasis specialist. The use of tranexamic acid in such patients should be carried out under careful medical supervision.

The use of tranexamic acid in patients with DIC syndrome is contraindicated in most cases. Tranexamic acid can be used in such patients only if the patient has symptoms of predominant activation of the fibrinolytic system with acute severe bleeding. In such acute cases, a single administration of tranexamic acid at a dose of 1 g is often sufficient to stop the bleeding.

The use of tranexamic acid in DIC syndrome should be performed only in the presence of appropriate laboratory examination data and after evaluation of these data by a specialist.

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

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.

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.