Composition:

Each ampoule (5ml) contains 500mg tranexamic acid (100mg/ml)

Mechanism of Action:

Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin's matrix structure.

Pharmacokinetics:

Absorption:

Peak plasma concentrations of tranexamic acid are obtained rapidly after a short intravenous infusion after which plasma concentrations decline in a multi-exponential manner.

Distribution:

Tranexamic acid is 3% bound to plasma proteins with no apparent binding to albumin. the initial volume of distribution isabout 9 to 12 liters 

Tranexamic acid crosses the placenta. 

Tranexamic acid diffuses rapidly into joint fluid and the synovial membrane. Following administration of an intravenous injection of 10 mg/kg to 17 patients undergoing knee surgery, concentrations in the joint fluids were similar to those seen in corresponding serum samples.

Tranexamic acid concentration in cerebrospinal fluid is about one tenth of the plasma concentration.

The drug passes into the aqueous humor of the eye achieving a concentration of approximately one tenth of plasma concentrations.

Tranexamic acid has been detected in semen where it inhibits fibrinolytic activity but does not influence sperm migration.

Excretion:

It is excreted mainly in the urineas unchanged drug. Excretion of tranexamic acid is about90% within the first 24 hours after intravenous administration of 10 mg/kg body weight. Half-life of tranexamic acid is approximately 3 hours.

 Indications:

Prevention and treatment of haemorrhages due to general or local fibrinolysis in adults and children from one year.

Specific indications include:

Haemorrhage caused by general or local fibrinolysis such as:

- Menorrhagia and metrorrhagia.

- Gastrointestinal bleeding.

- Haemorrhagic urinary disorders, further to prostate surgery or surgical procedures affecting the urinary tract.

- Ear Nose Throat surgery (adenoidectomy, tonsillectomy, dental extractions).

- Gynaecological surgery or disorders of obstetric origin.

- Thoracic and abdominal surgery and other major surgical intervention such as cardiovascular surgery.

- Management of haemorrhage due to the administration of a fibrinolytic agent.

Contraindications:

• Hypersensitivity to the active substance or to any of the excipients.
• Acute venous or arterial thrombosis
• Fibrinolytic conditions following consumption coagulopathy except in those with predominant activation of the fibrinolyticsystem with acute severe bleeding
• Severe renal impairment (risk of accumulation)
• History of convulsions
• Intrathecal and intraventricular injection, intracerebral application (risk of cerebral oedema and convulsions)

Dosage and Administration:

Posology: Adults:

Unless otherwise prescribed, the following doses are recommended:

1- Local Fibrinolysis:

500 mg (1 ampoule of 5 ml) to 1000 mg (2 ampoules of 5 ml) tranexamic acid by slow intravenous injection (= 1 ml/minute) two to three times daily.

2- General Fibrinolysis:

1000 mg (2 ampoules of 5 ml) tranexamic acid by slow intravenous injection (= 1 ml/minute) every 6 to 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 patient with severe renal impairment. For patient with mild to moderate renal impairment, the dosage of tranexamic acid should be reduced according to the serum creatinine level:

Administration

Dose IV

Serum Creatinine

mg/10 ml

μmol/l

Every 12 hours

10 mg/kg body weight

1.35 to 2.82

120 to 249

Every 24 hours

10 mg/kg body weight

2.82 to 5.65

250 to 500

Every 24 hours

5 mg/kg body weight

> 5.65

> 500

Hepatic Impairment:

No dose adjustment is required in patient with hepatic impairment.

Pediatric Population:

In children from 1 year, for current approved indications, the dosage is in the region of 20 mg/kg/day. However, data on efficacy, posology and safety for these indications are limited.

The efficacy, posology and safety of tranexamic acid in children undergoing cardiac surgery have not been fully established.

Elderly:

No reduction in dosage is necessary unless there is evidence of renal failure.

Method of Administration:

The administration is strictly limited to slow intravenous injection.

Side Effects:

Drug Interactions:

No interaction studies have been performed. 

Simultaneous treatment with anticoagulants must take place under the strict supervision of a physician experienced in this field. Medicinal products that act on haemostasis should be givenwith caution to patients treated with tranexamic acid. There is a theoretical risk of increased thrombus-formationpotential, such as with oestrogens. Alternatively, the antifibrinolytic action of the drug may be antagonised with thrombolytic drugs.

Precautions:

The indications and method of administration indicated above should be followed strictly:

1- Intravenous injections should be given very slowly.

2- Tranexamic acid should not be administered by the intramuscular route.

Convulsions:

Cases of convulsions have been reported in association with tranexamic acid treatment. In coronary artery bypass graft (CABG) surgery, most of these cases were reported following intravenous (IV) injection of tranexamic acid in high doses. With the use of the recommended lower doses of tranexamic acid, the incidence of post-operative seizures was the same as that in untreated patients.

Visual disturbances:

Attention should be paid to possible visual disturbances including visual impairment, vision blurred, impaired colour vision and if necessary the treatment should be discontinued. With continuous long-term use of tranexamic acid solution for injection, regular ophthalmologic examinations (eye examinations including visual acuity, colour vision, fundus, visual field etc.) are indicated. With pathological ophthalmic changes, particularly with diseases of the retina, the physician must decide after consulting a specialist on the necessity for the long-term use of TXA solution for injection in each individual case.

Haematuria:

In case of haematuria from the upper urinary tract, there is a risk for urethral obstruction.

Thromboembolic Risk:

Before use of tranexamic acid, risk factors of thromboembolic disease should be considered. In patients with a history of thromboembolic diseases or in those with increased incidence of thromboembolic events in their family history (patients with a high risk of thrombophilia), Tranexamic acid solution for injection should only be administered if there is a strong medical indication after consulting a physician experienced in hemostaseology and under strict medical supervision.

Tranexamic acid should be administered with care in patients receiving oral contraceptives because of the increased risk of thrombosis.

Disseminated Intravascular Coagulation:

Patients with disseminated intravascular coagulation (DIC) should in most cases not be treated with tranexamic acid.

Pregnancy:

Women of childbearing potential have to use effective contraception during treatment.

Tranexamic acid is not recommended during the first trimester of pregnancy. Limited clinical data on the use of tranexamic acid in different clinical haemorrhagic settings during the second and third trimesters did not identify deleterious effect for the foetus. Tranexamic acid should be used throughout pregnancy only if the expected benefit justifies the potential risk.

Breastfeeding:

Tranexamic acid is excreted in human milk. Therefore, breastfeeding is not recommended.

Overdose:

No cases of overdose have been reported.

Symptoms:

Signs and symptoms may include dizziness, headache, hypotension, and convulsions. It has been shown thatconvulsions tend to occur at higher frequency with increasing dose.

Management:

Management of overdose should be supportive.