Actranex

Tranexamic acid.

Each mL contains: Tranexamic Acid, BP 100 mg.

Pharmacotherapeutic group: Antihemorrhagics, Antifibrinolytics, Amino acids.
Pharmacology: Pharmacodynamics: Tranexamic acid exerts an antihaemorrhagic activity by inhibiting the fibrinolytic properties of plasmin.
A complex involving tranexamic acid, plasminogen is constituted; the tranexamic acid being linked to plasminogen when transformed into plasmin.
The activity of the tranexamic acid-plasmin complex on the activity on fibrin is lower than the activity of free plasmin alone.
In vitro studies showed that high tranexamic dosages decreased the activity of complement.
Paediatric population: In children over one year old: Literature review identified 12 efficacy studies in paediatric cardiac surgery which have included 1073 children, 631 having received tranexamic acid. Most of them were controlled versus placebo. Studied population was heterogenic in terms of age, surgery types, dosing schedules. Study results with tranexamic acid suggest reduced blood loss and reduced blood product requirements in paediatric cardiac surgery under cardiopulmonary bypass when there is a high risk of haemorrhage, especially in cyanotic patients or patients undergoing repeat surgery. The most adapted dosing schedule appeared to be: first bolus of 10 mg/kg after induction of anaesthesia and prior to skin incision; continuous infusion of 10 mg/kg/h or injection into the CPB pump prime at a dose adapted on the CPB procedure, either according to patient weight with a 10 mg/kg dose, either according to CPB pump prime volume; last injection of 10 mg/kg at the end of CPB.
While studied in very few patients, the limited data suggest that continuous infusion is preferable, since it would maintain therapeutic plasma concentration throughout surgery.
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: The plasma protein binding of tranexamic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Tranexamic acid does not bind to serum albumin. The initial volume of distribution is about 9 to 12 liters.
Tranexamic acid passes through the placenta. Following administration of an intravenous injection of 10 mg/kg to 12 pregnant women, the concentration of tranexamic acid in serum ranged 10-53 μg/mL while that in cord blood ranged 4-31 μg/mL. 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. The concentration of tranexamic acid in a number of other tissues is a fraction of that observed in the blood (breast milk, one hundredth; cerebrospinal fluid, one tenth; aqueous humor, one tenth). Tranexamic acid has been detected in semen where it inhibits fibrinolytic activity but does not influence sperm migration.
Elimination: It is excreted mainly in the urine as unchanged drug. Urinary excretion via glomerular filtration is the main route of elimination. Renal clearance is equal to plasma clearance (110 to 116 mL/min). Excretion of tranexamic acid is about 90% within the first 24 hours after intravenous administration of 10 mg/kg body weight. Half-life of tranexamic acid is approximately 3 hours.

It is used in the treatment and prophylaxis of haemorrhage associated with excessive fibrinolysis. It is also used in the prophylaxis of hereditary angioedema.

For short-term use in haemorrhage, when given by slow intravenous injection doses are 0.5 to 1 g (or 10 mg/kg) 3 times daily. Tranexamic acid is given by continuous infusion at a rate of 25 to 50 mg/kg daily. Children may be given doses of 10 mg/kg intravenously, usually 2 or 3 times daily, depending on the indication. Or as prescribed by the physicians.

Signs and symptoms may include nausea, vomiting, dizziness, headache, hypotension, and convulsions. It has been shown that convulsions tend to occur at higher frequency with increasing dose. Management of overdose should be supportive.
Maintain a high fluid intake to promote renal excretion. Anticoagulant treatment should be considered. There is a risk of thrombosis in predisposed individuals.

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 fibrinolytic system 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).

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 Tranexamic Acid 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 events: 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. If tranexamic acid is given it must be restricted to those in whom there is predominant activation of the fibrinolytic system with acute severe bleeding. Characteristically, the haematological profile approximates to the following: reduced euglobulin clot lysis time; prolonged prothrombin time; reduced plasma levels of fibrinogen, factors V and VIII, plasminogen fibrinolysin and alpha-2 macroglobulin; normal plasma levels of P and P complex; i.e. factors II (prothrombin), VIII and X; increased plasma levels of fibrinogen degradation products; a normal platelet count. The foregoing presumes that the underlying disease state does not of itself modify the various elements in this profile. In such acute cases a single dose of 1 g tranexamic acid is frequently sufficient to control bleeding. Administration of Tranexamic acid in DIC should be considered only when appropriate haematological laboratory facilities and expertise are available.

Pregnancy: There are insufficient clinical data on the use of tranexamic acid in pregnant women. As a result, although studies in animals do not indicate teratogenic effects, as a precaution for use, 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.
Lactation: Tranexamic acid is excreted in human milk. Therefore, breastfeeding is not recommended.

Tranexamic acid appears to be well tolerated. It can produce dose-related gastrointestinal disturbances. Hypotension has occurred, particularly after rapid intravenous dosage. Thrombotic complications have been reported in patients receiving tranexamic acid, but these are usually a consequence of its inappropriate use. There have been a few instances of transient disturbances of colour vision associated with use of tranexamic acid; in such cases the drug should be stopped. Hypersensitivity skin reactions have also been reported.

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 given with caution to patients treated with tranexamic acid. There is a theoretical risk of increased thrombus formation potential, such as with oestrogens. Alternatively, the antifibrinolytic action of the drug may be antagonised with thrombolytic drugs.

Store at temperatures not exceeding 30°C. Protect from light.

Haemostatics

B02AA02 - tranexamic acid ; Belongs to the class of amino acid antifibrinolytics. Used in the treatment of hemorrhage.

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