Tranexamic Acid

Tranexamic Acid

100mg/ml Injection (I.V.)

Drug Category: Antifibrinolytic agent

Chemical Name and Molecular Formula:

Trans-4-(Aminomethyl) cyclohexanecarboxylic acid. C₈H₁₅NO₂

Pharmacology:

Tranexamic acid is an antifibrinolytic drug, which inhibits breakdown of fibrin clots. It acts primarily by blocking the binding of plasminogen and plasmin to fibrin; direct inhibition of plasmin occurs only to a limited degree. Tranexamic acid is a competitive inhibitor of plasminogen activation, and at much higher concentrations, a noncompetitive inhibitor of plasmin, i.e., actions similar to aminocaproic acid. Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak receptor sites of the plasminogen molecule in a ration corresponding to the difference in potency between the compounds.

Pharmacokinetics:

Absorption: Tranexamic acid can be administered by slow intravenous injection or continuous infusion. After an intravenous dose of 1 g, the plasma half-life is about 2 hours for the terminal elimination phase. The plasma protein binding of tranexamic acid is about 3% at therapeutic plasma levels.

Distribution: Tranexamic acid is widely distributed throughout the body. Tranexamic acid diffuses rapidly into joint fluid, the synovial membrane, CSF, aqueous humor and semen. If diffuses across the placenta and is distributed into breast milk. The concentration in cord blood after an intravenous injection of 10mg/kg to pregnant women is about 30mg/liter, as high as in the maternal blood.

Metabolism: Only a small fraction of the drug is metabolized.

Excretions: It is excreted in the urine mainly in unchanged drug. Excretion of tranexamic acid is about 90% at 24 hours after intravenous administration of 10mg/kg body weight.

Indications:

In the treatment and prophylaxis of hemorrhage associated with excessive fibrinolysis. In patients with hemophilia for short term use 2-8 days to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction.

Contraindications:

Tranexamic acid is contraindicated in patients with acquired defective color vision, subarachnoid hemorrhage and active intravascular clotting.

Precautions and Warnings:

The dose of tranexamic acid injection should be reduced in patient with renal insufficiency because of the risk of accumulation. Caution should be exercised in the patients with upper urinary tract bleeding which may cause the ureteral obstruction due to clot formation. Venous and arterial thrombosis or thromboembolism has been reported in patients treated with tranexamic acid. In addition, cases of central retinal artery and central retinal vein obstruction have been reported.

Used with caution in patients with a previous history of thromboembolic disease which may be at increased risk for venous or arterial thrombosis. Strict supervision by physician should be done while administrating tranexamic acid to the patients with disseminated intravascular coagulation.

An ophthalmic examination, including visual acuity, color vision, eye-ground and visual fields, is advised for patients who are to be treated continually for longer than several days and drug should be discontinued if changes in examination results are found.

Dosage adjustment should be done in the patients with moderate to severe impaired renal function.

Use in Pregnancy and Lactation:

There are no adequate and well-controlled studies in pregnant women. However, tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration. Therefore, drug should be used during pregnancy only if clearly needed.

Tranexamic acid is present in the mother's milk at a concentration of about a hundredth of the corresponding serum levels. Caution should be exercised when tranexamic acid is administered to a nursing woman.

Drug Interactions:

Caution should be exercised when concomitant administration of drugs with actions on homeostasis is given in the patient with antifibrinolytic therapy. Care should be taken while concurrently administrating of estrogen, because it may increase the potential for thrombus formation. Tranexamic acid should not be administered concomitantly with Factor IX Complex concentrates or Anti-inhibitor Coagulant concentrates, as the risk of thrombosis may be increased.

Adverse Effects:

Gastrointestinal disturbances (nausea, vomiting, diarrhea) may occur but disappear when the dosage is reduced. Orthostatic symptoms and hypotension have been reported occasionally. Hypersensitivity skin reactions have also been reported. Hypotension has been observed when intravenous injection is too rapid.

Dosage and Administration:

Adults:

Parenteral Therapy: 10mg/kg 3-4 times daily.

Immediately before dental extraction in patients with hemophilia: 10mg/kg intravenous together with replacement therapy; following surgery, 25mg/kg given orally 3 or 4 times daily for 2-8 days.

Children:

Intravenous therapy: 10mg/kg 2-3 times daily.

Note:

• For intravenous infusion, tranexamic acid injection may be mixed with most solutions for infusion such as electrolyte solutions, carbohydrate solutions, amino acid solutions and dextran solutions.
• The mixture should be prepared the same day the solution is to be used. Heparin may be added to tranexamic acid injection.
• Tranexamic acid injection should NOT be mixed with blood.
• The drug is a synthetic amino acid, and should NOT be mixed with solutions containing penicillin.

Overdosage:

There is no known case of overdosage of tranexamic acid injection. Symptoms of overdosage may be nausea, vomiting, orthostatic symptoms and/or hypotension. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required.

Shelf-Life:

36 months from the date of manufacturing.

Storage Conditions:

Store at a temperatures not exceeding 30^oC. Protect from direct sunlight. Keep out of reach of children.