(tran'' ex am' ik) (as' id)
P : Caution when used during pregnancy
L : Caution when used during lactation
|| See TERMINOLOGY & ABBREVIATIONS |
|ATC Classification||B02AA02 - tranexamic acid; Belongs to the class of amino acid antifibrinolytics. Used in the treatment of hemorrhage.|
|Indication(s)||Haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis.
Local fibrinolysis may occur in the following conditions: Menorrhagia, prostatectomy and bladder surgery, haematuria, gastrointestinal haemorrhage, epistaxis, ulcerative colitis, conisation of the cervix, and dental extraction in patients with coagulopathies.
General fibrinolysis may occur in the following conditions and situations: Prostatic and pancreatic cancer, after thoracic and other major surgery, in obstetrical complications eg, ablatio placentae and postpartum haemorrhage, leukemia, liver diseases, in connection with thrombolytic therapy with streptokinase.
Hereditary angioneurotic oedema.
|Dosage & Administration||Recommended Standard Dose: 5-10 mL by slow IV injection at a rate of 1 mL/min or 2-3 tablets of 0.5 g 2-3 times daily.
General Fibrinolysis: 1 g (two ampoules of 5 mL) by slow IV injection every 6-8 hrs.
Prostatectomy: 0.5-1 g orally (1-2 tablets) (1-2 ampoules of 5 mL) by slow IV injection every 6-8 hrs (the 1st injection being given during the operation) for the 1st three days after surgery, thereafter, 1-1.5 g orally (2-3 tablets) 2-3 times daily until macroscopic haematuria is no longer present.
Haematuria: 1-1.5 g orally (2-3 tablets) 2-3 times daily until macroscopic haematuria is no longer present.
Epistaxis: 1.5 g orally (3 tablets) 3 times daily should be administered for 4-10 days. tranexamic acid solution for injection may be applied topically to the nasal mucosa of patients suffering from epistaxis, this can be done by soaking a gauze strip in the solution and then packing the nasal cavity.
Menorrhagia: 1-1.5 g orally (2-3 tablets) 3-4 times daily for 3-4 days. tranexamic acid therapy is initiated when bleeding has become profuse.
Conisation of the Cervix: 1.5 g orally (3 tablets) 3 times daily for 12-14 days postoperatively.
Dental Extraction in Patients with Coagulopathies: Immediately before surgery, tranexamic acid 10 mg/kg body weight should be given IV. After surgery, 25 mg/kg body weight are given orally 3-4 times daily for 6-8 days. Coagulation factor concentrate might be necessary to administer. This decision should be taken after consulting specialists on coagulation.
Hereditary Angioneurotic Oedema: 1-1.5 g orally (2-3 tablets) 2-3 times daily as intermittent or continuous treatment, depending on whether the patient has prodromal symptoms or not.
Patients with Moderate to Severe Impaired Renal Function: Recommended Dose: Serum Creatinine Clearance >500 micromol/L: 7.5 mg/kg body weight orally daily or 5 mg/kg body weight IV daily; 250-500 micromol/L: 15 mg/kg body weight orally daily or 10 mg/kg body weight IV daily; 120-249 micromol/L:15 mg/kg body weight orally twice daily or 10 mg/kg body weight IV twice daily.
Symptoms: Nausea, diarrhoea, dizziness, and headache. Orthostatic symptoms and hypotension may occur. Risk of thrombosis in predisposed individuals.
Toxicity: Tranexamic acid 37 g caused mild intoxication in a 17 yr old after gastric lavage.
|Contraindications||Active thromboembolic disease eg, deep vein thrombosis, pulmonary embolism and cerebral thrombosis.
Subarachnoid haemorrhage. The limited clinical experience shows that a reduced risk for re-bleeding is offset by an increase in the rate of cerebral ischaemia.
Hypersensitivity to tranexamic acid or any of the ingredients.
|Special Precautions||Patients with irregular menstrual bleeding should not use tranexamic acid until the cause of the irregularity has been established.
If menstrual bleeding is not adequately reduced by tranexamic acid, an alternative treatment should be considered.
Patients with a high risk for thrombosis (a previous thromboembolic event and a family history of thromboembolic disease) should use tranexamic acid only if there is a strong medical indication and under strict medical supervision.
Patients with disseminated intravascular coagulation, who require treatment with tranexamic acid, must be under the strict supervision of a physician experienced in treating this disorder.
The blood levels are increased in patients with renal insufficiency. Therefore a dose reduction is recommended, see Dosage & Administration.
In haematuria from the upper urinary tract blood clots can, in a few cases, lead to ureteric obstruction.
Effects on the Ability to Drive or Operate Machinery: Tranexamic acid may cause dizziness and therefore may influence the ability to drive or use machines.
Impairment of Fertility: There is no clinical data in humans supporting the impact of tranexamic acid on fertility. Fertility was not affected in male or female rats at high oral doses up to approximately 850-880 mg/kg/day.
|Adverse Drug Reaction(s)||Gastrointestinal disturbances occur in >30% of the patients at an oral administration of 6 g/day. The disturbances disappear when the dose is reduced.
Giddiness, nausea and hypotension occur when the IV injection is too fast.
Allergic skin reactions have been reported as an uncommon adverse reaction.
Common (>1/100): Gastrointestinal Disorders: Nausea, vomiting, diarrhoea.
Uncommon: Immune System Disorders: Allergic dermatitis.
Post-market Surveillance: The following adverse events have been reported in association with tranexamic acid therapy.
Nervous System Disorders: Convulsion, dizziness.
Eye Disorders: Chromatopsia, visual impairment.
Vascular Disorders: Embolism, hypotension (after fast injection).
|Drug Interactions||Clinically important interactions have not been observed with tranexamic acid. Because of the absence of interaction studies, simultaneous treatment with anticoagulants must take place under the strict supervision of a physician experienced in this field.
Incompatibilities: For IV infusion, tranexamic acid for injection may be mixed with most solutions for infusion eg, electrolyte, carbohydrate, amino acid and dextran solutions. The solution should be prepared the same day it is to be used.
tranexamic acid injection may be mixed with heparin.
tranexamic acid injection should not be added to blood for transfusion or to injections containing penicillin.
|Use in Pregnancy||
Use in pregnancy: Tranexamic acid crosses the placenta and appears in cord blood at concentrations approximately equal to maternal concentration. Clinical experience of use in pregnant women is limited. Animal studies have not supplied any evidence of an increased incidence of foetal damage.
|Storage||Tablet: Do not store above 25Â°C.
Injection: Do not store above 25Â°C. Protect from freezing.
|Pharmacology||Pharmacodynamics: Tranexamic acid is a competitive inhibitor of plasminogen activation, and at much higher concentrations, a noncompetitive inhibitor of plasmin, ie, actions similar to aminocaproic acid. Tranexamic acid is about 10 times more potent in vitro than aminocaproic acid.
Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak receptor sites of the plasminogen molecule in a ratio corresponding to the difference in potency between the compounds. Tranexamic acid in a concentration of 1 mg/mL does not aggregate plateletsin vitro.
Tranexamic acid in concentrations up to 10 mg/mL blood has no influence on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood from normal subjects. However, tranexamic acid in concentrations of 10 mg/mL and 1 mg/mL blood prolongs the thrombin time.
Pharmacokinetics: 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.
After an IV dose of 1 g, the plasma concentration time curve shows a triexponential decay with a tÂ½ of about 2 hrs for the terminal elimination phase. The initial volume of distribution is about 9-12 L. Urinary excretion via glomerular filtration is the main route of elimination. Overall renal clearance is equal to overall plasma clearance (110-116 mL/min) and >95% of the dose is excreted in the urine as the unchanged drug. Excretion of tranexamic acid is about 90% at 24 hrs after IV administration of 10 mg/kg body weight.
An anti-fibrinolytic concentration of tranexamic acid remains in different tissues for about 17 hrs, and in the serum, up to 7 or 8 hrs.
Tranexamic acid passes through the placenta. The concentration in cord blood after an IV injection of 10 mg/kg to pregnant women is about 30 mg/L, as high as in the maternal blood.
Tranexamic acid diffuses rapidly into joint fluid and the synovial membrane. In the joint fluid the same concentration is obtained as in the serum. The biological tÂ½ of tranexamic acid in the joint fluid is about 3 hrs.
The concentration of tranexamic acid in a number of other tissues is lower than in blood. In breast milk the concentration is about 1/100 of the serum peak concentration. Tranexamic acid concentration in cerebrospinal fluid is about 1/10 of that of the plasma. The drug passes into the aqueous humor, the concentration being about 1/10 of the plasma concentration.
Tranexamic acid has been detected in semen where it inhibits fibrinolytic activity but does not influence sperm migration.
Toxicology: Preclinical Safety Data: An increased incidence of leukemia in male mice receiving tranexamic acid in food at a concentration of 4.8% (equivalent to doses as high as 5 g/kg/day) may have been related to treatment. Female mice were not included in this experiment.
Hyperplasia of the biliary tract and cholangioma and adenocarcinoma of the intrahepatic biliary system have been reported in one strain of rats after dietary administration of doses exceeding the maximum tolerated dose for 22 months. Hyperplastic, but not neoplastic, lesions were reported at lower doses. Subsequent long-term dietary administration studies in a different strain of rat, each with an exposure level equal to the maximum level employed in the earlier experiment, have failed to show such hyperplastic/neoplastic changes in the liver. No mutagenic activity has been demonstrated in several in vitro and in vivo genotoxicity testing systems.
In published, pre-clinical animal studies, epileptic activities were induced by topical application of tranexamic acid to the cortex of anesthetized cats. Similarly, IV infusion of high doses (500-600 mg/kg) of tranexamic acid induced seizure-like activity in conscious cats. Severe hind limb spasms developed into generalized convulsions in a rat model following application of tranexamic acid to the lumbar spinal cord. Tranexamic acid within a fibrin sealant similarly induced limb spasms and convulsions in this rat model. Fibrin sealant containing tranexamic acid evoked generalized seizures in rats following application to the cerebral cortex of anesthetized rats. Central nervous system hyperexcitability may be the result of antagonism of Î³-aminobutyric acidA receptors by tranexamic acid.
|Brand Name||Manufacturer/Marketer||Composition||Dosage Form||Pack Size & Price|
|ANAXYL||ACI Ltd.||Tranexamic acid 500mg||Capsule||20's: 301.20 MRP|
|ANAXYL Injection||ACI Ltd.||Tranexamic acid (I/V)500mg/5ml||Injection||5 amps: 250.95 MRP|
|ENCLOT||Opsonin Pharma Limited||Tranexamic acid 500mg||Capsule||20's: 300.00 MRP|
|ENCLOT Injection||Opsonin Pharma Limited||Tranexamic acid (I/V) 500mg/5ml||Injection||5 amps: 250.00 MRP|
|FIBRINO||Eskayef Bangladesh Ltd||Tranexamic Acid 500mg||Capsule||18's MRP: 270.00|
|FIBRINO Injection||Eskayef Bangladesh Ltd||Tranexamic Acid 500mg/5ml Injection||Injection||5 amps, MRP: 250.00|
|FRABEX 500||Square Pharmaceuticals Ltd.||Tranexamic Acid 500mg||Capsule||2x10's: 400.00 MRP|
|FRABEX 500 IV||Square Pharmaceuticals Ltd.||Tranexamic Acid 500mg/5 ml||IV Injection||3x2's: 300.00 MRP|
|HEMOSTAT||Aristopharma Ltd.||Tranexamic acid 500mg||Capsule||20's: 300.00 MRP|
|HEMOSTAT Injection||Aristopharma Ltd.||Tranexamic acid (I/V)250mg/5ml||Injection||5 amps: 150.00 MRP|
|HEMOSTOP||Apex Pharmaceuticals Ltd.||Tranexamic acid 500mg||Capsule||20's: 210.00 MRP|
|Intrax||Incepta Pharmaceuticals Limited||Tranexamic Acid 500 mg Capsule||Capsule||4x5's:MRP 320 Tk|
|Intrax Injection||Incepta Pharmaceuticals Limited||Tranexamic Acid 500mg/5ml Injection||Injection||1x5's:MRP 250 Tk|
|TRACID||The Acme Laboratories Ltd.||Tranexamic acid 500mg||Tablet||20's, 30's: 301.00 & 451.50 MRP|
|TRACID Injection||The Acme Laboratories Ltd.||Tranexamic acid (I/V) 500mg/5ml||Injection||3 amps: 150.60 MRP|
|TRAMIC||Pacific Pharmaceuticals Ltd.||Tranexamic acid 500mg||Capsule||30's: 570.00 MRP|
|TRANEXIL||Beximco Pharmaceuticals Ltd||Tranexamic Acid 500 mg/5ml||Injection||5's: 250.00 MRP|
|TRAXYL||Nuvista Pharma Limited||Tranexamic acid 500mg||Capsule||20's: 404.00 MRP|
|TRAXYL Injection||Nuvista Pharma Limited||Tranexamic acid (I/V)250mg/5ml||Injection||5 amps: 176.00 MRP|
|TREXAM||Healthcare Pharmacuticals Ltd.||Tranexamic Acid 500mg||Capsule||30's MRP 450 Tk|
|XAMIC||Renata Limited||Tranexamic acid 500mg||Capsule||20's: 301.00 MRP|
|XAMIC Injection||Renata Limited||Tranexamic acid (I/V)I.M 500mg/5ml||Injection||5 amps: 250.95 MRP|