1 ml contains: tranexamic acid 100 mg.
The pH is 6.5 to 8.0.
Excipient/Inactive Ingredient: Water for injection.
Pharmacology: Pharmacodynamics: 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 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 platelets in 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 as low as 1 mg per mL can prolong 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 intravenous dose of 1 g, the plasma concentration time curve shows a triexponential decay with a half-life of about 2 hours for the terminal elimination phase. The initial volume of distribution is about 9 to 12 liters. Urinary excretion via glomerular filtration is the main route of elimination. Overall renal clearance is equal to overall plasma clearance (110 to 116 mL/min) and more than 95% of the dose is excreted in the urine as the unchanged drug. Excretion of tranexamic acid is about 90% at 24 hours after intravenous administration of 10 mg/kg body weight.
An antifibrinolytic concentration of tranexamic acid remains in different tissues for about 17 hours, and in the serum, up to 7 or 8 hours.
Tranexamic acid passes through the placenta. The concentration in cord blood after an intravenous 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 half-life of tranexamic acid in the joint fluid is about 3 hours.
The concentration of tranexamic acid in a number of other tissues is lower than in blood. In breast milk the concentration is about one hundredth of the serum peak concentration.
Tranexamic acid concentration in cerebrospinal fluid is about one tenth of that of the plasma.
The drug passes into the aqueous humor, the concentration being about one tenth 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, intravenous 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. CNS hyperexcitability may be the result of antagonism of γ-aminobutyric acidA receptors by tranexamic acid.
Haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis. Local fibrinolysis may occur in the following conditions: menorrhagia, prostatectomy and bladder surgery, haematuria, gastro-intestinal 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 such as ablatio placentae and post partum haemorrhage, leukemia, liver diseases, in connection with thrombolytic therapy with streptokinase.
Hereditary angioneurotic oedema.
The recommended standard dose is 5 to 10 ml by slow intravenous injection at a rate of 1ml/minute two to three times daily.
For the indications listed below the following doses are recommended: General fibrinolysis: 1.0 g (2 ampoules of 5 ml) by slow intravenous injection every six to eight hours.
Prostatectomy: 1 to 2 ampoules of 5 ml by slow intravenous injection every six to eight hours (the first injection being given during the operation) for the first three days after surgery, thereafter an oral available form of tranexamic acid 1 to 1.5 g (2 to 3 tablets) two to three times daily until macroscopic haematuria is no longer present.
Epistaxis: Medsamic 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: Medsamic therapy is initiated when bleeding has become profuse.
Dental extraction in patients with coagulopathies: Immediately before surgery, Medsamic 10 mg per kg body-weight should be given intravenously. After surgery, 25 mg per kg bodyweight of an oral available form of tranexamic acid is given three to four times daily for six to eight days. Coagulation factor concentrate might be necessary to administrate. This decision should be taken after consulting specialists on coagulation.
For patients with moderate to severe impaired renal function, the following dosages are recommended: (See table.)
Click on icon to see table/diagram/image
Symptoms: Nausea, diarrhoea, dizziness, headache, and convulsions. Orthostatic symptoms and hypotension may occur.
Risk of thrombosis in predisposed individuals.
Treatment of overdosage: If justified, initiate vomiting, then gastric lavage, charcoal therapy and symptomatic treatment. Maintain adequate diuresis.
Toxicity: 37 g of tranexamic acid caused mild intoxication in a seventeen-year-old after gastric lavage.
Active thromboembolic disease, such as deep vein thrombosis, pulmonary embolism and cerebral thrombosis.
Subarachnoid haemorrhage. The limited clinical experience shows that a reduced risk for rebleeding is offset by an increase in the rate of cerebral ischaemia.
Hypersensitivity to tranexamic acid or any of the ingredients.
Patients with irregular menstrual bleeding should not use Medsamic until the cause of the irregularity has been established. If menstrual bleeding is not adequately reduced by Medsamic, 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 Medsamic only if there is a strong medical indication and under strict medical supervision.
Patients with disseminated intravascular coagulation (DIC), who require treatment with Medsamic, 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.
Clinical experience with tranexamic acid in menorrhagic children under 15 years of age is not available.
Convulsions have been reported in association with tranexamic acid treatment.
Effects on ability to drive and use machines: Tranexamic acid may cause dizziness and therefore may influence the ability to drive or use machines.
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.
Lactation: Tranexamic acid is excreted into breast milk.
Fertility: There are 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.
Gastro-intestinal disturbances occur in more than 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 intravenous injection is too fast. Allergic skin reactions have been reported as an uncommon undesirable effect.
Common (>1/100): Gastrointestinal Disorders:
nausea, vomiting, diarrhoea.
Uncommon (≥ 1/1 000 to <1/100): Immune System Disorders:
Post-market Surveillance: The following adverse events have been reported in association with tranexamic acid therapy.
Nervous System Disorders:
chromatopsia, visual impairment.
embolism, hypotension (after fast injection).
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.
Special precautions for disposal and other handling: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: Solution for injection of tranexamic acid should not be added to blood for transfusion or to injections containing penicillin.
Store below 30°C in the original package.
Shelf-Life: 3 years.
B02AA02 - tranexamic acid ; Belongs to the class of amino acid antifibrinolytics. Used in the treatment of hemorrhage.
Soln for inj (amp) (clear, colourless soln) 10 mg/mL x 5 mL x 10's, 10 mL x 10's.