In physiological conditions, fibrinolysis affects enhancements of vascular permiability, and relevant to the development, progression and healing of hemorrhage, allergy and other biological reactions induced by plasmin. Tranexamic acid inhibits the activity of plasmin, thereby exhibiting antihemorrhagic, antiallergic and anti-inflammatory effects.
Tranexamic acid inhibits the binding of plasmin or plasminogen to fibrin by strongly binding to the lysine binding site (LBS), of fibrin, which is also the binding site for plasmin and plasminogen. Therefore, tranexamic acid strongly inhibits fibrinolysis induced by plasmin. In addition, in the presence of antiplasmins eg, α2
-macroglobulin in the plasma, the antifibrinolytic action of tranexamic acid is even further strengthened.
When the blood level of plasmin is abnormally elevated, various phenomena occur eg, inhibition of platelet aggregation and decomposition of coagulation factors, occur. Even slight elevation in the blood level of plasmin specifically induces fibrinolysis. Tranexamic acid is considered to exhibit a hemostatic effect by inhibiting fibrinolysis in common hemorrhages.
Antiallergic and Anti-inflammatory Action:
Tranexamic acid inhibits plasmin-induced production of kinin and other active peptides, that cause enhancement of vascular permeability, allergy and anti-inflammatory lesions (as demonstrated in guinea pigs and rats).
Pharmacokinetics: Blood Concentrations: Capsule:
The concentrations in the blood, when 250 and 500 mg of tranexamic acid were administered orally to healthy adults, reached peak values of 3.9 mcg/mL (250-mg administration) and 6 mcg/mL (500-mg administration) 2-3 hrs after administration. The biological half-lives were 3.1 and 3.3 hrs, respectively.
When a single dose of tranexamic acid 500 mg was administered IM or 1000 mg was administered IV to healthy adults, the time-plasma concentration were as follows. (See table.)
Plasma Concentration after Single IV and IM Doses of Tranexamic Acid:
Click on icon to see table/diagram/image
Click on icon to see table/diagram/image
When 250 mg/500 mg of tranexamic acid was administered orally to healthy adults, urinary excretion rate was 40-70% by 24 hrs after administration.
Clinical Studies: Antihemorrhagic Action: Capsule:
In an open-labelled clinical trial performed on 2802 patients with hemorrhagic tendencies during leukemia, aplastic anemia or purpura thought to involve systemic hyperfibrinolysis or with pulmonary, genital or renal hemorrhage or abnormal hemorrhage during or after prostate operation thought to involve local hyperfibrinolysis, Transamin showed hemostatic effects in 73.6% (2063 cases).
A hemostatic effect of Transamin was observed in 594 out of 709 patients (83.8%) with a bleeding tendency eg, leukemia, aplastic anemia and purpura, which are considered to be associated with systemic hyperfibrinolysis or abnormal bleeding eg, pulmonary, nasal, vaginal, renal, prostatic hemorrhage, and intra- and postoperative bleeding.
Antiallergic and Anti-inflammatory Actions: Capsule: Skin Disorders:
The effects of Transamin against pruritus, rubor and swelling were compared to placebo in a double-blind clinical trial in 67 patients (Transamin 35, placebo 32) with skin disorders (eczema or similar diseases, toxicoderma and/or drug eruption) were examined.
The result showed that 22 patients (62.9%) in the Transamin group and 10 patients (31.3%) in the placebo group had a response more than good and a significant difference was recognized between these groups (p<0.05).
An open-labelled clinical study in 223 patients with skin diseases (eczema or similar diseases, urticaria, drug rash, toxicoderma) showed that this drug was effective against pruritus, swelling and erythema in 135 patients (60.5%).
Symptoms of skin disorders eg, eczema and similar conditions or urticaria, improved in 220 out of 283 patients (77.7%).
Otolaryngological Disorders: Capsule:
The effects against pain, swelling and rubor, in a double-blind clinical trial in 168 patients (Transamin 84, placebo 84) with otolaryngological disorders (acute laryngopharyngitis, acute tonsillitis and stomatitis) were examined.
The result showed that 44 patients (52.4%) in Transamin group and 22 patients (26.2%) in placebo group had a response more than good and a significant difference was recognized between these groups (p<0.05). In an open-labelled clinical trial performed on 168 patients with tonsillitis, laryngopharyngitis, stomatitis and gingivitis, the effects against pain, swelling, rubor, were observed in 119 patients (70.8%).
Adverse Reactions: Capsule:
The major adverse reactions reported in 2954 patients in clinical trial (including double-blind clinical trial) were anorexia in 0.61% (18 cases), nausea in 0.41% (12 cases), vomiting in 0.2% (6 cases), heartburn in 0.17% (5 cases), itching 0.07% (2 cases) and rash in 0.07% (2 cases).
The major adverse reactions reported in 2972 patients administered Transamin were anorexia in 0.07% (2 cases), vomiting in 0.17% (5 cases), nausea in 0.03% (1 case), diarrhea in 0.07% (2 cases) and drowsiness in 0.03% (1 case).
Nonclinical Studies: Metabolism:
C-tranexamic acid was administered IV to rats, it was almost all excreted in the unchanged form.
C-tranexamic acid was orally administered to rats, the concentrations in most organs reached peak values as well as the blood concentrations after 2 hrs.
Levels in kidney and liver were higher and those of other organs were lower than that of the blood.
C-tranexamic acid was administered IV or IM to mice, the distribution in the tissues was highest in the liver, kidneys and pulmonary, followed by pancreas, adrenals, spleen, prostate, colon, uterus, heart and muscle. Levels in the brain were low.
Metabolism and Excretion: Injection:
When a single dose of tranexamic acid 500 mg was administered IM or 1000 mg was administered IV to healthy adults, it was rapidly absorbed and about 80% and 76% of the administered dose, was respectively, excreted unchanged form in the urine within 24 hrs of administration.
Toxicology: Single-Dose Toxicity: Capsule:
values of oral administration were >10 g/kg in mice and rats and >5 g/kg in dogs.
values of IV administration were 1.35 g/kg in mice and 1.41 g/kg in rats.
values of SC administration were 5.31 g/kg in mice and 4.62 g/kg in rats.
Repeated-Dose Toxicity: When tranexamic acid was orally administered to rats for 6 months continuously and their general condition, blood, organs were examined, no abnormalities were seen up to a dose of 1.5 g/kg, but at doses of ≥3 g/kg, diarrhea appeared and at 4 g/kg the body weight gain was inhibited only in males.
Teratogenicity: Fetal Test: Capsule:
In oral administration test, no teratogenic action was seen at dose of 1.5 g/kg in mice and rats.
No mutagenicity was seen in the Rec-assay, Ames test, chromosome test or dominant lethality test.
In a carcinogenicity test performed by administering 2.5% or 5% of tranexamic acid mixed with the feed for 19 months, no carcinogenicity was observed.