Tranexamic acid - How It Works
Clinical pharmacology details from the US FDA-approved label: how Tranexamic acid works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin’s matrix structure. The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains 4 to 5 lysine binding sites with low affinity for tranexamic acid (K d = 750 μmol/L) and 1 with high affinity (K d = 1.1 μmol/L). The high affinity lysine site of plasminogen is involved in its binding to fibrin. Saturation of the high affinity binding site with tranexamic acid displaces plasminogen from the surface of fibrin. Although plasmin may be formed by conformational changes in plasminogen, binding to and dissolution of the fibrin matrix is inhibited.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin.
In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin’s matrix structure.
The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen.
Native human plasminogen contains 4 to 5 lysine binding sites with low affinity for tranexamic acid (K d = 750 μmol/L) and 1 with high affinity (K d = 1.1 μmol/L).
The high affinity lysine site of plasminogen is involved in its binding to fibrin.
Saturation of the high affinity binding site with tranexamic acid displaces plasminogen from the surface of fibrin.
Although plasmin may be formed by conformational changes in plasminogen, binding to and dissolution of the fibrin matrix is inhibited.
12.2 Pharmacodynamics Tranexamic acid, at in vitro concentrations of 25–100 μM, reduces by 20–60% the maximal rate of plasmin lysis of fibrin catalyzed by tissue plasminogen activator (tPA).
Elevated concentrations of endometrial, uterine, and menstrual blood tPA are observed in women with heavy menstrual bleeding (HMB) compared to women with normal menstrual blood loss.
The effect of tranexamic acid on lowering endometrial tPA activity and menstrual fluid fibrinolysis is observed in women with HMB receiving tranexamic acid total oral doses of 2–3 g/day for 5 days.
In healthy subjects, tranexamic acid at blood concentrations less than 10 mg/mL has no effect on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood.
Tranexamic acid, however, at blood concentrations of 1 and 10 mg/mL prolongs the thrombin time.
Cardiac Electrophysiology The effect of tranexamic acid USP tablets on QT interval was evaluated in a randomized, single-dose, 4-way crossover study in 48 healthy females aged 18 to 49 years.
Subjects received tranexamic acid USP tablets 1300 mg tranexamic acid USP tablets 3900 mg (three times the maximum recommended single dose), moxifloxacin 400 mg, and placebo.
There was no significant increase in the corrected QT interval at any time up to 24 hours after the administration of either dose of tranexamic acid USP tablets.
Moxifloxacin, the active control, was associated with a maximum 14.1 msec mean increase in corrected QT interval (moxifloxacin – placebo) at 3 hours after administration.
12.3 Pharmacokinetics Absorption After a single oral administration of 1300 mg of tranexamic acid USP tablets, the peak plasma concentration (C max ) occurred at approximately 3 hours (T max ).
The absolute bioavailability of tranexamic acid USP tablets in women aged 18–49 is approximately 45%.
Following multiple oral doses (1300 mg tablets three times daily) administration of tranexamic acid USP tablets for 5 days, the mean C max increased by approximately 19% and the mean area under the plasma concentration-time curve (AUC) remained unchanged, compared to a single oral dose administration (1300 mg ).
Plasma concentrations reached steady state at the 5th dose of tranexamic acid USP tablets on Day 2.
Pharmacokinetics
12.3 Pharmacokinetics Absorption After a single oral administration of 1300 mg of tranexamic acid USP tablets, the peak plasma concentration (C max ) occurred at approximately 3 hours (T max ). The absolute bioavailability of tranexamic acid USP tablets in women aged 18–49 is approximately 45%. Following multiple oral doses (1300 mg tablets three times daily) administration of tranexamic acid USP tablets for 5 days, the mean C max increased by approximately 19% and the mean area under the plasma concentration-time curve (AUC) remained unchanged, compared to a single oral dose administration (1300 mg ). Plasma concentrations reached steady state at the 5th dose of tranexamic acid USP tablets on Day 2. The mean plasma pharmacokinetic parameters of tranexamic acid determined in 19 healthy women following a single (1300 mg ) and multiple (1300 mg tablets three times daily for 5 days) oral dose of tranexamic acid USP tablets are shown in Table 3. Table 3. Mean (CV%) Pharmacokinetic Parameters Following a Single (1300 mg) and Multiple Dose (1300 mg three times daily for 5 days) Oral Administration of tranexamic acid USP tablets in 19 Healthy Women under Fasting Conditions Parameter Arithmetic Mean (CV%) Single dose Multiple dose C max = maximum concentration AUC tldc = area under the drug concentration curve from time 0 to time of last determinable concentration AUC inf = area under the drug concentration curve from time 0 to infinity T max = time to maximum concentration t 1/2 = t