Indications
Tranexamic Acid is orally administered for the management of several conditions, including hereditary angioedema, cyclic heavy menstrual bleeding in premenopausal females, and significant bleeding associated with hyperfibrinolysis. When given intravenously, it is used on a short-term basis, typically between 2 to 8 days, to help patients with hemophilia reduce or prevent bleeding following dental extractions.
Pharmacodynamics
As an antifibrinolytic agent, tranexamic acid functions by competitively inhibiting the conversion of plasminogen to plasmin. At elevated concentrations, it acts as a noncompetitive inhibitor of plasmin, resembling the behavior of aminocaproic acid, albeit with ten times the potency. Tranexamic acid binds more effectively to both strong and weak receptor sites on the plasminogen molecule compared to aminocaproic acid, reflecting its increased efficacy. In the context of hereditary angioedema, the inhibition of plasmin formation and activity by tranexamic acid can decrease the activation of the first complement protein (C1) through plasmin, potentially preventing angioedema attacks. However, off-target effects include antagonism of GABA(A) receptors, potentially leading to convulsions and hyperexcitability, particularly with improper administration or in cardiovascular surgical settings. EEG monitoring is advised for patients with a history of seizures.
Absorption
The oral bioavailability of tranexamic acid is approximately 30 to 50% and is not influenced by the intake of food. Following administration of multiple oral doses (1300 mg three times daily for 5 days), the maximum concentration (Cmax) achieved is 16.41 mcg/mL, with a time to reach this concentration (Tmax) of 2.5 hours.
Metabolism
The metabolic pathway of tranexamic acid is not extensively characterized and does not appear to play a significant role in its elimination. Prescribing information indicates that about 1% of an orally administered dose is excreted as a dicarboxylic acid and 0.5% as an acetylated metabolite.
Mechanism of Action
Tranexamic Acid functions through a competitive and reversible inhibition of plasminogen activation. This is achieved by its binding to multiple sites on plasminogen, including several low-affinity sites and a critical high-affinity site. The high-affinity site is crucial for plasminogen's interaction with fibrin. Normally, the binding of plasminogen to fibrin initiates fibrinolysis, leading to clot dissolution. By occupying these essential binding sites, Tranexamic Acid effectively prevents the breakdown of fibrin, thereby stabilizing the clot and reducing the risk of hemorrhage.
