Tranexamic Acid: Pharmacological Effects and Adverse Effects

General Description

Tranexamic acid exerts its therapeutic effects by inhibiting plasmin formation, enhancing hemostasis, and modulating melanocyte activity. It displays anti-inflammatory and antiallergic properties, making it useful in treating conditions like melasma and menorrhagia. Pharmacokinetically, it is rapidly absorbed, primarily eliminated through renal excretion, and has a short half-life. Adverse effects include gastrointestinal discomfort, musculoskeletal pain, and the potential for ocular toxicity, although evidence of retinal damage in humans is lacking. Despite these side effects, Tranexamic acid is considered safe, with limited evidence linking it to increased thromboembolic risk when used as prescribed for melasma and menorrhagia.

Figure 1. Tranexamic acid

Pharmacological Effects

Tranexamic acid exerts its therapeutic effects through its unique mechanism of action and pharmacokinetic properties. As a synthetic derivative of the amino acid lysine, Tranexamic acid binds to lysine residues of plasminogen, thereby inhibiting its conversion to plasmin, a key enzyme in the fibrinolytic cascade. By preventing plasmin formation, Tranexamic acid effectively halts fibrinolysis, leading to enhanced hemostasis. This mechanism underlies its primary use in surgical procedures and the treatment of conditions such as menorrhagia, where controlling bleeding is paramount. Beyond its hemostatic effects, Tranexamic acid exhibits anti-inflammatory and antiallergic properties. Research suggests that Tranexamic acid inhibits epidermal melanocyte tyrosinase activity, thereby interfering with the production of melanin. Moreover, it blocks the interaction between melanocytes and keratinocytes by inhibiting the plasminogen/plasmin system. This inhibition not only affects melanocyte activity but also decreases the production of inflammatory mediators, such as arachidonic acid and prostaglandins, which stimulate melanocytes. Additionally, Tranexamic acid prevents UV light-induced plasmin activity, reduces mast cell activity, and inhibits fibroblast growth factor, leading to decreased vascularity and mast cell numbers in the dermis. Regarding its pharmacokinetics, Tranexamic acid is typically administered orally or intravenously and has a relatively short half-life. After administration, it is rapidly absorbed, with peak plasma concentrations reached within a few hours. The drug is primarily eliminated through renal excretion, with minimal metabolism in the liver. In summary, Tranexamic acid's mechanism of action involves inhibition of plasmin formation, leading to enhanced hemostasis and modulation of melanocyte activity. Its pharmacokinetic profile includes rapid absorption, renal elimination, and a short half-life, contributing to its efficacy and safety profile in various clinical settings. ¹

Adverse Effects

Tranexamic Acid is a medication commonly used for various conditions, including melasma and menorrhagia. While it has shown efficacy in managing these conditions, concerns have been raised regarding its adverse effects profile, particularly the risk of thromboses. Studies have highlighted several adverse effects associated with Tranexamic Acid use. These include nasal and sinus discomfort, back pain, musculoskeletal pain, oligomenorrhea, and abdominal cramps. Notably, ocular toxicity, including retinal damage, has been a concern based on animal studies with higher doses of Tranexamic Acid. However, long-term human studies, such as that conducted by Theil, have found no evidence of ocular toxicity, specifically no retinal damage. In addition to these side effects, nausea and diarrhea have been commonly reported with Tranexamic Acid use, particularly in studies evaluating its use for hemorrhagic conditions. Despite these side effects, there is limited evidence linking Tranexamic Acid to an increased risk of thromboembolic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE). Population-based studies have further supported the safety profile of TXA, demonstrating no increased risk of DVTs or PE with TXA treatment compared to control groups. The dosing of Tranexamic Acid varies depending on the condition being treated. For melasma, doses typically range from 500 to 1,500 mg daily, with a typical regimen of 250 mg twice daily for 8 to 12 weeks. In contrast, for menorrhagia, higher doses of 3.9 to 4 g daily for up to 5 days per month are commonly used. In summary, while Tranexamic Acid may cause some mild adverse effects such as gastrointestinal discomfort and musculoskeletal pain, evidence suggests that it is generally safe for use in the management of melasma and menorrhagia, with a low risk of thromboembolic events when used as directed. ²

Reference

1. Callender ST, Warner GT, Cope E. Treatment of menorrhagia with tranexamic acid. A double-blind trial. Br Med J. 1970; 4: 214–216.

2. Bala HR, Lee S, Wong C, Pandya AG, Rodrigues M. Oral Tranexamic Acid for the Treatment of Melasma: A Review. Dermatol Surg. 2018; 44(6): 814-825.

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