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Topical Tranexamic Acid: A New Improved Formulation for Melasma

Despite the many treatment options available, melasma remains a challenging clinical problem to manage because of its chronic recurring and resistant nature.  There is increasing evidence for the off label use of tranexamic acid (TXA) to treat melasma. While oral TXA has been most commonly used for this purpose, it is promising that the benefits of TXA can be achieved through a safer option — topical application.

What is Tranexamic Acid?

Oral Tranexamic acid (TXA) is indicated to treat and control excessive bleeding in cases such as heavy periods and nose bleeds. “Recently, several studies have shown that the off-label use of oral TXA is effective as an adjunctive treatment in melasma, especially for recalcitrant cases,” explained Dr. Mark Tang, Medical Director and Consultant Dermatologist at The Skin Specialists and Laser Clinic.

TXA has been shown to inhibit vascular and melanogenic mediators that stimulate melanocytes that are responsible for the increased epidermal pigmentation in melasma.1,2 Likewise, it controls pigmentation by inhibiting the release of inflammatory mediators, specifically prostaglandins, which are involved in melanogenesis. As a plasmin inhibitor, TXA also suppresses angiogenesis and inhibits neovascularization induced by basic fibroblast growth factor (bFGF), which stimulates the proliferation of melanocytes.2

“It is important to emphasize that TXA is used as an off-label option in melasma treatment,” stated Dr. Tang. “Hence, physicians need to carefully ensure that the correct diagnosis, indication, contraindications and risks-benefit ratio has been fully discussed and explained to the patient before use,” he added.

Tranexamic Acid – Routes of Administration

According to Dr. Tang, TXA can be administered in various formulations, topical creams, intradermal injections and oral tablets, when used to treat melasma.1,3,4

A recent retrospective study done in Singapore showed that oral TXA 250mg twice daily for a median of 4 months resulted in improvement of melasma severity in 90% of 561 patients.3 Adverse events were reported in 7.1% of patients, which were mainly mild, such as gastrointestinal discomfort, but 1 patient developed deep vein thrombosis and was later discovered to have familial protein S deficiency.3

Another study using intradermal TXA was found to yield significant reduction in melasma area severity index (MASI) at 8 and 12 weeks, with a significant reduction in melanin values at 4 weeks. There were minimal side effects, and all the patients in the study tolerated the treatment well.4

“The main concerns for systemically administered tranexamic acid are the potential side effects, especially for long term use” said Dr. Tang. Intradermal TXA is also semi-invasive with risks of pain, discomfort, risks of skin sepsis and swelling.

Various studies on systematically administered TXA reported side effects such as hypomenorrhea, epigastric discomfort, oligomennorhea, heartburn, headache, nausea, vomiting, gastrointestinal issues, abdominal and flank pain, as well as edema of the hands and feet.1,3,4,5 Careful screening for personal and familial risk factors for thromboembolism should be done before initiation.

Topical Tranexamic Acid

With reported side effects of systematically administered TXA, topical TXA may be a safer treatment option. Several studies have assessed the efficacy of topical TXA and have demonstrated improvement in MASI scores. 6,7,8 Various topical formulations, such as creams, solutions and liposomal creams were used, either as monotherapy or in combination with laser or chemical peels. One study showed that topical TXA was as effective as topical hydroquinone in treatment of melasma.11

To enhance the penetration of TXA into the skin to reach its target site, a novel topical 2% TXA cream has been formulated using a revolutionary patented delivery system called XCELAREV®. In a recently published study, it showed that this topical TXA cream achieved 8.5 times and 11 times more TXA concentration within the epidermis and dermis layers respectively, in an in-vitro skin model, compared to a non-enhanced brand.9

Topical TXA is an important option in the armamentarium for the management of melasma. With the availability of this new topical TXA cream formulated with an enhanced delivery system, melasma patients will have a new option for long-term maintenance topical therapy, without the fear of adverse systemic side effects. Nonetheless, further clinical studies are necessary to determine the efficacy of topical TXA, especially if it should be combined with other lightening agents or physical modalities, such as laser therapy.

References:

  1. Zhang L, Tan WQ, Fang QQ, et al. Tranexamic Acid for Adults with Melasma: A Systematic Review and Meta-Analysis. Biomed Res Int. 2018;2018:1683414.
  2. Zhu JW, Ni YJ, Tong XY, Guo X, Wu XP, Lu ZF. Tranexamic Acid Inhibits Angiogenesis and Melanogenesis in Vitro by Targeting VEGF Receptors. Int J Med Sci. 2020;17(7):903–911.
  3. Lee HC, et al. Oral tranexamic acid in the treatment of melasma: A retrospective analysis Journal of the American Academy of Dermatology, 2016: 75: 385 – 392.
  4. Wang JV, Jhawar N, Saedi N. Tranexamic Acid for Melasma: Evaluating the Various Formulations. J Clin Aesthet Dermatol. 2019;12(8):E73–E74.
  5. Canuto Verussa MJM, Steiner D. Oral Tranexamic Acid to Treat Melasma: A Literature Review. J Dermatol Surg Res Ther 2019: 51-58.
  6. Ebrahimi B, Naeini FF. Topical tranexamic acid as a promising treatment for melasma. J Res Med Sci. 2014;19(8):753–757.
  7. Steiner D, et al. Study evaluating the efficacy of topical and injected tranexamic acid in treatment of melasma. Surgical and Cosmetic Dermatology 2009; 1(4):174-177.
  8. Banihashemi M, et al. Comparison of therapeutic effects of liposomal Tranexamic Acid and conventional hydroquinone on melasma. J Cosmet Dermatol 2015; 14:174-7
  9. Ng SP, et al. In vitro human skin concentrations following topical application of 2% tranexamic acid in co-enhancer cream and branded cream formulations. J Cosmet Dermatol. 2020 – https://doi.org/10.1111/jocd.13301

An Expert Opinion by:

Dr. Mark Tang
Medical Director and Consultant Dermatologist
The Skin Specialists and Laser Clinic
Mt Alvernia Medical Centre
Singapore