Findings published in JDD suggest topical tranexamic acid can be used as first-line monotherapy.
A recent study published in the Journal of Drugs in Dermatology reviewed topical tranexamic acid (TXA) as a practical treatment option for melasma. Seemal R. Desai, MD, FAAD, and colleagues, sought to understand the current gaps in the treatment of melasma, and how TXA may provide relief as monotherapy or combination therapy. Desai et al noted that managing melasma is difficult due to its complex pathogenesis, chronicity, and high recurrence rates. Many physicians choose a multimodal therapeutic plan to address the complexity of melanogenesis and deeper melasma.1
Patients with melasma should avoid intense sun exposure, especially from 10am to 3pm. Broad spectrum UVA, UVB, and visible light filter sunscreens are needed to prevent the exacerbation of melasma. For topical therapy treatment, hydroquinone concentrations of 2% to 4%are typically used as the gold standard of melasma therapy. Hydroquinone does have the possibility of causing irritant contact dermatitis and should not be used for extended durations. Triple combination therapy of 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide can be used as first-line therapy. The combination can be used as a maintenance regimen for 8 weeks or more with a maximum limit of 1 year in daily or intermittent or tapering dose regimen.
Chemical peels can be added to topical regimens for increased results. If there is no improvement with chemical peels, a combination of first-line treatment plus laser and/or light therapy can be used. It is important to note that laser and light therapy can be associated with long-term complications, specifically in patients with skin of color. Pulsed radiofrequency waves can be used to target both melanin pigment deposits and abnormal vasculature to strengthen the basement membrane that is compromised in melasma. Desai et al noted, “Given the global negative impact of melasma on QoL, the quest for effective topical treatments that offer sustained long-term remission for melasma is ongoing.”
Oral TXA can be used alone or as an adjuvant to certain conventional topical drugs or when other topical treatments fail. TXA is anti-inflammatory and can even prevent UV-induced pigmentation. Desai et al stated that clinical trials evaluating oral TXA are limited because the studies do not have a control group, the overall the studies have small sample sizes and varying dosage and duration requirements. Additionally, some physicians still have concerns related to the safety of oral TXA, as it has the potential to induce thromboembolic phenomena. Common adverse events of tranexamic acid use include mild gastrointestinal discomfort, hypomenorrhea, allergic skin rashes, alopecia, and mild elevations in alanine transaminase levels. “There is a need to stress the importance of patient education and the need for a better method to predict the efficacy of conventional therapies in patients as they lose confidence when treatments fail (i.e., laser therapy may lead to post-inflammatory hypo/hyperpigmentation),” said Desai et al.
According to the study investigators, TXA’s prevention of the binding of plasminogen to keratinocytes inhibits UV-induced plasmin activity, and melanogenesis is then reduced by the decreased production of PGs. Melasma typically responds well to oral and/or locally injected TXA. Unlike oral and injectable TXA, some topical formulations cannot achieve robust therapeutic concentrations at the dermo-epidermal junction target site in the skin and therefore becomes a limitation of topical TXA.
“A variety of topical formulations and regimens have been evaluated in trials, including 3% cream for 12 weeks, 5% gel for 12 weeks, 3% solution for 12 weeks, 5% liposome for 12 weeks, and 2% formulation for 12 weeks, with varying results. Hence, not all topical TXA can be deemed the same, with the resulting variability of efficacy likely due to formulation-based differences in skin penetration and delivery of the required dose to the targeted site,” said study investigators. Additionally, topical TXA can be combined with skin lightening and antioxidant agents such as niacinamide, which already has lightening properties. Topical TXA can also be used with lactobionic acid which increases skin cell turnover.
Certain preclinical results support conducting further topical tranexamic studies, including a double-blind placebo-controlled clinical study on topical TXA 2% with patented delivery technology.
A panel of 10 dermatologists from the Philippines, Indonesia, Singapore, Vietnam, and the United States, and one aesthetic practitioner from Indonesia met in July 2021 to discuss the challenges of melasma management in their regions, with a specific focus on existing treatment strategies and their limitations. Specific challenges physicians face include compliance and unrealistic patient expectations. The panelists decided on 5 practice points based on their research and discussions.
The study investigators concluded that “Topical TXA can be offered as first-line monotherapy for induction of mild to moderate melasma. Current evidence highlights the role that topical TXA or combination formulations with TXA play in the management of melasma patients. Topical TXA is effective in certain situations, such as in patients with are unable to tolerate the adverse events associated with hydroquinone or oral TXA, those who are unresponsive to conventional therapies for melasma, or switch therapy or maintenance treatment for those in need of drug holidays.”