SAN DIEGO (FRONTLINE MEDICAL NEWS) – The use of tranexamic acid, a prothrombotic agent approved in the United States for treatment of menorrhagia, is “truly a breakthrough” in the treatment of melasma, according to Amit Pandya, MD.

Tranexamic acid is also used to treat intraoperative hemorrhage, is available over the counter in some countries, and is used widely for treating melasma in East Asia, Dr. Pandya said at a meeting of the Skin of Color Society, held the day before the annual meeting of the American Academy of Dermatology.

Its use for treatment of melasma was first reported in 1979. Results in patients with melasma have been “amazing,” said Dr. Pandya, although he was initially skeptical when he heard reports about the beneficial effects of tranexamic acid for melasma ( J Cosmet Dermatol. 2013 Mar;12[1]57-66] ).

Dr. Pandya, professor of dermatology at the University of Texas Southwestern, Dallas, described a woman with a 20-year history of melasma who had been treated with triple combination creams, chemical peels, and Fraxel lasers “to no avail,” similar to patients he sees in his practice every week. But after 3 months of treatment with 325 mg of tranexamic acid twice daily, triple combination cream, and visible light sunscreen, she was clearer than she had been for some time, he said.

Tranexamic acid “ blocks keratinocytes from causing plasminogen to go into plasmin,” and plasmin stimulates fibroblast growth factor production, which is “one of the most potent stimulants of melanin,” he explained.

In a retrospective study published in 2016, conducted by investigators at the National Skin Center in Singapore, 561 patients with melasma were treated with oral tranexamic acid for a median of 4 months, almost 90% of the patients improved. There was one serious adverse event, a deep vein thrombosis ( J Am Acad Dermatol. 2016 Aug;75[2]:385-92 ). The other adverse effects were mild. When Dr. Pandya spoke with the investigators about this patient, he was told that the patient had not disclosed her true medical history, which included protein S deficiency and a strong family history of thrombotic events, which would have excluded her from treatment.

Of 2,000 published cases of melasma treated with tranexamic acid to date, “this is the only severe event ever seen with tranexamic acid,” he noted.

Dr. Pandya and his associates recently published the results of a study evaluating tranexamic acid in 44 Latino women with moderate to severe melasma, which he said was the first study of tranexamic acid in the Western hemisphere. For 3 months, the women were treated with 250 mg of tranexamic acid or placebo in combination with sunscreen in both groups, then sunscreen only for 3 months in both groups. The primary outcome was the change in the modified Melasma Area and Severity Index (mMASI) score.

“Results were spectacular,” he said. At 3 months, the mMASI score had improved by 49% among those in the tranexamic acid group, compared with 18% among those on placebo and sunscreen. After 3 months on sunscreen only, there was a 26% reduction in the mMASI score from baseline among those treated with tranexamic acid, compared with 19% in the placebo group. None of the patients in either group had severe adverse events ( J Am Acad Dermatol. 2018 Feb;78[2]:363-9 ). Side effects include GI upset, reduced menstrual flow, myalgias, and headache.

Rebound after cessation of therapy is an issue, however, and was worse in the treated group “because more melanocytes are actually created when you reduce melanin. So once you stop the tranexamic acid, it rebounds,” Dr. Pandya said. Patients should use triple combination cream when they stop taking tranexamic acid, he advised.

However, he said that patients have called him within 1 month of stopping tranexamic acid, asking to restart treatment. He has had patients on tranexamic acid for 1 year or longer, without any side effects.

Women who are pregnant or nursing, have had two or more spontaneous abortions, are on oral contraceptives or other hormone-based birth control, have a history of thrombosis, are on blood thinners, are smokers, or have significant cardiovascular or respiratory disease, subarachnoid hemorrhage, any DVT, or a strong family history of thromboembolic events should not be treated with tranexamic acid.

Dr. Pandya pointed out that the 250-mg dose used in the study is not available in the United States, where only the 650-mg dose is available. So he writes a prescription for 650 mg a day, and tells patients to cut the pill in half and take a 325-mg dose twice a day (half in the morning and half at night).

At the Skin of Color Society meeting, Nahla Shihab, MD, of Universitas Indonesia, Jakarta, presented the results of a randomized, placebo-controlled study evaluating oral tranexamic acid plus hydroquinone cream in patients with moderate to severe melasma, in collaboration with UT Southwestern and Dr. Pandya. Patients were randomized to treatment with topical hydroquinone 4% cream, sunscreen, and tranexamic acid (250 mg twice a day), or hydroquinone 4% cream, sunscreen, and placebo for 3 months, followed by 3 months of sunscreen only.

At 12 weeks, those in the tranexamic acid group had a 55% decrease in the mMASI score, compared with 10.9% in the control group. After stopping treatment, some patients experienced relapses, similar to what has been observed in other studies, but “the severity was still lower than baseline,” Dr. Shihab reported.

In addition, the improvement in the mMASI score was higher than that seen in other studies, which could be due to a synergistic effect of the fibrin inhibitor with hydroquinone, she added. Another important finding was that improvements were noticeable after 2 weeks of treatment, “which suggests that the combination of oral tranexamic acid and hydroquinone has a rapid onset of action,” she said.

In both groups, 6% of the patients experienced erythema and pruritus, which resolved with continued use of hydroquinone, and one woman on tranexamic acid had menstrual cycle changes. Further studies should evaluate a longer duration of treatment and follow-up, with tranexamic acid and hydroquinone, and in combination with other treatments, Dr. Shihab said.

Dr. Pandya reported that he is a consultant to Aclaris Therapeutics and Pfizer, and has received grants/research funding from Incyte Corp. Dr. Shihab had no disclosures.