Tranexamic acid in melasma: A focused review on drug administration routes.

BACKGROUND: Melasma is a disorder of hyperpigmentation and vascularization often found in women between the ages of 20 and 40. The pathogenesis is unknown, but melasma often occurs in sun-exposed areas of the face, forearms, and back. Risk factors include family history, increased estrogen/progesterone, certain medications, and UV exposure. Melasma is typically treated with topical hydroquinone (HQ); however, it is often refractory to treatment. Tranexamic acid (TXA) is a plasmin inhibitor used off-label in the treatment of melasma. TXA can be administered orally, topically, or intralesionally. AIMS: The purpose of this review is to characterize the wide variety of TXA delivery methods for melasma treatment and the efficacy of these methods compared with traditional treatments. PATIENTS/METHODS: A comprehensive PubMed and Embase search was conducted in May 2022 using the phrases tranexamic acid and melasma. Forty-six articles were included in this review. RESULTS: Oral, intralesional, and topical TXA is safe and effective treatments for melasma. They have been studied in a variety of randomized controlled trials and have been compared with several traditional treatments. Overall, MASI scores in patients using TXA in any form improved. CONCLUSIONS: Oral TXA was found to be the most effective, especially in cases of refractory melasma; however, it caused GI upset and menstrual irregularities in many patients. The pro-thrombotic nature of this drug must be considered before safely prescribing to patients. Intralesional injections and microneedling with topical TXA were found to be effective alternatives to oral treatment. Lastly, topical TXA alone was found to be the least effective method but can be combined with other cosmeceuticals to improve outcomes. Topical TXA was also found to be better tolerated than hydroquinone, a traditional topical melasma treatment.

Tranexamic Acid in Patients Undergoing Noncardiac Surgery.

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).

Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial.

RATIONALE: Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth. METHODS AND DESIGN: Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework. HYPOTHESIS: In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo. SAMPLE SIZE ESTIMATES: A sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients. INTERVENTION: Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo. PRIMARY EFFICACY MEASURE: The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan. DISCUSSION: We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.