Is oral tranexamic acid (TXA) effective and safe for treating melasma?

Oral Tranexamic Acid for Melasma

Oral tranexamic acid is effective and safe for treating melasma, with a recommended starting dose of 250 mg twice daily for 12-16 weeks, showing significant improvement in melasma severity scores without increased thromboembolic risk. 1, 2, 3

Evidence for Efficacy

Multiple studies demonstrate that oral tranexamic acid effectively reduces melasma severity:

• All doses from 250 mg daily to 1,500 mg daily show clinical efficacy, with improvement correlating with both treatment duration and dosage 2
• Both 250 mg once daily and 500 mg twice daily produce comparable therapeutic efficacy at 16 weeks, though the higher dose shows earlier MASI score reduction at 4 weeks 4
• Studies consistently show significant reduction in modified Melasma Area and Severity Index (mMASI) scores across various dosing regimens 1
• Patient satisfaction is high with long-term treatment, and most patients tolerate extended therapy well 2

Recommended Dosing Protocol

Start with 250 mg orally twice daily (total 500 mg/day) for 12-16 weeks as the optimal balance between efficacy and safety 4, 5, 3:

• This dose can be used alone or combined with topical hydroquinone, kojic acid, and sunscreen 5
• Lower doses (250 mg once daily) are effective but show slower initial response 4
• Higher doses up to 1,500 mg daily are safe but offer no significant additional benefit in MASI reduction 2
• Treatment duration of 8-12 weeks minimum is required for visible improvement 3

Pre-Treatment Evaluation

Before initiating oral tranexamic acid, obtain the following:

• History of thromboembolism risk factors, cardiovascular disease, and menstrual disorders 5
• Baseline coagulation profile in all patients 5
• More extensive testing (CBC, LFTs, protein C and S) in patients with high thromboembolism risk 5

Safety Profile

The safety data for oral tranexamic acid in melasma is reassuring:

• No increased thromboembolic risk demonstrated in large meta-analyses of over 125,550 participants across clinical settings 6, 7
• Common side effects are mild: stomach upset and decreased menstruation, which rarely require discontinuation 2
• Oligomenorrhea and abdominal discomfort occur in some patients but do not necessitate stopping treatment 4
• Oral tranexamic acid has a good safety profile even with doses ranging from 250 mg to 1,500 mg daily for 2 weeks to 6 months 8

Monitoring During Treatment

• Repeat coagulation profile at 3-month intervals, especially in patients with clinically higher thromboembolism risk 5
• No routine monitoring required in low-risk patients, though baseline coagulation studies are recommended 5

Treatment Duration and Discontinuation

• Treatment can be stopped abruptly after improvement; no tapering required 5
• Relapses are common after discontinuation, requiring repeated courses 4, 5
• Lower relapse rates observed with 250 mg once daily (4.7%) compared to 500 mg twice daily (10.8%) at 28 weeks follow-up 4

Combination Therapy Approach

Oral tranexamic acid works best as part of a comprehensive regimen:

• Combine with effective home care routine and strict sun protection 1
• Can be used with topical agents (hydroquinone, kojic acid, tretinoin, corticosteroids) 1, 5
• Manage melasma as a chronic condition requiring regular follow-up 1

Contraindications

Avoid oral tranexamic acid in:

• Active thromboembolic disease or history of thrombosis 9
• Active intravascular clotting or disseminated intravascular coagulation 6
• Severe hypersensitivity to tranexamic acid 6
• Use with extreme caution in patients on oral contraceptive pills due to increased thrombosis risk 6

Clinical Implementation Algorithm

1. Screen for contraindications and thromboembolism risk factors
2. Obtain baseline coagulation profile (and extended testing if high-risk)
3. Start 250 mg orally twice daily with meals
4. Combine with topical therapy and strict photoprotection
5. Follow up at 4-week intervals to assess MASI score reduction
6. Continue for minimum 12-16 weeks
7. Repeat coagulation profile at 3 months if high-risk
8. Stop abruptly once adequate improvement achieved
9. Anticipate need for repeated courses upon relapse

Important Caveats

The evidence base is strongest in Asian populations with darker skin types 3, though efficacy has been demonstrated across various skin types. Oral tranexamic acid should be considered for cases unresponsive to topical hydroquinone and combination therapy over approximately 12 weeks 3. The treatment requires patient commitment to sun protection and home care, as melasma is a chronic relapsing condition 1.