For a patient with melasma, should I start with topical tranexamic acid 10% cream and, if there is no improvement after a few weeks, switch to oral tranexamic acid, and is oral therapy required long‑term; also, will tranexamic acid be effective for non‑melasma hyperpigmentation?

Topical Tranexamic Acid 10% Cream for Melasma

Start with triple combination cream (hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%) plus strict sun protection rather than topical tranexamic acid 10% cream, as this is the American Academy of Dermatology's recommended first-line therapy; topical tranexamic acid has not demonstrated superiority over vehicle in controlled trials. 1, 2

Why Topical Tranexamic Acid Is Not Recommended as First-Line

• A double-blind randomized controlled trial of topical 5% tranexamic acid showed that lightening of pigmentation was neither superior nor different compared to vehicle (p > 0.05), despite 78.2% of patients showing some melanin index decrease 2
• Topical tranexamic acid produced significant erythema (p < 0.05) compared to vehicle, adding an unwanted side effect without proven efficacy advantage 2
• No high-quality evidence supports 10% topical tranexamic acid cream as effective monotherapy for melasma 1, 3, 4

The Correct First-Line Approach

Begin with triple combination cream applied nightly plus SPF 50+ broad-spectrum sunscreen reapplied every 2-3 hours during outdoor exposure. 1

• Triple combination cream contains hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% 1
• Corticosteroids in the formulation reduce irritation and enhance penetration of active ingredients 1
• Continue this regimen for 8-12 weeks before considering escalation 3

Essential Sun Protection Measures

• Apply SPF 50+ broad-spectrum sunscreen reapplied every 2-3 hours during outdoor exposure 1, 3
• Wear wide-brimmed hats (>3-inch brim) when outdoors 1
• Seek shade during peak UV hours (10 a.m. to 4 p.m.) 1
• Use UV-protective clothing with tight weave fabrics and darker colors 1

When and How to Use Oral Tranexamic Acid

If inadequate response after 8-12 weeks of topical therapy, add oral tranexamic acid 250 mg twice daily (total 500 mg/day) for 12 weeks, not topical formulations. 3, 5, 6

Oral Dosing Protocol

• The optimal dose is 250 mg three times daily (750 mg/day) for 12 weeks based on network meta-analysis, but 250 mg twice daily (500 mg/day) is acceptable for adherence 6
• Even low doses (500 mg daily) over 8-12 weeks have demonstrated clear efficacy in Asian skin 5
• Treatment duration should be 12 consecutive weeks for optimal results 6

Is Lifelong Oral Therapy Required?

No, oral tranexamic acid is not taken lifelong; it is prescribed for 12-16 weeks as adjunctive therapy, with maintenance achieved through continued sun protection and intermittent topical agents. 3, 4

• After the initial 12-16 week course, discontinue oral tranexamic acid 3
• Melasma is a chronic condition with high recurrence rates, so maintenance therapy is essential but does not require continuous oral medication 1, 4
• Maintenance consists of strict sun protection indefinitely plus intermittent use of topical agents 3, 4
• Consider maintenance intradermal PRP treatments every 6 months if you escalate to that level 1, 3, 4

Safety Screening Before Starting Oral Tranexamic Acid

• Screen for absolute contraindications: recent thrombosis and active thromboembolic disease 3
• Screen for relative contraindications: atrial fibrillation, known thrombophilia, and history of venous thromboembolism 3
• Studies show oral tranexamic acid does not increase thromboembolic risk when patients are screened carefully 5
• Side effects are few and mild, including mild stomach upset and decreased menstruation 7

Efficacy for Non-Melasma Hyperpigmentation

Yes, oral tranexamic acid works for non-melasma hyperpigmentation disorders, but evidence is less robust than for melasma. 8

• Oral tranexamic acid has been used for postinflammatory hyperpigmentation (treatment and prevention), lichen planus pigmentosus, ashy dermatosis, and Riehl melanosis 8
• Doses range from 250 mg per day to 1500 mg per day for 2 weeks to 6 months with variable efficacy and good safety profile 8
• It is a promising treatment option for hyperpigmentation disorders refractory to topical treatment, though more randomized controlled trials are needed 8

If First-Line Therapy Fails: The Superior Alternative

If inadequate response after 8-12 weeks of triple combination cream plus oral tranexamic acid, escalate to intradermal PRP injections, which are significantly more effective than tranexamic acid injections. 1, 3, 4

PRP Treatment Protocol

• Administer 4 intradermal PRP treatment sessions spaced every 2-3 weeks 1, 4
• Inject intradermally at 1 cm intervals across affected areas 1
• Follow-up evaluation one month after the last treatment 1, 4
• PRP shows significantly better results than intradermal tranexamic acid injections with similar side effect profiles 9, 1, 4
• PRP combined with oral tranexamic acid 250 mg twice daily demonstrates 90.48% total efficacy versus 73.68% with tranexamic acid alone 1, 3, 4

Measuring Success

• Use modified Melasma Area and Severity Index (mMASI) scores at baseline, 4 weeks, 8 weeks, and end of treatment 3
• MASI reduction >90% = excellent response 1
• MASI reduction 60-90% = moderate improvement 1
• MASI reduction 20-60% = mild improvement 1

Critical Pitfalls to Avoid

• Do not discontinue treatment too early—melasma requires long-term maintenance therapy even after initial clearing 1, 4
• Do not forget to reapply sunscreen after swimming, sweating, or after 2-3 hours of continuous exposure 1
• Do not use laser therapy in Fitzpatrick skin types IV-VI due to markedly higher risk of burns, post-inflammatory hyperpigmentation, and hypopigmentation 1
• Do not expect topical tranexamic acid alone to work—it has not proven superior to vehicle in controlled trials 2