What is the role of oral tranexamic acid (TXA) in treating hyperpigmentation other than melasma?

Oral Tranexamic Acid for Hyperpigmentation Other Than Melasma

Oral tranexamic acid (TXA) has limited evidence supporting its use for hyperpigmentation disorders other than melasma, with doses ranging from 250-1500 mg daily for 2 weeks to 6 months showing variable efficacy and should be considered only for refractory cases unresponsive to topical treatments. 1

Mechanism and Evidence

• Tranexamic acid is a synthetic derivative of lysine that functions as an antifibrinolytic agent, originally FDA-approved for treating cyclic heavy menstrual bleeding and preventing bleeding in hemophilia patients undergoing tooth extraction 1
• TXA has been used off-label in dermatology primarily for melasma, with emerging evidence for other hyperpigmentation disorders 1
• While oral TXA has demonstrated clear efficacy for melasma in Asian skin at doses as low as 500 mg daily over 8-12 weeks, evidence for non-melasma hyperpigmentation is much more limited 2

Potential Applications in Non-Melasma Hyperpigmentation

• Oral TXA has been investigated for several hyperpigmentation disorders including:
  • Post-inflammatory hyperpigmentation (both treatment and prevention)
  • Lichen planus pigmentosus
  • Ashy dermatosis
  • Riehl melanosis 1

Dosing and Duration

• For non-melasma hyperpigmentation, dosing has ranged from 250 mg to 1500 mg daily 1
• Treatment duration varies widely from 2 weeks to 6 months depending on the condition and response 1
• For comparison, in melasma studies, doses of 250 mg twice daily have shown significant improvement with mean treatment periods of approximately 4 months 3

Safety Considerations

• TXA generally has a good safety profile but requires careful patient screening 2
• Common side effects include headaches, malaise, nausea, gastrointestinal upset, and menstrual irregularities 4
• Serious adverse events are rare but can include deep vein thrombosis, particularly in patients with underlying thrombophilic disorders 5
• Contraindications include:
  • History of thromboembolic disorders
  • Active cardiovascular disease
  • Renal dysfunction
  • Pregnancy
  • Concurrent use of oral contraceptives 2

Treatment Algorithm

1. First-line approach:

   • Begin with topical treatments and strict sun protection 6
   • Ensure proper photoprotection with SPF 30+ sunscreen, reapplied every 2-3 hours during outdoor exposure 6

2. Consider oral TXA when:

   • Hyperpigmentation is refractory to topical treatments for at least 8-12 weeks 1
   • Patient has no contraindications to oral TXA 2
   • Starting dose of 250 mg twice daily is reasonable based on melasma experience 3

3. Monitoring:

   • Assess response after 2 months of treatment 5
   • Continue for 3-6 months if responding well 1
   • Discontinue if side effects occur or no improvement after 3 months 4

Important Caveats

• The evidence for oral TXA in non-melasma hyperpigmentation is primarily from small studies and case reports 1
• More robust evidence from randomized controlled trials is needed to establish definitive efficacy 1
• Relapse rates may be high after discontinuation, as seen in melasma studies (approximately 27%) 5
• Patients should be thoroughly screened for personal and family history of thromboembolism before initiating therapy 5
• For comparison, in melasma, PRP injections combined with oral TXA have shown higher efficacy (90.48%) than TXA alone (73.68%) 7