Tranexamic Acid (TXA) in Dermatology

A Detailed Note for the Dermatology Resident

1. Introduction and Pharmacology

"Tranexamic acid is a synthetic analogue of lysine that exhibits anti-fibrinolytic activity by competitively inhibiting transformation of plasminogen to plasmin."

• Goodman & Gilman's Pharmacological Basis of Therapeutics, Treatment of Hyperpigmentation section

• Heavy menstrual bleeding (oral, 1 g four times daily for 4 days)
• Prevention of hemorrhage in patients with hemostatic defects undergoing dental extraction

2. Mechanism of Action in Dermatology

1. UV radiation induces plasminogen activator production by keratinocytes.
2. Plasmin (derived from plasminogen activation) stimulates melanocytes via:
   • Arachidonic acid release
   • Fibroblast growth factor (FGF) stimulation
   • Vascular endothelial growth factor (VEGF) stimulation (leading to neovascularisation)
3. TXA blocks plasminogen activation, thereby interrupting this UV-triggered melanogenesis cascade.
4. Additional proposed mechanisms include antioxidant activity (inhibiting reactive oxygen species) and direct inhibition of the plasmin-mediated increase in melanocyte-stimulating factors.

"UV radiation induces plasminogen activator production by keratinocytes, which leads to increased melanogenesis through stimulation of melanocytes by plasmin, arachidonic acid, and fibroblast growth factor, and thence to increased neovascularization via vascular endothelial growth factor stimulation. Tranexamic acid mitigates this UV-induced melanogenesis and neovascularization through inhibition of plasminogen activation."

• Goodman & Gilman's, Treatment of Hyperpigmentation, lines 2667-2669

"Plasmin inhibition; antioxidant"

• Fitzpatrick's Dermatology (8th Ed.), Table on Lightening Agents, line 5526

3. Available Formulations and Dosing

3.1 Topical TXA

• Concentration: 2%-5% formulation
• Frequency: Twice daily
• Duration: Several weeks to months
• Generally well-tolerated; may cause mild irritant contact dermatitis

Listed as an adjunctive topical therapy for melasma at 2%-5%

• Dermatology 2-Volume Set, 5e (Bolognia), Chapter on Melasma, lines 318-320

Available as topical 2%-5% BID

• Goodman & Gilman's, lines 2668-2669

3.2 Oral TXA

• Dose for melasma: 250 mg twice daily (BID) for 8-12 weeks
  • Some sources quote 500-700 mg/day in divided doses
• Dose for HAE prophylaxis: 1 g four times daily (adults); 500 mg four times daily (children) for 48 hours around procedures

"Tranexamic acid (250 mg BID for 8-12 weeks)" as an adjunctive oral therapy for melasma

• Dermatology 5e (Bolognia), Adjunctive oral therapies table, line 326

"When used as an adjunct in low doses (500 to 700 mg daily) over a few months, it is efficacious and safe in treatment-resistant cases."

• Fitzpatrick's Dermatology, Melasma MANAGEMENT section, line 5597

Andrews' Diseases of the Skin cites the Tse TW et al. reference: "Tse TW, et al: Tranexamic acid. J Cosmet Dermatol 2012; 12: 57." in the MELASMA (CHLOASMA) section, confirming TXA's place in melasma management.

• Andrews' Diseases of the Skin, Clinical Dermatology, Melasma section, line 712

3.3 Intradermal (Microinjection) TXA

• Concentration: 4 mg/mL
• Frequency: Once weekly to once monthly
• Most common side effect: Injection site burning/erythema

"Tranexamic acid has been used topically as a 2% to 5% formulation twice daily or intradermally at a concentration of 4 mg/mL with injection frequency ranging from once weekly to once monthly."

• Goodman & Gilman's, lines 2668-2669

3.4 Comparative Efficacy Summary

4. Dermatological Indications

4.1 Melasma (Primary and Most Evidence-Based Use)

• Listed as an adjunctive topical agent alongside L-ascorbic acid, kojic acid, and niacinamide
• Listed as an adjunctive oral therapy alongside first-line treatments (hydroquinone, retinoids, triple combination)
• Effective in treatment-resistant cases when combined with other modalities

"Recently, tranexamic acid has been proven to lighten epidermal and dermal melasma. It has been used in topical, intralesional, and oral forms."

• Fitzpatrick's Dermatology, Melasma Management section, line 5597

From the melasma treatment algorithm (Table 67.4):

• Adjunctive topical: TXA 2-5%
• Adjunctive oral: TXA 250 mg BID for 8-12 weeks
• Long-term maintenance: topical TXA 2-5%
• Dermatology 5e (Bolognia), block 15, lines 316-351

• Oral TXA + low-fluence Q-switched Nd:YAG laser (laser toning) - particularly effective in Asian skin
• Oral TXA + hydroquinone
• Topical TXA + kojic acid + niacinamide

"Low-fluence quality-switched Nd:YAG and 'laser toning' have demonstrated moderate improvements in Asian skin and have even been used in combination with oral tranexamic acid and hydroquinone."

• Fitzpatrick's Dermatology, Riehl Melanosis MANAGEMENT section, line 5710

4.2 Riehl Melanosis (Pigmented Contact Dermatitis)

"More recent reports describing treatment with lasers and oral tranexamic acid. Intense pulsed-light therapy has been helpful in some cases... Low-fluence quality-switched Nd:YAG and 'laser toning' have demonstrated moderate improvements in Asian skin and have even been used in combination with oral tranexamic acid and hydroquinone."

• Fitzpatrick's Dermatology, Riehl Melanosis Management section, lines 5710-5711

4.3 Post-Inflammatory Hyperpigmentation (PIH)

4.4 Chronic Urticaria (Limited Evidence)

"Miscellaneous drug therapies described for chronic urticaria include tranexamic acid, heparin, and warfarin, but convincing evidence for their use is lacking and there are no specific situations where they appear to be better than other treatments."

• Dermatology 5e (Bolognia), Urticaria Drug Therapies section, lines 547-548

4.5 Hereditary Angioedema (HAE) / C1 Esterase Inhibitor Deficiency

• Adults: 1 g four times daily for 48 hours before and after minor surgical procedures
• Children: 500 mg four times daily for the same period

"For minor surgical procedures, oral tranexamic acid (1 g four times daily in adults or 500 mg four times daily in children) for 48 hours before and after the procedure... can be effective prophylaxis."

• Dermatology 5e (Bolognia), C1 Esterase Inhibitor Deficiency section, lines 578

"As a result, the use of anabolic steroids (see above) and tranexamic acid have declined. The latter is an inhibitor of the activation of plasminogen to plasmin and is contraindicated if there is a history of thrombosis; with chronic administration, regular eye examinations and liver function tests are recommended."

• Dermatology 5e (Bolognia), lines 579-580

5. Side Effects and Safety Profile

5.1 Topical

• Generally well-tolerated
• Occasional mild erythema, itching, stinging
• No systemic concerns at low topical concentrations

5.2 Intradermal

• Injection site burning (most common)
• Transient erythema

5.3 Oral - Systemic TXA

"The most common side effect is abdominal bloating or headache. Patients should be screened for thromboembolic risk factors prior to systemic use."

• Goodman & Gilman's, line 2669

"With chronic administration, regular eye examinations and liver function tests are recommended."

• Dermatology 5e (Bolognia), line 580

6. Contraindications and Precautions

• Active thromboembolic disease (DVT, PE, thrombotic stroke)
• History of thrombosis

• Risk factors for thromboembolism (oral contraceptive pill, smoking, immobility, clotting disorder, family history)
• Pregnancy (crosses placenta - though oral TXA is FDA-approved for heavy menstrual bleeding and risk categorisation is evolving)
• Ureteral obstruction/haematuria: risk of ureteral obstruction from organised clot
• Renal impairment: drug accumulation, dose adjustment required

"Patients should be screened for history of and risk factors for thromboembolism."

• Dermatology 5e (Bolognia), line 357 (footnote to melasma treatment table)

"Tranexamic acid...is contraindicated if there is a history of thrombosis"

• Dermatology 5e (Bolognia), line 580

7. Monitoring

• Baseline: Thromboembolic risk factor screening, renal function
• Ongoing: Liver function tests (LFTs), ophthalmological review (colour vision, retinal assessment)

8. Place in Therapy - Melasma Treatment Algorithm

First-line:
├── Broad-spectrum sunscreen (mandatory) + sun avoidance
├── Triple combination (HQ 4% + tretinoin 0.05% + topical corticosteroid) or HQ 4% alone
└── Azelaic acid 15-20%

Adjunctive topicals (alongside first-line):
├── L-ascorbic acid 10-15%
├── Kojic acid 1-4%
├── Tranexamic acid 2-5% ← TXA
└── Niacinamide 4%

Adjunctive oral:
└── Tranexamic acid 250 mg BID × 8-12 weeks ← TXA

Second-line:
└── Chemical peels (glycolic 30%+ or salicylic 20-30%) every 4-6 weeks

Third-line:
├── Non-ablative fractional laser
├── IPL
├── Low-fluence Q-switched lasers
└── Picosecond lasers

Long-term maintenance:
├── Daily sunscreen
├── Topical retinoid
└── Topical adjuncts including TXA 2-5%

9. Recent Evidence Update (PubMed, 2023-2026)

1. Liang R et al. (2024) - Network meta-analysis in Journal of Cosmetic Dermatology (PMID: 38059683) comparing efficacy and safety of TXA by different administration methods for melasma. Concluded TXA is highly efficacious across all routes.
2. Olugbade ID & Negbenebor NA (2024) - Systematic review in Cutis (PMID: 39298769) specifically on TXA combined with microneedling for melasma treatment.
3. Alghamdi SMH et al. (2025) - Systematic review and meta-analysis in Archives of Dermatological Research (PMID: 40167772) comparing fractional Er:YAG laser + TXA (various delivery methods) versus TXA alone.

10. Key Points Summary for Clinical Practice

Sources and References