Skip to main content
Log in

A Comprehensive Review of the Long-Term and Short-Term Treatment of Melasma with a Triple Combination Cream

  • Leading Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript


Melasma is a common disorder of hyperpigmentation and generally involves areas of the face and neck. Hyperpigmentation is especially prevalent in darker complected patients and is often difficult to treat. Hydroquinone, tretinoin, and topical corticosteroids are well established monotherapeutic agents for treating melasma and hyperpigmentation; however, a stable, once-daily formulation triple combination cream containing 0.05% tretinoin, 4.0% hydroquinone, and 0.01% fluocinolone acetonide (Tri-Luma®) represents the only commercially available combination of all three agents. This product is approved by the US FDA for the treatment of facial melasma. A number of publications have described the safety and efficacy of triple combination cream in over 2000 patients with melasma, some of whom were treated for >12 months.

In the initial 8-week study, 29% of patients experienced complete clearing of melasma by week 8, and 77% were clear or almost clear by week 8. Similarly, good results were seen in the two long-term studies, with the clear/mild rate ranging from 78% to 84% of patients at month 6 and from 81% to 94% of patients at month 12. Adverse events were almost always mild in severity and typically occurred only at the application site. The primary concern for most physicians using corticosteroid-containing products on the face is skin atrophy. However, only two cases of skin atrophy were reported across the three published studies.

Overall, the results of these extensive studies indicate that triple combination cream is efficacious in treating melasma and exhibits a safe profile with low potential for adverse events.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II
Table III
Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others


  1. The use of trade names is for product identification purposes only and does not imply endorsement.


  1. Grimes PE. Melasma: etiologic and therapeutic considerations. Arch Dermatol. 1995; 131 (12): 1453–7

    Article  PubMed  CAS  Google Scholar 

  2. Sanchez NP, Pathak MA, Sato S, et al. Melasma: a clinical, light microscopic, ultrastructural, and immunofluorescence study. J Am Acad Dermatol. 1981; 4 (6): 698–710

    Article  PubMed  CAS  Google Scholar 

  3. Kauh YC, Zachian TF. Melasma. Adv Exp Med Biol. 1999; 455: 491–9

    Article  PubMed  CAS  Google Scholar 

  4. Pathak MA, Fitzpatrick TB, Kraus EW. Usefulness of retinoic acid in the treatment of melasma. J Am Acad Dermatol. 1986; 15 (4 Pt 2): 894–9

    Article  PubMed  CAS  Google Scholar 

  5. Menter A. Rationale for the use of topical corticosteroids in melasma. J Drugs Dermatol. 2004; 3 (2): 169–74

    PubMed  Google Scholar 

  6. American Academy of Dermatology. Dermatologists dispatch dark side of melasma [online]. Available from URL: [Accessed 2005 Dec 22]

    Google Scholar 

  7. Taylor SC. Epidemiology of skin diseases in people of color. Cutis. 2003; 71 (4): 271–5

    PubMed  Google Scholar 

  8. Balkrishnan R, McMichael AJ, Camacho FT, et al. Development and validation of a health-related quality of life instrument for women with melasma. Br J Dermatol. 2003; 149 (3): 572–7

    Article  PubMed  CAS  Google Scholar 

  9. Katsambas A, Antoniou C. Melasma: classification and treatment. J Fur Acad Dermatol Venereol. 1995; 4: 217–23

    Article  Google Scholar 

  10. Engasser PG, Maibach HI. Cosmetic and dermatology: bleaching creams. J Am Acad Dermatol. 1981; 5 (2): 143–7

    Article  PubMed  CAS  Google Scholar 

  11. Kimbrough-Green CK, Griffiths CE, Finkel LJ, et al. Topical retinoic acid (tretinoin) for melasma in black patients: a vehicle-controlled clinical trial. Arch Dermatol. 1994; 130 (6): 727–33

    Article  PubMed  CAS  Google Scholar 

  12. Sanchez JL, Vazquez M. A hydroquinone solution in the treatment of melasma. Int J Dermatol. 1982; 21 (1): 5–8

    Google Scholar 

  13. Haddad AL, Matos LF, Brunstein F, et al. A clinical, prospective, randomized, double-blind trial comparing skin whitening complex with hydroquinone vs. placebo in the treatment of melasma. Int J Dermatol. 2003; 42 (2): 153–6

    Article  PubMed  CAS  Google Scholar 

  14. Griffiths CE, Finkel LJ, Ditre CM, et al. Topical tretinoin (retinoic acid) improves melasma: a vehicle-controlled, clinical trial. Br J Dermatol. 1993; 129 (4): 415–21

    Article  PubMed  CAS  Google Scholar 

  15. Taylor SC, Torok H, Jones T, et al. Efficacy and safety of a new triple-combination agent for the treatment of facial melasma. Cutis. 2003; 72 (1): 67–72

    PubMed  Google Scholar 

  16. Torok H, Taylor S, Baumann L, et al. A large 12-month extension study of an 8-week trial to evaluate the safety and efficacy of triple combination (TC) cream in melasma patients previously treated with TC cream or one of its dyads. J Drugs Dermatol. 2005; 4 (5): 592–7

    PubMed  Google Scholar 

  17. Torok HM, Jones T, Rich P, et al. Hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%: a safe and efficacious 12-month treatment for melasma. Cutis. 2005; 75 (1): 57–62

    PubMed  Google Scholar 

  18. Grimes P, Kelly AP, Torok H, et al. Community-based trial of a triple-combination agent for the treatment of facial melasma. Cutis. 2006; 77 (3): 177–84

    PubMed  Google Scholar 

  19. Gano SE, Garcia RL. Topical tretinoin, hydroquinone, and betamethasone valerate in the therapy of melasma. Cutis 1979; 23 (2): 239–41

    PubMed  CAS  Google Scholar 

  20. Kang WH, Chun SC, Lee S. Intermittent therapy for melasma in Asian patients with combined topical agents (retinoic acid, hydroquinone and hydrocortisone): clinical and histological studies. J Dermatol. 1998; 25 (9): 587–96

    PubMed  CAS  Google Scholar 

  21. Berardesca E, Maibach H. Ethnic skin: overview of structure and function. J Am Acad Dermatol. 2003; 48 (6 Suppl.): S139–42

    Article  PubMed  Google Scholar 

  22. Balkrishnan R, Kelly AP, McMichael A, et al. Improved quality of life with effective treatment of facial melasma. J Drugs Dermatol. 2004; 3 (4): 247–51

    Google Scholar 

  23. Giannotti B, Melli MC. Current approaches to the treatment of melasma. Clin Drug Invest. 1995; 10 Suppl. 2: 57–64

    Google Scholar 

  24. Kligman LH, Schwartz E, Lesnik RH, et al. Topical tretinoin prevents corticosteroid-induced atrophy without lessening the anti-inflammatory effect. Curr Probl Dermatol. 1993; 21: 79–88

    PubMed  CAS  Google Scholar 

  25. McMichael AJ, Griffiths CE, Talwar HS, et al. Concurrent application of tretinoin (retinoic acid) partially protects against corticosteroid-induced epidermal atrophy. Br J Dermatol. 1996; 135 (1): 60–4

    Article  PubMed  CAS  Google Scholar 

Download references


The author has acted as a consultant for Galderma Laboratories LP, Intendis, Coria, and Barrier Therapeutics; as a speaker for Galderma Laboratories LP, Allergan, Novartis, Amgen, and Genentech; and as an investigator for Collagenex, Medicis, Stiefel, and Dermik. No sources of funding were used to assist in the preparation of this review.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Helen M. Torok.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Torok, H.M. A Comprehensive Review of the Long-Term and Short-Term Treatment of Melasma with a Triple Combination Cream. Am J Clin Dermatol 7, 223–230 (2006).

Download citation

  • Published:

  • Issue Date:

  • DOI: