Side Effects of Kligman Formula
An Expert Opinion Study in Iraq
DOI:
https://doi.org/10.32007/jfacmedbaghdad3348Keywords:
Hydroquinone;, Kligman formula, Melasma, Skin Lightening, Triple formulaAbstract
Background: Kligman's formula (the triple formula) is a skin-lightening product used to treat hyperpigmentation. It is widely used and is generally abused by non-dermatologists in addition to self-prescription. Despite its popularity, Kligman’s formula is not free of side effects.
Objectives: To explore the side effects of Kligman's formula as observed by specialised dermatologists, and their beliefs and future advice regarding its use.
Methods: A descriptive cross-sectional study was conducted in Iraq from July 1, 2021, to June 1, 2022, and included 103 dermatologists. A structured questionnaire was developed by the researcher, including 21 questions covering the characteristics of the Klingman formula prescription, its effectiveness, side effects, participants' beliefs, and future recommendations. Descriptive statistics, including frequencies and percentages, were used to summarise the data.
Results: Approximately half of the participants reported that they were often confronted with the side effects of the Klingman formula. most reported side effects were irritation (73.79%), redness (61.17%), and irregular pigmentation (41.75%). Approximately 78.7% of the participants reported irrational prescriptions of the Klingman formula by non-dermatology specialists, pharmacists, and beauty experts. Approximately 80.6% of the participants reported that melasma became more difficult to manage after using Klingman formula, and 16.5% of them were advised to stop its use.
Conclusion: The Klingman formula is irrationally prescribed, mainly by non-dermatology specialists. The side effects of this formula are frequently observed. The main observed side effects were irritation, redness, and irregular pigmentation. A majority of the participating dermatologists reported that melasma became more difficult to manage after using the Klingman formula, and 16.5% of them advised to stop using it.
Received: 02 May 2026
Revised: 12 July 2026
Accepted: 08 Aug. 2026
Published Online: Aug. 2026
References
Handel AC, Miot LD, Miot HA. Melasma: a clinical and epidemiological review. An Bras Dermatol. 2014;89(5):771-782. https://doi.org/10.1590/abd1806-4841.20143063
2. Bertold C, Fontas E, Singh T, et al. Efficacy and safety of a novel triple combination cream compared to Kligman's trio for melasma: A 24-week double-blind prospective randomized controlled trial. J Eur Acad Dermatol Venereol. 2023;37(12):2601-7. https://doi.org/10.1111/jdv.19455
3. Kasraee B. Skin depigmenting agents: where do we stand? In: Aghaei S, editor. Pigmentation Disorders - Etiology and Recent Advances in Treatments. London: Intech Open; 2023. https://doi.org/10.5772/intechopen.106791
4. Al Dhafiri M, Almutairi M, Alutaibi HM, et al. Attitude toward using the triple combination bleaching formula and related outcomes: A cross-sectional study. Cureus. 2021;13(12):e20542. https://doi.org/10.7759/cureus.20542
5. Aghdam SB, Mohammad AP, Hosseini‐Baharanchi FS, et al. Efficacy, safety, tolerability and treatment durability of microneedling plus topical tranexamic acid in combination with topical modified Kligman lightening formula for melasma: A four‐arm assessor and analyst blinded randomized controlled clinical trial. J Cosmet Dermatol. 2024; 23(11):3585-97. https://doi.org/10.1111/jocd.16464
6. Tantanasrigul P, Sripha A, Chongmelaxme B. The efficacy of topical cosmetic containing alpha‐arbutin 5% and kojic acid 2% compared with triple combination cream for the treatment of melasma: a split‐face, evaluator‐blinded randomized pilot study. Journal of Cosmetic Dermatology. 2025 Jan;24(1): e16562. https://doi.org/10.1111/jocd.16562
7. Salman HA, Abedalrida RI. Evaluating the efficacy of Kligman plus modified Kligman formula versus the same treatment combined with kojic acid, vitamin C, glycolic acid and glutathione mesotherapy in the treatment of melasma. Iraqi Postgrad Med J. 2023;22(4):486-90. https://doi.org/10.52573/ipmj.2023.182310
8. Zito PM, Bhojwani A. Drugs in dermatology: Kligman's solution (triple combination cream of tretinoin, hydroquinone, and topical corticosteroid) for use in hyperpigmentation. J Dermatol Nurses Assoc. 2017;9(6):323-5. https://doi.org/10.1097/JDN.0000000000000350
9. Besra L, Tripathy R, Srivastava V, et al. Comparative evaluation of safety and economic burden due to topical steroid misuse in patients with self-medication and prescribed medication. J Pharmacol Pharmacother. 2024;14(4):290-5. https://doi.org/10.1177/0976500X241230801
10. Malakooti S, Nasrollahi SA, Kashani MN, et al. Formulation of triple cream for treatment of melasma. Jundishapur J Nat Pharm Prod. 2020;15(2): e62252. https://doi.org/10.5812/jjnpp.62252
11. Elethawi AMD, Al-Gurairi FT. The Impact of Intense-pulsed Light and Modified Kligman’s Formula for Management of the Moderate to Severe Melasma: A Comparative Study. J. Adv. Med. Med. Res. 2024 Feb. 6;36(2):1-8. https://doi.org/10.9734/jammr/2024/v36i25362
12. Majid I, Aleem S. Melasma: update on epidemiology, clinical presentation, assessment, and scoring. Journal of Skin and Stem Cell. 2021 Jan 1;8(8):e122154. https://doi.org/10.5812/jssc.120283
13. Shrestha S, Joshi S, Bhandari S. Prevalence of misuse of topical corticosteroid among dermatology outpatients. JNMA: Journal of the Nepal Medical Association. 2020 Nov 30;58(231):834. https://doi.org/10.31729/jnma.5271
14. Mar K, Khalid B, Maazi M, et al. Treatment of post-inflammatory hyperpigmentation in skin of colour: a systematic review. Journal of cutaneous medicine and surgery. 2024 Sep;28(5):473-80. https://doi.org/10.1177/12034754241265716
15. Al-Battat R, Aram D, Hanoon A, et al. Awareness about Sun Protection among Medical Students. Ann Romanian Soc Cell Biol. 2021 Jul 4;25(6):15216-27. http://www.annalsofrscb.ro/index.php/journal/article/view/8570
16. Pollock S, Taylor S, Oyerinde O, et al. The dark side of skin lightening: An international collaboration and review of a public health issue affecting dermatology. Int J Women's Dermatol. 2021;7(2):158-64. https://doi.org/10.1016/j.ijwd.2020.09.006
17. Akhtar N, Hassan T, Shahzad MK, et al. Comparison between efficacy of serial glycolic acid peel with modified Kligman's regimen vs modified Kligman's regimen alone in epidermal melasma. Pak J Health Sci. 2024; 5(3):29-33. https://doi.org/10.54393/pjhs.v5i03.1284
8. Saeedi M, Khezri K, Seyed Zakaryaei A, et al. A comprehensive review of the therapeutic potential of α‐arbutin. Phytotherapy Research. 2021 Aug;35(8):4136-54. https://doi.org/10.1002/ptr.7076
19. Alrayyes SF, Alrayyes SF, Farooq UD. Skin-lightening patterns among female stuents: A cross-sectional study in Saudi Arabia. Int J Women's Dermatol. 2019;5(4):246-50. https://doi.org/10.1016/j.ijwd.2019.04.026
20. Susmitha M, Divya K, Ramachandra B, et al. Evaluation of therapeutic efficacy of tranexamic acid compared to Kligman formula in the management of melasma. Indian J Clin Exp Dermatol. 2022;8(2):124-31. https://doi.org/10.18231/j.ijced.2022.027
21. Sahu PJ, Singh AL, Kulkarni S, et al. Study of oral tranexamic acid, topical tranexamic acid, and modified Kligman's regimen in treatment of melasma. J Cosmet Dermatol. 2020;19(6):1456-62. https://doi.org/10.1111/jocd.13430
22. Mansouri P, Farshi S, Hashemi Z, et al. Evaluation of the efficacy of cysteamine 5% cream in the treatment of epidermal melasma: A randomized double-blind placebo-controlled trial. Br J Dermatol. 2015;173(1):209-17. https://doi.org/10.1111/bjd.13424
23. King S, Campbell J, Rowe R, et al. A systematic review to evaluate the efficacy of azelaic acid in the management of acne, rosacea, melasma and skin aging. Journal of cosmetic dermatology. 2023 Oct;22(10):2650-62. https://doi.org/10.1111/jocd.15923
24. Boo YC. Mechanistic basis and clinical evidence for the applications of nicotinamide (niacinamide) to control skin aging and pigmentation. Antioxidants. 2021 Aug 21;10(8):1315. https://doi.org/10.3390/antiox10081315
25. Aithal A, Aithal PS. Development and validation of survey questionnaire & experimental data–a systematical review-based statistical approach. International Journal of Management, Technology, and Social Sciences (IJMTS). 2020 Nov 3;5(2):233-51. https://dx.doi.org/10.2139/ssrn.3724105
26. Hizli P, Kiliç FA, İçöz Aytaç S. Melasma revisited: National survey reveals how dermatologists diagnose and treat this complex skin condition. J Cosmet Dermatol. 2025;24(1):e16630. https://doi.org/10.1111/jocd.16630
27. Kanechorn Na Ayuthaya P, Niumphradit N, Manosroi A, et al. Topical 5% tranexamic acid for the treatment of melasma in Asians: a double-blind randomized controlled clinical trial. J Cosmet Laser Ther. 2012;14(3):150-4. https://doi.org/10.3109/14764172.2012.685478
28. Majid I. Mometasone-based triple combination therapy in melasma: is it really safe? Indian J Dermatol. 2010;55(4):359-62. https://doi.org/10.4103/0019-5154.74545
29. Alghamdi SM, Alahmadi MA, Alghanmi RM, et al. Efficacy and safety of Kligman's formula in the treatment of melasma: a systematic review and meta analysis. Archives of Dermatological Research. 2025 Sep 17;317(1):877. https://doi.org/10.1007/s00403-025-04369-7
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