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For Physicians

Physicians have been safely and effectively using hydroquinone for the treatment of disorders of pigmentation, most commonly hyperpigmentation, for over 40 years.  The use of the product was reaffirmed by the American Academy of Dermatology’s 2006 letter to the FDA which outlined  their scientific belief that 4% hydroquinone is safe and effective and an important therapy for many patients.

A number of leading dermatologists continue to do research on hydroquinone in the academic and clinical setting in order to determine how to best manage a variety of hyper- and hypopigmentation disorders.

 

Rationale for Safety of 4% Hydroquinone (HQ)

There is a large body of observational data which documents that 4% hydroquinone is a safe and effective treatment when used under a physician’s care as well as several published studies:

  • A 2006 comprehensive scientific literature review discussing the safety of hydroquinone can be reviewed in the Journal of the European Academy of Dermatology and Venereology. The abstract states: “Hydroquinone is one of the most effective molecules for the treatment of hyperpigmentary disorders with over 40 years of efficacy and safety data . . . despite 40-50 years of use of hydroquinone for medical conditions, there has not been a single documented case of either a cutaneous or internal malignancy associated with this drug.” [1]
  • Howard I. Maibach, M.D., professor of dermatology at the University of California School of Medicine, San Francisco and expert in the field, summarizes the safety profile of hydroquinone as follows: “Overall, adverse events reported with the use of hydroquinone…have been relative few and minor in nature… hydroquinone is undoubtedly the most active and safest skin-depigmenting substance.”
  • A 2006 letter by the American Academy of Dermatology to the FDA reaffirmed their scientific belief that 4% hydroquinone is safe and effective and an important therapy for many patients.  The letter provides a review of safety data and also provides the rationale for continued use of over-the-counter (OTC) and prescription hydroquinone under current GRASE and DESI II classifications.
  • Large epidemiological studies on workers exposed to hydroquinone through occupational exposure (e.g., workers in film development, lithography, chemical processing plants) over many years confirm its lack of carcinongenicity in humans.  For example, in-depth surveys of 9,000 workers involved in the manufacture of hydroquinone at chemical plants who had prolonged exposure to high concentrations of hydroquinone have demonstrated lower premature death rates and reduced cancer rates in exposed workers compared to nonexposed controls. [2],[3]

 

This represents only a few cases of the documented safety and efficacy; additional literature is noted below for reference:

  • DeCaprio AP. The toxicology of hydroquinone – relevance to occupational and environmental exposure. Crit Rev Toxicol. 1999;29(3):283-330.
  • Deisinger PJ, Hill TS, English JC. Human exposure to naturally occurring hydroquinone. J Toxicol Environ Health. 1996;47(1):31-46.
  • Wester RC, Melendres J, Hui X, Cox R, Serranzana S, et al. Human in vivo and in vitro hydroquinone topical bioavailability, metabolism, and disposition. J Toxicol Environ Health A. 1998; 26;54(4):301-317.
  • Grimes P. Letters to the Editor: The safety of hydroquinone. J Cosmetic Derm. 2006;5:168-170

 

Frequently Asked Questions:

Q1.         How common are disorders of skin pigmentation?

A1.         The American Academy of Dermatology recognizes dyschromias as an important cutaneous disease with significant patient morbidity. They note that millions of patients each year are affected by dyschromias which include melasma, vitiligo, post-inflammatory hyperpigmentation, solar lentigines, and uneven skin tone.  In addition, National Ambulatory Care Survey data identifies about three million dermatologist’s office visits for the treatment of dyschromias. [4] Moreover, there are several million additional cases that are unreported as these individuals do not see a physician for evaluation and treatment of their dyschromias but utilize OTC products.

Q2.         What are the known side effects of hydroquinone?

A2.         Physicians are deeply aware of some of the common and rare adverse effects of hydroquinone and have reported successful management through careful explanation of the appropriate use of the product.

The most common reports of adverse effects include skin irritation, hyper- and hypopigmentation, and nail discoloration.  A more rare side effect is the occurrence of ochronosis, a cutaneous disorder characterized by discoloration at the site of application of chemicals to the skin, which has been successfully managed through proper use of the product and the use of sunscreen.  Exogenous ochronosis secondary to hydroquinone was first described by Findlay et al in South Africa. [5] In this original group of patients, hydroquinone containing creams in concentrations of 5% or more applied to areas of hyperpigmentation for an average of 3 years, and without the use of sunscreen, resulted in exogenous ochronosis.  However, the American Academy of Dermatology emphasizes that exogenous ochronosis is a remarkably uncommon disorder in the United States.  In fact, industry estimates are of at least 10 million users of hydroquinone containing products in the past 40 years there have been only 15 reported case reports of exogenous ochronosis in the United States.

There has also been some evidence of carcinogenicity in rats and mice were exposed to high oral doses of hydroquinone in OTC skin bleaching products.3 However, carcinogenicity in humans is not supported by any case reports of renal or hepatic neoplasms or leukemia in individuals with normal use of hydroquinone over a 50 year span or for those individuals with excessive hydroquinone exposures including in industrial workers.

Q3.         Is Hydroquinone an approved drug by the FDA?

A3. Hydroquinone 4% as a single active ingredient product is one of many drugs which physicians are currently allowed to prescribe without  formal FDA approval.  Were FDA aware of a health or safety concern with hydroquinone 4%, it has the right to take prompt action as it has done with other unapproved marketed drugs that they believed presented health issues, such as trimethobenzamide, papain, and ergotamine.  There are between 1,000 and 2,000 other products on the market which fall into a very similar category. These are all products that have been on market for many years without being required to undergoe the current formal FDA approval process.

Based on the absence of any evidence to suggest that hydroquinone poses a health risk at either concentration or any reported cases in the U.S. of injury or illness as a result of its use, the FDA has, to date, not required a NDA approval for its continued marketing.

 

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[1] Norlund JJ, Grimes PE, Ortonne JP. The safety of hydroquinone.  Journal of the European Academy of Dermatology and Venereology 20(7), 781-787.

[2] DeCarpio AP. The toxicology of hydroquinone – relevance to occupational and environmental exposure.  Crit Rev Toxicol 1999: 29 (3): 283-330.

[3] Pifer JW, Hearne FT, Friedlander BR, McDonough JL.  Mortality study of men employed at a large chemical plant, 1972 through 1982.  J Occup Med 1986; 28: 438-44.

[4] National Center for Health Statistics: Ambulatory Health Care Data http://www.cdc.gov/nchs/about/major/ahcd/sampnam.htm

[5] Findlay GH, Morrison JGL, Simson IW.  Exogenous ochronosis and pigmented colloid milium from hydroquinone bleaching creams.  Br J Dermatol 1975; 93: 613-22.