Drug Safety Alert: Products with Hydroquinone
Hydroquinone has been popularly used for decades as a bleaching agent for treating skin pigmentation, as well as freckles and age spots. However, on January 2001, the European Union (EU) banned the use of hydroquinone in cosmetics due to mid-term side effects such as leukomelanderma en confettu and exogenous ochronosis. Other health agencies including Health Canada, US Food and Drugs Administration (FDA), and the Philippine FDA have regulated the use of hydroquinone due to its potential adverse effects.
According to Administrative Order 90 s 2003 in the Philippines, concentrations of hydroquinone more than two percent (2%) to four percent (4%) should be classified as over the counter, while preparations more than four percent (4%) of hydroquinone but less than five percent (5%) require a prescription. Both preparations need the presence of a pharmacist for dispensing in a registered drug outlet. Any preparations containing five percent (5%) or more hydroquinone are not allowed and are prohibited from being registered. These specifications are also applicable to hydroquinone in combination products (Hydroquinone + Tretinoin).
Unfortunately, several products have shown to be non-compliant by the PH FDA and advised the public to be vigilant against the use and purchase of these cosmetics (Refer to Table 1). As mentioned by the PH FDA, these products may cause untoward side effects such as skin irritation, itchiness, anaphylactic shock, and organ failure. (Note that these products also contain tretinoin.)
Table 1. Cosmetic Products Containing which tested positive for Hydroquinone and Tretinoin from the FDA Advisories No. 2018-026 and 2018-092
|1||Skin Magical Rejuvenating Cream No. 1|
|2||Skin Magical Rejuvenating Facial Toner No. 1|
|3||I Cosmetica Skin Care Enterprise Rejuvenating Toner|
|4||I Cosmetica Skin Care Enterprise Rejuvenating Cream|
|5||New Brilliant Skin Essential Rejuvenating Facial Toner|
|6||Speaks G Skin Essential Brightening Rejuvenating Toner|
|7||Cosmetic Buffet Bleaching Cream|
|8||Cosmetic Buffet Rejuvenating Toner|
|9||Moleek Skincare Anti Pigmentation Cream Plus|
|10||Dnars Yellow Gold Collagen|
|11||Luffiya Night Cream 1|
|12||Tati Therapy Cream 2|
Besides the short to mid-term adverse effects, hydroquinone has shown to be carcinogenic in animal models. Hepatocellular and renal tubule adenomas have been reported in animal studies. Human studies may be inadequate to prove carcinogenicity of hydroquinone in humans, but this paucity in data should not be confused with the absence of risk. Nephrotoxicity has also been reported.
A review by Kooters and Westerhoff have discussed the biologic plausibility of hydroquinone’s carcinogenicity. Hydroquinone is one of the metabolites of benzene, a known carcinogen. One possible mechanism of the benzene’s carcinogenicity, by means of its metabolites, is attributed to its ability to covalently bond with DNA and induce DNA oxidation. Both mechanisms can lead to chromosomal damage resulting in mutagenicity. The study also mentioned that topical administration may pose an increased risk of cancer due to faster uptake, rapid distribution, and less detoxification by the liver compared to inhalational and oral routes.
As pharmacists, advise your patients to use hydroquinone at appropriate amounts for the recommended specified duration of time. In addition, inform your patients to consult their healthcare provider if hyperpigmentation gets worse after hydroquinone use.