In recent months, the aesthetics industry has been abuzz with confusion wondering: where did the hydroquinone go? The ‘gold standard’ treatment for hyperpigmentation has virtually disappeared from United States skincare shelves — an unwitting casualty of the 2020 CARES Act. Show
Yep, you read that right. The pandemic-inspired economic relief bill also contained a provision for modernizing the way the United States Food and Drug Administration (FDA) regulates over-the-counter (OTC) drugs. The law reforms the agency’s notoriously cumbersome rulemaking system (in place since the 1970s) responsible for creating drug monographs — essentially rulebooks that OTC drug manufacturers can use to bypass the costly drug approval process. The CARES Act resolved all of the pending regulations that were stalled out by decades-old bureaucracy, declaring that “the most recently applicable proposal” would be considered final. Problem is, the monograph for OTC skin bleaching products was still under review. Hydroquinone, which had initially been considered GRASE (read: generally recognized as safe), had been downgraded to ‘not GRASE’ in the most recent recommendation. Without a final monograph and a tentative categorization as unsafe, OTC hydroquinone was toast. Here’s everything you need to know about the compelling (and controversial!) history of hydroquinone in skincare. Naturally found in a variety of plants (including coffee), hydroquinone was first distilled in 1820 and soon became one of the primary chemicals in photographic developing solutions. An antioxidant, it’s commonly used as a stabilizer in paints and motor fuels. The skin bleaching properties of hydroquinone were discovered by accident in 1938 when a group of Chicago leather tannery workers sued the factory owner after they developed depigmented patches (a.k.a. leukoderma) on their hands and forearms. The patches corresponded to areas covered by factory-provided rubber gloves — which had been manufactured using a chemical called monobenzyl ether of hydroquinone. In the following decades, researchers performed a variety of in vitro (i.e. test tube) and in vivo (a.k.a. animal or human) research using various concentrations and formulations of hydroquinone. They found the organic compound to be generally effective at reducing hyperpigmentation in both white and black test subjects — though the dark patches typically returned after discontinued use. What Does Hydroquinone Treat?Clinically, hydroquinone is used to treat dyschromia (read: skin discoloration or patches of uneven skin color). Variations include:
Hydroquinone’s most common use is in patients with PIH and melasma, while its chemical cousin — monobenzyl ether of hydroquinone — is FDA approved to treat severe cases of vitiligo. More often than not, the more you learn about hydroquinone, the more questions you have. From dispelling common myths (i.e. hydroquinone equals bleach) to clearing up confusion (so, what’s the deal with FDA approval?), we’re breaking down some of the most frequently asked questions about hydroquinone. 1. Does Hydroquinone Bleach Skin?Time for another biology lesson: When applied topically, hydroquinone has several effects on the skin cells that produce melanin. These melanocytes are found in the basal layer of the epidermis, where they produce eumelanin (brown or black pigments) and pheomelanin (yellow or red pigments). This process is facilitated by an enzyme called tyrosinase. Hydroquinone impacts this phenomenon (known as melanogenesis) in a couple of ways:
So, technically speaking, hydroquinone isn’t a bleach. Instead, it restricts the skin’s ability to produce melanin, which has the effect of lightening the complexion — but only while you’re using the medication. 2. What Are the Side Effects of Hydroquinone?When used as directed, hydroquinone in concentrations up to 4 percent has relatively mild side effects. Common side effects include:
With that said, rare but serious side effects have also been documented. These include:
It’s worth noting that there have been just 22 documented cases of exogenous ochronosis in the U.S. Worldwide, severe side effects are most commonly associated with prolonged usage of the drug against physician or labeling recommendations or when the hydroquinone is combined with dangerous ingredients like mercury. 3. Does Hydroquinone Cause Cancer?Additionally, There have been quite a few studies trying to conclusively determine the safety of hydroquinone. Research from the Environmental Protection Agency (EPA) and the National Toxicology Program have provoked FDA concern. Here are the takeaways:
4. Is Hydroquinone FDA Approved?A deep dive into hydroquinone regulation in the U.S. reveals a little-known fact — not all drugs (even prescriptions!) sold in America are approved by the FDA. Let’s review how drugs are marketed:
To bridge the gap between what’s clinically needed and what’s approved for prescribing, the Federal Food, Drug, and Cosmetic Act (FD&C Act) allows compounding pharmacies to prepare and dispense drugs that haven’t been formally approved by the FDA. 503A compounding facilities produce drugs for individual patients on a case-by-case basis, while 503B facilities primarily supply bulk drugs for physicians to distribute in-office. 5. Did the CARES Act Ban Hydroquinone?From 2006 to 2020, hydroquinone was in regulatory limbo. With no formal FDA ruling in place, the drug was readily available in both over-the-counter and prescription forms, including at strengths that exceeded the agency’s original recommendations. Under the CARES Act, any drugs that were awaiting a final monograph and were deemed GRASE would be allowed to remain on the market without submitting a new drug application (NDA). Meanwhile, those drugs that did not have a final or tentative final monograph and were not considered GRASE (like hydroquinone) would be considered new drugs and required to submit an NDA within 180 days or face FDA enforcement. The net net: all OTC hydroquinone had to be removed from the market. Manufacturers have the option to file for a new drug application, but the process is no joke. It’s estimated that the median cost of the application and approval process (including fees, clinical studies, etc.) is $19 million and can take about a year. 6. Can You Still Get Hydroquinone in the U.S.?Understandably, many doctors are unclear about how the CARES Act impacts their ability to offer hydroquinone as a treatment option for patients with pigmentation concerns. “There really is no system in place or an alert that tells doctors ‘this is what you can, and cannot do,’” explains Allyson Avila, a partner at Gordon Rees Scully Mansukhani, LLP, and one of the country’s leading lawyers for the medical aesthetics industry. She advises doctors to contact their state drug regulators and/or an attorney for guidance. Here is how Avila summarizes the law as it now stands:
With so many patients relying on hydroquinone to treat hyperpigmentation, dermatologists and plastic surgeons alike are concerned about its continued availability. This is particularly true for BIPOC patients, who are often disproportionately affected by dyschromia. With an FDA-approved formulation and inclusion on the Bulk Substances list for compounding, many experts feel it’s unlikely that the FDA will entirely remove hydroquinone from the U.S. market anytime soon. But the controversy surrounding the drug has spurred efforts to find safe and effective alternatives to treat hyperpigmentation. A Brief History of Hydroquinone
Why was hydroquinone banned?FDA has received reports of serious side effects including skin rashes, facial swelling, and ochronosis (discoloration of skin) from the use of skin lightening products containing hydroquinone.
Where is hydroquinone found naturally?Free HQ was found in coffee (0.2 ppm), red wine (0.5 ppm), wheat cereals (0.2-0.4 ppm), and broccoli (0.1 ppm). After consuming a meal including arbutin- and HQ-containing foods, volunteers showed significant increases in plasma and urinary levels of HQ and its conjugated metabolites (total HQ).
Is hydroquinone a steroid?Fluocinolone is a corticosteroid (steroid medicine), hydroquinone is a bleaching agent, and tretinoin is a retinoid (related to vitamin A). This medicine is available only with your doctor's prescription. This product is available in the following dosage forms: Cream.
Does hydroquinone affect liver?► Hydroquinone may cause a skin allergy. ► Long term exposure may affect the liver and kidneys.
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