Changes to FDA regulations have been implemented as part of the CARES Act, leaving dermatologists and their patients confused about how to access hydroquinone. This article will clarify what prescribers and their patients need to know and also dig deeper into alternative treatment options.
What Is The CARES Act?
The Coronavirus Aid, Relief, and Economic Security Act (the CARES Act) was signed into law in March 2020. Its purpose is to provide emergency assistance and health care response for individuals, families, and businesses affected by the COVID-19 pandemic.
However, subtitle F of the act imposes substantial reform of the regulatory framework for nonprescription drugs, which is the largest shake-up of the review process for over-the-counter (OTC) drugs since the process was first implemented. Given these changes, the CARES Act goes far beyond addressing the current public health emergency and has a major impact on our access to commonly-used ingredients, such as hydroquinone.
The Impact of the CARES Act on the Use of Hydroquinone
Hydroquinone is a category 1 substance on the Food and Drug Administration’s (FDA) “503B Bulk Drug Substances List,” meaning that items from 503B facilities with this ingredient are not allowed to be dispensed at this time unless they have been FDA-approved through the new drug application (NDA) process. 503B pharmacies typically produce large batches of compounded drugs for “office use.” The activities of such facilities have been severely restricted and are now unable to collaborate with physicians on customized formulas until the compounds have been submitted for testing and stability studies.
If prescribers wish to use hydroquinone for their patient’s aesthetic issues, they must engage the services of a 503A compounding pharmacy, such as VLS Pharmacy. 503A compounding pharmacies are traditionally patient-focused compounding facilities, meaning that they are able to fulfill individual, patient-specific prescriptions approved by a prescribing practitioner. There is a strict requirement, however, that the medications must be shipped directly to the patient and not dispensed from the prescriber’s office.
It’s also important to note that physicians must comply with FDA guidelines as well as state and local pharmacy regulations before filling prescriptions with hydroquinone.
2 to 4% hydroquinone has been widely prescribed for the topical treatment of hyperpigmentation, which results from uneven production of melanin by the skin. It remains the most frequently-used whitening constituent in its category. It acts by reducing the number of melanocytes in the treated area and decreasing the production of melanin by the remaining melanocytes, resulting in localized bleaching of the melanin pigment in the skin.
Hyperpigmentation is often more apparent in skins that are naturally darker and, therefore, contain more melanin. Such hyperpigmentation may be triggered by several factors, including:
- Hormonal changes (melasma)
- Pregnancy: Chloasma is often called “the mask of pregnancy”
- Oral contraceptives
- Inflammatory response
- Exposure to ultraviolet light
- Senile lentigines (also called age spots or liver spots)
The Fitzpatrick Scale
The Fitzpatrick scale was developed by an American dermatologist as a way to estimate the skin’s photosensitivity or the response of different types of skin to ultraviolet light. The table below lists the skin-type categories that the scale applies:
|Type I||0 – 6||Always burns/never tans (palest)|
|Type II||7 – 13||Usually burns/tans minimally|
|Type III||14 – 20||Sometimes mild burn/tans uniformly|
|Type IV||21 – 27||Burns minimally/always tans well (moderate brown)|
|Type V||28 – 34||Very rarely burns/tans very easily (dark brown)|
|Type VI||35 – 36||Never burns (deeply pigmented dark brown to darkest brown)|
Those patients who fall into the Fitzpatrick scale range of IV to VI have longer and larger melanocyte dendrites, resulting in their melanin residing in the upper layers of the skin. The size of the pigment granule is also larger in people with darker skin tones, which explains why incidents of overstimulation of melanocytes are often more apparent with darker skins. While the tendency toward forming darker patches of skin is purely a cosmetic concern, it is often deeply tied with a person’s self-confidence, making effective treatment and prevention an important factor in many people’s lives.
Since hydroquinone was first introduced 50 years ago, various issues and concerns have been raised with regards to its potential dermatological and systemic side effects. It was even considered for removal from the market by the FDA in 2006. With hydroquinone’s safety profile still under investigation, it is important to ensure that its use is closely monitored by a professional and that patients are advised to be aware of potential immediate side effects, which include:
- Skin dryness
- Irritation or a burning sensation
- Mild contact dermatitis or allergic reactions
Long-term use of hydroquinone may increase susceptibility to ochronosis, which causes a blue-black pigmentation and/or caviar-like spots to develop on the skin. Other phenol-based compounds (including phenol carbolic acid), as well as systemic antimalarials (including intravenous quinine and oral antimalarials), have also been associated with ochronosis.
VLS Pharmacy and New Drug Loft are able to support physicians who wish to continue prescribing hydroquinone-based treatments for their patients. However, monitoring of the patient’s progress should be undertaken with all of these potential side effects in mind. Also, as previously mentioned, the compounding must be performed specifically for the patient, and the medication must be shipped directly to the patient and not to the prescriber’s office.
Alternative Treatments to Hydroquinone
With the uncertain future of hydroquinone and the current regulations invoked by the CARES Act, which prevent OTC dispensing of the ingredient, alternative agents with comparable efficacy for treating melasma, sun damage, and hyperpigmentation are urgently required. Several such options are available, including:
- Tranexamic acid: Tranexamic acid (trans-4-aminomethyl cyclohexane carboxylic acid) was first registered as a blood-clotting antifibrinolytic drug. Its use was extended to a dermatological application as a general depigmenting agent for hormone-induced, ultraviolet-induced, and post-inflammatory hyperpigmentation.
- Niacinamide: Niacinamide is a form of vitamin B3 that has been shown to be effective in reducing the skin’s pigmentation when applied topically as a 5% niacinamide moisturizer. It is already part of many dermatologists’ treatment packages because it’s also efficacious in the treatment of acne.
- Azelaic acid: Azelaic acid is a naturally occurring dicarboxylic acid found in wheat, rye, and barley. The 15% topical gel of azelaic acid is FDA-approved for the treatment of mild to moderate rosacea. The use of azelaic acid topical gel is also often applied off-label for the treatment of acne and hyperpigmentation. Thanks to its excellent safety profile and how well it is tolerated, azelaic acid, either as a monotherapy or in combination, is also an effective first-line or alternative treatment for hyperpigmentation.
- Kojic acid: Kojic acid is found naturally occurring in several different types of fungi and as a by-product of fermentation in certain foodstuffs. Kojic acid inhibits melanin production, making it an effective treatment for hyperpigmentation. It has been approved for use in cosmetic products in concentrations of 1% or less. Kojic acid is not tolerated as well as azelaic acid, especially in patients with sensitive skin. Most side effects are the symptoms of contact dermatitis, such as redness; irritation or itchiness; rashes; swollen skin; and pain or discomfort.
- Retinoids: Retinoids are a class of chemicals related to vitamin A. Topical application of a first-generation retinoid, called Tretinoin (Retinoic Acid), is effective in the treatment of post-inflammatory hyperpigmentation of darker skins. Tolerance varies across individuals and may improve with use over time. It is important, therefore, to closely monitor patient progress when using retinoid therapies.
- Butylresorcinol: A potential new treatment, 4-butyl resorcinol, is already available on several international markets. Butylresorcinol demonstrates excellent efficacy for treating melanin-related skin disorders. It may be that the FDA will consider it safe enough to be classified as an OTC treatment in the United States in the future. Reference
The Use of Chemical Peels
An alternative strategy to address hyperpigmentation is to undertake therapeutic chemical peels. Our pharmacists at VLS Pharmacy and New Drug Loft are experts at crafting custom peels to address aesthetic concerns. By collaborating with prescribers, we develop formulas to provide effective treatments at affordable rates, ensuring that the treatment fits the patient’s unique requirements. We also offer a comprehensive menu of peels.
Choosing the constituents of a chemical peel is a specialized skill. Consider the following:
- Trichloroacetic acid (TCA) 10–80%: TCA has higher efficacy than several common peeling agents, such as salicylic acid and glycolic acid. It is often the first choice to rejuvenate skin in one treatment. It is vital to establish with your patients whether they require a pre-TCA regimen, as TCA peels are contraindicated in patients undergoing treatment with retinoid creams or medications.
- Glycolic acid 20–50%: A glycolic acid or alpha-hydroxy acid (AHA) peel is a chemical exfoliation treatment. It’s an effective choice to combat skin discoloration. Glycolic acid peels are contraindicated in patients taking prescribed acne products or suffering from rosacea.
- Jessner Peel (Resorcinol 14% / Salicylic Acid 14% / Lactic Acid 14%): Jessner Peel combinations are effective in treating acne and reducing the appearance of freckles, sun damage, dark spots, and scars. Jessner Peel is considered safe for Fitzpatrick skin types IV-VI without increasing the risk of associated damage. The Jessner Peel is contraindicated, however, in patients with very fair or sensitive skin and we often modify the formula by removing resorcinol and replacing it with mandelic acid 10%.
Prevention Rather Than Cure: Good Sun Hygiene
One of the most important interventions is to take a prophylactic approach to prevent hyperpigmentation from occurring. The easiest exposure factor to control is ultraviolet exposure. The sun’s ultraviolet rays can damage the skin in as little as 15 minutes. Patients predisposed to hyperpigmentation should be counseled to practice good sun hygiene and to use sunblock.
The American Academy of Dermatology Association advises that most people apply only 25 to 50% of the recommended amount of sunscreen, noting that adults need about 1 ounce (a shot glass volume) to fully cover their body. They recommend that people should:
- Apply sunscreen to dry skin 15 minutes before going outdoors.
- Apply sunscreen to the tops of feet, neck, ears, and the top of the head (if applicable).
- Protect lips with a lip balm or lipstick that contains sunscreen with an SPF of 30 or higher.
- Reapply sunscreen approximately every two hours and after swimming or sweating.
Not only does enforcing good sun hygiene reduce the incidence of discoloration and hyperpigmentation of the skin, but it also reduces the risk of developing melanoma — a risk that doubles in individuals who have had five or more sunburns.
Compounding for Hyperpigmentation
Our pharmacists provide the expertise to create custom compounds to address both medical skin conditions and aesthetic concerns. We collaborate with prescribers to develop formulas to provide effective treatments at affordable rates. To treat the causes of hyperpigmentation, we have developed:
- Allergen and preservative-free formulas
- Antioxidant creams and serums
- Bleaching agents
- Customized blends, working with prescribers to choose a base as well as ingredient combinations of ingredients for maximum compliance and efficacy
Reach out to our team to learn about best practices and to partner with our experts and learn about custom compounded medications and peels for your dermatology patients.
All medications from VLS Pharmacy are prepared in a lab that follows safety and quality standards per our status as a 503A pharmacy.
Covid-19 Vaccine at VLS Pharmacy
VLS Pharmacy is currently administering the Moderna Vaccine by appointment only to those age 18 and older. If appointments are unavailable, please check back frequently as New York State is systematically allocating vaccines. As we receive more vaccines, more spots will open. Please note: we CANNOT book your appointment over the phone due to the screening requirements.