THE PCCA BLOG

Compounding Ideas for Hair Growth and Anti-Aging

Tue, 25 Feb 2025 20:01:21 GMT

by Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist

Both hair growth and anti-aging fall beneath the dermatology umbrella: hair is an appendage of the skin, while anti-aging is directly related to skin aesthetics and health. Dermatologists often refer patients to compounding pharmacies for personalized solutions to issues in these areas. In this article, we review specific hair growth solutions and preparations as well as anti-aging compounds.

Hair Growth

The majority of hair growth preparations are topical solutions that use minoxidil as the active pharmaceutical ingredient (API). Minoxidil solubility is pH dependent — especially in higher concentrations — so most compounded solutions require acidification. Due to the poor water solubility of minoxidil, a popular formula for 10% minoxidil solution contains 30% of a mixture of ethyl alcohol and propylene glycol (ppg) for improved solubility, allowing the formula to contain more than 50% Purified Water USP. The formula uses sulfuric acid solution to acidify and adjust the pH to approximately 4.4.

PCCA’s minoxidil lotion formulas employ Atrevis Hydrogel® (PCCA #30-4986) diluted with Preserved Water (Parabens) (USP 51 Study) to a lotion consistency, suspending APIs rather than dissolving them. This negates the need for pH adjustment, which saves time when compounding. The solubilizers in the gel base likely enhance permeation to the follicle, which is the target for optimal results.

Anti-Aging

One hot, new API for anti-aging is Methylene Blue USP (PCCA #30-1115); though known for its bright blue hue, there’s no fear of skin turning blue when preparations use low concentrations. Incorporating concentrations that range from 0.5 to 2.5 micromolar will retain antiaging effects without any discoloration.

The PCCA formula database features anti-aging formulas using VersaBase® Cream (PCCA #30-3641), along with some API formulas that combine Estriol USP Micronized (E3) (PCCA #55-1714) for females, which can stimulate collagen formation, as well as Dimethylaminoethanol (2) (Liquid) (DMAE) (PCCA #50-1986) and PCCA Sodium Hyaluronate (Cosmetic Grade) (PCCA #30-3856) for male and female patients. Additionally, PCCA Formula #15350 combines methylene blue and DMAE into a commonly requested anti-aging compounded preparation.

PCCA members with clinical services access may view and/or download applicable formulas after logging on to our Members-Only Website. Clinical services access also allows members to contact our Clinical Services team for additional information on compounding preparations for patients with hair loss/alopecia and anti-aging issues, as well as other compounding concerns.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.

What’s in Store at the LDN Virtual Conference

Fri, 15 Nov 2024 03:53:03 GMT

Individuals who suffer from symptoms of gastrointestinal, autoimmune, dermatological and pain conditions make up 80% of the patient population. But here’s the good news: multiple studies indicate that low-dose naltrexone (LDN) may potentially help many of these conditions. Take a sneak peek at topics our Clinical Services team will discuss during the Low-Dose Naltrexone One-Day Virtual Conference on Thursday, November 21, 2024.

The Immune System — Autoimmune Conditions and the Benefits of LDN

by Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

LDN has long been touted for its effects in autoimmune disorders. Understanding the mechanisms of LDN action involves diving deeper into immune system function and the irregularities that occur in autoimmune disorders. We’ll explore the data related to LDN’s various mechanisms for improving disease symptomatology and quality of life, as well as review real world published studies and cases of LDN use in various autoimmune disorders.

Dermatological Inflammatory Diseases and LDN

by Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist

LDN is growing in popularity in the dermatology world. It has proven to be beneficial for pruritus and inflammation due to its ability to attenuate toll-like receptors found in the skin. We’ll discuss two cases: one of a tattoo allergic reaction and one of hidradenitis suppurativa (HS). Tattoo reactions to the coloring agents can be intense and difficult to treat. HS is a chronic inflammatory, potentially scarring, skin disease primarily affecting apocrine gland-rich areas of the body (axillary, groin, perianal, perineal regions and abdominal folds), often mediating pain and considerable morbidity, both physical and psychological.

The Use of LDN in Veterinary Patients

by Katy Hecker, PharmD, PCCA Clinical Compounding Pharmacist

As pet owners, we lovingly share many things with our pets including treats, affection and half of the bed. Research suggests we also share similarities in physiological function, disease state manifestation and treatment modalities utilized. Join in the discussion and learn more about the science behind LDN for veterinary clinical indications including behavioral disorders, atopic dermatitis, osteoarthritis, cancer, inflammatory bowel disease (IBD) and more!

Perimenopause and Menopause Are Inflammatory Conditions: The Use of LDN for Hormones and Weight Loss

by Sara Hover, RPh, FAARM, PCCA Director of Clinical Services

Understanding the inflammatory processes that characterize perimenopause and menopause will shed light on how the hormonal changes contribute to weight gain and obesity. Central to this discussion is the shift in estrogen profiles — from estradiol, which possesses anti-inflammatory properties, to estrone, a pro-inflammatory estrogen that becomes predominant during menopause. This hormonal transition fosters an inflammatory state that can disrupt metabolism and promote adiposity. Additionally, the presentation will explore various options aimed at reducing inflammation and managing weight effectively. Key strategies include optimizing sleep quality, utilizing probiotics to support gut health and implementing LDN as an innovative therapeutic approach. Attendees will gain a comprehensive understanding of the biological mechanisms linking menopause to inflammation and weight gain, along with practical interventions to enhance health and well-being during this pivotal life stage.

Using LDN for Chronic Pain Conditions

by Tricia Heitman, PharmD, PCCA Clinical Compounding Pharmacist

LDN is gaining attention for its anti-inflammatory properties and its ability to manage pain and opioid addiction. By acting on the opioid receptors at lower doses, LDN enhances endorphin production, which can help reduce inflammation and alleviate pain associated with various conditions such as arthritis, fibromyalgia and autoimmune disorders. Many patients report significant relief from chronic pain and inflammation while taking LDN. We will discuss the appropriate doses and review the literature associated with LDN and pain.

LDN for Gut Inflammatory Disorders

by Ranel A. Larsen, PharmD, PCCA Clinical Compounding Pharmacist

LDN is emerging as a promising therapeutic option for enhancing gut health, particularly in the context of IBD and irritable bowel syndrome (IBS). LDN helps to regulate immune responses, improve epithelial barrier function and reduce inflammation within the gut, all of which are critical for maintaining intestinal homeostasis. In IBD, LDN may lower disease activity and enhance quality of life, while in IBS, it can alleviate symptoms such as pain and bloating. Overall, LDN's role in improving gut health underscores its therapeutic potential to support management of complex gastrointestinal disorders.

How to Market LDN Studies

by Mark Gonzalez, PharmD, PCCA Clinical Compounding Pharmacist

Today’s compounding pharmacist wanting to effectively market LDN to practitioners and patients has access to tools that were not as available 20 years ago when LDN started to become popular. Clinical studies, therapeutic reviews and case series are now readily available to substantiate what were once only theories on the effectiveness of naltrexone in autoimmune disorders. These studies span a wide array of specialties and medical conditions. Research groups such as the LDN Research Trust, publications such as the series of three LDN books and many of the clinical presentations given on the subject of LDN all reference these studies. The pharmacist and marketer must leverage the power of this data as part of their communication to both the practitioner and the patient they are marketing to. With the additional aid of social media, positive patient stories can accompany the data from these clinical studies to make for attractive and effective marketing.

Register for the Low-Dose Naltrexone One-Day Virtual Conference today and get more details — plus more information — on the potentials of LDN. We look forward to additional discussions and answering your questions!

Antiaging: Estrogen and a Woman’s Skin

Wed, 31 Jul 2024 16:09:00 GMT

Studies show how estrogen deficiency in women decreases skin firmness, impairs wound healing, increases the number and depth of wrinkles, and contributes to skin thinning and dryness.

by Chelsea Turner, PharmD Candidate, Clinical Services Intern, and Beau Harger, PharmD, PCCA Clinical Compounding Pharmacist/Training Instructor

Skin aging can simply be defined as changes to the skin that occur due to growing older.¹ Oftentimes, many think skin aging correlates with chronological age; however, skin aging actually correlates to the period of estrogen deficiency, especially in menopausal women.² Studies indicate both collagen atrophy and estrogen deficiency have implications on the skin’s elasticity and firmness, as well as wrinkles.³ Estrogen replacement therapy might be an answer for aging skin, as it can increase collagen content, dermal thickness and elasticity; stimulate connective-tissue turnover; and decrease the likelihood of dry skin.⁴

Estrogen’s Role

Estrogen has more than 400 functions in a woman’s body and manifestations of estrogen deficiency may appear in various ways. In menopausal and postmenopausal women, estrogen deficiency is evidenced by decreased skin firmness, impaired wound healing, increased number and depth of wrinkles, skin thinning and skin dryness.

An extremely important role of estrogen is its relationship with structural components — collagen and elastin fibers — that naturally occur in human skin.

The reduction of collagen is traditionally considered the principal factor in the progressive degeneration of skin elasticity; retaining estrogen levels, however, inhibits collagen degradation by helping to maintain collagen balance. Elastin fibers are another structurally important component of skin that help prevent accelerated degenerative changes in the dermis. Studies indicate topical estrogen increases the number and thickness of elastic fibers in the skin.

One of the most common complaints from older women regarding their skin is dryness. Healthy skin requires a substantial amount of water content, which is significantly impacted by a woman’s menstrual cycle and age. Clinical studies indicate topical estrogen therapy can lead to increased water capacity by increasing naturally occurring moisturizing factors such as hyaluronic acid.² The activity of sebaceous secretions is also very important, as their activity is regulated by levels of circulating hormones. Estrogen replacement alone has a sebum-suppressive effect, which can decrease the size and number of sebaceous glands; the addition of progesterone, however, results in increased skin surface lipids.⁵

Topical Estrogen Replacement

The number of estrogen receptors is much greater in facial skin than in breast or thigh skin.⁶ Topical estrogens, such as estriol, have improved both elasticity and firmness, as well as decreased wrinkle depth and pore size by 61–100 percent, when applied to the face and neck.⁷

Compounded preparations offer individualized treatment options for patients and can include a wide variety of active pharmaceutical ingredients. For example, a formula of a topical estrogen, such as estriol, could be prescribed by a practitioner and compounded with VersaBase Cream by a pharmacist to potentially prevent signs of aging in the skin and possibly minimize systemic effects. VersaBase Cream is a great option for application to the face and neck, as it stimulates the natural moisturizing barrier through its emulsion system, leaving a soft and silky feel. VersaBase Cream is noncomedogenic, hypoallergenic, nonirritating and odor-free.

PCCA members with clinical services access may contact our Clinical Services team for help with antiaging formulas and other compounding concerns.

References

Wong, Q. Y. A., & Chew, F. T. (2021). Defining skin aging and its risk factors: a systematic review and meta-analysis. Scientific reports, 11(1), 22075. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/34764376/
Brincat, M. P., Baron, Y. M., & Galea, R. (2005). Estrogens and the skin. Climacteric : the journal of the International Menopause Society, 8(2), 110–123. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/16096167/
Calleja-Agius, J., Muscat-Baron, Y., & Brincat, M. P. (2007). Skin ageing. Menopause international, 13(2), 60–64. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/17540135/
Calleja-Agius, J., & Brincat, M. P. (2009). Effects of hormone replacement therapy on connective tissue: why is this important?. Best practice & research. Clinical obstetrics & gynaecology, 23(1), 121–127. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/19095501/
Sator, P. G., Schmidt, J. B., Sator, M. O., Huber, J. C., & Hönigsmann, H. (2001). The influence of hormone replacement therapy on skin ageing: a pilot study. Maturitas, 39(1), 43–55. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/11451620/
Punnonen, R., Lövgren, T., & Kouvonen, I. (1980). Demonstration of estrogen receptors in the skin. Journal of endocrinological investigation, 3(3), 217–221. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/7430556/
Schmidt, J. B., Binder, M., Demschik, G., Bieglmayer, C., & Reiner, A. (1996). Treatment of skin aging with topical estrogens. International journal of dermatology, 35(9), 669–674. Int J Pharm Compd. 1998;2(4):270-274. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/8876303/

From Sunburns to Campfire Burns: Prevention and Treatment of Summer Burns

Wed, 03 Jul 2024 19:47:08 GMT

Summer is synonymous with outdoor adventures, from basking in the sun to gathering around a campfire. However, these enjoyable activities can sometimes lead to unfortunate situations like burns, ranging from a mild sunburn to a more severe campfire burn. Understanding how to prevent and treat these burns is crucial to ensure a safe and enjoyable summer.

Sunburn: Causes and Prevention

Sunburns occur due to overexposure to ultraviolet (UV) rays from the sun. Several medications can predispose people to an elevated risk of sunburn, including thiazide diuretics, sulfonamides, fluoroquinolones, nonsteroidal anti-inflammatory drugs (NSAIDs), retinoids, tetracycline antibiotics such as doxycycline, and St. John's wort. Severity of a sunburn can range from mild redness to painful blistering and peeling.

To prevent sunburns, it's essential to use a broad-spectrum sunscreen with an SPF of at least 30. Applying sunscreen generously and reapplying every two hours, as well as after swimming or sweating, is crucial. Also, sunscreens do expire, so make sure to check the product’s expiration date. Seeking shade during peak hours, typically between 10 a.m. and 4 p.m., can significantly reduce your risk of sunburn. Wearing protective clothing, such as long-sleeved shirts, wide-brimmed hats and sunglasses, adds an extra layer of defense against harmful UV rays. Clothing and apparel accessories with an SPF rating have become popular as another barrier of skin protection. It is also important to maintain adequate hydration by drinking plenty of water as well as an appropriate amount of electrolytes to help keep your skin resilient against sun damage.1

Treatment for Sunburns

If you do get sunburned, prompt and effective treatment is essential. Start by taking a cool bath or shower to soothe the skin while avoiding soap or shower gel cleansers. Cleaning the skin with soap after sun exposure can be drying as it removes the oils from your skin, so cleansers should be avoided for a few days. After cooling down the affected area, apply aloe vera or moisturizer to keep the skin hydrated. Silicon-based gels, like PracaSil®-Plus or silicon sheets, can be used to hydrate the skin and potentially reduce discomfort. Over-the-counter pain relievers such as ibuprofen can help reduce pain and inflammation. A formula of a topical NSAID such as ketoprofen could be prescribed by a practitioner and compounded with PracaSil-Plus by a pharmacist to possibly minimize systemic effects. Drinking extra water with adequate electrolytes is vital to help your body recover from the dehydration caused by sunburn. Finally, avoid further sun exposure until your skin has fully healed to prevent additional damage.1

Campfire Burns: Risks and Prevention

Campfires are a beloved summer tradition, but they pose significant burn risks. With the increase in popularity of fire pits, childhood burns have increased and are one of the leading causes of preventable injuries in children. To enjoy campfires safely, maintain a safe distance from the fire and keep children and pets away. Using a designated fire ring or pit helps contain the fire and prevent it from spreading. Never leave a campfire unattended and always ensure it's completely extinguished before leaving the site. Keeping a bucket of water or a hose nearby is a good precaution in case of emergencies. Wearing appropriate clothing, avoiding loose garments that can easily catch fire, also adds to your safety.2

Treatment for Campfire Burns

Campfire burns require immediate action and attention. Start by running cool (not cold) water over the burn for 10-20 minutes to reduce pain and swelling. Protect the area with a clean, nonstick bandage or cloth. Avoid applying ice directly to the burn as it can cause further damage. Silicon-based gels, such as PracaSil-Plus or sheets, are excellent for covering the burn, helping to keep the wound moist and potentially reducing the risk of scarring. Over-the-counter pain relievers can help manage discomfort. For severe burns or if the burn is larger than the palm of the victim's hand, immediately seek professional medical help.3

Other Types of Burns

Aside from sunburns and campfire burns, summer activities can expose you to other types of burns. Be cautious around grills, stoves and hot sand. Using protective gear and being mindful of where you step and what you touch can prevent accidental burns. Additionally, be aware of pool chemicals and cleaning agents that can cause chemical burns.3 Always follow safety instructions and wear appropriate protective gear when handling these substances.

Burns, whether from the sun or a campfire, can be painful and potentially dangerous. By taking preventive measures and knowing how to treat burns effectively, you can enjoy your summer activities safely. Remember, prevention is always better than treatment, so take steps to protect yourself and your loved ones from summer burns. Stay safe and enjoy the sunny days!

References

Guerra, K. C., & Crane, J. S. (2023). Sunburn. In StatPearls. StatPearls Publishing. Accessed June 2024 at https://pubmed.ncbi.nlm.nih.gov/30521258/
Flaherty, M. R., & Sheridan, R. (2019). Fire Pit-Related Burn Injuries in Children and Adolescents. Journal of burn care & research : official publication of the American Burn Association, 40(6), 943–946. Accessed June 2024 at https://pubmed.ncbi.nlm.nih.gov/31289816/
Żwierełło, W., Piorun, K., Skórka-Majewicz, M., Maruszewska, A., Antoniewski, J., & Gutowska, I. (2023). Burns: Classification, Pathophysiology, and Treatment: A Review. International journal of molecular sciences, 24(4), 3749. Accessed June 2024 at https://pubmed.ncbi.nlm.nih.gov/36835171/

Acne Patients: You’re Not Alone

Wed, 05 Jun 2024 21:20:46 GMT

Although acne commonly occurs in adolescents and some adults, it can leave lasting effects, including scarring. With June designated as Acne Awareness Month, gain clinical understanding of causes and potential treatments that may help your patients.

by Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist

Acne is the most common dermatologic disease, with a cumulative prevalence approaching 100 percent in males and females as they near puberty. In most cases, acne becomes less active as adolescence ends. However, the intensity and duration can vary among individuals — 20 percent will experience severe acne that can result in scarring.

The presence of acne may profoundly limit self-esteem and self-confidence, placing individuals at risk for developing depression and anxiety. Acne may also be associated with increased risk of self-injury and suicide attempts.¹

Pathophysiology

Acne pathophysiology is multifactorial: sebum alteration, aberrant follicular keratinization and Cutibacterium acnes (C. acnes, formerly known as Propionibacterium acnes or P. acnes) combine to cause comedones that can lead to inflammation and acne lesions.

Lightbox

Acne has multiple contributing factors, including hormones and neuropeptides, sebum production, the microbiome, as well as innate and adaptive immune functions. Androgens (dihydrotestosterone) stimulate sebocyte proliferation, which ultimately increases sebum production — a substrate for C. acnes growth — as well as lipid and triglyceride formation. Collectively, these factors induce the excessive shedding of skin cells, or hyperkeratinization, of the uppermost section of the hair follicle near the opening of pores, known as the follicular infrainfundibulum.

Diets comprised of high-glycemic-index foods, dairy and whey protein contribute to acne through stimulation of insulin-like growth factor-1 (IGF-1), while omega-3-fatty acids and low-glycemic-load diets are protective because they downregulate IGF-1. This suggests that increasing the ratio of monounsaturated to saturated fatty acids in sebum is proinflammatory and may promote acne.

Lesion Types & Treatment

Targeting inflammation is an important aspect of acne treatment. C. acnes stimulate inflammation via innate toll-like receptors (TLRs) and adaptive immunity (IL-17A and IFN-γ secretion from CD4+ T cells) and promote production of matrix metalloproteinases that contribute to scarring. C. acnes also form biofilms, which create a pro-inflammatory sebum concentration via increased lipase activity and promote resistance to treatment with antimicrobial agents.² Because low-dose naltrexone (LDN) attenuates activation of TLRs in the skin, it can be used as an adjunct therapy to treat acne (and other inflammatory skin diseases) in resistant cases.³

There are different types of acne lesions: open comedones (blackheads), closed comedones (whiteheads), inflammatory lesions (where the follicular wall ruptures, releasing sebum, cells and bacteria into the surrounding tissue, causing inflammation and redness) and cystic lesions that can lead to atrophic scars (icepick and boxcar).

Lightbox

Treatment of acne depends on severity (mild, moderate or severe), type of lesion and location. Acne lesions can appear on the face, forehead, chest, upper back and shoulders, or in combination of these areas, because these areas have the highest concentration of sebaceous glands. For a successful outcome, it is recommended that acne patients have a thorough regimen addressing all aspects of the disease.

Most regimens include:

A cleansing routine (usually twice daily) with a cleanser that removes dirt but does not strip all the oils from the skin to allow for healthy barrier function, followed by a light non-comedogenic moisturizer (such as VersaBase® Cream).
An exfoliation process 1-3 times a week, depending on severity.
Active treatment of some single API or combination of an antibacterial and a keratolytic. If using nightly tretinoin, exfoliation may not be necessary.

In severe cases, isotretinoin may be considered with usual precautions for reproductive-age female patients.1 Compounding formulations (non-cosmetic), especially combinations, are very useful and often more convenient for patients who require more than one API in a single application. Compounding APIs include:

Keratolytics
- Tretinoin
- Salicylic Acid
- Benzoyl Peroxide (also antibacterial)
Antibacterial
- Clindamycin
- Erythromycin
- Minocycline
- Sulfacetamide
- Tea Tree Oil
Sebostatic
- Niacinamide
- Azelaic Acid (also antibacterial)
Miscellaneous
- Progesterone (5α-reductase inhibitor)
- Spironolactone (DHT receptor antagonist)

PCCA bases often used in acne formulations include VersaBase Cream, VersaBase Gel, Clarifying™, PracaSil®-Plus, Occlusaderm® and WO6® Anhydrous Topical Gel (sometimes with the addition of PermE8® Anhydrous Gel to modestly enhance penetration through the stratum corneum).

Therapy should always be tailored to the patients’ needs — sensitivities and exceptions are always the rule. Remember to let your patients know that you’re here to help and they are not alone combating acne! PCCA members may access formulations developed for compounded preparations on the Members-Only Website, including a new formulation that uses aminolevulinic acid* in a topical gel with PermE8 Anhydrous Gel and WO6 Anhydrous Topical Gel.

*Aminolevulinic acid (ALA) is a compound used in photodynamic therapy (PDT) to treat acne vulgaris. Although the mechanism of action of ALA with PDT is not fully understood, it is believed to reduce sebum excretion by suppression of the sebaceous gland function. ALA-PDT was shown to be effective for acne and did not exhibit severe side effects.⁴

Members with clinical services access may contact our Clinical Services team for help with acne preparations and other compounding concerns.

References

Gupta, N., & Gupta, M. (2023). The Controversies Surrounding Acne and Suicide: Essential Knowledge for Clinicians. Cureus, 15(8), e43867. Accessed May 2024 at https://doi.org/10.7759/cureus.43867
Cruz, S., Vecerek, N., & Elbuluk, N. (2023). Targeting Inflammation in Acne: Current Treatments and Future Prospects. American journal of clinical dermatology, 24(5), 681–694. Accessed May 2024 at https://doi.org/10.1007/s40257-023-00789-1
Jaros, J., & Lio, P. (2019). Low Dose Naltrexone in Dermatology. Journal of drugs in dermatology: JDD, 18(3), 235–238. Accessed May 2024 at https://jddonline.com/articles/low-dose-naltrexone-in-dermatology-S1545961619P0235X/
Asayama-Kosaka, S., Akilov, O. E., and Kawana, S. (2014). Photodynamic Therapy with 5% δ-Aminolevulinic Acid is Safe and Effective Treatment of Acne Vulgaris in Japanese Patients. Laser therapy, 23(2), 115–120. Accessed May 2024 at https://doi.org/10.5978/islsm.14-OR-09

The Storied Past of Quinacrine HCI

Wed, 15 May 2024 13:09:50 GMT

As one of the most studied synthetic drugs in modern history, quinacrine HCI was first used as an antimalarial and later to treat rheumatic skin diseases, including lupus. With May designated as Lupus Awareness month, learn more about quinacrine HCI and the twists and turns of its storied past.

Quinacrine hydrochloride (HCI) (atabrine, mepacrine, chinacrin), developed in the late 1920s, was the first synthesized form of quinine — a natural alkaloid isolated from the South American cinchona bark tree that was used for centuries by indigenous people to treat fevers, chills and other malaria-type symptoms.^1-3

During World War II (WWII), quinacrine replaced quinine for use in U.S. soldiers as an antimalarial prophylaxis and to treat soldiers infected with malaria — most notably those stationed in the South Pacific. According to a U.S. Surgeon General Office report, quinacrine was administered to more than three million soldiers. The soldiers were routinely monitored for safety and efficacy, which made quinacrine one of the most extensively studied synthetic drugs in the history of modern medicine.^1,2 The monitoring also led to recognition of symptom relief in soldiers afflicted with differing types of lupus.

It's important to note that quinacrine was not the only drug synthesized from quinine pre- and post-WWII. Chloroquine phosphate was developed in 1934; however, due to an initial evaluation that determined toxicity levels were too high for human use, chloroquine was not used as an antimalarial until after the conclusion of WWII.³ Hydroxychloroquine sulfate, developed in the 1950s to reduce the toxicity of chloroquine, is another synthesized form.⁴

Chloroquine phosphate and hydroxychloroquine sulfate are substituted 4-amino quinoline compounds that differ only by a hydroxy group. Quinacrine hydrochloride also has the 4-amino quinoline radical but has, in addition, a benzene ring; it is classified as an acridine compound.⁵

Collectively, antimalarials quinacrine, chloroquine and hydroxychloroquine were studied throughout the decades following WWII. Although the mode of action remains disputed, the antimalarials would ultimately gain recognition as effective treatments for systemic lupus erythematosus and cutaneous lupus erythematosus.^1-4

Types of Lupus: Systemic & Cutaneous

An autoimmune disease, where a person’s immune system attacks healthy tissue, lupus often causes pain and inflammation in any part of an afflicted person’s body. In addition to affecting skin and joints, lupus can also affect internal organs. Lupus primarily affects women, with onset generally occurring between ages 15 – 45.

Systemic lupus erythematosus (SLE) is the most prevalent form of lupus. Although symptoms vary among individuals, typical symptoms include arthritis; fevers; fatigue; a malar or “butterfly” rash that appears across the nose and cheeks; hair loss; sensitivity to the sun; swollen glands; swelling in the legs or around the eyes; pain when breathing deeply or lying down; headaches, dizziness, depression, confusion or seizure; and abdominal pain. Inflammation caused by SLE can led to damage in internal organs, including kidney failure (lupus nephritis); seizures and memory problems; heart valve damage due to scarring, inflammation of the lining around the heart muscle (pericarditis) and inflammation of the heart muscle itself (myocarditis); inflammation of blood vessels (vasculitis); blood clots due to high levels of antiphospholipid antibodies; low blood cell counts; and inflammation of tissue that surrounds the lungs (pleurisy).⁶

Cutaneous lupus erythematosus (CLE) primarily affects the skin and is composed of three main types: acute cutaneous lupus (acute skin lupus), subacute cutaneous lupus (subacute lupus) and chronic cutaneous lupus (discoid lupus), the latter of which is the most common type.7 Discoid lupus appears on the scalp or in the bowl of the ear as a red to purple rash that causes discoloration, scarring and hair loss. Although CLE primarily affect the skin, providers are advised to closely monitor patients to ensure the disease does not affect internal organs.⁸

Quinacrine HCI: First Use in Lupus Treatment

In October 1951, Francis Page reported in Lancet his observations on the treatment of 18 cases of lupus erythematosus with quinacrine HCI at daily doses ranging from 100 to 300 mg. Of the 18, 14 patients showed good or excellent improvement of skin lesions. Three patients showed slight improvement, while one patient had no visible change.⁹

The success of quinacrine HCI spurred others to conduct similar studies. In 1953, Bernard L. Rhodes, M.D., and Manuel F. Allende, M.D., reported before the California Medical Association that 25 patients with chronic discoid lupus erythematosus were administered 100 mg. of quinacrine HCI three times daily for two to three weeks, followed by 100 mg. daily until satisfactory results were obtained. Twenty-one of the 25 patients showed satisfactory improvement, seven of whom had complete clearing of lesions. The remaining four did not improve.¹⁰

Throughout the following decades, quinacrine HCI — often compounded with hydroxychloroquine or chloroquine — remained a standard treatment for SLE and CLE.^1-6

DQSA Regulation

Section 503A and 503B of the Drug Quality and Security Act (DQSA) establish criteria for bulk drug substances used in the respective compounding environments. FDA has also issued interim policies while they work to finalize lists of bulk substances for 503A and 503B; items that appear on Category 1 of the interim lists may be eligible for enforcement discretion until the FDA issues a final rule on those items. In 2016, PCCA nominated quinacrine HCI for inclusion on the 503A Bulks List. However, during the FDA evaluation process, several FDA Divisions and Committees, including the Pharmacy Compounding Advisory Committee (PCAC) and the Office of New Drugs (OND), raised safety concerns about quinacrine HCI. Remarkably, the OND advised that “although quinacrine might be safe at the 100 mg/day dose prescribed for rheumatic skin diseases, generalists might prescribe the drug at higher doses and for alternative indications that were not formally studied.” As a consequence, the PCAC voted against adding quinacrine to the 503A Bulks List. However, FDA ultimately placed quinacrine HCI on Category 1 with a restriction, “(except for intrauterine administration),” allowing for oral use in compounded preparations by 503A compounding pharmacies. FDA also placed quinacrine HCl on the 503B Category 1 interim bulks list with the restriction “for oral use only.”^11,12

FDA Acceptance

The FDA proposed a final rule for the inclusion of quinacrine HCI in March 2021 to the 503B Bulks List for oral dosage forms, stating “it meets a clinical need for patients with CLE…and has a long history of use in compounding, in addition to a significant body of literature demonstrating its potential effectiveness for the treatment of patients with CLE.”¹¹ The FDA added quinacrine HCI — for oral use only — to the 503B Positive Bulks List on April 6, 2023.¹³To date, the FDA has not issued a rule for quinacrine in 503A pharmacies; as such, quinacrine HCI remains part of the interim policy.

Listen as PCCA Vice President of Clinical Services, A.J. Day, PharmD, discusses the return of quinacrine HCI for patient care on the Mortar & Pestle podcast.

References

Kumar, M., Sarkar, A.( 2022) Repurposing of Anti-Malarial Drug Quinacrine for Cancer Treatment: A Review. Scientia Pharmaceutica.; 90(1):12. Accessed May 2024 at https://doi.org/10.3390/scipharm90010012
Kalia, S., Dutz, J. P. (2007). New concepts in antimalarial use and mode of action in dermatology. Dermatologic therapy, 20(4), 160–174. Accessed May 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163426/
Lowe, D. (2020) Chloroquine, Past and Present. Science. Accessed May 2024 at https://www.science.org/content/blog-post/chloroquine-past-and-present
Ben-Zvi, I., Kivity, S., Langevitz, P., et al. (2012). Hydroxychloroquine: from malaria to autoimmunity. Clinical reviews in allergy & immunology, 42(2), 145–153. Accessed May 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091063/
Tanenbaum, L., Tuffanelli, D.L. (1980) Antimalarial Agents: Chloroquine, Hydroxychloroquine, and Quinacrine. Arch Dermatol. 116(5):587–591. Accessed May 2024 at doi:10.1001/archderm
NIH-National Institute of Arthritis and Muscoloskeletal and Skin Diseases. (Last reviewed October 22). Health Topics: Systemic Lupus Erythematosus (Lupus). Accessed May 2024 at https://www.niams.nih.gov/health-topics/lupus
McDaniel, B., Sukumaran, S., Koritala, T., et al. (Last updated 2023). Discoid Lupus Erythematosus. Continuing Education: StatPearls. Accessed May 2024 at https://www.ncbi.nlm.nih.gov/books/NBK493145/
Eastham, A.B., Vleugels, R.A. (2014) Cutaneous Lupus Erythematosus. JAMA Dermatol. 150(3):344. Accessed May 2024 at doi:10.1001/jamadermatol.2013.10393
Courville, C.J., Perry, E.T. (1953) Quinacrine (atabrine) in the Treatment of Lupus Erythematosus.AMA Arch Derm Syphilol.; 67(5):510–511. Accessed May 2024 at doi:10.1001/archderm.1953.01540050074015
Rhodes, B.L., Allende, M.F. (1953). Treatment of Chronic Discoid Lupus Erythematosus with Quinacrine. From the Department of Medicine, Subdepartment of Dermatology, University of California School of Medicine, San Francisco. Accessed May 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1531780/pdf/califmed00290-0013.pdf
Rocchio, R., Kneeream, E., Shetty, D., et al. (2021) Regulatory History and Safety of Quinacrine HCI, 2021 FDA Science Forum. Accessed May 2024 at https://www.fda.gov/science-research/fda-science-forum/regulatory-history-and-safety-quinacrine-hc
FDA. (Content current as of December 2023). Bulk Drug Substances Used in Compounding Under Section 503B of the FD&C Act. Accessed May 2024 at https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503b-fdc-act
FDA. (Content current as of April 2023). Compounding Safety Information: Quinacrine Hydrochloride. Accessed May 2024 at https://www.fda.gov/drugs/human-drug-compounding/compounding-safety-information-quinacrine-hydrochloride

Wound Pathophysiology and Compounded Options

Wed, 13 Dec 2023 22:16:00 GMT

by Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist

Getting involved in wound care can be a very rewarding clinical niche. Many medical practitioners have limited experience and training in treating wounds, so when pharmacists have knowledge and compounded options to share, it is usually greatly appreciated. Understanding the pathophysiology of wounds and the pharmacology of the active pharmaceutical ingredients (APIs) used in wound care are needed to interact with prescribers and to formulate a patient-specific compound.

Although there are many types of wounds, this article only focuses on cutaneous wounds. Common types of cutaneous wounds include surgical, arterial, venous stasis, pressure and diabetic.

After a wound occurs, there are four phases of wound healing: hemostasis, inflammatory, proliferative and remodeling.¹

Thiruvoth F.M., Mohapatra D.P., Kumar D., et al. (2015) Current concepts in the physiology of adult wound healing. Plast Aesthet Res 2015;2:250-6. Open Access publication at http://dx.doi.org/10.4103/2347-9264.158851

When a cutaneous injury occurs, hemostasis is initiated by platelets through fibrin clot formation. Platelets also release cytokines, chemokines and growth factors to attract macrophages and fibroblasts to the site of tissue injury. The inflammatory phase begins with the arrival of neutrophils, followed by macrophages and lymphocytes, which are essential for effective decontamination at the wound site. The proliferative phase is characterized by new blood vessel formation (angiogenesis), synthesis of collagen, extracellular matrix (ECM) components and re-epithelialization. In the remodeling phase, the collagen laid down during proliferation is gradually replaced by a more stable interwoven type III collagen, along with vascular maturity and regression; this process typically lasts 6-24 months from the time of injury.¹

The complex process of wound healing is influenced by a variety of factors. At each healing stage, a different set of specific cytokines and growth factors must interact with their receptors, other growth factors and ECM components at their target sites (see Figures A and B).

Cutaneous wounds 3 days (A) and 5 days (B) after injury. Growth factors such as fibroblast growth factor (FGF), insulin-like growth factor (IGF), keratinocyte growth factor (KGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF) and vascular endothelial growth factor (VEGF), and proteases such as matrix metalloproteinases (MMPs) and plasminogen activator (PA), are thought to be necessary for cell movement.²

Exudate is produced by a complex osmotic and hydrostatic pressure, resulting in a cyclic process that delivers oxygen, nutrients, white blood cells and chemical messengers to the wound site. Wounds can have varying levels of exudate — from leaking to no exudate. Treatment of highly exudative wounds requires frequent dressing changes, along with a base with good adherence and preferably some capacity for absorption.³

Prior to dressing, debridement is a necessary first step for proper wound care.⁴ A wound formula containing APIs that help facilitate healing is usually needed for successful closure. Commonly used APIs for wound care formulas include misoprostol, phenytoin, naltrexone, minoxidil, N-acetylcysteine and calcium channel blockers, such as amlodipine and nifedipine.

Combination synergy has been observed with misoprostol and phenytoin, as well as with amlodipine and phenytoin; other ingredients, however, have also shown to be beneficial. Hormones and non-API substances — insulin, aloe, arginine, beta glucan and dexpanthenol — may also help wound closure.^5-7

When there is justification to treat an infection, antimicrobials may also be used. A partial list includes:

Metronidazole
Mupirocin
Chloramphenicol

The vehicle base chosen to incorporate APIs can be critical to the success of wound closure; appropriate choices are often contingent on the type of wound. For example, an absorptive powder is a good choice for an exudative wound, whereas a hydrating base is beneficial for a dry to normal wound.

In addition, the frequency of wound cleaning and dressing (including instillation of wound formula) also depend on the type, size and status of the wound.

Members with clinical services access may contact our Clinical Services team for help with compounding for wounds and other compounding-related concerns.

A complete version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.

References

Cundell, J. (2016) Chapter Two - Diabetic Foot Ulcers: Assessment, Treatment, and Management. Smart Bandage Technologies Design and Application, Academic Press. 37-61. https://doi.org/10.1016/B978-0-12-803762-1.00002-3
Park, J.W., Hwang, S.R., Yoon, I-S. (2017) Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration. Molecules. 22(8):1259. Open Access publication at https://www.mdpi.com/1420-3049/22/8/1259
Bradley P. (2018). Wound Exudate. Brit J Comm Nursing, 23(Sup12), S28–S32. https://doi.org/10.12968/bjcn.2018.23.Sup12.S28
Thomas, D. C., Tsu, C. L., Nain, R. A., et al. (2021). The role of debridement in wound bed preparation in chronic wound: A narrative review. Ann Med Surg (2012), 71, 102876. https://doi.org/10.1016/j.amsu.2021.102876
Riepl M. (2022). A Compendium of Compounding Agents and Formulations, Part 2: Metronidazole, Misoprostol, and Phenytoin. Intl J Pharma Compd. 26(2), 94–98.
Vetvicka, V., & Vetvickova, J. (2011). ß (1-3)-D-glucan affects adipogenesis, wound healing and inflammation. Oriental Pharmacy and Experimental Medicine, 11(3), 169-175
Heise, R., Skazik, C., Marquardt, Y., et al. (2012). Dexpanthenol modulates gene expression in skin wound healing in vivo. Skin Pharmacology and Physiology, 25(5), 241-248. doi:10.1159/000341144

Mutual Purpose. Shared Innovation.

Wed, 29 Nov 2023 22:20:07 GMT

Mutual Purpose. Shared Innovation.

by Mark Gonzalez, PharmD, PCCA Clinical Compounding Pharmacist

Your “purpose” to help patients and providers is what motivates us to innovate, create, test, formulate and introduce new bases.

Behind every new base and subsequent formulation development, our purpose is to help you create in the lab, help patients and providers in new and exciting ways, and ultimately strengthen the relationships you have worked so hard to build and maintain.

Our revolutionary new base, EctoSeal P2G, is no exception in our purpose to serve you, your patients and prescribers.

CREATE

EctoSeal P2G is one of the first bases in the industry to combine a variety of clinical applications with three different dosage forms: topical powder, topical powder for reconstitution and topical hydrogel. The flexibility that comes with this base is unparalleled.

EctoSeal P2G can be mixed with a variety of active pharmaceutical ingredients (APIs) that, after dispensing and at time of use, can be insufflated — or sprinkled —directly onto a wound. Dispensing in a topical powder dosage form provides the potential for longer beyond-use dates for your pharmacy and convenience for your patients. The topical powder dosage form absorbs the exudate of wet wounds and quickly transforms into a hydrogel that, as it dries, forms a protective film that may help APIs better adhere to the wound bed. In addition, the protective film can potentially secure a moistened environment.

For dry wounds, the powder can be applied directly to the wound and moistened with purified water, sterile water or saline to induce the film-forming effect. The topical powder application is helpful with larger, deeper wounds, and also has excellent application for common abrasions, burns and exudative, eruptive sites of infection.

EctoSeal P2G can also be dispensed as a topical powder for reconstitution, where the powder is mixed with appropriate API(s), brought to volume (q.s.) with maltodextrin and dispensed in a jar. At time of use, the compounded preparation is measured in level scoops and placed in a medicine cup. Purified water, sterile water or saline is then added, and the preparation is mixed by hand for about 15 seconds to create a hydrogel, which is then applied to the affected area. When dispensed as a powder for reconstitution, most EctoSeal P2G compounds can be assigned a BUD of 180 days.

Dispensing as a topical hydrogel dosage form is another option. To dispense as a topical hydrogel, the EctoSeal P2G powder is first mixed with relevant APIs, then with an appropriate wetting agent, preservative and purified water. When dispensed as a hydrogel, the BUD should not exceed more than 14 days if unpreserved.

Regardless of dosage form, when moistened, EctoSeal P2G forms a strong yet pliable film as it dries. The protective film may provide longer-term delivery of APIs. In addition, the preparation develops a mostly clear thin film as it dries, allowing a protective, moist environment recognized to help wound healing. Even better, EctoSeal P2G easily reverts from a film to a gel when remoistened, making wound cleaning easier and less painful for patients.

HELP

As soon as I was introduced to this base during pre-launch discussions, my mind began to race with all of the potential applications and how they would be able to help patients, as well as help practitioners prescribe a potentially more efficacious, patient-friendly and environmentally-friendly option. Specialties such as:

Wound care
Post-surgical care (e.g., initial care of suture sites)
Hospice
Geriatrics
Dermatology (e.g., acne, warts, infections, hidradenitis supurativa)
Pediatrics
Podiatry (e.g., onychomycosis, ingrown toenail pain relief)
Proctology (e.g., external hemorrhoids/fissures)
Veterinary

Strengthen

You became a compounder with the objective of being able to create preparations, help patients and strengthen your relationships with patients and providers. EctoSeal P2G is an exciting way to reignite those initial passions or flame your passions as a novice compounder.

Don’t let EctoSeal P2G be another base that you wait years to use. Take advantage of its versatility, ease of application and the potential promise to help you solve some of the most common medical issues confronting patients, providers and your pharmacy. Experience EctoSeal P2G today to create topical preparations, help your patients and build relationships with prescribers within your community. Members with clinical service access may contact the Clinical Services team for additional help with EctoSeal P2G or other compounding concerns.

Tune in to the Mortar & Pestle podcast to hear PCCA Chief Scientific Officer Gus Bassani and PCCA Director of Research and Development Daniel Banov discuss the science behind our revolutionary new base.

A complete version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.

Compounding Opportunities for Summer

Wed, 02 Jun 2021 14:40:08 GMT

By Beau Harger, PharmD, PCCA Clinical Compounding Pharmacist

Compounders are the ultimate problem-solvers in the health care industry, and summer presents some potential opportunities for them that otherwise may not be considered. As the warm months approach, physicians and patients may look to compounding pharmacists to help address their seasonal and travel needs through customized medications. To give you some ideas to discuss in these conversations, below are common issues that come up in summer along with potential options that compounding pharmacies may be able to offer prescribers and their patients.

Sun Protection

Regular sunscreen usage has been shown to be protective against skin damage and also to slow skin aging.¹ However, common sunscreens contain organic ultraviolet filters like oxybenzone and octinoxate, which are sometimes referred to as “chemical sunscreens” and have caused concern for some due to potential health hazards and possible toxic effects on the environment.² Oxybenzone has been reported to cause topical allergic skin reactions, and there are concerns about it being an endocrine disruptor. Reports have shown oxybenzone in various concentrations in certain water systems as well.² If prescribers come to you with concerns about these issues, you might consider bringing up compounded sunscreens with inorganic ultraviolet filters such as zinc oxide, which are often referred to as “physical” or “mineral sunscreens” and may be alternatives as it relates to systemic absorption, topical allergic skin reactions and effects on the environment.³It is important for compounders to know that compounded sunscreens cannot claim an SPF designation since they have not been tested as such.

Sunburn

As we all know, spending excessive time in the sun without adequate protection can lead to sunburn. This can even happen on overcast days in some circumstances. In fact, one poll showed that 42% of people experience at least one sunburn per year.⁴ However, a PCCA case study involving a compounded medication with our PracaSil^®-Plus as the base showed significant skin healing and regeneration of a second-degree burn.⁵ If prescribers or patients ask about customizable options, compounded formulations containing PracaSil-Plus as the vehicle could be considered for patients with sunburns.

Insect Bites

Summer is the season for spending more time in the great outdoors and enjoying activities such as hiking through a national park or spending time on the water. As refreshing as they are, though, these outdoor activities can lead to insect bites. Skin reactions caused by bites from mosquitoes, chiggers and other insects are characterized by inflammation and severe itching. Mosquito bite reactions can be relieved with antihistaminic drugs. ⁶ Both pramoxine and hydrocortisone have been shown to be effective for helping with itch.⁷ Agents such as menthol that provide a cooling effect can add temporary relief to itch associated with bug bites as well as dermatitis.^8,9 Compounders could work with prescribers and combine these to make custom preparations that are clinically relevant and convenient for the patient.

Poison Ivy

The great outdoors also means potential exposure to plants that can cause irritation. Poison ivy, for instance, is the leading cause of allergic contact dermatitis. Short-term therapy with topical steroids has been shown to help with symptoms of allergic contact dermatitis.^10,11 Therefore, combining the steroid hydrocortisone with the antihistamine diphenhydramine can help with itch and inflammation. ^7,10,11

Motion Sickness

For some people, traveling by car, boat or plane can cause motion sickness characterized by nausea and vomiting. The use of transdermal scopolamine has been shown to be effective in preventing motion sickness.¹² However, patch delivery systems may not be suitable for some patients because of topical hypersensitivity reactions and problems with the adhesives.^13,14 Promethazine is another option and has also been shown to be helpful for motion sickness.¹⁵ For patients with such issues, compounders may be able to work with prescribers to develop a custom topical preparation to deliver scopolamine or promethazine through the skin while avoiding side effects.

Toenail Fungus

Hot, humid conditions especially in footwear can lead to increased fungal infections, particularly toenail fungus.¹⁶ One challenge with traditional therapies such as oral antifungal medications, though, is that they may cause interactions with other medications and even require liver-function monitoring.¹⁷ However, topical fluconazole alone and in combination with urea has been shown to be effective for treating onychomycosis (toenail fungus).¹⁸ Ibuprofen has also demonstrated synergistic antifungal effects in combination with azole antifungals.¹⁹ Tea tree oil is another ingredient that has shown to be effective in treating toe nail fungus and could be incorporated into a formula.²⁰ This gives compounders options to present to practitioners for their patients who may need alternatives to commonly prescribed medications for toenail fungus.

Marketing your compounding services according to the changing seasons is often overlooked and can give your pharmacy a new way of presenting your services to physicians and patients. The ideas presented above are not all inclusive, but they can get you started, and PCCA members with Clinical Services support can contact our clinical compounding pharmacists to discuss more options. They can also access a list of PCCA compounding formulas that are commonly requested during the summer.

Also on The PCCA Blog: Unique Dosage Forms and Flavor Ideas That Are Perfect for Summer

Beau Harger, PharmD, is a graduate of the University of Mississippi. He joined the staff of PCCA in January 2015 as a full-time clinical compounding pharmacist after working as a part-time consultant for the previous year and a half. He came to PCCA with 15 years of compounding experience. He also taught pharmacology at William Carey College in Gulfport, Mississippi, and was the pharmacist in charge of Nucara Compounding Pharmacy in Austin, Texas, for eight years.

References

1. Hughes, M. C. B., Williams, G. M., Baker, P., & Green, A. C. (2013). Sunscreen and prevention of skin aging: A randomized trial. Annals of Internal Medicine, 158(11), 781–790. https://doi.org/10.7326/0003-4819-158-11-201306040-00002

2. DiNardo, J. C., & Downs, C. A. (2018). Dermatological and environmental toxicological impact of the sunscreen ingredient oxybenzone/benzophenone-3. Journal of Cosmetic Dermatology, 17(1), 15–19. https://doi.org/10.1111/jocd.12449

3. Mohammed, Y. H., Holmes, A., Haridass, I. N., Sanchez, W. Y., Studier, H., Grice, J. E., Benson, H., & Roberts, M. S. (2019). Support for the safe use of zinc oxide nanoparticle sunscreens: Lack of skin penetration or cellular toxicity after repeated application in volunteers. The Journal of Investigative Dermatology, 139(2), 308–315. https://doi.org/10.1016/j.jid.2018.08.024

4. Land, V., & Small, L. (2008). The evidence on how to best treat sunburn in children: A common treatment dilemma. Pediatric Nursing , 34(4), 343–348.

5. PCCA Science. (2018). Second-degree skin burn injury caused by domestic incident [PCCA Document #99516]. http://beta.pccarx.com/pdf_files/99516_CS_SkinBurn_SpiraPrac.pdf

6. Reunala, T., Brummer-Korvenkontio, H., Lappalainen, P., Räsänen, L., & Palosuo, T. (1990). Immunology and treatment of mosquito bites. Clinical and Experimental Allergy, 20(Suppl. 4), 19–24. https://doi.org/10.1111/j.1365-2222.1990.tb02472.x

7. Zirwas, M. J., & Barkovic, S. (2017). Anti-pruritic efficacy of itch relief lotion and cream in patients with atopic history: Comparison with hydrocortisone cream. Journal of Drugs in Dermatology, 16 (3), 243–247.

8. Liu, B., & Jordt, S.-E. (2018). Cooling the itch via TRPM8. The Journal of Investigative Dermatology, 138(6), 1254–1256. https://doi.org/10.1016/j.jid.2018.01.020

9. Tey, H. L., Tay, E. Y., & Tan, W. D. (2017). Safety and antipruritic efficacy of a menthol-containing moisturizing cream. Skinmed, 15(6), 437–439.

10. Kaidbey, K. H., & Kligman, A. M. (1976). Assay of topical corticosteroids. Efficacy of suppression of experimental Rhus dermatitis in humans. Archives of Dermatology, 112(6), 808–813. https://doi.org/10.1001/archderm.112.6.808

11. Nassau, S., & Fonacier, L. (2020). Allergic contact dermatitis. The Medical Clinics of North America, 104(1), 61–76. https://doi.org/10.1016/j.mcna.2019.08.012

12. Spinks, A., & Wasiak, J. (2011). Scopolamine (hyoscine) for preventing and treating motion sickness. The Cochrane Database of Systematic Reviews, 2011(6). https://doi.org/10.1002/14651858.CD002851.pub4

13. Olthoff, M. V., Kunkeler, A., van Hunsel, F., Beekwilder, J., & Borgsteede, S. D. (2019). Overgevoeligheid voor hulpstoffen in pleisters [Hypersensitivity reactions to excipients in patches].Nederlands Tijdschrift voor Geneeskunde [ Dutch Journal of Medicine], 163.

14. Romita, P., Foti, C., Calogiuri, G., Cantore, S., Ballini, A., Dipalma, G., & Inchingolo, F. (2018). Contact dermatitis due to transdermal therapeutic systems: A clinical update. Acta Bio Medica, 90(1), 5–10. https://doi.org/10.23750/abm.v90i1.6563

15. Southard, B. T., & Al Khalili, Y. (2020). Promethazine. In StatPearls.

16. Sasagawa, Y. (2019). Internal environment of footwear is a risk factor for tinea pedis. The Journal of Dermatology, 46(11), 940–946. https://doi.org/10.1111/1346-8138.15060

17. Haria, M., Bryson, H. M., & Goa, K. L. (1996). Itraconazole. A reappraisal of its pharmacological properties and therapeutic use in the management of superficial fungal infections. Drugs, 51 (4), 585–620. https://doi.org/10.2165/00003495-199651040-00006

18. Bassiri-Jahromi, S., Ehsani, A. H., Mirshams-Shahshahani, M., & Jamshidi, B. (2012). A comparative evaluation of combination therapy of fluconazole 1% and urea 40% compared with fluconazole 1% alone in a nail lacquer for treatment of onychomycosis: Therapeutic trial. The Journal of Dermatological Treatment, 23(6), 453–456. https://doi.org/10.3109/09546634.2011.588191

19. Pina-Vaz, C., Sansonetty, F., Rodrigues, A. G., Martinez-de-Oliveira, J., Fonseca, A. F., & Mårdh, P. A. (2000). Antifungal activity of ibuprofen alone and in combination with fluconazole againstCandida species. Journal of Medical Microbiology, 49(9), 831–840. https://doi.org/10.1099/0022-1317-49-9-831

20. Buck, D. S., Nidorf, D. M., & Addino, J. G. (1994). Comparison of two topical preparations for the treatment of onychomycosis:Melaleuca alternifolia (tea tree) oil and clotrimazole. The Journal of Family Practice, 38(6), 601–605.

Low-Dose Naltrexone in Dermatological Compounding

Wed, 10 Mar 2021 15:25:26 GMT

By Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist

If there were such an award, naltrexone would certainly be nominated as the drug of the last decade. It has been over fifty years since its discovery in 1963, and we are still uncovering uses for this versatile substance at various dosages. As our knowledge of its pharmacology and corresponding mechanistic physiology improves over time, we continue to uncover more data as to how it works on a plethora of disease states. As has been discussed in medical literature for decades, naltrexone is an oral opioid receptor antagonist primarily used to help maintain an opiate-free state in patients with opiate addiction.¹ However, in the past 30 years, it has become a novel treatment for over 100 different diseases in doses far lower than the standard 50 mg manufactured tablets, which is why we often talk about low-dose naltrexone (LDN). While there are no large, randomized clinical trials for each disease state for which LDN has been tried, there are a number of smaller studies, and the evidence is starting to mount.

What Is LDN Therapy?

LDN therapy, defined by some as dosages between 0.5 mg and 5 mg daily, was developed in 1985 by a physician from New York: Bernard Bihari, MD, a doctor of internal medicine, psychiatry and neurology. Dr. Bihari changed his research interest from addiction to AIDs in the early 1980s when the AIDS epidemic began. He discovered that AIDS patients had 20% of the normal endorphin levels of healthy patients. His key discovery was that 1% of the normal 50 mg dose of naltrexone caused an unusual effect of a 300% increase in endorphin levels.² It is estimated that by his time of death in 2010, there were over 30,000 patients on LDN worldwide. Dr. Bihari’s standard dosing protocol titrates patients with weekly increases starting at 1.5 mg orally at bedtime, next up to 3 mg and then to a maintenance dose of 4.5 mg, pending assessment of patient tolerance and clinical progress.

In addition to this increase in endorphin levels following the short blockade of opioid receptors, LDN exhibits anti-inflammatory effects by inhibiting nonopioid receptors. Naltrexone blocks toll-like receptor 4 (TLR4), which is found on keratinocytes and also on macrophages such as microglia.³ These macrophages also contain inflammatory compounds such as tumor necrosis factor α and interleukin 6. Low-dose naltrexone can suppress levels of these inflammatory markers. It is important to note that these anti-inflammatory effects have not been observed at the standard higher doses of naltrexone.⁴

LDN and Dermatology

Doctors have more widely prescribed LDN in recent years, and patients have begun reporting improvements in their health to others with similar conditions, including autoimmune inflammatory dermatologic conditions. The list of those maladies includes Hailey-Hailey disease, lichen planopilaris, psoriasis and various types of pruritus.^5,6,7 Journals have published multiple case studies (see table below). Two case reports in particular describe significant improvement of patients with Hailey-Hailey disease after LDN had been used as a single-agent treatment. The disease was intractable in all four patients within these reports. In the first case, the patient drastically improved in clinical status, and the severity of the disease fell on the dermatology quality-of-life index scale from 29 to 4 in just seven months.⁸ The second case report describes three patients who experienced at least an 80% reduction in the extent of their disease within three months of starting LDN as their only treatment. Also, the frequency of recurrence was reduced, and no drug-induced side effects were reported.⁹ A common thread in all of these case reports was that the patients requested LDN as a treatment, indicating that this therapy is largely patient-driven. More LDN research in the future would be useful to improve the level of evidence and provide a more robust understanding of the broader effects on larger numbers of patients.

Published LDN Case Studies of Dermatological Conditions
Disease State	Patients	LDN Dosage Used	Citation
Hailey-Hailey	1	4.5 mg/day	Campbell, V., McGrath, C., & Corry, A. (2018). Low-dose naltrexone: A novel treatment for Hailey-Hailey disease. British Journal of Dermatology, 178(5), 1196–1198. https://doi.org/10.1111/bjd.16045
Hailey-Hailey	3	1.5–3 mg/day	Ibrahim, O., Hogan, S. R., Vij, A., & Fernandez, A. P. (2017). Low-dose naltrexone treatment of familial benign pemphigus (Hailey-Hailey disease). JAMA Dermatology, 153(10), 1015–1017. https://doi.org/10.1001/jamadermatol.2017.2445
Psoriasis	1	4.5 mg/day	Bridgman, A. C., & Kirchhof, M. G. (2018). Treatment of psoriasis vulgaris using low-dose naltrexone. JAAD Case Reports, 4(8), 827–829. https://dx.doi.org/10.1016%2Fj.jdcr.2018.06.001
Lichen planopilaris	4	3 mg/day	Strazzulla, L. C., Avila, L., Lo Sicco, K., & Shapiro, J. (2017). Novel treatment using low-dose naltrexone for lichen planopilaris. Journal of Drugs in Dermatology, 16(11), 1140–1142. Retrieved September 14, 2020, from https://jddonline.com/articles/dermatology/S1545961617P1140X

Dermatologists are seeing increasing rates of autoimmune disease manifesting in primary skin conditions that are often difficult to manage without a risk of immunosuppressive therapies. LDN influences a variety of systemic pathways, including the immune system, and this phenomenon has piqued the interest of researchers and practitioners regarding its potential in the treatment of several autoimmune conditions without suppressing the immune system’s functionality. Specifically, researchers have noted that LDN has the potential for the treatment of chronic inflammatory skin conditions.⁴

In addition to oral LDN therapy for dermatologic conditions, topical naltrexone has also shown promise. In one case study, a 1% naltrexone cream was compared to a vehicle alone for the treatment of pruritus, commonly known as itchy skin. Patients using this topical cream reported a 30% decrease in scores on the visual analog scale for acute and chronic pain, and it took effect 30 minutes faster than the vehicle. Patients with chronic episodes of pruritus responded better than those with acute episodes.¹⁰

Naltrexone has potential utility in various topical formulas for a number of situations where there is a need for anti-inflammatory and immune enhancement functions. In addition to permeation-enhanced topical pain formulas, topical naltrexone combinations for dermatological applications are often prescribed with one or more other active ingredients, such as antihistamines, mast cell stabilizers, corticosteroids, calcineurin inhibitors and/or sodium channel blockers for myriad conditions. These formulations create great opportunities for pharmacy compounding to fit the individualized needs of your dermatology patients.

PCCA members with Clinical Services support can find a list of commonly requested LDN formulas related to dermatology in our formula database. If they have any questions about compounding LDN for dermatology, please contact our Clinical Services department at 800.331.2498.

Nat Jones, RPh, FAPC, graduated from the Virginia Commonwealth University, Medical College of Virginia’s School of Pharmacy in 1979. In 2014, after 20 years of owning a compounding pharmacy, he joined PCCA’s staff. Nat has given continuing education lectures at medical professional seminars and webinars on numerous topics, including general compounding, wound care, pain management, nutrition, otolaryngology, women’s health, sexual dysfunction, insulin resistance, hormone replacement therapy, neurotransmitter imbalance and dermatology. He has published many articles and case studies in magazines and professional journals along with an open-access ebook titled Advances in Psoriasis with Avid Science. Since 2016, Nat has served on the Texas State Palliative Care Interdisciplinary Advisory Council.

A version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.

References

1. Toljan, K., & Vrooman, B. (2018). Low-dose naltrexone (LDN) — Review of therapeutic utilization. Medical Sciences, 6(4). https://doi.org/10.3390/medsci6040082

2. Schopick, J., (2013). Bernard Bihari, MD: Low-dose naltrexone for normalizing immune system function. Alternative Therapies in Health and Medicine, 19(2), 56–65. Retrieved September 14, 2020, from https://todayspractitioner.com/wp-content/uploads/2013/10/Bernard-Bihari-MD-Low-dose-Naltrexone-for-Normalizing-Immune-System-Function-athm_19_2_bihari_56_65.pdf

3. Lee, B., & Elston, D. M. (2019). The uses of naltrexone in dermatologic conditions. Journal of the American Academy of Dermatology, 80 (6), 1746–1752. https://doi.org/10.1016/j.jaad.2018.12.031

4. Younger, J., Parkitny, L., & McLain, D. (2014). The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology, 33(4), 451–459. https://doi.org/10.1007/s10067-014-2517-2

5. Ekelem, C., Juhasz, M., Khera, P., & Mesinkovska, N. A. (2019). Utility of naltrexone treatment for chronic inflammatory dermatologic conditions: A systematic review. JAMA Dermatology, 155 (2), 229–236. https://doi.org/10.1001/jamadermatol.2018.4093

6. Bridgman, A. C., & Kirchhof, M. G. (2018). Treatment of psoriasis vulgaris using low-dose naltrexone. JAAD Case Reports, 4 (8), 827–829. https://dx.doi.org/10.1016%2Fj.jdcr.2018.06.001

7. Strazzulla, L. C., Avila, L., Lo Sicco, K., & Shapiro, J. (2017). Novel treatment using low-dose naltrexone for lichen planopilaris. Journal of Drugs in Dermatology, 16(11), 1140–1142. Retrieved September 14, 2020, from https://jddonline.com/articles/dermatology/S1545961617P1140X

8. Campbell, V., McGrath, C., & Corry, A. (2018). Low-dose naltrexone: A novel treatment for Hailey-Hailey disease. British Journal of Dermatology, 178(5), 1196–1198. https://doi.org/10.1111/bjd.16045

9. Ibrahim O., Hogan, S. R., Vij, A., & Fernandez, A. P. (2017). Low-dose naltrexone treatment of familial benign pemphigus (Hailey-Hailey disease). JAMA Dermatology, 153(10), 1015–1017. https://doi.org/10.1001/jamadermatol.2017.2445

10. Bigliardi P. L., Stammer, H., Jost, G., Rufli, T., Büchner, S., & Bigliardi-Qi, M. (2007). Treatment of pruritus with topically applied opiate receptor antagonist. Journal of the American Academy of Dermatology, 56(6), 979–988. https://doi.org/10.1016/j.jaad.2007.01.007

Compounding Ideas for Fall and Winter

Tue, 12 Jan 2021 14:56:55 GMT

By Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist

As colder weather descends in the fall and winter months, a few health challenges come with it. Because of the use of heating systems that dehumidify the air, we consequently dry our skin and mucous membranes, decreasing the functionality of our natural barriers to dermatological and respiratory conditions. This puts more stress on our immune systems. Some of the various common fall and winter health issues include viral infections (COVID-19, flu, common colds, sore throat (pharyngitis is most likely viral)) and a couple of unique dermatological problems as a result of mask-wearing. I will cover some compounding and nutritional suggestions for these problems in this article. There are additional commonly observed problems this time of year that involve poor indoor air quality, sedentary living, unhealthy eating habits and seasonal depression, to name a few, that are beyond the scope of this article. However, I will also provide some practical tips for keeping your pharmacy customers informed so that they can make healthy decisions, and I’ll point out a few additional resources you can look to if you want to learn more.

Preventive Measures for Common Fall & Winter Conditions

The potential of viral infections is certainly heightened during flu season. People are understandably concerned about exposure. While there is no guaranteed method of protection, many patients will be seeking advice for nutritional supplements to support their immune systems during this time of year. Common recommendations include vitamin D3, curcumin, antioxidants (buffered vitamin C, vitamin E, quercetin, epigallocatechin-3-O-gallate (EGCG)) and zinc.

EGCG, the major catechin component of green tea, has been shown to have antiviral activity by interfering with the viral membrane protein functions and inhibiting attachment.¹ Vitamin D3, quercetin and zinc have been shown to lower interleukin-6 levels,^2,3,4 which may therefore support a healthy immune response and help control inflammation.^5,6 Wellness Works offers all of these options and many more to pharmacies, which allows them to provide their patients professional-grade supplements.

Addressing Symptoms of Common Fall & Winter Conditions

In some upper respiratory infections or after endoscopic sinus surgery, patients may need nasal and sinus irrigation with formulations including ingredients such as antihistamines, corticosteroids and even leukotriene antagonists in combination for symptomatic relief. Nonsterile compounding options would include formulas made with our dispersion powder bases LoxaSperse ^® and XyliFos ^® . If the clinician suspects microbial involvement other than a virus (i.e., bacteria or fungi), they may request the addition of antibiotics such as aminoglycosides or fluoroquinolones, or antifungal ingredients such as itraconazole and even amphotericin B to these combinations. Many of these ingredients are not water soluble, and inclusion of LoxaSperse^® and XyliFos^® improve the solubilization and dispersion of these drugs.

Additionally, upper respiratory symptoms often include cough, but some patients don’t want or can’t have alcohol in their cough medicine. Formulations in SuspendIt ^® (our all-in-one base for oral suspensions that has a patented polymer complex) with the opioid cough suppressant hydrocodone in combination with guaifenesin and pseudoephedrine can serve a real need in these cases. Prescribers and pharmacists might also consider other compounded multi-ingredient formulas using decongestants, antihistamines and dextromethorphan for non-opioid options.

Nasal symptoms including rhinitis and congestion often associated with nasal polyps may be treated with combinations of mast cell stabilizer/antihistamines like azelastine and corticosteroids such as budesonide. Prescribers commonly request compounded formulations like this.

Something else to consider is an indirect complication of COVID-19 known as “maskne.” It is a new term describing acne caused by wearing masks. The current pandemic and the need to cover our mouths and noses has led us to an increase in dermatological problems for many people in various fields, especially those who work long hours wearing a mask. Dermatologists describe maskne as a variation of “acne mechanica,” which usually occurs when skin is pressed against heavy clothing or bulky protective gear. In other words, having to wear a mask for protection has created the perfect conditions for facial acne and other types of skin irritation. Some people are not getting comedones (the small bumps we think of as acne), so they technically do not have acne, but they are getting redness, inflammation and irritation caused by the effects of wearing a mask.

If the mask-wearing is truly causing comedones, then patients should try a regimen of washing the face twice with a gentle cleanser that removes dirt and oils but does not strip all of the natural barrier from the skin. Additionally, practitioners might consider prescribing a compounded formula based on age and severity of acne to possibly include tretinoin, clindamycin and/or niacinamide in either PCCA’s Clarifying^™ Base or WO6^® Anhydrous Topical Gel . Research has shown that niacinamide may decrease sebum production. ⁷ Using WO6 as the base will allow for longer BUDs. If mask-wearing is only causing irritation and not acne, prescribers might consider a compound containing ketotifen and possibly naltrexone in either Clarifying, WO6 or VersaBase^® Cream .

Helping Your Patients Make Healthy Decisions

Prevention starts with the knowledge your patients need to make good decisions for their health, so it might be helpful to share practical tips for cold and flu season. Pharmacists may want to consider adding public service messaging to their websites and on-hold messaging for their phone systems that can possibly include variations of these messages:

Get immunized, especially if you or your loved ones are at risk; wash your hands; and cover your mouth when you cough or sneeze
Stay active, maintain a healthy diet and be sure to get enough sleep each night
Don’t wait for winter health problems. Get proactive and take your supplements to help support your immune system
Talk to our pharmacist when you experience symptoms. You don’t have to wait for your symptoms to get “bad enough” before seeking advice or treatment

Where You Can Learn More

We have more information and related resources available for helping your community stay healthy during the colder months of the year. You can read these articles on The PCCA Blog:

“ What is ‘maskne,’ and what can we do about it? ”
“ Compounding Opportunities for Winter ”

PCCA members can also find our extensive document Commonly Requested Compounding Ideas and Products for Patients During the Winter & Flu Season (PCCA Document #97852) on our Members-Only Website. It has many commonly requested formula examples, including some that are related to what I have covered above.

PCCA members can hear Nat talk more about compounding ideas for fall and winter in our October 2020 Marketing & Sales Power Hour recording on PCCA Play

References

1. Kaihatsu, K., Yamabe, M., & Ebara, Y. (2018). Antiviral mechanism of action of epigallocatechin-3-O-gallate and its fatty acid esters. Molecules, 23(10). https://doi.org/10.3390/molecules23102475

2. De Haes, P. Garmyn, M., Degreef, H., Vantieghem, K., Bouillon, R., & Segaert, S. 1,25-dihydroxyvitamin D3 inhibits ultraviolet B-induced apoptosis, Jun kinase activation, and interleukin-6 production in primary human keratinocytes. Journal of Cellular Biochemistry, 89 (4), 663–673. https://doi.org/10.1002/jcb.10540

3. Mlcek, J., Jurikova, T., Skrovankova, S., & Sochor, J. (2016). Quercetin and its anti-allergic immune response. Molecules, 21(5). https://doi.org/10.3390/molecules21050623

4. Hatakeyama, D., Kozawa, O., Otsuka, T., Shibata, T., & Uematsu, T. (2002). Zinc suppresses IL-6 synthesis by prostaglandin F2alpha in osteoblasts: Inhibition of phospholipase C and phospholipase D. Journal of Cellular Biochemistry, 85(3), 621–628. https://doi.org/10.1002/jcb.10166

5. Tanaka, T., Narazaki, M., & Kishimoto, T. (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harbor Perspectives in Biology, 6(10). https://dx.doi.org/10.1101%2Fcshperspect.a016295

6. Aziz, M., Fatima, R., & Assaly, R. (2020). Elevated interleukin-6 and severe COVID-19: A meta-analysis. Journal of Medical Virology, 92(11), 2283–2285. https://doi.org/10.1002/jmv.25948

7. Draelos, Z. D., Matsubara, A., & Smiles, K. (2006). The effect of 2% niacinamide on facial sebum production. Journal of Cosmetic and Laser Therapy, 8(2), 96–101. https://doi.org/10.1080/14764170600717704

What is “maskne,” and what can we do about it?

Tue, 22 Sep 2020 12:56:10 GMT

By Jane H. Jones, RPh, PCCA Clinical Compounding Pharmacist

This article was updated September 22, 2020

What is “maskne”? It is a new term describing the acne caused by wearing masks. It is also simply referred to as “mask acne.” The CDC is recommending everyone to wear masks to help slow the spread of COVID-19, especially when out in public, and says that “your cloth face covering may protect them. Their cloth face covering may protect you.”¹ This current health crisis and the need to cover our faces has led us to this new medical condition, particularly for health care and front-line workers who work long hours and wear one, two or even three masks as protective barriers daily. Dermatologists describe maskne as “acne mechanica,” the type of acne caused by repetitive physical trauma to the skin, usually by rubbing or scratching. Having to wear a mask for protection has created the perfect storm of oil, sweat, heat, bacteria and friction now called maskne.

Preventing Maskne

Can I prevent maskne? There are many ways to try to avoid getting mask acne. It is important to wash your face before and after wearing a mask with a gentle cleanser. You should moisturize your skin after cleansing to prevent dryness and, if possible, avoid heavy cosmetic use or wearing makeup under a mask. There are many options for face masks available out there. A 100% cotton one would be best if choosing a cloth type and washing daily after each use. It is also important to dispose of and not reuse disposable masks. But with rising summer temperatures, and especially for those who must wear masks for work, it may be difficult to prevent getting maskne.

There are already several cosmetic websites offering products to treat maskne online. There are also standard single-therapy agents to treat acne commercially, but we as compounders have so many more options to help our patients. PCCA also has many formulas that allow PCCA members with Clinical Services access to choose between bases and combine different active ingredients to potentially fit all patient needs.

Depending on patient-specific needs, a facial cleanser formulation may be recommended:

PCCA Formula #9564 – salicylic acid, niacinamide and NataPres ® cleansing pads
PCCA Formula #10096 – salicylic acid, mandelic acid and NataPres facial foam cleanser
PCCA Formula #7489 – salicylic acid and glycolic acid facial foam cleanser

Potential Compounded Options for Maskne

There are many options when choosing a base to compound with. Our PCCA PracaSil®-Plus gel has properties that nourish the skin, and when used as a base, it may promote faster relief and recovery. This base also provides moisture and protects the skin’s barrier. It is rich in skin-friendly fatty acids and lipids. PracaSil-Plus is commonly selected as a delivery vehicle in compounded medications for scar therapy but may also be prescribed in formulations for patients with other skin conditions, including acne.

For patients who have minor skin irritation, itching, redness and mild blemishes, physicians often recommend these formulas :

PCCA Formula #11966 – naltrexone and pramoxine topical gel in PracaSil-Plus
PCCA Formula #12546 – ketotifen and naltrexone topical gel in PracaSil-Plus
PCCA Formula #12683 – naltrexone, aloe vera and beta glucan topical gel in PracaSil-Plus

Our anhydrous topical gel base WO6 ® can be compounded with a 180 beyond-use date (BUD) by default, just like our PracaSil-Plus formulas, and is another consideration. PCCA’s Clarifying ™ base is a cream emulsion that compounders can recommend for patients with all forms of problem skin, including acne. It is noncomedogenic and has moisturizing properties along with natural ingredients that may improve the appearance of red and blotchy skin.

For patients with severe cases, physicians may recommend these formulas :

PCCA Formula #10012 – niacinamide and potassium azelaoyl diglycinate topical cream
PCCA Formula #13313 – niacinamide, tretinoin and hyaluronic acid topical gel in WO6
PCCA Formula #13336 – clindamycin, niacinamide and tretinoin topical gel in WO6
PCCA Formula #10901 – clindamycin and benzoyl peroxide topical gel in PracaSil-Plus
PCCA Formula #11635 – niacinamide, biotin and potassium azelaoyl diglycinate topical cream in Clarifying
PCCA Formula #11708 – tretinoin and sodium hyaluronate topical cream in Clarifying

We are all in it together during this pandemic. Stress and diets high in sugar and processed foods may exacerbate all forms of acne. Reducing stress, getting plenty of sleep, exercising and staying hydrated are simple tasks, yet sometimes they’re very difficult to do on a daily basis. With compounded options, we may be able to provide relief and help patients address the breakouts and flares caused by maskne.

How effective are different types of face mask? Check out our recent blog post “ Hand-Washing, Nasal Sprays and Masks — What Research Is Saying .”

Jane H. Jones, RPh, joined PCCA’s Clinical Services department in January of 2005. She is a 1996 graduate of the Medical College of Virginia in Richmond, Virginia. Prior to PCCA, she worked in management with several retail pharmacies. Her professional experience includes working with organ transplant patients, pediatrics and neonatal intensive care infants at Texas Children’s Hospital in Houston, Texas. Her compounding interests are in pediatrics, veterinary and topical delivery systems. She always looks forward to meeting and helping her fellow pharmacists solve patient challenges via compounding.

Reference

1. Centers for Disease Control and Prevention. (2020). Use of cloth face coverings to help slow the spread of COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/diy-cloth-face-coverings.html

Compounding Opportunities for Winter

Wed, 05 Feb 2020 15:37:03 GMT

By Melissa Merrell Rhoads, PharmD, PCCA Director of Formulation Development, and Andrea Branvold-Herr, MS, RPh, PCCA Clinical Resources Manager

The winter season is often accompanied by health challenges. The cold air can contribute to various skin conditions, and it can dampen the immune system, leading to illness as well. Fortunately, where patients need help, compounders are there with unique options. Over the years, we have published some great information on compounding for this season in our members-only magazine, the Apothagram, so we thought it would be helpful to bring some of it together into one place and share it here. Below you will find excerpts from some of these past Apothagram articles. Enjoy!

Compounding for Patients with Dry, Cracked and Itchy Skin
From “Compounding for Winter Conditions,” by Ranel Larsen, PharmD, PCCA Clinical Compounding Pharmacist, in the December 2015 Apothagram.

A big complaint of the winter months is dry skin, or xerosis. Temperature and humidity are some of the factors that can influence the water content of the skin. Without adequate hydration, the skin can dry out and crack. This can cause itching, inflammation, scaling and rough texture, and can lead to infection.1 It is common to experience dryness in the winter months when we all spend more time indoors in low-humidity environments. One of the most effective ways to treat dry skin is to increase the moisture content. This can be accomplished by using PracaSil®-Plus. It contains silicones and pracaxi oil, which is rich in fatty acids and lipids. An excellent ingredient to consider with this base is urea, which can be used to increase the water-holding capacity of the skin. It promotes hydration by increasing stratum corneum water uptake and enhances the water-binding capacity. It also has a mild keratolytic action, removing excess keratin in dry skin conditions.2 PCCA Formula #10417 uses urea in PracaSil-Plus as a topical gel.

Another option is compounding a lotion bar. You can use many different molds for this. PCCA Formula #10925 is our basic lotion bar formula, containing 33% coconut oil. Coconut oil has emollient properties and significantly improves the hydration of skin.3 This oil also contains 62% medium-chain fatty acids, which in addition to its antioxidant properties are believed to be responsible for its anti-inflammatory activity.4

XemaTop™ is another option as well. It’s a compounding base that was specifically designed for the topical delivery of active ingredients in formulations for patients with dry skin conditions. It replenishes the lipids within the skin and helps restore the skin’s barrier, nourishing the skin and preventing water loss.

From “6 Easy Compounding Formulas for Itchy Winter Skin,” by Jerra Banwarth, RPh, FAPC, PCCA Education and Training Manager, in the December 2014 Apothagram.

What recommendations can we as compounders make for dry skin? Patients who complain of dry, cracked skin, or itchy and scaly skin may benefit from some of the suggestions below.

These formulations use different ratios of PracaSil-Plus and Spira-Wash® Gel. Because it’s silicone-based, PracaSil-Plus can help soften and soothe irritated skin. Spira-Wash Gel is a water-washable base that can solubilize added ingredients in formulations, and it’s also a humectant.

Commonly Requested Hydrating Formula
PCCA Formula #10416, urea in PracaSil-Plus and Spira-Wash Gel, is great for moisturizing the feet, elbows and hands. Apply a light application to these areas several times per day to encourage hydration. If knuckles or hands crack, an application after hand-washing may be beneficial.

Commonly Requested Formula for Patients with Psoriasis
PCCA Formula #11026, which is zinc pyrithione, clobetasol propionate and cyanocobalamin in PracaSil-Plus and Spira-Wash Gel, may be beneficial. Clobetasol propionate is a potent corticosteroid used to help reduce itching and the inflammatory response, and zinc pyrithione has antibacterial and fungistatic properties.

Commonly Requested Formulas for Patients with Eczema
PCCA Formula #11187, cyanocobalamin and urea in PracaSil-Plus, is suitable for children. Vitamin B12 (cyanocobalamin) topically has been studied in children and is applied twice daily.⁵ Cyanocobalamin has been shown to reduce inflammatory cytokines associated with eczema.⁶ Orally, cyanocobalamin has poor bioavailability; therefore, topical application has been the preferred route, studied in both children and adults.

Since many people ski at this time of year, consider a cosmetic formula containing sunscreens as well, such as PCCA Formula #10752, oxybenzone and octinoxate in PracaSil-Plus.

PCCA members with Clinical Services access can find the formulas for dry, cracked and itchy skin listed above in our formula database.

Compounding for Flu Season
From “Compounding Opportunity!” by Melissa Merrell Rhoads, PharmD, PCCA Director of Formulation Development, in the February 2014 Apothagram.

Flu season is upon us, and with that often comes the shortage of Tamiflu® Oral Suspension due to a strong demand. PCCA has several formulas to support our members as they serve their patients and practitioners.

PCCA Formula #9360, an oseltamivir oral suspension, provides compounders with a formulation that has gone through stability testing. Please refer to the March/April 2007 issue of The International Journal of Pharmaceutical Compounding (Vol. 11, No. 2) for a copy of the published study, “Stability of Oseltamivir in Various Extemporaneous Liquid Preparations,” which was co-authored by PCCA’s Lawson Kloesel, RPh. This formula is unflavored because it was a direct copy from the study in order to obtain the extended beyond-use date of 90 days.

We have also added other formulas to our database that were written to be more palatable with the addition of sweeteners and choice of flavor. However, since they differ from the one used in the stability study, the beyond-use date is only 14 days per USP guidelines.

PCCA Members with Clinical Services access can view the oseltamivir formulas mentioned above in our formula database.

Recommended Flavors to Add

Cotton Candy – 2% concentration
Strawberry Natural & Artificial Oil – 1–2% (mixed with Polysorbate 20 NF 1%)
Tutti Frutti, Artificial – 2%
Bubble Gum Concentrate (Colorless) – 2%

Recommended Combinations of Flavors to Add

Tutti Frutti, Artificial, 1% + Bubble Gum Concentrate (Colorless) 1%
Strawberry Natural & Artificial Oil 1% + Cotton Candy 1–2% (mixed with Polysorbate 20 NF 1%)
Chocolate 2% + English Toffee, Artificial, 2%

For more compounding opportunities during the flu season, PCCA members can look at our compounding ideas for winter and flu season document on the Members-Only Website. For nutritional supplement options, they can see Wellness Works’ newsletter on immune support. If PCCA members with Clinical Services access have questions about compounding options for winter conditions, please contact our clinical compounding pharmacists at 800.331.2498.

Melissa Merrell Rhoads, PharmD, PCCA Director of Formulation Development, received her pharmacy degree from Mercer University in Atlanta, Georgia, in 1995. She currently is involved with and oversees the development and implementation of new formulas at PCCA. She had more than six years of compounding experience with pharmacies in Georgia and Florida prior to joining the PCCA staff in 2004. Her areas of interest include women’s health, veterinary and pain management compounding.

Andrea Branvold-Herr, MS, RPh, PCCA Clinical Resource Manager, is interested in all areas of pharmacy, but in particular women’s health, marketing and sales. Before joining PCCA’s Business Intelligence team in her current role of managing the Concierge Compounding program, Andrea was a PCCA pharmacy consultant for 20 years. She holds a MS in pharmacy administration from The University of Texas, a BS in pharmacy from the University of Houston and a BBA in finance from The University of Texas.

A version of this article previously appeared in PCCA’s members-only magazine, the Apothagram.

References

Allen, L. V. (2003). Basics of compounding for dry-skin conditions. The International Journal of Pharmaceutical Compounding, 7(6), 460–463. Retrieved from https://www.ijpc.com/
Urea. (2018). In Clinical Pharmacology. Retrieved from http://www.clinicalpharmacology-ip.com/Forms/Monograph/monograph.aspx?cpnum=634&sec=monmech&t=0
Agero, A. L., & Verallo-Rowell, V. M. (2004). A randomized double-blind controlled trial comparing extra virgin coconut oil with mineral oil as a moisturizer for mild to moderate xerosis. Dermatitis, 15(3), 109–116. https://doi.org/10.2310/6620.2004.04006
Evangelista, M. T., Abad-Casintahan. F., & Lopez-Villafuerte, L. (2014). The effect of topical virgin coconut oil on SCORAD index, transepidermal water loss, and skin capacitance in mild to moderate pediatric atopic dermatitis: A randomized, double-blind, clinical trial. International Journal of Dermatology, 53(1), 100–108. https://doi.org/10.1111/ijd.12339
Januchowski, R. (2009). Evaluation of topical vitamin B12 for the treatment of childhood eczema. The Journal of Alternative and Complementary Medicine, 15(4), 387–389. https://doi.org/10.1089/acm.2008.0497
Stücker, M., Pieck, C., Stoerb, C., Niedner, R., Hartung, J., & Altmeyer, P. (2004). Topical vitamin B12 — A new therapeutic approach in atopic dermatitis — Evaluation of efficacy and tolerability in a randomized placebo-controlled multicentre clinical trial. British Journal of Dermatology, 150(5), 977–983. https://doi.org/10.1111/j.1365-2133.2004.05866.x

More Than a Cover-Up: Options for Patients with Periorbital Hyperpigmentation

Wed, 12 Jun 2019 13:04:21 GMT

By Sara Hover, RPh, FAARM, PCCA Clinical Compounding Pharmacist

Periorbital hyperpigmentation is a skin disorder that appears in those with darker skin pigmentation. It is also known as idiopathic cutaneous hyperchromia of the orbital region or, commonly, “dark circles.” Clinically, it presents with medium to deep brown hyperpigmentation around the bilateral orbital skin and eyelid, sometimes extending to the upper nose and between the eyebrows. The discoloration may be present on the upper, lower or both eyelids.¹ It can be a significant cosmetic concern for patients, especially when they feel it makes themselves appear sad, tired, stressed or older than they are.² But it also could be a warning sign of more serious medical problems, including disorders of the liver, heart, thyroid or kidneys; hereditary blood disorders; allergic reactions; nutrient deficiency, such as that of vitamin K; Addison’s disease; circulatory conditions resulting in fluid retention; or even sleep disturbance.^2,3

Causes
Periorbital hyperpigmentation is caused by various external and internal factors, which makes it very complex to treat. The factors can include genetics, excessive pigmentation from melanin deposited in the epidermis and dermis, post-inflammatory hyperpigmentation due to contact or atopic dermatitis, periorbital edema, excessive vascularity, reduced thickness of the epidermis, and tear troughs associated with aging.^2,4

Latanoprost Warning
Latanoprost, bimatoprost and other prostaglandin analogs can also cause periorbital hyperpigmentation. These are often used as ocular hypotensive eye drops for patients with glaucoma or lash growth. When bimatoprost drops cause this condition, it usually develops between three and six months after initiating the treatment. The likely mechanism of action is due to an increase in melanogenesis in dermal melanocytes and increased transfer of melanin granules to the basal epidermis. However, the hyperpigmentation typically reverses when the treatment is discontinued.⁴

Testing
Because of the various potential causes of this condition, testing to determine the underlying cause can be helpful in developing a course of treatment. One option is a dermoscopy, which may reveal if the pigmentation is due to melanin or underlying vasculature.² Histopathologic examination is another option. This can help determine if it is epidermal, dermal, or mixed pigmentation with no other significant changes. A Fontana-Masson silver stain is an option for detecting melanin, and a Perls’ potassium ferricyanide stain can detect hemosiderin deposits in the tissue.³ Hemosiderin staining (iron staining) of the tissue is treated differently since it isn’t related to excessive melanin.

Potential Treatment Options

Here are some potential options to consider:
Periorbital hyperpigmentation caused by melanin is typically treated with hydroquinone and similar ingredients along with lasers³
Hydroquinone is an antagonist of tyrosinase, a copper-containing enzyme that factors heavily in pigmentation. A range of hydroquinone concentrations can be compounded. Using around 2–8% concentration may stabilize the melanocytes and decrease pigmentation locally³
Kojic acid binds to copper, also blocking the tyrosinase pathway³
Cases caused by vascularity are often treated by targeting the vessel walls to stabilize them, and the use of ascorbic acid (vitamin C), phytonadione (vitamin K1) and tretinoin may help³
Ascorbic acid can effectively lighten pigmentation, possibly due to an increase in dermal thickness that reduces dark discoloration from underlying congested blood⁴
Retinoids are vitamin A derivatives, like tretinoin, that decrease the appearance of hyperpigmentation through multiple pathways. They promote collagen synthesis and reorganization. They also decrease melanin content³
Mixed-type periorbital hyperpigmentation may respond best to combination therapy³
Concealers and cosmeceuticals are the least invasive options. Optical diffusers can reduce the appearance of dark circles, but these only cover up the condition³

Something New
Hydroquinone and ascorbic acid are not new to this clinical area, but having a base that can stabilize them is. PCCA’s W06™ Anhydrous Topical Gel is a base that has a water activity below 0.6 (Aw < 0.6). It was created to accommodate challenging active pharmaceutical ingredients like hydroquinone and ascorbic acid while giving longer beyond-use dates by default. As well as being a great base, W06 provides moisture and softens the skin.

Example Formulas
PCCA has several formulas that compounders can consider as options when working with practitioners and their patients. PCCA members with Clinical Services access can view these formulas here, and if they have questions about compounding for patients with periorbital hyperpigmentation, they can contact our Clinical Services department at 800.331.2498.

Sara Hover, RPh, FAARM, has been a compounding pharmacist for over 20 years and joined the PCCA Clinical Services team in June 2013. Before joining the PCCA staff, she was the owner and pharmacist of Creative Compounds in Prosper, Texas, an independent, compounding-only pharmacy that focused on women’s health and nutrition. In addition to her expertise in hormone replacement therapy, Sara possesses a vast knowledge of homeopathics as well as herbal and vitamin supplements. Sara obtained her Bachelor of Science degree from the University of Texas at Austin in 1994. She is a lifetime member of the University of Texas College of Pharmacy Alumni Association.

A version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.

References
1.   Vashi, N. A., Wirya, S. A., Inyang, M., & Kundu, R. V. (2017). Facial hyperpigmentation in skin of color: Special considerations and treatment. American Journal of Clinical Dermatology, 18(2), 215–230. https://doi.org/10.1007/s40257-016-0239-8
2.   Jage, M., & Mahajan, S. (2018). Clinical and dermoscopic evaluation of periorbital hyperpigmentation. Indian Journal of Dermatopathology and Diagnostic Dermatology, 5(1), 42–47. https://doi.org/10.4103/ijdpdd.ijdpdd_2_18
3.   Daroach, M., & Kumaran, M. S. (2018). Periorbital hyperpigmentation − An overview of the enigmatous condition. Pigment International, 5(1), 1–3.
4.   Sarkar, R., Ranjan, R., Garg, S., Garg, V. K., Sonthalia, S., & Bansal, S. (2016). Periorbital hyperpigmentation: A comprehensive review. The Journal of Clinical and Aesthetic Dermatology, 9(1), 49–55.

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The references cited did not necessarily evaluate PCCA products or formulas included in these statements. The information contained herein is not intended to replace or substitute for conventional medical care, or encourage its abandonment.

Compounding for Dermatology and Cosmeceuticals? Here’s a New Anhydrous Base for You

Mon, 14 Jan 2019 17:22:25 GMT

Compounding for Dermatology and Cosmeceuticals? Here’s a New Anhydrous Base for You

At International Seminar last year, we introduced a new compounding base to help pharmacies creating customized medications for dermatology as well as cosmeceuticals: W06™ Anhydrous Topical Base. While there are already some high-performing dermatological bases, such as Clarifying™ and XemaTop™, we also wanted to develop an anhydrous option for compounding pharmacies.

W06 has a water activity below 0.6 (Aw < 0.6), which is where it gets its name, and which classifies it as an anhydrous base. This allows for prolonged default beyond-use dates (BUDs). We have also tested and shown W06 to be able to accommodate sensitive active pharmaceutical ingredients, such as hydroquinone and ascorbic acid.

As with any great base for dermatology and cosmeceutical compounding, W06 also has an elegant, refined feel, and its emollient properties moisturize and soften the skin as it delivers active pharmaceutical ingredients.

We have already developed and tested over 35 formulas with W06, and we will continue to create more. PCCA members can access them here.

Benefits for Compounders

Lower Operating Costs
W06 is anhydrous, which allows for prolonged default BUDs without having to spend thousands of dollars on stability testing, and it can increase operational efficiency for compounders making anticipatory batches
Broad Application
W06 is suitable for a variety of dermatological or cosmetic applications and is capable of accommodating challenging ingredients, including hydroquinone and ascorbic acid

Benefits for Patients

Convenience
It’s anhydrous, which allows for longer BUDs and less-frequent prescription refills
Easy application
W06 is smooth and creamy, offering a refined cosmetic feel to customized medications without a greasy or tacky residue
Soft skin
W06 has emollient properties, moisturizing and softening the skin as it delivers APIs

Note

We still recommend that compounders consider Clarifying in formulations for patients with acne and rosacea, and XemaTop in formulations for patients with psoriasis, eczema and dry skin. We have several XemaTop-based formulas with extended BUDs that have been studied using stability-indicating methods. But for compounders who need prolonged BUDs for formulas that do not have stability studies behind them, or who are working with sensitive ingredients, we recommend using W06.

If PCCA members have questions about compounding with W06 Anhydrous Topical Gel, they can contact our Pharmacy Consulting Department at 800.331.2498.