THE PCCA BLOG

Easing Drug & Disease Side Effects in Hospice Patients

Fri, 03 Jan 2025 00:30:22 GMT

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

The fundamental purpose of hospice is to help patients retain comfort, dignity and quality of life as they approach the end of life. During this stage, nausea and vomiting — either caused by medication side effects or from symptoms of a disease — are common. These and other side effects may lead to unnecessary stress and patient discomfort.¹ In the following article, we review a commonly used topical gel that lessens nausea and vomiting,² as well as the PCCA base vehicle that may enhance penetration of active pharmaceutical ingredients (APIs).

ABH Gel: Common & Customized

ABH gel is often used to help patients with nausea, vomiting and delirium during hospice and palliative care. The gel’s name comes from the API brands that are used in it — lorazepam (Ativan^®), diphenhydramine (Benadryl^®) and haloperidol (Haldol^®).

Lorazepam is a short-acting benzodiazepine used in patients with anxiety, shortness of breath and nausea. It acts on postsynaptic GABA receptors — a type of receptor in the brain that responds to the neurotransmitter gamma-aminobutyric acid (GABA) — located in multiple sites within the central nervous system (CNS). Sedation and confusion are common side effects.

Diphenhydramine is a first-generation antihistamine that acts on the histamine-1 (H-1) receptor. It is used for sedation, nausea and the extrapyramidal effects — the involuntary movement disorders such as tardive dyskinesia — of dopamine antagonists. Considered an anticholinergic medication, it causes a variety of side effects, including drowsiness, constipation, confusion, dry mouth, agitation, anxiety and urinary retention.

Haloperidol is a first-generation antipsychotic that acts primarily by inhibiting the D2 dopaminergic receptor — a protein that plays a key role in many brain functions. The API is used to sedate and calm patients. It carries an increased risk of extrapyramidal side effects, and oral haloperidol has a higher risk of delirium and mortality in palliative care patients.³

As a topical application, ABH gel is typically administered on the wrist, rubbed behind the ears or on the bottom of the feet.

Since ABH gel is not commercially available, compounding pharmacies may compound ABH preparations tailored to meet the unique needs of individual patients. The formulation should use a base vehicle that is smooth to the touch and that delivers exceptional API permeation through various levels of the skin.

Studied Results: PermE8^® Anhydrous Gel

PermE8 Anhydrous Gel ticks all of these boxes. Not only does it feature a silky texture that spreads quickly compared to other topical preparations, but it also can hold multiple APIs — including salt forms — in one compounded preparation. And due to water activity (Aw) of less than 0.6 (<.6), PermE8 offers the potential for longer beyond-use dates (BUDs).* Extended BUDs benefit not only compounding pharmacies by helping to lower operating costs but also hospice providers and caretakers due to fewer pharmacy refills.⁴

The need to deliver exceptional API permeation through various levels of the skin was supported in an independent study that compared the percutaneous absorption of ketoprofen in a formulation using PermE8 Anhydrous Gel to a formulation using PCCA Lipoderm®. Results indicated no significant difference between the two formulations (see Figure 1). Researchers concluded that the extent and rate of absorption in the PermE8 formulation is comparable to the industry-leading, permeation-enhancing Lipoderm.⁴

Figure 1
Across donor summary: the mean percutaneous absorption and distribution of ketoprofen in two compounded formulas after 48 hours diffusion.

PCCA members with clinical services access may view and/or download PCCA formulations to compound ABH gel preparations 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 ABH gel, hospice and palliative care or 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.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

References

Blaszczyk AT, Bailey TA, Tapia S. ABH Gel: Comforting Cure or Pricey Placebo?. J Am Med Dir Assoc. 2021;22(1):23-27. Accessed December 2024 at https://pubmed.ncbi.nlm.nih.gov/33246839/
Moon RB. ABHR Gel in the Treatment of Nausea and Vomiting in the Hospice Patient. Int J Pharm Compd. 2006;10(2):95-98. Abstract accessed December 2024 at https://pubmed.ncbi.nlm.nih.gov/23974181/
Dahal A, Neupane R, Boddu SH, et al. Percutaneous Absorption of Lorazepam, Diphenhydramine Hydrochloride, and Haloperidol from ABH Gel. Int J Pharm Compd. 2020;24(2):168-175. Abstract accessed December 2024 at https://pubmed.ncbi.nlm.nih.gov/32196480/
PCCA Science. PCCA PermE8™ Anhydrous Ge Product Information Sheet. Document number 99608; 2018. Accessed December 2024 at PCCA Members-Only Website
PCCA Science. (2018) PermE8/Lipoderm Technical Report: Evaluation of the in vitro Human Skin Percutaneous Absorption of Ketoprofen in PCCA PermE8 Anhydrous Gel vs. PCCA Lipoderm . Document number 99732. Accessed December 2024 at PCCA Members-Only Website.

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.

Microdosing GLP-1 RAs: Fad or Forever?

Fri, 22 Nov 2024 15:58:06 GMT

by Jennifer Lines, PharmD Candidate, PCCA Clinical Services Intern, and Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized metabolic health and weight management, leading to a host of new weight loss wonder drugs. But did you know that recent evidence shows these new drugs may do more than just help with weight loss and diabetes? And at a fraction of the standard dose?

Looking Back on GLP-1 RAs

Originally discovered in the saliva of the Gila monster, exenatide — a GLP-1 RA— was approved as a twice-daily injection by the FDA in 2005 for adults with type 2 diabetes.¹ Within the past decade, longer-acting GLP-1 RA formulations entered the market as once-weekly, self-administered injectable pens — most notably, semaglutide.

Recent FDA approvals and indications for products containing semaglutide include the reduction of cardiovascular risk in patients with type 2 diabetes and body weight reduction for obesity. New research, however, reveals the potential for additional benefits of the drugs.

Potential Benefits of GLP-1 RAs

Known for their metabolic benefits, emerging studies suggest GLP-1 RAs may help improve kidney function, cardiovascular health, non-alcoholic fatty liver disease, Alzheimer's disease and Parkinson’s disease.²

GLP-1 RAs, such as semaglutide, also show potential anti-inflammatory properties. Although the specific mechanisms are not understood, reports indicate that semaglutide can modulate inflammatory processes by reducing levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hsCRP).

In an animal model, semaglutide demonstrated neuroprotective effects and improved cognitive function by inhibiting the release of inflammatory cytokines mediated by the NLRP3 inflammasome, a protein involved in regulating the innate immune system and inflammatory responses.

GLP-1 receptors are also found on different immune cells, such as neutrophils and eosinophils, and their activation has modulatory effects on immune responses and inflammatory processes associated with these types of cells.³

What Is Microdosing?

Microdosing is not an official medical term; it refers to taking less than the standard dose of a medication to achieve benefits while potentially minimizing undesirable side effects.

The term microdosing has risen in popularity in recent years. Initially, it referred to taking small doses of psychedelic drugs to alleviate symptoms of depression and anxiety, or boost mood and creativity. Interest in microdosing GLP-1 RAs is growing among many holistic physicians.⁴

Endogenous GLP-1 vs. Exogenous GLP-1 RAs

At normal physiological levels, active GLP-1 levels peak around 30-60 minutes after ingesting a meal before being rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). During DPP-4 inhibition, levels of active GLP-1 increase up to 2-3 times. However, with exogenous GLP-1 RAs, active levels of GLP-1 RAs can rise to 10-30 times the normal physiological levels (depending on the agent used) and maintain steadily high levels independent of meal ingestion. One of the most common reasons patients discontinue GLP-1 RA treatment is due to gastrointestinal side effects, which could be attributed to the markedly high GLP-1 RA levels.⁵

Microdosing GLP-1 RAs

Anecdotal discussions between holistic practitioners suggest microdosing semaglutide may help people lose weight while limiting side effects. Naturopathic physician Dr. Tyna Moore, for example, suggests people with reduced GLP-1 levels may benefit from lower dosing and slowly increasing to the patient’s normal physiological levels. Dr. Moore also believes that slower, more sustainable weight loss allows the body more time to adjust to changes in weight, reducing the side-effect profile and potentially leading to better long-term success.⁶

While there are no clinical studies exploring the concept of microdosing GLP-1 RAs, it may be a useful tool for a holistic metabolic health strategy. It is important to remember that GLP-1 RAs are only one piece of the puzzle and should always be recommended in conjunction with diet, exercise and lifestyle modifications.

Smaller doses of GLP-1 RAs may not benefit those with severe metabolic dysfunction or those needing substantial weight loss. However, it may be helpful to those seeking a more gradual approach to weight loss while potentially providing overall health benefits like anti-inflammatory and neuroprotective effects.

While the safety of GLP-1 RAs is well established, current scientific evidence on the efficacy of microdosing GLP-1 RAs is lacking and further research is required to assess its benefits at lower doses.⁷

PCCA members with clinical services access may contact our Clinical Services team for help with microdosing GLP-1 RAs and other compounding concerns.

References

Paternoster S, Falasca M. Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1. Front Endocrinol (Lausanne). 2018;9:584. Published 2018 Oct 11. doi:10.3389/fendo.2018.00584
Laurindo LF, Barbalho SM, Guiguer EL, et al. GLP-1a: Going beyond Traditional Use. Int J Mol Sci. 2022;23(2):739. Published 2022 Jan 10. doi:10.3390/ijms23020739
Yaribeygi H, Maleki M, Jamialahmadi T, et al. Anti-inflammatory benefits of semaglutide: State of the art. J Clin Transl Endocrinol. 2024;36:100340. Published 2024 Mar 28. doi:10.1016/j.jcte.2024.100340
Mammoser G. (fact checked by Seladi-Shulman J.) Ozempic Microdosing Is Gaining Popularity. Does It Work for Weight Loss? Healthline. Published 2024 Oct 17. https://www.healthline.com/health-news/ozempic-microdosing-weight-loss
Smits MM, Holst JJ. Endogenous glucagon-like peptide (GLP)-1 as alternative for GLP-1 receptor agonists: Could this work and how?. Diabetes Metab Res Rev. 2023;39(8):e3699. doi:10.1002/dmrr.3699
Fitzgerald, J. (Host). (2023, October 12). Is Ozempic a miracle medicine? Heal Thy Self w/ Dr. G #283 [Video]. YouTube. https://www.youtube.com/watch?v=xI37HDVEMjo
Smits MM, Van Raalte DH. Safety of Semaglutide [published correction appears in Front Endocrinol (Lausanne). 2021 Nov 10;12:786732. doi: 10.3389/fendo.2021.786732]. Front Endocrinol (Lausanne). 2021;12:645563. Published 2021 Jul 7. doi:10.3389/fendo.2021.645563

Mitochondrial Health: The Key to Longevity?

Wed, 25 Sep 2024 17:34:52 GMT

In the race to unlock the secrets of longevity, one of the most exciting areas of research is mitochondrial health. These tiny organelles, often referred to as the "powerhouses" of the cell, are responsible for producing the energy (ATP) that fuels every cell in the body. As we age, mitochondrial function tends to decline, leading to reduced energy, increased oxidative stress and accelerated aging. Maximizing mitochondrial health has emerged as a key strategy for extending both lifespan and health span — how long we live and how well we live.¹

The Latest Breakthroughs in Mitochondrial Health

Recent research has identified several pathways to optimize mitochondrial function. One major discovery involves the molecule nicotinamide adenine dinucleotide (NAD+), which plays a crucial role in mitochondrial energy production.² As we age, NAD+ levels decline, leading to less efficient energy production and greater cellular damage. Boosting NAD+ through precursors like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) has shown promise in improving mitochondrial function and extending the lifespan of various organisms in laboratory studies.³ How this translates to human longevity — that is the question!

Another fascinating area is mitophagy, the process by which cells clear out damaged or dysfunctional mitochondria. With age, the body's ability to efficiently remove these damaged mitochondria diminishes, leading to cellular dysfunction. Promoting mitophagy through intermittent fasting or caloric restriction can help maintain a population of healthy mitochondria, thereby improving metabolic efficiency and reducing oxidative stress. Compounds such as creatine and urolithin A have been shown to stimulate mitophagy, offering potential therapeutic benefits for aging populations.^4,5

Maximizing Mitochondrial Health for Longevity

Dietary Interventions: Nutrients like coenzyme Q10, alpha-lipoic acid and omega-3 fatty acids (especially from fresh fish) directly support mitochondrial energy production.⁶
Exercise: Regular physical activity, particularly high-intensity interval training (HIIT), has been shown to enhance mitochondrial biogenesis. It is interesting how FEW individuals in their 40s and older do exercises that really elevate their heart rate.⁷
Cold Exposure: Cold thermogenesis, or exposing the body to cold temperatures (e.g., ice baths or cold showers), stimulates the production of mitochondria and enhances their efficiency, offering a novel way to boost energy and longevity.⁸
Sleep and Stress Reduction: Poor sleep and chronic stress are mitochondrial toxins. Prioritizing restorative sleep and managing stress through practices like mindfulness meditation or yoga can promote mitochondrial repair and rejuvenation.⁹

Maintaining optimal hormone levels as we age plays a crucial role in supporting mitochondrial health. Hormones like estrogen, testosterone and thyroid hormones are vital regulators of mitochondrial function, helping to enhance mitochondrial biogenesis (the creation of new mitochondria) and optimize energy production. Adequate levels of these hormones, monitored through optimal testing, also promote mitochondrial repair.¹⁰

By integrating these strategies on a regular basis, we can enhance mitochondrial function, slow down the aging process and increase both lifespan and health span for a brighter, more energized future.

References

López-Otín C, Blasco MA, Partridge L, et al. Hallmarks of aging: An expanding universe. Cell. 2023;186(2):243-278. Accessed September 2024
Zhao Y, Zhang J, Zheng Y, et al. NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway. J Neuroinflammation. 2021;18(1):207. Published 2021 Sep 16. Accessed September 2024 at https://pubmed.ncbi.nlm.nih.gov/34530866/
Lapatto HAK, Kuusela M, Heikkinen A, et al. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Sci Adv. 2023;9(2):eadd5163. Accessed September 2024 at https://pubmed.ncbi.nlm.nih.gov/35276888/
Marshall RP, Droste JN, Giessing J, Kreider RB. Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review. Nutrients. 2022;14(3):529. Published 2022 Jan 26. Accessed September 2026 at https://pubmed.ncbi.nlm.nih.gov/35276888/
Pagano G, Pallardó FV, Lyakhovich A, et al. Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures. Int J Mol Sci. 2020;21(19):7060. Published 2020 Sep 25. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582285/
Pagano G, Pallardó FV, Lyakhovich A, et al. Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures. Int J Mol Sci. 2020;21(19):7060. Published 2020 Sep 25. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582285/
San-Millán I. The Key Role of Mitochondrial Function in Health and Disease. Antioxidants. 2023; 12(4):782. Accessed September 2024 at https://www.mdpi.com/2076-3921/12/4/782
Chung N, Park J, Lim K. The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue. J Exerc Nutrition Biochem. 2017;21(2):39-47. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545200/
Zielinski MR, Systrom DM, Rose NR. Fatigue, Sleep, and Autoimmune and Related Disorders. Front Immuno. 2019;10. Accessed September 2024 at https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01827/full
Klinge CM. Estrogenic control of mitochondrial function. Redox Biol. 2020;31:101435. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212490/

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/

Biohacking Explained

Thu, 27 Jun 2024 20:26:54 GMT

Many unknowingly practice it on a daily basis. Others recognize it as a global movement. So what exactly is biohacking. So what exactly is biohacking?

Broadly speaking, biohacking is any method employed by an individual to enhance their health, performance and longevity. It can range from small diet and lifestyle changes to wearable devices or self-experimentation.¹

Although the first known use of the term “biohacking” occurred in 1992,² its practice took hold in the mid-2000s after genetic analysis became widely available and wearable devices became common and affordable. Individuals now use the vast amounts of physiological data generated from these and other technologies to improve their physical and mental performance, monitor their health and increase their lifespan.³

Prominent biohackers believe individuals can change their external and internal environments, resulting in full control of their biologic destiny.⁴Some believe biohacking leads to greater efficiencies and faster development of innovative therapeutics.⁵

General Types of Biohacking

Given its broad definition, the types of biohacking are endless. General types, however, have been defined and accepted by the biohacking community.

Lifestyle biohacking focuses on making positive health and behavior choices to embrace and increase biologic performance and longevity. For example, changing diets, practicing meditation and increasing exercise are all examples of lifestyle biohacking.

Molecular biohacking is the use of natural and synthetic substances to enhance biological functions. Substances include vitamins, minerals or peptides. Nootropics, also called smart drugs, are used to boost brain performance. Familiar over-the-counter nootropics include caffeine, L-theanine (an amino acid found in black and green teas), omega-3 fatty acids and ginkgo biloba.⁶

Technology-based biohacking includes wearable devices. Advanced devices — hyperbaric chambers or electromagnetic stimulators — are used for faster physiological changes or healing.³

Common Biohacking Practices and Real-World Applications

Dietary biohacking involves consumption of dietary supplements such as vitamins, minerals, prebiotics and probiotics to improve metabolism, boost energy production, improve physical performance, prevent chronic disease and increase lifespan. It can also include a specific type of diet — a ketogenic diet or intermittent fasting — for energy production and metabolism. Understanding nutrigenomics, or the relationship between a human genome, nutrition and health, is important. Some people also employ cellular metabolism monitoring devices such as glucose monitors or ketone breath analyzers.

Energy biohacking relates to sleep support and stress reduction. Light therapy is used to regulate the circadian rhythm, sleep tracking devices are used to monitor daily sleep patterns and meditation apps are used for sleep support and stress relief. Other techniques include consumption of vitamin B12 and magnesium supplements and wearing blue light protection glasses.

Physical health biohacking is popular among athletes to improve performance or expedite recovery from injuries. Common methods include cold therapy, heat therapy, whole body vibration therapy, pulsed electromagnetic field therapy, red light therapy for healing and consumption of supplements, electrolytes and energy drinks.

Age biohacking focuses on cellular senescence, or damaged cells. The goal is to improve longevity by inhibiting the production or reversing the process of cellular senescence and promoting cellular regeneration. Methods include red light therapy, stem cell therapy, cryotherapy, non-ablative laser therapy and consumption of antiaging and mitochondrial support supplements.

Brain biohacking combines exercise with nootropics to enhance cognitive efficiency. Other techniques include brainwave entrainment, transcranial magnetic stimulation therapy, neurofeedback therapy, brainwork and meditation.³

Learn more about how Dave Asprey, “The Father of Biohacking,” hacked his own health to transform his physicality, increase his IQ and reduce the total age of his biochemistry at ThinkNext International Seminar 2024.

References

Schroeder, K. (2022). Biohackers and DIY Gene Therapy. Front Line Genomics. Accessed June 2024 at https://frontlinegenomics.com/biohackers-and-diy-gene-therapy/
Merriam-Webster. (n.d.) Biohacking. In Merriam-Webster.com dictionary. Accessed June 2024 at https://www.merriam-webster.com/dictionary/biohacking#h1
Dutta, S.S. (n.d.) The Truth About Biohacking. News Medical Life Sciences. Accessed June 2024 at https://www.news-medical.net/health/The-Truth-About-Biohacking.aspx
Neumann, K.D. (2024) Biohacking: What Is It And How Does It Work? Forbes Health. Accessed June 2024 at https://www.forbes.com/health/wellness/biohacking/
Rasmussen, L. M., Guerrini, C. J., Kuiken, T., et al. (2020). Realizing Present and Future Promise of DIY Biology and Medicine through a Trust Architecture. The Hastings Center report, 50(6), 10–14. Accessed June 2024 at https://doi.org/10.1002/hast.1194
Berry, J. (2019) What are nootropics (smart drugs)? Medical News Today. Accessed June 2024 at https://www.medicalnewstoday.com/articles/326379

Potential Options for Migraine Patients

Wed, 12 Jun 2024 14:54:28 GMT

June is National Migraine and Headache Awareness Month and we want you to be well equipped to care for your migraine and headache patients.

by Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

Migraines affect roughly 14-15% of people globally each year and is just one of more than 200 headache disorders.¹ If you’ve ever been a migraine patient or treated a migraine patient, you know how challenging it can be to find the right treatment for acute migraines and the best prophylaxis for chronic migraines.

Acute Migraines

The current standard of care for acute migraine involves use of NSAIDs, ergotamine derivatives, triptans, gepants and ditans. Combination therapy with antiemetics and/or caffeine is also a mainstay of treatment.² With the loss of isometheptene from the market, many compounders have been searching for a replacement. Since there are so few options for treating migraines, losing an agent that is effective for some patients leaves a gap that can be difficult to fill.

In the PCCA Clinical Services department, we have recently helped many members find an alternative option for patients who were previously using isometheptene. The way that isometheptene is thought to work is by constricting the cranial arteries. Caffeine is another cranial vasoconstrictor, often used in migraine headache formulations.³For patients who were previously experiencing relief with isometheptene, caffeine would be a reasonable inclusion in their formula.

One of my favorite formulas to recommend for acute migraine is piroxicam 40 mg/ondansetron 2 mg/caffeine troches. The combination of ingredients treats pain and nausea associated with migraine headaches and may provide faster relief due to the route of administration. As an anhydrous formula, both compounders and patients can benefit from the potential of longer beyond-use dates (BUDs).*

Another unique compounding option for acute migraine is intranasal lidocaine, which has been shown to decrease pain intensity and the need for rescue medications. It has been used in varying concentrations of 4-10% in each nostril. The benefit of this formula is that it provides a non-oral, non-injectable route of administration that can be useful in patients experiencing significant nausea. Combining lidocaine with ketorolac in a nasal spray is another option that has been studied and found to have even greater pain relief than lidocaine alone.⁴ Before choosing this combination, it is important to remember that the use of ketorolac is limited to five days, regardless of route of administration. Evaluating the number of headache days per month that a patient has can help determine if this is an appropriate treatment.⁵

Migraine Prophylaxis

While the goals of therapy for acute migraine are to relieve symptoms as quickly as possible — with as few side effects as possible — we also need to avoid medication overuse headaches (a headache that results from the frequent use of acute medicines or painkillers).⁶ In any migraine patient, prevention is an important piece of the puzzle. Current migraine prophylaxis medications include beta-blockers (propranolol), anticonvulsants (valproate, topiramate), antidepressants (amitriptyline) and calcitonin gene-related peptide receptors (CGRPs) (erenumab).⁷ These prophylactic medications have varying success rates, with the new class of CGRPs having the greatest efficacy.⁸ Unfortunately, all of these medications come with the risk of adverse events and some come with a significant financial burden.

Alpha-lipoic acid and riboflavin are two agents that have been shown to help with migraine prophylaxis. A study found that a dose of riboflavin 400 mg/day for three months reduced headache days, as well as the duration, frequency and pain score of migraine attacks.⁹ Another study found similar results with alpha-lipoic acid 300 mg twice daily for 12 weeks.¹⁰ Alpha-lipoic acid has also been studied as a preventative agent in adolescents.¹¹A benefit of these two agents is that they are generally well-tolerated and may be less expensive than other options. These agents can be used alone or as an adjunct to other prophylactic measures.

Treatment Success

In helping your patients navigate migraine treatment and prophylactic options, there are some key strategies and counseling points to consider. Many patients expect full resolution of their migraine symptoms and frequency and may give up on a treatment option too soon if those expectations aren’t managed. Most prophylactic measures must be taken daily for at least two months before a determination can be made about the success of the treatment. Encourage patients to keep a headache diary to collect data about their headache days, severity and other details related to their migraines.⁶

As pharmacists, we are also uniquely placed to screen for potential medication overuse. Medication overuse headaches are typically seen in patients with 15 or more headache days per month. Most migraine prophylactics won’t be effective in these patients until they go through a detox period from acute migraine treatments.¹²The most effective detox programs for medication overuse headaches include complete withdrawal from acute treatments and initiation of preventative medications.^13,14

You have the opportunity to make a significant impact on the lives of your patients who suffer with debilitating headache disorders. This article covered just a few of the creative ways that compounding pharmacists are contributing to solutions for migraines.

PCCA members with clinical services access may contact our Clinical Services team for help when compounding for patients with migraines and other compounding concerns.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

References

Steiner, T. J., & Stovner, L. J. (2023). Global epidemiology of migraine and its implications for public health and health policy. Nature reviews. Neurology, 19(2), 109–117. Accessed May 2024 at https://doi.org/10.1038/s41582-022-00763-1
Ailani, J., Burch, R. C., & Robbins, M. S. (2021). The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache: The Journal of Head and Face Pain, 61(7), 1021–1039. Accessed May 2024 https://doi.org/10.1111/head.14153
Drugs.com (Last updated June 2023). Isometheptene, Caffeine, and Acetaminophen Tablets. Accessed May 2024 at https://www.drugs.com/pro/isometheptene-caffeine-and-acetaminophen-tablets.html
Chi, P. W., Hsieh, K. Y., Chen, K. Y., et al. (2019). Intranasal lidocaine for acute migraine: A meta-analysis of randomized controlled trials. PloS one, 14(10), e0224285. Accessed May 2024 at https://doi.org/10.1371/journal.pone.0224285
Pfaffenrath, V., Fenzl, E., Bregman, D., et al. (2012). Intranasal ketorolac tromethamine (SPRIX®) containing 6% of lidocaine (ROX-828) for acute treatment of migraine: Safety and efficacy data from a phase II clinical trial. Cephalalgia, 32(10), 766–777. Accessed May 2024 at https://doi.org/10.1177/0333102412451359
The Migraine Trust. (2021). Medication overuse headache. Accessed May 2024 at https://migrainetrust.org/understand-migraine/types-of-migraine/medication-overuse-headache/
Kumar, A., & Kadian, R. (2020). Migraine Prophylaxis. PubMed; StatPearls Publishing. Accessed May 2024 at https://www.ncbi.nlm.nih.gov/books/NBK507873/
Lampl, C., MaassenVanDenBrink, A., Deligianni, C.I. et al. The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis. J Headache Pain 24, 56 (2023). Accessed May 2024 at https://doi.org/10.1186/s10194-023-01594-1
Chen, Y.-S., Lee, H.-F., Tsai, C.-H., et al. (2021). Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis. Nutritional Neuroscience, 1–12. Accessed May 2024 at https://doi.org/10.1080/1028415X.2021.1904542
Kelishadi, M.R., Naeini, A.A., Khorvash, F. et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep 12, 271 (2022). Accessed May 2024 at https://doi.org/10.1038/s41598-021-04397-z
Puliappadamb, H. M., Satpathy, A. K., Mishra, et al. (2023). Evaluation of Safety and Efficacy of Add-on Alpha-Lipoic Acid on Migraine Prophylaxis in an Adolescent Population: A Randomized Controlled Trial. Journal of clinical pharmacology, 63(12), 1398–1407. Accessed May 2024 at https://doi.org/10.1002/jcph.2331
D'Amico, D., & Tepper, S. J. (2008). Prophylaxis of migraine: general principles and patient acceptance. Neuropsychiatric disease and treatment, 4(6), 1155–1167. Accessed May 2024 at https://doi.org/10.2147/ndt.s3497
Carlsen, L. N., Munksgaard, S. B., Jensen, R. H. et al. (2018). Complete detoxification is the most effective treatment of medication-overuse headache: A randomized controlled open-label trial. Cephalalgia : an international journal of headache, 38(2), 225–236. Accessed May 2024 at https://doi.org/10.1177/0333102417737779
Nielsen, M., Carlsen, L. N., Munksgaard, S. B., et al. (2019). Complete withdrawal is the most effective approach to reduce disability in patients with medication-overuse headache: A randomized controlled open-label trial. Cephalalgia, 39(7), 863–872. Accessed May 2024 at https://doi.org/10.1177/0333102419828994

Essential Supplements for Adults

Wed, 01 May 2024 19:37:37 GMT

In today's fast-paced world, maintaining optimal health can be a challenge. Despite the best intentions, many adults struggle to meet their nutritional needs through diet alone — that's where supplements can play a crucial role.

by Stephanie Allen, ASIN, DCN, DSS, CPES, Wellness Works Manager

Here are five supplements that adults should consider incorporating into their daily routine:

Multivitamin: According to the CDC, most Americans fall short of meeting their nutrient needs through diet alone. A high-quality multivitamin can help fill in the gaps, providing essential vitamins and minerals necessary for overall health and well-being.^1,2
Probiotic: A balanced microbiome in the gut is essential for digestive health, a robust immune system and even mood regulation. Probiotic supplements can help support the diversity of beneficial bacteria in the gut, promoting optimal gut function and overall wellness.^3-5
Fish Oil: Rich in omega-3 fatty acids EPA and DHA, fish oil supplements have been associated with numerous health benefits. The American Heart Association recommends a daily intake of at least 250 to 500 milligrams of EPA+DHA to support heart health and overall well-being.⁶
Vitamin D: Often referred to as the “sunshine vitamin,” vitamin D plays a crucial role in bone health, immune function and mood regulation. However, an estimated 88% of the population doesn't receive enough vitamin D from sunlight alone. Supplementation can help ensure adequate levels, especially for those who spend limited time outdoors or live in regions with limited sunlight.⁷
Magnesium: This essential mineral is involved in over 300 biochemical reactions in the body, including muscle function, nerve function and energy production. Despite its importance, studies suggest that approximately 75% of American adults don't meet the recommended daily intake of magnesium. Supplementation can help bridge this gap and support overall health and vitality.^8,9

While these supplements can be beneficial for many individuals, it's essential to remember that they are not a substitute for a balanced diet and healthy lifestyle. Additionally, it's always advisable to consult a healthcare professional before starting any new supplement regimen.

References

CDC. (Updated 2021). Only 1 in 10 Adults Get Enough Fruits or Vegetables. Accessed April 2024 at https://www.cdc.gov/nccdphp/dnpao/division-information/media-tools/adults-fruits-vegetables.html
U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020 - 2025. Accessed April 2024 at https://www.dietaryguidelines.gov/sites/default/files/2020-12/Dietary_Guidelines_for_Americans_2020-2025.pdf
Olvera-Rosales, L. B., Cruz-Guerrero, A. E., Ramírez-Moreno, E., et al. (2021). Impact of the Gut Microbiota Balance on the Health-Disease Relationship: The Importance of Consuming Probiotics and Prebiotics. Foods (Basel, Switzerland), 10(6), 1261. Accessed April 2024 at https://doi.org/10.3390/foods10061261
Appleton J. (2018). The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health. Integrative Medicine (Encinitas, Calif.), 17(4), 28–32. Accessed April 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469458/
Hemarajata, P., & Versalovic, J. (2013). Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therapeutic Advances in Gastroenterology, 6(1), 39–51. Accessed April 2024 at https://doi.org/10.1177/1756283X12459294
Williamson, L. (2023). Are you getting enough omega-3 fatty acids? American Heart Association News Stories. Accessed April 2024 at https://www.heart.org/en/news/2023/07/05/are-you-getting-enough-omega-3-fatty-acids
NIH Office of Dietary Supplements. (Updated 2023). Vitamin D Fact Sheet for Health Professionals. Accessed April 2024 at https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
Schwalfenberg, G. K., & Genuis, S. J. (2017). The Importance of Magnesium in Clinical Healthcare. Scientifica, 2017, 4179326. Accessed April 2024 at https://doi.org/10.1155/2017/4179326
DiNicolantonio, J. J., O'Keefe, J. H., & Wilson, W. (2018). Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open Heart, 5(1), e000668. Accessed April 2024 at https://doi.org/10.1136/openhrt-2017-000668

These statements have not been evaluated by the Food and Drug Administration. Products referenced in this article are not intended to diagnose, treat, cure or prevent any disease.

Decoding the Intricacies of Infertility

Wed, 24 Apr 2024 15:48:11 GMT

In recognition of National Infertility Awareness Week, April 21-27, PCCA Director of Clinical Services Sara Hover, RPh, FAARM, discusses how fertility is increasingly viewed as an indicator of overall health; how the intertwine of metabolic balance, hormone production and mitochondria impact fertility; as well as a way compounders can help those whose individual needs exceed commercially available medicines.

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

In the complicated web of human biology, fertility stands as a vital sign, signaling the well-being of our reproductive health, as well as our overall health. Yet, behind the veil of conception lies a labyrinth of factors — from genetics to lifestyle — and even the most minute cellular processes. Infertility, a silent struggle for many, sheds light on the multifaceted nature of reproduction, intertwining with metabolic health, regulation of hormones — including estrogen and progesterone — mitochondrial function, as well as the important role that melatonin plays.

Fertility as a Vital Sign

Traditionally, vital signs such as heart rate, blood pressure and body temperature have served as indicators of overall health. However, fertility, often overlooked in routine medical assessments, is increasingly recognized as another crucial marker of well-being.¹ Heavy cramping is a red flag that there is a problem with nutrients, like magnesium, as well as a problem with the gut or hormonal imbalance.² While the ability to conceive may seem solely reproductive, it reflects broader physiological harmony within the body.

Reproduction and Metabolic Health

The interplay between reproductive health and metabolic well-being is profound. Research suggests that conditions such as obesity, insulin resistance and diabetes can significantly impact fertility. Metabolic imbalances disrupt hormonal equilibrium, impairing ovulation in women and sperm production in men.³Furthermore, excess adipose tissue can lead to the overproduction of estrogen, disrupting the delicate hormonal dance essential for conception.

Hormonal Balance

Estrogen and progesterone prepare the uterus for implantation. The changes that occur in the uterus have been termed endometrial receptivity. The window that is optimal for implantation of a fertilized egg is very narrow and for those patients with luteal phase defect — when the body prepares the uterus for pregnancy — the chances of being successful are greatly diminished.⁴Many women rely on progesterone to supplement the luteal phase of their cycle. Although there are many commercial product options, some may require a compounded prescription to meet their individual needs.

Adhering to the Vaginal Mucosa

Getting the hormone to adhere to the mucosal tissue is important, especially with progesterone and its need to maintain contact with the endometrium. One of our bases, MucoLox™ (PCCA #30-4782), is the perfect delivery vehicle because it adheres to the vaginal mucosal tissue, thereby increasing contact time with the mucosal surfaces. This makes it an ideal choice for use in vaginal compounded preparations.⁵

The Role of Mitochondria

Within the intricate machinery of cellular function, mitochondria emerge as powerhouse organelles crucial for energy production. Surprisingly, these tiny structures play a pivotal role in fertility. Mitochondria provide the energy needed for sperm motility, egg maturation and embryo development. Any compromise in mitochondrial function can undermine reproductive success, highlighting the intricate link between cellular health and fertility.^6,7

Mitochondria and Melatonin

Melatonin, often associated with sleep regulation, exerts profound effects on reproductive function. Emerging research suggests that melatonin receptors are present in the ovaries, testes and placenta, indicating involvement in reproductive processes. Moreover, melatonin's antioxidant properties safeguard reproductive cells from oxidative stress, essential for maintaining integrity and viability. Disruptions in melatonin signaling, whether due to sleep disturbances or environmental factors, can adversely affect fertility.^8-10

Putting It All Together

Infertility transcends mere reproductive challenges; it illuminates the intricate interplay between our bodies' myriad of systems. Understanding fertility as a vital sign underscores its significance in gauging overall health. From metabolic balance to mitochondrial function and the regulation of hormones like estradiol, progesterone and melatonin, every aspect of our physiology contributes to the delicate dance of conception. By unraveling the complexities of infertility, we pave the way for more holistic approaches to reproductive health, ensuring that every individual has the opportunity to embark on the journey of parenthood if desired.

References

Su, R.W., Fazleabas, A.T. (2015). Implantation and Establishment of Pregnancy in Human and Nonhuman Primates. Adv Anat Embryol Cell Biol.216:189-213. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/26450500/
Naraoka, Y., Hosokawa, M., Minato-Inokawa, S., et al. (2023). Severity of Menstrual Pain Is Associated with Nutritional Intake and Lifestyle Habits. Healthcare (Basel). 11(9):1289. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/37174831/
Marinelli, S., Napoletano, G., Straccamore, M., et al. (2022). Female obesity and infertility: outcomes and regulatory guidance. Acta Biomed. 93(4):e2022278. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/36043953/
Lessey, B.A., Young, S.L. (2019). What exactly is endometrial receptivity? Fertil Steril. 111(4):611-617. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/30929718/
PCCA Science. (2015). Evaluation of the Safety and Toxicological Profile of MucoLox: Human Oral Mucosa, Nasal Mucosa and Vaginal Mucosa (Part 3/3). PCCA Document #98929
Beikoghli, K.S., Kararigas G. (2022). Oestrogenic Regulation of Mitochondrial Dynamics. Int J Mol Sci. 23(3):1118. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/35163044/
May-Panloup, P., Chretien, M-F., Malthiery, Y., et al. (2007). Mitochondrial DNA in the Oocyte and the Developing Embryo. Curr Top Dev Biol. 77:51-83. Accessed April 2024 at https://www.sciencedirect.com/science/article/abs/pii/S007021530677003X?via%3Dihub
Reiter, R.J., Sharma, R., Romero, A,, et al. (2023). Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue. Antioxidants (Basel). 12(3):695. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/36978942/
Batıoğlu, A.S., Sahin, U., Gürlek, B., et al. (2012). The efficacy of melatonin administration on oocyte quality. Gynecol Endocrinol. 28(2):91-3. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/21770829/
Tamura ,H., Takasaki, A., Miwa, I., et al. (2008). Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res. 44(3):280-7. Accessed April 2024 at https://pubmed.ncbi.nlm.nih.gov/18339123/

Detoxification in the New Year

Wed, 03 Jan 2024 15:37:00 GMT

by Stephanie Allen, ASIN, DCN, DSS, CPES, Wellness Works Manager

Toxic Exposure

Everything from clothing and furniture to the air and soil has some level of chemical contaminants that can be harmful to health. Many of these are deemed “safe” individually and in very small volumes, but they build up over time. Multiple exposures to combinations of many different chemical toxins can lead to health problems such as metabolic syndrome.

Toxins are often stored in the adipose tissues and released back into circulation during weight loss, increasing autoimmune responses and leading to feelings of fatigue, increased allergies and illness. Therefore, a quality detoxification protocol is also an important part of any weight loss program.

To lessen the exposure and subsequent toxic load in the body, adopting a healthful diet that is low in processed foods, preservatives and pesticides is a good first step. Choose organic fruits and vegetables whenever possible. Decreasing any unnecessary over-the-counter medications, limiting alcohol intake and avoiding any nicotine products are very important steps to lessen the burden on the body. We are also unnecessarily exposed to foreign chemicals through our personal-care products. The United States allows more than 1,600 chemicals in personal care products that are banned in most of Europe due to health concerns.¹ We should regularly review used hygiene products, cosmetics and fragrances that may increase toxic exposure.

The Environmental Working Group is a great resource and contains lists of fruits and vegetables with the least and most pesticide, as well as information on toxins in personal care and cosmetic products. The regularly updated lists can be viewed on their website at ewg.org.

Boosting the Body’s Natural Processes

Lessening exposure to environmental toxins and chemicals is only part of decreasing our toxic load for optimal health. Boosting the body’s natural ability to process and eliminate toxins is another necessary step. Processes and metabolic systems of the kidneys, skin, liver and lungs, for example, rid the body of foreign chemicals. Movement and exercise, especially activities that generate sweat, are a great way to help promote clearing through increased lymph flow and cleansing through the pores in the skin. Steam baths and warm showers are a great way to destress and detox too, and increased water consumption helps eliminate broken-down toxins from the body.

Diet is also crucial. Cruciferous vegetables contain indole-3-carbinol (I3C), a strong antioxidant shown to improve detoxification processes and promote healthy metabolic pathways. Increased consumption of colorful vegetables also provides beneficial antioxidants that counteract free radicals formed when toxins break down. Some great dietary additions include blueberries, broccoli and Brussels sprouts. Herbal teas that contain dandelion, milk thistle, ginger, rooibos, green tea and burdock — or any combination of these — will provide chemicals and compounds that assist in detoxification. Beware of detox teas that contain large amounts of senna. Senna is a natural laxative and may lead to dehydration or poor absorption of needed nutrients if used too often or in too large a dose.

Adding Nutritional Supplements

Ingesting enough fiber is also paramount for clearing foreign materials. The Wellness Works combination product, Colon Health Support (WW #10370), is a proprietary blend of fibers, fructooligosaccharides (FOS), pectin and detoxifying herbs, as well as ingredients that support the detoxifying and cleansing pathways. Glutathione is a powerful antioxidant that helps clear free radicals that form during the breakdown of toxins, as well as supports the regeneration of antioxidants in the body. The liposomal form available in Liposomal Glutathione (WW #10325) — provided in a purified phosphatidylcholine delivery system — helps protect glutathione bonds from degradation during digestion. The liposomal delivery system also offers enhanced absorption due to the hydrophilic nature of the phospholipids. Studies have shown that the Setria^® glutathione, available in L-Glutathione Reduced (WW #10389), supports enhanced immune cell function and increases levels of glutathione in the blood. Liposomal Glutathione and L-Glutathione Reduced are good options to add into a detoxification routine or for daily use.

Milk thistle provides silymarin, a highly active botanical that works to protect the liver from free radical damage and supports glutathione concentrations. In addition to herbal teas, milk thistle is also available in Milk Thistle Plus (WW #10110). Our supplement provides 175 mg of milk thistle extract and is standardized to contain a minimum of 80% silymarin.

During the holidays, it is also common to overindulge in alcohol. For those looking to specifically provide the body with the depleted nutrients caused by excessive drinking or limit its impact with nutrients prior to alcohol consumption, we offer Alcohol Detox (WW #10395). Our Alcohol Detox formula combines micronutrients and cofactors essential to supporting healthy liver function and proper alcohol metabolism.²

References

Zhou, L., Martiner, J. (2022, Oct. 25) Personal care product chemicals banned in Europe but still found in U.S. Accessed November 2022 at https://www.ewg.org
Lieber C. S. (2003). Relationships between nutrition, alcohol use, and liver disease. Alcohol Res Health. 2003;27(3):220-231. (3), 220–231. Accessed November 2022 at https://pubmed.ncbi.nlm.nih.gov/15535450/

These statements have not been evaluated by the Food and Drug Administration. Products referenced in this article are not intended to diagnose, treat, cure or prevent any disease.

Hypogonadism & Men’s Health

Wed, 27 Sep 2023 13:17:52 GMT

Hypogonadism in men is primarily a state involving lower than expected levels of testosterone. Traditionally, the condition has been treated almost exclusively with testosterone supplementation. However, low testosterone can be fairly complex, involving a myriad of factors including the inability of the testes to produce sufficient testosterone, improper brain signaling and excess estrogen.

Primarily seen as female hormones, estrogens are also very important in men since declining testosterone can alter the androgen:estrogen (T:E2) relationship. While there is not an established target value, changes in the T:E2 ratio can result in complications such as declining prostate health.¹

In some men, clear reasons behind low testosterone can be difficult to determine. The consequences, however, can be the same: insufficient testosterone that results in an unhealthy life, often characterized by symptoms such as loss of libido, erectile dysfunction, hair loss, depressed mood and lethargy. After proper diagnosis, including testing for testosterone, estrogen and luteinizing hormone (LH), properly directed therapy might dramatically reverse these symptoms and provide a healthier, more robust lifestyle.

Least Invasive Estrogen Reduction

For many men, the simplest and least invasive ways to reduce estrogen levels are to lose weight, replace fatty diets with low-fat alternatives and engage in regular exercise. This is because aromatase, an enzyme responsible for converting testosterone to estradiol (as well as converting androstenedione to estrone) is more abundant in adipose tissue. Adipose tissue can also affect the secretion of gonadotropin, which influences the formation of androgen in the testes.²

Three specific nutrients appear to be particularly useful in elevating low testosterone: magnesium, vitamin D and zinc. Magnesium supplementation was shown to increase free and total testosterone, with even higher increases in men who supplemented magnesium and exercised regularly.³Additionally, a study showed an association between vitamin D levels and testosterone levels (i.e., men who had low vitamin D levels frequently also had low levels of testosterone).⁴ And lastly, a study proved low zinc levels correlated with low testosterone levels; restoration of the zinc deficiencies restored testosterone levels.⁵

Wellness Works recently launched nutritional supplements specifically designed to support men’s health. Nutritional supplements include Men’s Complete Whole Food Multi, Male Virility Support and Prostate Health Support.

Testosterone Supplementation

For many men, testosterone supplementation is the treatment of choice — it is easily understood and, when properly administered, can be very effective in boosting testosterone levels. However, a decrease in sperm production is common in testosterone supplementation. Therefore, in men who wish to maintain their fertility and testicular size, options to boost testosterone production, rather than supplementation itself, should be considered.

Topical administration appears to be the most effective way of dosing testosterone. While creams, solutions and lotions have been used, over the past dozen years the greatest benefit seems to come from topical gels.

Testosterone is a lipophilic steroid hormone and is absorbed well in topical preparations. The delivery system, however, absolutely makes a difference. An alcohol-free compounding base, such as Atrevis Hydrogel®, eliminates the possibility of skin irritation. In addition, alcohol evaporates, which causes the concentration of the gel to change and may cause variations in dosage. Atrevis is a water-based gel with specific penetration enhancers that help drive the testosterone through skin. The skin-permeation enhancers, one of which is patented, improve the solubility and dispersibility of testosterone, making it easier to be absorbed.

Daily topical dosing with testosterone in Atrevis helps maintain steady-state levels: The patient will likely not have the peak-and-valley experience that is common with testosterone injections. I suggest starting with 50 mg topically in Atrevis with an expected topical dose range of 40–120 mg daily. Transfer to a child or female is a risk of topical dosing and every precaution should be taken to mitigate that risk.

Members with clinical services access may contact our Clinical Services team for help with compounding preparations for low testosterone levels in men and other compounding concerns.

This Blog is a compilation of several PCCA Documents (#99637, #99533, #99198, #98474 and #97028) authored by retired PCCA Clinical Compounding Pharmacist Bruce Biundo, RPh, FACA, and reviewed by Sara Hover, RPh, FAARM, PCCA Clinical Services Manager. Members may access these and other documents at Members-Only Website > Documents.

Everyone is invited to listen to The Mortar & Pestle podcast, “Men’s Health: Testosterone with Bruce Biundo,” broadcasted on August 17, 2023, where Bruce discusses new major studies — including the TRAVERSE Study that reviews testosterone and cardiovascular risk. You can also access the podcast on your device using your favored podcast application.

References

Lee, H. K., Lee, J. K., & Cho, B. (2013). The role of androgen in the adipose tissue of males. The world journal of men's health, 31(2), 136–140. https://doi.org/10.5534/wjmh.2013.31.2.136
Prins, G. S., & Korach, K. S. (2008). The role of estrogens and estrogen receptors in normal prostate growth and disease. Steroids, 73(3), 233–244. https://doi.org/10.1016/j.steroids.2007.10.013
Cinar, V., Polat, Y., Baltaci, A.K., & Moqulkoc, R. (2011). Effects of magnesium supplementation on testosterone levels of athletes and sedentary subjects at rest and after exhaustion. Biological Trace Elements Research, 140(1), 18-23. doi:10.1007/s12011-010-8676-3
Lee, D.M., Tajar, A., Pye, S.R., Boonen, S., Vanderschueren, D., Bouillon, R., Wu, F.C. (2012). Association of hypogonadism with vitamin D status: the European Male Ageing Study. European Journal of Endocrinology, 166(1), 77-85. doi:10.1530/EJE-11-0743
Prasad, A.S., Mantzoros, C.S., Beck, F.W., Hess, J.W., & Brewer, G.J. (1996). Zinc status and serum testosterone levels of healthy adults. Nutrition, 12(5), 344-348.

Supporting the Immune System

Wed, 23 Aug 2023 13:51:46 GMT

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

In today's world, where the threat of diseases and infections looms large, it comes as no surprise that people are increasingly interested in boosting their immune system and strengthening their natural defense mechanisms. The immune system, a complex network of cells, tissues and organs, plays a pivotal role in protecting the body against harmful pathogens and maintaining overall health. Its importance cannot be overstated, as a robust immune system not only helps ward off infections but also promotes faster recovery while supporting long-term well-being. As individuals strive to lead healthier lives and safeguard themselves from illnesses, the quest for enhancing immunity has become a priority, driven by a deep understanding of the crucial role the immune system plays in maintaining vitality and resilience.

One of the key aspects of immunity that has garnered significant attention is its intricate connection with inflammation. Inflammation, typically a natural response to injury or infection, is a crucial component of the immune system's defense mechanism. It involves the release of various immune cells, chemicals and hormones to combat harmful agents and initiate the healing process. However, when inflammation becomes chronic or dysregulated, it can have detrimental effects on the body. Chronic inflammation has been linked to a range of health issues, including autoimmune disorders, cardiovascular diseases and even certain types of cancer. Therefore, individuals are motivated to improve their immune function not only to enhance protection against pathogens but also to maintain a balanced inflammatory response, fostering a state of optimal health and well-being.

Dietary modifications have emerged as a powerful tool in managing inflammation and promoting a healthy immune system. Certain foods possess anti-inflammatory properties and can help reduce excessive inflammation in the body. Incorporating a diet rich in fruits, vegetables, whole grains and lean proteins provides essential nutrients, antioxidants and phytochemicals that support immune function and help combat inflammation. Omega-3 fatty acids found in fatty fish, flaxseeds and chia seeds have been shown to possess potent anti-inflammatory effects. Similarly, spices like turmeric, ginger and garlic contain compounds that can help reduce inflammation. On the other hand, processed foods, sugary beverages and excessive consumption of saturated fats and trans fats can promote inflammation and weaken the immune system.

In addition to dietary modifications, there are some key supplements that have shown promise in decreasing inflammation and supporting the immune system. One of these is palmitoylethanolamide (PEA). PEA is an endocannabinoid receptor agonist that is found in all tissues, including the brain. It is naturally produced as a direct response to inflammatory markers, promoting healthy function of the body’s endocannabinoid system and maintaining cellular homeostasis. PEA is produced “on demand” in response to actual or potential damage for protective purposes. However, with age or chronic inflammation, endogenous production of PEA is generally insufficient to meet the required needs. Supplementing with PEA may help patients decrease inflammation and enhance their immune system. Interestingly, the use of PEA dates back to the 1960s, when it was first marketed for prophylactic treatment of influenza and the common cold.

Pro-resolving lipid mediators (PRMs) are another key supplement that can help support the immune system. PRMs encourage the production of specialized pro-resolving mediators (SPMs) in the body. SPMs are unique molecules that promote a healthy response to physical stress and play extensive roles in host defense, tissue remodeling and organ support. Recent studies suggest that in disease, SPM production becomes dysregulated, which may hinder the body’s ability to effectively resolve an immune response that can impact overall wellness. SPMs have been shown to signal the immune system to stop actively responding to pro-inflammatory signals and accelerate the return to homeostasis. They have even been shown to facilitate the resolution of prolonged or chronic inflammation. Supplementing with PRMs and the subsequent increase in SPMs can result in an improved resilience in recovery from injury, inflammation and/or disease.

Wellness Works’ Factor Series features PEAk Factor (WW #10422) and Resilience Factor (WW #10415). PEAk Factor contains 300 mg of bioavailable PEA (Levagen®+) and 150 mg alpha lipoic acid (ALA) per capsule. Levagen®+, powered by LipiSperse®, helps to increase absorption by reducing surface tension. It effectively eliminates the usual size absorption problems with standard PEA particles. A pharmacokinetics study revealed that Levagen®+ had 1.8 times more bioavailability compared to standard PEA. Resilience Factor is formulated with 400 mcg of PRMs derived from fractionated marine lipids that are both molecularly distilled and put through a supercritical extraction process for purity. Both PEAk Factor and Resilience Factor can help restore immune balance and resolution of immune responses, which are critical for optimal health.

References

Petrosino S., Schiano Moriello A. (2020) Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries-A Systematic Review. Int J Mol Sci. 15;21(24):9526. Accessed May 2023 at https://pubmed.ncbi.nlm.nih.gov/33333772/
Rankin L., Fowler C.J. (2020) The Basal Pharmacology of Palmitoylethanolamide. Int J Mol Sci. 26;21(21):7942. Accessed May 2023 at https://pubmed.ncbi.nlm.nih.gov/33114698/
Clayton P., Hill M., Bogoda N., et al. (2021) Palmitoylethanolamide: A Natural Compound for Health Management. Int J Mol Sci. 18;22(10):5305. Accessed May 2023 at https://pubmed.ncbi.nlm.nih.gov/34069940/
Petrosino S., and Di Marzo V. (2017) The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. British Journal of Pharmacology, 174: 1349– 1365. Accessed May 2023 at https://pubmed.ncbi.nlm.nih.gov/27539936/
Norling L.V., Ly L., Dalli J. (2017) Resolving inflammation by using nutrition therapy: roles for specialized proresolving mediators. Curr Opin Clin Nutr Metab Care. 20(2):145-152. Accessed May 2023 at https://pubmed.ncbi.nlm.nih.gov/28002074/
Silverman, R. (2017) Specialized pro-resolving mediators: A new tool for resolving inflammation. Integrative Practitioner. Accessed May 2023 at https://www.integrativepractitioner.com/about/integrative-healthcare-symposium/specialized-pro-resolving-mediators-new-tool-resolving-inflammation

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

The Art and Science of Topical Minoxidil Formulas

Wed, 26 Jul 2023 12:55:17 GMT

by Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist, and Fabiana Banov, RPh, MS, PCCA Senior Formulation Pharmacist

Minoxidil is the number one ingredient used in topical hair restoration formulas worldwide since hypertrichosis was discovered as an adverse event when minoxidil was used to treat hypertension. It is the only topical active pharmaceutical ingredient (API) that is FDA approved for androgenic alopecia in both men and women.

Biomarker for Efficacy

Minoxidil is a pro-drug requiring bioactivation into minoxidil sulfate. The enzyme that catalyzes this reaction in the hair follicle is minoxidil sulfotransferase (SULT1A1).¹ Due to the prolonged duration of therapy required (approximately 6 months) for an effective response, expression of SULT1A1 as a biomarker for predicting treatment response can be an important predictive clinical tool. Studies show that sulfation is a critical step for the hair-growth effects of minoxidil and that the sulfated metabolite directly affects hair follicles.

Assays of SULT1A1 activity indicated that vibrissae follicles metabolize minoxidil to minoxidil sulfate. Dose-response studies showed that minoxidil sulfate is 14 times more potent than minoxidil in stimulating cysteine incorporation in cultured follicles.² Variations between individuals in sulfotransferase activity may be the cause of the discrepancy in minoxidil efficiency.³

Known & Unknown Mechanism of Action

Minoxidil shortens the telogen phase, causing the follicles to prematurely enter the anagen phase, which may induce telogen effluvium after the initiation of therapy. It also extends the duration of the anagen phase and increases both hair length and diameter. This effect takes about eight weeks to occur and maximizes after four months.

Minoxidil appears to act on the potassium channels of vascular smooth muscles and hair follicles, which may induce the following effects:

Stimulation of the microcirculation near the hair follicles by inducing arteriolar vasodilation, which may cause hair growth.
Induction of vascular endothelial growth factor (VEGF) expression, which increases vascularization around the hair follicles and contributes to hair growth.
Activation of the prostaglandin-endoperoxide synthase, one of which stimulates hair growth.
Inhibition of androgen, which affects the androgen-sensitive hair follicles.
Direct stimulation of the hair follicles: minoxidil may act as an “epidermal growth factor” on matrix cells and delay their aging, thus prolonging the duration of the anagen phase via the activation of the beta-catenin pathway.⁴

Oral vs. Topical

In a study conducted on 435 people using oral minoxidil, 2% experienced postural hypotension and 8% had general symptoms of lightheadedness. Of those experiencing lightheadedness, 11% needed to stop treatment. Although the study authors concluded oral minoxidil is effective at stimulating hair growth, adverse events occurred: 93% experienced hypertrichosis, 10% experienced pedal edema and 10% experienced ECG alteration. The authors also noted these adverse events were not seen in people using topical minoxidil in previous studies.⁵

Androgenic alopecia (AA) is one of the most common chronic problems seen by dermatologists. When treating AA in men or women, suppression of the 5α-reductase-driven conversion of testosterone to dihydrotestosterone (DHT) is essential in controlling the stimulation of the hair loss. As such, the addition of a 5α-reductase inhibitor to formulas is necessary for long-term treatment success.

Formula APIs

For this reason, additional APIs used in combination with minoxidil in compounded formulas include finasteride, dutasteride, azelaic acid, progesterone (the body’s own natural 5α-reductase inhibitor), tretinoin, latanoprost, clobetasol propionate, melatonin and others, with finasteride used most often. Finasteride has shown synergism with minoxidil, resulting in significant increase in hair counts when combined with topical minoxidil, with maintenance of good hair density in combination with topical 5% minoxidil.^6,7

Tretinoin is another valuable API for these formulations because it enhances sulfotransferase activity. It is also known as a keratolytic and is believed to enhance minoxidil penetration.⁸

Compounding Preparations

Minoxidil may appear as a challenging API when compounding preparations. The API is prone to crystallization, insolubility, pH instability, precipitation and more. As such, it is important to use the correct PCCA formula and PCCA ingredient, or combination of PCCA ingredients, to ensure a more stable preparation.

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

References

Pietrauszka, K., & Bergler-Czop, B. (2022). Sulfotransferase SULT1A1 activity in hair follicle, a prognostic marker of response to the minoxidil treatment in patients with androgenetic alopecia: a review. Postepy dermatologii i alergologii, 39(3), 472–478. Accessed May 2023 at https://doi.org/10.5114/ada.2020.99947
Buhl, A. E., Waldon, D. J., Baker, C. A., & Johnson, G. A. (1990). Minoxidil sulfate is the active metabolite that stimulates hair follicles. J Invest Dermatol.95(5), 553–557. Accessed May 2023 at https://doi.org/10.1111/1523-1747.ep12504905
Freire, P. C. B., Riera, R., Martimbianco, A. L. C., et al. (2019). Minoxidil for patchy alopecia areata: systematic review and meta-analysis. J Eur Acad Dermatol Venereol: JEADV, 33(9), 1792–1799. Accessed May 2023 at https://doi.org/10.1111/jdv.15545
Talel, B., Nessel, T.A., Kumar, D. (Updated February 21, 2023) Minoxidil. NIH StatPearls [Internet]. Accessed May 2023 at https://www.ncbi.nlm.nih.gov/books/NBK482378/
Sanabria, B., Vanzela, T. N., Miot, H. A., et al. (2021). Adverse effects of low-dose oral minoxidil for androgenetic alopecia in 435 patients. J Am Acad Dermatol, 84(4), 1175–1178. Accessed May 2023 at https://doi.org/10.1016/j.jaad.2020.11.035
Tanglertsampan C. (2012). Efficacy and safety of 3% minoxidil versus combined 3% minoxidil / 0.1% finasteride in male pattern hair loss: a randomized, double-blind, comparative study. J Med Assoc Tha, 95(10), 1312–1316. Accessed May 2023 at https://pubmed.ncbi.nlm.nih.gov/23193746/
Chandrashekar, B. S., Nandhini, T., Vasanth, V., Sriram, R., et al. (2015). Topical minoxidil fortified with finasteride: An account of maintenance of hair density after replacing oral finasteride. Indian Dermatol Online J, 6(1), 17–20. Accessed May 2023 at https://doi.org/10.4103/2229-5178.148925
Sharma, A., Goren, A., Dhurat, R., et al. (2019). Tretinoin enhances minoxidil response in androgenetic alopecia patients by upregulating follicular sulfotransferase enzymes. Dermatol Ther, 32(3), e12915. Accessed May 2023 at https://doi.org/10.1111/dth.12915

How to Establish Yourself as a Men’s Health Consultant

Wed, 22 Jan 2020 18:52:35 GMT

By Bruce Biundo, RPh, FACA, PCCA Clinical Compounding Pharmacist

Where do your male patients get their information about testosterone? About prostate health? About supplements that may help them? From my own observations, many are hearing about these things from ads running on sports talk shows, the internet or other non-medical sources. Listening to and reading some of these advertisements, I see how many men can form unrealistic notions of what “natural testosterone boosters” can do for them, or even what the appropriate and expected benefits of testosterone itself would be. And how about your physicians? While many of them are interested in helping these male patients, they may find it difficult to keep up with what you, the pharmacist, can offer them in terms of treatment options, such as who is a good candidate for testosterone, who is not and what kinds of dosing options you can provide.

Very importantly, you are likely interested in how you can initiate or increase these services to help your pharmacy improve profitability in these challenging times. As a former independent pharmacy owner myself, and longtime community pharmacist, I am very interested in helping you help your bottom line by becoming more established as a men’s health consultant. So let’s take a look at what is involved.

Have Men’s Health Information Readily Available
There are numerous sources of useful information that can help your male patients become more knowledgeable about men’s health issues. A couple books that can be very helpful are Testosterone for Life, by Abraham Morgentaler, MD, and Saving Your Sex Life, by John P. Mulhall, MD. These can be great references for you and your patients. I also find the monthly magazine Men’s Health often provides useful, up-to-date news that both you and your patients can find beneficial. With either the books or the magazine, your male patients will likely become better informed and more interested in what your pharmacy provides.

Offer Private Patient Consultation
Well-established by many pharmacists over the past 20+ years, a private consultation can be a key component in your practice. You should have an appropriate setting for this, preferably a private room, which enhances the patient’s comfort level. You should also charge appropriate professional fees for this service — for example, $60–$100 for a 20–30 minute session, more for consults lasting up to an hour. It is not uncommon for consultation fees of $175–$200 for those of sufficient skills. If you do this on a regular basis and become proficient at it, private consultations can become a lucrative part of your practice.

A typical session could include a brief discussion on testosterone, a review of the patient’s laboratory values and then a walk-through of the patient’s screening form, which he would have previously filled out. During this time, the patient will be free to ask questions on the topic, and in this environment, you, the pharmacist, can satisfy the concerns expressed. The consultation concludes with you making a therapeutic recommendation to the patient’s physician and, often, a specific recommendation to the patient for nutritional supplements. These supplements, of course, are items that your pharmacy could offer, so the patient would be able to get exactly what you recommend.

Offer Nutritional Supplements
There are many excellent products out there that are very helpful, but I want to mention three specific nutrients that appear to be particularly useful relative to male hypogonadism, or low testosterone: magnesium, vitamin D and zinc. A study showed that magnesium supplementation increased free and total testosterone, with even higher increases in men who supplemented magnesium and exercised regularly.¹ Another study showed an association between vitamin D levels and testosterone levels (i.e., men who had low vitamin D levels frequently also had low levels of testosterone).² Other articles have shown the same association. And lastly, researchers have correlated zinc status with testosterone levels; specifically, low zinc levels correlated with low testosterone levels, and restoration of the zinc deficiencies restored testosterone levels.³

Wellness Works offers professional-quality nutritional supplements for pharmacies to offer their customers, including magnesium chelate tablets, magnesium glycinate powder, vitamin D softgels, zinc monomethionine tablets and zinc lozenges.

Keep up with Testosterone Supplementation Updates
The use of testosterone by injection has been long studied; what is newer is the interest in subcutaneous injections of testosterone. An article by Kaminetsky, Jaffe and Swerdloff revealed that patients obtained consistently high levels of testosterone with 100 mg subcutaneously, as contrasted with the bi-weekly intramuscular (IM) dose of 200 mg. They cited patient comfort and convenience as advantages over the more conventional IM dosing.⁴ Subcutaneous dosing has become much more common in recent years, and may be an excellent alternative to IM injections.

At PCCA, we get many calls on sublingual dosing of testosterone as well, and it seems to be increasing in preference compared with the past use. Sublingual dosing has unique characteristics. Because of the rapid absorption and relatively short half-life of testosterone, it is best done several times a day at doses of 15–25 mg, as opposed to high doses once a day. The difference can be readily seen in measured hormone levels: high doses produce very high testosterone levels, but for relatively short periods of time. Better to do a lower dose several times a day, as that will be more like the body’s usual production than the high, once-a-day dose. PCCA members can see our recommended dosing-range chart for various dosage forms.

However, do you give testosterone to all men who are clearly symptomatic and low on measured levels? No. Consider the age of the patient, and inquire as to his desire to maintain fertility. Testosterone supplementation can definitely suppress spermatogenesis, resulting in decreased fertility. Consider clomiphene for those men who are low in testosterone but want to maintain fertility.⁵ Another useful agent is anastrozole, widely used as an aromatase inhibitor, which can block the production of estrogen. Given the strong influence that estradiol has in the production/suppression of the messenger hormone responsible for testosterone production, anastrozole has also shown to be somewhat useful in increasing the production of testosterone in many men.⁶ It may be considered as an alternative to clomiphene in that regard.

PCCA members with Clinical Services access can view related testosterone formulas in our database, including some in Atrevis Hydrogel®.

Develop Collegial Relationships with Physicians
This is probably the most important part of establishing yourself as a men’s health consultant: forming and maintaining professional, mutually beneficial relationships with physicians and other health care providers who are interested in working with you in caring for patients. Fortunately, doctors want your knowledge, your skills and your ability to offer useful solutions to their patients’ needs. And we help PCCA members by offering treatment options, treatment documents and up-to-date information, all of which they can share with practitioners. PCCA members can see our concise yet wide-ranging Male Hypogonadism Packet for discussion of what is involved in treating male patients with low testosterone.

I advise PCCA members to also look at our newly revised Men’s Health Reference Guide, which meticulously indexes and provides links to abstracts for over seven hundred clinical articles. I think they will find it a valuable resource for their toolkits.

Finally, always remember that we are just one call away for PCCA members with Clinical Services access. For questions, they can contact our team of clinical compounding pharmacists at 800.331.2498.

Bruce Biundo, RPh, FACA, PCCA Clinical Compounding Pharmacist, joined the PCCA staff in 1997 after many years as a community pharmacist. In 1998, as PCCA was beginning to develop educational seminars, he realized that there wasn't much focus on men and testosterone issues, and began research on the subject. In April 1999, Bruce presented what is likely the first educational event on low testosterone in men at the PCCA International Seminar. Over the years, he has made presentations at dozens of hormone seminars to physician groups locally and internationally, and has many articles published, mostly dealing with men’s health. In addition, he was a contributor to Remington: The Science and Practice of Pharmacy, 22nd edition, and is the co-author of the nutrition chapter in Aging Men's Health.

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

References

Cinar, V., Polat, Y., Baltaci, A. K., & Moqulkoc, R. (2011). Effects of magnesium supplementation on testosterone levels of athletes and sedentary subjects at rest and after exhaustion. Biological Trace Elements Research, 140(1), 18–23. https://doi.org/10.1007/s12011-010-8676-3
Lee, D. M., Tajar, A., Pye, S. R., Boonen, S., Vanderschueren, D., Bouillon, R., … Wu, F. C. (2012). Association of hypogonadism with vitamin D status: the European Male Ageing Study. European Journal of Endocrinology, 166(1), 77–85. https://doi.org/10.1530/EJE-11-0743
Prasad, A. S., Mantzoros, C. S., Beck, F. W., Hess, J. W., & Brewer, G. J. (1996). Zinc status and serum testosterone levels of healthy adults. Nutrition, 12(5), 344–348.
Kaminetsky, J., Jaffe, J. S., & Swerdloff, R. S. (2015). Pharmacokinetic profile of subcutaneous testosterone enanthate delivered via a novel, prefilled single-use autoinjector: A phase II study. Sexual Medicine, 3(4), 269–279. https://doi.org/10.1002/sm2.80
Moskovic, D. J., Katz, D. J., Akhavan, A., Park, K., & Mulhall, J. P. (2012). Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU International, 110(10), 1524–1528. https://doi.org/10.1111/j.1464-410X.2012.10968.x
Leder, B. Z., Rohrer, J. L., Rubin, S. D., Gallo, J., & Longcope, C. (2004). Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. The Journal of Clinical Endocrinology & Metabolism, 89(3), 1174–1180. https://doi.org/10.1210/jc.2003-031467

Tadalafil in Pharmacy Compounding

Wed, 13 Feb 2019 18:59:44 GMT

By Nat Jones

Originally designed to treat cardiovascular diseases, phosphodiesterase-5 (PDE5) inhibitors made a major splash on the pharmaceutical market in 1998 with the approval of Viagra®. By far, it was the blockbuster drug of the decade. Other PDE5 inhibitors were soon to follow, and patent expiration dates have been an interesting phenomenon to watch, with multiple extensions involved. The good news is that tadalafil is now free of patents, and compounding pharmacies have some opportunities to use this drug in various customized medications.

Current Uses and Further Research
Tadalafil has labeled uses for benign prostatic hyperplasia, erectile dysfunction (ED) (including patients with diabetes mellitus or following radical prostatectomy), and improvement in exercise ability for patients with World Health Organization Group I pulmonary hypertension. There is a sub-group combination for benign prostatic hyperplasia and ED as well. Off-label uses include altitude-sickness prophylaxis (specifically prevention of high-altitude pulmonary edema), and treatment of sexual dysfunction in males receiving antidepressant therapy.¹

Researchers have looked at or are currently looking at tadalafil in many other areas of interest as well. These include treatment for fetal growth restriction, Duchenne and Becker muscular dystrophies, male reproduction (increase in semen quality), improved endothelial function, passage of distal ureteral stones, treatment of myocardial ischemia/reperfusion injury and heart failure along with bladder ischemia, and aging bladder dysfunction.^2,3,4,5

It is rare and also very exciting when compounders get such a new, widely researched and proven option for our tool boxes. With the current indications and potential uses, we will be able to use this ingredient in many ways with a variety of dosage forms to meet patient needs.

Potential Compounding Options with Tadalafil
The obvious compounding use for this ingredient is in various dosage forms for ED in men. For patients whose needs are not met with commercial products, we have created a variety of formulas (oral, sublingual/buccal, rapid dissolve, and nasal) of different strengths, following the FDA essential-copy guidance document, with dosages compliant in the potency differences from manufactured products where appropriate for individual patients.

Additional options include interesting combinations of ingredients. For example, activated vitamin B6 (pyridoxal 5 phosphate) can help decrease pituitary secretions, including prolactin, and excess prolactin is associated with decreased arousal in both men and women.^6,7,8 Apomorphine has shown to be effective and well tolerated in the treatment of ED.⁹ There is an interesting link with vitamin B6 deficiency and increased risk of cardiovascular disease as well as high homocysteine levels linked to ED, suggesting that folate and vitamin B12 could also be beneficial.^10,11

We have also received anecdotal reports of patients experiencing benefit with a combination of sildenafil and tadalafil.* It is important to understand that many of these formulas can be used for multiple reasons. Also, please note that this drug is not without adverse events, contraindications/precautions and drug-drug interactions, etc., when given percutaneously (transdermal or vaginal), because if it is absorbed, it can have an effect and must be excreted in some way.

PCCA has many related formulations with tadalafil in a variety of strengths and dosage forms. PCCA members can access them here.

Apart from sexual aversion, vaginal pain and vaginal atrophy, there are four main problematic aspects to female sexual dysfunction caused by multiple factors: desire, arousal, orgasm and sexual satisfaction. Tadalafil orally may be effective for sexual desire, sexual arousal, sexual orgasm and sexual satisfaction. Not only does it increase nitric oxide in the corpus cavernosum of men, but in women, it also results in the relaxation of clitoral and vaginal smooth muscle and increased blood flow in these sites, a normal step in arousal and necessary to achieve orgasm.¹² This mechanism makes it likely to improve the arousal aspect, possibly leading to improved orgasmic outcome. There are also case studies showing improved libido and anorgasmia from oral use in patients on serotonin reuptake inhibitors.¹³

Wound care is another logical use for tadalafil. With the exception of exudative types (e.g., venous stasis), most wounds benefit from increased nitric oxide availability to help improve blood flow.¹⁴ A formulation with Spira-Wash® Gel would be a potential option for patients with wounds, but may also be considered for those with female sexual dysfunction and applied externally or vaginally.

Tadalafil has also been studied in patients with ED when applied transdermally with nanoparticles.15 We obviously can’t compound nanoparticle size emulsions, but we can deliver it transdermally with Lipoderm®. PCCA Formula #13276 in Lipoderm is one potential option. This formula could also be clinically appropriate for patients with scleroderma, which is another possible use for tadalafil.16 For patients with ED and premature ejaculation, PCCA Formula #13277 in Lipoderm may be applicable. (PCCA members can access these formulas here.)

PCCA’s formulas are a great way to start using tadalafil for a variety of your patients. If PCCA members have other formula ideas or any questions, they can contact our Clinical Services Department at 800.331.2498.

Nat Jones, RPh, FIACP, is a Clinical Compounding Pharmacist at PCCA. He has over 30 years of experience in hospital and community pharmacy, and he owned and operated independent pharmacies for almost 20 years before joining PCCA in 2012. Nat is also a fellow of the International Academy of Compounding Pharmacists. He has delivered presentations at professional seminars for over 15 years on topics including general pharmacy compounding, wound care, pain management, hormone replacement therapy for men and women, dermatology and cosmetics, among others.

A version of this article was originally published the winter 2019 issue of the Apothagram, PCCA’s members-only magazine.

References
1.   Tadalafil – Drug Summary. (n.d.). In Prescribers’ Digital Reference. Retrieved from https://www.pdr.net/drug-summary/Adcirca-tadalafil-2115
2.   Umekawa, T., Maki, S., Kubo, M., Tanaka, H., Nii, M., Tanaka, K., . . . Ikeda, T. (2018). TADAFER II: Tadalafil treatment for fetal growth restriction - A study protocol for a multicenter randomised controlled phase II trial. BMJ Open, 8(10). http://dx.doi.org/10.1136/bmjopen-2017-020948
3.   Amano, T., Earle, C., Imao, T., Matsumoto, Y., & Kishikage, T. (2018). Administration of daily 5 mg tadalafil improves endothelial function in patients with benign prostatic hyperplasia. Aging Male, 21(1), 77-82. https://doi.org/10.1080/13685538.2017.1367922
4.   Bai, Y., Yang, Y., Wang, X., Tang, Y., Han, P., & Wang, J. (2017). Tadalafil facilitates the distal ureteral stone expulsion: A meta-analysis. Journal of Endourology, 31(6), 557–563. https://doi.org/10.1089/end.2016.0837
5.   Andersson, K.-E., Boedtkjer, D. B., & Forman, A. (2017). The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction. Therapeutic Advances in Urology, 9(1), 11–27. https://dx.doi.org/10.1177%2F1756287216675778
6.   Moretti, C., Fabbri, A., Gnessi, L., Bonifacio, V., Fraioli, F., & Isidori, A. (1982). Pyridoxine (B6) suppresses the rise in prolactin and increases the rise in growth hormone induced by exercise. The New England Journal of Medicine, 307(7), 444-445. https://doi.org/10.1056/NEJM198208123070719
7.   Krysiak, R., Drosdzol-Cop, A., Skrzypulec-Plinta, V., & Okopien, B. (2016). Sexual function and depressive symptoms in young women with elevated macroprolactin content: A pilot study. Endocrine, 53(1), https://doi.org/10.1007/s12020-016-0898-5
8.   Buvat, J. (2003). Hyperprolactinemia and sexual function in men: A short review. International Journal of Impotence Research, 15(5), 373-377. https://doi.org/10.1038/sj.ijir.3901043
9.   Mullhall, J. P., Bukofzer, S., Edmonds, A. L., & George, M. (2001). An open-label, uncontrolled dose-optimization study of sublingual apomorphine in erectile dysfunction. Clinical Therapeutics, 23(8), 1260–1271.
10.   Baghdadi, H. H., Allam, A., & Sheweita, S. A. (2013). Erectile dysfunction medication induced-changes in plasma levels of homocysteine and antioxidant enzyme activities as risk factors for cardiovascular disease. Journal of Taibah University Medical Sciences, 8(3), 151–156. https://doi.org/10.1016/j.jtumed.2013.04.003
11.   Friso, S., Lotto, V., Corrocher, R., & Choi, S. W. (2012). Vitamin B6 and cardiovascular disease. In J. R. Harris (Ed.), Subcellular Biochemistry (Vol. 56, pp. 265–290). https://doi.org/10.1007/978-94-007-2199-9_14
12.   Borghi, C., & Dell'Atti, L. (2017). Tadalafil once daily: Narrative review of a treatment option for female sexual dysfunctions (FSD) in midlife and older women. Archivio Italiano di Urologia e Andrologia, 89(1), 7–11. https://doi.org/10.4081/aiua.2017.1.7
13.   Ashton, A. K., & Weinstein, W. (2006). Tadalafil reversal of sexual dysfunction caused by serotonin enhancing medications in women. Journal of Sex Marital Therapy, 32(1), 1–3. https://doi.org/10.1080/00926230500229079
14.   Davenport, C., & Dubin, A. (2015). Tadalafil therapy and severe chronic foot wound resolution. International Wound Journal, 12(6), 733–736. https://doi.org/10.1111/iwj.12378
15.   Han, G., Tar, M., Kuppam, D. S., Friedman, A., Melman, A., Friedman, J., & Davies, K. P. (2010). Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction. The Journal of Sexual Medicine, 7(1), 224–233. https://doi.org/10.1111/j.1743-6109.2009.01507.x
16.   Patel, R. M., & Nagle, D. J. (2012). Nonoperative management of scleroderma of the hand with tadalafil and subatmospheric pressure wound therapy: Case report. The Journal of Hand Surgery, 37(4), 803–806. https://doi.org/10.1016/j.jhsa.2011.12.030

*As of this publication, sildenafil is still patented in the United States.

THE PCCA BLOG

Easing Drug & Disease Side Effects in Hospice Patients

ABH Gel: Common & Customized

Studied Results: PermE8® Anhydrous Gel

References

Microdosing GLP-1 RAs: Fad or Forever?

Looking Back on GLP-1 RAs

Potential Benefits of GLP-1 RAs

What Is Microdosing?

Endogenous GLP-1 vs. Exogenous GLP-1 RAs

Microdosing GLP-1 RAs

References

Mitochondrial Health: The Key to Longevity?

The Latest Breakthroughs in Mitochondrial Health

Maximizing Mitochondrial Health for Longevity

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

Sunburn: Causes and Prevention

Treatment for Sunburns

Campfire Burns: Risks and Prevention

Treatment for Campfire Burns

Other Types of Burns

References

Biohacking Explained

General Types of Biohacking

Common Biohacking Practices and Real-World Applications

References

Potential Options for Migraine Patients

Acute Migraines

Migraine Prophylaxis

Treatment Success

References

Essential Supplements for Adults

References

Decoding the Intricacies of Infertility

Fertility as a Vital Sign

Reproduction and Metabolic Health

Hormonal Balance

Adhering to the Vaginal Mucosa

The Role of Mitochondria

Mitochondria and Melatonin

Putting It All Together

References

Detoxification in the New Year

Toxic Exposure

Boosting the Body’s Natural Processes

Adding Nutritional Supplements

References

Hypogonadism & Men’s Health

Least Invasive Estrogen Reduction

Testosterone Supplementation

References

Supporting the Immune System

The Art and Science of Topical Minoxidil Formulas

Biomarker for Efficacy

Known & Unknown Mechanism of Action

Oral vs. Topical

Formula APIs

Compounding Preparations

How to Establish Yourself as a Men’s Health Consultant

Tadalafil in Pharmacy Compounding

Studied Results: PermE8^® Anhydrous Gel