THE PCCA BLOG

Cannabidiol Is Now Available for Pharmacy Compounding

Wed, 19 Feb 2020 15:42:39 GMT

By Gus Bassani, PharmD, PCCA Chief Scientific Officer

There has been a considerable amount of interest over the past few years regarding the potential clinical use of various cannabinoids found in Cannabis sativa L. (hemp). The body’s endocannabinoid system, and the receptors associated with it, present an opportunity for health care practitioners to impact the progression of a number of medical conditions. However, until now, there was not a legal avenue for a cannabinoid to be used in pharmacy compounding as a bulk drug substance — or active pharmaceutical ingredient (API) — other than dronabinol, which has not really been a molecule of interest.

That’s why we at PCCA are excited to announce the availability of Cannabidiol (>98% Powder) for use as an API in pharmacy compounding. It is produced by an FDA-registered manufacturer in full compliance with current good manufacturing practices (CGMPs), and meets all of the requirements of section 503A of the U.S. Food, Drug and Cosmetic Act (FD&C Act) for use as a bulk drug substance in compounding.

What Is Cannabidiol?
It is important to have a clear understanding of what this API is, and what it is not. There have been so many nomenclature errors in the media, various industries and medical literature with regard to cannabinoids that it is easy to get confused. Much of the confusion comes from the misuse of the term “CBD.” Technically, “CBD” refers only to cannabidiol, which is a single cannabinoid among a sea of cannabinoids. Unfortunately, so many hemp-based products on the shelves of stores prominently display the term “CBD,” despite the fact that they are not just cannabidiol, but contain a mixture of cannabinoids and other phytochemicals found in the hemp plant. Additionally, the FDA views CBD as a drug and thus not legal to be marketed in the manner most of these retail products are marketed. Compounding pharmacists were also not allowed to use any of these cannabinoids as an API in compounded preparations because they did not meet the requirements of section 503A of the FD&C Act — until now.

As a refresher, Section 503A of the FD&C Act states that a bulk drug substance can be used in compounding if:

It is manufactured by an FDA-registered manufacturer
It is accompanied by a valid certificate of analysis
It is contained within an FDA-approved product, has an applicable USP/NF monograph or is on one of the bulk drug substance lists generated by the FDA (Category 1 of the interim list or the official “positive list”)

PCCA Cannabidiol (>98% Powder) is an API that can be used in prescription compounding because it fulfills these requirements:

It is made by a FDA-registered and -inspected manufacturer in full compliance with CGMPs
It is contained within an FDA approved product (Epidiolex®)
It is a pharmaceutical-grade, high-purity, synthetic cannabidiol powder with a minimum assay (purity) of 98% that is accompanied by a valid certificate of analysis

Additionally, it is not a controlled substance according to the U.S. DEA, and it has a delta-9-tetrahydrocannabinol (THC) content specification of less than 0.1%. Because it is synthetic, there is not a concern that it would contain pesticides or other plant components. The assay on our most recent lot showed 100.3% cannabidiol. Because PCCA’s Cannabidiol (>98% Powder) is a drug, it is for prescription compounding only.

For the purposes of clarity, PCCA’s Cannabidiol (>98% Powder) is:

Not hemp oil
Not medical marijuana and is not extracted from marijuana
Not a full-spectrum mixture of cannabinoids
Not an over-the-counter (OTC) drug and not for OTC compounding
Not a dietary supplement

It is an API, just like any of the other prescription drugs used as active ingredients in compounding. Compounders should treat it accordingly.

For an in-depth explanation of what pharmacies can compound with according to section 503A of the FD&C Act, visit our blog post “FDA Guidance Explained: Compounding with Bulk Drug Substances.”

Having cannabidiol powder available for use as an API in compounding is valuable to patients, prescribers and pharmacists. Finally, prescribers can have confidence in the quality and dosing accuracy of the cannabidiol being used by their patients, and can be more personalized in their approach. Most importantly, the patient will be treated under medical supervision and can be monitored appropriately.

Cannabidiol Formulas
PCCA’s Formulation Development team has been hard at work on a variety of cannabidiol formulas, including capsules, troches, topical creams and gels, permeation-enhancing creams and gels, and suppositories. We will be assessing the physicochemical stability of this new active under a variety of conditions. As we’ve seen from early testing, and from a review of the literature, cannabidiol is light sensitive. Pharmacists need to protect the final preparation from light and not allow the API to be exposed to excessive light during compounding. One of the nice attributes of PCCA’s Cannabidiol (>98% Powder) is that it is nearly tasteless, and is very soluble in oils and organic solvents. PCCA members with Clinical Services access should check our Members-Only Website for the latest cannabidiol formulas.

When working with this API, it is important to remember that section 503A of the FD&C Act prohibits compounders from making what is considered to be “essentially a copy” of a commercially available product. The commercial solution must never be copied, unless there is a drug shortage or unless the patient has a documented allergy or sensitivity to an ingredient in the commercial product.

If compounders work with prescribers who have an interest in the use of cannabidiol for their patients, there is now a high-quality, FDA-registered and -inspected source of the API that can legally be used in compounding!*

Gus Bassani, PharmD, PCCA Chief Scientific Officer, has been with PCCA since September 2002. Prior to that, he was a formulation pharmacist in the product development lab of a veterinary pharmaceutical company. He has worked in multiple pharmacy practice settings in Alaska, Iowa and Kansas, and has taught extemporaneous compounding principles to pharmacy students in Drake University's Pharmaceutics Laboratory course. Gus earned his Doctor of Pharmacy degree from the Drake University College of Pharmacy and Health Sciences. He is a member of the 2015–2020 United States Pharmacopeia Council of Experts – Compounding Expert Committee, and served on the 2012–2014 Drake University College of Pharmacy and Health Sciences National Advisory Council. He is a member of the American Pharmacists Association (APhA), Alliance for Pharmacy Compounding (APC), and American Association of Pharmaceutical Scientists (AAPS).

*Cannabidiol is currently listed as a controlled substance and is not eligible for pharmacy compounding in the states of Idaho (Statute 37-2701), Nebraska (Revised Statute 28-401) and South Dakota (Statute 34-20B). To PCCA’s knowledge, all other states have adopted the DEA’s definition of cannabidiol as not a controlled substance.

Quality Control Then and Now: PCCA’s 2019 QC Lab Renovation

Wed, 12 Feb 2020 15:35:29 GMT

In 2018, we renovated our chemical repackaging facilities, which allow us to take large containers of chemicals from manufacturers and repackage them in smaller containers for compounding pharmacies. We inspect every one of those large containers when we receive them, and we test the chemicals inside them to ensure they meet the high bar we set for the products we offer pharmacies. We even retest all active pharmaceutical ingredient chemical lots again after they are repackaged. It’s not enough to make sure that the chemical is of high quality when we receive it; we also need to confirm that it’s properly labeled and packaged in the appropriate container, as well as conduct secondary identification testing after we have repackaged it. These processes all go into The PCCA Standard™, our commitment to going above and beyond what is required to ensure that we provide the best products possible every single time. A big part of this is our Quality Control (QC) department, and at its heart is the QC lab, where all of that crucial testing takes place.

Since PCCA moved into our current location in 1996, we have had a QC lab that allowed us to consistently and accurately test the chemicals we receive from manufacturers, but as a company, we are always looking to progress. Two of our core values — Innovate Everywhere and Deliver Quality without Compromise — drive us to find ways to improve what we create, what we provide, what we do and where we do it. For these reasons, we renovated our QC lab in the summer of 2019.

The project planning began over two years ago, and by early 2019, we had completed the design for the new lab that took into account not just regulations and guidelines, but also optimized efficiency to ensure that our QC lab works for our employees and, ultimately, for compounding pharmacies’ needs. “The lab is designed in a way that provides everyone ample space to work and allows QC analysts and analytical chemists to carry out their work efficiently, helping to ensure the fulfillment of customer orders in an orderly and timely manner,” said Star Boxie, PCCA Director of QC/QA and Regulatory Affairs.

The whole renovation process included several PCCA departments from QC itself to Information Technology and Facilities as well as several outside vendors. Demolition and the subsequent build-out lasted from May to July 2019. In the end, we had expanded our QC lab by 280 ft² to accommodate new equipment, such as three powder containment hoods ranging from 4 ft to 6 ft, an 8 ft fume hood, an instrument for measuring water activity, pH meters, a Fourier transform infrared spectrometer, labware and personal protective equipment, and additional equipment for working with hazardous chemicals.

“With the additional space and new lab instruments, the QC lab is able to perform more tests to ensure the identification and quality of every product is verified,” said Brooke Lyons, PCCA QA/QC Manager. Blanca Stuhr, PCCA Quality Control Supervisor, added, “The redesign of work space and stations has had a positive impact on safety and productivity due to the improved workflow of the lab.” The new QC lab even takes advantage of the 5S workplace organization system, which helps to decrease the amount of waste while maintaining an efficient, safe and clean work environment.

The results speak for themselves. After more than a year and a half of planning, design and execution, our QC lab is an advanced testing facility that stands as an integral part of The PCCA Standard. This allows us to continue to meet the needs of compounding pharmacies into the foreseeable future.

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

Profile In Personalized Medicine - Michelle Moser

Fri, 07 Feb 2020 15:32:27 GMT

by PCCA

This Profile in Personalized Medicine highlights Michelle Moser, RPh, FACA, FACVP, of Makers Compounding Pharmacy- in Mount Vernon, Washington. A PCCA member since 2011, Michelle graduated from the University of Washington in 1987 with her Bachelors of Science in Pharmacy.

When did you start compounding? What led you to PCCA?
I started compounding in 1989 but found out about PCCA when I changed employers in 1999.

What was your toughest patient problem? How did you solve it?
A patient had been prescribed topical testosterone, but it seemed like with every base we made his prescription in, the preparation would bead up rather than absorb into the skin. We tried several bases during subsequent refills. I then found out that he was going through heavy-metal detox, so we asked him to change shower soaps. That allowed him to start absorbing his testosterone compound.

What has been your most satisfying patient experience?
We have so many success stories of women who finally have their lives back after balancing their hormones through testing and individualizing their estrogen, progesterone and testosterone doses. This includes a gynecologist who had written me an email in which she stated that she believed an “equine estrogen product was much closer to that of a human structure than a plant could ever be.” She was therefore very resistant to write any bioidentical hormone replacement therapy (BHRT) prescriptions. When she hit menopause, I was there for her, and now she is on BHRT herself.

What’s the biggest “aha” moment you’ve had as a member of PCCA?
It’s a tie between two events: After many years of not wanting to spend the extra money, I joined PCCA’s Compounding Pharmacy Management Services (CPMS). Every month, I find value in having Bryan Prescott, PCCA’s Director of Management Coaching Services, look over my numbers to validate the wonderful gains our team makes on a monthly basis. The other is when we joined PCCA Concierge Compounding Group #9. I was welcomed by warm friendships — the sharing is open and always useful.

What is your favorite PCCA base, and why?
WO6® Anhydrous Topical Gel— It’s just so easy, and now we can extend the BUD for many compounds.

What is your favorite PCCA educational event?
Concierge Congress, hands down.

When was the last time a patient thanked you, and why?
About an hour ago, because I took the time to listen to the patient’s needs and find professional-grade supplements and a compounded prescription to help them feel better. This is after they had been searching for the right provider for many, many years.

What is the one thing you would say to new compounders?
Take time to invest in yourself to gain knowledge of how to compound, when to compound and why to compound. It’s a passion, not just a profit center.

What is your favorite thing about your job right now?
I absolutely love my staff. They are amazing, support each other and are always looking to make compounding better. They really take care of our customers.

What do you enjoy doing for fun?
Cooking for my family, talking around the dinner table and just spending time with them.

What is the best word to describe your life?
Blessed.

My personal motto/words to live by:
Don’t worry, just believe.

Compounding Opportunities for Winter

Wed, 05 Feb 2020 15:37:03 GMT

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Recommended Flavors to Add

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

Recommended Combinations of Flavors to Add

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

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

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

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

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

References

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

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.

Clinical Services Spotlight - Matt Martin

Fri, 31 Jan 2020 18:34:30 GMT

By Seth Humble, Digital Content Specialist

Kentucky is a special kind of place. Roving through its rolling hills, blanketed in the wind-swept, world-famous bluegrass from which the state takes its nickname, people find themselves taken aback, perhaps even awestruck. Kentucky is a place of dusky beauty. It’s a state physically gowned and culturally capped in blue. From the roots of terra firma to the soaring musical top of the Foggy Mountain Boys, Kentucky is the kind of humble place that crafts a humble man.

“You can say that blue has always been a big part of my life,” says Matt Martin, PharmD, a PCCA clinical compounding pharmacist. “I went to Moorehead State for undergraduate work, then the University of Kentucky for my pharmacy education. So, blue and blue. And surprise, I’m a Dodgers fan — blue there, too. And now, I work for PCCA, which is of course, famously blue.

We go through the normal, beginning particulars of every get-to-know-you scenario over the phone. He works for PCCA remotely from his home state. The first thing Matt wants to tell me is about his family.

“I have a lovely wife and we have four kids: three girls and one boy. We’ve also got a 6-year-old pup named Tiny,” he says. There is a distinct kind of nostalgia that rings in Matt’s voice when he tells me about the family he grew up with. His father, an aluminum-parts production supervisor who served at the same company loyally for 40 years, encouraged Matt’s love for collecting baseball memorabilia — especially baseball cards. His mother is a deaf schoolteacher at the Kentucky School for the Deaf, but you would never know it by her incredible proficiency at reading lips. Matt talks about his young life with a breezy ease; the trademark of the Southern raconteur.

When we talk about what Matt does for PCCA, his tone changes. It’s still calm, smooth and direct, but there is a dynamism that flows into his voice when he starts talking about pharmacy compounding guidelines and regulations.

“I talk with pharmacies, especially about regulation,” he says. “I help them understand where to find resources to best equip themselves to handle often-changing interpretation of the regulatory landscape. Legislation dictates how pharmacies are able to compound, what they are able to compound with; that legislation dictates how or if a pharmacy can help a patient. That can be very frustrating. It’s my job to help those pharmacies navigate those scenarios.”

“Legislation is something you’re clearly passionate about,” I say.

“To me, that’s why ACT is so important and, honestly, encouraging because of how many new faces I see each year that want to serve as advocates for patients,” Matt says of PCCA’s annual legislative conference in Washington, D.C. “ACT lets them share their concerns with congressional offices and advocate for patients’ access to customized medicine. It’s important to recognize that our voice, the voice of compounders, is a big voice in regulation, but not the only voice. So conveying our message in person does make a difference.”

The phone goes quiet, but I can feel the wheels of Matt’s mind turning.

“I don’t mean to go on, but something that I think is important is this: One word can have so much power to change the interpretation and the outcome for patient care,” Matt says. “So, no matter if it’s sterile or nonsterile compounding, or we’re dealing with USP guidelines it’s important to know that it takes care and focus to really navigate these documents. I want pharmacies to be able to help people, and in order to do that, I am striving to stay on top of this ever evolving regulatory system.”

I ask him what he does to understand these finer points.

“Understanding the documents, going through them line by line carefully,” he responds. “And honestly, it’s people — talking with people during inspections. Those are tense, high-pressure situations. In those moments, you want to let those people know that they are not alone, that there is someone they can talk to, someone that can help them walk through these situations. Being a person who helps them is very special to me.”

“So what can people do to prepare for those kinds of situations?” I ask.

“Pharmacies should practice for the inspection with assigned roles of who does what when the inspectors arrive. Knowing that and practicing that eases the tension if a real inspection occurs.”

“Anything else?” I follow up.

He laughs; it is a slow, self-effacing sound. “Yeah. Call me. Let’s get prepared. Let’s talk about what you should consider about your facilities, personnel, procedures, and how you can be a voice for continued access to needed compounded medications.”

This is Matt Martin — an eagle scout and native son of the Bluegrass State, who loves fall camping in the Red River Gorge. A clinical compounding pharmacist who believes that sharing special experiences with those we love is essential to a meaningful life. He was PCCA’s 2018 Employee of the Year and is a compounding legislation and regulation hawk, always looking for every possible way to empower the pharmacies he speaks to on a daily basis. PCCA is proud to call him one of our own.

LDN Study, Extended BUDs and More from PCCA Science

Mon, 27 Jan 2020 16:42:48 GMT

By Yi Liu, PharmD, PhD, PCCA Research Pharmacist

Peer-reviewed journals have recently published a lot of PCCA’s original research as well as that of independent researchers studying PCCA products. We have been investigating novel therapies, extending beyond-use dates (BUDs) for compounded formulations, evaluating pharmacy compounding equipment and much more. Here is a brief summary.

Naltrexone in Dermatology
The journal Archives of Dermatological Research recently published our study entitled “In Vitro Evaluation of Naltrexone HCl 1% Topical Cream in XemaTop™ for Psoriasis.” We investigated the mechanism of action, in vitro efficacy and stability of this topical cream containing low-dose naltrexone (LDN) in PCCA’s base XemaTop for the treatment of psoriasis. This article provides a basis for potential psoriasis treatment options and may be useful to clinicians who are interested in LDN as well. PCCA members who would like more information about this study can contact PCCA Science for the full text of the article or further discussion.

We were also honored to have this novel research in psoriasis therapy selected as an oral presentation at the 79th International Pharmaceutical Federation World Congress of Pharmacy and Pharmaceutical Science, held in Abu Dhabi, United Arab Emirates, in September 2019. Suki Pramar, PhD, from our Clinical Services team presented the data to a full auditorium. The presentation slides are publicly available online.

Stability of APIs in SuspendIt^®
In its November/December 2019 issue, The International Journal of Pharmaceutical Compounding published a bracketed stability study of amlodipine besylate in SuspendIt, PCCA’s proprietary suspending agent, granting an extended BUD for the formulation in the study. This follows previously published stability studies of common active pharmaceutical ingredients (APIs) in this base. These previous studies have established extended BUDs for naltrexone hydrochloride, ursodiol, trimethoprim and sulfadiazine, spironolactone, fluconazole and clindamycin in SuspendIt.

Minimizing Powder Exposure for USP <800>
To help comply with USP General Chapter <800> and explore more strategies for compounders, Chad Hutson, PharmD, PCCA Clinical Compounding Pharmacist, and A. J. Day, PharmD, PCCA Vice President of Clinical Services, have performed a study to evaluate the efficacy of a containment ventilated enclosure (CVE). They found strong evidence that a properly calibrated CVE for containment of hazardous aerosol-generating compounding activities is effective in minimizing powder chemical exposure to the compounder. This research is also available in the November/December 2019 issue of The International Journal of Pharmaceutical Compounding with the title “Evaluation of Containment Ventilated Enclosure Performance in Absence of Negative Pressure Containment Secondary Engineering Control.”

Case Study: Pain Management for Achilles Tendonitis
We in PCCA Science are still diligently working with members on case studies. On the PCCA Science webpage, we recently published a new case study, “Achilles Tendonitis: Pain Management by Compounding,” submitted by Jim Perry, RPh, from District Drugs & Compounding Center in Rock Island, Illinois. The study evaluated the effectiveness of diclofenac and lidocaine in Lipoderm® for two patients with Achilles tendonitis.

New Independent Compounding Research
Outside PCCA, independent researchers have constantly presented data of PCCA products that are consistent with our findings, which further demonstrate the quality and reliability of our products. In the November/December 2019 issue of The International Journal of Pharmaceutical Compounding, a study validated the compatibility of two PCCA flavors in an omeprazole oral liquid. In another study published in that issue, gabapentin in a Lipoderm formulation once again showed fast release and high skin permeation. Lipoderm was recommended by the authors as “the most practical option for compounding.”¹

PCCA member pharmacies who are interested in conducting and publishing research with PCCA are welcome to contact PCCA Science at pccascience@pccarx.com.

Yi Liu, PharmD, PhD, is a research pharmacist in the Research and Development department at PCCA. She joined PCCA as a clinical pharmacy researcher in the Clinical Services department in 2018 and started her current role in 2019. Yi graduated from Ohio University with a PhD in molecular and cellular biology in 2012. She also worked as a postdoctoral research fellow in the Houston Methodist Research Institute for three years prior to starting pharmacy school. Yi received her PharmD from the University of Houston College of Pharmacy in 2019.

Reference
1. Shakshuki, A., & Agu, R. U. (2019). Compounded topical gabapentin for neuropathic pain: Does choice of base affect efficacy? The International Journal of Pharmaceutical Compounding, 23(6), 496–503. Retrieved from https://www.ijpc.com/

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

Does Your DMSO Pass These 2 Tests?

Wed, 15 Jan 2020 21:01:56 GMT

By Don Bottoni, RPh, FACA, PCCA Clinical Compounding Pharmacist

Dimethyl sulfoxide (DMSO) is an interesting substance, and it has many uses in the pharmacy world. It is classified as an aprotic solvent, which means that it does not contain any hydrogen atoms and is not capable of being a proton donor. This property makes it an ideal solvent in which most chemicals are stable. It is miscible with many other solvents as well, including water. It has a high boiling point, so it will not rapidly evaporate at room temperature. It can freeze at temperatures around 68° F. If a pharmacy receives a shipment of DMSO that contains crystals, simply place the container in a warm water bath, and the crystals will dissolve. It is best not to use the DMSO until the crystals have dissolved and the container is shaken well. If the crystals are not dissolved, the liquid portion can contain a higher concentration of impurities.

Among other applications, DMSO has historically been used in compounded creams and gels as a permeation enhancer, though modern compounding bases such as Lipoderm® and PermE8® Anhydrous Gel provide superior delivery without some of the harsh properties of DMSO. Despite its prevalence, however, not all DMSOs are created equal, and there are a couple easy ways to determine if yours might be of questionable quality.

Test 1
Does the DMSO you are using have an odor? If it does, it may mean that you are using an inferior quality product. There are several grades of this chemical that are used in different industries and for various purposes, including analytical applications and the manufacturing of semiconductor devices. However, a high-quality, USP-grade DMSO — which is what we must use in pharmacy compounding — should be virtually odorless.

Test 2
Recently, we have heard from some compounders that crystals are forming when they add their DMSO to water. DMSO is a nontoxic solvent obtained as a by-product of the paper-making industry, and lower grades of it may contain other distillates and contaminants that are not freely soluble in water. Therefore, if your DMSO is forming crystals when you add it to water, it may be because of a higher level of impurities. This should not happen with a high-quality, USP-grade DMSO.

Many years ago, PCCA set the standard by finding the highest grade chemicals for the compounding pharmacies we work with. This means we offer USP-grade DMSO that contains few if any impurities and is almost odorless. It does not form crystals when added to water. This high purity may help reduce any irritations when used in topical preparations as well. We compounders are mandated by USP to use the highest grade chemicals possible. Using USP-grade DMSO helps to ensure that you are following USP guidelines and that you are compounding a quality product.

PCCA members can learn more by reading the document Not All DMSOs Are the Same on our Members-Only Website. They can also see more details on the proper thawing procedure for DMSO.

Don Bottoni, RPh, FACA, joined the staff of PCCA in January 2010 after 40 years of practice in independent pharmacies. He graduated from Texas Tech University in 1966 with a BA in chemistry and The University of Texas College of Pharmacy with a BS in pharmacy in 1969. Don’s areas of interest include nutrition, sterile compounding, bioidentical hormone replacement therapy and men’s health. Don has been a presenter at many PCCA International Seminars and at University of Texas continuing-education seminars, and he taught several classes on nutrition for PCCA in the mid-1990s.

Profile in Personalized Medicine - Rachelle Whitaker

Mon, 13 Jan 2020 18:39:53 GMT

By PCCA

Our January Profile in Personalized Medicine highlights Rachelle Whitaker, CPhT, a compounding technician at The Compounding Lab in Huber Heights, Ohio. The Compounding Lab is owned by PCCA member Tim Clark, RPh, and led by compounding pharmacist Robyn Crow, RPh.

For how long have you been compounding?
I was 19 years old when I started compounding. I took my first pharmacy job in 2004 at a long-term care pharmacy. Since that time, I have had the opportunity to work in several different compounding settings.

When did you learn about compounding? Why did you start compounding?
Over the years, I've learned sterile and nonsterile compounding working in long-term care, a home infusion pharmacy and a local hospital. I took my love for compounding to a new level when I joined The Compounding Lab in 2017.

I was so excited to learn how to make things like capsules, suppositories, lollipops (my favorite), troches and more. Robyn Crow, our compounding pharmacist, and the other techs taught me so much, and I am truly grateful for the knowledge they have given me. One of the things I think we do best at The Compounding Lab is hormone replacement therapy. Robyn is so great at working with doctors to develop the best regimen for each individual patient. Hormone issues affect such a large percentage of our population; I know this personally, as I suffer with polycystic ovary syndrome (PCOS). When hormones are out of whack, they can really take a toll on your physical and mental well-being, so I find it very rewarding that we are able to help our patients get that part of their lives back. Pediatric medications are another one of my favorites.

What do you find most fulfilling about compounding?
I love that we can make a medication for our patients who are children that may not be commercially available in a pediatric dosage, but could be very beneficial to their treatment. Not only does it help the child with their condition, but it also gives the parent(s) peace of mind.

What are some of your favorite PCCA formulas? What do you like about them?
My favorite PCCA formula to compound is for tetracaine lollipops (PCCA Formula #5380). We have received very good feedback from patients and their doctors. They are fun to compound, and it makes me happy that we can help these patients.

PCCA members with Clinical Services access can see Rachelle’s favorite formula for tetracaine lollipops in our formula database.

What is one of your favorite compounding success stories?
We have a young patient with rheumatoid arthritis who was practically bedridden before her doctor ordered allergy testing and found that the medications she was taking to help her arthritis were actually making her sick. Since coming to us to make her medications allergen free, she has been able to enjoy a higher quality of life.

What advice would you give to a new compounder?
I would tell them to take it slow. It takes time and patience to develop good technique. Also, take notes and do your research. There is so much to learn that it can seem overwhelming at times. I have been doing this for years and feel like I learn something new almost every day. If you stick with it, and it is something you really enjoy, it can be the best career path you will ever take!

Compounding Update: HCG

Wed, 08 Jan 2020 19:07:47 GMT

By Matt Martin, PharmD, PCCA Clinical Compounding Pharmacist, and Melissa Merrell Rhoads, PharmD, PCCA Director of Formulation Development

The FDA has provided a preliminary list of products that were originally approved as drug products, but that will be considered biologic products as of March 23, 2020.¹ Human chorionic gonadotropin, or HCG, is one of these drugs that will now be deemed a biologic product. This means that, starting on March 23, 2020, pharmacies will no longer be able to compound with HCG, and we will be retiring all PCCA formulas that include it at that time.

Background

“Drugs” are generally approved under Section 505 of the Food, Drug, & Cosmetic Act (FD&C Act) while “biologics” generally receive a biologics license under Section 351 of the Public Health Service Act (PHS Act). Traditional pharmacies compounding medications and dispensing them by prescription are considered 503A pharmacies under the FD&C Act. While Section 503A of the FD&C Act provides pharmacies some exemptions, it does not provide an exemption from requiring approval for a biologics license under Section 351 of the PHS Act — meaning that pharmacies cannot compound with biologic products.² You can read more about this framework in the FDA’s guidance document titled “Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application.”

Potential Compounding Options

However, compounding is about attempting to solve the needs of patients through innovation in a partnership with the patient and their practitioner. For PCCA members with Clinical Services access, our team of pharmacists are ready to help examine formulations in our database and evaluate if they might be appropriate for patients.

With that in mind, we have a number of potential compounded formulations for compounders’ consideration if FDA-approved products do not meet the needs of their patients. When HCG had previously been part of a regimen for testosterone therapy, one option for men’s health is the use of anastrozole, as it will help the body continue to make testosterone to minimize the negative-feedback effects of testosterone therapy.^3,4,5

PCCA members with Clinical Services access can find a list of example formulas that include anastrozole and testosterone in a variety of dosage forms on our Members-Only Website.

Matt Martin, PharmD, is a Clinical Compounding Pharmacist at PCCA. He joined the PCCA Clinical Services department in September 2014. Matt graduated from Morehead State University with a BS in Chemistry in 2002, and received his PharmD from the University of Kentucky College of Pharmacy in 2006. Prior to joining the PCCA team, Matt worked in compounding pharmacy for more than eight years, and has experience with both sterile and non-sterile preparations.

References
1.   U.S. Food & Drug Administration. (2019). Preliminary list of approved NDAs for biological products that will be deemed to be BLAs on March 23, 2020 [PDF File]. Retrieved from https://www.fda.gov/media/119229/download
2.   U.S. Food & Drug Administration. (2018). Mixing, diluting, or repackaging biological products outside the scope of an approved biologics license application: Guidance for industry [PDF File]. Retrieved from https://www.fda.gov/media/90986/download
3.   Charnow, J. A. (2013). Anastrozole improves testosterone therapy. Renal & Urology News. Retrieved from https://www.renalandurologynews.com/home/departments/mens-health-update/hypogonadism/anastrozole-improves-testosterone-therapy/
4.   DiGiorgio, L., & Sadeghi-Nejad, H. (2016). Off label therapies for testosterone replacement. Translational Andrology and Urology, 5(6), 588–849. https://dx.doi.org/10.21037%2Ftau.2016.08.15
5.   National Institute on Aging. (2018). Effects of aromatase inhibition versus testosterone in older men with low testosterone: Randomized-controlled trial. Retrieved from https://clinicaltrials.gov/ct2/show/NCT00104572

Thank You for Your Inspiration and Support

Wed, 18 Dec 2019 15:30:28 GMT

by Jim Smith, PCCA President

We love the combination of clinical expertise and entrepreneurial innovation PCCA members offer their communities through personalized medicine services. It is an honor and a privilege to be on their team making incredible things happen for patients and doctors.

PCCA member, T.W. Taylor from Virginia, shared at a recent conference that he is focusing on patient wellness instead of focusing on bringing in more prescriptions. As a result, his overall business is booming, including his prescriptions!

Vince and Mary Canzanese in Pennsylvania are putting every square foot of their pharmacy to productive use leveraging sterile services, successful advocacy for payment of personalized medications for marginalized patients, and individual patient counseling and group education.

We have about 3000 of these stories because everyone is doing something unique with the circumstances, opportunities and challenges given to them. What an exciting aspect of medicine to support.

2019 has been a transitional year for the industry. Regulatory realities brought change to how many pharmacies choose to do business. We have had our fair share of transitions at PCCA. Most especially, we express gratitude to our members for helping us shift our clinical services offering to a monthly subscription plan. This change positions our clinical services teams to continue developing their capacity to serve.

In 2020 we’ll be redoubling our commitment to stay abreast of and meet our members’ current needs. We look forward to upping the game in our first-class service and quality offerings. Bringing meaningful value to our clients is at the forefront of our desires. As an example, a major remodel of our training lab and class structure will innovatively adapt them to changes the industry is undergoing.

While we are in a different era for compounding than we were five years ago, the expertise and innovation of our members to remain relevant in their communities continues to inspire us. Thank you to all our members and customers for this inspiration and support. We hope our service-culture reciprocates value to our clients as we use our resources to innovate advancing personalized medicine.

Jim Smith, MBA, a long-time member of the Strategic Management team, was named PCCA President in April 2009. Jim joined the staff of PCCA in 2000 after serving in significant leadership positions at other organizations. Since joining PCCA, he has served as Chief Operating Officer, as Vice President of Sales and Marketing, and as a vital member of the Strategic Management team, working to continuously improve PCCA's core competencies. Jim received his BS with majors in chemistry and biology in 1982 from West Texas A&M University and then served a two-year mission in the Dominican Republic. He received his MBA from The University of Portland in 1987 and has spent his career leading organizations in home health, DME, respiratory pharmacy, long-term care pharmacy and compounding support.

Clinical Services Spotlight - Tricia Heitman

Mon, 16 Dec 2019 15:13:48 GMT

by Seth Humble, Digital Content Specialist

Though winter is at its full height when we meet, Tricia Heitman brandishes an unyielding summertime smile. After a few minutes of typical introductions, I ask, “You’ve been at PCCA for...”

Her eyes widen with excitement. “I’ve been at PCCA for 20 years, six months, and six days.”

“What does two decades mean to you?”

“I started right out of college here. After my father convinced me to get my PharmD, I became a resident at PCCA under Andy Glasnapp. Andy saw something in me that I never would have seen. I remember very vividly that on my first day, I took 11 calls. These days I take about 25 calls a day. Dave Sparks was my first boss, and he was so incredibly supportive and good to me. I’m very thankful for how this opportunity started.”

She sighs, her eyes drifting upward into a cloud of memories. “A lot of maturing happened here. I started here when I was 25. That maturing could be summed up in how I have learned how to help people who are in stressful situations or people who disagree with me. It has taught me how to listen better, try to understand people’s needs better. That is a large part of our job here in Clinical Services, and I think that is why we are so effective. Everyone in our department works hard to listen actively. It is a great joy to be able to help people that way, especially pharmacies. When I listen well to them, it means that I’m listening to the patients they serve, and I get to help them both.”

“So,” I interject, “you might say that listening well has a compounding effect.”

It’s a criminally bad pun.

Tricia laughs, mostly out of what I assume is politeness.

Sitting there, I cannot help but hear the sincere gratitude in her voice. I ask her why being in Clinical Services for PCCA has been so rewarding for her. Her answer does not disappoint.

“I like to imagine all the people we’ve helped over the years. Clinical Services’ reach doesn’t just touch the lives of people working in compounding pharmacy, it touches the lives of patients and the families of those patients. When we help pharmacists apply solutions to their patients’ problems, it means the next time they experience that same issue, they’ve been equipped with a solution.”

“So would you say that personalized medicine has a rippling effect?” I ask.

Tricia’s eyes light up, confirming. “Oh, absolutely.”

“What area have you found the most rewarding?”

“I’ve always been invested in pediatrics. Don’t get me wrong, I love helping people with all sorts of questions and challenges, but I started in pediatrics. I was headed to Children's Hospital Colorado to accept a residency before Andy asked me to be a resident at PCCA. There’s no way to know everything in pediatrics. It is a huge sphere of knowledge, but it doesn’t scare me — it excites me. I want to help kids; my heart goes out to them. I want children to have the very best medicine and the absolute best experience with their medicine. My knowledge in pediatrics is probably the biggest thing I bring to the table, but everyone in Clinical Services is always happy to pitch in. And that’s really what makes our team so powerful: We aren’t just a group of pharmacists, we’re a community. We’ve built that up over years and years and years together; that’s really important, knowing that there is a trust there that’s been earned. We’re a team, a real team, and that trust is a trust all of us lean on.”

“If you hadn’t gone into pharmacy, what would you have become?” I ask.

“A horticulturist. I would have absolutely loved that.”

“Do you dabble?”

“I do! I have a tiny garden, a little herb garden, and an antique rose garden. I’m into succulents. But I’m also a good Texas girl, so I have cabbage and collard greens. Gardening is very spiritual for me; it’s mindless, so it allows me to reflect and focus on growing things.”

“And that helps you with the clinical side of your life, being able to grow things?” I ask.

“Without a doubt. But my clinical work is extremely important to me.” There’s a lilt in Tricia’s voice when she mentions the importance of her work.

“What would be an example of your clinical work?” I ask.

“Take for example — I’ll give you one that came up twice. There was a 5-year-old with ovarian cancer who was having a lot of perineal pain. Knowing the signs of pain and how children in pain behave, I could clearly see that this was neuropathic pain. The child wasn’t sleeping more than two to three hours a night, and with the laundry list of medications she was on, she was just absolutely miserable when trying to sleep. Her doctor wanted to take a certain track with her pain treatment, but I suggested that before they take that road, to give us a chance to help her pain. We did a great deal of research, and we collaborated, and with patience and time and literature, we were able to advise on a path of treatment. We work diligently to understand medications, their side effects, and how physiology will respond to those medications. I’m really proud of my years here. There are always challenges, but I’m so happy I chose this profession. I think helping patients like this is proof that personalized medicine is worth fighting for.”

This is Tricia Heitman.

At the time of this article’s completion, she has worked at PCCA for 20 years, six months and 15 days. She believes in growing things. From growing the succulents, herbs and roses in her home garden to laboring the well-tilled soil of knowledge inside her mind, or enjoying the fruits of community in our Clinical Services department. It’s clear after meeting her that Tricia’s sunny disposition, diligence and hard work are how she’s managed to grow so many things so quickly.

The Top 5 Blog Posts of 2019

Wed, 11 Dec 2019 16:29:53 GMT

By PCCA

And just like that, The PCCA Blog is closing its first full calendar year in the world. Between January and November of 2019, we published 71 blog posts and attracted tens of thousands of readers just like you, many of whom have subscribed as well. Thank you to all of our readers and subscribers for making it a wonderful year. We’re grateful to be able to produce content that professionals in the pharmacy compounding industry find valuable. Below are some of our top-performing posts of the year, reflecting some of the biggest changes that our area of health care is experiencing along with the ever-present need for research-based clinical information.

1. Notable Changes in the New USP <795>
Even though implementation of the new USP General Chapter <795> has been delayed due to appeals, it is still crucial to have a full and nuanced understanding of it. In this post, PCCA Clinical Compounding Pharmacist Matt Martin, PharmD, addresses notable changes to the new USP guidelines and provides some considerations for implementation.

2. An Innovative Option for Hirsutism: Topical Metformin
Clinically, hirsutism “refers to women with excess growth of stiff, pigmented hair (known as ‘terminal hair’) in a male pattern,” explains PCCA Clinical Compounding Pharmacist Sara Hover, RPh, FAARM. But she has exciting news about a potential option for women with hirsutism as well.

3. Oral vs. Topical Estrogen: What the Literature Is Showing about Health Risk
Compounded bioidentical hormone replacement therapy (BHRT) is an important treatment option for women around the world. Colleagues and patients alike come to experts like Pamela Smith, Nat Jones and Sara Hover for guidance. In this two-part post, they cover this all-too-important topic in the BHRT conversation, showing what current literature says about the usage of oral vs. topical estrogen.

4. Upcoming Changes to PCCA Formulas per the New USP <795>, <797> and <800>
The new and revised USP chapters affect many aspects of compounding, including formulas. In this post, PCCA Director of Formulation Development Melissa Merrell Rhoads, PharmD, details the updates we’re planning to make to our formulas based on the new USP guidelines. Pro tip: Look at the types of updates we’re going to make to our formulas as a guide for changes you should consider in your own.

5. Notable Changes in the New USP <797>
The new USP General Chapter <797> implementation is delayed because of appeals just like USP <795>, and that gives compounders more time to become familiar with it. Let Dylan Herr, RA/QA Development Manager at Eagle, help with that. She understands that this version makes significant revisions to the old one, and in this post, she provides you with an overview of those changes and strategies for implementing them.

We’re hard at work planning more content for 2020 that we hope will help you serve patients and grow your business, so keep an eye on The PCCA Blog. If you like what you see, consider subscribing. We’ll send you email notifications when we publish new posts. And if you’re already a subscriber, sit back and relax. We’ll be in touch.

Profile in Personalized Medicine - Charles Wall

Fri, 06 Dec 2019 18:42:08 GMT

This Profile in Personalized Medicine highlights Charles Wall, DPh, owner of Heartland Apothecary located in Knoxville, Tennessee. A PCCA member since 2009, Charles graduated from Samford University for both his undergraduate and pharmacy school education.

How did you start compounding? What led you to PCCA?
After being in sterile IV pharmacy for the first 15 years of my career, I completed the nuclear pharmacy program at Purdue University and needed my practical hours. I trained at a nuclear-medicine site that also made a few compounds a day and found this model interesting. When I started the pharmacy, I intended to open as a nuclear site first and add compounding to our pharmacy services later, but due to the market, I flipped the model and started compounding first and never looked back. I had known about PCCA for a long time and reached out to Tim Adams of PCCA Outside Sales with some general questions, and we just took it from there.

What was your toughest patient problem? How did you solve it?
We had a patient with recurrent vaginal yeast who was unresponsive to commercially available products. So we worked with her health care provider to develop a suppository that included four antibiotics and antifungals that we recommended based on her lab test results. After two rounds of therapy, the patient reported improvement and the symptoms have subsided. The patient is experiencing a reduction in pain as well as other issues. We used PCCA formulas and combined a couple in order to offer the patient ease of application, and the results have been well received.

What has been your most satisfying patient experience?
Extending the life of an elderly canine patient who was experiencing seizures. She enjoyed a year of nearly seizure-free life.

What is the biggest “aha” moment you’ve had as a member of PCCA?
The exposure to others who practice at the cutting edge of the profession. Seeing others approaching this niche area and using it to springboard onto other things and not be boxed in .

What is your favorite PCCA base, and why?
LoxaSperse® . It has so many useful applications and great results. One patient in particular had issues absorbing drugs. We tried several different capsule formulas and fillers, and we achieved adequate absorption by adding a low percentage of LoxaSperse to the formula. The resulting levels have stabilized, and the patient is now enjoying better quality of life.

What is your favorite PCCA educational event, and why?
In my first C3 compounding course at PCCA, I made some lifelong friends and was exposed to more about compounding than I ever would have expected.

When was the last time a patient thanked you?
It seems almost daily we hear from patients on hormone replacement therapy about how it has improved their lives and their spouses’ lives.

What is the one thing you would say to new compounders?
I preach it to students in each pharmacy school rotation: Use the profession as an entry to other things you enjoy — be it investing, another hobby or another profession. Pharmacy compounding allows you to grow quickly, so use that opportunity early, and you will reap many benefits later.

‘Tis the Season to Say Thank You: Using Gratitude to Grow Your Business

Wed, 20 Nov 2019 16:42:19 GMT

by Erin Michael, MBA, MS, CPhT, PCCA's Director of Outside Sales

In today’s crowded pharmacy world, it is very important to make sure that you stand out. What is it that you do differently? What sets you apart from your competition? Have you defined what your competitive advantages are and how are you using them to promote your practice? Are your patients and practitioners promoting your practice because of the amazing experience they have had with you? As the year-end approaches, it is a perfect time to take an internal look at your business and try to find the answers to these questions.

I was re-reading the book Raving Fans by Ken Blanchard last week, and it reminded me how important it is to make sure every encounter with a potential patient or practitioner is a memorable one. Not only will you gain a loyal customer or colleague, but they will become your “raving fans” and start to do the marketing for you. So, as we move into the time of year where it is typical to thank your patients and your practitioners for their continued loyalty, I would challenge you to ask yourself, what will you do to set yourself apart and take your “raving fans” status to the next level?

I used to ask myself this question every year in the fourth quarter as I started to think about what I was going to do for my patents and practitioners to say “thank you.” I did things like giving candy, fruit baskets, calendars, wine baskets and more. My partner and I included a personal thank-you card with every gift, and we hand-delivered them to prescribers’ offices about one week before Christmas. We even had a holiday open house for our patients to let them know how much they meant to us. Over the years, as competition increased, we started to notice that others were following suit. We were no longer doing something that set us apart. So we decided to give our thank-you during a time that was truly designated as a time for reflection and appreciation. We started giving Thanksgiving appreciation to our patients and practitioners in November. This really was a game changer for us. It was unexpected, and the staff at the prescribers’ offices loved it. Our patients raved about how we took care of them, and we truly appreciated their business. This was what we needed to be different.

Another tactic that worked very well for us was carefully choosing the words we used to express our thanks. It is so easy to say “thank you” when you are ringing up a customer at the register or before you hang up the phone with a practitioner, but have you ever thought of taking your verbal cues to the next level? Using words like “appreciation,” “grateful” and “recognize” in your thank-you messaging will also help to strengthen you overall message. Using these words shows a deeper level of gratitude and truly shows your customers how much you appreciate them. This is a great time of year to revisit your overall customer experience and look at things through a different lens: How can you appreciate your customers today and enhance their experience for a lifetime?

So what will be your game changer? How will you gain additional loyalty from your already “raving fans”? Will it be that celebration you enjoy around New Year’s to thank your supporters and get them excited for things to come? What about delivering a single yellow rose to each mom who works at the practitioners’ offices or who comes into your pharmacy in honor of Mother’s Day? Whatever you do to thank your fans, make sure to be unique. Do something that will be different and be remembered for years to come. Happy Selling!

Erin Michael, MBA, MS, CPhT, PCCA Director of Outside Sales, joined the PCCA staff in July 2006. She has been working in pharmacy for more than 25 years, of which 23 have been in compounding and promoting the practice of pharmacy. She previously worked for an independent pharmacy owner and was the general manager of multiple locations. Erin was instrumental in developing and implementing programs to promote and grow the compounding and traditional parts of that business. She holds an MBA in healthcare administration and an MS in hospitality management. She was recognized as PCCA Technician of the Month in August 1999 and California Pharmacists Association Technician of the Year in 2003.

Clinical Services Spotlight - Nat Jones

Mon, 18 Nov 2019 14:57:46 GMT

by Seth Humble, PCCA's Digital Content Specialist

Since the beginning of time, human beings have asked important questions — questions that seek to provide a balm of existential comfort to the worldly fears looming over the human condition. Philosophers from Plato to Borgmann, Stoic to Postmodern, have probed the depths of the human mind, investigated the mystery of the human soul. Under the intellectual care of their collective wisdom, we are confronted by the one, truly impossible question.

It is the question that can potentially divide parent and child, split the closest of friends.

It is the question ever lingering on the lips of every human heart.

“Who is the greatest lead singing front man of all time?”

Nat Jones, RPh, FIACP, of PCCA Clinical Services, hears my question, and immediately, his eyes roll upward as he falls back in his chair. A smile splits his lips. “Oh, man.”

He reaches up and slides his fingers over his white goatee, giving the end a little tug; it’s a gesture that I quickly recognize to be his absent-minded tick of consideration.

Nat Jones, like any great band’s lead singer, is a specialist. Nat works as PCCA’s liaison to the United Kingdom. Make no mistake though, Nat isn’t a one trick pony. Published author, former pharmacy owner of twenty years, medical formula inventor, respected speaker and consultant in the compounding industry, Nat Jones is a polymath, a modern Renaissance man.

“I specialize in the areas of hormone replacement therapy, pain management, ENT and dermatology,” he tells me. “I typically focus in those areas. It makes me happy to help with difficult HRT questions; I’ve spent much my career in that area.” Not only a seasoned Clinical Services consultant, Nat is also PCCA’s official liaison to bespoke medication (the U.K.’s terminology for pharmacy compounding) compounders in the U.K. Nat spends a significant portion of his time lecturing across the pond, educating people on the power of personalized medicine.

“There aren’t a large number of compounding pharmacies in the U.K., but our facility still needs a clinical consultant. It’s important for us to represent and advocate for personalized medication there. Important for us to lead the way, like we did here in the United States.

I ask him, “What does your role look like when you are there?”

“I’m giving lectures all the time, so I’m constantly building power point presentations,” he says, a rue smile on his face. “For me, it’s about being prepared and practice, practice, practice. I spend hours focusing on exactly what I’m going to say when talking about bespoke medication, to make sure that when I say it, it has the largest amount of impact.” Nat is comfortable at center stage. When the lights come on, he shines bright as they do. The PCCA employee chalks this skill up to having been in a rock band since he was 12 years old.

Music is an enormous influence on Nat’s life — everything from country to rock to pop. Nat talks about bands the way other people talk about relatives: He knows them by name, tells me about their accolades, what makes them special.

“Okay,” I start in on him, “What was your favorite band growing up?”

Again, his head rolls back. “Oh, of course it was the Beatles. Geez Louise.”

“And which Beatle were you?”

“None of them,” he says, then grants himself the latitude to reconsider. “Well, maybe Paul. But, he’s a leftie,” referring to Paul McCartney’s left-handed guitar playing.

Nat is clear about two things: One, he loves helping people through customized medicine from both the lectern and the phone. Two, he’s a right-handed guitar player who is looking to give his audience what he calls, “a fat sound.”

“Fat sound?” I ask.

“It’s got a fullness to it. All the singular instruments playing are individually heard, but never overpower the harmony. I cover mostly pop and country stuff. Everybody likes pop. People like to sing along with pop. It makes them feel upbeat, connected. Giving people that feeling is extremely rewarding. When I play for people, I play music that will hold the audience. At least one Johnny Cash song, Garth Brooks’ “Friends in Low Places,” people love that. But I try to keep it current with songs by John Mayer and Ed Sheeran. Ed’s got a really great sound.”

Like many people who are confronted with a tough question, Nat has spent this entire time evading my original question. I fire it back over to him. “So, that in mind,” I say, “who is the greatest front man of all time?”

A little hum of dissatisfaction escapes his lips, but Nat acquiesces: “Well, it’s got to be Mick Jagger.”

I counter, telling him that I think Freddie Mercury is the, unquestionably the, greatest front man of all time.

Nat, a man with a much more seasoned ear for music than I have, lets my opinion roll right over him. He lets out a chuckle, nice enough not to say that it’s at my expense. “Freddie was good too, yeah.”

“Here’s the thing about front men,” Nat leans in, as if we’re about to share a secret. “It’s all practice. I’ve played in front of hundreds, heck, a thousand people from the time I was a kid. Fifty-one years, I’ve been in front of a crowd, either playing or speaking in front of pharmacists at conventions. It’s all practice. It’s like any band — in order to give people the show you want to give them, you have to practice. Practice where the beats fall, where the pauses are. I sit down by myself in a room, get out my slides, and give my lecture to an empty room. I’m rehearsing, always asking myself, “How can I help these people understand compounded medication, but also entertain them. The joke here, a funny slide there. That’s how people remember it. And those things only work because you’ve practiced them.”

I realize in that moment that this is the secret to Nat Jones’s charm: It isn’t his vast knowledge of the intricate systems of the U.K.’s compounding rules and regulations, nor is it his decades-spanning experience with helping treat patients when they feared there was no solutions to their problems.
Nat Jones is a rock star talent with a journeyman’s work ethic, a man who did not allow the early fruits of an innate gift to whither on the vine of half-ripened satisfaction. He cultivated his talent, made it grow.

This is Nat Jones.

A dedicated PCCA Clinical Services team member. He travels across the Atlantic half-a-dozen times a year just to try and spread the word about all the good things pharmacy compounding can do in people’s lives. For over fifty years, he’s been practicing and performing, smiling and singing. He’s a compounding expert with a medical mind as keen as a C-sharp. He is the living embodiment of Beethoven’s heartfelt sentiment about practice:

“Do not only practice your art, but force your way into its secrets, for it and knowledge can raise men to the divine.”

It is no secret that PCCA is proud to name him among our Clinical Services team.

Oral vs. Topical Estrogen: What the Literature Is Showing about Health Risk (Part Two)

Wed, 13 Nov 2019 14:48:48 GMT

By Pamela W. Smith, MD, MPH, MS; Nat Jones, RPh, FIACP, PCCA Clinical Compounding Pharmacist; and Sara Hover, RPh, FAARM, PCCA Clinical Compounding Pharmacist

In the first part of this article, we introduced some new information that is important to consider for patients who need bioidentical hormone replacement therapy (BHRT). Recent medical literature is shedding more light on the risk of venous thromboembolism (VTE) associated with estrogen and how the route of administration can affect its likelihood. Specifically, we reviewed what the literature is showing and discussed compounded sublingual and buccal estrogen. Here, we will continue the discussion further with compounded topical estrogen.

Compounded Topical Estrogen
In addition to sublingual and buccal estrogen, another common route for compounded hormone replacement is topical. Many times, the terms “topical” and “transdermal” are used interchangeably. Strictly speaking, topical refers to the delivery of a drug into the skin to treat a dermal disorder, with the skin as the target tissue. In contrast, transdermal, or percutaneous, absorption refers to the delivery of a drug through the skin for systemic effect. However, we often refer to BHRT compounds as topical because they are topically applied. So when we talk about topical BHRT here, these compounds are intended for hormone delivery through the skin.

There are many factors to consider with absorption through the skin: physical and chemical properties of the drug, molecular weight, solubility, partition coefficient and dissociation constant, the nature of the carrier vehicle, and the condition of the skin. With hormones, the most important factors are the molecular weight and the vehicle or base.

The low molecular weight of hormones definitely lends them to topical delivery as an excellent option. However, we also have to consider the size of the drug particle. When a drug is reduced to a number of smaller particles, or micronized, the total surface area is greater, which results in an increased rate of dissolution. As Allen and Ansel point out, “Due to the different rates and degrees of absorption obtainable from drugs of various particle size, it is conceivable that products of the same drug substance prepared by two or more reliable pharmaceutical manufacturers may result in different degrees of therapeutic response in the same individual.”¹ In other words, the particle size of a hormone can make a clinical difference, so it’s an important consideration in compounding for BHRT.

The base of the compounded preparation is also critical. The type of base and permeation enhancers used can affect absorption of hormones, and the delivery system must be able to release the drug in a reproducible way. As we mentioned in part one, hormones are lipophilic, and a good base will enhance their diffusion through the stratum corneum.¹ In-depth discussion of the importance of a proper base is outside the scope of this article, but we mention this aspect of hormone absorption to stimulate thought.

The main advantage of topical administration is bypassing the first-pass effect.² Estrogen that is absorbed orally passes through the portal vein into the liver, where it is heavily conjugated before being released into the systemic circulation, which may account for the negative effects we listed in the first part of this article. Since this is only seen with oral administration, it is reasonable to hypothesize that this is related to first-pass hepatic metabolism.

One of the disadvantages of topical delivery is the potential for transference to family members and pets. Therefore, compounders should counsel their patients to be aware of contact with others and identify areas to apply creams that will minimize exposure to others. Another perceived disadvantage to topical hormone delivery relates to the limitations of different types of lab testing. The gold standard is serum testing, for example, but topical hormone application does not typically show up in blood serum results. It shows in the saliva. We could write an entire book explaining and debating the differences between serum testing and saliva testing. Each type of testing is looking at a specific compartment of the body and provides different information. We will leave this topic for a future article. Despite the disadvantages of transference or the debate over testing, topical delivery of estrogen is a practical, proven compounding option, and as we have seen in this article, it is safer than oral delivery for postmenopausal women.

The risk of VTE is a very important consideration for choosing the route of estradiol administration, and being cognizant of the possibility of oral absorption from other dosage forms, such as troches, is an important factor to be aware of as well. While a certain type of compound may be popular, the risk of potential harm must take precedence over convenience when making a dosage form recommendation. Consequently, after review of the medical literature, topically applied estrogen is the only form of estrogen replacement that we recommend for a postmenopausal woman.

Pamela W. Smith, MD, MPH, MS, spent 20 years as an emergency room physician with the Detroit Medical Center and then 24 years as an anti-aging/functional medicine specialist. She is a diplomat of the Board of the American Academy of Anti-Aging Physicians and is an internationally known speaker and author on the subject of metabolic, anti-aging and personalized medicine. She has been featured on CNN, PBS and many other television networks; has been interviewed in numerous consumer magazines; and has hosted two of her own radio shows. She is currently the Director of the Center for Personalized Medicine and the founder of The Fellowship in Anti-Aging, Regenerative, and Functional Medicine. Dr. Smith is also the co-director of the Master’s Program in Metabolic and Nutritional Medicine at the Morsani College of Medicine, University of South Florida. Additionally, she is the Director of Medical Education for the American Academy of Anti-Aging Medicine. She is the author of the best-selling books HRT: The Answers, What You Must Know about Women’s Hormones, and many others.

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

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

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

References
1. Allen, L. V., Jr., & Ansel, H. C. (2013). Ansel's pharmaceutical dosage forms and drug delivery systems (10th ed.). Baltimore, MD: Lippincott Williams & Wilkins.
2. Goodman, M. P. (2012). Are all estrogens created equal? A review of oral vs. transdermal therapy. Journal of Women’s Health, 21(2), 161–169. https://doi.org/10.1089/jwh.2011.2839

Oral vs. Topical Estrogen: What the Literature Is Showing about Health Risk (Part One)

Mon, 11 Nov 2019 17:06:34 GMT

By Pamela W. Smith, MD, MPH, MS; Nat Jones, RPh, FIACP, PCCA Clinical Compounding Pharmacist; and Sara Hover, RPh, FAARM, PCCA Clinical Compounding Pharmacist

Compounded bioidentical hormone replacement therapy (BHRT) is an important treatment option for women around the world. Colleagues and patients alike come to us for guidance about this, and our recommendations should be based in part on knowledge about the available delivery options and their impact on safety. In the area of BHRT, some new information has come to light in medical literature that is important to consider for patients. Therefore, we would like to review the risk of venous thromboembolism (VTE) associated with estrogen and how the route of administration can affect its likelihood. In the first part of this article, we will review what the literature is showing and discuss compounded sublingual and buccal estrogen. In the second part of this article we will discuss compounded topical estrogen.

VTE is a general term for a blood clot that forms in a vein. This can manifest as a deep vein thrombosis, where the clot forms in a deep vein of the leg, pelvis or arm.¹ VTE also encompasses pulmonary embolism, which is when a blood clot reaches the lungs.² According to the Centers for Disease Control and Prevention, these “are often underdiagnosed and serious, but preventable medical conditions” that can result in “serious illness, disability, and in some cases, death.”¹ Symptoms of deep vein thrombosis include redness of the skin in the affected area as well as swelling, pain and tenderness to the touch. Pulmonary embolism symptoms include low blood pressure, lightheadedness, fainting, difficulty breathing, fast or irregular heartbeat, chest pain, or even coughing blood. Both conditions are treatable through immediate medical care.¹ There are many risk factors for VTE, including recent surgery, long periods of immobilization and family history, among others.²

What the Literature Says
In recent years, there has been an enormous amount of discussion in the medical literature about estrogen and its route of administration for hormone replacement therapy. The overwhelming evidence has shown that oral estrogen replacement increases the risk of VTE in postmenopausal women with no previous thromboembolic events. Comparatively, non-oral estrogen use did not significantly affect their risk.

In the medical literature examining the relationship between VTE and hormone replacement in menopausal women, the route of administration has been primarily oral. However, studies have revealed that oral estrogen therapy may exert a prothrombotic effect through hepatic induction.^3,4 This is conceivably related to high concentrations of estrogen in the liver due to the liver’s “first-pass” effect. Likewise, a recent study revealed that compared with no hormone therapy, use of oral estradiol was associated with excess risk of VTE. In contrast, use of transdermal estradiol (most commonly used as a patch) was not associated with excess risk of VTE. In addition, the study authors concluded that “transdermal treatment appears to be underused, with the overwhelming preference still for oral preparations.”⁵

Furthermore, in addition to an increase in prothrombotic effects, studies have shown that oral estrogen use is related to other possible side effects^6–16:

Increase in blood pressure
Increase in triglycerides
Increase in estrone
Increase in occurrence of gallstones
Increase in liver enzymes
Increase in sex hormone binding globulin, which lowers available testosterone for the body to use
Interruption of tryptophan metabolism and consequently serotonin metabolism
Lower growth hormone levels
Increase in C-creative protein
Increase in carbohydrate cravings

Other medical trials that have compared oral and transdermal estrogen replacement also discovered that transdermally administered estrogen has little or no effect in increasing prothrombotic substances. Furthermore, transdermal estrogen may have beneficial effects on proinflammatory markers (such as C-reactive protein and prothrombin activation peptide) as well as antithrombin activity. It may have a suppressive effect on tissue plasminogen activator antigen and plasminogen activator inhibitor activity in contrast to oral estrogen as well, which would also be beneficial in many cases.^4,14,17–20

Other study authors also examined the risk of transdermal estrogen use compared to patients that did not use hormone replacement therapy and showed that there was no increased risk compared to nonusers.^21–25 Some research also suggested that transdermal estrogens may substantially improve the benefit/risk ratio of postmenopausal hormone therapy and should be considered as a safer option, especially for women at high risk for VTE.²¹ In fact, other studies revealed that women who were overweight⁸ and women who had prothrombotic mutations also had no increased risk of thrombosis with transdermal estrogen replacement therapy.²⁶

Lastly, researchers have also investigated whether patients with a previous thromboembolism, family history of thromboembolism or prothrombotic mutation could take estrogen replacement therapy. The studies revealed that the above were a strong contraindication to oral hormone replacement therapy, but transdermal estrogen could be considered after careful individual evaluation of the benefits and risks. Furthermore, these studies suggested that transdermal estrogen should also be the first choice for overweight and obese women requiring hormone replacement therapy.^27,28

Compounded Sublingual and Buccal Estrogen
When considering compounded estrogen delivery, there are several choices. The list includes multiple dosage forms, and two of the most common provide sublingual or buccal delivery and topical delivery (with or without permeation enhancement). While vaginal/labial applications, injections and pellets are also treatment options, we are going to focus on the more common ones.

Sublingual and buccal delivery are similar and often used in medicine for patients who either can’t swallow a solid dosage form or for specific medical reasons, such as hyperemesis (severe nausea and vomiting). Sublingual administration involves placing medication under the tongue to absorb through the mucosa into the bloodstream. Buccal administration involves placing a medication between the gum and the cheek, where it absorbs through the mucosa and into the bloodstream. Absorption is generally considered rapid and efficient, and these routes avoid first-pass metabolism, though many dosage forms that are intended for sublingual or buccal delivery commonly also allow oral intake through normal salivary action. Sublingual absorption occurs in part through the ventral surface of the tongue or the floor of the mouth into the reticulated vein. The main mechanism for the absorption of a drug into oral mucosa is via passive diffusion into the lipoidal membrane.

The sublingual area is more permeable than the buccal area, which is more permeable than the palatal area (top of the mouth). These differences are generally related to the relative thickness, blood supply and degree of keratinization of these membranes. For a drug to be absorbed completely through the sublingual route, it must have slightly higher lipid solubility for passive permeation, and luckily, estrogens are lipophilic (fat soluble).²⁹Notably, sublingual BHRT seems to be effective in reducing vasomotor, mood and quality-of-life symptoms experienced in postmenopausal women.³⁰

While compounders have prepared sublingual hormone drop formulas for years,³¹ troches are the most popular sublingual and buccal dosage form for BHRT. There is a lot of older pharmacokinetic data published on sublingual use from manufactured oral estradiol tablets.^32–34 This data clearly shows sublingual administration resulted in rapid absorption with significantly higher estradiol levels than did comparable oral dosing, and these increased levels fell rapidly over the first six hours, indicating the need for multiple daily doses considering the half-life of oral estradiol is approximately one to two hours at steady state. There are no similar pharmacokinetic studies for comparable compounded dosage forms (rapid dissolve tablets or tablet triturates), but assuming extremely close dissolution times, one could expect similar outcomes.

Even though sublingual and buccal absorption of estrogen is relatively rapid, troches dissolve more slowly than tablets (from 20 minutes to an hour depending on the formulation). Additionally, more than 50% of the troche is swallowed by the normal mechanism of saliva formation, and the remainder is absorbed transmucosally.³⁵ Because over half of the troche is swallowed, prescribers and compounders must be aware that estrogens given in this manner may have a similar risk of VTE as oral administration, and we therefore do not recommend estrogen troches for postmenopausal women.

Pamela Wartian Smith, MD, MPH, MS, spent 20 years as an emergency room physician with the Detroit Medical Center and then 24 years as an anti-aging/functional medicine specialist. She is a diplomat of the Board of the American Academy of Anti-Aging Physicians and is an internationally known speaker and author on the subject of metabolic, anti-aging and personalized medicine. She has been featured on CNN, PBS and many other television networks; has been interviewed in numerous consumer magazines; and has hosted two of her own radio shows. She is currently the Director of the Center for Personalized Medicine and the founder of The Fellowship in Anti-Aging, Regenerative, and Functional Medicine. Dr. Smith is also the co-director of the Master’s Program in Metabolic and Nutritional Medicine at the Morsani College of Medicine, University of South Florida. Additionally, she is the Director of Medical Education for the American Academy of Anti-Aging Medicine. She is the author of the best-selling books HRT: The Answers, What You Must Know about Women’s Hormones, and many others.

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

References
1.   Centers for Disease Control and Prevention. (2019). What is venous thromboembolism? Retrieved from https://www.cdc.gov/ncbddd/dvt/facts.html
2.   National Heart, Lung, and Blood Institute. (n.d.). Venous thromboembolism. Retrieved from https://www.nhlbi.nih.gov/health-topics/venous-thromboembolism
3.   Nabulsi, A. A., Folsom, A. R., White, A., Patsch, W., Heiss, G., Wu, K. K., & Szklo, M. (1993). Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. The New England Journal of Medicine, 328(15), 1069–1075. https://doi.org/10.1056/NEJM199304153281501
4.   Lowe, G. D., Upton, M. N., Rumley, A., McConnachie, A., O’Reilly, D. S., & Watt, G. C. (2001). Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein — A cross-sectional population survey. Thrombosis and Haemostasis, 86(2), 550–556.
5.   Vinogradova, Y., Coupland, C., & Hippisley-Cox, J. (2019). Use of hormone replacement therapy and risk of venous thromboembolism: Nested case-control studies using the QResearch and CPRD databases. The BMJ, 364.https://doi.org/10.1136/bmj.k4810
6.   Smith, P. (2010). What you must know about women’s hormones. Garden City Park, NY: Square One Publishing, 2010.
7.   Ballagh, S. A. (2005). Vaginal hormone therapy for urogenital and menopausal symptoms. Seminars in Reproductive Medicine, 23(2), 126–140. https://doi.org/10.1055/s-2005-869480
8.   Canonico, M., Oger, E., Conard, J., Meyer, G., Lévesque, H., Trillot, N., … Scarabin, P. Y. (2006). Obesity and risk of venous thromboembolism among postmenopausal women: Differential impact of hormone therapy by route of estrogen administration. The ESTHER Study. Journal of Thrombosis and Haemostasis, 4(6), 1259–1265. https://doi.org/10.1111/j.1538-7836.2006.01933.x
9.   Chetkowski, R. J., Meldrum, D. R., Steingold, K. A., Randle, D., Lu, J. K., Eggena, P., … Judd, H. L. (1986). Biologic effects of transdermal estradiol. The New England Journal of Medicine, 314(25), 1615–1620. https://doi.org/10.1056/NEJM198606193142505
10.   Pansini, F., Bergamini, C. M., Bonaccorsi, G., Breveglieri, P., Calisesi, M., Valpondi, V., … Mollica, G. (1990). Control of carbohydrate metabolism in menopausal women receiving transdermal estrogen therapy. Annals of the New York Academy of Sciences, 592(1), 460–462. https://doi.org/10.1111/j.1749-6632.1990.tb30374.x
11.   Scarabin, P. Y., Alhenc-Gelas, M., Plu-Bureau, G., Taisne, P., Agher, R., & Aiach, M. (1997). Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arteriosclerosis, Thrombosis, and Vascular Biology, 17(11), 3071–3078. https://doi.org/10.1161/01.atv.17.11.3071
12.   Vehkavaara, S., Silveira, A., Hakala-Ala-Pietilä, T., Virkamäki, A., Hovatta, O., Hamsten, A. … Yki-Järvinen, H. (2001). Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women. Thrombosis and Haemostasis, 85(4), 619–625.
13.   Vongpatanasin, W., Tuncel, M., Mansour, Y., Arbique, D., & Victor, R. G. (2001). Transdermal estrogen replacement therapy decreases sympathetic activity in postmenopausal women. Circulation, 103(24), 2903–2908. https://doi.org/10.1161/01.cir.103.24.2903
14.   Folsom, A. R., Lutsey, P. L., Astor, B. C., & Cushman, M. (2009). C-reactive protein and venous thromboembolism. A prospective investigation in the ARIC cohort. Thrombosis and Haemostasis, 102(4), 615–619. https://doi.org/10.1160/TH09-04-0274
15.   Rovinski, D., Ramos, R. B., Fighera, T. M., Casanova, G. K., & Spritzer, P. M. (2018). Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: A systematic review and meta-analysis. Thrombosis Research, 168, 83–95. https://doi.org/10.1016/j.thromres.2018.06.014
16.   Lissett, C. A., & Shalet, S. M. (2003). The impact of dose and route of estrogen administration on the somatotropic axis in normal women. The Journal of Clinical Endocrinology & Metabolism, 88(10), 4668–4672. https://doi.org/10.1210/jc.2003-022036
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Profile In Personalized Medicine - Karen Francis

Fri, 08 Nov 2019 15:16:42 GMT

By PCCA

This Profile in Personalized Medicine highlights Karen Francis, RPh, owner of Compounding Wellness Pharmacy located in St. John's, Newfoundland and Labrador, Canada. A PCCA member since 2003, Karen graduated in 1985 from the College of Trades and Technology, St. John's, Newfoundland and Labrador, Canada.

How did you start compounding? What led you to PCCA?

My interest in compounding sparked at a young age. In my last year of high school, I worked as a cashier in a family owned and operated independent community pharmacy. To help pay for university, I stayed on and worked part time during the school year and full time during the summers. My plan was to study French and linguistics. However, the owner of the pharmacy asked me if I'd like to work with him in the dispensary during the summer. Parkdale was the go-to pharmacy in St. John's. If you could not find something, you would go to Parkdale, and the owner would find it for you. He always said, "If you can't fill your customer's prescription, you shouldn't call yourself a pharmacy.” He always went that extra mile.
Their pharmacy was innovative, ahead of its time and, most importantly, always working to meet and exceed their customers’ needs. Compounding techniques were very different back then. I remember lots of powder papers, glass ointment slabs and the torsion balance. My career path changed because of the time I spent at Parkdale.

In 1995, I started my own business and opened my own community pharmacy in a neighboring city near St. John’s. I became a PCCA member in 2003. It was a natural fit for me. I never conformed to the fact that one size fits all in medicine. Becoming a compounding pharmacist and working closely with PCCA is a gift that keeps on giving. The guidance and partnership from PCCA, along with the wonderful, caring team of pharmacists, technicians and assistants I work with, has granted me the opportunity to continue Parkdale’s legacy, ideologies and values about patient care by taking it to the next level.

What was your toughest patient problem? How did you solve it?

A close friend ruptured his Achilles tendon and required surgery. Unfortunately, while recovering and wearing a boot cast, it became severely infected. Due to the location of the infection, traditional therapies for wound care were difficult to apply and therefore ineffective. As a favor, he asked me to look at it and perhaps give him some advice. I was a young compounder at that time and had no experience with wound care. I quickly remembered why I chose pharmacy as he removed the dressing and showed me the wound. It was difficult not to show emotion or get sick from the odor. I was anxious to help. We took photos, and I called PCCA for formula suggestions. The consultant who called back was knowledgeable, and he took the time to explain why he suggested each active pharmaceutical ingredient and base. The next step was to speak to his family doctor. The patient-doctor-nurse-pharmacist relationship is critical for optimal patient care. I offered him another option using multiple active ingredients and Polyox® powder as the base. He reluctantly agreed. With a few tweaks to the original formula (as each patient is unique), there was marked improvement within two weeks. This was noted by the wound care nurses responsible for his daily care. He had a long recovery with corrective skin surgery required, but he will be always grateful for our help.

What is your favorite PCCA base, and why?

MucoLox™. It's so versatile. It can be used in an endless number of applications. We have had great results both orally and vaginally.

What has been your most satisfying patient experience?

I have had so many satisfying patient experiences. I can't narrow it down to just one. As a women's health consultant and advocate, I have been blessed to have spoken to and have met with so many wonderful women from all age groups — each seeking advice and help in dealing with the numerous symptoms associated with hormone imbalances, nutrition and stress-related issues through the pre- to postmenopausal years. Most women "knew something wasn't right" anymore. Some may laugh, but in my little corner of the country, I've become known as "the hormone lady.” Women's health will always be my passion. I feel it's my responsibility as a pharmacist to correctly educate around the "taboo" subject of bioidentical hormone replacement therapy (BHRT), by providing each patient and her physician with the most current and up-to-date information and treatment options. This allows a woman and her physician to make an informed decision on if she should use BHRT or not, based on her own individual symptoms and risk factors. Knowledge is power.

Hopefully, the days of "one size fits all” medicine will soon be over. Compounding has opened so many doors for me. Cyril Lee, my marketer, and I have built relationships in the community by doing lunch and learns with small groups of physicians. These are unique opportunities to meet the doctors in local neighborhoods. Unlike traditional pharmaceutical sales, we are not promoting a particular drug or class of medication. We are adding tools to their repertoires. We give them an opportunity to think outside the box for individualized treatment options. PCCA has given me the confidence needed to advocate for all of my patients. They provide us with current and topic-related formulas and information sessions that are unbiased. They are constantly adding to their product line, making my role as a problem-solver even more exciting.

What’s the biggest “aha” moment you’ve had as a member of PCCA?

Probably the biggest "aha" would have to be the very first compound we prepared. It was actually a double "aha." A first-time mom had a young boy who was experiencing gastroesophageal reflux disease, and she was having a difficult time giving him the medication. He did not like the flavor. The only commercially available product at the time was Zantac®. She and her family were already patients at the pharmacy, so we already had an existing relationship, built on trust. As a young pharmacist, up to this point, I had not developed the confidence to speak to a physician on an equal level as a fellow professional. They would call in prescriptions; I would take their orders. However, I had just recently attended training at PCCA. I learned so much and gained confidence in my ability as a pharmacist. My brain was on overdrive. I wanted to share this new information with any and all who I felt could benefit.

I suggested to the mother that I would reach out to her son’s physician and suggest something else. This was unheard of at that time in my career. I gathered up the courage to make the phone call and dialed the number. Panic had taken over. He answered. I explained who I was and why I was calling, and I made my first recommendation. I'm sure he knew I was nervous. You could hear it in my voice.

To my amazement, he was interested! He absolutely approved, and we chatted for a few minutes longer. He thanked me. That was part one of this "aha." Some years later, I told him that story and we laughed.

To be honest, the preparation of that first simple compound probably took us about an entire day to complete. We decided to make a partially sugar-dipped, star-shaped medicated gummy in the color and flavor of his choice. We spoke with the consultants at PCCA many times that day. They held our hand through the entire process. I can't remember exactly how many times we remade it, trying to perfect it. The ultimate test would be with the young boy. He liked it and continued to take it. Mom was happy. We did it. It was a homerun!
I'll never forget the feeling on that day. That is what pharmacy is all about. This is the true role of a pharmacist. I'm a problem-solver — this was part two of my "aha." That day, we found our home with PCCA. I've never looked back.

What advice would you give new compounders?

Do not be afraid to step outside of your box. There are so many opportunities within compounding. Choose a subject area that you show interest in and become the expert in that area. Patients will seek you out.

Do not assume that your local physicians will know about compounding, and do not be afraid to go visit them. Some actually want to know more.

Most importantly: Learn something new every day.

Upcoming Changes to PCCA Formulas per the New USP <795>, <797> and <800> (Part Two)

Wed, 06 Nov 2019 14:52:37 GMT

By Melissa Merrell Rhoads, PharmD, PCCA Director of Formulation Development

As I wrote in the first part of this article, on June 1, 2019, the United States Pharmacopeial Convention published revisions to the compounding Chapters <795> and <797> in the United States Pharmacopeia and National Formulary, which were set to become official on December 1. However, USP later announced that they would postpone that official date because of pending appeals to certain parts of the revised chapters. The revisions in USP <795> and <797> affect the beyond-use date (BUD) that can be applied to compounded formulations, among other standards.

Even though the date when the revised chapters become official is postponed, our Formulation Development department is working on updates to our formulas to be compliant with the new USP standards. We will complete these updates within our formulation database when we are notified of the new official date and contents of the Chapters <795> and <797>, and they will go into effect in our database on the day that they become official. Therefore, it will be important for PCCA members to download the latest versions of PCCA formulas after the date that the new chapters become official (which has not been announced yet), as there will be changes that should be noted and documented for master formulas.

Therefore, we wanted to announce what these future changes will look like. Below is a summary of the formula changes based on the latest version of USP Chapter <797> as it is written currently. We will make further changes as needed based on the appeals outcome, and we will announce those changes as well.

Changes Related to USP <797>
Sterilization Procedures
Section 10 of the revised USP Chapter <797> discusses sterilization and depyrogenation for compounded sterile preparations (CSPs). The method of sterilization plays a role in establishing the BUD for CSPs. The chapter establishes two categories for CSPs: aseptically processed, which are sterilized by filtration, and terminally sterilized, which are sterilized by steam heat (autoclaving) or dry heat. We will update PCCA formulas to reflect these compounding processes and provide specific instructions to render the preparations sterile.

BUDs
Section 14 of USP Chapter <797> discusses the parameters for establishing BUDs for CSPs. Table 11 of the chapter covers the parameters in detail, but the BUDs are based primarily on factors that affect the achievement and maintenance of sterility (risk of microbial contamination). The chapter assumes that CSPs will remain chemically and physically stable within the container-closure systems used. Chapter <797> does not provide specific direction on chemical stability, but requires that compounders consider the chemical and physical properties of the drug and/or its formulation as well as the compatibility of the container-closure system with the finished preparation. Since establishing a BUD per these new guidelines depends on multiple factors, our sterile formulas (outside of FormulaPlus formulas) will no longer assign a specific BUD, but will rather provide the relevant guidelines for compounders to determine the maximum BUD they will be able to assign based on whether sterility testing was performed and passed and the temperature at which the preparation will be stored.

According to USP Chapter <797>, a multiple-dose CSP must additionally pass antimicrobial effectiveness testing in accordance with USP Chapter <51>. After the multiple-dose CSP is dispensed, and upon initially entering or puncturing the container for the first time, “the multiple-dose container must not be used for longer than the assigned BUD or 28 days if supported by antimicrobial effectiveness testing results (see <51>) on the CSP, whichever is shorter.” As an alternative, compounders may dispense the preparation in smaller, sealed, single-use, sterilized and depyrogenated container-closure systems.

According to the new guidelines as they are currently written in USP Chapter <797>, there are no means to extend a BUD beyond the dates listed in Table 11. However, PCCA’s data on our sterile FormulaPlus formulas is still a valuable resource. Since USP <797> does not address chemical stability, these studied formulas provide documented chemical stability and therefore ensure the chemical and physical stability of the preparation. We have 12 sterile FormulaPlus formulas, and several are bracketed studies allowing for a broad range of active ingredient concentrations. PCCA members can view these in the FormulaPlus master list.

Given the significant changes in pharmacy compounding recently, it is as important as ever to ensure that compounders comply with the latest standards. We hope that the updates we will make to our formulas when the new USP <795> and <797> become official — as well as the change we’ve implemented for compliance with USP <800> — will help them do just that. If PCCA members with Clinical Services access have questions about any of these changes, they can contact our Clinical Services department.

A version of this article previously appeared in PCCA’s members-only magazine, the Apothagram. PCCA members can find a more detailed description of these formula changes in the Fall 2019 issue.

Reference
United States Pharmacopeial Convention. (2019). General chapter <797> pharmaceutical compounding — Sterile preparations. In United States pharmacopeia and national formulary (USP 42nd ed. & NF 37th ed.). Rockville, MD: United States Pharmacopeial Convention, Inc.