Mortar & Pestle

Nebraska January/February 2020 | Volume 83, Number 1 MORTAR & PESTLE Official Publication of theNebraska Pharmacists Association

Pam Miller 2020 NPA President

Fraud, Waste, and Abuse USP Chapter <800> Handling Hazardous Drugs in 1.0 hour Knowledge-based CPE Activity Healthcare Setting: Considerations for STERILE Products $10 NPA Member | $20 NonMember and Compounding 1.0 hour Knowledge-based CPE Activity How to Engage Your Senators: You Can Make $25 NPA Member | $50 NonMember a Difference 1.0 hour Knowledge-based CPE Activity USP Chapter <800> Handling Hazardous Drugs in $0 NPA Member | $25 NonMember Healthcare Setting: Considerations for Non-Sterile Products and Compounding Nicotine Cessation Counseling: A Guide for Pharmacists 1.0 hour Knowledge-based CPE Activity 2.0 hours Knowledge-based CPE Activity $25 NPA Member | $50 NonMember $25 NPA Member | $50 NonMember

Risky Business: Assessment of Risk on Hazardous Drugs 1.0 hour Knowledge-based CPE Activity $25 NPA Member | $50 NonMember

NPA Staff Joni Cover, JD Marcia Mueting, PharmD Diane Webb Sarah Hunter Chief Executive Officer VP, Professional Affairs Finance & Marketing Project Coordinator

Pharmacy Technician Second class postage paid at Lincoln, Board of Directors Publisher Nebraska, and at additional mailing offices. Tyler Garrelts The Nebraska Mortar & Pestle (M&P) (ISSN President, Pam Miller Postmaster: send address changes to 0028-1891) is owned and published by Immediate Past President, Nebraska Mortar & Pestle, 6221 S 58th St, the Nebraska Pharmacists Association to Suite A, Lincoln, NE 68516-3687 or email Ally Dering-Anderson Students provide continuing pharmacy education, [email protected]. President-Elect, Brent Gollner Alexander Brown, CU drug information, news, and trends in Treasurer, Jeffrey Steffensmeier Cory Durbin, UNMC the profession of pharmacy. Opinions Chief Executive Officer, expressed by the contributors, whether Joni Cover Network Chairs signed or otherwise, do not necessarily Nebraska Pharmacists Association reflect the attitudes of the publisher nor are Academia/Specialty Practice, 6221 S 58th St, Suite A they responsible for them. Lincoln, NE 68516 District Members Alli Gabriel p: 402.420.1500 | f: 402.420.1406 District 1, Ken Kester Chain, Kendra Kapels The M&P is published six times a year District 1, Jeffrey Steffensmeier Hospital/Health-System, - February, April, June, August, October e: [email protected] | w: npharm.org and December. The subscription rate District 2, Jeanie Shipman Jerome Wohleb for non-members is $30 per year. The District 2, Eric Sundsboe Independent, Trevor Bertsch managing editor is Joni Cover. The office District 3, Beth Boals-Shively Industry, Ryan Flugge of publication is 6221 S 58th St, Suite A, District 3, Tim Redline Long-Term Care, Lincoln, NE 68516-3687. Mackenzie Farr New Practitioner, Jacelyn Watt

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In Case You Missed It Your NPA member benefits include a daily email with important drug and health information, as well as answers to member questions. Below is a partial list of some of the most recent Daily News Dose items and other important pharmacy news that you may have missed.

Annual Convention Change Foundation & NebPharmPAC Donors The NPA will not be hosting a full Many thanks to the generous pharmacists Membership Drawing convention this year. Instead, more who have donated to the Nebraska Pharmacy targeted CPE programs will be offered. Foundation and the NebPharmPAC. It's easy to Winners Congratulations to the following Please let us know what CPE topics donate! Call the NPA office at 402-420-1500 or NPA members who won a $50 and formats work best for you by email [email protected] and donate today. Amazon e-Gift for renewing contacting Marcia Mueting, PharmD, their 2020 membership before Vice President of Professional Foundation December 15, 2019. Affairs, at 402-420-1500 Sam Augustine Joseph Lathrop • Sheila Brumbaugh, RP, Red Cloud or [email protected]. Jeff Baldwin Robert Leopold • Rachel Forrest, RP, Omaha Dan Billerbeck Fred Massoomi • Jerry Jensen, RP, Kearney Kendra Bunkers Melvin Menke Nebraska Legislative Session • Jeanette Kadow, CPhT, Hastings New Legislative Bills have been Anne Bruckner William Michael Jeffrey Brommer Pam Miller And thanks to all of you for renewing introduced this year. The NPA's your membership for 2020! Long-Term Care Issues Work Group Joni Cover Charlie Moore Ally Dering-Anderson Marcia Mueting developed consensus language and Edward DeSimone Tracy Neujahr is exemplified in LB 847. The NPA also USP Chapter <800> Mackenzie Farr Gary Northouse According to the recently posted developed prescription adaptation Wendall Gaston Russ Rathjen USP <800> Frequently Asked language as drafted in LB 887. Tiffany Goeller Roger & Paula Riesberg Questions document, USP Chapter Thank you to Senator John Arch for Brent & Patty Gollner Gary Rihanek <800> (Hazardous Drugs— sponsoring these two bills. LB 922 was Donald Graham Niki Salomon Handling in Healthcare Settings) introduced by Senator Mark Kolterman John Guzallis Nancy Sloan Chapter <800> only applies when to mandate eprescribing of controlled Matt Guzallis Paula Stobbs a practitioner is compounding. It substances beginning 01/01/2021. Linda Guzman-Gonzales Arlin Stutheit Reg Hain Jenny Tilleman states that since administration and Watch your emails for NPA Hall County Bill Tooley dispensing final dosage forms are Legislative updates that are sent to Pharmaceutical Floyd VanEngen not compounding, Chapter <800> NPA members on Fridays during the Association Phil Vuchetich does not apply to those functions. Legislative Session. A link to the NPA's Roger Ladd Further, "Final dosage forms of Legislative Summary will also be HDs that do not require any further included in these emails. If you have NebPharmPAC manipulation may be dispensed any questions during the Session, without any further requirements for contact Joni Cover at [email protected] Clark Anderson Charlie Moore Roy Anderson Linda Myers-Bock containment unless required by the or at 402-420-1500. Sam Augustine Scott Persson manufacturer or if visual indicators Jeff Baldwin Charlie Pierce of HD exposure hazards are present NPA Pharmacy Law Manual Jeffrey Brommer Russ Rathjen (e.g., HD dust or leakage). These do The NPA Pharmacy Law Manual - Rick Clabaugh Roger & Paul Riesberg not require any additional storage updated with 2019 legislative changes Edward DeSimone Niki Salomon Tiffany Goeller Paula Stobbs or handling requirements according - is now available. Find Nebraska to USP <800> unless otherwise pharmacy statutes and regulations Brent & Patty Gollner Arlin Stutheit Matt Guzallis Bill Tooley required by the manufacturer." in one place. What a great pharmacy Linda Guzman-Gonzales Floyd VanEngen reference! No need to search the Reg Hain Phil Vuchetich internet or paper copies. Visit the NPA William Michael online store to order your copy www.npharm.org/store_home.asp.

www.npharm.org 3 Nebraska MORTAR & PESTLE President's Message Mindful of Your Trust Pam Miller, PharmD, RP

As we launch a new decade and I begin my new role as President, I am proud to count myself among you, my peers, as a pharmacist in Nebraska. Of all professions, the pharmacist is considered one of the most trusted of all.

I am very mindful of the trust that sustains and elevates our profession.

The Nebraska Pharmacists Association (NPA) is like a vault of information, best practices, and collective leadership established with a firm sense of responsibility bridging generations . . . past, present, and future.

We are facing a time when pharmacists and the NPA will need to be a resource to our legislative leadership in elected offices across the State. As their resource, we need to establish a relationship of trust throughout every county and voting district.

And, our most important tier of trust, pharmacy students of the future need to bank on what we do today as solid, ethical, and compassionate. They need to trust in our leadership and outcomes.

I would like welcome new Board members: President-Elect, Brent Gollner; District 3, Tim Redline; Academia/Specialty Network Chair, Alli Gabriel; Chain Network Chair, Kendra Kapels; and Pharmacy Technician Representative, Ty Garrlets. Thanks to outgoing Board members: Jenny Tilleman; Kelly Hamilton; Christina Gerard; and Nicole White for their service on the NPA Board.

I am sincerely looking forward to a great year!

Honored to have your trust,

Pam Miller, PharmD, RP NPA President

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UNMC College of Pharmacy faculty awarded Distinguished Scientist Awards

Kim Scarsi, Pharm.D. and Aaron Mohs, Ph.D. have been awarded the 2019 Distinguished Scientist Awards. The award recognizes them as research leaders at UNMC with a history of significant national funding and recognition based on their scholarly activity. The Distinguished Scientist Awards will be presented on March 3, 2020.

Dr. Scarsi’s research program works to optimize the pharmacologic treatment of persons living with HIV. Her ongoing projects include both domestic and international sites, with an emphasis on women living with HIV and persons co- infected with HIV and tuberculosis. Dr. Scarsi also serves as an investigator Kim Scarsi, Pharm.D. with the AIDS Clinical Trials Group.

Dr. Mohs’ research is focused on the development of new fluorescent imaging contrast agents to guide surgical removal of tumors. He has developed instruments that could one day be used in the operating room to see these contrast agents real time. As opposed to a paint by number, this is a Aaron Mohs, Ph.D. cut by color technology. His group has research projects focused on developing new drug delivery systems that target tumor metabolism and pathogen biosensing.

Don Ronning, Ph.D. joins the College of Pharmacy Don Ronning, Ph.D., joined the College of Pharmacy in January as Professor in the Depart- ment of Pharmaceutical Sciences Dr. Ronning received his Bachelor of Science in Biochemistry from University of Minnesota -Twin Cities and his Ph.D. in Biochemistry from Texas A & M Univer- sity.

Dr. Ronning’s research focuses on structural biology of microbial proteins, discovery and development of antibacterial compounds, and identifying mechanism-of-action of old antibacterial drugs. Dr. Ronning is an active member of American Chemical Society, the American Society of Microbi- ology and the American Association for the Advancement of Science.

High School Alliance When one thinks about coursework in high school, classes that often come to mind include English or Biology or even PE. But what if one could take a class in gross anatomy, microbiolo- gy, or even pharmacy? These are the types of classes offered to select Junior and Seniors en- rolled in the UNMC High School Alliance Program. In partnership with Omaha Public Schools, Millard Public Schools, Westside Public School and other schools in the Omaha-metropolitan area, approximately 60-70 students are chosen each year to participate in this enrichment program. Students meet on the UNMC campus during the afternoons for the entire academic year, taking 2 classes per semester. Classes in medical research, genetics, pathology, behavioral health and pharmacy are a sampling of the opportunities afforded to these students.

The "Introduction to Pharmacy" class was implemented in 2016, with approximately 100 students having completed the program to date. The goal of the class is to expose the students to the variety of options available within the field of pharmacy. The course begins with the field of pharmacognosy, followed by drug design and development, compounding of extemporaneous and aseptic products, and the FDA approval process. The second half of the semester is focused on cardiovascular disease. Students have an opportunity to examine human and porcine hearts, followed by in-depth therapeutic discussions about nutrition, hypertension, hyperlipidemia, stroke, and diabetes. Students are taught pharmacotherapeutics by existing pharmacy students, including the medications, therapeutic endpoints, and potential toxicities. High School Alliance students conclude the semester with pharmacogenomics and pharmacy ethics.

High school students frequently comment at the end of the semester how pharmacy is much "bigger" than what they initially perceived. The UNMC COP is beginning to see students from the program apply to pharmacy school. In fact, 2 students in this year's P1 class completed the High School Alliance Program. The students who successfully pass the program are guaranteed an interview for pharmacy school. The UNMC COP is excited about this partnership with the High School Alliance, and look forward to training the next generation of pharmacists. Individuals who may have questions about the program can contact Dr. Chris Shaffer at [email protected].

www.npharm.org 5 Nebraska MORTAR & PESTLE Member Spotlight

Sabrina Beck, PharmD, RP Pharmacy Supervisor

Where do you practice? I am a hospital pharmacist at CHI CUMC Bergan in Omaha where I have worked for the last five years. I feel fortunate to be a part of this team and I am proud of the work we do. What advice do you have for someone looking Where did you attend pharmacy school?

I graduated from the University of Nebraska Medical Center to pursue a career as a hospital pharmacist? I would encourage the person to be realistic about the College of Pharmacy. schedule. The role of the pharmacist is integrated into the healthcare team and sometimes that can mean a Why did you choose to pursue a career in challenging schedule that includes weekends, evenings, hospital pharmacy? and overnights. Knowing that you are helping people and As a high school student, I cashiered in a retail pharmacy having a passion for the work you are doing certainly makes and worked as a nurse’s aide in a hospital. Working as a up for a sometimes crazy schedule. nurse’s aide helped expose me to the challenges of nursing as well as the acute care environment. I had a mentor, Marcia Mueting, in the retail environment who helped me What is it like having your spouse also be a decide to pursue pharmacy as a career. I worked both hospital pharmacist? inpatient and outpatient as a pharmacy student. After It works out great. It is always nice to have a colleague graduation, I worked at the University of Nebraska Medical near to bounce ideas off of. Jon is very supportive and Center for Jim Dubé where I staffed on the medical/surgical understands that my position is unpredictable. I appreciate units and in the OR pharmacy. I eventually took a leadership that I can run into work without upsetting my spouse, and position in the central operations role. The experience was hopefully he feels the same way. invaluable and the personal and professional relationships I developed through that position continue to be of great value. Is there an NPA member who's work needs to What made you want to serve on the Board of be recognized? Contact NPA Project Coordinator, Pharmacy? Sarah Hunter, at 402-420-1500 or [email protected]. I thought it would be a great opportunity to advocate for We want to hear from you! my profession by being actively involved in protecting public health. My favorite part of being on the Board is the connections that I have made with representatives from the colleges, the NPA, DHHS staff, and other Board members.

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UPDATE FROM CREIGHTON UNIVERSITY SCHOOL OF PHARMACY AND HEALTH PROFESSIONS

Pharmacy Skills Lab Named in Greenwood Family’s Honor

Bob, BSPHA’77, and Cheryl “Chery” Greenwood, of Waterloo, Iowa, recently made a significant gift to the Creighton School of Pharmacy and Health Professions, and the University has renamed the newly renovated pharmacy skills lab in their family’s honor. The Greenwoods’ commitment to Creighton has stayed strong in the four decades since Bob graduated. His and Chery’s children all attended Creighton—Tim, BA’09, JD’13; Joe, PharmD’18; and Abby Greenwood, who finished her degree elsewhere. A 2014 recipient of the Alumni Merit Award, Bob has served on SPAHP’s alumni advisory board and this year joined Creighton’s Board of Trustees. He’s also taught at the University as an adjunct professor and preceptor. And he and Chery make it back to most Reunion Weekends and to as many Creighton basketball games as time allows.

“Creighton will always be a special place for our family,” Chery says. Bob also served as a leader for various professional “We’ve been very blessed, and Creighton is a big part of our success.” organizations, including the National Community Pharmacists Association, the American Pharmacists Shortly after graduating Creighton, Bob moved to Waterloo and Association and the Iowa Pharmacy Association. He also opened a pharmacy with a few partners. Within a decade, he and his served on Waterloo’s city council for 12 years. family would own a Waterloo pharmacy outright, gradually adding locations in the years that followed. Even in the thick of work, family, business, professional commitments and city council meetings, Bob and Chery Greenwood Pharmacy now offers a range of services, including retail, stayed plugged in to the University and helped to shape assisted living, immunizations, medication therapy management the School of Pharmacy and Health Professions. and long-term care practice. It was his clinical education, Bob says, that prepared him to offer such a diversity of services. Creighton affected the Greenwoods’ lives deeply. They, in turn, returned the favor. “I’ve always loved helping patients however I could,” he says. “And I’ve been able to help them in so many ways. That includes getting “I didn’t have the best grades, but I was driven, and people the medications they need and helping guide them through Creighton’s pharmacy school took a chance on me,” chronic disease states, like diabetes or congestive heart failure.” Bob says. “Creighton means a lot.”

DeSimone Appointed to Task Force Teply Publishes Project on Hepatitis C Virus Care

Edward DeSimone II, RPh, PhD, FAPhA, Robyn M. Teply, PharmD’07, MBA’07, BCACP, professor in the Department of Pharmacy associate professor in the Department Sciences, was appointed to the Substance of Pharmacy Practice, published a Use Disorders Special Interest Group, project with colleagues from Temple “Taskforce on Update of the 2010 Report of University, University of Illinois at the AACP Special Committee on Substance Chicago and Vanderbilt University, Abuse and Pharmacy Education,” “Expanding Hepatitis C Virus Care and was appointed to the Nebraska and Cure; National Experience Using Department of Health and Human Services a Clinical Pharmacist-Driven Model” Comprehensive Opioid Abuse Program. in Open Forum Infectious Diseases.

Save the Date: May 28–31, 2020 Visit creighton.edu/reunionweekend to stay up to date on details.

spahp.creighton.edu

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Continuing Pharmacy Education | Lesson #1

Vitiligo and Treatment Options

Written by Kristen Grimaldi This continuing pharmacy education lesson was written by Kristen Grimaldi, PharmD Candidate, University of Nebraska Medical Center College of Pharmacy who does not have any conflicts of interest, nor does she have any financial relationships with a commercial interest related to this continuing pharmacy education activity. This lesson will include a discussion of non-FDA approved (off-label) medication use.

Objectives first on sun-exposed areas such as the Vitiligo is the most common face, arms, legs, hands, and feet. There cause of skin depigmentation At the conclusion of this lesson, may also be depigmentation of the hair worldwide.2 The peak incidence pharmacists and pharmacy technicians on the scalp, eyelashes, eyebrows, occurs around the second or third should be able to: or other body hair of affected areas.3 decade of life.2,5 Vitiligo affects 0.5% 1. Explain the background of vitiligo. Some patients may experience itching to 2% of the population worldwide 2. List the different classifications of at the affected sites during active and may appear at any age ranging vitiligo. stages of pigment loss.4 Vitiligo is an from childhood to late adulthood.6,7 3. Identify treatment options based on unpredictable, progressive disease There is a higher impact of vitiligo the type of vitiligo. in which a patient may experience in patients with more pigmented a flare-up of depigmentation after a skin since it is more noticeable.5 stable period where the patient does Background not experience any spreading of In order to provide patients with Vitiligo is a noncontagious, the depigmentation. Stable periods proper care, healthcare professionals autoimmune skin condition with are defined as having no change or should be cognizant of how vitiligo white patches or spots caused by spread of depigmentation within a impacts a patient physically and depigmentation of the skin.1 In patients 12-month period.3 Currently, there mentally. Vitiligo can have a major with vitiligo, the immune system is no cure for vitiligo, but there are impact on a patient’s mental health attacks melanocytes resulting in areas treatments that work well for slowing and well-being.4 Patients are of pigment loss.2 Melanocytes are the or stopping the progression of the often misdiagnosed due to lack of pigment cells which give the skin its disease and allowing repigmentation. knowledge on the pathogenesis of the color. Depigmentation usually occurs

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Table 1. Unisegmental vitiligo is the most Focal skin lesions of common form of segmental vitiligo depigmentation that are small and Classifications of Vitiligo2 and occurs when at least one white isolated are considered unclassifiable Non-Segmental macule is present on only one side vitiligo if the lesions do not progress • General of the body.8 Unisegmental vitiligo to segmental or non-segmental • Mucosal occurs in a unilateral, band-shaped, vitiligo within one to two years.2,9 • Acrofacial dermatomal or quasi-dermatomal • Universal pattern along the trigeminal nerve. There are rare cases of vitiligo • Minor Pigment loss tends to stabilize which have been categorized as • Follicular rapidly and seldom spreads past the vitiligo minor and follicular vitiligo. dermatome, an area of skin supplied Segmental Vitiligo minor is a subcategory by a nerve root, that is affected.3 • Unisegmental of non-segmental vitiligo which • Bisegmental has been documented in patients • Plurisegmental Non-segmental vitiligo typically with darker skin. This subcategory Mixed appears bilaterally or symmetrically and involves an incomplete defect in • A combination of non-segmental and tends to progress over time.2 It can be pigmentation resulting in a lighter segmental further categorized into generalized, skin color in affected areas.2 mucosal, acrofacial, and universal subtypes.3,9 Generalized vitiligo usually disease. For example, vitiligo may be Non-segmental vitiligo typically occurs on areas of the body that confused with leprosy.3 Patients often targets epidermal melanocytes rather have experienced trauma, friction, or experience depression, emotional than follicular melanocytes, but pressure.8 This subcategory is defined distress, and social isolation due to follicular melanocytes are affected in by bilateral, depigmented patches that the social stigma associated with the follicular vitiligo. Follicular vitiligo is a are randomly spread on the skin.3,9 physical appearance of the condition.2 subcategory of non-segmental vitiligo This may result in impaired social that targets hair follicle melanocytes.9,10 development and decreased quality Mucosal vitiligo affects mucosa of life. In addition to understanding of the oral and/or genital regions. the psychological impact of vitiligo on It may happen on its own or in Theories of Pathogenesis a patient, phamacy personnel should conjunction with generalized vitiligo. The cause of vitiligo is not well know about the condition and the Mucosal vitiligo may only affect one understood but is believed to be the different treatments available in order site, or it may affect more than one result of a combination of genetic, to assist patients and prescribers. site.3,8 If only one mucosal site is immunologic, biochemical, and affected and no change in lesion neurogenic factors. There have characteristics are noted after two been multiple proposed theories Classification years, then it is considered an that include the autoimmune Vitiligo is separated into two major unclassifiable form of vitiligo.3,9 hypothesis, neural theory, biochemical classes: segmental or non-segmental. theory, zinc a2-glycoprotein Vitiligo may also be classified as mixed (ZAG) deficiency hypothesis, viral which is a combination of segmental Acrofacial vitiligo occurs when theory, and intrinsic theory.11 and non-segmental vitiligo.2 In mixed distal extremities and the face vitiligo, the segmental form precedes lose pigment. It may progress to The autoimmune hypothesis is the non-segmental form. Table 1 shows other areas of the body leading 9 based on the association of vitiligo and the different classifications of vitiligo. to generalized vitiligo. multiple other autoimmune disorders. Patients with vitiligo frequently have Segmental vitiligo, the least Universal vitiligo is the complete other autoimmune comorbidities, common type of vitiligo, occurs loss of skin pigment typically due such as thyroiditis, rheumatoid when depigmentation develops in to the progression of generalized arthritis, psoriasis, Addison’s disease, vitiligo. Some skin areas or hair may 1 one, two, or multiple segments of 9 alopecia, or diabetes mellitus. Patients the body. Segmental vitiligo may be be spared in universal vitiligo. with vitiligo may have antithyroid further described as unisegmental, antibodies, anti-thyroglobulin bisegmental, or plurisegmental.2 antibodies, anti-thyroperoxidase, and anti-smooth muscle antibodies that

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may be related to thyroid disease and reactive oxygen species may lead by the vitiligo.26 Keratinocyte- other autoimmune comorbidities.11 to cell death. The areas of skin derived c-kit stimulation is required According to one study, 20% of affected by vitiligo have increased to maintain melanocytes. These vitiligo patients had thyroid hormonal reactive oxygen species, such as intrinsic defects result in the death of profiles that showed autoimmune H2O2, due to imbalanced reduction- melanocytes in patients with vitiligo.27 thyroid dysfunction.12 Approximately oxidation and an inability to manage 80% of patients with vitiligo have stressors from cellular processes or increased immunoglobulin G and environmental factors. Oxidation of Treatment immunoglobulin M.13 In patients melanocytes from reactive oxygen While there is no cure for vitiligo, with active non-segmental vitiligo, species leads to the destruction and it is a treatable condition. This melanocyte death has been linked to detachment of pigment of the cells condition is effectively treated with higher serum levels of immunoglobulin leading to the depigmentation.20 immunosuppressive treatments. It G antimelanocytes. These antibodies may take approximately two years are believed to cause damage to for a patient to regain pigmentation.1 The zinc α2-glycoprotein (ZAG) melanocytes by antibody dependent Although regaining pigmentation deficiency hypothesis states there cytotoxicity and complement-mediated is possible with treatment, the is an association between ZAG and mechanisms. Alpha-melanocyte- repigmentation may not be complete. vitiligo proposing that vitiligo could be stimulating hormone (alpha-MSH) Patients may also experience caused by a reduction in ZAG.21 ZAG regulates pigmentation of skin, depigmentation again upon cessation influences melanocyte proliferation inflammation, and stress responses. of effective therapy.28 Pharmacists since it acts as a keratinocyte-derived Alpha-MSH binds to anti-melanocortin should refer patients to their factor. A reduction in ZAG results in 1 receptor (MC1R) on melanocytes. physician or a psychiatrist if they have diminished melanocyte adhesion to This interaction is believed to play a concerns related to mental health. surrounding cells.22 This is important role in the regulation of melanocytes because melanocyte loss plays an and skin pigmentation.14 Lower level important role in the pathogenesis of Topical Corticosteroids of alpha-MSH have been found vitiligo. The ZAG gene was detected Topical corticosteroids are effective in patients with vitiligo.15 Melanin on chromosome 7 and linkage signals in the treatment of vitiligo due to concentrating hormones receptor- on this chromosome have been suppression of the immune response. binding antibodies have also been documented in patients with vitiligo Intermediate- to very high-potency reported in patients with vitiligo. and associated autoimmune diseases.21 topical corticosteroids are used for These antibodies block the stimulation the treatment of vitiligo as shown in of the melanin concentrating Table 2.29 Topical corticosteroids are hormones receptor which could The viral theory suggests an more effective in combination with result in pigment changes.16 association between vitiligo and light therapy than light therapy alone certain viruses. There have been 30 studies suggesting an association for the induction of repigmentation. The neural theory states that between vitiligo and chronic hepatitis segmented vitiligo appears to C virus.23 In one study, patients with Light therapy, or phototherapy, follow the path of the dermatome.17 vitiligo were also reported to have involves exposure of the skin The production of melanin from hepatitis B virus sero-positivity.24 There to specific wavelengths of the melanocytes is disturbed by is an association between vitiligo light depending on the type dysfunction of the sympathetic and cytomegalovirus, herpes virus, of phototherapy. Examples of nervous system resulting in the loss of hepatitis E virus, Epstein-Barr virus, or phototherapy used for the treatment pigment. In patients with vitiligo, axonal the human immunodeficiency virus.25 of vitiligo include narrowband degeneration has been observed ultraviolet B phototherapy, psoralen further supporting the neural theory.18 The intrinsic theory states plus ultraviolet A photochemotherapy that patients with vitiligo have (PUVA), and target phototherapy. The biochemical theory suggests melanocytes with abnormalities. When large surface areas of the that reactive oxygen species These abnormalities include irregular body are affected by vitiligo, there are potential inducers of vitiligo. rough endoplasmic reticulum, low is concern for systemic absorption Reactive oxygen species, also melanocyte growth factors, and a low leading to adrenal suppression when known as free radicals, are unstable number of melanocytes expressing topical corticosteroids are used molecules that react with cellular 28 c-kit receptor in the areas affected for prolonged periods of time. molecules.19 An accumulation of

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then they should be given detailed Table 2. 29 instructions for use and schedule Topical Corticosteroid Potency regular follow-ups with their physician. Potency Generic Name (Brand Name) Formulation This phototherapy causes local immunosuppression. It helps to Very High Betamethasone dipropionate 0.25% Gel, lotion, ointment stimulate melanocyte-stimulating Clobetasol propionate 0.05% Cream, gel, lotion, ointment hormone, fibroblasts, growth factor, Diflorasone diacetate 0.05% Ointment and endothelin I. Narrowband ultraviolet B phototherapy increases Halobetasol propionate 0.05% Cream, ointment the production of melanocytes leading High Amcinonide 0.1% Cream, lotion, ointment to repigmentation.34 It has a good Betamethasone dipropionate 0.05% Cream, ointment safety profile and is the treatment of Betamethasone valerate 0.1% Ointment choice for vitiligo affecting greater than 10% of total body surface area.28 Desoximetasone 0.25% Cream, ointment Fluocinonide 0.05% Cream, ointment, gel Psoralen Plus Ultraviolet Halcinonide 0.1% Cream, ointment A Photochemotherapy Triamcinolone acetonide 0.5% Cream PUVA administered topically or Intermediate Betamethasone dipropionate 0.05% Lotion systemically was originally the Betamethasone valerate 0.1% Cream treatment of choice for vitiligo. Fluticasone propionate 0.005% Ointment PUVA is a combination of psoralen, a photoactive chemical, and Fluticasone propionate 0.05% Cream, lotion ultraviolet A (UVA).8 Patients either Mometasone furoate 0.1% Cream, ointment, lotion take the psoralen orally or apply Triamcinolone acetonide 0.025% or 0.1% Cream, ointment, lotion it topically before exposure to UVA.34 Narrowband ultraviolet B Topical Calcineurin Inhibitors Systemic Corticosteroids phototherapy has replaced PUVA due to its many adverse effects.2 These Topical calcineurin inhibitors are Systemic corticosteroids may be adverse effects include nausea and immunomodulatory drugs that used for stabilization of rapidly gastrointestinal discomfort from oral inhibit proinflammatory cytokines progressive vitiligo. Low doses of PUVA, itching, redness, blisters, burns, by modulating target cell functions. oral corticosteroids may be used freckles, and cataracts. Eye protection Examples of topical calcineurin in combination with narrowband labeled UV 400/UVB/UVA protection inhibitors are tacrolimus and ultraviolet B phototherapy to 100% is required for protection from pimecrolimus. These agents are being improve efficacy. There have been UVA for 12 to 24 hours after treatment used more frequently on vitiligo lesions studies showing the efficacy of with PUVA.34 PUVA also increase of the face.28,30 In one trial, patients oral corticosteroids in stopping a patient’s risk for skin cancer.28 were treated with topical clobetasol the spread of depigmentation in propionate 0.05%, topical tacrolimus vitiligo. Systemic corticosteroid 0.1%, or placebo. In patients with facial therapy should not be used for Target Phototherapy vitiligo, the rate of repigmentation was repigmentation of stable vitiligo due Target phototherapy uses lamps or 58% for both topical clobetasol and to lack of efficacy and adverse effects lasers with an emission of 308nm. topical tacrolimus. The success rate of of long-term corticosteroid use.33 This high intensity light may be repigmentation was defined at greater used to treat localized vitiligo.34 than 50%. In patients with nonfacial Narrowband Ultraviolet Treating the localized area helps to vitiligo, the repigmentation rate was B Phototherapy avoid higher cumulative ultraviolet higher in the topical corticosteroid B doses.35 Targeted phototherapy Narrowband ultraviolet B phototherapy group (39%) than the tacrolimus may be used concomitantly group (23%). The placebo group had uses UV lamps with peak emission of 8,34 with topical corticosteroids and 31 311 nm. Patients have the option to a repigmentation rate of 7%. Topical topical calcineurin inhibitors.28 tacrolimus and pimecrolimus have go to a clinic to receive phototherapy a boxed warning for a documented treatment or buy a home narrowband increased risk of skin cancers ultraviolet B phototherapy unit. If and lymphoma associated with a patient opts to use the handheld exposure to calcineurin inhibitors.32 phototherapy treatment at home,

www.npharm.org 11 Nebraska MORTAR & PESTLE

Off-Label Treatment There are six Fitzpatrick skin Other experimental, off-label Afamelanotide is a synthetic analogue phototypes based on distinct trends treatments include bimatoprost, of human α–melanocyte-stimulating of past sun reactions. Fitzpatrick prostaglandin E2, and topical hormone. This experimental therapy skin phototype I includes ivory skin ruxolitinib. Bimatoprost is an analog stimulates the skin and pigmentation color, light blue, gray or green eyes, of prostaglandin F2-alpha. It causes leading to tanning of the skin. It is natural red or light blonde hair, skin hyperpigmentation of periocular used in combination with narrowband always burns, peels or freckles from skin by increasing melanogenesis. ultraviolet B phototherapy for the the sun, and skin never tans. Topical bimatoprost is approved for treatment of vitiligo.28,36 A randomized, hypotrichosis of the eyelashes and glaucoma.39 In one study, efficacy was open label, Phase 1 study in adult Fitzpatrick skin phototype II compared for bimatoprost ophthalmic men and women diagnosed with includes fair or pale skin; blue, gray solution alone, bimatoprost topical non-segmental vitiligo involving 15% or green eyes; natural blonde hair; ophthalmic solution in combination to 50% of total body surface area skin usually burns; peels or freckles with topical mometasone, and topical assigned participants to combination from the sun; and skin rarely tans. therapy with narrowband ultraviolet mometasone alone in patients with phototherapy and afamelanotide non-segmental, stable, nonfacial Fitzpatrick skin phototype III or monotherapy with narrowband vitiligo. None of the patients reached includes fair to beige skin with golden ultraviolet phototherapy. The the primary end point of 50 to 75% undertones, light brown or hazel eyes, 40 combination regimen included repigmentation. Prostaglandin E2 natural dark blonde or light brown hair, narrowband ultraviolet phototherapy may be useful for stable localized skin might freckle or burn on occasion followed by alfamelanotide 16 mg vitiligo. It has stimulatory and from the sun, and skin sometimes tans. injection administered subcutaneously immunomodulatory effects on the 41 monthly for four months starting production of melanocytes. In one after one month of phototherapy. Fitzpatrick skin phototype IV study, about 71% of patients treated Phototherapy was continued in includes olive or light brown skin, with prostaglandin E2 gel experienced 42 the combination group throughout dark brown eyes, natural dark brown repigmentation. Topical ruxolitinib treatment. This study used two hair, skin rarely freckles or burns is an inhibitor of Janus kinase 1 and 43 validated scoring systems, Vitiligo from the sun, and skin tans often. 2. In a phase 2 trial, the cream was Area Scoring Index (VASI) and Vitiligo applied twice daily for 20 weeks to European Task Force (VETF) score, to participants with diagnosed vitiligo Fitzpatrick skin phototype V assess the degree of depigmentation. involving 1% or more of total body includes dark brown skin color, dark surface area. Some of the participants brown to black eyes, natural dark showed an improvement in the The primary efficacy outcome was brown to black hair, skin rarely freckles, Vitiligo Area Scoring Index.44 the change in pigmentation of the full almost never burns and always tans. body, face, trunk, and extremities from day 0 to 168 between the two groups. Non-pharmacological treatment Fitzpatrick skin phototype VI The secondary efficacy outcome was options for patients with segmental includes dark brown to darkest the time to onset of repigmentation. vitiligo that have not responded to brown skin, brownish black eyes, Repigmentation of the combination pharmacological therapy include natural black hair, and skin never group was 48.64% compared to surgery or depigmentation. Surgical freckles or burns, and skin always 33.26% for the monotherapy group options include minigrafts, autologous tans darkly.37 The study showed a at day 168. Both groups showed melanocyte cultures, hair follicle statistically significant improvement in statistically significant improvement transplantation, split-thickness VASI for Fitzpatrick skin phototypes in VETF scores, but the combination grafts, and autologous suction IV to VI. The Vitiligo Area Scoring 30 therapy group reached it at day blister grafts. Depigmentation is Index is a useful tool for assessing 56 compared to the monotherapy performed with topical monobenzyl the degree of depigmentation in group at day 84. No statistically ether of hydroquinone, also vitiligo in research.38 This study 45 significant difference was found known as monobenzone. showed that combination therapy between groups in patients with with afamelanotide and phototherapy Fitzpatrick skin phototypes III.36 had a faster, clinically evident, statistically significant repigmentation than using phototherapy alone.36

12 January/February 2020 Nebraska MORTAR & PESTLE

Place in Therapy First-line therapy for the stabilization of rapidly progressive The first-line therapy for stable non- disease is low dose oral segmental vitiligo involving less than corticosteroids. Rapidly progressive 10% of the total body surface area is disease occurs when depigmentation mid-potency or high-potency topical spreads over weeks to months. The corticosteroids. Topical corticosteroids, drug of choice is oral prednisone such as mometasone furoate, are 10 to 20 mg daily for up to 2 weeks. utilized due to fewer systemic side The course may be repeated in 4 effects. The topical corticosteroids to 6 weeks if necessary. Alternative are applied to the affected areas therapy options include an oral mini- 1 to 2 times daily, but duration of pulse therapy with dexamethasone treatment varies. Another first line 2.5 mg on 2 consecutive days each treatment includes topical calcineurin week for an average of 3 months or inhibitor, such as tacrolimus and intramuscular triamcinolone 40 mg pimecrolimus. Topical calcineurin once.28 The minipulse therapy helps inhibitors are typically applied to the to reduce adverse events from the affected areas 2 times daily. Topical corticosteroids.8 The intramuscular corticosteroids and topical calcineurin injection may be repeated in inhibitors may be used in combination 4 to 6 weeks up to a maximum for up to 2 months. If a patient is not of 3 injections if necessary. Oral responding to topical therapy, then corticosteroids may be given with narrowband ultraviolet B phototherapy or without narrowband may be used 2 times per week. For ultraviolet B phototherapy. patients with disseminated vitiligo if the patient is having continued Combination of phototherapy that is affecting multiple sites, but repigmentation with therapy. Once with systemic corticosteroids is overall depigmentation remains the patient reaches 24 months or recommended for patients with less than 10% of total body surface 200 sessions of phototherapy, the active disseminated disease located area, narrowband ultraviolet B therapy must be tapered off. Topical at multiple sites of the body. If phototherapy is recommended to be corticosteroids or topical calcineurin systemic corticosteroids cannot be used 2 to 3 times per week.2,28,46 inhibitors may be used concomitantly used, then narrowband ultraviolet 2,28,34 with the phototherapy. phototherapy may be used alone Patients with segmental vitiligo to attempt stabilization of the rapid affecting less then 10% of total body The first-line therapy for vitiligo progression of depigmentation.28 surface area are recommended to involving greater than 40% of the use topical corticosteroids, topical total body surface area is narrowband calcineurin inhibitors, or targeted ultraviolet B phototherapy.2,34 The Conclusion phototherapy as first-line therapies. regimen is also 2 to 3 times per week Pharmacy personnel should be able If a patient does not respond to over 9 to 12 months with the same to identify the different classifications topical therapy or phototherapy, limitations. If a patient with vitiligo of vitiligo. While there is no cure for then surgical procedures are an does not respond to repigmentation vitiligo, there are efficacious treatments option because segmental vitiligo modalities, then depigmentation of for vitiligo. Patients will be treated 28,30,34 tends to be more stable. remaining normally pigmented areas differently depending on the type may be performed with monobenzone. of vitiligo they have. Pharmacists should be able provide patients and The first-line therapy for stable The regimen includes monobenzone prescribers with appropriate advice non-segmental vitiligo involving 10 to 10% cream for 1 month followed and treatment recommendations. 40% of the total body surface area is by monobenzone 20% cream. narrowband ultraviolet B phototherapy. The depigmentation of residual Phototherapy is performed 2 to 3 pigmented areas may take one to 28 times per week over the course of 9 three years for best outcomes. to 12 months. Narrowband ultraviolet B phototherapy can be used for up to 24 months or 200 sessions

www.npharm.org 13 Nebraska MORTAR & PESTLE

References 1. Vitiligo Support International. What is Vitiligo 23. Akbayir N, Gokdemir G, Mansur T, et al. Is there any Policies for the Nebraska Mortar & website. https://vitiligosupport.org/what-is-vitiligo/. relationship between hepatitis C virus and vitiligo? J Pestle (M&P) continuing pharmacy Accessed July 8, 2019. Clin Gastroenterol. 2004;38(9):815-817. education lessons and quizzes: 2. Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. 24. Akcan Y, Kavak A, Sertbas Y, et al. The low Vitiligo. Lancet. 2015;386(9988):74-84. seropositivity of hepatitis B virus in vitiligo patients. 3. Grimes PE. Vitiligo: Pathogenesis, clinical features, J Eur Acad Dermatol Venereol. 2006; 20(1):110-111. 1. M&P Quizzes are valid only for the and diagnosis. UpToDate. http://www.utdol.com. 25. Toker SC, Sarycaoglu H, Karadogan SK, Mistik R, membership year in which they are Updated February 3, 2017. Accessed July 8, 2019. Baskan EB, Tunaly S. Is there any relation between published. Quizzes for the 2020 4. Alikhan A, Felsten LM, Daly M, Petronic-Rosic vitiligo and cytomegalovirus? J Eur Acad Dermatol Membership Year must be received V. Vitiligo: A comprehensive overview: Part I. Venereol. 2007;21(1):141-142. by December 14, 2020. Quizzes Introduction, epidemiology, quality of life, diagnosis, 26. Boissy RE, Liu YY, Medrano EE, Nordlund JJ. cannot be carried over to another differential diagnosis, associations, histopathology, Structural aberration of the rough endoplasmic etiology, and work-up. J Am Acad Dermatol. reticulum and melanosome compartmentalization membership year. 2011;65(3):473-491. in long-term cultures of melanocytes from vitiligo 2. If more than three questions are 5. Vitiligo Support International. Genetics and patients. J Invest Dermatol. 1991;97(3):395-404. missed, the quiz will be returned. Incidence website. https://vitiligosupport.org/ 27. Lee AY. Role of keratinocytes in the development of The quiz can be resubmitted. genetics-incidence/. Accessed July 8, 2019. vitiligo. Ann Dermatol. 2012;24(2):115–125. 3. CPE transcripts can be printed from 6. Kyriakis KP, Palamaras L, Tsele E, Michailides C, 28. Grimes PE. Vitiligo: Management and prognosis. NABP e-Profiles at www.nabp.net. Terzoudi S. Case detection rates of vitiligo by UpToDate. http://www.utdol.com. Updated May 5, gender and age. Int J Dermatol. 2009;48(3):328- 2017. Accessed July 10, 2019. 4. CPE credits are submitted to 329. 29. Topical Corticosteroids. Lexi-Drugs. Hudson, OH: NABP by the 15th of each month. 7. Kruger C, Schallreuter KU. A review of the Lexicomp, 2015. http://online.lexi.com/. Accessed For example, M&P CPE quizzes worldwide prevalence of vitiligo in children/ July 10, 2019. completed in the month of March adolescents and adults. Int J Dermatol. 30. Taieb A, Alomar A, Böhm M, et al, and the Vitiligo 2020 will be sent to NABP e-Profiles 2012;51(10):1206-1212. European Task Force (VETF), and the European by April 15, 2020. 8. Reichert-Faria A, Tarlé RG, Dellatorre G, Mira MT, Academy of Dermatology and Venereology Silva de Castro CC. Vitiligo - Part 2 - classification, (EADV), and the Union Europeenne des histopathology and treatment. An Bras Dermatol. Medecins Specialistes (UEMS). Guidelines for the The Nebraska Council 2014;89(5):784-90. management of vitiligo: the European Dermatology for Continuing Pharmacy 9. Ezzedine K, Lim HW, Suzuki T, et al. Revised Forum consensus. Br J Dermatol. 2013;168(1): 5–19. Education (NCCPE) classification/nomenclature of vitiligo and related 31. Ho N, Pope E, Weinstein M, Greenberg S, Webster is accredited by the issues: The Vitiligo Global Issues Consensus C, Krafchik BR. A double-blind, randomized, Conference. Pigment Cell Melanoma Res. placebo-controlled trial of topical tacrolimus 0.1% vs. Accreditation Council 2012;25(3):1-13. clobetasol propionate 0.05% in childhood vitiligo. for Pharmacy Education 10. Ezzedine K, Amazan E, Seneschal J, et al. Follicular Br J Dermatol. 2011;165(3):626. (ACPE) as a provider of continuing vitiligo: a new form of vitiligo. Pigment Cell 32. Tacrolimus. Lexi-Drugs. Hudson, OH: Lexicomp, pharmacy education (CPE). This CPE Melanoma Res. 2012;25(4):527-529. 2015. http://online.lexi.com/ Updated July 22, 2019. home study activity has been accredited 11. Mohammed GF, Gomaa AH, Al-Dhubaibi MS. Accessed July 23, 2019. for 1.0 contact hour or 0.10 CEU. UAN Highlights in pathogenesis of vitiligo. World J Clin 33. Bae JM, Yoo HJ, Kim H, Lee JH, Kim GM. Cases. 2015;3(3):221-230. Combination therapy with 308-nm excimer 0128-0000-20-001-H01-P for pharmacists 12. Gopal KVT, Rao GR, Kumar YH. Increased laser, topical tacrolimus, and short-term and UAN 0128-0000-20-001-H01-T prevalence of thyroid dysfunction and diabetes systemic corticosteroids for segmental vitiligo: a for pharmacy technicians. This is mellitus in Indian vitiligo patients: A case-control retrospective study of 159 patients. J Am Acad a knowledge-based CPE activity study. Indian Dermatol Online J. 2014;5(4):456-460. Dermatol. 2015;73(1):76-82. targeted to pharmacists and pharmacy 13. Harning R, Cui J, Bystryn JC. Relation between 34. Vitiligo Support International. Treatments website. technicians. the incidence and level of pigment cell antibodies https://vitiligosupport.org/phototherapy-treatment/. and disease activity in vitiligo. J Invest Dermatol. Accessed July 12, 2019. 1991;97:1078-1080. 35. Feldman SR. Targeted phototherapy. UpToDate. 14. Brenner M, Hearing VJ. Modifying skin pigmentation http://www.utdol.com. Updated April 11, 2019. The Nebraska Pharmacists Association - approaches through intrinsic biochemistry and Accessed July 12, 2019. disclaims any liability to you or your exogenous agents. Drug Discov Today Dis Mech. 36. Lim HW, Grimes PE, Agbai O, et al. Afamelanotide patients resulting from reliance solely 2008;5(2):189-199. and Narrowband UV-B Phototherapy for the upon the information contained herein. 15. Pichler R, Sfetsos K, Badics B, Gutenbrunner S, Treatment of Vitiligo: A Randomized Multicenter Aubock J. Vitiligo patients present lower plasma Trial. JAMA Dermatol. 2015;151(1):42–50. levels of alpha-melanotropin immunoreactivities. 37. Sachdeva S. Fitzpatrick skin typing: Applications in Neuropeptides. 2006;40(3):177-183. dermatology. Indian J Dermatol Venereol Leprol. 16. Gottumukkala RV, Gavalas NG, Akhtar S, et al. 2009;75(1):93-96 Function-blocking autoantibodies to the melanin- 38. Komen L, da Graca V, Wolkerstorfer A, de Rie Quiz Answers may be submitted: concentrating hormone receptor in vitiligo patients. MA, Terwee CM, van der Veen JP. Vitiligo Area Lab Invest. 2006;86:781-789. Scoring Index and Vitiligo European Task Force Online: www.npharm.org 17. Koga M, Tango T. Clinical features and course assessment: reliable and responsive instruments to Fax: 402-420-1406 of type A and type B vitiligo. Br J Dermatol. measure the degree of depigmentation in vitiligo. Email: [email protected] 1988;118(2):223-228. Br J Dermatol. 2015;172(2):437-443. Mail: Nebraska Mortar & Pestle 39. Bimatoprost. Lexi-Drugs. Hudson, OH: Lexicomp, 18. Al-Abadie MS, Warren MA, Bleehen SS, 6221 S 58th St, Ste A Gawkrodger DJ. Morphologic observations on the 2015. http://online.lexi.com/ Updated July 8, 2019. dermal nerves in vitiligo: an ultrastructural study. Int Accessed July 14, 2019. Lincoln, NE 68516 J Dermatol. 1995;31(12):837-840. 40. Grimes, PE. Bimatroprost 0.03% solution for the 19. Ray PD, Huang BW, Tsuji Y. Reactive oxygen treatment of nonfacial vitiligo. J Drugs Dermatol. species (ROS) homeostasis and redox regulation in 2016;15(6):703-710. cellular signaling. Cell Signal. 2012;24(5):981–990. 41. Parsad D, Pandhi R, Dogra S, Kumar B. Topical 44. Rothstein B, Joshipura D, Saraiya A, et al. Treatment 20. Khan R, Satyam A, Gupta S, Sharma A. Circulatory prostaglandin analog (PGE2) in vitiligo- a of vitiligo with the topical Janus kinase inhibitor levels of antioxidants and lipid peroxidation in preliminary study. Int J Dermatol. 2002;41(12):942- ruxolitinib. J Am Acad Dermatol. 2017;76(6):1054- Indian patients with generalized and localized 945. 1060. vitiligo. Arch Dermatol Res. 2009;301(10):731-737. 42. Kapoor R, Phiske MM, Jerajani HR. Evaluation of 45. Monobenzone. Lexi-Drugs. Hudson, OH: Lexicomp, 21. Bagherani N, Yaghoobi R, Omidian M. Hypothesis: safety and efficacy of topical prostaglandin E2 in 2015. http://online.lexi.com/ Updated February 22, zinc can be effective in treatment of vitiligo. Indian J treatment of vitiligo. Br J Dermatol. 2009;160(4):861- 2019. Accessed July 15, 2019. Dermatol. 2011;56(5):480-484. 863. 46. Vitiligo Support International. Treatments website. 22. Hassan MI, Waheed A, Yadav S, Singh TP, Ahmad 43. Ruxolitinib. Lexi-Drugs. Hudson, OH: Lexicomp, https://vitiligosupport.org/topical-therapies-for- F. Zinc alpha 2-glycoprotein: a multidisciplinary 2015. http://online.lexi.com/ Updated July 15, 2019. vitiligo/. Accessed July 12, 2019. protein. Mol Cancer Res. 2008;6(6):892-906. Accessed July 15, 2019.

14 January/February 2020 Nebraska MORTAR & PESTLE

Vitiligo and Treatment Options Quiz #1, January/February 2020, ACPE 0128-0000-20-001-H01-P/T 1. Which of the following is true about vitiligo? 6. What is the mechanism of action of afamelanotide? a. Patients experience depression, emotional distress, a. Causes depigmentation of normally pigmented areas and social isolation. of the skin. b. Vitiligo is a noncontagious, autoimmune skin condition b. Inhibits proinflammatory cytokines by modulating target with white patches or spots caused by depigmentation cell functions. of the skin. c. Stimulates the skin and pigmentation leading to tanning c. Vitiligo is the most common cause of skin of the skin. depigmentation worldwide. d. Suppresses the immune response. d. All of the above. 7. What is afamelanotide used in combination with? 2. What is the most common form of segmental vitiligo? a. Narrowband ultraviolet B phototherapy a. Bisegmental b. Oral corticosteroids b. Mucosal c. Topical calcineurin inhibitors c. Plurisegmental d. Topical corticosteroids d. Unisegmental 8. What is the first-line therapy for stable non-segmental 3. How long may it take for a patient with vitiligo to regain vitiligo involving less than 10% of the total body surface pigmentation? area? a. 1 week a. Mid-potency or high potency topical corticosteroids b. 1 month b. Psoralen plus ultraviolet A chemotherapy c. 2 years c. Topical calcineurin inhibitors d. Patients will never regain pigmentation. d. Both a and c

4. What treatment may topical corticosteroids be used 9. What is the first-line therapy for vitiligo involving greater in combination with to increase effectiveness of than 40% of the total body surface area? repigmentation induction? a. Mid-potency to high potency topical corticosteroids a. Oral corticosteroids b. Narrowband ultraviolet B phototherapy b. Light therapy c. Psoralen plus ultraviolet A chemotherapy c. Topical calcineurin inhibitors d. Topical calcineurin inhibitors d. Topical monobenzone cream 10. What is the first-line therapy for stabilization of rapidly 5. What class of topical agent is being used more frequently progressive disease? on vitiligo lesions of the face? a. Low dose oral corticosteroids a. Topical Aquaphor b. Topical calcineurin inhibitors b. Topical calcineurin inhibitors c. Topical corticosteroids c. Topical corticosteroids d. Topical corticosteroids d. None of the above

Keep the TOP portion for your records. Return the BOTTOM portion to the NPA office. Or, take this quiz online at www.npharm.org

Name ______2020 Quiz #1 - Vitiligo and Treatment Options ACPE #0128-0000-20-001-H01-P for pharmacists Mailing Address______ACPE #0128-0000-20-001-H01-T for technicians City/State/Zip______1.0 Contact Hour - Knowledge Based CPE Activity

The deadline for this quiz is December 14, 2020 Circle one (1) Answer: CPE Home Study Evaluation 1. a b c d 6. a b c d 1. Rate this lesson: (Excellent) 5 4 3 2 1 (Poor) 2. a b c d 7. a b c d 2. Did this lesson meet each of its objectives? ___ Yes ___ No 3. Was the content without commercial bias? ___ Yes ___ No 3. a b c d 8. a b c d If not, please explain______4. a b c d 9. a b c d 4. Did the lesson meet your educational/practice needs? __ Yes __ No 5. a b c d 10. a b c d 5. Comments/future topics are welcome. ______

www.npharm.org 15 Pharmacy Insurance

Tomorrow. Imagine That.

All products may not be available in all states and territories. Nebraska MORTAR & PESTLE

AND THE LAW CONTROLLED SUBSTANCES

The opioid crisis has brought a the triplicate DEA Form 222 to transfer provisions also. Sometimes these less lot of attention to the prescribing and Schedule II substances. Another reason common situations are problem-prone dispensing of opioids. This attention has to refresh our memories periodically is because we aren't as familiar with the also extended to the prescribing and that requirements change and if we rely situation. Suppose one of your patients dispensing of all controlled substances. only on our memories, we may not be has a valid prescription for a C-IV I recently attended a seminar which current. The DEA recently announced the medication and requests that you send a contained a number of sessions on phase out of the triplicate form over the refill to their vacation home in Bermuda. opioids and controlled substances. next two years. Can you send that refill to a foreign One of these sessions suggested that The DEA Form 222 is also country? Not unless you are registered every pharmacist should read the DEA's mentioned in the section of the manual with the DEA as an exporter and have Pharmacist's Manual.1 That suggestion on ordering of controlled substances. obtained the necessary permits or caused me to ask myself when was the Topics here include how to order the submitted the necessary declarations for last time I had read it. One human trait is Form 222, who is authorized to sign the export. The pharmacist might assume it that we tend to forget details over time forms, and what to do if the forms are is permissible to send the refill because and our memory becomes a little less lost or stolen. The manual also contains there is a valid prescription on file. sharp. There have been a number of useful information on what to do when This is an example where a seemingly times when I was sure what a contract controlled substances are stolen or lost. reasonable conclusion is incorrect. provision said, only to go back, read the The DEA must be notified, in writing, The periodic review of the DEA's document, and find that what it stated within one business day of the discovery Pharmacist's Manual is a good risk was slightly different from my memory. of the theft or loss. Completion of the management tool. During my years This same phenomenon applies to the DEA Form 106 in this situation can of practice, none of my employers Pharmacist's Manual.The manual is about be made easier by using the biennial recommended or required that I review 80 pages, but it is much more readable inventory and prescription records it. My working knowledge of the DEA than the actual statute and regulations. because you can use these records to regulations was what I drew from my The speaker at the seminar determine how much product was stolen pharmacy law class and any updates explained that many pharmacists or lost. There is also an entire section that I may have read and retained. feel their duty is to make sure that a of recordkeeping requirements. While Given the scrutiny that is currently being controlled substance prescription isn't many pharmacies are using a perpetual given to the dispensing of controlled forged or altered. While that is true, the inventory system today, that does not substances, an annual review of the duty is much broader. For a controlled replace the required biennial inventories. Pharmacist's Manual is an excellent risk substance prescription to be valid, it Physical inventories are required for a management tool to help the pharmacist must be issued for a legitimate medical new registrant (either opening a new and pharmacy avoid a potential problem purpose in the usual course of the pharmacy or taking over an existing one) brought on by foggy memory of the prescriber's professional practice. The and for products that are newly added to requirements. In addition, a review of law does not require a pharmacist to a schedule. your state statutes and regulations dispense a questionable prescription. The manual also contains helpful should also be done because your state The DEA has provided some red flags information for the review and dispensing may have more restrictive standards that may indicate diversion. Those are of controlled substance prescriptions. which you are required to follow. discussed in 2018 decision and order.2 It provides what information is required Corresponding Responsibility is a topic to be on the prescription itself and 1. https://www.deadiversion.usdoj.gov/pubs/manuals/pharm2/ pharm_manual.pdf that requires its own forum so I won't the information required to be on the 2. https://www.deadiversion.usdoj.gov/fed_regs/actions/2018/ delve more deeply into it now. prescription label. Partial fill situations fr0220_4.pdf#search=red%20flag%20diversion The Pharmacist's Manual contains are addressed as is the dispensing information on a number of topics. of controlled substances without a This series, Pharmacy and the Law, is presented by Pharmacists Besides a basic introduction to the prescription. The record of over the Mutual Insurance Company and the Nebraska Pharmacists Association through Pharmacy Marketing Group, Inc., a company Schedules, there is a lot of practical counter sales of controlled substances dedicated to providing quality products and services to the information in the manual. There is a is required to be kept in a bound record pharmacy community. section on the transfer and disposal book. These types of sales must be ©Written by Don R. McGuire Jr, RPh, JD, General Counsel, Senior Vice President, Risk Management & Compliance at Pharmacists of controlled substances. This covers made by a pharmacists and cannot be Mutual Insurance Company. This article discusses general principles of law and risk management. It is not intended as transfer to another pharmacy, the original delegated to a non-pharmacist. While legal advice. Pharmacists should consult their own attorneys and manufacturer, or a reverse distributor. the manual contains a lot of practical insurance companies for specific advice. Pharmacists should be familiar with policies and procedures of their employers and There are numerous reminders to use information, there are some uncommon insurance companies, and act accordingly.

www.npharm.org 17 Nebraska MORTAR & PESTLE

Continuing Pharmacy Education | Lesson #2

BAQSIMI A New Way to Deliver Glucagon

Written by Sara Bichlmeier This continuing pharmacy education lesson was written by Sara Bichlmeier, PharmD Candidate, University of Nebraska Medical Center College of Pharmacy who does not have any conflicts of interest, nor does she have any financial relationships with a commercial interest related to this continuing pharmacy education activity.

Objectives There are two main types of ounce solution containing 75 grams of At the conclusion of this lesson, diabetes: type 1 and type 2. Type glucose. After two hours the patient’s pharmacists and pharmacy technicians 1 diabetes occurs when the body blood glucose is then tested again. should be able to: does not produce insulin, requiring This test informs providers how that 1. Describe the signs and symptoms exogenous insulin to process patient processes glucose. Diagnostic of hypoglycemia and their carbohydrates. Type 2 diabetes occurs criteria include an A1c of > 6.5%, a treatment. when the body does not use the insulin fasting plasma glucose of > 126 mg/dL, 2. Explain the differences between it produces appropriately, also known or an oral glucose tolerance test of 3 intranasal and injectable glucagon. as insulin resistance. At the onset of > 200 mg/dL. 3. List side effects and drug-drug type 2 diabetes the body makes extra interactions of Baqsimi. insulin to compensate, but over time Prevalence the body cannot make enough insulin In the United States, approximately to keep up with demands.2,3 30.3 million people have diabetes; Diabetes Summary Diabetes is diagnosed based Diabetes is a chronic metabolic (9.4%) of those, 23.1 million are on three criteria: A1c, fasting plasma disorder characterized by resistance diagnosed and 7.2 million are glucose, and an oral glucose tolerance 4 to the action of insulin, insufficient undiagnosed. test. A1c is a test that measures the insulin secretion, or both which results In Nebraska, almost 1 in 10 average blood glucose over the past as hyperglycemia or high blood adults (9.2%) reported having ever two to three months. A fasting blood sugars.1 Diabetes occurs because been diagnosed with diabetes in glucose test is performed when fasting the body’s pancreas, which makes 2014. Diabetes accounted for 2,207 after not eating or drinking anything the hormone insulin, either does not hospitalizations among residents. It (except water) for eight hours. This produce enough of its own insulin or was also the primary cause of 472 test usually takes place in the morning it cannot effectively use the insulin it deaths ranking it as the 7th most before breakfast. The oral glucose 5,6,7 does produce. Insulin helps drive sugar common cause of death. tolerance test is performed over two that is consumed into the cells. When The highest prevalence of patients hours. First, a fasting blood glucose is insulin does not work effectively, there with diabetes are those who are 55 tested, then the patient drinks an eight- is an excess of sugar in the blood.2 years and older. Patients who have a

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tongue, or cheeks; clumsiness; color with type 1 diabetes are at the highest Table 1. draining from the skin; or seizures. The risk for hypoglycemia due to insulin 5 Race/Ethnicity Prevalence only way to know if a diabetic patient is dependency. Newer insulins are Prevalence hypoglycemic is to test his or her blood preferred over regular insulin or Race/Ethnicity among adults sugar. If symptoms make it difficult to NPH (neutral protamine Hagedorn) test, the patient should be treated for because they cause less hypoglycemia Non-Hispanic multiracial 15% hypoglycemia.3 especially during the night. Patients American Indian 14.3% To treat hypoglycemia, use need to be aware when taking insulin the “Rule of 15”. In the Rule of 15, that they are using the right type, Black 13.8% patients ingest 15 grams of fast-acting dose, and that they are injecting the Other 13.3% carbohydrates, wait 15 minutes, then insulin correctly to reduce the chance Hispanic 12.8% test the patient’s blood glucose. If the of hypoglycemia. Another group of blood glucose has not risen above medications that can cause low blood Asian/Pacific Islander 7.6% 70 mg/dL, the patient should eat sugars are sulfonylureas (glipizide, White 7.6% another 15 grams of carbohydrates. glyburide, glimepiride). An important Fast-acting carbohydrates should counseling tip for patients is to eat college degree are less likely to be be used to treat hypoglycemia. See when taking these medications to diagnosed than those with a lower Table 2 for examples of 15 grams of avoid low blood sugars. Patients level of education. The prevalence fast-acting carbohydrates. Once a should also be aware of the food they is higher among lower income patient’s blood glucose has increased are eating when using insulin. They individuals. Non-Hispanic multiracial past 70 mg/dL, the patient should need to be sure that they are eating individuals have the highest rates of eat a meal or snack so that his or enough food to balance the amount of diabetes (15%). See Table 1 for race/ her blood sugars do not lower again insulin they are taking, and if they are ethnicity details.5 and to restore glycogen in the liver. varying from their consistent diet, they Eating a snack or meal with protein is are still getting enough carbohydrates. Hypoglycemia important for the body to maintain an Physical activity can also cause Hypoglycemia is a major complication optimal blood glucose. Be aware when hypoglycemia. Exercise can have of diabetes. Hypoglycemia occurs treating children and adolescents both short-term and long-term effects when blood glucose is too low. It is with hypoglycemia. Often, they do not on blood glucose. It is important for at this point the patient needs to take require 15 grams of carbohydrates but patients to check their blood sugars action to avoid adverse effects of a lesser amount. Infants may only need before they exercise to know if they hypoglycemia, such as coma or death, 6 grams, toddlers 8 grams, and small need to eat before exercising in order and bring their blood glucose back children 10 grams. It is important to to avoid low blood sugars. The long- into the target range.3 According to not over-treat hypoglycemic episodes. term effects usually occur overnight.3 the American Diabetes Association Patients prefer to eat until they feel Severe hypoglycemia happens guidelines, level one hypoglycemia is better, but this can cause blood when blood glucose goes so low that a blood glucose < 70 mg/dL; level two glucose to increase too much and the patient is no longer able to treat hypoglycemia is < 54 mg/dL; and level become hyperglycemic.3 themselves by using the Rule of 15 three is a severe event characterized Hypoglycemia can occur due to and another person is required to by altered mental status and/or a number of different causes, one help. When this happens, glucagon physical status requiring assistance.8 of which is medications. Insulin is is the treatment of choice. Glucagon Although these values are helpful, the most common medication that is a hormone that is produced by the they are not universal for everyone. causes low blood sugars. Patients pancreas which stimulates the liver Each patient reacts differently to low blood glucose, but there are some Table 2. common signs and symptoms that Fast-Acting Carbohydrates (15 Grams)3 patients experience including: feeling shaky, nervous or anxious; sweating; • ½ cup (4oz) juice chills and clamminess; irritability or • Glucose tablets (4 tablets) impatient; confusion; tachycardia; • Glucose gel (one 15-gram pouch or 1/3 of a 45 gram tube) feeling light headed or dizzy; hungry; • ½ cup (4oz) regular soda nauseous; sleepy; weak or having • 1 cup (8oz) 1% milk no energy; blurred or impaired • 1 tablespoon of sugar, honey, or corn syrup vision; headaches; feeling tingling • Hard candies: jellybeans, gumdrops (not chocolate). Read food labels to know how or numbness specifically in the lips, many carbohydrates to consume

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to release stored glucose into the levels than recommended which can lower peak plasma concentrations, blood stream.3 Glucagon requires a lead to a higher rate of micro- and but it is not significantly different from prescription. macrovascular complications in the injectable glucagon when looking at future. time to normal glucose levels. Side Current Treatment: In 2001, a study evaluated parents effects with intranasal glucagon were of children with diabetes use of also very minimal including nasal Injection glucagon for difficulty in administration, irritation and mild sneezing. When Until recently, the only way to treat time taken for the procedure, developing the intranasal glucagon, severe hypoglycemia was by using an and accuracy of the dose using a particle size was designed in a way injectable glucagon. One example of simulation technique. In this simulation, to prevent the medication from an injectable glucagon is a Glucagon the parents were timed on how long being delivered to the lungs after Kit. This kit comes in a red box and it took to give the glucagon injection administration. The drug is absorbed contains instructions for use, a needle and their techniques were checked by through the nasal mucosa without and syringe containing diluent, and a trained diabetes educators. Diabetes any need for the patient to inhale or vial of glucagon powder containing health professionals also participated to breathe deeply, ensuring effective 1 mg of glucagon. To use the kit, a in the simulation to compare times dosing even in unconscious patients.12 person who is not the diabetic patient and techniques. In conclusion, 69% In a randomized crossover study needs to reconstitute the glucagon of parents experienced handling to demonstrate noninferiority to by injecting the diluent in the syringe difficulties which included difficulty intramuscular glucagon administration into the vial of glucagon powder and in opening the pack, sheath removal, when compared to intranasal gently swirling the vial until the mixture mixing and damaging the needle. administration, insulin was used to becomes clear with a water-like The average time taken to complete induce hypoglycemia in type 1 diabetic consistency. The mixture then needs to the simulation was 2 minutes and 30 patients. In this trial, success was be drawn back up into the syringe and seconds, ranging from 30 seconds to defined as an increase in plasma injected intramuscularly into the patient 12 minutes 30 seconds. On average, glucose to > 70 mg/dL from the experiencing severe hypoglycemia. 24% of the glucagon was not injected. glucose nadir within 30 minutes If a patient weighs 44 pounds or less, With the group of professionals there after receiving glucagon. The nadir only half of the contents (0.5 mg) were no observed errors, but they did concentrations were 44 + 8 mg/ should be drawn up and injected. comment on how difficult it was to dL for intranasal and 47 + 8 mg/dL After giving the injection, the person administer a glucagon injection. The for intramuscular administration. should turn the patient onto his or her average time it took for a professional Success was met for 74 out of the 75 side and call 911 immediately. If the to complete the injection was 1 minute participants (98.7%) in the intranasal patient is not awake within 15 minutes, and 28 seconds, ranging from 55 group and all 75 participants (100%) a second dose should be given if seconds to 1 minute 45 seconds.10 in the intramuscular group. The one available.9 There are multiple steps In 2015, a review was done to failure in the intranasal group reached involved in preparing the medication focus on the status of alternative goal blood glucose levels without any and when a patient is unconscious routes of administration of glucagon. other interventions but outside of the or seizing, it can be very stressful for Glucagon is a peptide hormone. 30-minute time window defined as the person preparing the injection. Peptide hormones cannot be a success. Average time to success Although glucagon injection is the administered by the oral route was 13 minutes with the intramuscular treatment of choice for a patient who is because they are inactivated in the administration and 16 minutes in the experiencing severe hypoglycemia and gastrointestinal tract due to first intranasal administration showing a lag is unconscious, often times caregivers pass metabolism, ultimately leading time of three minutes between the two are either too reluctant or anxious to to loss of efficacy. Glucagon is treatments. Even though the symptoms inject glucagon.10 different compared to some other of hypoglycemia lasted longer in the peptide hormones as it requires a intranasal group, the overall magnitude From Injection to precise dose-response for safety and of hypoglycemia symptoms was not Intranasal effectiveness of the medication. When different, likely due to similar nadir Investigations into using the nasal studied it was shown that it was not glucose levels achieved. Nausea route for administering glucagon required for intranasal glucagon to and vomiting are well-known side began in 1983.11 Many diabetic patients reach a very high blood glucagon level, effects of glucagon, the side effects and family members have fears as it was with injectable glucagon, of nausea and vomiting occurred at relating to hypoglycemia.10,11,12,13,14,15,16 to achieve a clinically equivalent similar frequencies between the two Due to these fears, many patients’ pharmacodynamic response. The groups, 36% of patients after intranasal blood glucoses are kept at higher bioavailability of intranasal glucagon administration and 38% of patients is less than injectable which leads to after intramuscular administration.

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The conclusion of this study stated the 2 mg dose was slower to increase caregivers administered partial doses that intranasal glucagon is effective blood glucose. It took 20 minutes to and the remaining eight caregivers for the correction of insulin-induced increase all patients’ blood glucose (50%) did not give any glucagon. The hypoglycemia in adults with type 1 who received the 2 mg dose by reasons for not administering any diabetes and intranasal glucagon > 25 mg/dL where it took only 15 glucagon were that they injected delivery showed to be promising minutes for the 3 mg dose. In a the diluent only, they injected insulin and will have a substantial beneficial 20-minute time frame, the 3 mg dose instead, or they bent the needle. Some impact on the treatment of severe increased the blood glucose by an of the caregivers did not inject the hypoglycemia.13 average of 70 mg/dL where the 2 mg glucagon into the correct injection sites A phase one trial was completed only increased by an average of 60 of the buttocks, arm, or thigh because to compare the pharmacokinetic mg/dL. The study showed that there they were used to injecting into other and pharmacodynamics of intranasal does not need to be an age or weight sites or a belief that the wrist was a glucagon against intramuscular adjustment when it comes to intranasal better site with more blood vessels. glucagon in children and adolescents, glucagon and that the 3 mg dose Five caregivers injected insulin, two of ages 4 to < 17 years. This trial looked should be used for all. In conclusion, the five got the glucagon and insulin at the safety of use and doses the authors pointed out that this study confused. One caregiver was going needed to effectively treat this age took place in a controlled environment to inject the insulin because they group. The participants were split and both the intranasal and injectable believed this was the correct treatment up into three groups based on age glucagon was administered by trained but bent the insulin needle and then to more accurately assess the dose professionals. It is unknown whether switched and injected the glucagon. needed. The study was conducted the same results would happen in The final two caregivers that injected in a crossover fashion. Participants a real world setting with potentially insulin, one believed that it was the received either the 2 mg intranasal combative or seizing children.11 correct treatment for hypoglycemia glucagon, 3 mg intranasal glucagon, A simulation study performed and the other believed that all diabetic or 1 mg injectable glucagon. Success on manikins compared the ability medication was insulin. It took an was defined as a rise in blood glucose of people who were trained versus average of 7.2 minutes to inject the > 25 mg/dL in a 20-minute time period untrained to administer the different glucagon. When giving the intranasal after the selected form of glucagon forms of glucagon. Those who were glucagon, all but one caregiver was was given. All patients in the injectable untrained represented a person able to administer the dose. The one glucagon group had a 100% success who would come upon a patient who did not give the dose did not rate. The intranasal group had all but experiencing a hypoglycemic event in depress the plunger all of the way one success. The patient who had a public setting. These study subjects resulting in no glucagon being given. an unsuccessful attempt with the were referred to as acquaintances. The Two caregivers also administered intranasal glucagon blew his nose trained participants were caregivers insulin to the manikin believing that after being administered the dose of diabetic patients. The simulation insulin was always an appropriate leading to almost all of the medication was set up as if the diabetic patient treatment for people with diabetes. being expelled from the body. To was taught how to use the devices at The average time of administration was compare the pharmacokinetics a clinic visit, then upon arrival at home, 16 seconds and all doses were given in and pharmacodynamics of the two the patient taught his or her caregivers less than one minute.14 different formulations, injection and how to use the devices. With each In the group of acquaintances, intranasal, the average maximal manikin, there was a backpack where there were also many failures to deliver glucose concentration was recorded. the glucagon was located as well as the dose of injectable glucagon. None For intranasal delivery it ranged from other diabetic supplies that a diabetic in this group delivered the full dose 178-208 mg/dL, for injection it ranged patient would normally carry such as a of glucagon, and only 3 out of the 15 from 194-211 mg/dL. When looking at glucometer, test strips, lancets, alcohol delivered a partial dose. Many did not adverse events, the most common was pads, insulin, and insulin syringes reconstitute the glucagon believing nausea with or without vomiting. In and needles. The study evaluated that the diluent in the syringe was the the injectable group, 67% experienced the ease of use, speed, effectiveness medication needed. Other reasons this side effect while in the 3 mg of delivering the dose, and user for not injecting a dose included intranasal group 43% of participants preference.14 bending the needle on the vial cap had this side effect and only 39% of In the trained group when using because they did not remove it; after the 2 mg intranasal participants. When the injectable glucagon, there were reconstitution a participant could not comparing the 2 mg dose to the 3 mg many failures and mistakes. Only figure out how to get the medication dose of the intranasal formulation, 2 out of 16 caregivers successfully out of the vial; one participant refused it was determined that although the reconstituted the glucagon and to give an injection and was going to 2 mg dose had fewer adverse effects, administered a full dose. Six other call emergency personnel; one injected

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an empty syringe; and one injected above 70 mg/dL and awakening or New Treatment: insulin instead. For the acquaintances returning to normal status within 30 who administered a partial dose of minutes. At the conclusion of this Intranasal Baqsimi™ is the first and only approved glucagon, the times ranged from study, all hypoglycemic events were intranasal glucagon. It was approved 1.3 minutes to 4 minutes. When resolved, and patients returned to by the FDA on July 24, 2019. The administering the intranasal glucagon, normal status within 30 minutes of powder formulation is available in a the full dose was administered by all being given intranasal glucagon. 3 mg dose and is approved for ages participants but one who was unaware More than half (54.5%) of patients 4 years and older. It is marketed as a they had to push the plunger all of recovered within 10 minutes. Out of single pack or a two pack with WAC the way in order to give the dose. No the 33 hypoglycemic events, 17 were pricing of $280.82 and $561.60. acquaintances administered insulin considered clinically significant with The device comes packaged in a with the nasal glucagon. The average blood glucoses dropping to less than tube which is shrink-wrapped for time it took to administer it was 26 54 mg/dL. In all of these clinically its protection. The wrapping on the seconds.14 significant events every blood glucose tube contains directions for use. The When asked if the participants of rose about 70 mg/dL within 15 minutes device has a tip that is inserted into the this study had any fear or hesitation of the intranasal glucagon and all nose, a plunger, and a green line on before administering the injectable patients fully recovered by 30 minutes. the end of the plunger. It is important glucagon the majority said they did, When surveyed on ease of use 93.3% that the shrink-wrap is not removed 50% in the caregiver group and 60% of caregivers said the intranasal from the tube until it is needed. If the in the acquaintance group. When glucose was easy or very easy to use wrapping is removed the device can the diabetic patients (who were with during a hypoglycemic episode. All be exposed to moisture decreasing the caregivers) were asked which caregivers were able to administer its effectiveness. The plunger should method they would prefer 69% said the glucagon within two minutes of not be pushed or tested before it is the intranasal glucagon. The patients recognizing the hypoglycemic child ready to use. Each device contains thought that the intranasal glucagon and 60.6% of caregivers were able only one dose and cannot be reused. was easier to use, teach, and carry to administer it in 30 seconds or less. Baqsimi is for nasal use only.17 Baqsimi with no chance of needle breakage or The caregivers reported that it would will work even if the patient has a accidental needle stick. The caregivers be less intimidating to use intranasal cold or is taking cold medicine.16,17 were also asked which method they glucagon in a hypoglycemic event No inhalation or other cooperative would prefer to use. Eighty-one than an injectable glucagon. They also measure is required from the patient percent chose the intranasal glucagon agreed that it would be easy to teach as absorption takes place through the saying how it was easier to use, less another how to use the intranasal nasal mucosa.13,16 stressful, and less embarrassing if glucagon and that would be something they were in public. Two caregivers they would be willing to carry should To Use Baqsimi: (13%) said they would prefer the a hypoglycemic event happened; 1. Instruct the person who will be glucagon injection, but neither of the caregiver could easily access it. administering the Baqsimi to these caregivers who chose the All participants experienced adverse remove the shrink wrap by pulling injectable option delivered a full dose events due to the intranasal glucagon; on the red stripe. during the simulation activity. All the three participants withdrew from the 2. Open the lid and remove the device acquaintances said they would prefer study due to severe nasal discomfort from the tube, being cautious not to using the intranasal glucagon.14 following a treatment. Other common push the plunger. A phase three trial was completed adverse events included watery 3. Have the person hold the device to examine the effectiveness, safety, eyes, headache, runny nose, nasal between the fingers and the thumb. tolerability, and ease of use of congestion, sneezing, and redness of 4. The person then needs to insert intranasal glucagon in children and the eyes.15 the tip gently into one nostril of the adolescents with type 1 diabetes in A study was completed to hypoglycemic patient until his or “real world” setting. A hypoglycemic see how a patient experiencing her fingers touch the outside of the event was characterized as a blood nasal congestion and a patient nose. glucose reading of less than or who has already taken a nasal 5. Finally, have the person push equal to 70 mg/dL with or without decongestant respond to intranasal the plunger firmly and all the symptoms of neuroglycopenia. A glucagon. There was no significant way in. The dose is completely severe hypoglycemic event was difference in pharmacokinetics and administered when the green line at defined as severe neuroglycopenia pharmacodynamics. The patients the end of the plunger disappears. resulting in coma or seizure. No severe still absorbed adequate doses of hypoglycemia events occurred during glucagon to treat severe hypoglycemic this trial. Success was characterized symptoms.16 as an increase of blood glucose to

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After the person has a pre-filled syringe (Gvoke PFS™) and administered the dose of Baqsimi, Table 3. an auto-injector (Gvoke HypoPen™). call 911 immediately. If the patient is Ccommon Side Effects The pre-filled syringe is currently unconscious the patient should be Associated with the use available and the auto-injector will turned onto his or her side. Discard the of Baqsimi18,19 be available in 2020. It is supplied used device and tube.17,19 in two different doses: 0.5mg/0.1mL for pediatric patients and 1mg/0.2mL • Nausea Storage and Handling Store the for adolescence and adults. Gvoke is shrink-wrapped tube at temperatures • Vomiting different than the currently available up to 86OF (30OC). Replace Baqsimi • Headache injectable glucagon options as it is before the expiration date printed on • Runny nose administered subcutaneously, as 17,19 the tube. • Discomfort in the nose opposed to intramuscularly. Three • Stuffy nose Phase 3 clinical trials were completed Side Effects Baqsimi has a number where there was 100% treatment of side effects. The most serious side • Redness in the eyes success in children and 99% treatment effects include high blood pressure, • Itchy nose, throat and eyes success in adults. When evaluating low blood sugar, and serious allergic • Watery eyes usability there was nearly a 100% reaction including anaphylactic shock success rate in delivering a full dose with difficulty breathing. These serious of glucagon. Gvoke has the same side side effects are uncommon only Other Warning and Precautions effects and drug-drug interactions as occurring in 1% to 10% of patients. Patients who receive Baqsimi should Baqsimi.20 High blood pressure can occur in talk to their health care providers patients with tumors in their adrenal about all of their other medical conditions before using Baqsimi Conclusion glands. Low blood glucose can occur Baqsimi is a new option for caregivers including: having a tumor in the in patients who have tumors in their to use for patients experiencing pancreas; not having food or drink pancreas. If a serious allergic reaction severe hypoglycemia. In 2011, it was for an extended period of time due to occurs, the observer of the reaction reported that 282,254 emergency fasting or starvation; if the patient is should inform the emergency medical room visits were due to hypoglycemia pregnant or plans to become pregnant; personnel of the reaction as soon as in the United States.14 A few studies and if the patient is breastfeeding they arrive. Serious allergic reactions showed that using injectable glucagon or plans of breastfeeding. At this include rash, difficulty breathing, or can lead to suboptimal use of 18,19 time, it is unknown if Baqsimi passes low blood pressure. See Table 3 for effective medication, unnecessary into the breast milk. It is important common side effects associated with delays in treatment, and costly use of for the patient to discuss with their the use of Baqsimi. emergency medical systems including provider and decide if Baqsimi should ambulance services, emergency room be used by the patient if they are Drug-Drug Interactions The most visits, and hospital administration.12,13 breastfeeding.18,19 common drug-drug interactions There is a slight delay in glycemic Certain patients should not use with Baqsimi include beta-blockers, response for intranasal glucagon, Baqsimi. These patients include those indomethacin, warfarin, and but this would likely be clinically who have a tumor on their adrenal anticholinergic agents. When taken inconsequential, and in many gland located on top of the kidney, with beta-blockers, there may be a circumstances might be offset by the (a pheochromocytoma); a tumor in transient increase in pulse and blood time required, errors, and failures to the pancreas (an insulinoma); or if the pressure after Baqsimi is given. When deliver among nonmedical caregivers patient is allergic to glucagon or any of taken with indomethacin, it decreases in preparing and administering the the ingredients in Baqsimi.18,19 the effect of the glucagon. When injectable intramuscular formulation.13 taken with warfarin, it may enhance All caregivers, co-workers, and the anticoagulation effects of warfarin. More Formulations of friends of diabetic patients should When taken with anticholinergic Glucagon Coming Soon be educated on this new device so agents such as atropine, benztropine, On September 10, 2019, a new that anyone could use it. Due to the dicyclomine, and oxybutynin, glucagon glucagon that is a pre-mixed, ready effectiveness and ease of use of this can increase the gastrointestinal side to use, stable at room temperature device, fear of hypoglycemia could effects of glucagon such as nausea liquid injection was approved by the decrease ultimately improving overall and vomiting.18,19 FDA called Gvoke™. It is available in diabetes control. two different administration options,

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References Policies for the Nebraska Mortar & 1. Triplitt CL, Repas T, Alvarez C. 12. Pontiroli AE. Intranasal glucagon: a Pestle (M&P) continuing pharmacy Diabetes Mellitus. In: DiPiro JT, Talbert promising approach for treatment of education lessons and quizzes: RL, Yee GC, Matzke GR, Wells BG, severe hypoglycemia. J Diabetes Sci Posey LM eds. Pharmacotherapy: A Technol. 2015;9:38-43. 1. M&P Quizzes are valid only for the Pathophysiologic Approach, 10e. New 13. Rickels MR, Ruedy KJ, Foster NC, et al.; membership year in which they are York, NY: McGraw-Hill; 2017:1139-1181. Intranasal Glucagon for treatment of published. Quizzes for the 2020 2. Kelly J. Diabetes. Center for Disease insulin-induced hypoglycemia in adults Membership Year must be received Control and Prevention. https://www. with type 1 diabetes: a randomized by December 14, 20209. Quizzes cdc.gov/media/presskits/aahd/diabetes. crossover noninferiority study. Diabetes cannot be carried over to another pdf. Publication date unavailable. Care. 2016;39:264-270. membership year. Accessed August 5, 2019. 14. Yale JF, Dulude H, Egeth M, et al.; Faster 2. If more than three questions are 3. American Diabetes Association. http:// use and fewer failures with needle-free missed, the quiz will be returned. www.diabetes.org/living-with-diabetes/ nasal glucagon vs. injectable glucagon The quiz can be resubmitted. treatment-and-care/blood-glucose- in severe hypoglycemia rescue: a 3. CPE transcripts can be printed from NABP e-Profiles at www.nabp.net. control/hypoglycemia-low-blood. simulation study. Diabetes Technol 4. CPE credits are submitted to html?loc=lwd-slabnav. Publication date Ther. 2017;19:423-432. NABP by the 15th of each month. unavailable. Updated February 11, 2019. 15. Deeb L, Dulude H, Guzman C, Zhang For example, M&P CPE quizzes Accessed August 5, 2019. S, Reiner B, Piche C, Pradhan S, Zhang completed in the month of March 4. Centers for Disease Control and M. A phase 3 multicenter, open-label, 2020 will be sent to NABP e-Profiles Prevention. National Diabetes Statistics prospective study designed to evaluate by April 15, 2020. Report. https://www.cdc.gov/diabetes/ the effectiveness and ease of use of data/statistics/statistics-report.html. nasal glucagon in the treatment of The Nebraska Council Published 2017. Updated February 24, moderate and severe hypoglycemia in for Continuing Pharmacy 2018. Accessed August 5, 2019. children and adolescents with type 1 Education (NCCPE) 5. Diabetes in Nebraska, Fact Sheet. http:// diabetes in the home or school setting. is accredited by the dhhs.ne.gov/Reports/Diabetes%20 Pediatric Diabetes. 2018;19:1007-1013. Accreditation Council in%20Nebraska%20-%202018.pdf. 16. Guzman CB, Dulude H, Piche C, for Pharmacy Education Published 2018. Accessed August 5, et al. Effects of common cold and (ACPE) as a provider of continuing 2019. concomitant administration of nasal pharmacy education (CPE). This 6. Nebraska Department of Health and decongestant on the pharmacokinetics CPE home study activity has been accredited for 1.0 contact hour or 0.10 Human Services, Division of Public and pharmacodynamics of nasal CEU. UAN 0128-0000-20-002-H01-P Health. State Health Assessment: glucagon in otherwise healthy participants: a randomized clinical trial. for pharmacists and UAN Nebraska. http://dhhs.ne.gov/Reports/ 0128-0000-20-002-H01-T for pharmacy Diabetes Obes Metab. 2018;20:646- Statewide%20Health%20Needs%20 technicians. This is a knowledge-based Assessment%20-%202016.pdf. 653. CPE activity targeted to pharmacists and Published September 2016. Accessed 17. Instruction For Use, Baqsimi nasal pharmacy technicians. August 5, 2019. powder. http://pi.lilly.com/us/baqsimi- 7. Centers for Disease Control and us-ifu.pdf. Issued July 2019. Accessed The Nebraska Pharmacists Association Prevention. Diabetes Report Card 2017. August 5, 2019. disclaims any liability to you or your https://www.cdc.gov/diabetes/pdfs/ 18. Patient Information, Baqsimi nasal patients resulting from reliance solely library/diabetesreportcard2017-508.pdf. powder. http://pi.lilly.com/us/baqsimi- upon the information contained herein. Published 2018. Accessed August 5, us-ppi.pdf. Issued July 2019. Accessed 2019. August 5, 2019. 8. Riddle MC, Bakris G, 2019 19. Baqsimi-glucagon powder, Full Quiz Answers may be submitted: ADA guideline Diabetes Care. Prescribing Information. http://uspl.lilly. 2019;42(Suppl. 1):S61-S70. https://care. com/baqsimi/baqsimi.html#pi. Updated Online: www.npharm.org diabetesjournals.org/content/diacare/ July 2019. Accessed August 12, 2019. Fax: 402-420-1406 suppl/2018/12/17/42.Supplement_1. 20. FDA Approves Gvoke, the First Ready- Email: [email protected] DC1/DC_42_S1_2019_UPDATED.pdf. to-use Stable Liquid Glucagon for Mail: Nebraska Mortar & Pestle 6221 S 58th St, Ste A Accessed August 12, 2019. Severe Hypoglycemia. https://www. Lincoln, NE 68516 9. Glucagon, Information For The User. drugs.com/newdrugs/fda-approves- http://uspl.lilly.com/glucagon/glucagon. gvoke-glucagon-first-ready-stable-liquid- html#ppi. Updated July 2018. Accessed glucagon-severe-hypoglycemia-5049. August 7, 2019. html?utm_source=ddc&utm_ 10. Harris G, et al.; Glucagon administration medium=email&utm_ – underevaluated and undertaught. campaign=Daily+News+Summary+- Practical Diabetes Int.2001;18:22-25. +September+11%2C+2019&utm_conte 11. Sherr JL, Ruedy KJ, Foster NC, et al.; nt=FDA+Approves+Gvoke+%28glucag Glucagon nasal powder: a promising on%29%2C+the+First+Ready-to-use+S alternative to intramuscular glucagon table+Liquid+Glucagon+for+Severe+H in youth with type 1 diabetes. Diabetes ypoglycemia#moreResources. Issues Care. 2016;39:555-562. September 2019. Accessed September 16, 2019.

24 January/February 2020 Nebraska MORTAR & PESTLE

Baqsimi - A New Way to Deliver Glucagon Quiz #2, January/February 2020, ACPE 0128-0000-20-002-H01-P/T

1. In 2014, how many Nebraskans had ever been 6. What was a failure for injectable use in the study diagnosed with diabetes? of trained caregivers? a. 1 in 5 c. 1 in 10 a. Injected diluent only b. 1 in 8 d. 1 in 12 b. Injected insulin instead of glucagon c. Bent the needle 2. How does the American Diabetes Association define d. All of the above the three levels of hypoglycemia? a. Level 1: < 60 mg/dL, Level 2: < 50 mg/dL, 7. Which method of glucagon administration did both Level 3: < 40 mg/dL the diabetic patients and caregivers prefer to use? b. Level 1: < 70 mg/dL, Level 2: < 50 mg/dL, a. Injection Level 3: Altered mental and/or physical status b. Intranasal requiring assistance c. Injection done by a health professional c. Level 1: < 54 mg/dL, Level 2: < 30 mg/dL, d. Intranasal done by a health professional Level 3: < 25 mg/dL d. Level 1: < 70 mg/dL, Level 2: < 54 mg/dL, 8. Which of the following are correct regarding effective Level 3: Altered mental and/or physical status intranasal glucagon administration? requiring assistance a. The glucagon is absorbed by the nasal mucosa. b. The patient must inhale when administering the dose 3. What are common signs and symptoms of to be effective. hypoglycemia? c. A patient can blow their nose after administration a. Chills and clamminess, irritability or impatience, without affecting the medication. confusion d. The dose will not be effective if the patient has nasal b. Feeling shaky, nervous or anxious, sweating congestion. c. Tachycardia, lightheaded or dizzy, hungry d. All of the above 9. What are common side effects that occur with Baqsimi? a. Nausea, vomiting, headache 4. How should a patient appropriately treat his or her b. Runny nose, discomfort in the nose, stuffy nose hypoglycemia? c. Redness in the eyes, Itchy nose, throat and eyes, a. Eat a entire chocolate bar watery eyes b. Take a nap d. All of the above c. Take insulin d. Use the Rule of 15 (eat 15 grams of carbohydrates, 10. Which of the following drug-drug interactions occurs wait 15 minutes and check blood glucose) with Baqsimi? a. Indomethacin increases the effect of the Baqsimi. 5. Which medication most commonly causes b. Baqsimi decreases the anticoagulation effects of hypoglycemia? warfarin. a. Glipizide c. Metformin c. Anticholinergic agents may increase the b. Insulin d. Glimepiride gastrointestinal side effects of Baqsimi. d. A transient decrease in pulse and blood pressure with beta-blockers. Keep the TOP portion for your records. Return the BOTTOM portion to the NPA office. Or, take this quiz online at www.npharm.org Name ______2020 Quiz #2 - Baqsimi - A New Way to Deliver Glucagon ACPE #0128-0000-20-002-H01-P for pharmacists Mailing Address______ACPE #0128-0000-20-002-H01-T for technicians City/State/Zip______1.0 Contact Hour - Knowledge Based CPE Activity Circle one (1) Answer: The deadline for this quiz is December 14, 2020. 1. a b c d 6. a b c d CPE Home Study Evaluation 2. a b c d 7. a b c d 1. Rate this lesson: (Excellent) 5 4 3 2 1 (Poor) 3. a b c d 8. a b c d 2. Did this lesson meet each of its objectives? ___ Yes ___ No 3. Was the content without commercial bias? ___ Yes ___ No 4. a b c d 9. a b c d If not, please explain______5. a b c d 10. a b c d 4. Did the lesson meet your educational/practice needs? __ Yes __ No 5. Comments/future topics are welcome. ______

www.npharm.org 25 Nebraska MORTAR & PESTLE Financial Forum Why Do You Need A Will? It may not sound enticing, but creating a will puts power in your hands.

According to the global analytics is unable to fulfill the obligation. percentages. For example, you firm Gallup, only about 44% of Some families name multiple may decide to give 45% each to Americans have created a will. This children as co-executors, with two children and the remaining finding may not surprise you. After the intention of thwarting sibling 10% to your sibling. all, no one wants to be reminded discord, but this can introduce of their mortality or dwell on what a logistical headache, as all the A do-it-yourself will may be might happen upon their death, so executors must act unanimously.2,3 acceptable, but it may not be writing a last will and testament is advisable. The law does not require a seldom prioritized on the to-do list Guardians will to be drawn up by a professional, of a Millennial or Gen Xer. What may A will allows you to designate a so you could create your own will, surprise you, though, is the statistic guardian for your minor children. with or without using a template. If cited by personal finance website The The designated guardian you you make a mistake, however, you will Balance: around 35% of Americans appoint must be able to assume not be around to correct it. When you aged 65 and older lack wills.1,2 the responsibility. For many draft a will, consider enlisting the help people, this is the most important of a legal, tax, or financial professional A will is an instrument of power. part of a will. If you die without who could offer you additional insight, By creating one, you gain control over naming a guardian, the courts will especially if you have a large estate or the distribution of your assets. If you decide who takes care of your a complex family situation. die without one, the state decides children. what becomes of your property, with Remember, a will puts power in no regard to your priorities. A will is a Gifts your hands. You have worked hard to legal document by which an individual This section enables you to create a legacy for your loved ones. or a couple (known as “testator”) identify people or organizations You deserve to decide how that legacy identifies their wishes regarding the to whom you wish to give gifts of is sustained. distribution of their assets after death. money or specific possessions, A will can typically be broken down such as jewelry or a car. You can Citations into four parts: also specify conditional gifts, such 1. https://news.gallup.com/poll/191651/ as a sum of money to a young majority-not.aspx [4/24/18] Executors daughter, but only when she 2. https://www.thebalance.com/ Most wills begin by naming reaches a certain age. wills-4073967 [4/24/18] an executor. Executors are 3. https://www.nolo.com/legal- encyclopedia/naming-more-one-executor. responsible for carrying out the Estate html [12/3/18] wishes outlined in a will. This Your estate encompasses involves assessing the value everything you own, including real This series, Financial Forum, is presented by PRISM Wealth Advisors and the NPA through Pharmacy Marketing Group, Inc., a company dedicated to providing quality products and of the estate, gathering the property, financial investments, services to the pharmacy community. Pat Reding and Bo Schnurr may be reached at 800-288- 6669 or [email protected]. Registered Representative of and securities and investment assets, paying inheritance tax cash, and personal possessions. advisory services offered through Berthel Fisher & Company Financial Services, Inc. Member FINRA/SIPC. PRISM Wealth Advisors, LLC is independent of Berthel Fisher & Company Financial and other debts (if necessary), Once you have identified specific Services, Inc. This material was prepared by MarketingLibrary.Net Inc., and does not necessarily and distributing assets among gifts you would like to distribute, represent the views of the presenting party, nor their affiliates. All information is believed to be from reliable sources; however we make no representation as to its completeness or accuracy. beneficiaries. It is recommended you can apportion the rest of your Please note - investing involves risk, and past performance is no guarantee of future results. The publisher is not engaged in rendering legal, accounting or other professional services. If that you name an alternate estate in equal shares among assistance is needed, the reader is advised to engage the services of a competent professional. executor in case your first choice your heirs, or you can split it into This information should not be construed as investment, tax or legal advice and may not be relied on for the purpose of avoiding any Federal tax penalty. This is neither a solicitation nor recommendation to purchase or sell any investment or insurance product or service, and should not be relied upon as such. All indices are unmanaged and are not illustrative of any particular investment.

26 January/February 2020 Surf’s Up! Join us in California! April 23-26, 2020 • Huntington Beach, CA Hyatt Regency Huntington Beach Resort & Spa

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Continuing Pharmacy Education | Lesson #3 TRIPLE THERAPY A New Approach to Treat COPD

Written by Brittani Bjelland This continuing pharmacy education lesson was written by Brittani Bjelland, PharmD Candidate, University of Nebraska Medical Center College of Pharmacy who does not have any conflicts of interest, nor does she have any financial relationships with a commercial interest related to this continuing pharmacy education activity.

Objectives released their updated consensus In Nebraska, according to data At the conclusion of this lesson, report to better manage patients with collected for 2014, about 1 in 17 adults pharmacists and pharmacy technicians COPD. (5.8%) reported having ever been should be able to: told by a medical professional that 1. Describe the prevalence, Epidemiology they have COPD. In comparison to symptoms, and risk factors for COPD is currently the fourth leading national data, Nebraska residents COPD. cause of death in the world and is were slightly less likely to report a 2. Identify the active ingredients, projected to be the third by 2020.3,4 COPD diagnosis. In 2014, the mortality effectiveness, dosage schedule and The projected increase is due to of COPD in Nebraska compared to common side effects of Trelegy. continued exposure to various risk national data was higher than the factors. In 2012, more than three million national average. COPD caused 1,088 people worldwide died of COPD.5 The deaths in Nebraska or about 6.8% of Introduction the population.1 Chronic Obstructive Pulmonary prevalence of COPD worldwide was Disease (COPD) is a chronic lung consistently higher in men than women disease that is characterized by in all world regions, settings, and Clinical Presentation 6 shortness of breath, frequent income categories. Noticing the signs and symptoms of coughing, wheezing, and tightness in In the United States, COPD is COPD and having an early diagnosis the chest.1 COPD is a term to describe the fourth leading cause of death is important for successful treatment. chronic lung diseases that include behind heart disease, cancer, and The most common signs and 7 emphysema and chronic bronchitis. accidents/unintentional injuries. The symptoms of COPD include chronic Emphysema is a condition in which true incidence, however, is likely under cough, shortness of breath, frequent there is damage to the alveoli in the reported because most people believe respiratory infections, blueness of the lungs. Chronic bronchitis is defined as being short of breath or being less lips or fingernail beds, fatigue, mucus 8 8 irritated and swollen bronchial tubes active is related to their age. In 2010, production, and wheezing. that cause coughing and shortness of the cost of COPD was approximately breath.2 COPD cannot be cured, but $32.1 billion in which 51% was paid for Risk Factors with the right treatment, COPD and my Medicare, 25% paid by Medicaid COPD is considered a preventable the symptoms can be managed. In and 18% paid by private insurance. The disease; however, some risk factors 2018, the Global Initiative for Chronic CDC projects that by 2020 the cost will increase a patient’s chance of 9 Obstructive Lung disease (GOLD) be around $49 billion. developing COPD. The most common

28 January/February 2020 Nebraska MORTAR & PESTLE risk factor of COPD is smoking. This Additional Treatments combination therapies include an ICS includes cigarette, pipe, cigar, and with a bronchodilator (beta -agonist or Inhaled Corticosteroids (ICS) 2 marijuana. Other major risk factors Inflammation is a main anticholinergic). include indoor/outdoor air pollution, pathophysiologic issue behind COPD. occupational exposures, genetics, Inhaled corticosteroids (ICS) are Trelegy older age, female gender, lung growth responsible for anti-inflammatory An FDA approved triple therapy inhaler and development, socioeconomic activity. However, ICS have been called Trelegy is a combination of a status, previous infections, and history shown to increase the incidence LAMA, LABA, and ICS (umeclidinium 10 of asthma. Knowing these risk factors of pneumonia. Also, ICS are only 62.5 mcg/vilanterol 25 mcg/fluticasone and avoiding them can help prevent indicated in COPD when combined furoate 100 mcg). Trelegy works by COPD. with another agent (i.e. LABA).11 opening and keeping the airways open to reduce inflammation in the lungs. Drug Therapies Methylxanthines are a class of There are two main trials that The use of bronchodilators is the medications that have been around support the use of Trelegy: IMPACT mainstay of COPD treatment.10 There for a long time. This class includes and FULFIL. The IMPACT trial was a are various types of bronchodilators theophylline and aminophylline. This 52-week randomized, double-blind, and it is important to select the class exerts their bronchodilation parallel-group study that included more correct one(s) to manage a patient’s effect through various ways including than 10,000 COPD patients with a COPD. The available classes of inhibition of phosphodiesterase, history of exacerbations. Patients were bronchodilators include beta2-agonists inhibiting calcium ion influx into randomized to receive Trelegy, Breo and anticholinergics. the smooth muscle, prostaglandin (fluticasone furoate 100 mcg/vilanterol antagonism, and stimulation of 25 mcg), or Anoro (umeclidinium

Beta2-agonists exert their endogenous catecholamines. With 62.5 mcg/vilanterol 25 mcg). The bronchodilation by stimulating the increased availability and positive primary outcome was the annual rate adenyl cyclase to increase the of moderate or severe exacerbations outcomes with beta2-agonists and formation of cAMP (cyclic adenosine anticholinergics, this class has fallen during the treatment. Patients that monophosphate) which is responsible out of favor.11 received Trelegy had an annual rate for relaxing the bronchial smooth of 0.91 per year compared with 1.07 muscles. There are short-acting (SABA) Phosphodiesterase-4 Inhibitors per year (Breo) and 1.21 (Anoro). The and long-acting (LABA) agents within (PDE-4 Inhibitors) are a small rate of exacerbations was significantly this class. The short-acting are best class of medications used in COPD. lower in the Trelegy group versus the for acute, quick-acting relief, while the PDE-4 is found in the airway smooth Breo (p<0.001) and Anoro (p<0.001) long-acting are best for patients with muscle cells and inflammatory cells groups.13 The FULFIL trial was a 24 persistent symptoms.11 that are responsible for degrading week phase III, randomized, double- cAMP. When PDE-4 is inhibited, the blind, double-dummy, parallel-group, Anticholinergics produce smooth muscle cells are relaxed multicenter study where patients bronchodilation by inhibiting and there is decreased activity of received treatment of either Trelegy cholinergic receptors in the inflammatory cells. Roflumilast is a once-daily and twice-daily placebo or bronchial smooth muscle which medication within this class that has twice-daily Symbicort (budesonide 400 blocks acetylcholine. By blocking been used to decrease exacerbations mcg/formoterol 12 mcg) and once-daily acetylcholine, there is a reduction in patients with COPD. Two studies placebo. The primary endpoints were in cGMP (cyclic guanosine have found that when roflumilast was to evaluate lung function and health- monophosphate) which normally added to a patient’s regimen, the related quality of life of these patients. constricts bronchial smooth muscles. amount of exacerbations and need for Lung function was measured using

Similar to beta2-agonists, there are hospitalization decreased. However, the change of FEV1 from baseline, short-acting (SAMA) and long-acting there is little evidence to show long- 2 weeks, 4 weeks, 12 weeks and 24 (LAMA) agents available. The benefit term benefit with PDE-4 inhibitors.11 weeks. Trelegy showed significant of the long-acting agents is that improved lung function at all measured they are more selective in blocking Combination Therapy time points versus Symbicort (142 certain muscarinic receptors.11 In Since COPD is a progressive disease, it mL vs. -29 mLrespectively; p<0.001). the UPLIFT trial, tiotropium showed is common for agents to be added onto Quality of life was assessed using the significant improvement in FEV1 from treatment regimens over-time. This led St. George’s Respiratory Questionnaire baseline compared to placebo and to developing combination therapies (SGRQ) when Trelegy showed benefited from increased quality of for patients for easier administration of significant improvement in quality of life, reduced exacerbations, and fewer these medications. The most common life measures versus the Symbicort hospitalizations.12 group (-6.6 units vs. -4.3 units; p<0.001).14

www.npharm.org 29 Nebraska MORTAR & PESTLE

Trelegy is administered as one patients on the proper use of inhalers inhalation, once daily. Since it includes to ensure that each patient has the Policies for the Nebraska Mortar & an ICS, patients should rinse their best outcomes from his/her treatment Pestle (M&P) continuing pharmacy education lessons and quizzes: mouths with water after each inhalation plan. to decrease the risk of developing 1. M&P Quizzes are valid only for the oropharyngeal candidiasis. Trelegy References membership year in which they are is contraindicated in patients with a 1. Nebraska Department of Health and Human published. Quizzes for the 2020 Services, Division of Public Health. State Membership Year must be received severe hypersensitivity to milk proteins by December 14, 2020. Quizzes Health Assessment: Nebraska. http://dhhs. or if they showed hypersensitivity to cannot be carried over to another ne.gov/Reports/Statewide%20Health%20 membership year. fluticasone furoate, umeclidinium, or Needs%20Assessment%20-%202016. 2. If more than three questions are vilanterol in the past. Trelegy should pdf. Published September 2016. Accessed missed, the quiz will be returned. not be used in patients with asthma. August 5, 2019. The quiz can be resubmitted. The most common side effects of 2. COPD Foundation. Understanding COPD. 3. CPE transcripts can be printed from Trelegy include headache, back pain, COPD Foundation website. https://www. NABP e-Profiles at www.nabp.net. copdfoundation.org/What-is-COPD/ dysgeusia, diarrhea, cough, upper 4. CPE credits are submitted to Understanding-COPD/What-is-COPD.aspx. NABP by the 15th of each month. respiratory infection, pneumonia and Accessed August 5, 2019. For example, M&P CPE quizzes oral candidiasis/pain. Trelegy should 3. Lozano R, Naghavi M, Foreman K, et al. completed in the month of March be used with caution in patients on Global and regional mortality from 235 2020 will be sent to NABP e-Profiles MAOIs, TCAs, drugs that prolong QTc causes of death for 20 age groups in 1990 by April 15, 2020. and 2010: a systematic analysis for the global interval, beta-blockers, non-potassium- burden of disease study 2010. The Lancet. The Nebraska Council sparing diuretics, and anticholinergic 2013; 380: 2095-2128. for Continuing Pharmacy medications.14 4. Sin D, Anthonisen N, Soriano J, Agusti A. Education (NCCPE) Mortality in COPD: role of comorbidities. Eur is accredited by the Respir J. 2006; 28:1245-1257. Accreditation Council Conclusion 5. Mathers C, Loncar D. Projections of global for Pharmacy Education COPD is a chronic disease that is mortality and burden of disease from 2002 (ACPE) as a provider of continuing an increasingly prevalent issue that to 2030. PLoS Medicine. 2006; 3(11): 2011- pharmacy education (CPE). This CPE home study activity has been continues to be ranked as one of the 2030. 6. Adeloye D, Chua S, Lee C, et al. Global and accredited for 0.5 contact hour or 0.05 top causes of death in the United CEU. UAN 0128-0000-20-004-H01-P regional estimates of COPD prevalence: for pharmacists and UAN States. With continued exposure to risk Systematic review and meta-analysis. Journal 0128-0000-20-004-H01-T for pharmacy factors (e.g. smoking, pollution), COPD of Global Health. 2015; 5: 1-17. technicians. This is a knowledge-based 7. Xu J, Murphy S, Kochanek K, et al. (2018) will continue to be an issue for many CPE activity targeted to pharmacists and patients. Deaths: final data for 2016. Natl Vital Stat Rep pharmacy technicians. Inhalers are the most commonly 67: 1-20. 8. American Lung Association (ALA). Lung used medications in the treatment of The Nebraska Pharmacists Association Health and Diseases. ALA website. https:// disclaims any liability to you or your COPD. Most patients will require the www.lung.org/lung-health-and-diseases/lung- patients resulting from reliance solely use of a rescue inhaler (short-acting disease-lookup/copd/. Published November upon the information contained herein. 2016. Accessed August 5, 2019. beta2-agonist) that should only be used on an as needed basis. Additionally, 9. Centers for Disease Control and Prevention (CDC). What is COPD? CDC website. https:// Quiz Answers may be submitted: patients may require a scheduled www.cdc.gov/copd/index.html. Published medication/inhaler that may either be a June 2018. Accessed August 5, 2019. Online: www.npharm.org dual or triple-combination product.10 10. Global initiative for chronic obstructive Fax: 402-420-1406 Trelegy is the only triple- lung disease: Pocket guide to COPD Email: [email protected] therapy inhaler that is currently diagnosis, management, and prevention. Mail: Nebraska Mortar & Pestle (2018). Bethesda, MD: U.S. Dept. of Health 6221 S 58th St, Ste A available. The IMPACT and FULFIL and Human Services, National Institutes Lincoln, NE 68516 trials have shown superiority in the of Health, National Heart, Lung, and Blood use of Trelegy over dual-therapy Institute. inhalers in patients that have a high 11. Bourdet SV, Williams DM. Chronic pulmonary disease. N Engl J Med. 2008; symptom burden. In addition to Obstructive Pulmonary Disease. In: DiPiro 359: 1543-1554. JT, Talbert RL, Yee GC, Matzke GR, Wells pharmacologic interventions, it is 13. Lipson D, Barnhart F, Brealey N, et al. Once- BG, Posey L. eds. Pharmacotherapy: A daily single-inhaler triple versus dual therapy important for patients to stay current Pathophysiologic Approach, 10e New York, in patients with COPD. N Engl J Med. 2018; on immunizations and include non- NY: McGraw-Hill; http://accesspharmacy. 378: 1671-1680. pharmacologic interventions. One of mhmedical.com.library1.unmc.edu:2048/ 14. Lipson D, Barnacle H, Birk R, et al. FULFIL the most important non-pharmacologic content.aspx?bookid=1861§ion trial: once-daily triple therapy for patients id=146058280. Accessed August 5, 2019. interventions is smoking cessation.10 As with chronic obstructive pulmonary disease. 12. Tashkin D, Celli B, Senn S, et al. A 4-year 2017; 196: 438-446. pharmacists, it is important to educate trial of tiotropium in chronic obstructive

30 January/February 2020 Nebraska MORTAR & PESTLE

Triple Therapy - A New Approach to Treat COPD Quiz #3, January/February 2020, ACPE 0128-0000-20-004-H01-P/T

1. COPD is the ______leading cause of death in 5. What was the effect on FEV1 in patients that the United States. used Trelegy versus Symbicort in the FULFIL a. first trial? b. second a. -29 mL c. fourth b. -15 mL d. fifth c. 121 mL d. 142 mL 2. The most common symptoms of COPD include: a. Cough 6. How is Trelegy administered? b. Mucus production a. One inhalation, once daily c. Shortness of breath b. One inhalation, twice daily d. All the above c. Two inhalations, once daily d. Two inhalations, twice daily 3. Which of the following is/are the most common risk factor(s) for developing COPD? 7. Which of the following describes the most a. Smoking cigarettes common side effects of relegy?T b. Smoking cigars a. Back pain, cough, vomiting c. Smoking marijuana b. Cough, sneezing, leg pain d. All the above c. Headache, back pain, cough d. Headache, sneezing, leg pain 4. What is the correct triple-therapy combination of Trelegy? a. Umeclidinium + olodaterol + budesonide b. Umeclidinium + vilanterol + fluticasone furoate c. Tiotropium + olodaterol + fluticasone d. Tiotropium + vilanterol + budesonide

Keep the TOP portion for your records. Return the BOTTOM portion to the NPA office. Or, take this quiz online at www.npharm.org

Name ______2020 Quiz #3 - Triple Therapy - A New Approach to Treat COPD ACPE #0128-0000-20-004-H01-P for pharmacists Mailing Address______ACPE #0128-0000-20-004-H01-T for technicians City/State/Zip______0.5 Contact Hour - Knowledge Based CPE Activity

The deadline for this quiz is December 14, 2020.

Circle one (1) Answer: CPE Home Study Evaluation 1. a b c d 5. a b c d 1. Rate this lesson: (Excellent) 5 4 3 2 1 (Poor) 2. Did this lesson meet each of its objectives? ___ Yes ___ No 2. a b c d 6. a b c d 3. Was the content without commercial bias? ___ Yes ___ No 3. a b c d 7. a b c d If not, please explain______4. a b c d 4. Did the lesson meet your educational/practice needs? __ Yes __ No 5. Comments/future topics are welcome. ______

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