nebraska mortar & pestle - npharm.org · your npa member benefits include a daily email with...

Nebraska

Official Publication of the Nebraska Pharmacists Association

Member Spotlight - Sabrina Beck | Pg 6

Vitiligo & Treatment Options | Pg 8

Rx and The Law | Pg 17

Baqsimi - New Delivery for Glucagon | Pg 18

Financial Forum | Pg 26

Trelegy - New Triple Therapy | Pg 28

For NPA Members

MORTAR & PESTLEJanuary/February 2020 | Volume 83, Number 1

Pam Miller2020 NPA President

2 January/February 2020

Nebraska MORTAR & PESTLE

CPE Programs

Board of DirectorsPresident, Pam Miller Immediate Past President, Ally Dering-Anderson President-Elect, Brent Gollner Treasurer, Jeffrey Steffensmeier Chief Executive Officer, Joni Cover District Members District 1, Ken Kester District 1, Jeffrey Steffensmeier District 2, Jeanie Shipman District 2, Eric Sundsboe District 3, Beth Boals-Shively District 3, Tim Redline

Pharmacy Technician Tyler Garrelts

Students Alexander Brown, CU Cory Durbin, UNMC Network Chairs Academia/Specialty Practice, Alli Gabriel Chain, Kendra Kapels Hospital/Health-System, Jerome Wohleb Independent, Trevor Bertsch Industry, Ryan Flugge Long-Term Care, Mackenzie Farr New Practitioner, Jacelyn Watt

PublisherThe Nebraska Mortar & Pestle (M&P) (ISSN 0028-1891) is owned and published by the Nebraska Pharmacists Association to provide continuing pharmacy education, drug information, news, and trends in the profession of pharmacy. Opinions expressed by the contributors, whether signed or otherwise, do not necessarily reflect the attitudes of the publisher nor are they responsible for them.

The M&P is published six times a year - February, April, June, August, October and December. The subscription rate for non-members is $30 per year. The managing editor is Joni Cover. The office of publication is 6221 S 58th St, Suite A, Lincoln, NE 68516-3687.

Second class postage paid at Lincoln, Nebraska, and at additional mailing offices. Postmaster: send address changes to Nebraska Mortar & Pestle, 6221 S 58th St, Suite A, Lincoln, NE 68516-3687 or email [email protected].

NPAStaff

Joni Cover, JDChief Executive Officer

Marcia Mueting, PharmDVP, Professional Affairs

Diane WebbFinance & Marketing

Nebraska Pharmacists Association6221 S 58th St, Suite A Lincoln, NE 68516p: 402.420.1500 | f: 402.420.1406e: [email protected] | w: npharm.org

Sarah HunterProject Coordinator

Fraud, Waste, and Abuse1.0 hour Knowledge-based CPE Activity$10 NPA Member | $20 NonMember How to Engage Your Senators: You Can Make a Difference1.0 hour Knowledge-based CPE Activity$0 NPA Member | $25 NonMember

Nicotine Cessation Counseling: A Guide for Pharmacists2.0 hours Knowledge-based CPE Activity$25 NPA Member | $50 NonMember Risky Business: Assessment of Risk on Hazardous Drugs1.0 hour Knowledge-based CPE Activity$25 NPA Member | $50 NonMember

USP Chapter <800> Handling Hazardous Drugs in Healthcare Setting: Considerations for STERILE Products and Compounding1.0 hour Knowledge-based CPE Activity$25 NPA Member | $50 NonMember

USP Chapter <800> Handling Hazardous Drugs in Healthcare Setting: Considerations for Non-Sterile Products and Compounding1.0 hour Knowledge-based CPE Activity$25 NPA Member | $50 NonMember

npharm.org/npacpeprograms

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In Case You Missed ItYour 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 ChangeThe NPA will not be hosting a full convention this year. Instead, more targeted CPE programs will be offered. Please let us know what CPE topics and formats work best for you by contacting Marcia Mueting, PharmD, Vice President of Professional Affairs, at 402-420-1500 or [email protected].

Nebraska Legislative SessionNew Legislative Bills have been introduced this year. The NPA's Long-Term Care Issues Work Group developed consensus language and is exemplified in LB 847. The NPA also developed prescription adaptation language as drafted in LB 887. Thank you to Senator John Arch for sponsoring these two bills. LB 922 was introduced by Senator Mark Kolterman to mandate eprescribing of controlled substances beginning 01/01/2021.

Watch your emails for NPA Legislative updates that are sent to NPA members on Fridays during the Legislative Session. A link to the NPA's Legislative Summary will also be included in these emails. If you have any questions during the Session, contact Joni Cover at [email protected] or at 402-420-1500.

NPA Pharmacy Law ManualThe NPA Pharmacy Law Manual - updated with 2019 legislative changes - is now available. Find Nebraska pharmacy statutes and regulations in one place. What a great pharmacy reference! No need to search the internet or paper copies. Visit the NPA online store to order your copywww.npharm.org/store_home.asp.

Foundation & NebPharmPAC DonorsMany thanks to the generous pharmacists who have donated to the Nebraska Pharmacy Foundation and the NebPharmPAC. It's easy to donate! Call the NPA office at 402-420-1500 or email [email protected] and donate today.

Membership Drawing WinnersCongratulations to the following NPA members who won a $50 Amazon e-Gift for renewing their 2020 membership before December 15, 2019.

• Sheila Brumbaugh, RP, Red Cloud• Rachel Forrest, RP, Omaha• Jerry Jensen, RP, Kearney• Jeanette Kadow, CPhT, Hastings

And thanks to all of you for renewing your membership for 2020!

USP Chapter <800>According to the recently posted USP <800> Frequently Asked Questions document, USP Chapter <800> (Hazardous Drugs—Handling in Healthcare Settings) Chapter <800> only applies when a practitioner is compounding. It states that since administration and dispensing final dosage forms are not compounding, Chapter <800> does not apply to those functions.

Further, "Final dosage forms of HDs that do not require any further manipulation may be dispensed without any further requirements for containment unless required by the manufacturer or if visual indicators of HD exposure hazards are present (e.g., HD dust or leakage). These do not require any additional storage or handling requirements according to USP <800> unless otherwise required by the manufacturer."

FoundationSam AugustineJeff BaldwinDan BillerbeckKendra BunkersAnne BrucknerJeffrey BrommerJoni CoverAlly Dering-AndersonEdward DeSimoneMackenzie FarrWendall GastonTiffany GoellerBrent & Patty GollnerDonald GrahamJohn GuzallisMatt GuzallisLinda Guzman-GonzalesReg HainHall County Pharmaceutical AssociationRoger Ladd

Joseph LathropRobert LeopoldFred MassoomiMelvin MenkeWilliam MichaelPam MillerCharlie MooreMarcia MuetingTracy NeujahrGary NorthouseRuss RathjenRoger & Paula RiesbergGary RihanekNiki SalomonNancy SloanPaula StobbsArlin StutheitJenny TillemanBill TooleyFloyd VanEngenPhil Vuchetich

NebPharmPACClark AndersonRoy AndersonSam AugustineJeff BaldwinJeffrey BrommerRick ClabaughEdward DeSimoneTiffany GoellerBrent & Patty GollnerMatt GuzallisLinda Guzman-GonzalesReg HainWilliam Michael

Charlie MooreLinda Myers-BockScott PerssonCharlie PierceRuss RathjenRoger & Paul RiesbergNiki SalomonPaula StobbsArlin StutheitBill TooleyFloyd VanEngenPhil Vuchetich



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

President'sMessageMindful of Your TrustPam Miller, PharmD, RP

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Kim Scarsi, Pharm.D.

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 in-ternational sites, with an emphasis on women living with HIV and persons co-infected with HIV and tuberculosis. Dr. Scarsi also serves as an investigator 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 cut by color technology. His group has research projects focused on developing new drug delivery systems that target tumor metabolism and pathogen biosensing.

UNMC College of Pharmacy faculty awarded Distinguished Scientist Awards

High School Alliance

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 develop-ment 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.

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, com-pounding 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].

Aaron Mohs, Ph.D.



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.

Where did you attend pharmacy school?I graduated from the University of Nebraska Medical Center College of Pharmacy.

Why did you choose to pursue a career in hospital pharmacy?As a high school student, I cashiered in a retail pharmacy and worked as a nurse’s aide in a hospital. Working as a 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 decide to pursue pharmacy as a career. I worked both inpatient and outpatient as a pharmacy student. After graduation, I worked at the University of Nebraska Medical Center for Jim Dubé where I staffed on the medical/surgical units and in the OR pharmacy. I eventually took a leadership position in the central operations role. The experience was invaluable and the personal and professional relationships I developed through that position continue to be of great value.

What made you want to serve on the Board of Pharmacy? I thought it would be a great opportunity to advocate for 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.

What advice do you have for someone looking to pursue a career as a hospital pharmacist? I would encourage the person to be realistic about the schedule. The role of the pharmacist is integrated into the healthcare team and sometimes that can mean a challenging schedule that includes weekends, evenings, and overnights. Knowing that you are helping people and having a passion for the work you are doing certainly makes up for a sometimes crazy schedule.

What is it like having your spouse also be a hospital pharmacist?It works out great. It is always nice to have a colleague near to bounce ideas off of. Jon is very supportive and understands that my position is unpredictable. I appreciate that I can run into work without upsetting my spouse, and hopefully he feels the same way.

MemberSpotlightSabrina Beck,PharmD, RPPharmacy Supervisor


Is there an NPA member who's work needs to be recognized? Contact NPA Project Coordinator, Sarah Hunter, at 402-420-1500 or [email protected]. We want to hear from you!

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UPDATE FROM CREIGHTON UNIVERSITY SCHOOL OF PHARMACY AND HEALTH PROFESSIONS

Pharmacy Skills Lab Named in Greenwood Family’s HonorBob, 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.

spahp.creighton.edu

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

Edward DeSimone II, RPh, PhD, FAPhA, professor in the Department of Pharmacy Sciences, was appointed to the Substance Use Disorders Special Interest Group,

“Taskforce on Update of the 2010 Report of the AACP Special Committee on Substance Abuse and Pharmacy Education,” and was appointed to the Nebraska Department of Health and Human Services Comprehensive Opioid Abuse Program.

Robyn M. Teply, PharmD’07, MBA’07, BCACP, associate professor in the Department of Pharmacy Practice, published a project with colleagues from Temple University, University of Illinois at Chicago and Vanderbilt University,

“Expanding Hepatitis C Virus Care and Cure; National Experience Using a Clinical Pharmacist-Driven Model” in Open Forum Infectious Diseases.

“Creighton will always be a special place for our family,” Chery says. “We’ve been very blessed, and Creighton is a big part of our success.”

Shortly after graduating Creighton, Bob moved to Waterloo and opened a pharmacy with a few partners. Within a decade, he and his family would own a Waterloo pharmacy outright, gradually adding locations in the years that followed.

Greenwood Pharmacy now offers a range of services, including retail, assisted living, immunizations, medication therapy management and long-term care practice. It was his clinical education, Bob says, that prepared him to offer such a diversity of services.

“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 people the medications they need and helping guide them through chronic disease states, like diabetes or congestive heart failure.”

Bob also served as a leader for various professional organizations, including the National Community Pharmacists Association, the American Pharmacists Association and the Iowa Pharmacy Association. He also served on Waterloo’s city council for 12 years.

Even in the thick of work, family, business, professional commitments and city council meetings, Bob and Chery stayed plugged in to the University and helped to shape the School of Pharmacy and Health Professions.

Creighton affected the Greenwoods’ lives deeply. They, in turn, returned the favor.

“I didn’t have the best grades, but I was driven, and Creighton’s pharmacy school took a chance on me,” Bob says. “Creighton means a lot.”

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



Continuing Pharmacy Education | Lesson #1

ObjectivesAt the conclusion of this lesson, pharmacists and pharmacy technicians should be able to:1. Explain the background of vitiligo.2. List the different classifications of

vitiligo.3. Identify treatment options based on

the type of vitiligo.

BackgroundVitiligo is a noncontagious, autoimmune skin condition with white patches or spots caused by depigmentation of the skin.1 In patients with vitiligo, the immune system attacks melanocytes resulting in areas of pigment loss.2 Melanocytes are the pigment cells which give the skin its color. Depigmentation usually occurs

VitiligoandTreatmentOptions

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.

Kristen GrimaldiWritten by

first on sun-exposed areas such as the face, arms, legs, hands, and feet. There may also be depigmentation of the hair on the scalp, eyelashes, eyebrows, or other body hair of affected areas.3 Some patients may experience itching at the affected sites during active stages of pigment loss.4 Vitiligo is an unpredictable, progressive disease in which a patient may experience a flare-up of depigmentation after a stable period where the patient does not experience any spreading of the depigmentation. Stable periods are defined as having no change or spread of depigmentation within a 12-month period.3 Currently, there is no cure for vitiligo, but there are treatments that work well for slowing or stopping the progression of the disease and allowing repigmentation.

Vitiligo is the most common cause of skin depigmentation worldwide.2 The peak incidence occurs around the second or third decade of life.2,5 Vitiligo affects 0.5% to 2% of the population worldwide and may appear at any age ranging from childhood to late adulthood.6,7 There is a higher impact of vitiligo in patients with more pigmented skin since it is more noticeable.5

In order to provide patients with proper care, healthcare professionals should be cognizant of how vitiligo impacts a patient physically and mentally. Vitiligo can have a major impact on a patient’s mental health and well-being.4 Patients are often misdiagnosed due to lack of knowledge on the pathogenesis of the

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disease. For example, vitiligo may be confused with leprosy.3 Patients often experience depression, emotional distress, and social isolation due to the social stigma associated with the physical appearance of the condition.2 This may result in impaired social development and decreased quality of life. In addition to understanding the psychological impact of vitiligo on a patient, phamacy personnel should know about the condition and the different treatments available in order to assist patients and prescribers.

ClassificationVitiligo is separated into two major classes: segmental or non-segmental. Vitiligo may also be classified as mixed which is a combination of segmental and non-segmental vitiligo.2 In mixed vitiligo, the segmental form precedes the non-segmental form. Table 1 shows the different classifications of vitiligo.

Segmental vitiligo, the least common type of vitiligo, occurs when depigmentation develops in one, two, or multiple segments of the body. Segmental vitiligo may be further described as unisegmental, bisegmental, or plurisegmental.2

Unisegmental vitiligo is the most common form of segmental vitiligo and occurs when at least one white macule is present on only one side of the body.8 Unisegmental vitiligo occurs in a unilateral, band-shaped, dermatomal or quasi-dermatomal pattern along the trigeminal nerve. Pigment loss tends to stabilize rapidly and seldom spreads past the dermatome, an area of skin supplied by a nerve root, that is affected.3

Non-segmental vitiligo typically appears bilaterally or symmetrically and tends to progress over time.2 It can be further categorized into generalized, mucosal, acrofacial, and universal subtypes.3,9 Generalized vitiligo usually occurs on areas of the body that have experienced trauma, friction, or pressure.8 This subcategory is defined by bilateral, depigmented patches that are randomly spread on the skin.3,9

Mucosal vitiligo affects mucosa of the oral and/or genital regions. It may happen on its own or in conjunction with generalized vitiligo. Mucosal vitiligo may only affect one site, or it may affect more than one site.3,8 If only one mucosal site is affected and no change in lesion characteristics are noted after two years, then it is considered an unclassifiable form of vitiligo.3,9

Acrofacial vitiligo occurs when distal extremities and the face lose pigment. It may progress to other areas of the body leading to generalized vitiligo.9

Universal vitiligo is the complete loss of skin pigment typically due to the progression of generalized vitiligo. Some skin areas or hair may be spared in universal vitiligo.9

Focal skin lesions of depigmentation that are small and isolated are considered unclassifiable vitiligo if the lesions do not progress to segmental or non-segmental vitiligo within one to two years.2,9

There are rare cases of vitiligo which have been categorized as vitiligo minor and follicular vitiligo. Vitiligo minor is a subcategory of non-segmental vitiligo which has been documented in patients with darker skin. This subcategory involves an incomplete defect in pigmentation resulting in a lighter skin color in affected areas.2

Non-segmental vitiligo typically targets epidermal melanocytes rather than follicular melanocytes, but follicular melanocytes are affected in follicular vitiligo. Follicular vitiligo is a subcategory of non-segmental vitiligo that targets hair follicle melanocytes.9,10

Theories of PathogenesisThe cause of vitiligo is not well understood but is believed to be the result of a combination of genetic, immunologic, biochemical, and neurogenic factors. There have been multiple proposed theories that include the autoimmune hypothesis, neural theory, biochemical theory, zinc a2-glycoprotein (ZAG) deficiency hypothesis, viral theory, and intrinsic theory.11

The autoimmune hypothesis is based on the association of vitiligo and multiple other autoimmune disorders. Patients with vitiligo frequently have other autoimmune comorbidities, such as thyroiditis, rheumatoid arthritis, psoriasis, Addison’s disease, alopecia, or diabetes mellitus.1 Patients with vitiligo may have antithyroid antibodies, anti-thyroglobulin antibodies, anti-thyroperoxidase, and anti-smooth muscle antibodies that

Table 1.Classifications of Vitiligo2

Non-Segmental• General• Mucosal• Acrofacial• Universal• Minor• Follicular

Segmental• Unisegmental• Bisegmental• Plurisegmental

Mixed• A combination of non-segmental and

segmental



may be related to thyroid disease and other autoimmune comorbidities.11 According to one study, 20% of vitiligo patients had thyroid hormonal profiles that showed autoimmune thyroid dysfunction.12 Approximately 80% of patients with vitiligo have increased immunoglobulin G and immunoglobulin M.13 In patients with active non-segmental vitiligo, melanocyte death has been linked to higher serum levels of immunoglobulin G antimelanocytes. These antibodies are believed to cause damage to melanocytes by antibody dependent cytotoxicity and complement-mediated mechanisms. Alpha-melanocyte-stimulating hormone (alpha-MSH) regulates pigmentation of skin, inflammation, and stress responses. Alpha-MSH binds to anti-melanocortin 1 receptor (MC1R) on melanocytes. This interaction is believed to play a role in the regulation of melanocytes and skin pigmentation.14 Lower level of alpha-MSH have been found in patients with vitiligo.15 Melanin concentrating hormones receptor-binding antibodies have also been reported in patients with vitiligo. These antibodies block the stimulation of the melanin concentrating hormones receptor which could result in pigment changes.16

The neural theory states that segmented vitiligo appears to follow the path of the dermatome.17 The production of melanin from the melanocytes is disturbed by dysfunction of the sympathetic nervous system resulting in the loss of pigment. In patients with vitiligo, axonal degeneration has been observed further supporting the neural theory.18

The biochemical theory suggests that reactive oxygen species are potential inducers of vitiligo. Reactive oxygen species, also known as free radicals, are unstable molecules that react with cellular molecules.19 An accumulation of

reactive oxygen species may lead to cell death. The areas of skin affected by vitiligo have increased reactive oxygen species, such as H2O2, due to imbalanced reduction-oxidation and an inability to manage stressors from cellular processes or environmental factors. Oxidation of melanocytes from reactive oxygen species leads to the destruction and detachment of pigment of the cells leading to the depigmentation.20

The zinc α2-glycoprotein (ZAG) deficiency hypothesis states there is an association between ZAG and vitiligo proposing that vitiligo could be caused by a reduction in ZAG.21 ZAG influences melanocyte proliferation since it acts as a keratinocyte-derived factor. A reduction in ZAG results in diminished melanocyte adhesion to surrounding cells.22 This is important because melanocyte loss plays an important role in the pathogenesis of vitiligo. The ZAG gene was detected on chromosome 7 and linkage signals on this chromosome have been documented in patients with vitiligo and associated autoimmune diseases.21

The viral theory suggests an association between vitiligo and certain viruses. There have been studies suggesting an association between vitiligo and chronic hepatitis C virus.23 In one study, patients with vitiligo were also reported to have hepatitis B virus sero-positivity.24 There is an association between vitiligo and cytomegalovirus, herpes virus, hepatitis E virus, Epstein-Barr virus, or the human immunodeficiency virus.25

The intrinsic theory states that patients with vitiligo have melanocytes with abnormalities. These abnormalities include irregular rough endoplasmic reticulum, low melanocyte growth factors, and a low number of melanocytes expressing c-kit receptor in the areas affected

by the vitiligo.26 Keratinocyte-derived c-kit stimulation is required to maintain melanocytes. These intrinsic defects result in the death of melanocytes in patients with vitiligo.27

TreatmentWhile there is no cure for vitiligo, it is a treatable condition. This condition is effectively treated with immunosuppressive treatments. It may take approximately two years for a patient to regain pigmentation.1 Although regaining pigmentation is possible with treatment, the repigmentation may not be complete. Patients may also experience depigmentation again upon cessation of effective therapy.28 Pharmacists should refer patients to their physician or a psychiatrist if they have concerns related to mental health.

Topical CorticosteroidsTopical corticosteroids are effective in the treatment of vitiligo due to suppression of the immune response. Intermediate- to very high-potency topical corticosteroids are used for the treatment of vitiligo as shown in Table 2.29 Topical corticosteroids are more effective in combination with light therapy than light therapy alone for the induction of repigmentation.30

Light therapy, or phototherapy, involves exposure of the skin to specific wavelengths of light depending on the type of phototherapy. Examples of phototherapy used for the treatment of vitiligo include narrowband ultraviolet B phototherapy, psoralen plus ultraviolet A photochemotherapy (PUVA), and target phototherapy. When large surface areas of the body are affected by vitiligo, there is concern for systemic absorption leading to adrenal suppression when topical corticosteroids are used for prolonged periods of time.28

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Topical Calcineurin InhibitorsTopical calcineurin inhibitors are immunomodulatory drugs that inhibit proinflammatory cytokines by modulating target cell functions. Examples of topical calcineurin inhibitors are tacrolimus and pimecrolimus. These agents are being used more frequently on vitiligo lesions of the face.28,30 In one trial, patients were treated with topical clobetasol propionate 0.05%, topical tacrolimus 0.1%, or placebo. In patients with facial vitiligo, the rate of repigmentation was 58% for both topical clobetasol and topical tacrolimus. The success rate of repigmentation was defined at greater than 50%. In patients with nonfacial vitiligo, the repigmentation rate was higher in the topical corticosteroid group (39%) than the tacrolimus group (23%). The placebo group had a repigmentation rate of 7%.31 Topical tacrolimus and pimecrolimus have a boxed warning for a documented increased risk of skin cancers and lymphoma associated with exposure to calcineurin inhibitors.32

Table 2.Topical Corticosteroid Potency29

Potency Generic Name (Brand Name) Formulation

Very High Betamethasone dipropionate 0.25% Gel, lotion, ointment

Clobetasol propionate 0.05% Cream, gel, lotion, ointment

Diflorasone diacetate 0.05% Ointment

Halobetasol propionate 0.05% Cream, ointment

High Amcinonide 0.1% Cream, lotion, ointment

Betamethasone dipropionate 0.05% Cream, ointment

Betamethasone valerate 0.1% Ointment

Desoximetasone 0.25% Cream, ointment

Fluocinonide 0.05% Cream, ointment, gel

Halcinonide 0.1% Cream, ointment

Triamcinolone acetonide 0.5% Cream

Intermediate Betamethasone dipropionate 0.05% Lotion

Betamethasone valerate 0.1% Cream

Fluticasone propionate 0.005% Ointment

Fluticasone propionate 0.05% Cream, lotion

Mometasone furoate 0.1% Cream, ointment, lotion

Triamcinolone acetonide 0.025% or 0.1% Cream, ointment, lotion

Systemic CorticosteroidsSystemic corticosteroids may be used for stabilization of rapidly progressive vitiligo. Low doses of oral corticosteroids may be used in combination with narrowband ultraviolet B phototherapy to improve efficacy. There have been studies showing the efficacy of oral corticosteroids in stopping the spread of depigmentation in vitiligo. Systemic corticosteroid therapy should not be used for repigmentation of stable vitiligo due to lack of efficacy and adverse effects of long-term corticosteroid use.33

Narrowband Ultraviolet B PhototherapyNarrowband ultraviolet B phototherapy uses UV lamps with peak emission of 311 nm.8,34 Patients have the option to go to a clinic to receive phototherapy treatment or buy a home narrowband ultraviolet B phototherapy unit. If a patient opts to use the handheld phototherapy treatment at home,

then they should be given detailed instructions for use and schedule regular follow-ups with their physician. This phototherapy causes local immunosuppression. It helps to stimulate melanocyte-stimulating hormone, fibroblasts, growth factor, and endothelin I. Narrowband ultraviolet B phototherapy increases the production of melanocytes leading to repigmentation.34 It has a good safety profile and is the treatment of choice for vitiligo affecting greater than 10% of total body surface area.28

Psoralen Plus Ultraviolet A PhotochemotherapyPUVA administered topically or systemically was originally the treatment of choice for vitiligo. PUVA is a combination of psoralen, a photoactive chemical, and ultraviolet A (UVA).8 Patients either take the psoralen orally or apply it topically before exposure to UVA.34 Narrowband ultraviolet B phototherapy has replaced PUVA due to its many adverse effects.2 These adverse effects include nausea and gastrointestinal discomfort from oral PUVA, itching, redness, blisters, burns, freckles, and cataracts. Eye protection labeled UV 400/UVB/UVA protection 100% is required for protection from UVA for 12 to 24 hours after treatment with PUVA.34 PUVA also increase a patient’s risk for skin cancer.28

Target PhototherapyTarget phototherapy uses lamps or lasers with an emission of 308nm. This high intensity light may be used to treat localized vitiligo.34 Treating the localized area helps to avoid higher cumulative ultraviolet B doses.35 Targeted phototherapy may be used concomitantly with topical corticosteroids and topical calcineurin inhibitors.28



Off-Label TreatmentAfamelanotide is a synthetic analogue of human α–melanocyte-stimulating hormone. This experimental therapy stimulates the skin and pigmentation leading to tanning of the skin. It is used in combination with narrowband ultraviolet B phototherapy for the treatment of vitiligo.28,36 A randomized, open label, Phase 1 study in adult men and women diagnosed with non-segmental vitiligo involving 15% to 50% of total body surface area assigned participants to combination therapy with narrowband ultraviolet phototherapy and afamelanotide or monotherapy with narrowband ultraviolet phototherapy. The combination regimen included narrowband ultraviolet phototherapy followed by alfamelanotide 16 mg injection administered subcutaneously monthly for four months starting after one month of phototherapy. Phototherapy was continued in the combination group throughout treatment. This study used two validated scoring systems, Vitiligo Area Scoring Index (VASI) and Vitiligo European Task Force (VETF) score, to assess the degree of depigmentation.

The primary efficacy outcome was the change in pigmentation of the full body, face, trunk, and extremities from day 0 to 168 between the two groups. The secondary efficacy outcome was the time to onset of repigmentation. Repigmentation of the combination group was 48.64% compared to 33.26% for the monotherapy group at day 168. Both groups showed statistically significant improvement in VETF scores, but the combination therapy group reached it at day 56 compared to the monotherapy group at day 84. No statistically significant difference was found between groups in patients with Fitzpatrick skin phototypes III.36

There are six Fitzpatrick skin phototypes based on distinct trends of past sun reactions. Fitzpatrick skin phototype I includes ivory skin color, light blue, gray or green eyes, natural red or light blonde hair, skin always burns, peels or freckles from the sun, and skin never tans.

Fitzpatrick skin phototype II includes fair or pale skin; blue, gray or green eyes; natural blonde hair; skin usually burns; peels or freckles from the sun; and skin rarely tans.

Fitzpatrick skin phototype III includes fair to beige skin with golden undertones, light brown or hazel eyes, natural dark blonde or light brown hair, skin might freckle or burn on occasion from the sun, and skin sometimes tans.

Fitzpatrick skin phototype IV includes olive or light brown skin, dark brown eyes, natural dark brown hair, skin rarely freckles or burns from the sun, and skin tans often.

Fitzpatrick skin phototype V includes dark brown skin color, dark brown to black eyes, natural dark brown to black hair, skin rarely freckles, almost never burns and always tans.

Fitzpatrick skin phototype VI includes dark brown to darkest brown skin, brownish black eyes, natural black hair, and skin never freckles or burns, and skin always tans darkly.37 The study showed a statistically significant improvement in VASI for Fitzpatrick skin phototypes IV to VI. The Vitiligo Area Scoring Index is a useful tool for assessing the degree of depigmentation in vitiligo in research.38 This study showed that combination therapy with afamelanotide and phototherapy had a faster, clinically evident, statistically significant repigmentation than using phototherapy alone.36

Other experimental, off-label treatments include bimatoprost, prostaglandin E2, and topical ruxolitinib. Bimatoprost is an analog of prostaglandin F2-alpha. It causes hyperpigmentation of periocular skin by increasing melanogenesis. Topical bimatoprost is approved for hypotrichosis of the eyelashes and glaucoma.39 In one study, efficacy was compared for bimatoprost ophthalmic solution alone, bimatoprost topical ophthalmic solution in combination with topical mometasone, and topical mometasone alone in patients with non-segmental, stable, nonfacial vitiligo. None of the patients reached the primary end point of 50 to 75% repigmentation.40 Prostaglandin E2 may be useful for stable localized vitiligo. It has stimulatory and immunomodulatory effects on the production of melanocytes.41 In one study, about 71% of patients treated with prostaglandin E2 gel experienced repigmentation.42 Topical ruxolitinib is an inhibitor of Janus kinase 1 and 2.43 In a phase 2 trial, the cream was applied twice daily for 20 weeks to participants with diagnosed vitiligo involving 1% or more of total body surface area. Some of the participants showed an improvement in the Vitiligo Area Scoring Index.44

Non-pharmacological treatment options for patients with segmental vitiligo that have not responded to pharmacological therapy include surgery or depigmentation. Surgical options include minigrafts, autologous melanocyte cultures, hair follicle transplantation, split-thickness grafts, and autologous suction blister grafts.30 Depigmentation is performed with topical monobenzyl ether of hydroquinone, also known as monobenzone.45

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Place in TherapyThe first-line therapy for stable non-segmental vitiligo involving less than 10% of the total body surface area is mid-potency or high-potency topical corticosteroids. Topical corticosteroids, such as mometasone furoate, are utilized due to fewer systemic side effects. The topical corticosteroids are applied to the affected areas 1 to 2 times daily, but duration of treatment varies. Another first line treatment includes topical calcineurin inhibitor, such as tacrolimus and pimecrolimus. Topical calcineurin inhibitors are typically applied to the affected areas 2 times daily. Topical corticosteroids and topical calcineurin inhibitors may be used in combination for up to 2 months. If a patient is not responding to topical therapy, then narrowband ultraviolet B phototherapy may be used 2 times per week. For patients with disseminated vitiligo that is affecting multiple sites, but overall depigmentation remains less than 10% of total body surface area, narrowband ultraviolet B phototherapy is recommended to be used 2 to 3 times per week.2,28,46

Patients with segmental vitiligo affecting less then 10% of total body surface area are recommended to use topical corticosteroids, topical calcineurin inhibitors, or targeted phototherapy as first-line therapies. If a patient does not respond to topical therapy or phototherapy, then surgical procedures are an option because segmental vitiligo tends to be more stable.28,30,34

The first-line therapy for stable non-segmental vitiligo involving 10 to 40% of the total body surface area is narrowband ultraviolet B phototherapy. Phototherapy is performed 2 to 3 times per week over the course of 9 to 12 months. Narrowband ultraviolet B phototherapy can be used for up to 24 months or 200 sessions

if the patient is having continued repigmentation with therapy. Once the patient reaches 24 months or 200 sessions of phototherapy, the therapy must be tapered off. Topical corticosteroids or topical calcineurin inhibitors may be used concomitantly with the phototherapy.2,28,34

The first-line therapy for vitiligo involving greater than 40% of the total body surface area is narrowband ultraviolet B phototherapy.2,34 The regimen is also 2 to 3 times per week over 9 to 12 months with the same limitations. If a patient with vitiligo does not respond to repigmentation modalities, then depigmentation of remaining normally pigmented areas may be performed with monobenzone. The regimen includes monobenzone 10% cream for 1 month followed by monobenzone 20% cream. The depigmentation of residual pigmented areas may take one to three years for best outcomes.28

First-line therapy for the stabilization of rapidly progressive disease is low dose oral corticosteroids. Rapidly progressive disease occurs when depigmentation spreads over weeks to months. The drug of choice is oral prednisone 10 to 20 mg daily for up to 2 weeks. The course may be repeated in 4 to 6 weeks if necessary. Alternative therapy options include an oral mini-pulse therapy with dexamethasone 2.5 mg on 2 consecutive days each week for an average of 3 months or intramuscular triamcinolone 40 mg once.28 The minipulse therapy helps to reduce adverse events from the corticosteroids.8 The intramuscular injection may be repeated in 4 to 6 weeks up to a maximum of 3 injections if necessary. Oral corticosteroids may be given with or without narrowband ultraviolet B phototherapy. Combination of phototherapy with systemic corticosteroids is recommended for patients with active disseminated disease located at multiple sites of the body. If systemic corticosteroids cannot be used, then narrowband ultraviolet phototherapy may be used alone to attempt stabilization of the rapid progression of depigmentation.28

ConclusionPharmacy personnel should be able to identify the different classifications of vitiligo. While there is no cure for vitiligo, there are efficacious treatments for vitiligo. Patients will be treated differently depending on the type of vitiligo they have. Pharmacists should be able provide patients and prescribers with appropriate advice and treatment recommendations.



Policies for the Nebraska Mortar & Pestle (M&P) continuing pharmacy education lessons and quizzes:

1. M&P Quizzes are valid only for the membership year in which they are published. Quizzes for the 2020 Membership Year must be received by December 14, 2020. Quizzes cannot be carried over to another membership year.

2. If more than three questions are missed, the quiz will be returned. The quiz can be resubmitted.

3. CPE transcripts can be printed from NABP e-Profiles at www.nabp.net.

4. CPE credits are submitted to NABP by the 15th of each month. For example, M&P CPE quizzes completed in the month of March 2020 will be sent to NABP e-Profiles by April 15, 2020.

The Nebraska Council for Continuing Pharmacy Education (NCCPE) is accredited by the Accreditation Council for Pharmacy Education

(ACPE) as a provider of continuing pharmacy education (CPE). This CPE home study activity has been accredited for 1.0 contact hour or 0.10 CEU. UAN 0128-0000-20-001-H01-P for pharmacists and UAN 0128-0000-20-001-H01-T for pharmacy technicians. This is a knowledge-based CPE activity targeted to pharmacists and pharmacy technicians.

The Nebraska Pharmacists Association disclaims any liability to you or your patients resulting from reliance solely upon the information contained herein.

Quiz Answers may be submitted:

Online: www.npharm.orgFax: 402-420-1406Email: m&[email protected]: Nebraska Mortar & Pestle 6221 S 58th St, Ste A Lincoln, NE 68516

1. Vitiligo Support International. What is Vitiligo website. https://vitiligosupport.org/what-is-vitiligo/. Accessed July 8, 2019.

2. Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet. 2015;386(9988):74-84.

3. Grimes PE. Vitiligo: Pathogenesis, clinical features, and diagnosis. UpToDate. http://www.utdol.com. Updated February 3, 2017. Accessed July 8, 2019.

4. Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: A comprehensive overview: Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011;65(3):473-491.

5. Vitiligo Support International. Genetics and Incidence website. https://vitiligosupport.org/genetics-incidence/. Accessed July 8, 2019.

6. Kyriakis KP, Palamaras L, Tsele E, Michailides C, Terzoudi S. Case detection rates of vitiligo by gender and age. Int J Dermatol. 2009;48(3):328-329.

7. Kruger C, Schallreuter KU. A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol. 2012;51(10):1206-1212.

8. Reichert-Faria A, Tarlé RG, Dellatorre G, Mira MT, Silva de Castro CC. Vitiligo - Part 2 - classification, histopathology and treatment. An Bras Dermatol. 2014;89(5):784-90.

9. Ezzedine K, Lim HW, Suzuki T, et al. Revised classification/nomenclature of vitiligo and related issues: The Vitiligo Global Issues Consensus Conference. Pigment Cell Melanoma Res. 2012;25(3):1-13.

10. Ezzedine K, Amazan E, Seneschal J, et al. Follicular vitiligo: a new form of vitiligo. Pigment Cell Melanoma Res. 2012;25(4):527-529.

11. Mohammed GF, Gomaa AH, Al-Dhubaibi MS. Highlights in pathogenesis of vitiligo. World J Clin Cases. 2015;3(3):221-230.

12. Gopal KVT, Rao GR, Kumar YH. Increased prevalence of thyroid dysfunction and diabetes mellitus in Indian vitiligo patients: A case-control study. Indian Dermatol Online J. 2014;5(4):456-460.

13. Harning R, Cui J, Bystryn JC. Relation between the incidence and level of pigment cell antibodies and disease activity in vitiligo. J Invest Dermatol. 1991;97:1078-1080.

14. Brenner M, Hearing VJ. Modifying skin pigmentation - approaches through intrinsic biochemistry and exogenous agents. Drug Discov Today Dis Mech. 2008;5(2):189-199.

15. Pichler R, Sfetsos K, Badics B, Gutenbrunner S, Aubock J. Vitiligo patients present lower plasma levels of alpha-melanotropin immunoreactivities. Neuropeptides. 2006;40(3):177-183.

16. Gottumukkala RV, Gavalas NG, Akhtar S, et al. Function-blocking autoantibodies to the melanin-concentrating hormone receptor in vitiligo patients. Lab Invest. 2006;86:781-789.

17. Koga M, Tango T. Clinical features and course of type A and type B vitiligo. Br J Dermatol. 1988;118(2):223-228.

18. Al-Abadie MS, Warren MA, Bleehen SS, Gawkrodger DJ. Morphologic observations on the dermal nerves in vitiligo: an ultrastructural study. Int J Dermatol. 1995;31(12):837-840.

19. Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24(5):981–990.

20. Khan R, Satyam A, Gupta S, Sharma A. Circulatory levels of antioxidants and lipid peroxidation in Indian patients with generalized and localized vitiligo. Arch Dermatol Res. 2009;301(10):731-737.

21. Bagherani N, Yaghoobi R, Omidian M. Hypothesis: zinc can be effective in treatment of vitiligo. Indian J Dermatol. 2011;56(5):480-484.

22. Hassan MI, Waheed A, Yadav S, Singh TP, Ahmad F. Zinc alpha 2-glycoprotein: a multidisciplinary protein. Mol Cancer Res. 2008;6(6):892-906.

23. Akbayir N, Gokdemir G, Mansur T, et al. Is there any relationship between hepatitis C virus and vitiligo? J Clin Gastroenterol. 2004;38(9):815-817.

24. Akcan Y, Kavak A, Sertbas Y, et al. The low seropositivity of hepatitis B virus in vitiligo patients. J Eur Acad Dermatol Venereol. 2006; 20(1):110-111.

25. Toker SC, Sarycaoglu H, Karadogan SK, Mistik R, Baskan EB, Tunaly S. Is there any relation between vitiligo and cytomegalovirus? J Eur Acad Dermatol Venereol. 2007;21(1):141-142.

26. Boissy RE, Liu YY, Medrano EE, Nordlund JJ. Structural aberration of the rough endoplasmic reticulum and melanosome compartmentalization in long-term cultures of melanocytes from vitiligo patients. J Invest Dermatol. 1991;97(3):395-404.

27. Lee AY. Role of keratinocytes in the development of vitiligo. Ann Dermatol. 2012;24(2):115–125.

28. Grimes PE. Vitiligo: Management and prognosis. UpToDate. http://www.utdol.com. Updated May 5, 2017. Accessed July 10, 2019.

29. Topical Corticosteroids. Lexi-Drugs. Hudson, OH: Lexicomp, 2015. http://online.lexi.com/. Accessed July 10, 2019.

30. Taieb A, Alomar A, Bohm M, et al, and the Vitiligo European Task Force (VETF), and the European Academy of Dermatology and Venereology (EADV), and the Union Européenne des Médecins Spécialistes (UEMS). Guidelines for the management of vitiligo: the European Dermatology Forum consensus. Br J Dermatol. 2013;168(1): 5–19.

31. Ho N, Pope E, Weinstein M, Greenberg S, Webster C, Krafchik BR. A double-blind, randomized, placebo-controlled trial of topical tacrolimus 0.1% vs. clobetasol propionate 0.05% in childhood vitiligo. Br J Dermatol. 2011;165(3):626.

32. Tacrolimus. Lexi-Drugs. Hudson, OH: Lexicomp, 2015. http://online.lexi.com/ Updated July 22, 2019. Accessed July 23, 2019.

33. Bae JM, Yoo HJ, Kim H, Lee JH, Kim GM. Combination therapy with 308-nm excimer laser, topical tacrolimus, and short-term systemic corticosteroids for segmental vitiligo: a retrospective study of 159 patients. J Am Acad Dermatol. 2015;73(1):76-82.

34. Vitiligo Support International. Treatments website. https://vitiligosupport.org/phototherapy-treatment/. Accessed July 12, 2019.

35. Feldman SR. Targeted phototherapy. UpToDate. http://www.utdol.com. Updated April 11, 2019. Accessed July 12, 2019.

36. Lim HW, Grimes PE, Agbai O, et al. Afamelanotide and Narrowband UV-B Phototherapy for the Treatment of Vitiligo: A Randomized Multicenter Trial. JAMA Dermatol. 2015;151(1):42–50.

37. Sachdeva S. Fitzpatrick skin typing: Applications in dermatology. Indian J Dermatol Venereol Leprol. 2009;75(1):93-96

38. Komen L, da Graca V, Wolkerstorfer A, de Rie MA, Terwee CM, van der Veen JP. Vitiligo Area Scoring Index and Vitiligo European Task Force assessment: reliable and responsive instruments to measure the degree of depigmentation in vitiligo. Br J Dermatol. 2015;172(2):437-443.

39. Bimatoprost. Lexi-Drugs. Hudson, OH: Lexicomp, 2015. http://online.lexi.com/ Updated July 8, 2019. Accessed July 14, 2019.

40. Grimes, PE. Bimatroprost 0.03% solution for the treatment of nonfacial vitiligo. J Drugs Dermatol. 2016;15(6):703-710.

41. Parsad D, Pandhi R, Dogra S, Kumar B. Topical prostaglandin analog (PGE2) in vitiligo- a preliminary study. Int J Dermatol. 2002;41(12):942-945.

42. Kapoor R, Phiske MM, Jerajani HR. Evaluation of safety and efficacy of topical prostaglandin E2 in treatment of vitiligo. Br J Dermatol. 2009;160(4):861-863.

43. Ruxolitinib. Lexi-Drugs. Hudson, OH: Lexicomp, 2015. http://online.lexi.com/ Updated July 15, 2019. Accessed July 15, 2019.

44. Rothstein B, Joshipura D, Saraiya A, et al. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib. J Am Acad Dermatol. 2017;76(6):1054-1060.

45. Monobenzone. Lexi-Drugs. Hudson, OH: Lexicomp, 2015. http://online.lexi.com/ Updated February 22, 2019. Accessed July 15, 2019.

46. Vitiligo Support International. Treatments website. https://vitiligosupport.org/topical-therapies-for-vitiligo/. Accessed July 12, 2019.

References

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Vitiligo and Treatment OptionsQuiz #1, January/February 2020, ACPE 0128-0000-20-001-H01-P/T

Circle one (1) Answer:1. a b c d 6. a b c d2. a b c d 7. a b c d3. a b c d 8. a b c d4. a b c d 9. a b c d5. a b c d 10. a b c d

CPE Home Study Evaluation 1. Rate this lesson: (Excellent) 5 4 3 2 1 (Poor)2. Did this lesson meet each of its objectives? ___ Yes ___ No3. Was the content without commercial bias? ___ Yes ___ No

If not, please explain_______________________________________4. Did the lesson meet your educational/practice needs? __ Yes __ No5. Comments/future topics are welcome. ________________________

The deadline for this quiz is December 14, 2020

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

1. Which of the following is true about vitiligo? a. Patients experience depression, emotional distress, and social isolation. b. Vitiligo is a noncontagious, autoimmune skin condition with white patches or spots caused by depigmentation of the skin. c. Vitiligo is the most common cause of skin depigmentation worldwide. d. All of the above.

2. What is the most common form of segmental vitiligo? a. Bisegmental b. Mucosal c. Plurisegmental d. Unisegmental

3. How long may it take for a patient with vitiligo to regain pigmentation? a. 1 week b. 1 month c. 2 years d. Patients will never regain pigmentation.

4. What treatment may topical corticosteroids be used in combination with to increase effectiveness of repigmentation induction? a. Oral corticosteroids b. Light therapy c. Topical calcineurin inhibitors d. Topical monobenzone cream

5. What class of topical agent is being used more frequently on vitiligo lesions of the face? a. Topical Aquaphor b. Topical calcineurin inhibitors c. Topical corticosteroids d. None of the above

6. What is the mechanism of action of afamelanotide? a. Causes depigmentation of normally pigmented areas of the skin. b. Inhibits proinflammatory cytokines by modulating target cell functions. c. Stimulates the skin and pigmentation leading to tanning of the skin. d. Suppresses the immune response.

7. What is afamelanotide used in combination with? a. Narrowband ultraviolet B phototherapy b. Oral corticosteroids c. Topical calcineurin inhibitors d. Topical corticosteroids

8. What is the first-line therapy for stable non-segmental vitiligo involving less than 10% of the total body surface area? a. Mid-potency or high potency topical corticosteroids b. Psoralen plus ultraviolet A chemotherapy c. Topical calcineurin inhibitors d. Both a and c

9. What is the first-line therapy for vitiligo involving greater than 40% of the total body surface area? a. Mid-potency to high potency topical corticosteroids b. Narrowband ultraviolet B phototherapy c. Psoralen plus ultraviolet A chemotherapy d. Topical calcineurin inhibitors

10. What is the first-line therapy for stabilization of rapidly progressive disease? a. Low dose oral corticosteroids b. Topical calcineurin inhibitors c. Topical corticosteroids d. Topical corticosteroids

2020 Quiz #1 - Vitiligo and Treatment OptionsACPE #0128-0000-20-001-H01-P for pharmacistsACPE #0128-0000-20-001-H01-T for technicians1.0 Contact Hour - Knowledge Based CPE Activity

Name ___________________________________________

Mailing Address ____________________________________

City/State/Zip ______________________________________

Tomorrow.Imagine That.

Pharmacists Mutual Insurance Company | 808 Highway 18 W | PO Box 370 | Algona, Iowa 50511P. 800.247.5930 | F. 515.295.9306 | [email protected]

phmic.com

All products may not be available in all states and territories.

Pharmacy Insurance

www.npharm.org 17


AND THE LAW

The opioid crisis has brought a lot of attention to the prescribing and dispensing of opioids. This attention has also extended to the prescribing and dispensing of all controlled substances. I recently attended a seminar which contained a number of sessions on opioids and controlled substances. One of these sessions suggested that every pharmacist should read the DEA's Pharmacist's Manual.1 That suggestion caused me to ask myself when was the last time I had read it. One human trait is that we tend to forget details over time and our memory becomes a little less sharp. There have been a number of times when I was sure what a contract provision said, only to go back, read the document, and find that what it stated was slightly different from my memory. This same phenomenon applies to the Pharmacist's Manual.The manual is about 80 pages, but it is much more readable than the actual statute and regulations.

The speaker at the seminar explained that many pharmacists feel their duty is to make sure that a controlled substance prescription isn't forged or altered. While that is true, the duty is much broader. For a controlled substance prescription to be valid, it must be issued for a legitimate medical purpose in the usual course of the prescriber's professional practice. The law does not require a pharmacist to dispense a questionable prescription. The DEA has provided some red flags that may indicate diversion. Those are discussed in 2018 decision and order.2 Corresponding Responsibility is a topic that requires its own forum so I won't delve more deeply into it now.

The Pharmacist's Manual contains information on a number of topics. Besides a basic introduction to the Schedules, there is a lot of practical information in the manual. There is a section on the transfer and disposal of controlled substances. This covers transfer to another pharmacy, the original manufacturer, or a reverse distributor. There are numerous reminders to use

CONTROLLED SUBSTANCES

This series, Pharmacy and the Law, is presented by Pharmacists Mutual Insurance Company and the Nebraska Pharmacists Association through Pharmacy Marketing Group, Inc., a company dedicated to providing quality products and services to the pharmacy community.©Written by Don R. McGuire Jr, RPh, JD, General Counsel, Senior Vice President, Risk Management & Compliance at Pharmacists Mutual Insurance Company. This article discusses general principles of law and risk management. It is not intended as legal advice. Pharmacists should consult their own attorneys and insurance companies for specific advice. Pharmacists should be familiar with policies and procedures of their employers and insurance companies, and act accordingly.

the triplicate DEA Form 222 to transfer Schedule II substances. Another reason to refresh our memories periodically is that requirements change and if we rely only on our memories, we may not be current. The DEA recently announced the phase out of the triplicate form over the next two years.

The DEA Form 222 is also mentioned in the section of the manual on ordering of controlled substances. Topics here include how to order the Form 222, who is authorized to sign the forms, and what to do if the forms are lost or stolen. The manual also contains useful information on what to do when controlled substances are stolen or lost. The DEA must be notified, in writing, within one business day of the discovery of the theft or loss. Completion of the DEA Form 106 in this situation can be made easier by using the biennial inventory and prescription records because you can use these records to determine how much product was stolen or lost. There is also an entire section of recordkeeping requirements. While many pharmacies are using a perpetual inventory system today, that does not replace the required biennial inventories. Physical inventories are required for a new registrant (either opening a new pharmacy or taking over an existing one) and for products that are newly added to a schedule.

The manual also contains helpful information for the review and dispensing of controlled substance prescriptions. It provides what information is required to be on the prescription itself and the information required to be on the prescription label. Partial fill situations are addressed as is the dispensing of controlled substances without a prescription. The record of over the counter sales of controlled substances is required to be kept in a bound record book. These types of sales must be made by a pharmacists and cannot be delegated to a non-pharmacist. While the manual contains a lot of practical information, there are some uncommon

provisions also. Sometimes these less common situations are problem-prone because we aren't as familiar with the situation. Suppose one of your patients has a valid prescription for a C-IV medication and requests that you send a refill to their vacation home in Bermuda. Can you send that refill to a foreign country? Not unless you are registered with the DEA as an exporter and have obtained the necessary permits or submitted the necessary declarations for export. The pharmacist might assume it is permissible to send the refill because there is a valid prescription on file. This is an example where a seemingly reasonable conclusion is incorrect.

The periodic review of the DEA's Pharmacist's Manual is a good risk management tool. During my years of practice, none of my employers recommended or required that I review it. My working knowledge of the DEA regulations was what I drew from my pharmacy law class and any updates that I may have read and retained. Given the scrutiny that is currently being given to the dispensing of controlled substances, an annual review of the Pharmacist's Manual is an excellent risk management tool to help the pharmacist and pharmacy avoid a potential problem brought on by foggy memory of the requirements. In addition, a review of your state statutes and regulations should also be done because your state may have more restrictive standards which you are required to follow.

1. https://www.deadiversion.usdoj.gov/pubs/manuals/pharm2/pharm_manual.pdf2. https://www.deadiversion.usdoj.gov/fed_regs/actions/2018/fr0220_4.pdf#search=red%20flag%20diversion



BAQSIMIA New Way toDeliver Glucagon

ObjectivesAt the conclusion of this lesson, pharmacists and pharmacy technicians should be able to:1. Describe the signs and symptoms

of hypoglycemia and their treatment.

2. Explain the differences between intranasal and injectable glucagon.

3. List side effects and drug-drug interactions of Baqsimi.

Diabetes SummaryDiabetes is a chronic metabolic disorder characterized by resistance to the action of insulin, insufficient insulin secretion, or both which results as hyperglycemia or high blood sugars.1 Diabetes occurs because the body’s pancreas, which makes the hormone insulin, either does not produce enough of its own insulin or it cannot effectively use the insulin it does produce. Insulin helps drive sugar that is consumed into the cells. When insulin does not work effectively, there is an excess of sugar in the blood.2


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.

Sara BichlmeierWritten by

There are two main types of diabetes: type 1 and type 2. Type 1 diabetes occurs when the body does not produce insulin, requiring exogenous insulin to process carbohydrates. Type 2 diabetes occurs when the body does not use the insulin it produces appropriately, also known as insulin resistance. At the onset of type 2 diabetes the body makes extra insulin to compensate, but over time the body cannot make enough insulin to keep up with demands.2,3

Diabetes is diagnosed based on three criteria: A1c, fasting plasma glucose, and an oral glucose tolerance test. A1c is a test that measures the average blood glucose over the past two to three months. A fasting blood glucose test is performed when fasting after not eating or drinking anything (except water) for eight hours. This test usually takes place in the morning before breakfast. The oral glucose tolerance test is performed over two hours. First, a fasting blood glucose is tested, then the patient drinks an eight-

ounce solution containing 75 grams of glucose. After two hours the patient’s blood glucose is then tested again. This test informs providers how that patient processes glucose. Diagnostic criteria include an A1c of > 6.5%, a fasting plasma glucose of > 126 mg/dL, or an oral glucose tolerance test of > 200 mg/dL.3

PrevalenceIn the United States, approximately 30.3 million people have diabetes; (9.4%) of those, 23.1 million are diagnosed and 7.2 million are undiagnosed.4

In Nebraska, almost 1 in 10 adults (9.2%) reported having ever been diagnosed with diabetes in 2014. Diabetes accounted for 2,207 hospitalizations among residents. It was also the primary cause of 472 deaths ranking it as the 7th most common cause of death.5,6,7

The highest prevalence of patients with diabetes are those who are 55 years and older. Patients who have a

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Table 1.Race/Ethnicity Prevalence5

Race/Ethnicity Prevalence among adults

Non-Hispanic multiracial 15%

American Indian 14.3%

Black 13.8%

Other 13.3%

Hispanic 12.8%

Asian/Pacific Islander 7.6%

White 7.6%

college degree are less likely to be diagnosed than those with a lower level of education. The prevalence is higher among lower income individuals. Non-Hispanic multiracial individuals have the highest rates of diabetes (15%). See Table 1 for race/ethnicity details.5

HypoglycemiaHypoglycemia is a major complication of diabetes. Hypoglycemia occurs when blood glucose is too low. It is at this point the patient needs to take action to avoid adverse effects of hypoglycemia, such as coma or death, and bring their blood glucose back into the target range.3 According to the American Diabetes Association guidelines, level one hypoglycemia is a blood glucose < 70 mg/dL; level two hypoglycemia is < 54 mg/dL; and level three is a severe event characterized by altered mental status and/or physical status requiring assistance.8

Although these values are helpful, they are not universal for everyone. Each patient reacts differently to low blood glucose, but there are some common signs and symptoms that patients experience including: feeling shaky, nervous or anxious; sweating; chills and clamminess; irritability or impatient; confusion; tachycardia; feeling light headed or dizzy; hungry; nauseous; sleepy; weak or having no energy; blurred or impaired vision; headaches; feeling tingling or numbness specifically in the lips,

tongue, or cheeks; clumsiness; color draining from the skin; or seizures. The only way to know if a diabetic patient is hypoglycemic is to test his or her blood sugar. If symptoms make it difficult to test, the patient should be treated for hypoglycemia.3

To treat hypoglycemia, use the “Rule of 15”. In the Rule of 15, patients ingest 15 grams of fast-acting carbohydrates, wait 15 minutes, then test the patient’s blood glucose. If the blood glucose has not risen above 70 mg/dL, the patient should eat another 15 grams of carbohydrates. Fast-acting carbohydrates should be used to treat hypoglycemia. See Table 2 for examples of 15 grams of fast-acting carbohydrates. Once a patient’s blood glucose has increased past 70 mg/dL, the patient should eat a meal or snack so that his or her blood sugars do not lower again and to restore glycogen in the liver. Eating a snack or meal with protein is important for the body to maintain an optimal blood glucose. Be aware when treating children and adolescents with hypoglycemia. Often, they do not require 15 grams of carbohydrates but a lesser amount. Infants may only need 6 grams, toddlers 8 grams, and small children 10 grams. It is important to not over-treat hypoglycemic episodes. Patients prefer to eat until they feel better, but this can cause blood glucose to increase too much and become hyperglycemic.3

Hypoglycemia can occur due to a number of different causes, one of which is medications. Insulin is the most common medication that causes low blood sugars. Patients

with type 1 diabetes are at the highest risk for hypoglycemia due to insulin dependency. Newer insulins are preferred over regular insulin or NPH (neutral protamine Hagedorn) because they cause less hypoglycemia especially during the night. Patients need to be aware when taking insulin that they are using the right type, dose, and that they are injecting the insulin correctly to reduce the chance of hypoglycemia. Another group of medications that can cause low blood sugars are sulfonylureas (glipizide, glyburide, glimepiride). An important counseling tip for patients is to eat when taking these medications to avoid low blood sugars. Patients should also be aware of the food they are eating when using insulin. They need to be sure that they are eating enough food to balance the amount of insulin they are taking, and if they are varying from their consistent diet, they are still getting enough carbohydrates. Physical activity can also cause hypoglycemia. Exercise can have both short-term and long-term effects on blood glucose. It is important for patients to check their blood sugars before they exercise to know if they need to eat before exercising in order to avoid low blood sugars. The long-term effects usually occur overnight.3

Severe hypoglycemia happens when blood glucose goes so low that the patient is no longer able to treat themselves by using the Rule of 15 and another person is required to help. When this happens, glucagon is the treatment of choice. Glucagon is a hormone that is produced by the pancreas which stimulates the liver

Table 2.Fast-Acting Carbohydrates (15 Grams)3

• ½ cup (4oz) juice• Glucose tablets (4 tablets)• Glucose gel (one 15-gram pouch or 1/3 of a 45 gram tube)• ½ cup (4oz) regular soda• 1 cup (8oz) 1% milk• 1 tablespoon of sugar, honey, or corn syrup• Hard candies: jellybeans, gumdrops (not chocolate). Read food labels to know how

many carbohydrates to consume



to release stored glucose into the blood stream.3 Glucagon requires a prescription.

Current Treatment: InjectionUntil recently, the only way to treat severe hypoglycemia was by using an injectable glucagon. One example of an injectable glucagon is a Glucagon Kit. This kit comes in a red box and contains instructions for use, a needle and syringe containing diluent, and a vial of glucagon powder containing 1 mg of glucagon. To use the kit, a person who is not the diabetic patient needs to reconstitute the glucagon by injecting the diluent in the syringe into the vial of glucagon powder and gently swirling the vial until the mixture becomes clear with a water-like consistency. The mixture then needs to be drawn back up into the syringe and injected intramuscularly into the patient experiencing severe hypoglycemia. If a patient weighs 44 pounds or less, only half of the contents (0.5 mg) should be drawn up and injected. After giving the injection, the person should turn the patient onto his or her side and call 911 immediately. If the patient is not awake within 15 minutes, a second dose should be given if available.9 There are multiple steps involved in preparing the medication and when a patient is unconscious or seizing, it can be very stressful for the person preparing the injection. Although glucagon injection is the treatment of choice for a patient who is experiencing severe hypoglycemia and is unconscious, often times caregivers are either too reluctant or anxious to inject glucagon.10

From Injection to IntranasalInvestigations into using the nasal route for administering glucagon began in 1983.11 Many diabetic patients and family members have fears relating to hypoglycemia.10,11,12,13,14,15,16 Due to these fears, many patients’ blood glucoses are kept at higher

levels than recommended which can lead to a higher rate of micro- and macrovascular complications in the future.

In 2001, a study evaluated parents of children with diabetes use of glucagon for difficulty in administration, time taken for the procedure, and accuracy of the dose using a simulation technique. In this simulation, the parents were timed on how long it took to give the glucagon injection and their techniques were checked by trained diabetes educators. Diabetes health professionals also participated in the simulation to compare times and techniques. In conclusion, 69% of parents experienced handling difficulties which included difficulty in opening the pack, sheath removal, mixing and damaging the needle. The average time taken to complete the simulation was 2 minutes and 30 seconds, ranging from 30 seconds to 12 minutes 30 seconds. On average, 24% of the glucagon was not injected. With the group of professionals there were no observed errors, but they did comment on how difficult it was to administer a glucagon injection. The average time it took for a professional to complete the injection was 1 minute and 28 seconds, ranging from 55 seconds to 1 minute 45 seconds.10

In 2015, a review was done to focus on the status of alternative routes of administration of glucagon. Glucagon is a peptide hormone. Peptide hormones cannot be administered by the oral route because they are inactivated in the gastrointestinal tract due to first pass metabolism, ultimately leading to loss of efficacy. Glucagon is different compared to some other peptide hormones as it requires a precise dose-response for safety and effectiveness of the medication. When studied it was shown that it was not required for intranasal glucagon to reach a very high blood glucagon level, as it was with injectable glucagon, to achieve a clinically equivalent pharmacodynamic response. The bioavailability of intranasal glucagon is less than injectable which leads to

lower peak plasma concentrations, but it is not significantly different from injectable glucagon when looking at time to normal glucose levels. Side effects with intranasal glucagon were also very minimal including nasal irritation and mild sneezing. When developing the intranasal glucagon, particle size was designed in a way to prevent the medication from being delivered to the lungs after administration. The drug is absorbed through the nasal mucosa without any need for the patient to inhale or to breathe deeply, ensuring effective dosing even in unconscious patients.12

In a randomized crossover study to demonstrate noninferiority to intramuscular glucagon administration when compared to intranasal administration, insulin was used to induce hypoglycemia in type 1 diabetic patients. In this trial, success was defined as an increase in plasma glucose to > 70 mg/dL from the glucose nadir within 30 minutes after receiving glucagon. The nadir concentrations were 44 + 8 mg/dL for intranasal and 47 + 8 mg/dL for intramuscular administration. Success was met for 74 out of the 75 participants (98.7%) in the intranasal group and all 75 participants (100%) in the intramuscular group. The one failure in the intranasal group reached goal blood glucose levels without any other interventions but outside of the 30-minute time window defined as a success. Average time to success was 13 minutes with the intramuscular administration and 16 minutes in the intranasal administration showing a lag time of three minutes between the two treatments. Even though the symptoms of hypoglycemia lasted longer in the intranasal group, the overall magnitude of hypoglycemia symptoms was not different, likely due to similar nadir glucose levels achieved. Nausea and vomiting are well-known side effects of glucagon, the side effects of nausea and vomiting occurred at similar frequencies between the two groups, 36% of patients after intranasal administration and 38% of patients after intramuscular administration.

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The conclusion of this study stated that intranasal glucagon is effective for the correction of insulin-induced hypoglycemia in adults with type 1 diabetes and intranasal glucagon delivery showed to be promising and will have a substantial beneficial impact on the treatment of severe hypoglycemia.13

A phase one trial was completed to compare the pharmacokinetic and pharmacodynamics of intranasal glucagon against intramuscular glucagon in children and adolescents, ages 4 to < 17 years. This trial looked at the safety of use and doses needed to effectively treat this age group. The participants were split up into three groups based on age to more accurately assess the dose needed. The study was conducted in a crossover fashion. Participants received either the 2 mg intranasal glucagon, 3 mg intranasal glucagon, or 1 mg injectable glucagon. Success was defined as a rise in blood glucose > 25 mg/dL in a 20-minute time period after the selected form of glucagon was given. All patients in the injectable glucagon group had a 100% success rate. The intranasal group had all but one success. The patient who had an unsuccessful attempt with the intranasal glucagon blew his nose after being administered the dose leading to almost all of the medication being expelled from the body. To compare the pharmacokinetics and pharmacodynamics of the two different formulations, injection and intranasal, the average maximal glucose concentration was recorded. For intranasal delivery it ranged from 178-208 mg/dL, for injection it ranged from 194-211 mg/dL. When looking at adverse events, the most common was nausea with or without vomiting. In the injectable group, 67% experienced this side effect while in the 3 mg intranasal group 43% of participants had this side effect and only 39% of the 2 mg intranasal participants. When comparing the 2 mg dose to the 3 mg dose of the intranasal formulation, it was determined that although the 2 mg dose had fewer adverse effects,

the 2 mg dose was slower to increase blood glucose. It took 20 minutes to increase all patients’ blood glucose who received the 2 mg dose by > 25 mg/dL where it took only 15 minutes for the 3 mg dose. In a 20-minute time frame, the 3 mg dose increased the blood glucose by an average of 70 mg/dL where the 2 mg only increased by an average of 60 mg/dL. The study showed that there does not need to be an age or weight adjustment when it comes to intranasal glucagon and that the 3 mg dose should be used for all. In conclusion, the authors pointed out that this study took place in a controlled environment and both the intranasal and injectable glucagon was administered by trained professionals. It is unknown whether the same results would happen in a real world setting with potentially combative or seizing children.11

A simulation study performed on manikins compared the ability of people who were trained versus untrained to administer the different forms of glucagon. Those who were untrained represented a person who would come upon a patient experiencing a hypoglycemic event in a public setting. These study subjects were referred to as acquaintances. The trained participants were caregivers of diabetic patients. The simulation was set up as if the diabetic patient was taught how to use the devices at a clinic visit, then upon arrival at home, the patient taught his or her caregivers how to use the devices. With each manikin, there was a backpack where the glucagon was located as well as other diabetic supplies that a diabetic patient would normally carry such as a glucometer, test strips, lancets, alcohol pads, insulin, and insulin syringes and needles. The study evaluated the ease of use, speed, effectiveness of delivering the dose, and user preference.14

In the trained group when using the injectable glucagon, there were many failures and mistakes. Only 2 out of 16 caregivers successfully reconstituted the glucagon and administered a full dose. Six other

caregivers administered partial doses and the remaining eight caregivers (50%) did not give any glucagon. The reasons for not administering any glucagon were that they injected the diluent only, they injected insulin instead, or they bent the needle. Some of the caregivers did not inject the glucagon into the correct injection sites of the buttocks, arm, or thigh because they were used to injecting into other sites or a belief that the wrist was a better site with more blood vessels. Five caregivers injected insulin, two of the five got the glucagon and insulin confused. One caregiver was going to inject the insulin because they believed this was the correct treatment but bent the insulin needle and then switched and injected the glucagon. The final two caregivers that injected insulin, one believed that it was the correct treatment for hypoglycemia and the other believed that all diabetic medication was insulin. It took an average of 7.2 minutes to inject the glucagon. When giving the intranasal glucagon, all but one caregiver was able to administer the dose. The one who did not give the dose did not depress the plunger all of the way resulting in no glucagon being given. Two caregivers also administered insulin to the manikin believing that insulin was always an appropriate treatment for people with diabetes. The average time of administration was 16 seconds and all doses were given in less than one minute.14

In the group of acquaintances, there were also many failures to deliver the dose of injectable glucagon. None in this group delivered the full dose of glucagon, and only 3 out of the 15 delivered a partial dose. Many did not reconstitute the glucagon believing that the diluent in the syringe was the medication needed. Other reasons for not injecting a dose included bending the needle on the vial cap because they did not remove it; after reconstitution a participant could not figure out how to get the medication out of the vial; one participant refused to give an injection and was going to call emergency personnel; one injected



an empty syringe; and one injected insulin instead. For the acquaintances who administered a partial dose of glucagon, the times ranged from 1.3 minutes to 4 minutes. When administering the intranasal glucagon, the full dose was administered by all participants but one who was unaware they had to push the plunger all of the way in order to give the dose. No acquaintances administered insulin with the nasal glucagon. The average time it took to administer it was 26 seconds.14

When asked if the participants of this study had any fear or hesitation before administering the injectable glucagon the majority said they did, 50% in the caregiver group and 60% in the acquaintance group. When the diabetic patients (who were with the caregivers) were asked which method they would prefer 69% said the intranasal glucagon. The patients thought that the intranasal glucagon was easier to use, teach, and carry with no chance of needle breakage or accidental needle stick. The caregivers were also asked which method they would prefer to use. Eighty-one percent chose the intranasal glucagon saying how it was easier to use, less stressful, and less embarrassing if they were in public. Two caregivers (13%) said they would prefer the glucagon injection, but neither of these caregivers who chose the injectable option delivered a full dose during the simulation activity. All the acquaintances said they would prefer using the intranasal glucagon.14

A phase three trial was completed to examine the effectiveness, safety, tolerability, and ease of use of intranasal glucagon in children and adolescents with type 1 diabetes in “real world” setting. A hypoglycemic event was characterized as a blood glucose reading of less than or equal to 70 mg/dL with or without symptoms of neuroglycopenia. A severe hypoglycemic event was defined as severe neuroglycopenia resulting in coma or seizure. No severe hypoglycemia events occurred during this trial. Success was characterized as an increase of blood glucose to

above 70 mg/dL and awakening or returning to normal status within 30 minutes. At the conclusion of this study, all hypoglycemic events were resolved, and patients returned to normal status within 30 minutes of being given intranasal glucagon. More than half (54.5%) of patients recovered within 10 minutes. Out of the 33 hypoglycemic events, 17 were considered clinically significant with blood glucoses dropping to less than 54 mg/dL. In all of these clinically significant events every blood glucose rose about 70 mg/dL within 15 minutes of the intranasal glucagon and all patients fully recovered by 30 minutes. When surveyed on ease of use 93.3% of caregivers said the intranasal glucose was easy or very easy to use during a hypoglycemic episode. All caregivers were able to administer the glucagon within two minutes of recognizing the hypoglycemic child and 60.6% of caregivers were able to administer it in 30 seconds or less. The caregivers reported that it would be less intimidating to use intranasal glucagon in a hypoglycemic event than an injectable glucagon. They also agreed that it would be easy to teach another how to use the intranasal glucagon and that would be something they would be willing to carry should a hypoglycemic event happened; the caregiver could easily access it. All participants experienced adverse events due to the intranasal glucagon; three participants withdrew from the study due to severe nasal discomfort following a treatment. Other common adverse events included watery eyes, headache, runny nose, nasal congestion, sneezing, and redness of the eyes.15

A study was completed to see how a patient experiencing nasal congestion and a patient who has already taken a nasal decongestant respond to intranasal glucagon. There was no significant difference in pharmacokinetics and pharmacodynamics. The patients still absorbed adequate doses of glucagon to treat severe hypoglycemic symptoms.16

New Treatment:IntranasalBaqsimi™ is the first and only approved intranasal glucagon. It was approved by the FDA on July 24, 2019. The powder formulation is available in a 3 mg dose and is approved for ages 4 years and older. It is marketed as a single pack or a two pack with WAC pricing of $280.82 and $561.60. The device comes packaged in a tube which is shrink-wrapped for its protection. The wrapping on the tube contains directions for use. The device has a tip that is inserted into the nose, a plunger, and a green line on the end of the plunger. It is important that the shrink-wrap is not removed from the tube until it is needed. If the wrapping is removed the device can be exposed to moisture decreasing its effectiveness. The plunger should not be pushed or tested before it is ready to use. Each device contains only one dose and cannot be reused. Baqsimi is for nasal use only.17 Baqsimi will work even if the patient has a cold or is taking cold medicine.16,17 No inhalation or other cooperative measure is required from the patient as absorption takes place through the nasal mucosa.13,16

To Use Baqsimi:1. Instruct the person who will be

administering the Baqsimi to remove the shrink wrap by pulling on the red stripe.

2. Open the lid and remove the device from the tube, being cautious not to push the plunger.

3. Have the person hold the device between the fingers and the thumb.

4. The person then needs to insert the tip gently into one nostril of the hypoglycemic patient until his or her fingers touch the outside of the nose.

5. Finally, have the person push the plunger firmly and all the way in. The dose is completely administered when the green line at the end of the plunger disappears.

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Table 3.Ccommon Side Effects

Associated with the use of Baqsimi18,19

• Nausea• Vomiting• Headache• Runny nose• Discomfort in the nose• Stuffy nose• Redness in the eyes• Itchy nose, throat and eyes• Watery eyes

After the person has administered the dose of Baqsimi, call 911 immediately. If the patient is unconscious the patient should be turned onto his or her side. Discard the used device and tube.17,19

Storage and Handling Store the shrink-wrapped tube at temperatures up to 86OF (30OC). Replace Baqsimi before the expiration date printed on the tube.17,19

Side Effects Baqsimi has a number of side effects. The most serious side effects include high blood pressure, low blood sugar, and serious allergic reaction including anaphylactic shock with difficulty breathing. These serious side effects are uncommon only occurring in 1% to 10% of patients. High blood pressure can occur in patients with tumors in their adrenal glands. Low blood glucose can occur in patients who have tumors in their pancreas. If a serious allergic reaction occurs, the observer of the reaction should inform the emergency medical personnel of the reaction as soon as they arrive. Serious allergic reactions include rash, difficulty breathing, or low blood pressure.18,19 See Table 3 for common side effects associated with the use of Baqsimi.

Drug-Drug Interactions The most common drug-drug interactions with Baqsimi include beta-blockers, indomethacin, warfarin, and anticholinergic agents. When taken with beta-blockers, there may be a transient increase in pulse and blood pressure after Baqsimi is given. When taken with indomethacin, it decreases the effect of the glucagon. When taken with warfarin, it may enhance the anticoagulation effects of warfarin. When taken with anticholinergic agents such as atropine, benztropine, dicyclomine, and oxybutynin, glucagon can increase the gastrointestinal side effects of glucagon such as nausea and vomiting.18,19

Other Warning and Precautions Patients who receive Baqsimi should talk to their health care providers about all of their other medical conditions before using Baqsimi including: having a tumor in the pancreas; not having food or drink for an extended period of time due to fasting or starvation; if the patient is pregnant or plans to become pregnant; and if the patient is breastfeeding or plans of breastfeeding. At this time, it is unknown if Baqsimi passes into the breast milk. It is important for the patient to discuss with their provider and decide if Baqsimi should be used by the patient if they are breastfeeding.18,19

Certain patients should not use Baqsimi. These patients include those who have a tumor on their adrenal gland located on top of the kidney, (a pheochromocytoma); a tumor in the pancreas (an insulinoma); or if the patient is allergic to glucagon or any of the ingredients in Baqsimi.18,19

More Formulations of Glucagon Coming SoonOn September 10, 2019, a new glucagon that is a pre-mixed, ready to use, stable at room temperature liquid injection was approved by the FDA called Gvoke™. It is available in two different administration options,

a pre-filled syringe (Gvoke PFS™) and an auto-injector (Gvoke HypoPen™). The pre-filled syringe is currently available and the auto-injector will be available in 2020. It is supplied in two different doses: 0.5mg/0.1mL for pediatric patients and 1mg/0.2mL for adolescence and adults. Gvoke is different than the currently available injectable glucagon options as it is administered subcutaneously, as opposed to intramuscularly. Three Phase 3 clinical trials were completed where there was 100% treatment success in children and 99% treatment success in adults. When evaluating usability there was nearly a 100% success rate in delivering a full dose of glucagon. Gvoke has the same side effects and drug-drug interactions as Baqsimi.20

ConclusionBaqsimi is a new option for caregivers to use for patients experiencing severe hypoglycemia. In 2011, it was reported that 282,254 emergency room visits were due to hypoglycemia in the United States.14 A few studies showed that using injectable glucagon can lead to suboptimal use of effective medication, unnecessary delays in treatment, and costly use of emergency medical systems including ambulance services, emergency room visits, and hospital administration.12,13 There is a slight delay in glycemic response for intranasal glucagon, but this would likely be clinically inconsequential, and in many circumstances might be offset by the time required, errors, and failures to deliver among nonmedical caregivers in preparing and administering the injectable intramuscular formulation.13 All caregivers, co-workers, and friends of diabetic patients should be educated on this new device so that anyone could use it. Due to the effectiveness and ease of use of this device, fear of hypoglycemia could decrease ultimately improving overall diabetes control.













1. Triplitt CL, Repas T, Alvarez C. Diabetes Mellitus. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM eds. Pharmacotherapy: A Pathophysiologic Approach, 10e. New York, NY: McGraw-Hill; 2017:1139-1181.

2. Kelly J. Diabetes. Center for Disease Control and Prevention. https://www.cdc.gov/media/presskits/aahd/diabetes.pdf. Publication date unavailable. Accessed August 5, 2019.

3. American Diabetes Association. http://www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucose-control/hypoglycemia-low-blood.html?loc=lwd-slabnav. Publication date unavailable. Updated February 11, 2019. Accessed August 5, 2019.

4. Centers for Disease Control and Prevention. National Diabetes Statistics Report. https://www.cdc.gov/diabetes/data/statistics/statistics-report.html. Published 2017. Updated February 24, 2018. Accessed August 5, 2019.

5. Diabetes in Nebraska, Fact Sheet. http://dhhs.ne.gov/Reports/Diabetes%20in%20Nebraska%20-%202018.pdf. Published 2018. Accessed August 5, 2019.

6. Nebraska Department of Health and Human Services, Division of Public Health. State Health Assessment: Nebraska. http://dhhs.ne.gov/Reports/Statewide%20Health%20Needs%20Assessment%20-%202016.pdf. Published September 2016. Accessed August 5, 2019.

7. Centers for Disease Control and Prevention. Diabetes Report Card 2017. https://www.cdc.gov/diabetes/pdfs/library/diabetesreportcard2017-508.pdf. Published 2018. Accessed August 5, 2019.

8. Riddle MC, Bakris G, 2019 ADA guideline Diabetes Care. 2019;42(Suppl. 1):S61-S70. https://care.diabetesjournals.org/content/diacare/suppl/2018/12/17/42.Supplement_1.DC1/DC_42_S1_2019_UPDATED.pdf. Accessed August 12, 2019.

9. Glucagon, Information For The User. http://uspl.lilly.com/glucagon/glucagon.html#ppi. Updated July 2018. Accessed August 7, 2019.

10. Harris G, et al.; Glucagon administration – underevaluated and undertaught. Practical Diabetes Int.2001;18:22-25.

11. Sherr JL, Ruedy KJ, Foster NC, et al.; Glucagon nasal powder: a promising alternative to intramuscular glucagon in youth with type 1 diabetes. Diabetes Care. 2016;39:555-562.

References12. Pontiroli AE. Intranasal glucagon: a

promising approach for treatment of severe hypoglycemia. J Diabetes Sci Technol. 2015;9:38-43.

13. Rickels MR, Ruedy KJ, Foster NC, et al.; Intranasal Glucagon for treatment of insulin-induced hypoglycemia in adults with type 1 diabetes: a randomized crossover noninferiority study. Diabetes Care. 2016;39:264-270.

14. Yale JF, Dulude H, Egeth M, et al.; Faster use and fewer failures with needle-free nasal glucagon vs. injectable glucagon in severe hypoglycemia rescue: a simulation study. Diabetes Technol Ther. 2017;19:423-432.

15. Deeb L, Dulude H, Guzman C, Zhang S, Reiner B, Piche C, Pradhan S, Zhang M. A phase 3 multicenter, open-label, prospective study designed to evaluate the effectiveness and ease of use of nasal glucagon in the treatment of moderate and severe hypoglycemia in children and adolescents with type 1 diabetes in the home or school setting. Pediatric Diabetes. 2018;19:1007-1013.

16. Guzman CB, Dulude H, Piche C, et al. Effects of common cold and concomitant administration of nasal decongestant on the pharmacokinetics and pharmacodynamics of nasal glucagon in otherwise healthy participants: a randomized clinical trial. Diabetes Obes Metab. 2018;20:646-653.

17. Instruction For Use, Baqsimi nasal powder. http://pi.lilly.com/us/baqsimi-us-ifu.pdf. Issued July 2019. Accessed August 5, 2019.

18. Patient Information, Baqsimi nasal powder. http://pi.lilly.com/us/baqsimi-us-ppi.pdf. Issued July 2019. Accessed August 5, 2019.

19. Baqsimi-glucagon powder, Full Prescribing Information. http://uspl.lilly.com/baqsimi/baqsimi.html#pi. Updated July 2019. Accessed August 12, 2019.

20. FDA Approves Gvoke, the First Ready-to-use Stable Liquid Glucagon for Severe Hypoglycemia. https://www.drugs.com/newdrugs/fda-approves-gvoke-glucagon-first-ready-stable-liquid-glucagon-severe-hypoglycemia-5049.html?utm_source=ddc&utm_medium=email&utm_campaign=Daily+News+Summary+-+September+11%2C+2019&utm_content=FDA+Approves+Gvoke+%28glucagon%29%2C+the+First+Ready-to-use+Stable+Liquid+Glucagon+for+Severe+Hypoglycemia#moreResources. Issues September 2019. Accessed September 16, 2019.

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

2020 Quiz #2 - Baqsimi - A New Way to Deliver GlucagonACPE #0128-0000-20-002-H01-P for pharmacistsACPE #0128-0000-20-002-H01-T for technicians1.0 Contact Hour - Knowledge Based CPE Activity

Name ___________________________________________

Mailing Address ____________________________________

City/State/Zip ______________________________________

Circle one (1) Answer:1. a b c d 6. a b c d2. a b c d 7. a b c d3. a b c d 8. a b c d4. a b c d 9. a b c d5. a b c d 10. a b c d



The deadline for this quiz is December 14, 2020.


1. In 2014, how many Nebraskans had ever been diagnosed with diabetes? a. 1 in 5 c. 1 in 10 b. 1 in 8 d. 1 in 12

2. How does the American Diabetes Association define the three levels of hypoglycemia? a. Level 1: < 60 mg/dL, Level 2: < 50 mg/dL, Level 3: < 40 mg/dL b. Level 1: < 70 mg/dL, Level 2: < 50 mg/dL, Level 3: Altered mental and/or physical status requiring assistance c. Level 1: < 54 mg/dL, Level 2: < 30 mg/dL, Level 3: < 25 mg/dL d. Level 1: < 70 mg/dL, Level 2: < 54 mg/dL, Level 3: Altered mental and/or physical status requiring assistance

3. What are common signs and symptoms of hypoglycemia? a. Chills and clamminess, irritability or impatience, confusion b. Feeling shaky, nervous or anxious, sweating c. Tachycardia, lightheaded or dizzy, hungry d. All of the above

4. How should a patient appropriately treat his or her hypoglycemia?a. Eat a entire chocolate bar b. Take a nap c. Take insulin d. Use the Rule of 15 (eat 15 grams of carbohydrates, wait 15 minutes and check blood glucose)

5. Which medication most commonly causes hypoglycemia?a. Glipizide c. Metformin b. Insulin d. Glimepiride

6. What was a failure for injectable use in the study of trained caregivers? a. Injected diluent onlyb. Injected insulin instead of glucagonc. Bent the needled. All of the above

7. Which method of glucagon administration did both the diabetic patients and caregivers prefer to use?a. Injectionb. Intranasalc. Injection done by a health professionald. Intranasal done by a health professional

8. Which of the following are correct regarding effective intranasal glucagon administration?a. The glucagon is absorbed by the nasal mucosa.b. The patient must inhale when administering the dose to be effective.c. A patient can blow their nose after administration without affecting the medication.d. The dose will not be effective if the patient has nasal congestion.

9. What are common side effects that occur with Baqsimi?a. Nausea, vomiting, headacheb. Runny nose, discomfort in the nose, stuffy nosec. Redness in the eyes, Itchy nose, throat and eyes, watery eyesd. All of the above

10. Which of the following drug-drug interactions occurs with Baqsimi? a. Indomethacin increases the effect of the Baqsimi.b. Baqsimi decreases the anticoagulation effects of warfarin.c. Anticholinergic agents may increase the gastrointestinal side effects of Baqsimi.d. A transient decrease in pulse and blood pressure with beta-blockers.



Why Do You Need A Will?It may not sound enticing, but creating a will puts power in your hands.

Financial Forum

According to the global analytics firm Gallup, only about 44% of Americans have created a will. This finding may not surprise you. After all, no one wants to be reminded of their mortality or dwell on what might happen upon their death, so writing a last will and testament is seldom prioritized on the to-do list of a Millennial or Gen Xer. What may surprise you, though, is the statistic cited by personal finance website The Balance: around 35% of Americans aged 65 and older lack wills.1,2

A will is an instrument of power. By creating one, you gain control over the distribution of your assets. If you die without one, the state decides what becomes of your property, with no regard to your priorities. A will is a legal document by which an individual or a couple (known as “testator”) identifies their wishes regarding the distribution of their assets after death. A will can typically be broken down into four parts:

ExecutorsMost wills begin by naming an executor. Executors are responsible for carrying out the wishes outlined in a will. This involves assessing the value of the estate, gathering the assets, paying inheritance tax and other debts (if necessary), and distributing assets among beneficiaries. It is recommended that you name an alternate executor in case your first choice

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is unable to fulfill the obligation. Some families name multiple children as co-executors, with the intention of thwarting sibling discord, but this can introduce a logistical headache, as all the executors must act unanimously.2,3

GuardiansA will allows you to designate a guardian for your minor children. The designated guardian you appoint must be able to assume the responsibility. For many people, this is the most important part of a will. If you die without naming a guardian, the courts will decide who takes care of your children.

GiftsThis section enables you to identify people or organizations to whom you wish to give gifts of money or specific possessions, such as jewelry or a car. You can also specify conditional gifts, such as a sum of money to a young daughter, but only when she reaches a certain age.

EstateYour estate encompasses everything you own, including real property, financial investments, cash, and personal possessions. Once you have identified specific gifts you would like to distribute, you can apportion the rest of your estate in equal shares among your heirs, or you can split it into

Citations1. https://news.gallup.com/poll/191651/majority-not.aspx [4/24/18]2. https://www.thebalance.com/wills-4073967 [4/24/18]3. https://www.nolo.com/legal-encyclopedia/naming-more-one-executor.html [12/3/18]

percentages. For example, you may decide to give 45% each to two children and the remaining 10% to your sibling.

A do-it-yourself will may be acceptable, but it may not be advisable. The law does not require a will to be drawn up by a professional, so you could create your own will, with or without using a template. If you make a mistake, however, you will not be around to correct it. When you draft a will, consider enlisting the help of a legal, tax, or financial professional who could offer you additional insight, especially if you have a large estate or a complex family situation.

Remember, a will puts power in your hands. You have worked hard to create a legacy for your loved ones. You deserve to decide how that legacy is sustained.

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ObjectivesAt the conclusion of this lesson, pharmacists and pharmacy technicians should be able to:1. Describe the prevalence,

symptoms, and risk factors for COPD.

2. Identify the active ingredients, effectiveness, dosage schedule and common side effects of Trelegy.

IntroductionChronic Obstructive Pulmonary Disease (COPD) is a chronic lung disease that is characterized by shortness of breath, frequent coughing, wheezing, and tightness in the chest.1 COPD is a term to describe chronic lung diseases that include emphysema and chronic bronchitis. Emphysema is a condition in which there is damage to the alveoli in the lungs. Chronic bronchitis is defined as irritated and swollen bronchial tubes that cause coughing and shortness of breath.2 COPD cannot be cured, but with the right treatment, COPD and the symptoms can be managed. In 2018, the Global Initiative for Chronic Obstructive Lung disease (GOLD)


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.

Brittani BjellandWritten by

released their updated consensus report to better manage patients with COPD.

EpidemiologyCOPD is currently the fourth leading cause of death in the world and is projected to be the third by 2020.3,4 The projected increase is due to continued exposure to various risk factors. In 2012, more than three million people worldwide died of COPD.5 The prevalence of COPD worldwide was consistently higher in men than women in all world regions, settings, and income categories.6

In the United States, COPD is the fourth leading cause of death behind heart disease, cancer, and accidents/unintentional injuries.7 The true incidence, however, is likely under reported because most people believe being short of breath or being less active is related to their age.8 In 2010, the cost of COPD was approximately $32.1 billion in which 51% was paid for my Medicare, 25% paid by Medicaid and 18% paid by private insurance. The CDC projects that by 2020 the cost will be around $49 billion.9

In Nebraska, according to data collected for 2014, about 1 in 17 adults (5.8%) reported having ever been told by a medical professional that they have COPD. In comparison to national data, Nebraska residents were slightly less likely to report a COPD diagnosis. In 2014, the mortality of COPD in Nebraska compared to national data was higher than the national average. COPD caused 1,088 deaths in Nebraska or about 6.8% of the population.1

Clinical PresentationNoticing the signs and symptoms of COPD and having an early diagnosis is important for successful treatment. The most common signs and symptoms of COPD include chronic cough, shortness of breath, frequent respiratory infections, blueness of the lips or fingernail beds, fatigue, mucus production, and wheezing.8

Risk FactorsCOPD is considered a preventable disease; however, some risk factors increase a patient’s chance of developing COPD. The most common

TRIPLE THERAPYA New Approach to Treat COPD

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risk factor of COPD is smoking. This includes cigarette, pipe, cigar, and marijuana. Other major risk factors include indoor/outdoor air pollution, occupational exposures, genetics, older age, female gender, lung growth and development, socioeconomic status, previous infections, and history of asthma.10 Knowing these risk factors and avoiding them can help prevent COPD.

Drug TherapiesThe use of bronchodilators is the mainstay of COPD treatment.10 There are various types of bronchodilators and it is important to select the correct one(s) to manage a patient’s COPD. The available classes of bronchodilators include beta2-agonists and anticholinergics.

Beta2-agonists exert their bronchodilation by stimulating adenyl cyclase to increase the formation of cAMP (cyclic adenosine monophosphate) which is responsible for relaxing the bronchial smooth muscles. There are short-acting (SABA) and long-acting (LABA) agents within this class. The short-acting are best for acute, quick-acting relief, while the long-acting are best for patients with persistent symptoms.11

Anticholinergics produce bronchodilation by inhibiting cholinergic receptors in the bronchial smooth muscle which blocks acetylcholine. By blocking acetylcholine, there is a reduction in cGMP (cyclic guanosine monophosphate) which normally constricts bronchial smooth muscles. Similar to beta2-agonists, there are short-acting (SAMA) and long-acting (LAMA) agents available. The benefit of the long-acting agents is that they are more selective in blocking certain muscarinic receptors.11 In the UPLIFT trial, tiotropium showed significant improvement in FEV1 from baseline compared to placebo and benefited from increased quality of life, reduced exacerbations, and fewer hospitalizations.12

Additional TreatmentsInhaled Corticosteroids (ICS)Inflammation is a main pathophysiologic issue behind COPD. Inhaled corticosteroids (ICS) are responsible for anti-inflammatory activity. However, ICS have been shown to increase the incidence of pneumonia. Also, ICS are only indicated in COPD when combined with another agent (i.e. LABA).11

Methylxanthines are a class of medications that have been around for a long time. This class includes theophylline and aminophylline. This class exerts their bronchodilation effect through various ways including inhibition of phosphodiesterase, inhibiting calcium ion influx into the smooth muscle, prostaglandin antagonism, and stimulation of endogenous catecholamines. With the increased availability and positive outcomes with beta2-agonists and anticholinergics, this class has fallen out of favor.11

Phosphodiesterase-4 Inhibitors (PDE-4 Inhibitors) are a small class of medications used in COPD. PDE-4 is found in the airway smooth muscle cells and inflammatory cells that are responsible for degrading cAMP. When PDE-4 is inhibited, the smooth muscle cells are relaxed and there is decreased activity of inflammatory cells. Roflumilast is a medication within this class that has been used to decrease exacerbations in patients with COPD. Two studies have found that when roflumilast was added to a patient’s regimen, the amount of exacerbations and need for hospitalization decreased. However, there is little evidence to show long-term benefit with PDE-4 inhibitors.11

Combination TherapySince COPD is a progressive disease, it is common for agents to be added onto treatment regimens over-time. This led to developing combination therapies for patients for easier administration of these medications. The most common

combination therapies include an ICS with a bronchodilator (beta2-agonist or anticholinergic).

TrelegyAn FDA approved triple therapy inhaler called Trelegy is a combination of a LAMA, LABA, and ICS (umeclidinium 62.5 mcg/vilanterol 25 mcg/fluticasone furoate 100 mcg). Trelegy works by opening and keeping the airways open to reduce inflammation in the lungs.

There are two main trials that support the use of Trelegy: IMPACT and FULFIL. The IMPACT trial was a 52-week randomized, double-blind, parallel-group study that included more than 10,000 COPD patients with a history of exacerbations. Patients were randomized to receive Trelegy, Breo (fluticasone furoate 100 mcg/vilanterol 25 mcg), or Anoro (umeclidinium 62.5 mcg/vilanterol 25 mcg). The primary outcome was the annual rate of moderate or severe exacerbations during the treatment. Patients that received Trelegy had an annual rate of 0.91 per year compared with 1.07 per year (Breo) and 1.21 (Anoro). The rate of exacerbations was significantly lower in the Trelegy group versus the Breo (p<0.001) and Anoro (p<0.001) groups.13 The FULFIL trial was a 24 week phase III, randomized, double-blind, double-dummy, parallel-group, multicenter study where patients received treatment of either Trelegy once-daily and twice-daily placebo or twice-daily Symbicort (budesonide 400 mcg/formoterol 12 mcg) and once-daily placebo. The primary endpoints were to evaluate lung function and health-related quality of life of these patients. Lung function was measured using the change of FEV1 from baseline, 2 weeks, 4 weeks, 12 weeks and 24 weeks. Trelegy showed significant improved lung function at all measured time points versus Symbicort (142 mL vs. -29 mLrespectively; p<0.001). Quality of life was assessed using the St. George’s Respiratory Questionnaire (SGRQ) when Trelegy showed significant improvement in quality of life measures versus the Symbicort group (-6.6 units vs. -4.3 units; p<0.001).14













1. Nebraska Department of Health and Human Services, Division of Public Health. State Health Assessment: Nebraska. http://dhhs.ne.gov/Reports/Statewide%20Health%20Needs%20Assessment%20-%202016.pdf. Published September 2016. Accessed August 5, 2019.

2. COPD Foundation. Understanding COPD. COPD Foundation website. https://www.copdfoundation.org/What-is-COPD/Understanding-COPD/What-is-COPD.aspx. Accessed August 5, 2019.

3. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. The Lancet. 2013; 380: 2095-2128.

4. Sin D, Anthonisen N, Soriano J, Agusti A. Mortality in COPD: role of comorbidities. Eur Respir J. 2006; 28:1245-1257.

5. Mathers C, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Medicine. 2006; 3(11): 2011-2030.

6. Adeloye D, Chua S, Lee C, et al. Global and regional estimates of COPD prevalence: Systematic review and meta-analysis. Journal of Global Health. 2015; 5: 1-17.

7. Xu J, Murphy S, Kochanek K, et al. (2018) Deaths: final data for 2016. Natl Vital Stat Rep 67: 1-20.

8. American Lung Association (ALA). Lung Health and Diseases. ALA website. https://www.lung.org/lung-health-and-diseases/lung-disease-lookup/copd/. Published November 2016. Accessed August 5, 2019.

9. Centers for Disease Control and Prevention (CDC). What is COPD? CDC website. https://www.cdc.gov/copd/index.html. Published June 2018. Accessed August 5, 2019.

10. Global initiative for chronic obstructive lung disease: Pocket guide to COPD diagnosis, management, and prevention. (2018). Bethesda, MD: U.S. Dept. of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute.

11. Bourdet SV, Williams DM. Chronic Obstructive Pulmonary Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw-Hill; http://accesspharmacy.mhmedical.com.library1.unmc.edu:2048/content.aspx?bookid=1861&sectionid=146058280. Accessed August 5, 2019.

12. Tashkin D, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive

References

pulmonary disease. N Engl J Med. 2008; 359: 1543-1554.

13. Lipson D, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018; 378: 1671-1680.

14. Lipson D, Barnacle H, Birk R, et al. FULFIL trial: once-daily triple therapy for patients with chronic obstructive pulmonary disease. 2017; 196: 438-446.

Trelegy is administered as one inhalation, once daily. Since it includes an ICS, patients should rinse their mouths with water after each inhalation to decrease the risk of developing oropharyngeal candidiasis. Trelegy is contraindicated in patients with a severe hypersensitivity to milk proteins or if they showed hypersensitivity to fluticasone furoate, umeclidinium, or vilanterol in the past. Trelegy should not be used in patients with asthma.

The most common side effects of Trelegy include headache, back pain, dysgeusia, diarrhea, cough, upper respiratory infection, pneumonia and oral candidiasis/pain. Trelegy should be used with caution in patients on MAOIs, TCAs, drugs that prolong QTc interval, beta-blockers, non-potassium-sparing diuretics, and anticholinergic medications.14

ConclusionCOPD is a chronic disease that is an increasingly prevalent issue that continues to be ranked as one of the top causes of death in the United States. With continued exposure to risk factors (e.g. smoking, pollution), COPD will continue to be an issue for many patients.

Inhalers are the most commonly used medications in the treatment of COPD. Most patients will require the use of a rescue inhaler (short-acting beta2-agonist) that should only be used on an as needed basis. Additionally, patients may require a scheduled medication/inhaler that may either be a dual or triple-combination product.10

Trelegy is the only triple-therapy inhaler that is currently available. The IMPACT and FULFIL trials have shown superiority in the use of Trelegy over dual-therapy inhalers in patients that have a high symptom burden. In addition to pharmacologic interventions, it is important for patients to stay current on immunizations and include non-pharmacologic interventions. One of the most important non-pharmacologic interventions is smoking cessation.10 As pharmacists, it is important to educate

patients on the proper use of inhalers to ensure that each patient has the best outcomes from his/her treatment plan.

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

2020 Quiz #3 - Triple Therapy - A New Approach to Treat COPDACPE #0128-0000-20-004-H01-P for pharmacistsACPE #0128-0000-20-004-H01-T for technicians0.5 Contact Hour - Knowledge Based CPE Activity

Name ___________________________________________

Mailing Address ____________________________________

City/State/Zip ______________________________________

Circle one (1) Answer:1. a b c d 5. a b c d2. a b c d 6. a b c d3. a b c d 7. a b c d4. a b c d



The deadline for this quiz is December 14, 2020.


1. COPD is the ________ leading cause of death in the United States.a. firstb. secondc. fourthd. fifth

2. The most common symptoms of COPD include:a. Coughb. Mucus productionc. Shortness of breathd. All the above

3. Which of the following is/are the most common risk factor(s) for developing COPD?a. Smoking cigarettesb. Smoking cigarsc. Smoking marijuanad. All the above

4. What is the correct triple-therapy combination of Trelegy?a. Umeclidinium + olodaterol + budesonideb. Umeclidinium + vilanterol + fluticasone furoatec. Tiotropium + olodaterol + fluticasoned. Tiotropium + vilanterol + budesonide

5. What was the effect on FEV1 in patients that used Trelegy versus Symbicort in the FULFIL trial?a. -29 mLb. -15 mLc. 121 mLd. 142 mL

6. How is Trelegy administered?a. One inhalation, once dailyb. One inhalation, twice dailyc. Two inhalations, once daily d. Two inhalations, twice daily

7. Which of the following describes the most common side effects of Trelegy?a. Back pain, cough, vomitingb. Cough, sneezing, leg painc. Headache, back pain, coughd. Headache, sneezing, leg pain

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