North Carolina Pharmacist Volume 99 Number 4

North Carolina Pharmacist

Volume 99 Number 4 Fall 2018 Advancing Pharmacy. Improving Health.

U.S. Antibiotic Awareness Week November 12-18, 2018 www.cdc.gov/antibiotic-use

Official Journal of the North Carolina Association of Pharmacists ncpharmacists.org

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North Carolina Pharmacist Volume 99 Number 4

Fall 2018

Inside EDITOR-IN-CHIEF Tina Thornhill

• From the President .....................................................................................4

LAYOUT/DESIGN Rhonda Horner-Davis

• From the Executive Director ...........................................................................5

EDITORIAL BOARD MEMBERS

• Commentary: Antibiotic Awareness Week ............................................10

Anna Armstrong Jamie Brown Lisa Dinkins Jean Douglas Brock Harris Amy Holmes John Kessler Angela Livingood Ronald Small Bill Taylor

BOARD OF DIRECTORS EXECUTIVE DIRECTOR Penny Shelton

• Asthma Intervention Program ...............................................................14 • Inhaler Reference Guide ...............................................................16 • Convention Highlights ...................................................................................20 • Is Ramelteon Safe in Patients with COPD or OSA ...........................................27 • Resident-Run Residency Preparatory Program..................................................33 • Glaucoma Awareness Month ..........................................................................39 • Member Spotlights ..............................................................................................42

PRESIDENT Stefanie Ferreri

• New Practitioner Network: Personal Finance – Good Advice ..............................43

PRESIDENT-ELECT Debra Kemp

• Identify Patients at Risk for Opioid Overdose...............................................45

PAST PRESIDENT Stephen Eckel

• CE Program: Overview of 2017 Updates for CDI ............................................46

TREASURER Thomas D’Andrea BOARD MEMBERS Olivia Bentley Jamie Brown Lisa Dinkins Kira Harris Kevin Helmlinger Macary Marciniak Cortney Mospan Jason Moss Dave Phillips Sophie DeBerry Jennifer Wilson North Carolina Pharmacist (ISSN 0528-1725) is the official journal of the North Carolina Association of Pharmacists. An electronic version is published quarterly. The journal is provided to NCAP members through allocation of annual dues. Opinions expressed in North Carolina Pharmacist are not necessarily official positions or policies of the Association.

Publication of an advertisement does not represent an endorsement.

Nothing in this publication may be reproduced in any manner, either whole or in part, without specific written permission of the publisher.

North Carolina Pharmacist is supported in part by: • Smith Drug Company ...................................................................................2 • Epic Pharmacies Network .............................................................................9 • Pharmacists Mutual Companies ..................................................................19 • Pharmacy Technician Certification Board ...................................................26 • VIP Pharmacy Systems ...............................................................................32 • MedsOnCue ................................................................................................40 • NCAP Career Center ...................................................................................41 • Epic Pharmacies, Inc ...................................................................................44 • Pharmacy Quality Commitment ..................................................................52

ADVERTISING For rates and deadline information, please contact Rhonda Horner-Davis at rhonda@ncpharmacists.org

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•From the President • Stefanie Ferreri, PharmD

Speak Up or Be Left Out What an annual meeting! It was full of energy, ideas and celebration! I know I learned a lot, and I hope you did too. One thing that stuck with me when listening to our keynote speakers was that opioid abuse, misuse and addiction typically start with a simple procedure (e.g. a tooth extraction, a broken arm) that results in an opioid being prescribed for an appropriate indication to an opioid-naïve patient. In other words, patients do not know how they will react. Just like alcoholics don’t know how they will react to their first drink, opioid-naïve patients do not know how they will react to their first narcotic. Many of the patients who fall into addictive behavior are predisposed to opioid addiction. It is a brain disease. I never thought of it this way until the NCAP meeting – shame on me! Suddenly, I get it.

Just like many of us have a genetic pre-disposition to alcoholism or heart attack and stroke, many of us have a predisposition to opioid abuse, but we are not aware of it until our first exposure to opioids. What

a great opportunity for us as pharmacists. We can educate and follow-up with our opioidnaïve patients to prevent the abuse before it starts. This can occur in all pharmacy practice settings. Many of our awardees recognized at the luncheon were involved in taking steps to manage the opioid crisis in our state.

It was inspiring to be surrounded by talented leaders! Congratulations on your efforts and thank you for inspiring the profession to become engaged in this brain disease.

On day two of the meeting we had seven summit sessions to identify strategic initiatives for NCAP. The top three initiatives from each summit were shared with leadership, and the afternoon was filled with active discussion and several rounds of voting to finally narrow the strategic initiatives to the top three for NCAP to advance in 2019. Those initiatives will be provider status, advanced technician practice, and collaborative practice. Two items that did not make the top three, medical cannabis and telehealth, will also be added to the list because we know folks in Raleigh will be introducing legislation on these topics, and we need to be ready to determine our stance. If we do not speak up, we will be left out.

In my opinion, pharmacy should be leading the charge in both of these areas. We have the knowledge, accessibility and patients’

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best interest in everything we do.

Whether we agree with it or not, medical marijuana is available in several states. Some states have little to no pharmacy oversight, and other states such as Connecticut have 100 percent oversight. The public will be buying it, using it, and coming to ask us questions about it. So, we need to prepare pharmacists in North Carolina before it happens. The same is true for telehealth. It is already here, and we need to get ready.

Lastly, I want to encourage ALL pharmacists to support the collaborative practice that will be introduced into legislation. This is a great advancement for North Carolina pharmacy. This collaborative practice will expand the role of pharmacists across all practice settings. We have had little traction in expanding our collaborative practice in the past 18 years. This legislation is a giant step forward for our profession and a great opportunity for us to take care of our patients the way we want to. Advocacy for pharmacy needs to be done with the whole profession, no matter the practice setting in mind. We need to speak up or we will be left out, so let us know what you think. What ideas do you have for NCAP as it relates to our strategic initiatives?

Feel free to let me know your thoughts via email at stefanie_ ferreri@unc.edu or follow me on Twitter @stefanieferreri.

Volume 99 Number 4 Fall 2018

•From the Executive Director• Penny Shelton, PharmD, BCGP, FASCP start by dedicating this Executive Director column to the issue.

Our ‘State’ of Collaborative Care We tried something new at our Convention this past September.

We held individual summits for different sectors of pharmacy to discuss the issues deemed to be most impactful, either because the issue gave great cause for concern or presented ample opportunity for the profession. One of the top issues to emerge was collaborative practice and provider status designation. The importance of this issue coincided with the unveiling of talking points and proposed draft language for a bill to be run by NCAP during the upcoming 2019 legislative session. The NCAP Board of Directors (BOD), various task force groups, the Policy and Advocacy Committee, staff, and NCAP lobbyist have been working on a bill for the past two years, which if passed, would update our collaborative practice authority. To date, the majority of feedback on the bill has been positive; however, there were some concerns raised during Convention regarding specific elements of the bill. At the October BOD meeting, these concerns were reviewed. The BOD determined there are misperceptions and confusion regarding the bill, as well as a general lack of awareness regarding the state of collaborative practice nationwide; therefore, NCAP plans to provide additional information on the bill using a variety media between now and the new legislative session.

Furthermore, I have decided to

As healthcare needs, such as those associated with chronic disease, mental health and addiction continue to rise, there is a growing need in all practice settings for pharmacist-provided patient care services. This is particularly true given primary care and nursing shortages, as well as the increasing occurrence of provider burnout.

Collaborative care has been shown to improve patient outcomes, increase access to care, raise patient satisfaction, and share the care burden with physicians, which helps with physician job satisfaction and burnout.

The NCAP bill entitled “An Act to Improve Access to Patient Care Services via Collaboration between Physicians and Pharmacists” seeks to update our current collaborative practice authority statute, and thus the rules for implementation, making it easier for physicians and pharmacists to collaborate.

Specifically, the bill calls for four key changes (elements): 1. Allow any licensed pharmacist and any licensed physician to collaborate versus a set of criteria that only allow certain pharmacists to be able to enter into a collaborative agreement.

[Currently 29 states allow any licensed pharmacist, in any practice setting, to participate in a collaborative practice agreement.]

2. Move away from an approval process to a registry process. Currently a committee approves the application of the pharmacist as a CPP and approves

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the agreements (protocol).

Under the new process, agreements are negotiated by the physician and the pharmacist and maintained by the practitioners. Any pharmacist participating in a collaborative agreement will first have to register with the Board of Pharmacy. The Board of Pharmacy will maintain the registry similar to how the immunization registry is handled.

Practitioners engaged in collaborative agreements would be subject to abiding by the rules and could be audited. Physicians (or institutions such as with a hospital) establishing the agreement can require additional qualifications for their agreements if they wish. [Currently 26 states do not require approval of the pharmacist, review or submission of agreements.

One state does not require any approval of the pharmacist, review or submission of agreements, but does maintain a registry of collaborating pharmacists.

Eight other states do not have an approval process of the pharmacist or the agreement, but the agreement must be submitted to the BOP.] 3. Agreements allow for multiple physicians and multiple pharmacists on a single agreement. Institutions and large group practices could have institution-wide agreements. Individual pharmacists such as consultants or community pharmacists could have multiple physicians sign onto a single agreement. [Currently 29 states allow for multiple

Volume 99 Number 4 Fall 2018

pharmacists and multiple physicians on an agreement.]

4. Supervising physicians may allow their advanced practitioners (NP or PA) to participate in the agreement, but the supervision remains with the physician.

This allows for patients of NP and PA practitioners to be referred for patient care services with the pharmacist, but keeps the MD / DO as the supervising entity and avoids creating a threetiered hierarchy. [Currently 27 states allow nurse practitioner and physician assistants to participate.]

North Carolina was a pioneer in collaborative practice in the 90’s, but today, pharmacists might be surprised by how limited or restricted our current collaborative practice authority is when compared to other states. As noted above, the changes we seek for updating our collaborative practice are not unusual or even cutting edge, but rather necessary to help lift up our profession, for all pharmacists, and do away with restrictions that stymy innovation and make it more difficult for physicians to partner with pharmacists in various practice settings. Furthermore the changes we seek are all in alignment with the collaborative care model language published by the National Alliance of State Pharmacy Associations and endorsed by a number of organizations, including the American Medical Association.

There are two other elements to our bill that are important. One is that we are seeking these changes by updating versus replacing our existing collaborative practice authority, which is through the ‘clinical pharmacist practitioners’ (CPP) designation. The CPP is how NC carries out collaborative practice. It is also how pharmacists engaged in collaborative practice agreements are delegated

prescriptive authority and allowed to legally prescribe. Early on in our process of working with pharmacists from different practices and backgrounds, we agreed that we did not want to ‘hand-cuff’ our own profession by advocating that some pharmacists under a collaborative agreement could prescribe while others could not.

We also recognized that even new graduates are graduating with a far greater number of pharmacology and pharmacotherapy hours than a PA or NP, yet we never second guess their authority to prescribe, so why would we put limitations on our own profession? As part of our bill, any pharmacist engaged in a collaborative agreement would have to register with the NC Board of Pharmacy to be placed on the collaborative care (i.e., CPP) registry and receive a CPP number.

The ability to prescribe will still be left up to the supervising physician.

In addition, the supervising physician can require additional qualifications in order for the pharmacist to collaborate. For example, the pharmacist may have to get certified, maintain a specific number of professional development hours, or be residency trained; however, the statute should be more open and inclusive of the entire profession.

Secondly, the NCAP bill is pursuing an open scope of practice by incorporating the following language: “Under a collaborative practice agreement, a supervising physician may delegate to a licensed pharmacist any patient care services the supervising physician deems appropriate.” Furthermore the bill addresses the pharmacistphysician ratio giving more flexibility to the physician. It is also important to note that the pharmacist and supervising physician do not have to be under the same roof.

This will give community pharmacists, for example, the ability to establish agreements to treat positive flu tests, administer long-acting antipsychotic injections, or provide medication assisted treatment for addiction as well as many other services. This bill will give health

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systems much needed flexibility to expand pharmacist-provided outpatient and other clinical services. In addition, this bill should make it easier for long-term care pharmacists to utilize collaborative care in assisted living and skilled care settings.

In October 2017, Frost and Adams published a review of advanced practice pharmacist designations in the journal Research in Social and Administrative Pharmacy.

There are only four states, including NC, that have an advanced practice designation for pharmacists. Uptake of advanced practice pharmacist designations was found to be low, with less than 10% of the pharmacists in any of these states taking advantage.

Meanwhile, collaborative practice has advanced in a majority of states as noted above and to the point that those states with advanced practice designations have fewer practice gains than those without the advanced credential.

In NC, many of the restrictions to the existing CPP credential were put into place in 1998 at a time that precedes the all-PharmD mandate and when NC was one of the first states with the credential. It has been two decades now, and the way we teach and train pharmacists has changed tremendously in that timeframe, but perhaps more importantly, is that less than 2.5% of pharmacists in NC are CPPs. To bring about the change that is needed for patient care in our state, we need more pharmacists and physicians collaborating on all levels in all practice settings. Let us do the right thing and work together to update our collaborative authority statute.

To view the infographic and talking points on the proposed bill see pages 7-8 in this issue of the journal or go to https://www. ncpharmacists.org/content. asp?contentid=149 Penny

Volume 99 Number 4 Fall 2018

EXPANDING PATIENT ACCESS THROUGH

COLLABORATIVE PRACTICE Updating North Carolina’s Collaborative Practice Authority to Provide Better Care for Our Patients

1,902,580

89% of Americans live within

NC Residents live in Health Professional Shortage Areas1

5 miles of a pharmacy2

COLLABORATIVE PRACTICE AGREEMENTS: WHY ARE THEY IMPORTANT? The vast majority of North Carolina residents live very close to a pharmacy.

However, many residents live in areas that do not have enough other health care providers. Pharmacists, known as Clinical Pharmacist Practitioners (CPPs), can enter into trusting relationships with physicians, which enable them to collaboratively provide better patient care in these areas. Pharmacists in these agreements are critical in increasing access to care especially in rural areas, reducing fragmentation of care, improving health outcomes, and reducing physician burden/burnout.

12K

+

LICENSED PHARMACISTS

294

CPPS

27 0

IN COMMUNITY SETTINGS IN LONG-TERM CARE

WE ENCOURAGE CHANGE

Why change IS NEEDED:

- NC patients can't access needed care because of insufficient numbers of health professionals - Pharmacists can help fulfill this need, but current laws create unnecessary barriers - Through collaboration, pharmacists can help patients receive better quality care

How this bill enhances patient care: - Improves access to Medication Assisted Treatment (MAT) for opioid addiction - Reduces medication errors during transitions of care - Expands access to care in rural areas

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North Carolina Pharmacist

How this bill improves Team-Based care:

- Extends physician ability to provide

patient care by working together with pharmacists - Expands patients’ access to clinical pharmacy services - Allows physicians and pharmacists greater flexibility to best meet their unique patient care needs See Reverse For More Information

Page 7

Volume 99 Number 4 Fall 2018

Collaborative Practice Reform Updating North Carolina’s Collaborative Practice Authority to Provide Better Care for our Patients

Current State of Collaborative Practice

Key Proposed Changes

Strong evidence demonstrates the benefits of pharmacist-physician collaboration on patient care.

Since 1998 North Carolina has had a form of physician-pharmacist collaborative practice in which the pharmacists are known as clinical pharmacist practitioners (CPP). Despite being a pioneer in this type of practice, North Carolina has now been surpassed by other states and our collaborative practice is today one of the most restrictive in the nation. It is time to update the collaborative practice authority in North Carolina.

• •

• •

•

How this Bill Enhances Patient Care •

•

•

Reduces regulatory burden on physicians and pharmacists, allowing them to practice patient care as needed Current law and regulations are very restrictive: o Inhibits effectiveness and efficiency of care due to agreement limitations o Does not allow collaboration with physician designees like nurse practitioners and physician assistants o Restrict the number of pharmacists a physician can supervise As a result of this bill, CPPs will be able to: o Improve care for opioid addiction by overseeing Medication Assisted Treatment o Extend collaborative care in rural areas for patients regardless of disease states o Administer a rapid flu test and furnish antiviral medications under approved protocols without exposing patients with flu to ER and doctor offices o Enhance transitions of care and population health through flexible collaborative practice agreements which address medication safety concerns before they happen

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•

Any licensed physician and pharmacist can enter into a collaborative practice agreement.

Agreement is limited to patient care services allowed and identified by the supervising physician in the written agreement.

Allows for multiple physicians and pharmacists to sign onto a single agreement.

Allows for physicians who have nurse practitioners and physician assistants in their practice or on their care teams to also participate in the collaborative practice agreement with the pharmacist(s).

Gives the physician greater flexibility in the number of collaborative practice agreements in which he/she wishes to participate.

Changes current process from committee approval to a state-wide registry.

This Bill • •

•

ES

T

Seek autonomy of practice for pharmacists.

Create any new clinical acts or patient care services that is not already allowed under our existing clinical pharmacy practitioner rules.

Interfere or force a change within hospitals or other institutions’ internal requirements for collaborative practice.

1.

2.

Source: Bureau of Health Workforce, Health Resources and Services Administration (HRSA), U.S. Department of Health & Human Services, Designated Health Professional Shortage Areas Statistics: Designated HPSA Quarterly Summary, as of December 31, 2017 Source: National Association of Chain Drug Stores 2018 Pharmacy Opinion Research.

Access: https://accessagenda.nacds.org

Volume 99 Number 4 Fall 2018

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Volume 99 Number 4 Fall 2018

U.S. ANTIBIOTIC AWARENESS WEEK NOVEMBER 12-18 Commentary: United States Antibiotic Awareness Week 2018 Benjamin Tutterow, Dr. Brandon Hill, and Dr. Riley Bowers This year, U.S. Antibiotic Awareness Week (formerly “Get Smart about Antibiotics Week”) is November 12-18. It is an annual observance created by the Centers for Disease Control and Prevention (CDC) to raise awareness of the threats of antimicrobial resistance and the importance of appropriate use of antimicrobials. (1) Improving the way healthcare professionals prescribe antimicrobials will help keep us healthy now, combat the emergence of antimicrobial resistance, and ensure life-saving drugs are effective for future generations. This commentary is set to review the importance of appropriate antimicrobial prescribing and opportunities for pharmacists to aid in the fight against antimicrobial resistance. the threat of antimicrobial resistance continues to grow.

Antibiotic Misuse Antibiotic misuse is characterized by prescribing an incorrect or inappropriate drug, dose, and/or frequency. (1,2) Common antibiotic misuse occurs, for example, when antibiotics are prescribed for the treatment of acute respiratory conditions such as the common cold, bronchitis, or sore throat which are commonly caused by viral, not bacterial, infections.

(1,2) Multiple studies suggest inappropriate antibiotic use in the outpatient setting is estimated to be 50%. (2) In 2016 the CDC estimated that 30% of 154 million prescriptions written in primary care offices and emergency departments were considered unnecessary. (2) It is important to recognize unnecessary antibiotic prescribing is not without additional risks as

CDC Report on Resistance A report published in 2013 by the CDC outlined the top 18 drug-resistant threats in the United States. (3) The purpose of this report was to discuss the rise of antimicrobial resistance as one of the most serious public health threats to date. Examples of pertinent threats include rising rates of Clostridium difficile infections, drug-resistant Streptococcus pneumoniae, and Methicillin-resistant Staphylococcus aureus (MRSA). (3) In 2016 the White House released a National Action Plan to Combat Antibiotic-Resistant Bacteria with an overarching goal to reduce inappropriate antibiotic use by 50% over 4 years. (4) A key component to this plan is active involvement by pharma-

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cists in interdisciplinary antimicrobial stewardship efforts.

Antimicrobial Stewardship Antibiotic use is the single most important modifiable driver of antimicrobial resistance. (5) Antibiotics are also a common cause of adverse drug events (ADEs), accounting for up to 51.6% of all ADEs. (6) Minor decreases in inappropriate prescribing could result in important reductions of Clostridium difficile infections, antimicrobial resistance, ADEs, and overutilization of healthcare resources. The intent of antimicrobial stewardship is not to restrict, stop, or avoid all antibiotics. Stewards seek to achieve optimal clinical outcomes by: minimization of ADEs, allergy reconciliation, reduction in healthcare costs, and minimization of developing antimicrobial resistance.

The Infectious Diseases Society of American (IDSA) supports broad implementation of antimicrobial stewardship programs throughout the healthcare continuum. (7) Support stems from the established microbiological, antimicrobial, and financial benefits of having such programs.

Effective January 1, 2017, the Joint Commission required all hospitals, critical access hospi-

Volume 99 Number 4 Fall 2018

tals, and nursing care centers to establish antimicrobial stewardship as an organizational priority. (8) In response to this new standard, the CDC is working to help identify and implement effective stewardship strategies across the country. The Joint Commission explicitly lists the pharmacist (for their drug expertise) as a core member of the antimicrobial stewardship interdisciplinary team to improve antibiotic use. (8) Pharmacists are uniquely positioned as easily-accessible members of the healthcare continuum to provide assistance and education to both providers and patients.

Resources to Combat Antimicrobial Resistance Education Education is crucial to appropriate antimicrobial prescribing and use. The CDC provides information on updated treatment guidelines for common infections, as well as antibiotic prescribing trends state- and nation-wide. (1,2) They also provide tools for inpatient clinicians further explaining core elements of antimicrobial stewardship for improved implementation. Additionally, they produce videos and print materials to further educate patients and families regarding antibiotic resistance.

Opportunities for Pharmacist Interventions Various opportunities for implementing stewardship principles include identifying and recommending appropriate antibiotic alternatives when indicated, reconciling patient-specific anti-

biotic allergies, as well as providing continued education for both the patient and provider.

Pharmacists are positioned to provide interventional therapy when identifying appropriateness of antibiotic selection, dose, and duration, based on patient-specific parameters. By using cultures and microbiological data, pharmacists can more specifically target bacteria, thus decreasing the risk of antimicrobial resistance and C. difficile infections. A 2016 study from Powell et al. demonstrated increased rates of compliance to an institutional C.difficile treatment bundle secondary to pharmacist intervention. (9) Statistically significant decreases were observed in individual components of the bundle including initiation of appropriate treatment, discontinuation of promotility agents, discontinuation or de-escalation of acid-suppressive medications, and overall bundle compliance.

(9) In addition, pharmacists may lead a variety of outpatient stewardship initiatives including pharmacist-administered vaccination programs, rapid pointof-care testing for both influenza and Group A Streptococcus pharyngitis, comprehensive antibiotic medication review, patient counseling on appropriate antibiotic use, collaborative practices with other providers, medication take-back programs, informatics development for patients and providers, and social policies encouraging the appropriate use of antibiotics. (10) In a recent article published by the Journal of the American Pharmacists Association, the authors emphasize the critical

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role that pharmacists must play in the outpatient management of antimicrobial therapy. (10) These are just a few examples demonstrating positive impacts in patient care associated with pharmacists’ intervention in an effort to reduce negative effects of antibiotic overuse. (9,10) Summary Antibiotic resistance is an increasingly serious public health threat. According to the CDC, nearly 23,000 deaths each year are directly attributed to antibiotic-resistant bacteria. (1,2) Antimicrobial stewardship teams can assist in preventing antibiotic misuse through the combined efforts of an interdisciplinary team. Within this team, pharmacists can play instrumental roles in stewardship efforts by teaching clinicians and patients the importance of appropriate antibiotic use, providing vaccinations, or by simply utilizing their knowledge of specific antibiotics. As organizations and publications continue to recognize the benefits of pharmacist involvement to improve the use of antibiotics, more opportunities will arise for participation on interdisciplinary teams throughout the healthcare continuum.

For more information and resources to help celebrate U.S. Antibiotic Awareness Week please visit: https://www.cdc. gov/antibiotic-use/week/overview.html.

Benjamin Tutterow is a PharmD/MSCR Candidate (Class of 2020) at the Campbell University College of Pharmacy

Volume 99 Number 4 Fall 2018

& Health Sciences.

Brandon Hill, PharmD, BCPS (corresponding author) is a Clinical Specialist – Infectious Diseases/Antimicrobial Stewardship, Department of Pharmacy Clinical Services at the University of Virginia Health System.

Riley Bowers, PharmD, BCPS, is a Clinical Assistant Professor at the Campbell University College of Pharmacy & Health Sciences. email: brandon.hill@ virginia.edu

cdc.gov/antibiotic-use/stewardship-report/pdf/stewardshipreport.pdf. Accessed September 20, 2018.

3.

4.

References 1.

Centers for Disease Control and Prevention. U.S. Antibiotic Awareness Week. https://www. cdc.gov/antibiotic-use/week/ index.html/. Updated August 10, 2018. Accessed September 20, 2018.

5.

6.

2.

Center for Disease Control and Prevention. Antibiotic Use in the United States, 2017: Progress and Opportunities.https://www.

Center for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013. https://www.cdc. gov/drugresistance/pdf/arthreats-2013-508.pdf. Accessed September 20, 2018.

The White House. National Action Plan for Combating Antibiotic-Resistant Bacteria, 2015. https://www.whitehouse. gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria. pdf. Accessed September 21, 2018.

Shallcross LJ, Davies DS. Antibiotic overuse: a key driver of antimicrobial resistance. Br J Gen Pract. 2014;64(629):604-5.

Shehab N, Lovegrove MC, Geller AI, Rose KO, Weidle NJ, Budnitz DS. US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014.

JAMA. 2016;316(20):2115-2125.

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7.

Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51-77.

8.

Joint Commission. Approved: New Antimicrobial Stewardship Standard. Joint Commission Perspectives. https://www. jointcommission.org/assets/1/6/ New_Antimicrobial_Stewardship_Standard.pdf. 2016;36(7): 1-8.

9.

Powell K, Huang A, Revolinski S. Impact of Pharmacist Intervention on Compliance with Clostridium difficile Treatment Bundle. Open Forum Infectious Diseases. 2016;3(1):2122.

10.

Blanchette L, Gauthier T, Heil E, et al. The essential role of pharmacists in antibiotic stewardship in outpatient care: An official position statement of the Society of Infectious Diseases Pharmacists. Journal of the American Pharmacists Association. 2018;58:481-484.

Volume 99 Number 4 Fall 2018

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This study guide contains pertinent federal- and state-level statutes and regulations for the practice of pharmacy in North Carolina. There are 75 “Test Your Knowledge” questions spread throughout the sections of the study guide, and as an added bonus, the guide contains a mock test with 80 practice questions. The book will be shipped in the form of a binder with loose leaf pages for ease of highlighting and note taking. Purchase your copy today for $99 plus $10 shipping and handling.

North Carolina Pharmacist

Page 13 Volume 99 Number 4 Fall 2018

Asthma Intervention Program: Public Health Initiative and Pharmacy Collaboration

Dr. John M. Kessler Anne Lowry

What’s happening?

last 6 months.

The Chatham County Health Department, with approval from the Board of Health, is expanding its Asthma Intervention Program (AIP) to include an in-home assessment of medication-related triggers in children and adolescents residing in Chatham County. This program is offered at no cost to families whose children have uncontrolled asthma, as defined by the Centers for Disease Control and Prevention (CDC). Eligibility criteria include any one of the following in children 0-17 years of age: 1) poorly controlled persistent asthma, 2) hospital admission for asthma exacerbation in the last 12 months, 3) repeated Emergency Department or Urgent Care visits in the last 6 months, 4) overuse of rescue medicines in the last 6 months, or 5) more than one course of oral steroids in the

The AIP is intended to: 1) help identify indoor asthma triggers and other housing-related health hazards, 2) educate caregivers on steps to improve the health and quality of life, and 3) provide resources to help control the asthma triggers health hazards. The expanded program recognizes that an in-home assessment by the AIP nurse affords a unique opportunity to identify medication-related risk factors that might not be recognized during visits to the pediatrician or pharmacy.

What’s new?

In addition to using the Enviromental Protection Agency’s (EPAs) Asthma Home Environment Checklist (https://www. epa.gov/asthma/asthma-homeenvironment-checklist), the expanded AIP now includes an assessment of asthma control

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using the Asthma Trigger Nurse Assessment Questionnaire (ATNAQ), a history of recent urgent asthma treatments, a review of medications and how the child uses them, a review of the child’s Asthma Action Plan, a review of the caregiver’s confidence in administering the child’s medicines and their knowledge about the differences between rescue and control medications.

What’s the evidence?

Kearney et al published the results of a 6 month (Sep 2013Feb 2014) AIP pilot program in 19 children in eastern North Carolina. The researchers were able to demonstrate a 33% decrease in ED visits and a 76% decrease in rescue medication required use in the intervention group. In addition to reducing environmental triggers, the study also identified that when

Volume 99 Number 4 Fall 2018

the children were asked to demonstrate proper technique for using their medication inhalers, they observed that many of the children were either using them incorrectly, did not have an inhaler spacer, or had expired medication. The authors reported that they were reminded by caregivers of high medical costs and their limited ability to purchase asthma medication, with some caregivers acknowledging that daily albuterol or controller medicines were not being used in an effort to save money. Unexpectedly, in the control group, the self-reported use of rescue medication increased while the use of controller medications decreased.

Vorce et al authored a 2018 whitepaper on an AIP in Michigan that included home visits, medication assessment, and individualized support demonstrated that the percent of participants with at least one Emergency Department visit for asthma in the last 6 months dropped 51%. The percent of children who missed one or more days of school in the last 6 months due to asthma dropped 40%. The percentage of respondents missing at least one day of work dropped 63% at 6-months post discharge. Participants benefited from greater control over asthma exacerbations, avoided costly urgent and extended care visits, and there were fewer interruptions to daily activities for participants and their families.

In summary, both programs showed the potential for sig-

nificant cost savings for people with asthma and their insurance providers.

How can Public Health and Pharmacy Collaborate?

Pharmacists are well positioned to promote awareness of the AIP program and make referrals after identifying children at risk using a variety of inputs including: 1) the medication history and refill pattern, 2) signs of non-adherence including medication affordability, 3) awareness of the proper use of rescue and control medications, 4) awareness of recent exacerbations or urgent treatments for asthma, 5) improper inhaler technique, 6) lack of a written Asthma Action Plan, and 7) identifying unresolved patient concerns about treatments and triggers.

After households are enrolled in the AIP, pharmacists are also well-positioned to provide individualized medication monitoring and education, access to patient assistance programs that provide low or no-cost medications, and ongoing communications with the Health Department’s AIP team.

John M Kessler, BS Pharm, PharmD, is the Chief Clinical Officer at SecondStory Health, LLC and the Pharmacist Member and Past Chair of the Chatham County Board of Health. email: jkessler@secondstoryhealth.com.

Anne Lowry, REHS, is the Environmental Health Director at the Chatham County Public Health Department.

References Kearney, G. D., Johnson, L. C., Xu, X., Balanay, J. A. G., Lamm, K. M., & Allen, D. L. (2014). Eastern Carolina Asthma Prevention Program (ECAPP): An Environmental Intervention Study among Rural and Underserved Children with Asthma in Eastern North Carolina.

Environmental Health Insights, 8, 27–37. http://doi.org/10.4137/EHI. S16430 Vorce Tisa S., et al. Michigan’s Managing Asthma through Case Management in Homes (MATCH) Program: Evaluation Outcomes and Sustainability Success. May 2018. Michigan Department of Health and Human Services. https://getasthmahelp.org/managing-asthma-match.aspx

The AIP described above is specific to Chatham County; however, every Board of Health or Health Authority in the state has a pharmacist who can champion a similar program in their local county. Copies of the Chatham County Health Department Policy and AIP forms are available upon request.

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Volume 99 Number 4 Fall 2018

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Volume 99 Number 4 Fall 2018

Link to instructions for use

Additional Notes

Can Be Used With Spacer Prime Before First Use

Approved Ages

Formulation Type

Strength

Active Ingredient

Advair HFA

Alvesco Instructions for Use

Advair Diskus Patient Instructions

Advair HFA Patient Instructions

• Shaking is not necessary • Clean weekly with dry tissue • Do not wash

Yes

MDI Ages 12 and older Yes

80 mcg 160 mcg

ciclesonide

Alvesco

• Shake well before use • Clean weekly with damp tissue

Yes

No

• Do not wash

Yes

45mcg/21 mcg 115mcg/21 mcg 230mcg/21 mcg MDI Ages 12 and older

No

100 mcg/50 mcg 250 mcg/50 mcg 500 mcg/50 mcg DPI Ages 4 and older

fluticasone/salmeterol

Advair Diskus

Inhaler Reference Guide

DPI Ages 4 and older

110 mcg 220 mcg

Yes

MDI Ages 12 and older Yes

100 mcg 200 mcg

• Shake well before use • Do not wash; use dry tissue for cleaning at least once a week Asmanex Twisthaler Patient Information Asmanex HFA Patient Information

• Do not wash

No

No

Asmanex HFA

mometasone

Asmanex Twisthaler

By: Erin Mays and Dr. Cameron McKinzie

Breo Ellipta Instructions for Use

• Clean with dry tissue as needed

No

No

DPI Ages 18 and older

100 mcg/25 mcg 200 mcg/25mcg

fluticasone/ vilanterol

Breo Ellipta

1

DPI= dry powder for inhalation MDI= metered dose inhaler

Atrovent How to Use Guide

• Shaking is not necessary before use • Wash in warm water and air dry as needed

Yes

Yes

MDI Ages 12 and older

17 mcg

ipratropium

Atrovent HFA

North Carolina Pharmacist

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Volume 99 Number 4 Fall 2018

Link to instructions for use

Additional Notes

Can Be Used With Spacer Prime Before First Use

Approved Ages

Formulation Type

Strength

Active Ingredient

• Shake well before use • Clean mouthpiece with damp cloth at least once a week

Yes

Flovent HFA Patient Information

Flovent Diskus Patient Information

• Do not wash; use dry cloth or tissue for cleaning

• Shake well before use • Do not wash; use dry tissue for cleaning every 7 days

Dulera Patient Information

No

Yes

Yes

MDI

44 mcg 110 mcg 220 mcg

Ages 4 and older No

DPI

50 mcg 100 mcg 250 mcg

Flovent HFA

fluticasone

Flovent Diskus

Yes

Ages 12 and older

MDI

mometasone/ formoterol 100 mcg/5 mcg 200 mcg/5 mcg

Dulera

Yes

Yes

Ages 4 and older

MDI

Proventil

90 mcg

albuterol

Ventolin

ProAir Patient Information Proventil Instructions for Use Ventolin Prescribing Information

• Shake well before use • Wash in warm water and air-dry at least once a week

ProAir

2

DPI= dry powder for inhalation MDI= metered dose inhaler

ProAir RespiClick Instructions for Use

• Do not open the cap unless you are taking a dose • Do not wash; use dry cloth or tissue for cleaning

No

No

Ages 4 and older

DPI

ProAir RespiClick

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Volume 99 Number 4 Fall 2018

• Do not shake before use • Do not wash; use dry tissue for cleaning at least once a week

• Do not shake after loading • Do not wash; use dry tissue for cleaning at least once a week Qvar Redihaler Instructions for Use

No

Yes

Pulmicort Flexhaler Instructions for Use

No

Ages 4 and older

Ages 6 and older

No

MDI (breath-actuated)

40 mcg 80 mcg

90 mcg 180 mcg

DPI

beclomethasone

budesonide

Qvar RediHaler

• Clean mouthpiece with damp cloth at least once a week

Yes

Spiriva Handihaler Instructions for Use Spiriva Respimat Instructions for Use

• Do not shake before use • Wash in warm water and air dry as needed

No

No

Ages 6 and older

MDI

2.5 mcg 1.25 mcg

Spiriva Respimat

tiotropium

Not indicated for use in children No

DPI

18 mcg

Spiriva Handihaler

Symbicort HFA Patient Information

Xopenex HFA Patient Information

• Has no actuation counter • Shake well before use • Wash in warm water at least once a week

Yes

Yes

Ages 4 and older

MDI

100 mcg 200 mcg

levalbuterol

Xopenex HFA

3

DPI=Pulmonology dry powder for inhalation MDI= metered dose inhaler

• Shake well before use • Do not put in water; clean with dry cloth every 7 days

Yes

Yes

Ages 6 and older

MDI

80 mcg/4.5 mcg 160 mcg/4.5 mcg

budesonide/ formoterol

Symbicort HFA

Erin Mays is a P3 PharmD Candidate at the UNC Eshelman School of Pharmacy. Cameron J. McKinzie, PharmD, BCPPS, BCPS, CPP, is the Pediatric Residency Program Director, PGY2 Pediatrics, at the University of North Carolina Children’s Hospital. Email: Cameron.Mckinzie@unchealth.unc.edu

Link to instructions for use

Additional Notes

Can Be Used With Spacer Prime Before First Use

Approved Ages

Formulation Type

Strength

Active Ingredient

Pulmicort Flexhaler

Pharmacy

Tomorrow.

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Pharmacists Mutual Insurance Company | 808 Highway 18 W | PO Box 370 | Algona, Iowa 50511 P. 800.247.5930 | F. 515.295.9306 | info@phmic.com

phmic.com

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

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Volume 99 Number 4 Fall 2018

2018 Convention Sponosors

Convention Gold Sponsor

Thank You For Your Support!

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Volume 99 Number 4 Fall 2018

2018

Award Recipients

Bowl of Hygeia Davie Waggett (Accepted by Gray Stewart, pictured middle )

Excellence in Innovation Rebecca Grandy

Cardinal Rx Generation Award Vera Reinstein

(Pictured left)

(Pictured middle)

Don Blanton Award Cheryl Viracola

Distinguished Young Pharmacist Cortney Mospan

(Pictured left)

(Pictured left)

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Volume 99 Number 4 Fall 2018

Community Care Pharmacist of the Year Jennifer Burch

Health-System Pharmacist of the Year Amy Holmes (Accepted by Brock Harris, pictured left)

(Pictured middle)

(Pictured middle)

Mckesson Leadership Award NCPA Leadership Award Debra Kemp

NCAP President’s Award Stefanie Ferreri

President’s Service Award Nita Johnston

(Pictured right)

(Pictured left)

ASHP Leadership Award Kira Harris

North Carolina Pharmacist

(Pictured left)

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Volume 99 Number 4 Fall 2018

Silent Thank You to the following who donated to the Auction: Blue Ridge Pharmacy Jamie Brown Carolina Hurricanes Chronic Care Executive Committee (2) Tom D’Andrea Lisa Dinkins Durham Bulls Frame Warehouse, Durham (Eric Ardery, Manager) Linda Goswick Debra Kemp Cortney Mospan NASCAR Hall of Fame NCAP NC Football Club Dave Phillips Raylen – Winston-Salem Penny Shelton Sona Pharmacy Team Penske (NASCAR) Jenn Wilson Winston-Salem Marriott Winston-Salem Visitors Bureau

Congratulations to our Silent Auction Winners! The Silent Auction raised over $1885 for the NCAP Advocacy Fund North Carolina Pharmacist

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Volume 99 Number 4 Fall 2018

2018 Fifty Plus Club Mary Silver Adams – Raleigh Eugene Gibson Anderson – Elizabethtown Diane Baxter Brogden – Lincolnton Harry Lee Brogden – Lincolnton George M. Carter – Franklin Robert M. Cheskis – Cary Robert Wesley Cotten - Raleigh Nellie Silver Jones – Raleigh David Kendall Rickelton – Greensboro Carl Dewey Taylor – Chapel Hill

North Carolina Pharmacist

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Volume 99 Number 4 Fall 2018

Rite Of Roses 2018 Leslie Gordon Collins Leon Stanley Haywood Peter Thomas Milliones Richard Clyde Wagoner

In Memory of NCAP Members

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Volume 99 Number 4 Fall 2018

Is Ramelteon Safe in Patients with Chronic Obstructive Pulmonary Disease or Obstructive Sleep Apnea?

Sydney Brodeur and Dr. Scott Perkins

Background: Insomnia is defined by the American Academy of Sleep Medicine (AASM) as a “subjective report of difficulty with sleep initiation, duration, consolidation, or quality that occurs despite adequate opportunity for sleep, and that results in some form of daytime impairment.” (1) Approximately 9 to 12% of adults and 20% of the elderly will experience insomnia during their lifetime. Insomnia can develop secondary to several other conditions such as cardiovascular complications, sleep apnea, asthma, endocrine disorders, and depression. Stressful experiences and life events may also bring about symptoms of insomnia. These patients often feel distress due to their lack of sleep or fear of not being able to sleep at night impairing their ability to work efficiently during the day. The goal is to treat these patients to improve their quality of life without producing adverse effects. (2) According to the 2017 AASM guidelines for chron-

ic insomnia in adults, ramelteon, benzodiazepines (BZDs) including triazolam and temazepam, or short- or immediate-acting nonbenzodiazepine receptor agonists (BzRAs) including zaleplon, zolpidem, and eszopiclone, may be considered first-line options for treatment of insomnia in adults. No specific agent within this list of drugs is recommended over another, but consideration of symptom presentation, past response, cost, and patient preference is recommended when initiating therapy. (1) Although many medications are available to help improve sleep in patients with insomnia, many of these medications pose a safety concern when administered to individuals with certain comorbid disease states, such as chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), due to the risk of decreased oxygenation during sleep. According to the Centers for Disease Control and Prevention (CDC), nearly

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16 million Americans (6.4%) are diagnosed with COPD, a condition characterized by the inflammation of the airways often resulting from exposure to cigarette smoke, air pollution, or other toxins. (3,4) The exposure to these chemicals leads to the release of neutrophils which destroy the alveolar wall of the air sacs in the lungs, increase the secretion of mucus, and cause fibrosis of the lung tissue. The damage that happens over time in all individuals is accelerated in COPD leading to the irreversible loss of lung function. (4) When patients with COPD sleep, they experience decreased ventilation during all sleep stages due to the ineffectiveness of the chemical, mechanical, and cortical receptors of the respiratory system.

The lack of effective system management leads to increased end-tidal partial pressure of carbon dioxide (PCO2) proportional to the depth of sleep they are experiencing at that time. Additionally, lower partial pressure of oxygen (PO2) levels throughout

Volume 99 Number 4 Fall 2018

the day exaggerates the chemoresponse during sleep which predisposes these individuals to hypoxemia during the night.

(5) Interestingly, every individual experiences reduced respiratory muscle activity when they sleep leading to decreased oxygenation, but in COPD, this leads to periods of hypopnea which may escalate to hypoxemia and cause life-threatening consequences. (6) Ultimately, this process results in delayed sleep onset as well as frequent arousals and awakenings. This pattern of disrupted sleep at night can be troubling for COPD patients and can reduce their quality of life. (7) Although healthcare providers want to help these patients sleep, they may be hesitant to prescribe hypnotics because they fear that the risk of deoxygenation may outweigh the benefits in this patient population.

several times throughout each night. They will cease breathing following a drop in their oxygen saturation, and when they resume breathing, they are awoken. This causes some patients to have excessive daytime sleepiness, poor memory, and irritability which affects their quality of life. (2) Similar to patients with COPD who experience insomnia, medication therapy that results in decreased oxygen saturation is potentially dangerous in this population.

Of the first-line options indicated for treatment of insomnia, the BZDs, triazolam and temazepam, are the oldest and carry the greatest risk for pulmonary adverse events. Benzodiazepines enhance the gamma-aminobutyric acid (GABA) effects, particularly GABA-A which is located in the central nervous system which is believed to be coupled to the benzodiazepine 1 (BZ1), Obstructive sleep apnea, like BZ2, and BZ3 receptor subtypes.

COPD, is another comorbid (8) Activation of the BZ2 receptor disease state that raises conalso results in diminished muscle cern when treating insomnia contractility which can lead to with medications that decrease pulmonary muscle relaxation; oxygen saturation. Patients with therefore, based on the mechaOSA experience upper airway nism of this class, safety is a obstruction leading to desatumajor concern in patients with rated blood oxygen. Although the insomnia and comorbid COPD exact mechanism by which the and OSA. (8,9) obstruction occurs is unknown, BzRAs are newer than BZDs it is likely caused by several and are also indicated for the factors. Risk factors include treatment of insomnia. Their neck obesity, narrow airway, selectivity for BZ1 and BZ3 recepand enlarged tonsils, as well tor subtypes results in fewer side as various neurological condieffects, specifically with regard tions. Additionally, intraluminal negative pressure while inspiring to pulmonary function, while still providing its sedating effect. (9) can cause the upper airway to Unfortunately, mixed results in collapse. These factors lead to repeated instances of nocturnal the literature make it unclear as to the effects these agents have breathing cessation, which can on pulmonary function; therebe life-threatening. These patients experience disturbed sleep fore, a risk still exists that these North Carolina Pharmacist

Page 28

agents could lead to respiratory depression even if this risk is less than BZDs. (10) Additionally, the AASM guidelines caution the use of these agents in COPD and OSA patients due to the risk of respiratory depression. (1) Ramelteon is a potentially safe agent to use in these patient populations. Ramelteon was approved in 2005 for the treatment of insomnia characterized by difficulty with sleep onset.

Its effect on waking after sleep onset is minimal due to its short duration of action. The mechanism through which ramelteon promotes sleep is the activation of the MT1 and MT2 melatonin receptors in the hypothalamus leading to the release of endogenous melatonin by the pineal glands. Endogenous melatonin levels are at their highest during times of darkness and promote the drowsiness needed to help individuals fall asleep. (9,11) Ramelteon has not shown affinity for the GABA-A complex or receptor; therefore, ramelteon promotes sleep without producing the respiratory depression effects through the GABA-A complex. (12) As a result, ramelteon has a potential to be instrumental in promoting sleep onset in patients with COPD and OSA without the respiratory effects that should be avoided in this patient population.

Review of Literature: Currently, no studies have been conducted which compare ramelteon directly to any of the BZDs or BzRAs. Additionally, many studies which evaluate ramelteon for insomnia exclude patients with COPD or OSA. Although some published studies are available which provide

Volume 99 Number 4 Fall 2018

limited insight on the safety of ramelteon in patients with sleep apnea, the current package insert for ramelteon does not recommend its use in patients with OSA due to lack of studies with sufficient data. (11) A phase III study provided evidence to indicate multiple doses of ramelteon are more effective than and just as safe as placebo when used in patients with insomnia. This was a randomized, placebo-controlled, double-blind, crossover study assessing the efficacy, safety, and dose-response of ramelteon in patients with chronic primary insomnia.

The dosing sequence included 4, 8, 16, and 32 mg of ramelteon and found that the safety was similar to placebo at each dose.

(13) Patients were included if they met the following criteria: a diagnosis of primary insomnia for at least 3 months, a subjective sleep latency greater than 30 minutes and a subjective total sleep time of less than 6.5 hours per night, and daytime disturbances related to lack of sleep, but patients with OSA were specifically excluded. All doses of ramelteon resulted in a statistical decrease in latency to persistent sleep (p<0.001), which was defined as the time from lights out to the first epoch of the first 10 minutes of consecutive sleep on polysomnographic recording, but this study did not find a statistical difference in total sleep time.

Overall, the safety of this agent was comparable to that of a previous study by Roth and associates and no effects on oxygen saturation were identified. These studies found that ramelteon was well-tolerated and headache was the most common side effect reported. (13,14) The results

support the use of ramelteon to promote sleep onset in patients with insomnia without providing specific evidence of its use in patients with COPD or OSA. Few studies have been conducted investigating the safety of ramelteon in the patient populations of interest, but the studies available provide evidence that it may be safe in patients with comorbid COPD or OSA. In 2007, a double-blind, randomized, placebo-controlled, cross-over study was conducted to compare a single dose of ramelteon 16 mg to placebo in 26 patients with mild to moderate OSA. The primary outcome of this study was the difference in apneahypopnea index (AHI), defined as the total number of apneas or hypopneas divided by total sleep time in hours. Patients with COPD were excluded. No statistical difference was identified between the AHI scores of patients in the ramelteon group and those in the placebo group (11.4 vs 11.1, respectively; p=0.812).

Additionally, secondary outcome regarding SaO2 throughout the entire night, during awake stage, rapid eye movement (REM) stage, and non-rapid eye movement (NREM) stages were all similar between groups and the differences were not considered statistically significant (Table 1).

(12) This provides evidence to suggest that when used in patients with sleep apnea, oxygen saturation is preserved compared to no therapy, providing a possible benefit over therapies that may decrease saturation.

In a small 2008 study conducted

by Kryger and associates, 25 subjects with moderate to severe COPD were enrolled to

North Carolina Pharmacist

participate in a randomized, double-blind, placebo-controlled, cross-over study comparing a single dose of ramelteon 8 mg vs placebo. Patients in this study had COPD with Global Initiative for Chronic Obstructive Lung Disease classification of II or III (moderate or severe) with a formal diagnosis of insomnia.

The primary outcome was SaO2 during sleep for the full night.

This study found that there was no significant difference in the primary outcome between the treatment phases (95% CI: -1.09 to 0.62; p=0.576) suggesting that ramelteon does not appear to decrease oxygen saturation during sleep in patients with severe COPD. Other changes in SaO2 levels were also not significant (Table 1). Additionally, the difference in the mean AHI was not statistically significant (95% CI: -1.40 to 1.78; p=0.804) suggesting that the number of instances of sleep apnea episodes is not exacerbated in the presence of ramelteon. (7) The evidence suggests that oxygen saturation is maintained throughout the night comparable to placebo in patients with moderate-to-severe COPD. Although, a more apropos endpoint may have focused on the initial phases of sleep due to ramelteon’s short duration of action. This provides potential evidence supporting the safety of ramelteon in COPD patients over other available treatments that may compromise oxygen saturation.

Discussion and Recommendations: The studies described above provide evidence that ramelteon has limited detrimental effects on oxygen saturation in patients

Page 29 Volume 99 Number 4 Fall 2018

with OSA and COPD; however, more data are needed to determine the safety of this agent in patients with these comorbidities. Ramelteon is not approved for use in patients who are awoken often once sleep has initiated and has not been shown to be effective for this indication, so it should not be expected to help patients with COPD and OSA who experience these issues. Unfortunately, patients with either of these conditions often have issues waking after sleep onset; thus, while the use of ramelteon may have no significant impact on oxygen saturation, appropriate sleep hygiene and use of a continuous positive airway pressure (CPAP) device are vital in promoting sleep throughout the night for patients with these conditions.

Sydney Brodeur is a P-4 PharmD Candidate at the Campbell University College of Pharmacy & Health Sciences. Scott Perkins, PharmD is a Clinical Assistant Professor and Co-Director of the Drug Information Center at Campbell University College of Pharmacy and Health Sciences in Buies Creek, NC. email: perkins@campbell.edu

ment of Chronic Insomnia in Adults. J Clin Sleep Med. 2008;4(5):487-504.

3.

4.

Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary. Am J Respir Crit Care Med. 2017;

5.

Bhullar S, Phillips B. Sleep in COPD patients.

COPD. 2005;2(3):355-61.

6.

White, J. E., Drinnan, M. J., Smithson, A. J., Griffiths, C. J., & Gibson, G. J. Respiratory muscle activity during rapid eye movement (REM) sleep in patients with chronic obstructive pulmonary disease.

Thorax. 1995;50(4):376-382.

7.

References: 1.

2.

American Academy of Sleep Medicine. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349.

Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical Guideline for the Evaluation and Manage-

Wheaton A, Cunningham T, Ford E, Croft J. Employment and activity limitations among adults with chronic obstructive pulmonary disease.

MMWR. 2013;64(11):289295.

8.

Kryger M, Roth T, Wangweigand S, Zhang J. The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease. Sleep Breath.

2009;13(1):79-84.

Bailey L, Ward M, Musa MN. Clinical pharmacokinetics of benzodiazepines. J Clin Pharmacol. 1994;34:804-811.

9.

Roth T. Hypnotic use for insomnia management in chronic obstructive pulmonary disease. Sleep Med. 2009;10(1):19-25.

10.

Brandt J, Leong C. Benzo-

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diazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research.

Drugs R D. 2017;17(4):493507.

11.

Takeda Pharmaceuticals America, Inc. ROZEREMramelteon tablet, film coated. 2005 [rev. 2018 Jan; cited 2019 May]. In DailyMed [Internet]. Bethesda (MD): National Library of Medicine (US). Available from: https://dailymed. nlm.nih.gov/dailymed/drugInfo.cfm?setid=9de8231070e8-47b9-b1fc6c6848b99455#S8.7.

12.

Kryger M, Wang-weigand S, Roth T. Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea. Sleep Breath.

2007;11(3):159-64.

13.

Erman M, Seiden D, Zammit G, Sainati S, Zhang J. An efficacy, safety, and doseresponse study of Ramelteon in patients with chronic primary insomnia. Sleep Med. 2006;7(1):17-24.

14.

Roth T, Stubbs C, Walsh JK. Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment.

Sleep. 2005;28(3):303-7.

15.

American Academy of Sleep Medicine. Clinical guideline for evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009 Mar;5(3):263-276.

Volume 99 Number 4 Fall 2018

Table 1. Comparison of SaO2 Levels Overnight Ramelteon

Placebo

SaO2 (%)

SaO2 (%)

Statistical Significance

Obstructive Sleep Apnea Entire night

95.1

94.7

NS

Awake Stage

95.5

95.0

NS

REM Stage

95.2

94.5

NS

NREM state

95.0

94.6

NS

Chronic Obstructive Pulmonary Disease Entire night

92.2

92.5

NS

REM Stage

92.1

91.9

NS

NREM state

92.2

93.0

NS

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The NCAP On-Demand E-Learning library of offerings is expanding! These webinars are a member benefit as CE is FREE TO MEMBERS ONLY. Several clinical and other topics are now available. There is also a dedicated project team that is working this year to increase our E-Learning offerings.

Go to ncpharmacists.org and log-in for full access

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Volume 99 Number 4 Fall 2018

Implementation and Evaluation of a Resident-Run Residency Preparatory Program for Fourth-year Pharmacy Students at an Academic Medical Center Justin Arnall, Tina Thornhill, Jerod Braschler, Rebecca Bookstaver, Marie Cavalier Rush, Ashley Wester, Amanda Dombroski, Lindsey Koliscak Goldman, and Steven Davis Abstract: The demand for pharmacy residency programs continues to rise as the number of candidates exceeds the supply of available positions. The process of attaining a pharmacy residency is both intense and intimidating, and students often seek guidance from their clinical preceptors.

Many colleges of pharmacy across the country provide programming that increases student preparedness for navigating through the residency application and interview process. These programs are usually created, coordinated, and facilitated, by school faculty members. Insight from residents is also useful as expressed by students in reports of residency panels at pharmacy schools; however, little has been published to encourage residents or residency programs to coordinate preparatory programs for students. With the support of the residency program director and practicing school faculty, the residents at Wake Forest Baptist Health coordinated a residency preparatory program that was available for fourth (final) year students completing experiential training at the hospital and surrounding areas. This program included targeted presentations on key features of the application and interview process. Residents developed materials and shared their insight with student attendees. Although formal student feedback on the program was minimal, students expressed an enhanced understanding of the important elements of residency attainment and perceived benefit in the program. The leadership and teaching experience that the pharmacy residents gained was considered beneficial as well. Overall, the initial success of this residency preparatory series will promote its continuation and future development and hopefully encourage other pharmacy residents to share their insight with students aspiring to obtain postgraduate residency training.

Background National pharmacy societies encourage using residencytrained pharmacists for direct patient care; however, the number of residency candidates exceeds the supply of available positions. (1-5) In 2017–18, there were 4,913 applicants for 3,484 residency positions in the American Society of HealthSystem Pharmacists (ASHP) Resident Matching Program (“the Match”). Of these applicants, 1,678 pharmacists (34%) ultimately went unmatched.

(6) For many applicants, the decision to pursue a residency

position and the preparation required of students leading up to Match day can be stressful and confusing. (7,8) The application process requires the preparation of a curriculum vitae (CV), letter of intent, letters of recommendation, and effective submission of all necessary documents through ASHP’s web-based Pharmacy Online Residency Centralized Application Service (PhORCAS). Upon receiving interview invitations, the candidate prepares accordingly, then ranks the program(s) and position(s) for which they are wanting to obtain. This process is both intense and

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intimidating, and students often seek guidance from their clinical preceptors. (7,8) Due to the complicated and competitive process of attaining a pharmacy practice residency position, many colleges of pharmacy provide programming to enhance student preparedness for navigating through the residency application and interview process. (3, 9) These programs are usually created, coordinated, and facilitated by pharmacy faculty members. A previous study by Dunn et al. sought to understand how many schools offered specific programming to prepare their stu-

Volume 99 Number 4 Fall 2018

dents for residency. (3) Sixteen of the 71 responding institutions (22.5%) stated that a structured, formal program was offered.

Activities most commonly listed within the formal residency preparation programs included: presentations, online tools, reading materials, ASHP clinical skills competitions within local chapters, involvement in an IRB-approved research project, certifications in medication therapy management or immunization, as well as elective practice experiences that emphasize knowledge regarding residencies. Additionally, many student organizations within schools of pharmacy coordinate residency preparation programs, often collaboratively with school faculty, local practitioners, and current pharmacy residents. (8) To date, however, there are no reports of residency preparation programs for students coordinated and implemented solely by current pharmacy residents.

Discussions with students completing their advanced practice pharmacy experiences (APPEs) at Wake Forest Baptist Health (WFBH) revealed they were eager for opportunities to interact with residents and to learn about the residency application process regardless of their background preparation.

Consequently, early in the academic year, pharmacy residents at WFBH expressed interest in coordinating a residency preparatory program. With the support of the residency program director and on-site practicing college of pharmacy faculty, the residents coordinated a residency preparatory program that

was available for senior students completing their APPEs at the hospital and in the surrounding areas. We describe our Residency Preparatory Series (RPS) here.

Program Description The objectives of this program were twofold: (1) to assist students in preparing to apply for residencies, and (2) to offer the pharmacy residents at WFBH an opportunity for additional teaching experiences. Pharmacy residents at WFBH planned and implemented a five-part presentation series to offer guidance through the residency application process. Each one-hour presentation focused on key points in the application process and was organized so that students received the information at an appropriate time relative to the academic year. Residents communicated and worked with the on-site pharmacy school clinical faculty at WFBH to plan optimal times for the series sessions and to facilitate communication about the RPS with their students.

Because the programming was held after business hours, faculty provided dinner at each event. Faculty also regularly attended the sessions to offer further insight, guidance, and feedback to the residents. The timeline for the series is illustrated in Figure 1.

Preparatory Program Topics Why Choose a Residency?

In September, PGY-1 and PGY2 residents provided an informal panel discussion giving attendees advice and insight into

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the application process. The residents candidly discussed why they decided to do a residency and how they prepared for the application process. This session was primarily directed at students with an interest in pursuing a residency, but was intended to benefit all students since many of the topics were applicable to finding employment in a competitive job market.

How to Navigate a Showcase?

In October, the second session was held before the state-level residency showcase and the ASHP Midyear Clinical Meeting Residency Showcase. This session provided pearls for successfully navigating a showcase. Residents shared their personal experiences on the differences between showcase opportunities, preparing for showcases, how to dress, interacting with directors, residents, and other candidates, and ultimately how to be successful in the overall process. Residents shared their personal accounts of maneuvering through the showcases from both the candidate and active resident perspective.

Will They Write Me a Recommendation?

In November, following the opening of PhorCAS, the third session was held and focused on obtaining letters of recommendation. This program was timed to give students several weeks to seek recommendations. The importance of positive letters of recommendation was emphasized. Examples of

Volume 99 Number 4 Fall 2018

how to request letters of recommendation from preceptors, school faculty, and employers was discussed. Information was shared on what to provide the selected references that would give them the ability to write optimal and personalized recommendations. The residents along with faculty members discussed changes in strategies and considerations for recommendations within PhorCAS. The residents also highlighted other aspects of the residency application, specifically the CV, letters of intent, and college transcripts. Residents individually reviewed students’ CVs and letters of intent and provided specific feedback. At this point in the series, the residents considered the students to be well-prepared to interact with residency programs during the meeting showcases.

What is the Best Way to Prepare for Interviews?

The fourth RPS was held in January as students began to receive invitations for interviews. This session focused on the entire interview process including scheduling and preparing for interviews, the actual interview day experience, and professional follow-up. The important points of business etiquette when receiving invitations and developing a strategy for scheduling interviews was highlighted. Interview preparation (e.g., materials to carry, sample questions to anticipate and to ask) was discussed.

Finally, the students were engaged in an interactive session where they were placed into groups and rotated to each resi-

dent asking more individualized questions on the specific topics of preparation, interviewing, and follow-up.

How Does Ranking, the Match, and the Scramble Work?

The final session was held in March when most students were finished with their interviews and were in the process of finalizing their rankings. In this meeting, residents focused on how to rank programs, navigate the Match, and how to prepare for the Scramble (where unmatched programs and residents attempt to connect).

Students were encouraged to rank programs based on their personal evaluations. Multiple residents described how they evaluated and scored programs to develop their rank list. Additionally, the couple’s match for those students considering this option was also reviewed. At the end of the session, the residents offered to serve as mentors through the final process.

Series Evaluation and Results To formally assess the stated program goals, a survey was created and distributed after the initial session and following the conclusion of the program.

Scoring was via a Likert scale with grades 1 to 4, 1 representing little to no comfort or knowledge and 4 suggesting highest/ complete confidence and understanding. The post-session survey was distributed and collected at the final meeting of the series.

Sixteen students completed the pre-series survey. These stu-

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dents expressed the most interest in obtaining a better overall understanding of the residency application process and gaining confidence in the process.

They were also most interested in information about creating their CVs, resource retrieval, and asking for letters of recommendation. They were least interested in obtaining information about navigating Professional Placement Services and the Scramble.

There were only four students who completed the post-series survey; however, despite the low response, verbal feedback from all participants was very positive. Students completing the post-series evaluation applied to an average of 11.4 residency programs and received an average of 5.1 interviews. In all aspects of the residency attainment process, students expressed a high degree of confidence on the Likert scale >3.5 average (a score of 4 expressing highest confidence).

Students expressed the highest confidence in resource retrieval and asking for recommendation letters. Students expressed the lowest confidence in interviewing for residencies.

The students completing the survey indicated a better overall understanding of the residency application process and confidence with the process.

Although some students had already received information on obtaining a residency, the timing of this program allowed the information to be immediately applied.

Volume 99 Number 4 Fall 2018

Every participating pharmacy resident stated the program gave them additional opportunities to mentor student learners and helped them develop their teaching skills. Residents also reported being more motivated to action after hearing questions regarding the residency application process from multiple students.

Discussion Despite the increased demand for pharmacy residency training, the literature evaluating the education of pharmacy students about the residency process is limited. Various groups have reported their efforts to most effectively prepare students for the residency application process. For example, the University of Mississippi implemented a residency interest group to increase the knowledge, confidence, and preparedness for residency-related topics. (10) This interest group was a faculty-directed, residency-specific program designed for third and fourth (final year) students; moreover, it was supplemental to various activities previously held at the school that sought only to introduce students to specific residency programs.

This group engaged local residency directors, preceptors, current residents, students, and faculty in all program sessions.

Furthermore, a mentoring program was developed for which students could sign up. Group meetings consisted of four 2-3hour faculty presentation sessions on various topics related to professional development and residency attainment, guest speaker discussions, as well as

question and answer sessions.

Three sessions were held prior to the ASHP Midyear Meeting and the final session prior to the Match. Via pre- and postsession surveys the authors assessed students’ confidence in various aspects of the application process. Among the residency interest group attendees, statistically significant improvements in confidence were seen in resource retrieval and the overall composite score. Over a two-year period, 74% of the total number of students who obtained a residency position attended at least one residency interest group session. The authors concluded that their formalized program resulted in an increase in student preparedness for the residency application process and success with residency placement. (10) At some schools, student-led organizations take the initiative to coordinate residency preparatory programs. Students from the Ohio State University College of Pharmacy described a student-driven collaboration with the school faculty, residents and preceptors from the nearby University Medical Center. (8) The goal of their program was to give students opportunities to interact with and receive feedback from pharmacists and current residents in various practice settings and to highlight important aspects of the residency application process.

Students collaboratively hosted several preparation programs including a CV critique, mock residency interviews, a “Residency 101” presentation, and a Midyear-to-Match Residency

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series. These events were strategically scheduled throughout the year so they would be most relevant to those students actively engaged in the residency application process. At the end of the year, as part of the Residency 101 activity, these senior students were invited to speak about their experiences to the rest of the student body. The impact of this preparatory program was evaluated by the students via an electronic survey.

Overall, 77% of those students who applied for a residency reported obtaining a position with 65% of those respondents matching with a program in their top three ranked choices.

Students were also asked to rank their satisfaction with the various programs. The mock interviews received the highest satisfaction (most useful) score followed by those programs with the broadest overviews of the residency process and resident interactions (Residency 101 and Midyear to Match Residency Series), though all scores suggested a high level of satisfaction with the programs. From their experience, the authors identified a match rate almost 15% higher than the reported national average among those students who participated in the program, and students who participated generally found the program helpful. (8) The successes and experiences from this report continue to suggest that students desire education on navigating the residency application process and that they may be generally more successful after participating in such programs.

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Regardless of who organized the residency application programs, a common theme was the involvement of pharmacy residents. Our report is the first to describe a residentcoordinated residency preparatory series. Current resident involvement may be considered vital because of their recent and successful immersion in the application process as well as their relatability to students. Residents should seek to engage students and consider serving as a mentor throughout the application process.

did not consider students who attended sessions other than the first and last.

The average of number of interviews students received was greater than the average number of rankings submitted per applicant based on reported match statistics from 2015 of 4.1 per candidate. (6) While specific conclusions cannot be made based on our limited data, the overall feedback from the students was very positive, and consideration for developing similar programs should be made. For future programming, Considering the demanding it is recommended to capture schedule of many residency assessments at each individual programs and the limited session and to develop more amount of free-time, residency incentives for attendance and program directors and residents participation. Residents initiatmay be reluctant to offer a preing such programs should tailor paratory series. One advantage the structure of their activities to our program was the availto the needs and interest of the ability and cooperation of onstudents as well as the availsite college of pharmacy faculty ability and investment of local who coordinated the events. By school faculty. Finally, with the engaging faculty, the residents perceived success of this prepacould focus on program presen- ratory series for the student attations and discussions. Factendees, the program was also ulty involvement reduced the beneficial for the participating residents’ time commitment and residents. The series offered prevented any negative impact more opportunities for residents on their other residency respon- to present information and ideas sibilities. than were originally planned.

The residents interacted with Unfortunately, a notable limitastudents which fostered their tion of our RPS was the small ability to teach and mentor and number of participating stuthey had the opportunity to work dents. This limitation was collegially with pharmacy school influenced by the fact that the faculty. Due to the perceived program was developed and adsuccess and benefit to the stuvertised for a limited number of dents and residents at WFBH, students who were completing this RPS is now a requirement their APPEs at the hospital and for the residency program’s in the area who may or may not teaching certificate. have had an interest in completing a residency program. Our Conclusion pre- and post-survey analyses North Carolina Pharmacist

Through a resident-coordinated RPS, pharmacy students were educated on crucial elements of the residency application process. With strategic help from school faculty, residents were able to work together to design and implement a successful program that was appreciated by the students and was a beneficial experience for the residents. The involvement of on-site pharmacy school faculty was crucial in the success of the program. While the number of participating students was small and assessment data limited, the initial results suggest that such activities should be encouraged. Students benefit from an improved knowledge of the residency application process and residents benefit from the additional teaching opportunities and from the leadership skills gained to organize such a program. Future RPS programming will attempt to investigate future Match outcomes as well as identify more specifics regarding the benefits of these activities for the residents.

Justin Arnall, PharmD, BCOP, CPP, is the Clinical Coordinator for Hematologic Malignancies in the Department of Pharmacy at Levine Cancer Institute, Carolinas HealthCare System; Charlotte, NC. Tina Thornhill, PharmD, FASCP, BCGP, is an Associate Professor and Vice Chair for Professional Education in the Department of Pharmacy Practice at Campbell University College of Pharmacy & Health Sciences in Buies Creek, NC. Jerod Braschler, PharmD, MS, is the Pharmacy Manager in the Department of Pharmacy

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at Mission Health in Asheville, NC. Rebecca Bookstaver, PharmD, BSN, BCCCP, is a Clinical Pharmacist in Critical Care at Wake Forest Baptist Health in Winston-Salem, NC. Marie Cavalier Rush, PharmD, BCOP, is a Clinical Pharmacist in Hematology/Oncology at Wake Forest Baptist Health in Winston-Salem, NC. Ashley Wester, PharmD, BCPPS, is the Clinical Pharmacy Specialist in Pediatric Cardiology at C.S. Mott Children’s Hospital, Michigan Medicine in Ann Arbor, MI. Amanda Dombroski, PharmD, MS, is the Pharmacy Project Manager of Outpatient Pharmacy Services at Johns Hopkins Home Care Group in Baltimore, MD. Lindsey Koliscak Goldman, PharmD, BCPS, is a Specialty Infusion Pharmacist at Wake Forest Baptist Health in Winston-Salem, NC. Steven Davis, PharmD, BCGP is an Associate Professor at Campbell University College

of Pharmacy & Health Sciences and Clinical Pharmacist at Wake Forest Baptist Health in Winston-Salem, NC. Email: jarnall87@gmail.com References: 1.

McCarthy BC, Weber LM. Update on factors motivating pharmacy students to pursue residency and fellowship training. Am J Health-Syst Pharm. 2013; 70: 1397-403.

2.

Morton J, Koval P, Gal P. Pharmacy residency match rates and predictors. Am J Pharm Ed. 2013; 77(10), Article 212.

3.

Dunn BL, Ragucci KR, Garner S, et al. Survey of colleges of pharmacy to assess preparation for and promotion of residency training. Am J Pharm Ed. 2010; 74(3) Article 43.

4.

The census of the Pharmacy Practice Model Summit. Am J Health-Syst Pharm. 2011; 68: 1148-52. doi: 10.2146/ajhp110060 5.

Haas CE, Yee GC, Cohen LJ, et al. Board of Regents Commentary Qualifications of Pharma-

cists Who Provide Direct Patient Care: Perspectives on the Need for Residency Training and Board Certification. Pharmacotherapy.

2013; 33(8): 888-891.

6.

ASHP Resident Matching Program. Available: https://www. natmatch.com/ashprmp/. Accessed: October 29, 2017.

7.

McElhaney A, Weber R. Role of pharmacy residency training in career planning: a student’s perspective. Hosp Pharm. 2014; 49(11): 1074-1080.

8.

Koenigsfeld CF, Wall GC, Miesner AR, et al. A faculty-led mock residency interview exercise for fourth-year Doctor of Pharmacy students. J Pharm Pract. 25(1): 101-107.

9.

Rider SK, Oeder JL, Nguyen TT, Rodis JL. A collaborative approach to residency preparation programming for pharmacy students. Am J Health-Syst Pharm.

2014; 71: 950-955.

10.

Stover KR, Fleming LW, Riche DM, et al. Impact of a residency interest group on students applying for residency. Am J Pharm Ed. 2014; 78(6) Article 127.

Figure 1

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Volume 99 Number 4 Fall 2018

INSIGHT: January is Glaucoma Awareness Month

Dr. Tina Thornhill Glaucoma results when there is damage to the optic nerve fibers and they die. There are two main types: open-angle and closed-angle. Closedangle glaucoma occurs when there is an abrupt rise in intraocular pressure causing pain and other symptoms (e.g., nausea, vomiting) and requires immediate medical attention. Open-angle, the most common form, has a slow onset and no painful symptoms. Both types of glaucoma cause irreversible vision loss (especially peripherally) making early diagnosis critical to effective treatment.

There are approximately three million Americans who have glaucoma, but only half are aware of their condition. As much as 40% of vision can be lost before someone is aware - making glaucoma a leading cause of blindness. Blindness from glaucoma is nearly eight times more likely in African-Americans than in any other population. Risk factors for

glaucoma include: age (> 40 years), family history of glaucoma, African, Hispanic, or Asian heritage, use of long-term steroid medications, history of an eye injury, diabetes, migraines, hypertension, vascular disease, or high intra-ocular pressure.

Medications that can increase intraocular pressure include: agents with anticholinergic side effects, pseudoephedrine, sulfonamides, and prolonged steroid use.

The American Academy of Ophthalmology (AAO) recommends a routine eye examination based on age, risk factors, co-morbidities, and symptoms. A dilated eye exam is the most effective way of diagnosing glaucoma. Table 1 illustrates the AAO’s recommendation schedule for comprehensive medical ophthalmic examination unless otherwise directed by an ophthalmologist.

Table 1: AAO’s Recommendation for Comprehensive Medical Eye Exam Classification

Age (years)

Frequency of Evaluation

No risk factors for eye disease or glaucoma and asymptomatic adults

65 years and older

Every 1-2 years

55-64 years

Every 1-3 years

40-54 years

Every 2-4 years

40 years and under

Every 5-10 years

65 years and older

Every 1-2 years

55-64 years

Every 1-2 years

40-54 years

Every 1-3 years

40 years and under

Every 1-2 years

Type 1 diabetes

--

Initial exam: 5 years after onset, then annually

Type 2 diabetes

--

Initial exam: at diagnosis, then annually

Pregnancy (Type 1 or 2)

--

Initial exam: Before conception and early in the first trimester; Follow-up is based on the findings of the initial exam

Risk factor(s) for glaucoma

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Volume 99 Number 4 Fall 2018

While no known treatment will reverse vision loss due to glaucoma, topical treatments remain the standard of care and surgery may also be an option in select patients. Given the importance of proper administration and use of eye drops to vision preservation, it is estimated that between 25% and 90% of people who use eye drops do so incorrectly.

Studies have demonstrated that poor administration technique and lack of compliance lead to therapeutic failure, over-medication leading to systemic adverse effects, medication waste, and ocular disorders such as corneal abrasions, infections, and ulcerations. Senior patients using eye drops for chronic conditions such as glaucoma, may also have other chronic eye conditions (e.g., cataracts or macular degeneration) and when combined with age-related vision changes make reading medication and installation instructions very difficult. Older adults may also have problems with manual dexterity making it very difficult to self-administer eye drops.

The pharmacist can play a vital role in identifying patients at risk for glaucoma, recommending routine eye examinations based on the AAO’s guidelines, as well as counseling patients on the proper use of their eye medications. The following websites may be helpful to the pharmacist actively engaged in their patient’s eye care. http://www.safemedication.com/safemed/docs/ Eye-Drop-Flyer.pdf https://www.glaucoma.org/glaucoma/are-you-atrisk-for-glaucoma.php (information available in Spanish) https://www.glaucoma.org/GRF_Understanding_ Glaucoma_EN.pdf https://www.glaucoma.org/uploads/ug_es_ grf_2017.pdf (in Spanish) https://www.glaucoma.org/

Tina H. Thornhill, PharmD, FASCP, BCGP is an Associate Professor and Vice Chair for Professional Education at Campbell University College of Pharmacy & Health Sciences. Email: tina.h.thornhill@ gmail.com Bibliography Feder RS, Olsen TW, Prum Jr BE, et al. Comprehensive Adult Medical Eye Evaluation Preferred Practice Pattern Guidelines. Ophthalmology 2016; 123(1): P209-P236. Available at: https://www.aaojournal.org/article/S0161-6420(15)01269-5/pdf.

Gupta R, Patil B, Shah BM, et al. Evaluating eye drop instillation technique in glaucoma patients. J Glaucoma. 2012;21(3):189-192.

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Volume 99 Number 4 Fall 2018

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Volume 99 Number 4 Fall 2018

Member Spotlights!

New Practitioner Network – Spotlight

vacation time to make sure that the pharmacy did what it took to pass the accreditation process with flying colors. Again, this was not just so this pharmacy could have a check box for accreditation. Thanks to her efforts Rx Clinic Pharmacy can continue serving their patients in the community.

Huyen Dang, PharmD, is a 2014 graduate of the South University School of Pharmacy in Columbia, SC. She is a phenomenal community pharmacist because of the extra care and attention she provides to patients and the dedication she shows to her profession. With little to no experience, she was able to transform the Specialty Pharmacy program at Rx Clinic Pharmacy, an independent pharmacy in Charlotte, NC. This pharmacy provides life-saving specialty medications to hundreds of uninsured and underinsured people in the Charlotte community. In order to provide this service, they must be accredited

by URAC. Huyen came in as a pharmacy manager and had the task of getting the pharmacy reaccredited for URAC 3.0. This task was incredibly daunting, and the pharmacy was even told by the auditors that most independent pharmacies do not have the bandwidth or capacity needed to pass. Huyen spent countless hours even during her

Health-System Practice Forum – Spotlight Debra Pittman, PharmD, is the Assistant Director of Pharmacy and Residency Program Director at Carteret Health Care in Morehead City, NC. Debra received her doctor of pharmacy from Campbell University in 1992. She then completed a pharmacy practice residency at North Carolina Baptist Hospital in Winston-Salem, NC. Debra’s roles include overseeing all aspects of the medication use

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process, including procurement, prescribing, compounding, dispensing, storage of medications, administration, and monitoring.

She is responsible for quality improvement, medication safety, regulatory requirements, staff development, and the PGY-1 residency program.

Debra states that she “has been most proud of her team at Carteret for advancing the practice of pharmacy. We initiated a PGY-1 pharmacy residency program in 2012. This has taken the work of the entire team to build, develop, and improve our program. We also have an outstanding team of pharmacy technicians who are trained in multiple areas, with opportunities to advance into areas of oncology, preceptors, inventory, and information technology.” She adds that this highlights the fact that “advancing the practice of pharmacy can occur in all areas of our state.”

Debra has been a part of NCAP since completing her residency in 1993. “I am a strong believer in the power of our voices. NCAP has provided our pharmacists with opportunities to network, exchange innovative ideas, strengthen relationships among our practitioners, and quality CE programming. I encourage all staff to support NCAP.” Debra has most recently served as a member of the Health-System Practice Forum from 2013-2017.

Volume 99 Number 4 Fall 2018

New Practitioner Network: Personal Finance – Good Advice!

Dr. Vishal Barela Many people graduated from pharmacy school in May, and many more will soon graduate and enter the workforce. As a recent or soon-to-be grad, you are likely dealing with larger sums of money for the first time; therefore, managing money is more important now than ever.

What should you do with your new paycheck? Buy a car?

Take a great vacation? Although very tempting, two smart money moves you should consider include saving for retirement and creating an emergency fund.

Save for retirement now!

Although you are a new practitioner, take time now to think about saving for retirement!

Contemplate this question: what does retirement mean to you?

Does it mean a home in the mountains or at the coast? How about a part-time job and time with grandchildren? As a recent graduate, these questions may seem too far off to think about; however, it is a myth to think you have plenty of time to start saving for retirement. The longer your investments compound, the larger they will grow and increase your probability of attaining the retirement “dream” you want!

How can you start the saving process? First, take advantage of your employer’s retirement savings plan. These plans, called 401(k), 403(b), or 457(b), allow you to set aside a portion of your salary from each paycheck “pre-tax” permitting you to invest the money into tax advantaged accounts that also defers the taxes on the earnings you re-

ceive. These accounts allow you to compound the returns much faster than taxable investments.

Many employers offer matching contributions up to a specific dollar amount or percentage of your salary, which is more reason to utilize these retirement saving plans. Another advantage these plans offer is portability. You are allowed to transfer or “rollover” your account to your new employer’s plan if you leave your current employer.

Second, set-up automatic deductions from your payroll or checking account for deposit into an Individual Retirement Account (IRA.) These are tax advantaged accounts in which the individual contributes to the IRA and receives a tax deduction in the amount contributed if the individual’s income is below certain levels. The funds invested into the IRA are allowed to grow taxdeferred, meaning that the gains are not taxed until withdrawn.

Create an Emergency Fund!

What if something happens and you are out of work for several months? As a new earner one of the easiest and most effective savings goals is to create an emergency fund. An added bonus is that an emergency fund helps you get in the habit of saving. Financial advisors suggest that an emergency fund representing three to six months of living expenses be established for use in periods of unexpected financial difficulty. A frequent budgeting mistake is to save the amount you have left at the end of the month. When doing that, you of-

North Carolina Pharmacist

ten have nothing left for savings; therefore, make sure to deduct money from your paycheck as soon as you receive it. Most advisors recommend allocating a percentage of each paycheck to your emergency fund until you have the amount accumulated to meet your desired goal and then redirect this same amount towards your retirement account.

A word of caution: use your emergency fund for true emergencies! As your balance grows, it can be tempting to use that money to take a vacation. If impulsive spending is a problem, keep your fund in a separate savings account. This way, you are required to take several steps before getting access to those funds.

As a new practitioner, receiving a hefty paycheck for your hard work feels great, but spending impulsively lays down habits that can hurt you in the longrun.

Start your spending and saving habits on the right foot by saving for retirement and creating an emergency fund … you will never regret that you did!

Vishal Barela, PharmD; barnelavs@gmail.com Bibliography Kapoor J, Dlabay L, Hughes, Hart M. (2016) Focus on Personal Finance: An active approach to help you achieve financial literacy, 5th edition.

Ambrose E, Lankford K. (2018, March) Are you on Track to Retire? Kiplinger’s Personal Finance; 24 – 32.

Page 43 Volume 99 Number 4 Fall 2018

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Volume 99 Number 4 Fall 2018

Helping to Identify Patients at Risk for Opioid Overdose Improvements to the NC Controlled Substance Reporting System (CSRS) makes it easier for pharmacists to access important controlled substance related information for their patients. The system provides an “Overdose Risk Score” (ORS) that correlates with a daily morphine milliequivalent dose (MMED) range. Patients with a ORS of 450-650 equates to >50-90 MMED, and those with an ORS of 650 or greater have an MMED of greater than 90.

Patients at greater risk for overdose are: ·

MMED > 50

·

Concomitant use of an opioid and a benzodiazepine

·

Concomitant use of an opioid and alcohol

·

Patients with respiratory disease (including smoking), liver disease, renal disease, HIV/AIDS, or cardiac disease

Pharmacists can help make sure patients at greater risk for opioid overdose have naloxone on hand; and ensure that the patient can convey to family and friends, the signs and symptoms of an overdose, and how to administer naloxone in the event of an overdose.

Use the patient’s history, concomitant medications, and their ORS (calculated by the CSRS) to help identify patients for naloxone dispensing. The naloxone standing order can be used to dispense naloxone to patients you proactively identify as being at risk.

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Volume 99 Number 4 Fall 2018

CONTINUING EDUCATION PROGRAM FOR PHARMACISTS Overview of 2017 Updates to the Clinical Practice Guidelines for Clostridium Difficile Infection

By Dr. Allison Stilwell and Dr. Brandon Hill of this article, Clostridium difficile will continue to be referenced. (2)

Authors Allison Stilwell, PharmD (corresponding author) PGY2-Infectious Diseases Pharmacy Resident University of Virginia Health System Email: ams3vu@virginia.edu

Background

Brandon Hill, PharmD, BCPS Clinical Specialist – Infectious Diseases/Antimicrobial Stewardship University of Virginia Health System Objectives At the completion of this program, the participant will be able to: 1. Describe updates to Clostridium difficile infection (CDI) guideline recommendations 2. Identify target population for CDI testing and appropriate testing methodology 3. Utilize guideline recommendations to recommend appropriate treatment regimens for management of CDI in adult and pediatric patients

C. difficile is a Gram-positive, spore-forming anaerobic bacillus that is believed to be responsible for about 25% of all cases of infectious diarrhea. (3) Presence of C. difficile in stool is associated with various clinical manifestations from asymptomatic colonization to fatal colitis with associated septic shock. Pathogenesis centers on the disruption of normal gut microbiota by antimicrobial administration that allows for ingrowth of pathogenic microbes. (3) CDI is defined by the presence of symptoms (usually diarrhea) and either a stool test positive for toxins or detection of toxigenic C. difficile via molecular testing. The exact magnitude of CDI prevalence is difficult to quantify as diagnostic tests cannot differentiate colonization from infection.

Recent estimates based on positive laboratory results suggest 500,000 infections annually in the United States alone. (4) Elderly and immunocompromised patients are at highest risk for CDI; however, CDI should be considered in any patient presenting with a compatible clinical presentation.

Introduction

Mitigation of Risk Factors (1)

In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America issued an update to the 2010 clinical practice guideline for Clostridium difficile infection (CDI) in adults.

New recommendations have been made regarding testing and treatment considerations. For the first time in 30 years, treatment recommendations no longer include metronidazole as routine first-line treatment for CDI of any severity. (1) Also included are considerations for the management of C. difficile in children.

Of note, in 2018 the Clinical and Laboratory Standards Institute revised the nomenclature of Clostridium difficile to Clostridioides difficile, but for purposes North Carolina Pharmacist

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§ Minimizing frequency and duration of appropriate antimicrobial therapy § Implementation of an antimicrobial stewardship program § Restriction of inappropriate/overutilization of fluoroquinolones, clindamycin, and cephalosporins should be considered § Evaluation of appropriateness for ongoing proton pump inhibitor (PPI) use although there is insufficient evidence for discontinuation of PPIs as a measure for preventing CDI

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Diagnosis The available evidence for CDI diagnosis is poor. A defined threshold for number and frequency of loose stools has steadily declined in recent years. Updated recommendations state patients with “unexplained” and “new onset” of ≥ 3 unformed stools in 24 hours are the preferred target population for CDI, with the caveat that patients should not be tested after the receipt of laxatives in the preceding 48 hours.

Consensus regarding the best laboratory testing methods are lacking, but updated recommendations are contingent upon institutional criteria for patient stool submission (Figure 1). Various methods detect either C. difficile or its major toxins (A and B); the two toxins produce a marked inflammatory response in the colon, causing diarrhea and damage to mucosal epithelium. (3) Nucleic acid amplification tests (NAAT) detect toxin-producing genes, but whether this correlates with actual expression of toxin A or B is questionable. In other words, a positive NAAT can indicate colonization or infection; thus, stool samples should be appropriately evaluated prior to submission for diagnostic testing. (5) Glutamate dehydrogenase (GDH) immunoassays lack specificity, detecting a metabolic enzyme commonly present in all isolates of C. difficile.

A stool toxin test is a type of enzyme immunoassay (EIA) that uses antibodies to detect C. difficile toxins A and B. In order to increase sensitivity, GDH tests are best used as initial screening combined with toxin testing and/or molecular testing for gene detection.

If no institutional guidelines are in place (and thus specimens with a lower probability of having CDI may be routinely obtained), NAAT alone has an unacceptably high false-positive rate; therefore, a multistep approach incorporating stool toxin testing is preferred.

(1) Figure 1. Clostridium difficile infection laboratory test recommendations

North Carolina Pharmacist

GDH = glutamate dehydrogenase immunoassay EIA = enzyme immunoassay, type of stool toxin test NAAT= nucleic acid amplification test Adapted from Figure 2 in Clinical Practice Guidelines for Clostridium difficile Infection (1) If testing for CDI results are negative, repeat testing during the same episode of diarrhea should be avoided. It is now recommended not to retest within 7 days.

Previous studies have demonstrated a diagnostic yield of approximately 2% for repeat testing within 7 days. (6,7) Furthermore, greater than 60% of patients remain C. difficile positive after successful treatment, suggesting no clinical value in repeat testing to establish cure. (8,9) Treatment Recommendations (Table 1) Subtle changes have been made to severity definitions of CDI. Severity criteria used to guide treatment decisions were previously based on expert opinion and had not been validated at that time. (10) Recently published studies utilized WBC count and serum creatinine as supportive clinical data to differentiate CDI severity. (11) Mild or moderate severity is now categorized as non-severe and fulminant CDI has replaced the previously defined severe, complicated classification that may be characterized by hypotension, shock, ileus, or megacolon. The baseline creatinine has changed to an absolute value as true baseline values are not always available. Of note, these clinical criteria do not perform well for patients with underlying hematologic malignancies or renal insufficiency likely due to frequency of baseline abnormalities. (12) First and foremost, therapy with inciting antibiotic agent(s) should be discontinued if benefits outweigh risks as continued use has shown to decrease clinical response while increasing recurrence rates. The most common agents used for treatment of CDI include oral vancomycin, fidaxomicin, and metronidazole.

Vancomycin must be administered enterally due to inadequate gut lumen concentrations after intravenous administration. (13) Fidaxomicin is a macrocyclic antibiotic with minimal bioavailability and available only in oral dosages. (14) Neither vancomycin nor fidaxomicin is significantly absorbed when administered orally leading to few associated systemic adverse effects.

Their ability to achieve high fecal concentrations is the primary driver of treatment efficacy. Metronidazole is efficiently absorbed with small quantities reaching the colon, a disadvantage compared to the aforementioned agents. (15) Metronidazole can be associated with systemic side effects such as nausea, headache,

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taste perversion, and peripheral neuropathy. In addition, case reports exist where metronidazole induced encephalopathy in patients with liver disease. (16,17) Initial episode: non-severe and severe For an initial episode of CDI, either oral vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily is now recommended. In settings where access to oral vancomycin or fidaxomicin is limited, metronidazole may be used for an initial episode of nonsevere CDI only. The original evidence supporting the use of metronidazole for CDI is based on two small, randomized controlled trials conducted in the 1980s and 1990s that found no difference in outcomes compared to oral vancomycin. (18,19) Since 2000, additional randomized, placebo-controlled trials have demonstrated superiority of oral vancomycin over metronidazole in patients with severe CDI. (20, 21) Of note, cost and utilization analyses were not considered in the formulation of these recommendations.

Fidaxomicin is now placed as an alternative drug of choice for initial episodes of CDI following results of two large studies. (14,22) When compared to oral vancomycin, fidaxomicin was similar with regard to resolution of diarrhea at end of therapy; it was associated with significantly lower recurrence rates one month after completion. (14,22) Recommended treatment duration for both non-severe and severe CDI is 10 days of therapy. If patients have delayed response to therapy, 14 days is acceptable. (10) Delayed response was attributed to mean duration of symptoms in a retrospective study comparing response rates between oral vancomycin and metronidazole. Compared to metronidazole, oral vancomycin was associated with significantly shorter duration of symptoms (3 days vs 4.6 days; p<0.01). (23) Initial episode: fulminant For fulminant CDI, oral vancomycin at an increased dosage of 500 mg four times daily is recommended.

While the use of higher oral vancomycin doses is not evidence-based, authors for 2017 guideline updates state it seems prudent given the severity of illness. If ileus is present, recommendations exist to administer intravenous metronidazole in addition to oral or rectal vancomycin. This is centered around rationale that an ileus may impair delivery of orally administered vancomycin to the colon and intravenously administered metronidazole is likely to achieve therapeutic concentrations in an inflamed colon due to lack of dependence on gastrointestinal transit. In a single-center, retrospective, observational, comparative study of North Carolina Pharmacist

critically-ill patients, in-hospital mortality was higher in the oral vancomycin group compared to combination oral vancomycin plus intravenous metronidazole group (36.4% vs 15.9%; p=0.03, NNT=5). (24) Selected patients may require early surgery as illustrated by a retrospective cohort study of patients with CDI that required intensive care unit (ICU) admission or prolongation of ICU stay. Emergency colectomy reduced 30-day mortality in a subset of patients and rising WBC count (>20,000) or rising lactate level (2.2-4.9 mmol/L) were identified as markers of poor prognosis without surgery. (25) Recurrent CDI Treatment for recurrent CDI is dependent on therapy used to treat the initial episode. First recurrence after treatment with a standard 10-day course of oral vancomycin can be treated with oral vancomycin as a tapered and pulsed regimen (see Table 1) or with a 10-day course of fidaxomicin. If metronidazole was used for treatment of primary episode, a standard 10day course of oral vancomycin rather than a second course of metronidazole should be used. Of note, metronidazole should not be used for treatment of recurrent CDI due to potential cumulative neurotoxicity.

(16,17) Antibiotic treatment options for patients with more than one recurrence include tapered and pulsed oral vancomycin, a standard course of oral vancomycin followed by rifaximin or fidaxomicin.

Extended Duration of Therapy There are insufficient data to recommend extending the length of anti-C. difficile treatment beyond the standard treatment course (10-14 days) when a patient requires ongoing systemic antibiotic therapy for other infections. Similarly, there are insufficient data to recommend re-starting an anti-C. difficile agent empirically for patients who require re-treatment with antibiotics shortly after completion of CDI treatment.

There have been two retrospective cohort studies comparing the risk of recurrent CDI in patients receiving subsequent antibiotics that compared those who were empirically treated with another course of oral vancomycin and those who were not. (26,27) Both studies showed a decreased risk of subsequent CDI in patients treated empirically with oral vancomycin.

The updated stance of guideline experts is that there is insufficient evidence to recommend prophylaxis, but if utilized, lower doses of oral vancomycin (125 mg once daily) or fidaxomicin (200 mg once daily) may be advised while systemic antibiotics are administered as long-term effects are unknown.

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Fecal Microbiota Transplantation Previous guidelines discussed successes of stool instillation from a healthy donor in several uncontrolled case series, though the role of “fecal transplantation” remained questionable. (10) Evidence supporting fecal microbiota transplantation (FMT) has increased and FMT is considered an option for patients with multiple recurrences (at least 3 total CDI episodes) who have failed appropriate treatment. Patients not receiving anti-C. difficile treatment prior to planned FMT should receive an “induction course” of oral vancomycin for 3-4 days prior to FMT with a goal of reducing the burden of vegetative C. difficile. (28) It should be noted that FMT success rate is dependent on the route of instillation, with highest success rates associated with instillation via the colon.

Table 1. Treatment recommendations for Clostridium difficile Infection in Adults

Initial

Episode Type

Clinical Definition

Supportive Clinical Data

Non-severe

WBC ≤15,000 cells/mL and SCr <1.5 mg/dL

Severe

WBC ≥15,000 cells/mL or SCr >1.5 mg/dL

Fulminant

Hypotension, shock, ileus, or megacolon

Recommended Treatment VAN 125 mg PO QID for 10 days OR FDX 200 mg PO BID for 10 days Alternate: Metronidazole 500 mg PO TID for 10 days VAN 125 mg PO QID for 10 days OR FDX 200 mg PO BID for 10 days VAN 500 mg PO QID or by NG tube plus Metronidazole 500 mg IV TID Ileus: +/- rectal vancomycin, Metronidazole 500 mg IV TID If metronidazole for initial episode: VAN 125 mg PO QID for 10 days Standard vancomycin for initial episode: Prolonged tapered and pulsed VAN regimen: Example = 125 mg PO QID for 10-14 days, BID for 7 days, one time daily for 7 days, and every 2-3 days for 2-8 weeks OR FDX 200 mg PO BID for 10 days

Recurrence

1st recurrence

2nd or subsequent recurrence

VAN tapered/pulsed OR VAN 125 mg PO QID for 10 days followed by rifaximin 400 mg TID for 20 days OR FDX 200 mg PO BID for 10 days OR Fecal microbiota transplantation

WBC = white blood cells; SCr = Serum Creatinine; VAN = Vancomycin; PO = oral; BID = twice daily; NG = nasogastric; FDX = Fidaxomicin; IV = intravenous; TID = three times daily; QID = four times daily Adapted from Table 1 in Clinical Practice Guidelines for Clostridium difficile Infection (1) Pediatric Recommendations Due to high prevalence of asymptomatic carriage of toxigenic C. difficile in infants (10-55%), testing for CDI should never be routinely recommended for neonates or infants ≤12 months of age with diarrhea. (29) Additionally, testing for C. difficile should not be routinely performed in children with diarrhea who are 1-2 years of age unless other infectious or non-infectious causes have been excluded. For children greater than 2 years of age, C. difficile testing is recommended with prolonged or worsening diarrhea and risk factors (e.g., underlying inflammatory bowel disease or immunocompromising conditions) or relevant exposures (e.g., frequent contact with the healthcare system or recent antibiotics).

Treatment of CDI in pediatrics more closely mimics adult guideline recommendations from 2010. MetronidaNorth Carolina Pharmacist

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zole or oral vancomycin is a treatment option for initial episodes and first recurrence of non-severe CDI, due to less evidence of the comparative effectiveness of these agents in pediatrics. For children with an initial episode of severe CDI, oral vancomycin is recommended over metronidazole. Evidence for this is extrapolated from adult randomized controlled trials demonstrating improved outcomes in patients with severe CDI treated with oral vancomycin compared to oral metronidazole. Second or greater episodes of recurrent CDI should also be treated with oral vancomycin. (20,21) Similar to adults, FMT can be considered for pediatric patients with multiple recurrences of CDI following standard therapy.

Summary of Key Points

·

Significant changes to the clinical practice guidelines for CDI include testing methods for diagnosis and first-line treatment recommendations.

·

Testing for CDI is contingent upon institutional criteria for patient stool submission by clinicians and acceptance by laboratory personnel: NAAT alone or use of multi-step algorithms is preferred.

References 1. McDonald LC, Gerding DN, Johnson S, et al.

Clinical practice guidelines for Clostridium difficile infection in Adults and Children: 2017 Update by the Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48.

2. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 28th ed. CLSI supplement M100. Wanye, PA: Clinical and Laboratory Standards Institute; 2018.

3. Gerding DN and Young VB. “Chapter 256: Clostridium difficile infections.” Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 8eEds. John E. Bennett, Raphael Dolin, Martin J. Blaser. Philadelphia, PA: Elsevier/Saunders, 2015.

4. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States.

N Engl J Med. 2015; 372:824-34.

5. Burnham CA, Carroll JC. Diagnosis of Clostridium difficile infection: an ongoing conundrum for clinicians and for clinical laboratories. Clin Microbiol Rev. 2013; 26:604-30.

·

Treatment with metronidazole is no longer recommended as first-line therapy of non-severe, severe, or recurrent episodes of CDI.

6. Aichinger E, Schleck CD, Harmsen WS, Nyre Lm, Patel R. nonutility of repeat laboratory testing for detection of Clostridium difficile by use of PCR or enzyme immunoassay. J Clin Microbiol. 2008; 46:3795-7.

·

Either oral vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily for 10 days is recommended.

7. Cardona DM, Rand KH. Evaluation of repeat Clostridium difficile enzyme immunoassay testing.

J Clin Microbiol. 2008; 46:3686-9.

·

Intravenous metronidazole is recommended in addition to oral vancomycin in patients with fulminant CDI.

·

Recommended duration of therapy is 10 days, and treatment courses should not be extended for prolonged courses of systemic antibiotic therapy.

8. Abujamel T, Cardnum JL, Jury LA, et al. Defining the vulnerable period for re-establishment of Clostridium difficile colonization after treatment of C. difficile infection with oral vancomycin or metronidazole. PLoS One. 2013; 8:e76269.

The author(s), editorial staff, nor peer reviewers contributing to the content of this article have no relevant financial relationships with commercial interests to disclose.

The author(s), editorial board and the North Carolina Association of Pharmacists disclaim any liability to you or your patients resulting from reliance solely upon the information contained herein.

North Carolina Pharmacist

9. Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015; 313:1719-27.

10. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010; 31(5):431-455.

11. Bauer MP, Hensgens MP, Miller MA, et al. Renal failure and leukocytosis are predictors of a com-

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plicated course of Clostridium difficile infection if measured on day of diagnosis. Clin Infect Dis. 2012; 55(Suppl 2):S149-53.

non-inferiority, randomized controlled trial. Lancet Infect Dis. 2012; 12:281-9.

12. Shah DN, Bhatt NS, Welch JK, Koo HL, Garey KW. Defining acute renal dysfunction as a criterion for the severity of Clostridium difficile infection in patients with community-onset vs hospital-onset infection. J Hosp Infect. 2013; 83:294-9.

13. Martin, Steven, and Rose Jung. “Chapter 91.

Gastrointestinal Infections and Enterotoxigenic Poisonings.” Pharmacotherapy: A Pathophysiologic Approach, 9eEds. Joseph T. DiPiro, et al. New York, NY: McGraw-Hill, 2014.

23. Wilcox MH, Howe R. Diarrhoea caused by Clostridium difficile: response time for treatment with metronidazole and vancomycin. J Antimicrob Chemother. 1995;36:673-9.

24. Rokas KEE, Johnson JW, Beardsley JR, et al. The addition of intravenous metronidazole to oral vancomycin is associated with improved mortality in critically ill patients with Clostridium difficile infection. Clin Infect Dis. 2015 Sep 15; 61(6):934-41.

14. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011; 364:422-31.

25. Lamontagne F, Labbe AC, Haeck O, et al. Impact of emergency colectomy on surivival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg. 2007; 245:267-72.

15. Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile. Gut. 1986; 27:1169-72.

26. Carnignan A, Poulin S, Martin P, et al. Efficacy of secondary prophylaxis with vancomycin for preventing recurrent Clostridium difficile infections.

Am J Gastroenterol. 2016; 111:1834-40.

16. Yamamoto T, Abe K, Ankiki H, Ishii T, Kuyama Y. Metronidazole-induced neurotoxicity developed in liver cirrhosis. J Clin Med Res. 2012; 4:295-8.

27. Van Hise NW, Bryant AM. Hennessey EK, Crannage AJ, Khoury JA, Manian FA. Efficacy of oral vancomycin in preventing recurrent Clostridium difficile infection in patients treated with systemic antimicrobial agents. Clin Infect Dis. 2016; 63:6513.

17. Knorr JP, Javed I, Sahni N, Cankurtaran CZ, Ortiz JA. Metronidazole-induced encephalopathy in a patient with end-stage liver disease. Case Reports Hepatol. 2012; 2012:209258.

18. Teasley DG, Gerding DN, Olson MM, et al. Prospective randomized trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhea and colitis. Lancet. 1983; 2:1043-6.

19. Wenisch C, Parschalk B, Hasenhundl M, Hirschl AM, Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996; 22:813-8.

20. Zar FA, Bakkanagar SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007; 45:302-7.

21. Johnson S, Louie TJ, Gerding DN, et al. Polymer alternative for CDI treatment (PACT) investigators. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014; 59:345-54.

22. Cornely OA, Crooke DW, Esposito R, et al. OPT80-004 Clinical Study Group. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, North Carolina Pharmacist

28. Rubin TA, Gessert CE, Aas J, Bakken JS. Fecal microbiome transplantation for recurrent Clostridium difficile infection: report on a case series.

Anaerobe. 2013; 19:22-6.

29. Donta ST, Myers MG. Clostridium difficile toxin in asymptomatic neonates. J Pediatr. 1982; 100:4314.

This article and completion of the assessment quiz is a knowledge-based correspondence continuing education activity accredited by the North Carolina Association of Pharmacists as the provider of NC-CE continuing pharmacy education. This activity is approved for 1.0 correspondence hours (0.1 CEUs) under the NC-CE activity number NCP1018. To access the quiz for continuing education click here or go to https://www.ncpharmacists.org/quiz_list.asp

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