AJP Spring 2018

Arizona Journal of Pharmacy Spring 2018

AzPA Annual Convention

Ingredients

for

Success

June 14 - 17, 2018

The official publication of the Arizona Pharmacy Association brought to you by the Pharmacy Network of Arizona

Table of Contents

Board of Directors

President’s Message Association News

PAPA Message Legislative Update

Featured Highlights A Review of Pharmacologic Treatment Modalities for Post-Operative Phantom Limb Pain Financial Forum: Getting (Mentally) Ready to Retire

Continuing Education Role of the Pharmacist in Tuberculosis Management

Career Center

Check out the AzPA Career Center online. Find the best pharmacy-related jobs in the state, or search through resumes of the most highly qualified pharmacists Arizona has to offer. Ask about our employer advertising. azpa.webscribble.com

A r i z o n a P h a r m a c y A s s o c i a t i o n

2017-2018 Board of Directors

Officers

Lorri Walmsley Past President

az-aCCp Chapter Stacey Hollen, Chair

Boesen President Lisa Tonrey treasurer Whitney Rice secretary Jessica DiLeo President-elect

Industry representatIve John Fezza

CommunIty pharmaCy aCademy

Susana Horst, Chair Jaime Von Glahn, Chair-Elect

health-system aCademy

Jeannie Hong, Chair Aimee (Keller) Itaaehau, Chair-Elect

managed Care aCademy

James Montague, Chair Patrick Hryshko, Chair-Elect

student pharmaCIst aCademy

Brian Seigfried, Chair, MWU Justin Spicer, Chair-Elect, MWU Candice Eastman, Chair, U of A Kassie Notbohm, Chair-Elect, U of A

teChnICIan aCademy

J.R. Gill, Chair Kevin Reger, Chair-Elect

dIstrICt dIreCtors

Laura Moore, Northeast Lynette Wasson, Northwest Jacob Schwarz, Southwest

dean of Colleges Mitchell R. Emerson, Midwestern University CPG Rick G. Schnellmann, University of Arizona COP

legal Counsel Roger Morris azpa staff Kelly Fine, Chief Executive Officer Cindy Younger, Accounting Deborah Marcum, PAPA Taylor Daly, Membership Cindy Esquer, Operations Kathy Harty, Continuing Education

The interactive digital version of the Arizona Journal of Pharmacy is available for members only online at www.azpharmacy.org/ajp (480) 838-3385 web@azpharmacy.org

EDITOR’S NOTE: Any personal opinions expressed in this magazine are not necessarily those held by the Arizona Pharmacy Association. “Arizona Journal of Pharmacy” (ISSN 1949-0941) is published quarterly by the Pharmacy Network of Arizona at: 1845 E. Southern Avenue, Tempe, AZ 85282-5831.

edItor

Kelly Fine, R.Ph., FAzPA

Managing Editor

Cindy Esquer

Editorial Board

Lindsay Davis, Pharm.D. Whitney Rice, Pharm.D. Andrea Burns, Pharm.D. Christi Jen, Pharm.D. Nicole Scovis, Pharm.D.

Creative Coordinator

Kelly Fine, R.Ph., FAzPA

Keith

P r e s i d e n t ’s M e s s a g e

Dear AzPA Members,

Spring is in full effect and Summer will be on us before we know it. We have so much to celebrate since the last journal: the frost has melted, baseball has started, everything is blooming, it has not rained in months, the pollen count is ridiculous, and the dust storms along the freeway are a mess. Wow…my apologies, that list escalated quickly. Let’s try this again, the Association has several accomplishments worth celebrating!

• We had a successful legislative session with all of our bills of interest passing

• Launched a new website, which looks fantastic. Check it out today! azpharmacy.org

• The bylaws were voted by you…and passed!

The passing of the bylaws was very exciting for the Board of Directors. We put a great deal of work into those and honestly did so with the intentions of doing what we feel would be in the best interest of the association both now and in the future. The board would like to formally thank you all for voting and believing in our vision.

Speaking of the bylaws, it is time for everyone to vote for your next President Elect and four new Director at Large positions. The nomination committee did a great job of slating the ballet with well-qualified and diverse applicants from various practice settings, which was not easy with all of the amazing people whom were nominated.

Get online and VOTE…VOTE…VOTE…VOTE…VOTE!

Now let’s look towards the future, the Annual Convention is this June 14-17 at the Sheraton Grand at Wild Horse Pass in Phoenix! Early reports put the temps in the mid 80’s, perfect to learn, laugh, and lounge. Go online today (azpharmacy.org) to the events tab for more information on the meeting. Follow the simple links at “Register Today” and “Book My Room” to complete your registration. The theme this year is “Ingredients for Success.” This just might be my favorite convention yet as I look to embrace the role of Past President. Lorri Walmsley made the job of Past President look so easy and according to Facebook, she even got a cruise! Can’t wait to set sail.

All kidding aside, next year is going to be exciting with Jessica DiLeo as President. She will bring passion and enthusiasm to the association and our profession; I can’t wait for the year to come. It has been a fantastic year serving as President and I cannot thank the BOD, and the office enough for all of their work and support. Most importantly, it is the membership that I owe the greatest amount of thanks and praise. The engagement of the members is truly amazing and I want to thank every one of you for all the support and volunteer work you all do to make this association remarkable. The membership is what makes this association so strong and will lead to its success for years to come

Keith Boesen, PharmD, CSPI AzPA President 2017-2018

A s s o c i a t i o n N e w s

MISSION STATEMENT

AzPA serves and represents all pharmacy professionals by fostering safe and effective medication therapy, promoting innovative practice, and empowering its members to serve the health care needs of the public.

VISION

Empowering pharmacy professionals to provide optimal patient care.

AdvancingPharmacytoImproveHealthcare

WELCOME NEW MEMBERS

PHARMACISTS

Sara Bekele

DaVida Ashlee Eppes

Briana Fisher Shirley H. Diaz

Hernandez Michael A.Kaminski

Lessel K. Lamkin Kelsey Lombard Carla Martin Allan Miller

Nebil Mohammed Greg Roller Michael Spahich Madison Stevens Kelly Stone

Jeff Szubinski

Jessica K Trujillo

Ann Turner Beth Zerr

RESIDENTS

Corey Frahm Jonathan Harmon Kristyn Sanders

Thao T. Truong Ronald Velasquez

STUDENTS

Matthew Barber Tony Coombe Bradley Crotts

Andres Cruz Angelica Itliong Lu

Robert McMahon Crystal Pease Vinay Sanyasi Susan Shihale Ossy Sutjita

TECHNICIANS

Jermaine Amos Adriana Carrasco Stephanie E. Chacon Lynda Corngrinder

Ashley Nicole Mills Lorena Reyna Steven Walter

TECNICIANS IN TRAINING

Julia

NEW MEMBERS: Visit your Member Center to learn how to get more involved with AzPA.

Located on www.azpharmacy.org homepage.

Premraj

Pharmacists Assisting Pharmacists of Arizona (PAPA)

So now what do I do?

The unwelcome news that a loved one is abusing or possibly addicted to drugs or alcohol can be paralyzing; especially when you have no practical experience in dealing with this issue. Perhaps you have a number of relatives who have histories of addiction, but when it hits the immediate family circle, the impact is very different. The question often asked by family members facing the very real and very ugly truth that one of their family members has developed a drug or alcohol problem is, “So now what do I do?”

The Do’s Of Supporting an Addicted Loved One

Do support recovery. This must be your primary task. While that may have little meaning to you at this point, it truly is the foundation upon which everything else must be built. The message you need to send to your addicted loved one, as well as the other members of your family and close friends impacted by this news, is that you will support recovery no matter what it takes. Do educate yourself. The amount of education on addiction available to you is remarkable. As a discerning consumer of education you will need to be diligent in determining what information is sound and what is speculation or personal opinion. A frequently overlooked resource is available at treatment centers in your area. Good treatment programs include a family week or family weekend component. This provides families, with loved ones undergoing treatment, an opportunity to obtain cutting edge information on recovery and to interact with the treatment professionals working there. What you may not know is that most treatment programs will allow you to participate in their family program even if your loved one is not in treatment!

Do learn the myths and facts of addiction. While we live in an age of unparalleled access to information, the myths about addiction are as abundant as ever. The Internet has made good information abundantly available and has also provided a powerful medium for distortions, innuendo and outright falsehoods. The following link will lead you to a brief listing of some of these myths and facts: www.interventionaz.com. Also, check out the work of Dr. Daniel Amen at www. amenclinics.com. Dr. Amen is a leading researcher into the neurological aspects of addiction.

Dr.JerryLaw,D.Min.,MDAAC,CIP

(PAPA) Continued

Do ask your addicted loved one what you can do to help. You may be surprised at what he or she will tell you. Do listen with an open heart and mind. This may be very difficult, especially when everything inside you wants to scream, “Have you lost your mind?” Do be patient and practice non-judgmental communication. Remember that well over ninety percent of all communication is non-verbal. Do listen, but don’t fix. Recovery is about learning to live life on life’s terms and that includes abstinence from alcohol, drugs and many dysfunctional behaviors that rob people of the joys of life.

Do recommend professional help. Be discerning in how you suggest such help. Accusatory statements such as, “Man, you need help! Don’t you see it?” are likely to be met with great resistance. of presence. If your addicted loved one refuses to get help, by all means consider Intervention.

Do be honest. Do show love, care and concern. Your addicted loved one is living a world that is largely based on lies, deceit and manipulation. As terrible is it may be, you have been deceived. The loved one you thought you knew so well has lied to you and perhaps stolen your trust as well as your possessions in order to support their habit. Be honest with your loved one. Practice rigorous honesty that takes into consideration the well-being of your loved one rather than brutal honesty that is based in “what’s best for me” or worse yet a desire to punish.

Do be a good role model. Unfortunately, some family members may take the attitude of “I’ll drink anytime I feel like it. That’s his or her problem not mine.” Drinking or using drugs in front of your loved one is not going to send a message that supports recovery. Addiction is a family disease and recovery is a family journey. You do not have to tiptoe around a recovering addict, but there is no need to “rub his or her nose in it” either by intentionally participating in behaviors that are known triggers to relapse for your loved one.

Do understand that recovery takes time. As stated above, recovery is not just about abstinence. The recovering individual most likely did not become an addict overnight. The associated behaviors may be deeply ingrained. Just because he or she is dry does not mean the problems go away easily. Do go to meetings and get a sponsor. Do go to meetings and get a sponsor. Do go to meetings and get a sponsor! Family members need support systems too. Your own recovery is important! While your loved one pursues a path of recovery, take advantage of family support programs. Whether it is AlAnon, Nar-Anon, CODA, Celebrate Recovery, PALS or any of a wide variety of support groups, reach out for the help that is available for you.

The Don’ts Of Supporting An Addicted Loved One

The list of what to do in supporting an addicted loved one began with the simple recommendation to support recovery. In a similar manner, the don’ts of supporting your addicted loved one must begin with don’t support the disease Your best wishes, unaccompanied by the elimination of ways in which you support your loved one’s addiction, are unlikely to bring about any alteration in his or her dangerous behaviors.

(PAPA) Continued

Don’t enable your loved one. Enabling behaviors allow your loved one to continue in his or her disease. You are not helping when you do these things. You are enabling your loved one to continue down this destructive path. You are simply delaying the inevitable. Don’t enable!

Don’t try to control the life of your addicted loved one. Getting your loved one into treatment is not about controlling his or her life, it is about regaining control of yours! If he or she is a minor, however, make sure you understand your rights under state statutes and use the full leverage of the law to get your loved one help. His or her “rights” are not as important as his or her life. Don’t lay guilt or shame on your loved one. As much as you believe you are justified in pointing out how wrong your loved one may be or how he or she has been raised to know better, don’t give in to the temptation to blame. You will hand your loved one the very ammunition he or she is looking for to rationalize the continuation of the behavior.

Don’t take it personally. Your addicted loved one is “under the influence” twenty-four seven. While he or she may not be intoxicated all the time, the influence is still there. You may be called names or blamed for things you have nothing to do with. It is the disease talking, and you will need to remind yourself of this fact often.

Don’t tolerate any use of illegal drugs. By definition, even casual use of illegal drugs is a violation of the law. Do not tolerate the use of these products at any level. Be equally strong against the improper use of prescription drugs. Take a zero tolerance position in this issue.

The Do’s and Don’ts of Supporting an Addicted Loved One

Recommended Do’s

• Do support recovery

• Do educate yourself

• Do learn the myths and facts

• Do ask what you can do to help

• Do listen with an open heart and mind

• Do be patient and practice nonjudgmental communication

• Do ask how he or she is feeling

• Do listen, but don’t fix

• Do demonstrate that you want the best for your loved one

• Do recommend professional help

• Do be honest

• Do support all activities suggested by the treatment care team

• Do encourage social activities that do not include alcohol or drugs of

any kind

• Do understand your loved one is not looking for pity

• Do be a good role model

• Do understand that recovery takes time

• Do recognize that recovery work must be done by the addict

• Do go to Al-Anon meetings and get a sponsor for yourself

Recommended Don’ts

• Don’t Support the disease

• Don’t enable your loved one

• Don’t interfere with your loved one’s privacy

• Don’t try to control the life of your addicted loved one

• Don’t lay guilt or shame on your

Pharmacists Assisting Pharmacists of Arizona (PAPA)

loved one

• Don’t make threats

• Don’t make promises you cannot keep

• Don’t use scare tactics. They are generally futile

• Don’t offer more help than you are qualified to give

• Don’t take it personally

• Don’t promote opportunities for relapse

• Don’t tolerate any use of illegal drugs

• Don’t tolerate off-label use of legal

• drugs

If you or someone you care about is suffering from an alcohol and/or chemical dependency problem...help is available. Contact the AzPA Office at 480.207.7869 or papa@azpharmacy.org

Pharmacists Assisting Pharmacists of Arizona “A Partnership in Caring”

All calls confidential. Caller remains anonymous. PAPA is a program of the Arizona Pharmacy Foundation

L e g i s l a t i v e U p d a t e

2018 Legislative Update | Bill Tracking

SB 1001: Special Session

• Dispensing pharmacists will be required to review the PMP record of a patient receiving a CII for the preceding 12 months at the beginning of each new course of treatment.

• Prescribers can no longer dispense CII’s except for medicalassisted treatment (MAT) for substance abuse.

• A veterinarian who reasonably suspects or believes that a client or person is trying to obtain CS with an intent other than to treat the patient animal shall report that suspicion within 48 hours.

• Prescribers are required to limit initial prescriptions to no more than a 5-day supply and no more than 90 morphine milligram equivalents per day, except in specified circumstances.

• The initial five-day limitation does not apply if:

• The prescription is following a surgical procedure

• The patient has an active oncology diagnosis;

• The patient has a traumatic injury, excluding a surgical procedure;

• The patient is receiving hospice care, end-of-life care, palliative care, treatment for burns or skilled nursing care;

• The patient is receiving MAT for a substance use disorder; or

• The patient is an infant being weaned off opioids at the time of hospital discharge.

• The bill phases in a requirement that all CII’s must be dispensed with an electronic prescription order by July 1, 2019.

Status of Bill

• Signed by the governor on January 26th and goes into effect on April 26th.

HB 2086: Diabetes Management

• Amends diabetes management statute for districts and charters to include pharmacists as health professionals who may manage a student’s diabetes treatment and who may train volunteer diabetes care assistants.

Status of Bill

• AzPA’s diabetes management in schools bill was signed by the governor on April 16th.

HB 2107: Prescription Drug Costs; Patient Notification

• A pharmacy benefits manager (PBM) cannot prohibit a pharmacy or pharmacist from providing an insured individual information on the amount of the insured’s cost share for the insured’s prescription drug and the clinical efficacy of a more affordable alternative drug if one is available.

• A PBM cannot require a pharmacy or pharmacist to charge or collect from an insured a copayment that exceeds the total submitted charges by the network pharmacy. To the extent that these provisions are inconsistent or conflict with an applicable federal law, rule or regulation, the applicable federal law, rule or regulation applies. Applies to all contracts between a PBM and a pharmacy or a pharmacy’s contracting representative or agent that are entere4d into or renewed on or after the effective date of this legislation.

Status of Bill

• AzPA’s PBM bill as signed by the governor on April 5th.

HB 2149: Remote Dispensing Pharmacies

• For the purpose of pharmacy licensure and regulations, the definition of “pharmacy” is expanded to include a “remote dispensing site pharmacy” (defined) where a pharmacy technician or pharmacy intern prepares, compounds or dispenses prescription medications under “remote supervision by a pharmacist” (defined as a pharmacist directing and controlling their actions through the use of audio and visual technology).

• A remote dispensing site pharmacy is required to obtain and maintain a pharmacy license issued by the Board of Pharmacy. Additional licensing requirements for remote dispensing site pharmacies are established, including requirements for continuous video surveillance, a recordkeeping or inventory

requirements. Establishes minimum experience and professional education requirements a pharmacy technician must have before preparing, compounding or dispensing prescription medications at a remote dispensing site pharmacy.

• A pharmacist is limited to supervising one remote dispensing site pharmacy if the pharmacist is simultaneously supervising and dispensing at another licensed pharmacy, and is limited to two if the pharmacist is not simultaneously supervising and dispensing at another licensed pharmacy.

Status of Bill

• The telepharmacy bill was signed by the governor on March 20th.

SB 1034: Committee of Reference; Standing Committee

• Each standing committee of both legislative houses constitutes a committee of reference in the committee’s subject matter area and the committee’s respective house, instead of a committee of reference being a joint subcommittee composed of members of the appropriate standing committees of the House and Senate. Also modifies deadlines for the submission of various reports to or from committees of reference.

Status of Bill

• The sunrise reform bill passed House Rules on March 26th and went through the caucus on March 27th.

• It has been pulled from the consent calendar and will require additional floor amendment with a few clarifying and technical changes.

Who’s Representing

Kelly L. Fine, R.Ph., FAzPA AzPA Chief Executive Officer (left)

Jessie Armendt Compass Strategies

AzPA Contract Lobbyist (right)

Ken Bykowski, BS Pharm, MSHSA (left)

Mark Boesen, JD, Pharm.D., FAzPA (right)

AzPA Legislative Committee Co-Chairs

2018 Annual Convention

June 14-17, 2018

This four-day annual conference provides continuing education, recognition, and networking opportunities for pharmacy professionals of all practice settings.

Presented by:

Schedule at a Glance

Thursday June 14, 2018

8:00am - 5:00pm

8:00am - 5:00pm

8:00am - 5:00pm

5:30pm - 7:00pm

7:00pm - 8:00pm

Friday June 15, 2018

6:30am - 5:00pm

7:00am - 5:30pm

8:30am - 9:30am

9:45am - 10:45pm

11:00am - 12:00pm

1:00pm - 2:30pm

2:45pm - 3:45pm

4:00pm - 5:30pm

5:30pm - 7:00pm 7:00pm - 8:30pm

Morning Coffee & Lunch Included | *Separate, Pre-registration required for Certificate Programs

AzPA Immunization Certificate Program*

AzPA Psychiatric Certificate Program *

APhA’s The Pharmacist & Patient-Centered Diabetes Care Certificate Training Program* AzPA Board of Directors Meeting

Welcome Reception (Open to all Conference Registrants)

Lunch & Dinner Included

Registration Desk Hours

4th Annual Southwestern States Residency Conference (Separate registration fee)

General Session I

Breakout Sessions 1 & 2 Breakout Sessions 3 & 4

General Session II Breakout Sessions 5, 6 & 7

General Session III

Exhibit Hall with Dinner Buffet Dessert Reception hosted by Midwestern University- Glendale

Saturday June 16, 2018

6:30am - 5:00pm

8:30am - 10:00am

10:00am - 11:15am

10:00am - 11:15am

11:30am - 12:30pm 12:30am - 2:00pm 12:30pm - 2:00pm

2:15pm - 3:30pm

2:15pm - 3:30pm

3:45pm - 4:45pm

3:45pm - 5:15pm

5:30pm - 6:30pm

6:30pm - 7:30pm

8:00pm - 10:00pm

Registration Desk Hours

General Session IV

General Session V Preceptor Development Track #1 Breakout Sessions 8, 9 & 10 Exhibit Hall with Lunch Buffet Preceptor Development Track #2 - Poster Judging General Session VI - Keynote Preceptor Development Track # 3 Breakout Session 11 Breakout Session 12 Reception hosted by University of Arizona College of Pharmacy Past President’s Reception (Invitation only) Celebration Event

Sunday June 17, 2018

6:30am - 2:30pm

8:00am - 9:30am

9:45am - 10:45am

11:00am - 12:00pm

12:00pm - 1:30pm

1:45pm - 2:45pm

1:45pm - 3:15pm

3:30pm - 4:30pm

Breakfast and Lunch Included

Registration Desk Hours

General Session VII Breakout Sessions 13, 14 & 15 Breakout Sessions 16, 17, 18 & 19

Awards Luncheon Breakout Session 20 Breakout Session 21 Breakout Sessions 22 & 23

Breakfast and Lunch Included | Saturday includes Student Track & Preceptor Development Track

A n n u a l C o n v e n t i o n A g e n d a

Friday, June 15th

8:30AM-9:30AM: GENERAL SESSION I Effective Patient Communication

Speaker TBD

9:45AM-10:45AM: BREAKOUT SESSIONS 1 & 2

1: Now what? Looking for a Job after the Age of 50

Ann Sears Dotson, RPh; Shawn Tennant, PharmD, MBA Pharmacist Objectives:

• Identify the challenges of finding a job within the pharmacy profession after the age of 50.

• At specific intervals per or to the age of 50, selfevaluate professional situation to prepare for a job search after the age of 50.

• Identify continuing and post-graduate education that provide pharmacists over the age of 50 with the greatest job opportunities.

• Identify alternate careers that are conducive to pharmacists over the age of 50.

• List resources available for support in a job search after the age of 50.

• Identify social media networking opportunities and their importance in a job search after the age of 50.

2: Immunization Update 2018

Sophia Galloway, PharmD Pharmacist Objectives:

• List current vaccine recommendations.

• Evaluate proper use of vaccinations in special populations.

• Describe the Arizona State Immunization Information System (ASIIS).

11:00AM- 12:00PM BREAKOUT SESSIONS 3 & 4

3: Immunotherapy Emergencies: A Practical Guide for Clinical Pharmacists

Ali McBride, PharmD, MS, BCOP; Brian Do, PharmD Pharmacist Objectives:

• Identify recent and emerging efficacy and safety data for immunotherapeutic strategies in the treatment of cancer.

• Discuss the important features of patient selection for immunotherapies.

• Identify strategies to recognize and manage adverse events due to the use of immunotherapies.

4: Managing the Overflow: Generic Drug Management Strategies

Jason Kwan, PharmD, PGY-1 Pharmacist Objectives:

• Discuss best practices in monitoring the generic

drug landscape.

• Develop strategies to identify generics with the biggest predicted impact on cost.

Propose payer strategies for formulary decisionmaking for generics.

• Employ a process to transition patients from expensive generics to lower cost opportunities.

1:00PM-2:30PM: GENERAL SESSION II Combating the Opioid Epidemic

Alaa Abd-Elsayed, MD, MPH Pharmacist Objectives:

• Identify how changes in legislation/policy may positively affect the opioid abuse and misuse epidemic, but may negatively impact patients with legitimate medical need for opioids.

• Explain the pharmacists role in the interdisciplinary collaborative approach to combat the opioid epidemic.

• Compare and contrast scenarios where treatments could become cost prohibitive for some facilities and patients.

• Identify and apply measures to monitor and curb drug diversion and illegal prescribing habits.

2:45PM- 3:45PM: BREAKOUT SESSION 5, 6 & 7

5: Anti-infective Updates, What is New and What is Coming

Jacob Schwarz, PharmD, BCCP, BCPS Pharmacist Objectives: List newly approved anti-infective agents recently approved by the FDA.

• Discuss spectrum of activity, pharmacokinetics, indications, contraindications pertinent to the use of these agents.

• Assess the role of these newer agents in the treatment of infections.

• Identify anti-infective agents currently in development or trials and their possible roles in therapy.

6: Determining the Most Appropriate Treatment and Duration for Anticoagulant, Antiplatelet, or both Classes of Medication

Christa Tetuan, PharmD, PGY-2 Pharmacist Objectives:

• Discuss guideline based recommendations for outpatient, thrombus prevention for percutaneous coronary intervention, valve replacement, atrial fibrillation, stroke, and myocardial infarction.

• Evaluate current literature supporting the selection of antiplatelet, anticoagulant, or both classes of medications.

A n n u a l C o n v e n t i o n

• Recommend appropriate treatment duration for the selected class(es) of medications for specific conditions.

• Select appropriate therapy for patients with multiple indications for thrombus prevention.

7: Preceptor Happy Hour: Stories Shared, Lessons Learned

Janet Cooley, PharmD; Suzanne Larson, PharmD; Melinda Burnworth, PharmD, BCPS, FASHP, FAzPA; Lindsay Davis, PharmD, BCPS, FAzPA Pharmacist Objectives:

• Describe the use of storytelling as a teaching and precepting method.

• Identify “precepting pearls” from stories shared.

• Identify stories from authentic experiences that

could be used in experiential training. 4:00PM-5:00PM: (Non-accredited) Preceptor Feedback Session

4:00PM-5:30PM: GENERAL SESSION III Speed Networking and AzPA TownHall AzPA Board of Directors Pharmacist Objectives:

• Describe the new strategic vision of AzPA to transform our profession into the future.

• Identify opportunities for the association to better meet your needs as a pharmacy professional

• Examine different re-branding ideas that will contribute to the overall strategic plan.

Saturday, June 16th

8:30AM- 10:00AM: GENERAL SESSION IV 2018 Pharmacy Law Update

Roger Morris, RPh, JD Pharmacist Objectives:

• Identify major developments in U.S. pharmacy law and related fields.

• Describe the practical ramifications of proposed state and national legislative initiatives.

• Recognize emerging patterns that will broadly affect the healthcare profession and pharmacy practice.

10:00AM-11:15AM: GENERAL SESSION V Legislative Town Hall

Hear from your Arizona Legislators & AzPA Lobbyist Pharmacist Objectives:

• Recognize the impact the Pharmacist Political Action Committee (PPAC) of Arizona has in our state.

• Evaluate critical legislative issues that will impact the practice of pharmacy.

• Review legislation considered in Arizona that can impact the profession.

• Participate in an open forum discussion with current leadership to discuss practice changes.

10:00AM-11:15AM: PRECEPTOR DEVELOPMENT

TRACK #1

Effective Abstract and Poster Evaluation

Janet Cooley, PharmD

11:30AM- 12:30PM: BREAKOUT SESSIONS 8, 9 & 10

8: Gabapentin: An “Unnerving” New Trend in Prescription Drug Abuse

Alyssa Peckham, PharmD, BCPP Pharmacist Objectives:

Describe prevalence of gabapentin abuse in the U.S. as compared to known agents of abuse.

• Identify potential for drug-related harm and increased healthcare service utilization related to gabapentin abuse with or without concomitant opioids.

• Summarize potential economic impact along with ethical and legal ramifications for practicing pharmacists.

9: The Perfect Slice of (Preceptor Role) Pie: Just like Grandma Made Mindy Burnworth, PharmD, BCPS, FASHP, FAzPA Pharmacist Objectives:

• Define the four preceptor roles (direct instruction, modeling, coaching, facilitating).

• Design an individualized learning experience that layers in the four preceptor roles.

• Create an assessment plan for mastery of the four preceptor roles.

10: High and Dry: Anticholinergic Burden Implications

Jacqueline Hagarty, PharmD, PGY-2; Dawn KnudsenGerber, PharmD, CGP, FASCP Pharmacist Objectives:

• Discuss the risks of using anticholinergic medications in a geriatric population. Identify anticholinergic risk scales that can be used in practice.

• Assess a patient’s anticholinergic burden.

12:30PM-2:00PM: PRECEPTOR DEVELOPMENT

TRACK #2

Poster Contest Judging

A n n u a l C o n v e n t i o n

2:15PM- 3:30PM: GENERAL SESSION VI

Keynote Speaker Sponsored by APF Justin Luke Riley

2:15PM-3:30PM: PRECEPTOR DEVELOPMENT

TRACK #3

Promoting Resilience and Preventing Burnout

Anna Dopp, PharmD, Director; Clinical Guidelines & Qualify Improvement, ASHP

3:45PM-4:45PM: BREAKOUT SESSION

11: Updates in the Management of Osteoporosis

Erin Raney, PharmD, BCPS, BC-ADM

Pharmacist Objectives:

• Compare and Contrast current treatment Algorithms for osteoporosis in men and women.

• Evaluate clinical controversies related to bisphosphonates and their appropriate duration of use.

• Determine the place in therapy for recentlyapproved anabolic agents and other medications

in the development pipeline.

• Recommend strategies for the management of glucocorticoid-induced osteoporosis based upon recent guidelines.

3:45PM-5:15PM: BREAKOUT SESSION

12: From A to Z: Clinical Pearls for Pharmacists Variety of Speakers

Pharmacist Objectives:

• Evaluate clinical scenarios or “clinical pearls” that might not be widely known or published.

• Apply novel Clinical practice options for Patient care in various health settings.

• Value medication management strategies in difficult or controversial patient care situations.

• Assemble clinical information that can be applied to applicable work settings.

Sunday, June 17th

8:00AM-9:30AM: GENERAL SESSION VII

Effective Grassroots Involvement in the Policymaking Process

Heidi Ann Ecker, Senior Director, Govt. Affairs, NACDS Pharmacist Objectives:

• Describe the policymaking process, including how a bill becomes a law. Discuss ways to meaningfully communicate with policymakers.

• Describe the power of grassroots involvement in the pharmacy industry.

9:45AM-10:45AM: BREAKOUT SESSION 13, 14 & 15

13: Assessing QT Interval Prolongation in Hospitalized Patients to Guide Appropriate Medication Use and Monitoring

Khoa Dang Truong, PharmD, BCPS

Pharmacist Objectives:

• Identify medications and risk factors associated with QT interval prolongation.

• Identify patients with risk for QT prolongation and assist with clinically meaningful therapeutic interventions.

14: Emergency Medicine Pearls: Tips for the Everyday Pharmacist

Elizabeth Palmer, PharmD, BCPS; Mark Culver, PharmD, BCPS; Justin Fahringer, PharmD; Mindy Burnworth, PharmD, BCPS, FAzPA

Pharmacist Objectives:

• Evaluate the use of various doses of intravenous

ketorolac when used for analgesia in the emergency department.

• Identify common emergency medicine practices and evaluate their appropriateness based on current evidence.

• Illustrate the process for obtaining a special biologic or drug from the CDC and examine the corresponding drug information and paperwork received with the product.

• Review the evidence supporting and refuting the various approached to dosing PCC in the emergency department setting.

15: Yes, You Can! How Community Pharmacies have Profitably Implemented Enhanced Care Services

Bruce Kneeland, BA Pharmacist Objectives: List five patient centric care services being provided by community pharmacies.

• Recognize that patients and caregivers are often willing and able to pay for enhanced care services and name two health care services people commonly pay for in the community.

• List three critical success factors necessary to successfully provide and charge or bill for enhanced care services.

• Identify two or more ways they can find partners to help them implement the changes necessary.

A n n u a l C o n v e n t i o n

11:00AM-12:00PM: BREAKOUT SESSIONS 16, 17, 18 & 19

16: The Pharmacist Role in International Disaster Response

Lisa Tonrey, RPh, MHA, PhC, FAPhA

Pharmacist Objectives: Describe the work of U.S. Agency for International Development (USAID) and Office of Foreign Disaster Assistance (OFDA).

• Recognize disasters and public health and health related issues.

• Determine the importance of quality pharmaceuticals in disasters.

• Discuss the role and activities of OFDA pharmacists.

17: The Role of Pharmacy Technicians in Medication Therapy Management

Natasha Chappotin, CPhT (Tech-specific CE)

18: Everyday Leadership: The Pharmacist’s Role

Quincy Renee Ostrem, PharmD, MBA; Ndidi Precious Alino, PharmD, MS Pharmacist Objectives:

• Characterize leadership and what it means to be a leader.

• Assess different leadership styles.

• Distinguish the everyday pharmacist’s role in leadership.

• Identify skills that pharmacists can use to be effective everyday leaders.

19: Pit Viper Antivenoms: Past, Present, Future

Keith Boesen, PharmD, CSPI Pharmacist Objectives:

• Describe the symptoms commonly seen from pit viper envenomations.

• Contrast the differences in the pit viper antivenoms that have been approved by the FDA.

• Compare the potential advantage of a F(ab’)2 vs Fab in the treatment of pit viper envenomation’s.

12:00PM-1:30PM: AWARDS LUNCHEON

1:45PM-2:45PM: BREAKOUT SESSION

20: Web of Knowledge: Feedback vs Evaluation (from the Itsy Bitsy Spider’s Perspective

Mindy Burnworth, PharmD, BCPS, FASHP, FAzPA; Jane Stein, PharmD; Victor De Dios, PharmD Candidate Pharmacist Objectives: Compare and contrast formative feedback and summative evaluation.

• Design effective and meaningful feedback with a

“feel good” tone.

• Design quality feedback and evaluation that best matches the learning scenario while fostering learner enrichment.

1:45PM-3:15PM: BREAKOUT SESSION

21: New Drug Update 2018 Robert Lipsy, PharmD, BCPS, FASHP Pharmacist Objectives:

• Compare and contrast the benefits and risks of recently FDA approved drugs versus older drugs.

• Identify new therapeutic options for conditions with inadequate or no previous drug therapy options

• Identify potential severe and or life-threatening adverse drug reactions associated with newly approved drugs.

3:30PM-4:30PM: BREAKOUT SESSION 22 & 23

22: You Don’t Need More Time, You Need Better Strategy

Ndidi Precious Alino, PharmD, MS Pharmacist Objectives:

• Outline the ABC’s of time management

• Recognize the different energy sources and their role in effective time management and personal productivity.

• Apply the process of on-going personal productivity check for effective time management.

23: CPESN-Arizona | Enhanced Community Pharmacy Networks Speaker TBD Pharmacist Objectives:

• Discuss common characteristics of pharmacies in a community pharmacy enhanced service network.

• Describe how pharmacies are positioning themselves to integrate with care teams to lower health care costs and participate in new models of care and reimbursement.

F e a t u r e d H i g h l i g h t s

A Review of Pharmacologic Treatment Modalities for Post-Operative Phantom Limb Pain

Authors

Quincy R. Ostrem, PharmD, MBA

PGY-1 Health System Pharmacy Administration Practice Resident

Banner Boswell Medical Center 10401 W Thunderbird Blvd Sun City, AZ 85351

Steven MacKay, PharmD, BCPS, BCGP

Clinical Pharmacist

Banner Boswell Medical Center 10401 W Thunderbird Blvd Sun City, AZ 85351

The authors have no conflicts of interest to disclose.

ABSTRACT

Phantom limb pain affects 50-80% of patients following amputation. It may present in patients who have experienced traumatic or non-traumatic wounds resulting in amputation, but it may also present in patients who have experienced nerve damage from other sources. Originally thought to be of psychogenic origin, phantom limb pain has been further studied. It is now known that phantom limb pain can stem from one or a combination of mechanisms, including the growth of ‘nerve tumors,’ the breakdown of nerve cell connections, or the reorganization of the somatosensory cortex. No clear treatment algorithm is available to guide clinicians when treating phantom limb pain. Many agents with varying levels of evidence are available as potential options for treatment. Pharmacologic therapies supported by positive evidence for efficacy include bupivacaine, dextromethorphan, ketamine, gabapentin, opioids, and capsaicin. Treatment modalities with limited or no evidence of benefit include botulinum toxin, methylprednisolone with lidocaine, amitriptyline and memantine. Calcitonin has shown mixed results. When considering different pharmacologic treatment modalities for the management of phantom limb pain, clinicians should initially consider modalities with higher levels of evidence for efficacy. If these treatment options are not successful, clinicians should progress to therapies with less supportive evidence. Patient presentation and comorbidities should be taken into consideration when selecting agents. Patients should be reassessed and evaluated for response to treatment, which in turn should guide future therapies. Additional research is necessary prior to making generalizable, definitive recommendations for the treatment of phantom limb pain.

Background

Phantom limb pain is a type of pain that occurs following sensory nerve damage, frequently as a result of an amputation. This phenomenon can affect the patient’s quality of life, employment opportunities, and their lifestyle.1 While this most often occurs following a limb amputation, it has been reported following the removal of eyes, teeth, breasts, noses, and other body parts.2 This type of pain may be secondary to nerve damage, therefore it may occur following nerve severance without limb amputation. Phantom limb pain may onset immediately after surgery or injury, or up to years after. The onset of phantom limb pain most often occurs within one month of surgery or injury. In rare cases, the presentation of phantom limb pain may be delayed for years. The probability of occurrence is greatest during the first month and decreases over time.3

Phantom limb pain has been reported in 50-80% of amputees.4 Phantom limb pain has been documented to occur following both traumatic and non-traumatic injuries.5 Traumatic limb injury and subsequent amputation may be a result of a combat-related wound, or other injury occurring outside of an operating theater. A non-traumatic limb injury and amputation may be a result of diabetic foot complications, cancer, post-surgical emboli, or non-diabetes peripheral vascular disease.6

While cases of phantom limb pain commonly occur following amputation, it may also occur following nerve severance. Amputation, by definition, will damage other tissues in addition to nerves. This additional damage provides avenues for pain which are not classified as phantom limb pain. Distinguishing phantom limb pain from other types of traumatic or non-traumatic pain is essential to choosing appropriate treatment modalities. Amputation may result in many types of pain. Post-surgical pain occurs immediately after any surgical procedure. Residual limb pain occurs at the surgical site and presents either as bruising and chafing from the prosthesis, or as ischemic pain due to poor perfusion. Musculoskeletal pain may occur as a result of an altered gait pattern, modified posture secondary to amputation, or other medical comorbidities. This type of pain commonly occurs in regions other than the amputation site.5 Phantom limb pain presents with a variety of descriptors. Some patients describe it as a sharp or shooting pain, while others define their pain as dull or cramping. Phantom limb pain can be specific to one area of the missing limb, or affect the entire limb. Patients may experience symptoms that evolve over time.2

Historically, phantom limb pain was thought to be a psychogenic disease.2 Additional evidence has accumulated over the past few decades to support a physiologic origin. During amputation, nerves are damaged, resulting in a modified pattern of neuronal input flowing to the spinal cord. Three different mechanisms have been suggested to explain this phenomena. First, the pain may originate from peripheral nerve damage. Severed nerve endings may grow neuromas due to inflammation and regeneration. These painful growths are

F e a t u r e d H i g h l i g h t s

sometimes described as ‘nerve tumors.’ Neuromas are prone to increased sodium channel expression and therefore increased excitability and increased pain sensations.3 Second, the pain may originate at the spinal level.

Damage to nerves can lead to deafferentation, the degradation of afferent nerve cell connections. The afferent communication to the dorsal horn normally results in an inhibitory effect on sensory transmission. In patients who have experienced deafferentation, the absence of these inhibitory effects may result in autonomous dorsal horn neuron activity.2 Finally, the pain may originate at a supraspinal level. The somatosensory cortex may become reorganized following deafferentation. Researchers have observed participants experience phantom limb pain following stimulation to another part of the body, suggesting reorganization in the somatosensory cortex. This process can be time consuming, and may explain some cases of delayed onset phantom limb pain.2 As evidence has been found for each of these proposed mechanisms, researchers have suggested phantom limb pain may be due a combination of multiple proposed mechanisms.2

Treatment

The ideal treatment for phantom limb pain is unclear. No high quality, large trials have provided compelling evidence to use one therapy over another. Forty- three treatments were identified in 1980 as being used to treat this pain.4 Noting the variety of mechanisms that may result in phantom limb pain, it is reasonable to expect a variety of feasible treatments.

Preemptive analgesia, including intraoperative and immediately postoperative interventions, has been suggested as an option to reduce phantom limb pain. Epidural blockade and perineural analgesia have been used. Epidural blockade has been shown to reduce the incidence of phantom limb pain when administered over 72 hours. Evidence of benefit was not seen when administered over 18 hours.5 Perineural analgesia has shown no benefit in preventing phantom limb pain, although it has been shown to reduce surgical site pain post-operatively. Perineural analgesia attempts to decrease afferent discharge occurring as a result of nerve severance, by infiltrating the nerve with 0.25% bupivacaine prior to severance.5

A number of pharmaceutical agents have been administered via injection at the site of amputation in an effort to relieve phantom limb pain. One study compared botulinum toxin and methylprednisolone-lidocaine injections to each other. Neither of these interventions showed an improvement in pain.7 Bupivacaine 0.25% injected once was compared to a placebo injection. Bupivacaine showed significant reduction in pain versus placebo one hour after injection, but lasting effects were unknown.8

Tricyclic antidepressants have been suggested for the treatment of phantom limb pain as they are known to be efficacious for the treatment of other nervous

pain. A six month course of amitriptyline, when compared with active placebo benztropine, was not beneficial. The average pain scores and average functional independence measures were not significantly different after six weeks of therapy.9 Another study compared amitriptyline, tramadol, and placebo to reduce both stump and phantom limb pain. Response to treatment was defined as a decrease in pain score of at least 10 mm on a 100 mm VAS scale, compared to baseline. Following one month of treatment, 25 of 33 participants treated with amitriptyline, 22 of 33 tramadol, and 2 of 31 placebo showed response to treatment. No significant difference in pain scores between responders was seen. No major side effects were noted.10 Following assessment of fourteen studies analyzing the efficacy of the aforementioned phantom limb pain treatments, the authors of the 2016 Cochrane review of phantom limb pain concluded that more, high quality research is needed, in part due to the short duration of available trials.1

Two studies have compared the use of calcitonin infusion to placebo with conflicting results. One study showed significant benefit in reducing phantom limb pain; pain in the participants receiving 200 units of calcitonin was decreased from an average score of seven out of ten, to a score of four following treatment. Placebo did not affect pain scores.11 The other study showed no benefit to giving calcitonin to participants suffering from phantom limb pain. Pain intensity did not significantly decrease compared to the placebo group after forty-eight hours of treatment. The number of participants responding to calcitonin was similar to the number of patients responding to placebo.12

NMDA-receptor antagonists have had mixed results. Multiple trials assessed the use of 30mg memantine per day versus placebo, administered over a period of three to four weeks, but none showed benefit.10,13,14 Other NMDAreceptor antagonists, including dextromethorphan and ketamine, have also been compared with placebo. In a small, ten participant, double-blind, crossover study comparing dextromethorphan to placebo, participants received either 120 or 180 mg dextromethorphan daily. This study observed a fifty percent reduction in participant reported numerical pain scores following treatment.15 Another study evaluated the use of ketamine for phantom limb pain. Ketamine 0.4 mg/kg was administered to ten participants. Pain intensity, as reported by participants, decreased by fifty percent in the treatment group compared to the placebo group.12

Conflicting results suggest both the benefit and lack of benefit of gabapentin. The use of 2.4 grams per day has shown significant benefit in reducing pain scores associated with phantom limb pain. Two studies have compared gabapentin to placebo and both have shown significantly decreased pain scores.16,17 Other studies, however, have not shown benefit. According to the Department of Defense guideline, this agent may provide more benefit to patients who present with a higher level of pain prior to treatment.5

Both oral and intravenous morphine have been shown to decrease pain scores when compared with placebo. Oral morphine showed a fifty percent decrease in pain score in forty-two percent of patients treated. Patients experienced more adverse events, but reported greater treatment satisfaction with morphine compared to placebo.18,19

An open label, fourteen participant trial assessed the use of capsaicin patches for phantom limb pain. Patches were applied according to package labeling for post herpetic neuralgia: apply one to four patches for sixty minutes, repeat in three to six months as needed.20 This study assessed both stump pain and phantom limb pain, but requested participants to report pain scores separately for each type of pain. Participants experienced a statistically significant decrease in pain score of 1.41 points from baseline.21

Discussion

Some literature suggests basing treatment choice on likely mechanism of pain. Patients whose pain is likely of peripheral origin may see benefit from perineural botulinum toxin or local anesthetic injections, although placebo controlled trials have not provided evidence for this approach. Patients who present with pain originating from a spinal source may see the most benefit from an NMDAreceptor antagonist like ketamine or dextromethorphan, or opioids. Those patients whose pain is likely of supraspinal origin may see the most benefit from opioids or gabapentin.2 No trials have assessed the use of specific treatment modalities for specific mechanisms of phantom limb pain. Ultimately, treatment choice should be based on available literature, patient presentation, and patient preference.

Limitations

Phantom limb pain has been studied for decades in small, often short term studies. No clear recommendations have been made given the lack of compelling evidence for one treatment over another, and the fact that the trial evidence available is limited in number and quality.21

Conclusion

Due to the limited evidence for any single agent, and the lack of comparative trials, no agent is recommended above another. Clinicians should use appropriate clinical judgment when assessing a patient presenting with phantom limb pain. Limited evidence is available to support a guided approach to phantom limb pain management. Many pharmacologic therapies have been investigated for use in this disease. The trials are often small and may have notable limitations that limit the clinical significance of the conclusions. Clinicians should consider the options that have shown benefit when compared to placebo: bupivacaine injections, dextromethorphan or ketamine, gabapentin, opioids, and capsaicin. Treatment should be individualized and based on patient response. Therapies with less evidence should be attempted following failure of therapies

with higher quality evidence. Additionally, treatments with more documented adverse events, such as opioids, should be reserved for later in treatment. Further research, in the form of high quality trials specifically assessing phantom limb pain, is indicated prior to making definitive recommendations.

REFERENCES:

1. Alviar MJM, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain (review). Cochrane Database of Systematic Reviews 2016;10.

2. Hsu E, Cohen SP. Postamputation pain: epidemiology, mechanisms, and treatment. Journal of Pain Research 2013;6:121-136.

3. Subedi B, Grossberg GT. Phantom limb pain: mechanism and treatment approaches. Hindawi Publishing Corporation 2011.

4. Richardson C, Kulkarni J. A review of the management of phantom limb pain: challenges and solutions. Journal of Pain Research 2017;10:1861-1870.

5. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical practice guideline for rehabilitation of lower limb amputation. 2007.

6. Lazzarini PA, Clark D, Derhy PH. What are the major causes of lower limb amputations in a major Australian teaching hospital? The Queensland Diabetic Foot Innovation Project 2006-2007. J Foot Ankle Res 2011;4(Supp1):O24.

7. Wu H, Sultana R, Taylor KB, Szabo A. A prospective randomized double-blinded pilot study to examine the effect of botulinum toxin type A injection versus Lidocaine/Depomedrol injection on residual and phantom limb pain: initial report. Clinical Journal of Pain 2012;28(2):108–12.

8. Casale R, Ceccherelli F, Labeeb A, Biella G. Phantom limb pain relief by contralateral myofascial injection with local anaesthetic in a placebo-controlled study: preliminary results. Journal of Rehabilitation Medicine 2009;41(6):418–22.

9. Robinson L, Czerniecki J, Ehde D et al. Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study. Archives of Physical Medicine and Rehabilitation 2004;85(1):1–6.

10. Wilder-Smith CH, Hill LT, Laurent S. Postamputation pain and sensory changes in treatment-naive patients: characteristics and responses to treatment with tramadol, amitriptyline, and placebo. Anesthesiology 2005;103(3):619-28.

11. Jaeger H, Maier C. Calcitonin in phantom limb pain: a double-blind study. Pain 1992;48(1):21–7.

12. Eichenberger U, Neff F, Sveticic G et al. Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds. Anesthesia & Analgesia 2008;106(4):1265–73.

13. Maier C, Dertwinkel R, Mansourian N et al. Efficacy of the NMDA receptor antagonist memantine in patients with chronic phantom limb pain - results of a randomized double blinded, placebo-controlled trial. Pain 2003;103(3):277–83.

14. Schwenkreis P, Maier C, Pleger B et al. NMDA-mediated mechanisms in cortical excitability changes after limb amputation. Acta Neurologica Scandinavica 2003;108(3):179–84.

15. Abraham R, Marouani N, Weinbroum A. Dextromethorphan mitigates phantom pain in cancer amputees. Annals of Surgical Oncology 2003;10(3):268–74.

16. Bone M, Critchley P, Buggy D. Gabapentin in postamputation phantom limb pain: a randomized, double blind, placebo-controlled, cross-over study. Regional Anesthesia and Pain Medicine 2002;27(5):481–6.

17. Smith D, Ehde D, Hanley M et al. Efficacy of gabapentin in treating chronic phantom limb and residual limb pain. Journal of Rehabilitation Research & Development 2005;42(5):645–54.

18. Wu C, Tella P, Staats P et al. Analgesic effects of intravenous lidocaine and morphine on postamputation pain. Anesthesiology 2002;96(2):841–8.

19. Huse E, Larbig W, Flor H, Birbaumer N. The effect of opioids on phantom limb pain and cortical reorganization. Pain 2001;90(1-2):47–55.

20. Product Information: QUTENZA(TM) patch, capsaicin patch. NeurogesX, inc, San Mateo, CA, 2009.

21. Pritvitera R, Birch R, Sinisi M et al. Capsaicin 8% patch treatment for amputation stump and phantom limb pain: a clinical and functional MRI study. Journal of Pain Research 2017;10:1623-1634.

F e a t u r e d H i g h l i g h t s

Financial Forum: Getting (Mentally) Ready to Retire

Even those who have saved millions must prepare for a lifestyle adjustment.

A successful retirement is not merely measured in financial terms. Even those who retire with small fortunes can face boredom or depression and the fear of drawing down their savings too fast. How can new retirees try to calm these worries? Two factors may help: a gradual retirement transition and some guidance from a financial professional.

An abrupt break from the workplace may be unsettling. As a hypothetical example, imagine a well-paid finance manager at an auto dealership whose personal identity is closely tied to his job. His best friends are all at the dealership. He retires, and suddenly his friends and sense of purpose are absent. He finds that he has no compelling reason to leave the house, nothing to look forward to when he gets up in the morning. Guess what? He hates being retired. On the other hand, if he prepares for retirement years in advance of his farewell party by exploring an encore career, engaging in varieties of selfemployment, or volunteering, he can retire with something promising ahead of him. If he broadens the scope of his social life, so that he can see friends and family regularly and interact with both older and younger people in different settings, his retirement may also become more enjoyable. The interests and needs of a retiree can change with age or as he or she disengages from the working world. Retired households may need to adjust their lifestyles in response to this evolution.

Practically all retirees have some financial anxiety. It relates to the fact of no longer earning a conventional paycheck. You see it in couples who have

$60,000 saved for retirement; you see it in couples who have $6 million saved for retirement. Their retirement strategies are about to be tested, in real time. All that careful planning is ready to come to fruition, but there are always unknowns.

Some retirees are afraid to spend. They fear spending too much too soon. With help from a financial professional, they can thoughtfully plan a withdrawal rate. While no retiree wants to squander money, all retirees should realize that their retirement savings were accumulated to be spent. Being miserly with retirement money contradicts its purpose. The average 65-year-old who retires in 2017 will have a retirement lasting approximately 20 years, by the estimation of the Social Security Administration. So, why not spend some money now and enjoy retired life?1

Broadly speaking, our spending declines as we age. The average U.S. household headed by an 80-year-old spends 43% less money than one headed by a 50-year-old.1

Retirement challenges people in two ways. The obvious challenge is financial; the less obvious challenge is mental. Both tests may be met with sufficient foresight and dedication.

CITATIONS:

1 - tinyurl.com/ydedsyl5 [4/24/17]

Pat Reding and Bo Schnurr may be reached at 800288-6669 or pbh@berthelrep.com. Registered Representative of and securities and investment advisory services offered through Berthel Fisher & Company Financial Services, Inc. Member FINRA/SIPC. PRISM Wealth Advisors LLC is independent of Berthel Fisher & Company Financial Services Inc.

This series, Financial Forum, is presented by PRISM Wealth Advisors, LLC and your State Pharmacy Association through Pharmacy Marketing Group, Inc., a company dedicated to providing quality products and services to the pharmacy community.

T i m e C a p s u l e

Second Quarter 2018: Pharmacy Time Capsule

1993

• NABP Task Force on Pharmacy Technicians issued final report. One recommendation was to standardize the term pharmacy technician as a uniform title designating personnel that assist the pharmacist in the practice of pharmacy.

1968

• Successful human parenteral hyperalimentation first described. 1943

• Microbiologist Selman A. Waksman discovers the antibiotic streptomycin, later used in the treatment of tuberculosis and other diseases.

1918

• Prior to 1918, pharmacy services in PHS hospitals were provided through contract services or by Federal civilian employees. In 1918, a reserve corps composed of pharmacists, dentists and engineers were commissioned to serve with physicians in the PHS.

1893

• Virginia University College of Medicine Department of Pharmacy formed (became part of the Medical College of Virginia in 1913).

PharmacyTimeCapsuleprovidedby:DennisB.Worthen,PhD,Cincinnati,OH

OneofaseriescontributedbytheAmericanInstituteoftheHistoryofPharmacy,auniquenon-profit societydedicatedtoassuringthatthecontributionsofyourprofessionendureasapartofAmerica’shistory. Membershipoffersthesatisfactionofhelpingcontinuethisworkonbehalfofpharmacy,andbringsfiveor morehistoricalpublicationstoyourdooreachyear. Tolearnmore,checkout: www.aihp.org.

C o n t i n u i n g E d u c a t i o n

The Role of the Pharmacist in

Tuberculosis Management

ACPE UAN: 0129-0000-18-002-H01-P | 0.15 CEU

Author: Amanda R. Kriesen, RPh, PharmD

Dr. Amanda Kriesen has no relevant financial relationships to disclose.

Goal: The goal of this lesson is to provide an overview of the official American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America clinical practice guidelines for the treatment of drug-susceptible tuberculosis.

Objectives:

At the completion of this activity, the participant will be able to:

1. Recognize both the national and worldwide impact of tuberculosis

2. Identify risk factors and clinical presentation of patients with active tuberculosis infection.

3. Demonstrate an understanding of the goasl of therapy and treatment modalities associated with latent infection and active disease.

4. Recognize the role of therapeutic drug monitoring in specific patient populations

5. Identify pharmacologic options for the treatment of latent, active and drug-resistant tuberculosis, including common adverse effects.

6. Identify common drug-drug interactions associated with

particular antituberculosis agents.

Introduction:

Tuberculosis (TB) is one of the most deadly diseases, affecting onethird of the world’s population. In 2015, TB was responsible for 1.8 million deaths and remains the leading killer of HIV-infected individuals. According to the Centers for Disease Control and Prevention (CDC), an estimated 9,287 patients in the U.S. were newly diagnosed with TB in 2016. This provisional count represents the lowest number of TB cases in U.S. records and a 2.7 percent decrease in cases from 2015. TB adversely affects groups that have historically experienced greater barriers to healthcare based on their racial or ethnic group. The percentage of TB cases in Hispanics, African Americans, and Asians is higher than expected based on the percentage of these minorities in the U.S. population. In 2015, about 87 percent of the TB cases reported in the U.S. were in racial and ethnic minorities. The percentage of cases occurring in foreign-born residents was 66 percent of the national case

C o n t i n u e d

total in 2015. Studies have demonstrated improved outcomes and substantially better rates of treatment completion when pharmacists are directly involved in medication management. Due to complex medication regimens involved in the treatment of tuberculosis, pharmacists are in a position to play a pivotal role in the management of this patient population. Pharmacists are often on the front-line of patient care. By providing unique expertise within an interdisciplinary team approach, pharmacists may assess appropriateness, efficacy, and safety of anti-TB therapy by monitoring patients and ensuring medication adherence. Furthermore, pharmacists can educate patients and clinicians regarding expected therapeutic outcomes, potential adverse effects, and drug interactions with respect to antiTB medications.

The American Thoracic Society (ATS), Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) jointly sponsored the development of clinical guidelines for the treatment of drug-susceptible tuberculosis. This guideline provides recommendations with respect to clinical management of TB and will be the guideline utilized for the purpose of this lesson.

Etiology

Tuberculosis is caused by the bacterium Mycobacterium tuberculosis (M. tuberculosis) and transmitted

from person to person via inhalation of the airborne pathogen. TB is not spread by shaking hands, sharing food or drinks, touching bed linens or toilet seats, sharing toothbrushes or kissing. TB generally affects the lungs; however, it may also affect other parts of the body, such as the brain, kidneys, or spine. Most cases of TB are treatable and curable; however, it can be fatal without proper treatment.

Not everyone infected with TB bacteria shows signs and symptoms of the illness. As a result, two TB-related conditions exist: latent TB infection and active TB disease. Differences between latent and active TB are summarized in Table 1. The number of bacterial organisms inhaled, their virulence, and the host’s immune response determine whether the infection progresses to active TB or remains latent.

Latent TB infection (LTBI) occurs when a patient is infected by M. tuberculosis but does not show symptoms of active infection. While patients with LTBI may test positive for TB infection, they generally do not show outward signs or symptoms. Due to early intervention, many patients who have LTBI never develop active disease. In these persons, the TB bacteria re-main inactive for a lifetime without causing disease. In other cases, especially in cases of immunodeficiency, the bacteria become active, multiply, and cause TB disease. Overall, about 5 to 10 percent of infected persons who do not receive treatment for latent TB infection will develop active TB

C o n t i n u e d

Table 1

Differences between latent TB infection and active TB disease

Latent TB Infection

• Asymptomatic

• Does not “feel sick”

• Cannot spread TB bacteria to others

• Generally has positive skin or blood test result indicating TB infection

• Normal chest x-ray and/or sputum smear

• Treatment required for latent TB infection to prevent transition to active TB disease

Active TB Infection

• Symptomatic -Excessive cough lasting ≥3 weeks -Chest pain -Coughing up blood or sputum -Weakness or fatigue -Weight loss -Loss of appetite -Fever/chills -Night sweats

• Capable of spreading TB bacteria to others

• Generally has positive skin or blood test result indicating TB infection

• May have abnormal chest x-ray and/or sputum smear or culture

• Medication therapy required for treatment

disease at some time in their lives.

If a patient’s immune system in unable to prevent TB bacterial growth, active disease ensues. When TB bacteria actively multiply within the body, it is termed active TB disease (ATBD). Patients with ATBD are symptomatic and, therefore, capable of spreading the bacteria to people they come into contact with on a daily basis. Some patients develop ATBD soon after becoming infected (within weeks) before their immune system can fight the TB bacteria. Others may get sick several years later when their immune system becomes weakened for another

reason. For patients with preexisting immunodeficiency, especially those with HIV infection, the risk of developing TB disease is much higher than for individuals with normal functioning immune systems.

In rare instances, TB bacteria become resistant to the drugs used to treat infection. Drug-resistant TB (DRTB) occurs when drugs utilized in the normal recommended course of therapy can no longer kill the TB bacteria. DRTB is spread the same way that drugsusceptible TB is spread and may occur when medications used to treat TB infection are misused or

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mismanaged. The average cost of anti-TB treatment increases with increased medication resistance. While DRTB is relatively rare in the U.S. population, it bears a large financial impact on patients. In 2015, direct costs per patient averaged from $18,000 to treat drugsusceptible TB to $494,000 to treat the most drug-resistant form of the disease. When including productivity losses experienced by patients while undergoing treatment, costs are even greater.

Risk Factors, Diagnosis, and Clinical Presentation

A variety of risk factors for TB exists. Patients who were recently infected or those who are frequently in close proximity with TB, such as healthcare workers, are at a higher risk of acquiring disease. Other patients at high risk for TB include those born in or emigrated from countries with a high TB prevalence; patients who are homeless, incarcerated, live in unsanitary conditions; or those who use IV drugs. Hispanics, African Americans, and Asian Americans carry a greater risk of acquiring TB in comparison to Caucasians. Lastly, patients with weakened immune systems such as those with cancer, solid organ transplants, and HIV have an increased risk for TB.

The Mantoux test, more commonly known as the purified protein derivative (PPD) test, is the gold standard for TB testing. PPD testing is performed by injecting an intradermal dose of tuberculin. Patients who have had prior exposure to TB will produce a

delayed-type hypersensitivity reaction within 48 to 72 hours, denoted by inflammation and hardening of skin tissue surrounding the injection site. A positive skin test requires further examination to determine if a patient has LTBI versus ATBD. It is important to note that patients who have been vaccinated with the bacille CalmetteGuérin (BCG) vaccine or those who have been infected with nontuberculous mycobacteria may yield false positive results on a PPD skin test. In cases in which a false positive results, patients must undergo more specific testing.

While patients with LTBI do not show symptoms of TB, those with ATBD may exhibit a multitude of symptoms. Patients with ATBD may present with persistent productive cough (lasting three weeks or more), hemoptysis, fever, dull or aching chest pain, night sweats, loss of appetite, weight loss, and/or fatigue. Hematology tests may reveal moderate leukocytosis. Additionally, chest x-rays showing upper lobe nodular infiltrates or lung cavitation, and the presence of acid-fast bacilli in the sputum are all indicative of TB disease.

Goals of Therapy

TB treatment is focused on both curing the individual patient and reducing the transmission of Mycobacterium tuberculosis to others. Therefore, successful treatment is beneficial to both the individual patient and to the community in which the patient lives. The first goal of TB therapy involves rapid reduction in the quantity of actively growing bacilli, consequently

1

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Table 2

Drug regimens for microbiologically confirmed TB

Intensive Phase Continuation Phase

Regimen Drugs Interval/ Dose Drugs Interval/ Dose Comments

INH RIF PZA EMB

7 days/wk x 56 doses (8 wk) or 5 days/ wk x 40 doses (8 wk)

2

INH RIF PZA EMB

7 days/wk x 56 doses (8 wk) or 5 days/ wk x 40 doses (8 wk)

INH RIF 7 days/wk x 126 doses (18 wk) or 5 days/ wk x 90 doses (18 wk)

INH RIF 3 times weekly x 54 doses (18 wk)

Preferred regimen for patients with newly-diagnosed pulmonary TB

Preferred alternative where more frequent DOT during continuation is difficult to attain

3

INH RIF PZA EMB

3 times weekly x 24 doses (8 wk)

INH RIF 3 times weekly x 54 doses (18 wk)

Use with caution in HIV and/or cavitary disease. Missed doses may lead to tx failure, relapse, or acquired drug resistance.

4

INH RIF PZA EMB

7 days/wk x 14 doses, then 2 x weekly x 12 doses

INH RIF Twice weekly x 36 doses (18 wk)

Do not use 2 x weekly in HIV, smear-positive/ cavitary disease. Missed doses = substandard tx.

INH = isoniazid; RIF = rifampin; PZA = pyrazinamide; EMB = ethambutol. Regimen effectiveness increases from Regimen 4 to Regimen 1.

reducing disease severity, halting disease transmission, and preventing fatality. The second goal is aimed at eradication of persisting bacilli in order to prevent relapse after therapy completion. The last goal is to prevent drug resistance during therapy.

TB treatment requires a multi-drug regimen approach, administered

over the course of several months. Therefore, meaningful patient involvement remains a critical part of therapy decisions, supervision and overall care. Successfulness of antiTB therapy depends upon several factors, and numerous studies have found an increased risk of relapse among patients with signs of more extensive disease (i.e., cavitation, more ex-tensive disease on chest

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x-ray, and/or slower response to treatment).

Therapeutic Considerations

Given the critical importance of anti-TB therapy, both to the patient and the public, approaches to ensuring adherence to treatment regimens are a large focus of the overall management plan. Among various interventions, directlyobserved therapy (DOT), the practice of observing the patient swallow the anti-TB medications, has been widely accepted as the standard of practice in many TB programs. DOT has been associated with significantly improved treatment outcomes and with increased sputum smear conversion during treatment.

There have been no prospective randomized trials which have clearly defined the role of therapeutic drug monitoring (TDM) for antiTB medications. Experts generally utilize TDM as a specialized tool, providing insight into the adequacy of drug dosing in specific patients. For example, serum anti-TB drug concentrations are often lower among children and HIV-infected patients with TB com-pared to those in healthy volunteers.

Therapeutic drug monitoring consists of measurements of drug concentrations in serum specimens, typically collected at two and six hours after a dose of the drug in question has been administered. While TDM cannot determine who will be cured, or who will fail or relapse, it does allow for timely, informed decisions regarding dose adjustment. Experts suggest

that TDM may be particularly useful for situations in which drug malabsorption, under-dosing, or clinically important drug-drug interactions are suspected. Other examples in which TDM may be helpful include patients with delayed sputum conversion or treatment failure not explained by non-adherence or drug resistance; patients with medical conditions that are suspected of causing sub-therapeutic or toxic drug concentrations (e.g., decreased renal function); and those who are undergoing treatment for drugresistant TB.

Pharmacologic Therapy

Drug regimens for microbiologically confirmed TB caused by drugsusceptible organisms can be found in Table 2. Regimens consist of two phases: an intensive therapy phase and a continuation phase. Intensive phases consist of four drugs due to worldwide observance of isoniazid resistance. The preferred regimen for adults with TB of an unknown origin or suspected drug-resistant TB consists of an intensive initiation phase of two months isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambu-tol (EMB).

If therapy is initiated after drug susceptibility test results are known, and the patient’s isolate is susceptible to both INH and RIF, then EMB is unnecessary. Therefore, in this particular patient population, the intensive phase of therapy may consist of INH, RIF, and PZA only. EMB may be dis-continued as soon as drug susceptibility

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Table 3

Adult doses of first-line agents of antituberculosis drugs

Drug Preparation Daily Once Weekly Two Times Weekly Three Times Weekly

Isoniazid†

Tablets, 50 mg, 100 mg, 300 mg; elixir, 50 mg/5mL; aqueous solution for IV or IM injection

5 mg/kg (typically 300 mg)

15 mg/kg (typically 900 mg)

15 mg/kg (typically 900 mg)

15 mg/kg (typically 900 mg)

Rifampin

Capsules, 150 mg, 300 mg; powder may be suspended for PO administration; aqueous solution for IV injection

10 mg/kg (typically 600 mg)

10 mg/kg (typically 600 mg)

10 mg/kg (typically 600 mg)

Rifabutin

Rifapentine

Capsules, 150 mg 5 mg/kg (typically 300 mg)

Film-coated tablets, 150 mg 10-20 mg/ kg

Not recommended Not recommended

Pyrazinamide

Ethambutol

Scored tablets, 500 mg 56-75 kg: 1500mg 76-90kg: 2000mg

Tablets, 100 mg, 400 mg 56-75 kg: 16-21.4 mg/kg: 76-90 kg: 17.8-21.1 mg/kg

56-75 kg: 3000 mg 76-90 kg: 4000 mg

56-75 kg: 37.350 mg/kg; 76-90 kg: 44.452.6 mg/kg

56-75 kg: 2500 mg 76-90 kg: 3000 mg

56-75 kg: 26.735.7 mg/kg; 76-90 kg: 26.731.6 mg/kg

†Note. Pyridoxine 25-50 mg/day is given with isoniazid to all patients at risk of neuropathy; 100 mg/day is recommended for patients with peripheral neuropathy.

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results determine that the isolate is susceptible to INH and RIF. The intensive regimen is then followed by a four-month continuation phase of INH and RIF. A summary of recommended doses of anti-TB agents for adults is included in Tables 3 and 4.

Several factors are associated with the outcome of TB therapy. Patient-related factors such as age, comorbid conditions, immunologic competence, and nutritional status may affect various aspects of therapeutic response. Extent of disease, presence and size of cavities in the lungs, individual patient drug absorption and metabolism, adherence to therapy, and susceptibility all play a vital role in therapeutic success, as well.

In regard to administration schedule, the preferred frequency is once daily for both the intensive and continuation phases. While preferred frequency of administration is once daily, five days per week administration by directly-observed therapy is an acceptable alternative. During therapy, a sputum specimen for smear and culture are obtained monthly until two consecutive specimens are negative.

Pharmacologic agents are administered together at one dosing so as to achieve maximal peak serum concentrations and to further facilitate directly-observed therapy. All four agents involved in the initiation phase of TB therapy are most bioavailable when taken on an empty stomach. Parenteral

drug administration is reserved for severely ill patients who are unable to tolerate oral therapy, and may also be useful for complex patients and those with suspected or documented malabsorption.

Patients exposed to individuals with known drug-resistant tuberculosis (DRTB), those with active TB who have experienced treatment failure or relapse, individuals with continued positive sputum smears after two months of therapy, or those who travel to regions where DRTB is highly prevalent are at increased risk of infection with DRTB. Development of drug resistance is most frequently observed in patients with cavitary TB (involves the upper lobes of the lung, causes progressive lung destruction by forming cavities or enlarged air spaces, and occurs in reactivation disease), patients receiving inappropriate pharmacologic therapy, and in those who fail to adhere to the prescribed treatment regimen. For patients who are resistant to INH only, multimodal treatment with RIF, PZA, and EMB is recommended. A respiratory fluoroquinolone (i.e., levofloxacin, moxifloxa-cin) or an injectable agent (e.g., amikacin, cycloserine, streptomycin, etc.) may be added in patients with extensive disease.

Isoniazid. Isoniazid (INH) is one of the cornerstones of therapy in treating TB. Isoniazid exerts its effect by inhibiting the synthesis of mycolic acid, an essential component of the bacterial cell wall. At therapeutic levels, isoniazid exhibits bactericidal activity against

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Table 4

Adult doses of second-line agents of antituberculosis drugs Drug Preparation

Dose

Capsules, 250 mg

Cycloserine

Ethionamide

Streptomycin

Amikacin

Capreomycin

Para-amino salicylic acid

Levofloxacin

Moxifloxacin

10-15 mg/kg/day total (typically 250-500 mg one or two times a day)*

Tablets, 250 mg 15-20 mg/kg/day total (typically 250-500 mg one or two times a day)*

Aqueous solution,1 g, IM or IV 15 mg/kg/day. Some clinicians prefer 25 mg/kg three times weekly. Patients with poor renal function may require 15 mg/kg three times weekly.

Aqueous solution, 500 mg and 1 g, IM or IV

15 mg/kg/day. Some clinicians prefer 25 mg/kg three times weekly. Patients with poor renal function may require 15 mg/kg three times weekly.

Aqueous solution, 1 g, IM or IV 15 mg/kg/day. Some clinicians prefer 25 mg/kg three times weekly. Patients with poor renal function may require 15 mg/kg three times weekly.

Granules, 4 g packets 8-12 g/day total (typically 4000 mg two to three times daily)*

Tablets, 250, 500, 750 mg; aqueous solution, 500 mg vials, IV

Tablets, 400 mg; aqueous solution, 400 mg/250 mL, IV

500-1000 mg/day*

400 mg/day*

*Inadequate data to support intermittent administration

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actively growing intracellular and extracellular M. tuberculosis organisms.

The recommended dosage of INH is 5 mg/kg once daily. Pharmacists should note that metabolism of INH is genetically deter-mined. Approximately 50 percent of blacks and whites are “slow inactivators,” and the rest are “rapid inactivators.” The large majority of Eskimo and Asian patients are “rapid inactivators.” While metabolic rate does not significantly alter the efficacy, it may lead to higher blood levels and possibly an increase in adverse effects.

In addition to INH, pyridoxine (vitamin B6) is administered to all patients at risk of neuropathy (e.g., pregnant women; breastfeeding infants; HIV-infected patients; patients with diabetes, alcoholism, malnutrition, or chronic renal failure; or those of advanced age).

Adverse effects of INH include increased liver enzymes, peripheral neuropathy, memory impairment, psychosis, Lupus-like syndrome, nausea/vomiting, and pancreatitis.

In addition, INH carries a Black Box Warning with respect to the potential for patients to develop severe and sometimes fatal hepatitis which generally occurs within the first three months of treatment. In some cases, however, hepatitis may develop after several months of treatment. Fatal hepatitis associated with INH therapy may be increased in postpartum, black and Hispanic women. Therefore, these patients

should be monitored more closely. Patients should be required to report any early symptoms of hepatitis, such as fatigue, paresthesias of hands and feet, weakness, dark urine, rash, anorexia, nausea, fever >3 days’ duration, and/or abdominal pain (especially right upper quadrant discomfort), icterus, or vomiting. Patients should be instructed to immediately hold therapy if any of these symptoms occur, and contact their prescriber. Lastly, INH administration with food significantly reduces bioavailability. Therefore, patients should be advised to take INH on an empty stomach.

Rifamycins. The rifamycins are the other cornerstone of TB therapy. Rifamycins kill bacterial cells by inhibiting bacterial RNA synthesis. When administered in combination with INH, these are utilized in continuation therapy. Agents in this class include rifampin (RIF), rifabutin, and rifapentine, with rifampin being the most common agent used today. The recommended daily dosage of RIF is 10 mg/kg/day (typically 600 mg), though twice to three times weekly dosing is also appropriate under directly-observed therapy.

Adverse effects of rifamycins include increased hepatic enzymes, rash, abdominal cramps, diarrhea, nausea/ vomiting, pseudomembranous colitis, and pancreatitis. Additionally, rifamycins are strong inducers of the hepatic CYP3A4 enzyme system, a common enzyme system employed in drug metabolism. As a result, concomitant administration of these agents with medications metabolized

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by CYP3A4 (e.g., aripiprazole, erythromycin, rivaroxaban, ticagrelor, etc.) should be avoided, as the combination may decrease the serum concentration of such medications. Food decreases the extent to which RIF is absorbed. Hence, patients should be advised to take RIF with a glass of water on an empty stomach (i.e., one hour prior to, or two hours after, meals or antacids). However, rifabutin and rifapentine are recommended to be taken after meals to prevent nausea and vomiting.

Several other clinically sig-nificant drug-drug interactions involving rifamycins exist. While azithromycin has no significant interaction with rifamycins, other macrolide antibiotics (e.g., clarithromycin, erythromycin) do. Concomitant administration of clarithromycin and rifamycins may increase rifamycin concentrations to toxic levels. Concurrent adminis-tration of rifamycins with hormone therapy (e.g., ethinylestradiol, norethindrone) should prompt pharmacists to counsel patients regarding the addition of barrier contraception such as condoms, spermicidal foams, or sponges to prevent pregnancy. Patients on levothyroxine may require increased doses while taking rifamycin therapy. Corticosteroid doses may be depleted with coadministration; therefore, a two- to three-fold in-crease in corticosteroid dose should be considered. Pharmacists should be aware that patients on warfarin may require a two-to three-fold increase in dose since rifamycins may increase the

metabolism of warfarin. Lastly, when concurrently administered with methadone, rifampin and rifapentine may deplete serum methadone concentrations. Therefore, higher methadone doses may be required.

Pyrazinamide. Pyrazinamide (PZA) is an essential element of pharmacologic therapy during the therapeutic initiation phase. While its exact mechanism of action has not yet been elucidated, this agent exerts its effect after being converted to pyrazinoic acid in susceptible strains of mycobacterium, effectively lowering the pH of the environment and preventing the bacteria from thriving. PZA can act as both a bacteriostatic and bactericidal agent, depending on the drug’s concentration at the site of infection.

Adverse reactions of PZA include malaise, poor appetite, nausea/ vomiting, arthralgia, and myalgia. Like INH, PZA has the ability to diminish the therapeutic effect of the BCG vaccine and has a similar effect on the cholera vaccine. Although it is recommended to concomitantly administer both RIF and PZA during the initiation phase of therapy, clinicians should be advised that PZA may enhance the hepatotoxic effects of RIF. Therefore, the combination of RIF and PZA is not recommended in dual treatment of latent TB, especially since alternative options for dual therapy are available.

Ethambutol. Ethambutol (EMB) is the final essential agent utilized in quadruple therapy during the initiation phase of TB treatment

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and works by inhibiting arabinosyl transferase, an essential component of the bacterial cell wall. As a result, cell wall synthesis is inhibited and the mycobacterium can no longer grow.

Adverse reactions to EMB are relatively infrequent when compared to the other agents utilized during initial therapy. Patients have reported abdominal pain, confusion/disorientation, dizziness, hallucination, headache, malaise, and abnormal liver function tests.

Alternative Pharmacologic Therapies. Clinical practice guidelines report that once daily dosing of agents such as cycloserine, ethionamide, para-aminosalicylic acid, and levofloxacin is appropriate alternative therapy in patients who have extensive TB disease and/or are resistant to INH or RIF. These agents provide ad-equate coverage of Mycobacterium tuberculosis and are acceptable in cases of drug resistance or extensive cavitary disease.

Cycloserine can be bacteriostatic or bactericidal and works by competing with D-alanine for incorporation into the bacterial cell wall, thereby inhibiting bacterial cell wall synthesis. Less common ad-verse effects of cycloserine include cardiac arrhythmia and skin rash. Vitamin B-12 and folic acid deficiencies have been reported; there-fore, vitamin B-12 and folic acid supplementation may be required in some patients. Lastly, patients taking cycloserine may experience adverse neurologic effects such as confusion, dizziness,

drowsiness, paresthesia, psychosis, seizure, and vertigo. Alcohol may enhance the neurologic effects and is, therefore, considered a category X interaction with cycloserine.

Ethionamide is a bacteriostatic agent that acts by inhibition of bacterial peptide synthesis. Adverse reactions of ethionamide include orthostatic hypotension, altered sense of smell, depression, dizziness, psychiatric disturbance, acne vulgaris, purpura, goiter, gynecomastia, weight loss, abdominal pain, and increased liver enzymes. Neurotoxic effects of ethionamide may be relieved by the administra-tion of pyridoxine.

Para-aminosalicylic acid (PAS) is a highly-specific bacteriostatic agent active against M. tuberculosis. Structurally related to paraaminobenzoic acid (PABA), its mechanism of action is thought to be similar to that of sulfonamides, a competitive antagonism with PABA which disrupts plate biosynthesis in sensitive organisms. Adverse effects of PAS include vasculitis, skin rash, goiter, hypoglycemia, abdominal pain, nausea/ vomiting, agranulocytosis, and thrombocytopenia. Salicylates may enhance the effects of vitamin K antagonists, such as warfarin. Therefore, patients on concomitant therapy should have their INR checked regularly.

Para-amino salicylic acid is available as granules that may be mixed in and ingested in soft foods.

Fluoroquinolone antibiotics

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(levofloxacin, moxifloxacin) exert their effects by inhibiting DNA-gyrase in susceptible organisms, thereby inhibiting relaxation of supercoiled DNA and promoting breakage of DNA strands. Common adverse effects of fluoroquinolones include headache, insomnia, dizziness, skin rash, nausea/vomiting, diarrhea, and abdominal pain. Be-cause they are cleared extensively by the kidneys, fluoroquinolone doses must be adjusted to account for renal function. Gastric anti-secretory agents such as pantoprazole, lansoprazole, esomeprazole, or ranitidine may decrease the absorption of oral fluoroquinolones. Patients should be advised to space these agents out about two hours if they are required to take them concurrently.

Interruptions in Therapy

Continuous pharmacologic treatment is of utmost importance during the intensive phase of therapy, as this is when the bacterial concentration is at its highest and also when the risk of developing drug resistance is greatest. Conversely, during the continuation phase of TB treatment, the bacterial load is much lower and the goal of therapy is to kill any persisting organisms that were not killed during the initiation phase.

Given the extensive duration of therapy, interruptions in therapy of TB are common. In the event that therapeutic interruption oc-curs, the supervising physician is responsible for deciding between completely re-initiating a course of therapy or to simply continue therapy as originally

intended. Generally, the earlier the lapse in therapy and the longer its duration, the greater the negative impact and the higher likelihood of needing to restart therapy from the beginning. Duration of therapy interruption and the patient’s bacteriologic status prior to and after interruption are also important considerations.

Summary

Tuberculosis is one of the most deadly diseases worldwide. It is spread from person to person via inhalation of airborne droplets containing Mycobacterium tuberculosis, an acid-fast bacillus. Patients with latent TB show no outward signs or symptoms of infection and, therefore, are generally unable to spread TB bacteria to others. Those with active TB, however, commonly display symptoms of infection (i.e., excessive cough, chest pain, weakness/ fatigue, etc.) and are capable of spreading TB bacteria to others as an airborne pathogen. It has been well-established that appropriate treatment of TB renders the patient noninfectious, prevents drug resistance, minimizes the risk of TBrelated disability or death, and nearly eliminates the potential for relapse.

Treatment of TB focuses on both curing the individual patient and minimizing the transmission of M. tuberculosis to others. Hence, successful treatment of TB is beneficial for both the individual patient and the community in which the patient resides.

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A four-drug treatment regimen of isoniazid, rifampin, pyrazinamide, and ethambutol remains the recommended initial treatment for drug-susceptible TB. Pharmacologic therapy should be initiated promptly, often before microscopy, molecular tests, and/or bacterial culture results are known. While INH, RIF, PZA, and EMB are the four most common agents utilized for treatment of active TB, other agents such as fluoroquinolones, cycloserine, and ethionamide may be necessary in specific complex patient populations such as patients with extensive TB disease, those with documented treatment failure to the preferred therapeutic agents, patients with cavitation on chest X-ray, and those with concomitant HIV.

The author, the Ohio Pharmacists Foundation and the Ohio Pharmacists Association disclaim any liability to you or your patients resulting from reliance

solely upon the information contained herein. Bibliography for additional reading and inquiry is avail-able upon request.

This lesson is a knowledge-based CPE activity and is targeted to pharmacists in all practice settings. Disclosure: The OPF trustees and other individuals responsible for planning OPF continuing pharmacy education activities have no relevant financial relationships to disclose.

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C o n t i n u e d continuing education quiz

The Role of the Pharmacist in Tuberculosis Management

1.TB may affect all of the following EXCEPT the: a. lungs. c. heart. b. brain. d. spine.

2.All of the following persons are at higher risk for TB EXCEPT: a. Caucasians. b. those frequently in close proximity with TB. c. IV drug users. d. those who are immunocompromised.

3.Which of the following tests is the gold standard for TB testing?

a. Purified protein derivative c. Plasmapheresis b. Polymerase chain reaction

4.All of the following symptoms may be present in patients with active TB disease EXCEPT: a. persistent productive cough. c. loss of appetite. b. dull chest pain. d. headache.

5.The standard of practice that is widely accepted in the overall management of TB is: a. DOT (directly-observed therapy). b. TDM (therapeutic drug monitoring).

6.Which of the following is the recommended combination therapy for treatment in the intensive phase of TB therapy? a. Isoniazid + moxifloxacin + pyrazinamide + ethambutol b. Isoniazid + cycloserine + pyrazinamide + ethambutol c. Isoniazid + rifampin + ethionamide + ethambutol d. Isoniazid + rifampin + pyrazinamide + ethambutol

7.Isoniazid acts by: a. inhibiting synthesis of mycolic acid. b. inhibiting arabinosyl transferase. c. inhibiting bacterial RNA synthesis.

Completely fill in the lettered box corresponding to your answer.

1.[a] [b] [c] [d] 6. [a] [b] [c] [d] 11. [a] [b] [c] [d]

2.[a] [b] [c] [d] 7. [a] [b] [c] 12.[a] [b] [c] [d]

3.[a] [b] [c] 8.[a] [b] [c] [d] 13. [a] [b] [c] [d]

4.[a] [b] [c] [d] 9. [a] [b] [c] [d] 14. [a] [b] [c] [d]

5.[a] [b]10.[a] [b] [c] [d] 15. [a] [b] [c] [d]

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8.Pyridoxine supplementation is recommended as concurrent therapy with isoniazid in all of the following patients EXCEPT: a. pregnant women. c. formula-fed infants. b. HIV patients. d. diabetics.

9.Isoniazid carries a Black Box Warning with respect to the potential development of: a. lupus-like syndrome. c. pancreatitis. b. severe/fatal hepatitis. d. renal failure.

10.The recommended daily dose of rifampin is typically: a. 150 mg. c. 600 mg. b. 300 mg. d. 900 mg.

11.The rifamycins are strong inducers of which hepatic enzyme system? a. CYP3A4 c. CYP2D6 b. CYP2C19 d. CYP74A

12.Adverse effects of pyrazinamide include all of the following EXCEPT: a. malaise. c. arthralgia. b. nausea. d. dizziness.

13.Ethambutol acts by: a. competitively antagonizing para-amino-benzoic acid. b. inhibiting synthesis of mycolic acid. c. inhibiting arabinosyl transferase. d. inhibiting bacterial RNA synthesis.

14.Which of the following alternative pharmacologic agents for extensive TB disease may cause a deficiency of vitamin B-12 and folic acid? a. Fluoroquinolones c. PAS b. Cycloserine d. Ethionamide

15.Common adverse effects of fluoroquinolones include all of the following EXCEPT: a. abdominal pain. c. dizziness. b. constipation. d. vomiting.

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