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Summer 2013 Vol. 5, No. 3

Arizona Journal of Pharmacy

THE OFFICIAL PUBLICATION OF THE ARIZONA PHARMACY ASSOCIATION Brought to you by Pharmacy Network of Arizona

PHARMACY: A GLOBAL PROFESSION

ARIZONA PHARMACY ASSOCIATION 2013 ANNUAL CONVENTION & TRADE SHOW

THANK YOU TO OUR SPONSORS

Arizona Journal of Pharmacy

THE OFFICIAL PUBLICATION OF THE ARIZONA PHARMACY ASSOCIATION Brought to you by Pharmacy Network of Arizona

Vol. 5, No. 3

Summer 2013

In This Issue Columns

President’s Message CEO’s Message Academy News • Community Pharmacy Academy • Geriatric Care Academy • Health-System Academy • Managed Care Academy • Technician Academy • Student Pharmacist Academy

Featured Articles

The Golden Rule A Look Back - Patent Medicines Time Capsule Super Bugs Methylnaltrexone Bromide: Place in Therapy for Opioid-Induced Constipation An Evaluation of Pharmacy Regulation Waivers Granted to Arizona Pharmacies from 2002 through 2012

Departments

New Members Association News PAPA Legislative Update Arizona State Board of Pharmacy Feature Pharmacist • Caring for the Community on a Larger Scale Student Perspective • Student Leadership, Where Will it Take You Next? Drug Information Question In Memoriam Continuing Education

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Editor

Kelly Ridgway, R.Ph. Chief Executive Officer

www.azpharmacy.org

Managing Editor

Janet Weigel Marketing and Communications Manager

Editorial Board

Whitney Rice, Pharm.D. Laura Tsu, Pharm.D.

Tina Smith, Pharm.D., BCPS

Summer 2013 • Arizona Journal of Pharmacy • 1

President’s Message

Passages

Michael Dietrich, Pharm.D. AzPA President

This time of year has a tinge of nostalgia around it. Having completed my term as President of the Arizona Pharmacy Association, I look back on this past year and view this transition as not an end but a beginning. This year’s record-breaking attendance and outstanding continuing pharmacy education activities made the AzPA 2013 Annual Convention the best ever. We celebrated the diversity and worldwide significance of pharmacy. While we mark the change of our association leadership and honor our peers and colleagues at this annual event; it is also a time of renewal, reinvention, and revitalization. The convention was attended by student pharmacists who are just embarking on their careers; by veteran pharmacists who are responding to their vital role on the health care team; by retired and semi-retired pharmacists who are still passionate about our profession and are looking to enhance their skills; by pharmacy technicians who are preparing for their ever-expanding role in patient care. I always have a feeling of renewal following the annual convention, but this year it was especially strong as I saw the re-engagement of some of our members who had been inactive for a while.

My sincerest thanks to the retiring board members who served with me this past year on the AzPA Board of Directors. You are true leaders and stewards of our profession. The 2013 - 2014 Board was installed at the Annual Convention. Please give Ray Clark, your new President, and the entire board your support and involvement. Combined, the two colleges of pharmacy in Arizona recently graduated nearly 250 new pharmacists. Graduation may be the end of pharmacy school, but is the beginning of a new journey to advance the vision of pharmacy to provide optimal patient care. The new class of first-year pharmacy students is just arriving at pharmacy schools across the country, beginning the journey to their chosen career. They are charged with the responsibility to complete their education and write the next chapter in pharmacy. The future of our profession is bright with the talents and potential of these women and men. Transition also brings sadness and joy. This past year we said goodbye to too many of our pharmacy colleagues and friends: young and old, celebrated pioneers and promising rising stars. They will be missed. But we added many future pharmacists with the birth of dozens of babies to our pharmacy family. Congratulations to the parents! AzPA has actively championed the education of the public on the issues related to prescription drug abuse and misuse, promoted the prevention of medication errors through continuous quality improvement

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processes, and advocated with great success on behalf of the profession at the Arizona State Legislature. This past year has seen significant strides in the efforts for recognition of pharmacists as providers. Arizona has been at the forefront of this movement, but the crusade is far from over. Opponents still do not see pharmacists as health care professionals treating patients, but as “druggists” with “customers”. When I began my year as AzPA President I knew we had active and dynamic members who are passionate about what they do for pharmacy, their patients, and their communities. My hope was to engage and inspire you to be passionate stewards of pharmacy, making a difference in the lives of your patients. This year I saw you have a huge impact on our profession as providers, educators, mentors, and involved community citizens. Thank you for the opportunity to bear witness to and be a part of this incredible Association, its members, and its mission.

“The world is round and the place which may seem like the end may also be only the beginning.” Ivy Baker

CEO’s Message

The Goal Is In Sight I have spoken to you many times regarding the national and state efforts underway for pharmacists to be recognized as health care providers under the Social Security Act. I am more hopeful than ever that we can achieve this status, but we must continue to apply pressure to our national associations to keep the momentum and resources moving towards our goal. You have a role to play as well. The national and state associations will not be able to do this without your support on a grassroots level. Here are ways you can help: • Become a member of your state and national association. Your membership is important to our efforts. • Volunteer to support your national and state association by contacting your legislators, inviting policy makers to your practice site, gathering statements from your patients and providers demonstrating how you have impacted their health care. • Support your national and state political action committees. I ask for your help with another pressing issue. While we have seen great success in Arizona collaborating with our provider partners (MD, DO, NP), there is still some hesitancy among the national and state medical associations to allow pharmacists to work to the top of their degrees. At a recent American Medical Association (AMA) House of Delegates the following policy statement was approved:

AMA Resolution 218 – AMA Response to Drug Store Chain Intrusion into Medical Practice 1. That our American Medical Association deem inappropriate calls from pharmacists to verify the medical rationale behind prescriptions, diagnosis and treatment plans to be an inappropriate interference with the practice of medicine and unwarranted; and be it further 2. That our AMA work with pharmacy associations such as the National Association of Chain Drug Stores to engage with the Drug Enforcement Administration, the federal Department of Justice, and other involved federal regulators and stakeholders, for the benefit of patients, to develop appropriate policy for pharmacists to work with physicians in order to reduce the incidence of drug diversion and inappropriate dispensing; and be it further 3. That if the inappropriate pharmacist prescription verification requirements and inquiry issues are not resolved quickly, our AMA will advocate for legislative and regulatory solutions to prohibit pharmacies and pharmacists from denying medically necessary and legitimate therapeutic treatments to patients. (Directive to Take Action) The intent in sharing this policy statement is not to create animosity toward the AMA, but rather to challenge all of you to share what you are doing with your providers, patients, family, and friends. While the AMA’s primary reason for passing this resolution was to address prescription drug abuse,

Kelly Ridgway, R.Ph. AzPA CEO

there are definite opportunities to reach out to primary care providers and share what you are doing and how you can partner with them to care for our patients. This is not a turf issue. We are all on the same team working every day to ensure our patients achieve good health outcomes. We have worked hard in Arizona to establish collaborative practice laws that allow us to partner with providers to help manage patients’ drug therapy. We know pharmacists play a vital role on the health care team. We are the drug experts and need to be teaming up with providers to ensure patients are on the best drug therapy possible. Ultimately, pharmacists can ease the burden of drug therapy management allowing providers to see more patients. With millions of new patients being covered by the Affordable Care Act and a provider shortage, we need to ensure patients receive the care they require. Provider status is a worthwhile goal, but attaining it will partially depend on what you do next. Don’t miss this opportunity to advance the pharmacy profession. Do it today. The goal is in sight. Let’s reach it together.

Summer 2013 • Arizona Journal of Pharmacy • 3

New Members

WELCOME NEW MEMBERS PHARMACISTS Jay Chadderwala Tram P. Pham Audra Puodziukas Melissa Buchanan Angela Hamman Stephanie Hines Alison Sutton Robert Ferguson Usama Alkazaki Alissa Carter Tara Hall Georgina Peace Adeniyi Alo Tracy Andrewcavage Carolyn E. Beno Robert Carter III Julie Gordon-Smith Darren Kennedy Nicole Murdock Amy Namanny Ifeoma Ify Obiora Christopher Peric J. Carmelina Rivera Ann Sanders Julie Shepler Steven Spravzoff Jane Stein Yari Valle Carol Welch Albert Williams Darren Clonts Laura Allen Kimberly Andrews

JoLaine Draugalis Quentin Florence Martha Gans Hemantha Kesavadas Keith Wells Alaa Bagalagel David Black Holly Christianson Ashley Kalchthaler Eman Fakher Kirolos Laura Koury Stephanie Mansfield Suzanne Toyama-Bodnar William Fixler Randee Gelatic Carrie Hammer Hussam Kutbi Davena Norris Ashlee Gerfen Jenessa Burney Ralph Troller William Gault ASSOCIATES Scott Larson Bob Waski TECHNICIANS Crystal Barrett Harranna Begay Kayla Berry Richard Miller Cassandra Pacheco Bryon Pasley

Audrey Stewart Christina Abedi Joseph Alvarez Cheri Andrew Sascha Bianchi Eudora Burnham Amalia Gilbert Asima Khan Barbara Lampkin Lupe Rosario Kimberly Ann Smith Lisa Webster Laura Brittain Teri Mercer Laci Sorenson STUDENT PHARMACISTS Brooke McKinney Amy Nguyen Kaitlin Berger April Bills Emily Butts Courtney Deshauer Bac-Ai Dong Katie England Jared Evans Melissa Garner Taylor Goodman Van Ho Amy Johnson John Lewis Brian Lipski Jason McAddley

Katelyn McMillan Thi Lam Ngo Thuy Linh Ha Nguyen Shama Patel Samantha Selke Jay Sheth Ashley Stone May Sui Chelsea Warren Erica Wood Meridith Yannace Dimpa Choksi Kirla Barbosa Detoni Valerie Echols Steven Evenson Stephanie Funkhouser Evan Gilbo Brent Houston Paul Nguyen John O’Brien Juliana Pierson Hector Sandoval Abbey Siegler Chiu Jon Sam Tong Stephanie E. Campbell Garrett Coffee Shaimaa El-Gendy Kayla McGahey Marben Mopera Mark Smith Alexandra Trinh

Cheers for Volunteers! The Arizona Pharmacy Association staff is here to support YOU - our members. We acknowledge the contributions of the volunteers who have made a difference for our organization and their fellow pharmacy professionals. Thank you for all you do! Steve Warren Phil Schneider Erin Bonelle Vickie Crouch Tagg Daugherty Janet Cooley Crane Davis Martha Fankhauser Elizabeth Pogge

Lisa Goldstone Stacy Haber Kristyn Straw Nicole Henry Lindsay Davis Mindy Throm Burnworth Lindsay Kittler Laura Tsu Dawn Gerber Betty Louton Dean Wright Bill Jones Kevin Boesen Grace Akoh-Arrey Ruben Vital Jeff Marshall Tara Storjohann Asal Azizoddin Suzanne Larson

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Terri Warholak Neil MacKinnon Shrouq Qaisi Hussam Kutbi Carol Rollins Butch David Sandra Leal Jon Glover Scott Hall Matt Covert Christi Jen Stephen Perona Samantha Karr Jason Gertsner Ruth Demar Karen Ansaldo Carolyn Beno Suzanne Larson Ashlee Gerfen

Marcella Hoyland Erin Raney Shareen El-Ibiary Mark Boesen Hanna Phan Allison George Bob Lipsy Kelly Green Boesen Chris Peric Bao Nquyen Roger Morris

AzPA Installs 2013-2014 Board of Directors The Arizona Pharmacy Association (AzPA) announces the election of the 2013 - 2014 Board of Directors. Beginning their one-year terms in July 2013 are: Ray Clark, President Ann Sears, President-Elect Michael Dietrich, Past President Dawn Knudsen Gerber, Treasurer Scott Hall, Secretary Betty Louton, Community Pharmacy Academy Chair Grace Akoh-Arrey, Community Pharmacy Academy Chair-Elect Elizabeth Pogge, Geriatric Care Academy Chair Nicole Kitts, Geriatric Care Academy Chair-Elect Kristen Allison, Health-System Academy Chair Mitchell Buckley, Health-System Academy Chair-Elect Eric Luecht, Managed Care Academy Chair Paul Lynne, Managed Care Academy Chair-Elect Judith Day, Technician Academy Chair Reg Roy, Technician Academy Chair-Elect Pritesh Patel, Student Pharmacist Academy Chair University of Arizona COP Sabrina Pennock, Student Pharmacist Academy Chair Midwestern University CPG Pearce Engelder, Student Pharmacist Academy Chair-Elect University of Arizona COP Norbert Laskowski, Northwest District Director Laura Moore, Southwest District Director Ken Fletcher, Southeast District Director Greg Larson, Industry Representative J. Lyle Bootman, Dean, University of Arizona COP Dennis McCallian, Dean, Midwestern University CPG Roger Morris, Legal Counsel

Association News Election of the Student Pharmacist Academy Chair-Elect for Midwestern University College of Pharmacy Glendale will take place in August 2013. The 2013-2014 AzPA Board of Directors were installed during the AzPA Annual Convention at the Westin La Paloma Resort in Tucson, Arizona during the AzPA Annual Awards Luncheon on June 28, 2013.

PharmPAC Drawdown Raises $6100

The Pharmacists Political Action Committe of Arizona (PharmPAC) held its annual raffle to raises funds in support of pharmacy political action. The $6100 raised was split between the fund and 10 winning raffle tickets. Cash prizes totaling $2,033 were awarded: Paul Draugalis, Crane Davis, Terry Daane, Lee Ellershaw, Olanrewaju Lanre-Kolawole, Whitney Rice, Chad Schuster, and Stephanie Wernsman of Fry’s Food & Drug pooled their resources and had four winning tickets totaling $1,279.25! They each received over $159. Other winners were Ken Berry $457.50 Eric Luecht $ 59.25 Kris Kaniski $ 59.25 Ann Sears $ 59.25 Ruth Demar $ 59.25 Paul Stoneburg $ 59.25 Only AzPA members may participate in the PharmPAC Drawdown raffle. Contributions to the PharmPAC are not tax deductible. To make a contribution go to www.azpharmacy.org/PharmPAC.

Installation of the 2013-2014 Arizona Pharmacy Association Board of Directors: Front row, left to right: Greg Larson, Ken Fletcher, Norbert Laskowski, Sabrina Pennock, Judi Day, Elizabeth Pogge, Pritesh Patel, Laura Moore, Betty Louton, Ann Sears. Back row, left to right: Lyle Bootman, Pearce Engelder, Nicole Kitts, Grace Akoh-Arrey, Reg Roy, Scott Hall, Eric Luecht, Mike Dietrich, Dennis McCallian. Summer 2013 • Arizona Journal of Pharmacy • 5

Association News APF News At it’s June 28, 2013 board meeting, the Arizona Pharmacy Foundation installed the 2013-2014 Board of Directors: Ken Berry, President; Steve LeMahieu, Vice President; Terry Daane, Treasurer; Ken Mahan, Member-at-Large; Chris Lesaca, Member-at-Large; Ray Clark, AzPA Representative; and Roger Morris, Statutory Agent. Plans are underway for the 2014 APF Southwest Pharmacy Symposium. Details will be forthcoming. PAPA Breakfast The Foundation and PAPA (Pharmacists Assisting Pharmacists of Arizona) hosted a breakfast on Friday, June 28, 2013, for the Arizona State Board of Pharmacy Board of Directors and staff. The purpose of the breakfast was to provide an overview and update of the PAPA program to the current board, staff, and key guests. Presentations were made by PAPA counselors Jim Corrington and Dr. Julian Pickens, and PAPA Steering Committee Member Mark Murphy. The PAPA program, administered by the Arizona Pharmacy Foundation, provides assistance to any pharmacist, pharmacy student, or pharmacy technician with an impairment. The ultimate goal of the program is to help the recovering individual re-enter practice as a competent professional. Silent Auction The Foundation held its annual silent auction during the AzPA 2013 Annual Convention. Dr. Robert Kravetz, Phoenix gastroenterologist and pharmacy memorabilia enthusiast, generously donated items from his personal collection to the Foundation for this auction. The auction raised $925 for APF.

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Record Attendance at AzPA 2013 Annual Convention More than 450 pharmacy professionals attended the AzPA 2013 Annual Convention at the Westin La Paloma Resort and Spa in Tucson, Arizona from June 27 to 30, 2013. Pharmacists, student pharmacists, pharmacy technicians, and other pharmacy professionals participated in more than 30 continuing pharmacy education activities, social functions, and informational product sessions. Thank you to our exhibitors and sponsors whose contibutions are a huge part of the success of the annual convention. We truly couldn’t do it without your support! 2013 AzPA Exhibitors and Sponsors

Allison Medical American Regent AmerisourceBergen ARKRAY USA Avanir Pharmaceuticals Banner Health BD Diabetes Boehringer-Ingelheim CAPS Cardinal Health Cubist Pharmaceuticals CVS Caremark Eli Lilly Express Scripts Forest Pharmaceuticals Freedom Pharmaceuticals Fry’s Pharmacy Grifols, Inc. Humana RightSource Rx Lundbeck Pharmaceuticals McKesson Corporation

Meda Pharmaceuticals Merck Vaccines Midwestern University Novo Nordisk Otsuka America Pharmaceutical Otsuka Neuroscience Pharmacists Mutual Companies Pharmacy OneSource PharMEDium Services Prugen Pharmaceuticals Rare Disease Therapeutics Roche Diagnostics Rx Relief Rx Timer Cap Safeway Sanofi Cardiovascular Sanofi Diabetes Santarus, Inc. Sigvaris, Inc. Sunovion University of Arizona

Brian Willis (center) accepts the Pharmacy Appreciation Award on behalf of Cardinal Health. AzPA Fellows Inaugural Class: Jerome Wohleb, Terry Daane, Crane Davis, Kelly Ridgway, Kevin Boesen, Michael Dietrich. Mike Dietrich receives the Outstanding Leadership Award from Kevin Boesen. Paul Draugalis (center) receives the Fry’s Pharmacy Appreciation Award. Pharmacy Appreciation Award Recipients: Sandra Leal, Kelly Green Boesen, Chris Lesaca, Ken Fletcher. Ray Clark receives his “President” ribbon from Mike Dietrich.

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Association News AzPA 2013 Annual Convention Annual Awards Presentations Outstanding Leadership Award Michael Dietrich, Pharm.D. Outgoing President Award Sponsored by McKesson Michael Dietrich, Pharm.D. Pharmacy Leadership Award Sponsored by NCPA Ray Clark, Jr., Pharm.D. Incoming President Award Sponsored by AmerisourceBergen Ray Clark, Jr., Pharm.D. Pharmacy Appreciation Awards John Garigen Kelly Green Boesen, Pharm.D. Kenneth Fletcher, Pharm.D. Sandra Leal, Pharm.D. Chris Leo Lesaca, C.Ph.T. Corporate Appreciation Award Cardinal Health Fry’s Pharmacy

AzPA Honorary Membership Metta Lou Henderson, Ph.D., Hon.D. Distinguished Young Pharmacist of the Year Sponsored by Pharmacist Mutual Insurance Companies Dyan Cherry, Pharm.D. Excellence in Innovation Award Sponsored by Upsher-Smith Laboratories Amy Kennedy, Pharm.D. Exemplary Patient Care Award Carol Rollins, Pharm.D. Outstanding Pharmaceutical Representative William O’Neill, R.Ph., Boehringer Ingelheim Bowl of Hygeia Sponsored by APhA and NASPA with support from Boehringer Ingelheim Kathryn M. Labbe, R.Ph. Technician of the Year Award Andrea Arellano, C.Ph.T.

AzPA Hall of Fame J. Lyle Bootman, III, Ph.D. Richard N. Herrier, Pharm.D. AzPA Hall of Fame 2013 Posthumous Inductions Richard Hall Rufus Lyman Dennis Messier Henry W. Winshop, III Thomas Samuels Elias Schlossberg AzPA Fellows Inaugural Class Jerome Wohleb John Musil Terry Daane Crane Davis Linda McCoy Mark Boesen Kelly Ridgway Kevin Boesen Michael Dietrich

Pharmacist of the Year Jon J. Glover, Pharm.D.

1. Kathryn Labbe (center) receives the Bowl of Hygeia Award from Denise Ravenscroft of Boehringer-Ingelheim and Carl Labbe, her husband. 2. Reg Roy presents the Technician of the Year Award to Andrea Arrellano. 3. Jon Glover (right) accepts the Pharmacist of the Year Award from Greg Morrill. 4. Mike Dietrich recognizes Carol Rollins with the Exemplary Patient Care Award. 5. Ray Clark and Ryan Goodrich, Pharmacist Mutual, honor Dyan Cherry as the Distinguised Young Pharmcist. 6. Brian Erstad awards Amy Kennedy the Excellence in Innovation Award. 7. AzPA Hall of Fame inductees J. Lyle Bootman, III and Richard N. Herrier. Summer 2013 • Arizona Journal of Pharmacy • 7

Association News

2013 AzPA Annual Convention Photos 1. Carl and Dorrill Johnson 2. Scott and Alicia Hall 3. Ken and Falene Fletcher 4. Devi and Larry Anderson 5. JoLaine Draugalis, Hal Wand, and Paul Draugalis 6. Eileen Telles, Dana Acosta, and Julie Miramont of AmerisourceBergen 7. Carol Rollins and Martha Fankhauser 8. Amy Kennedy and Mary Gurney 9. Kari Bush and Naomi Rosenberg 10. Jenna Gianninoto, Kelly Kistler, and Kristin Calabro 11. Ray Clark and Ann Sears 12. Mark Redell, Jeremy Gerber, Dawn Gerber, and Soren Gerber 13. Imelda Gil (standing), Asima Khan, and Consuelo Pitpitan 8 â€˘ Arizona Journal of Pharmacy â€˘ Summer 2013

Association News

2013 AzPA Annual Convention Photos 1. Dusty Deschamps, Becky Deschamps, Betty Louton, and Mike Louton 2. ESI Booth: Kevin Dominguez, John Pierce, Bryan Olenik, Ann Sears, Marion Rizer, Ajay Desai, and Dennis McAllister 3. Reg Roy and Judi Day 4. Steve Spravzoff and Laura Moore 5. Safeway Booth: Joe Leyba, Gerald Denny, Boyd Hunsaker, June Piposar, Andrew Gaspar, Sean Duffy and David Carrick 6. Amy Shea and Ryan Gries 7. Joel Butler, Brad Crawford, Brian Willis, and Amber Graham of Cardinal Health 8. McKesson Booth: Mike Gibbons, Connie Williams, and Nuwang Kunga 9. Ruth DeMar, Kathy Huff, Charlotte Pendergast, and Robin Rice 10. Mindy Burnworth, Michelle Nemetz, and Kristina De Los Santos 11. Pritesh Patel, Kelly Ridgway, Lindsay Davis, and Eric Wong 12. Hanna Phan, Jill Augustine, Terri Warholak, and Amy Kennedy 13. Sophia Galloway

Visit the AzPA website at www.azpharmacy.org for more photos!

Summer 2013 • Arizona Journal of Pharmacy • 9

PAPA With Each New Day Comes New Strength and New Thoughts by Anonymous

My name is “Ralph” and I am an alcoholic. I was born on March 6, 1959, in Chicago, Illinois. I was the middle child of seven raised in a devout Roman Catholic family. For the most part I had a normal childhood and was raised with traditional Christian values. This meant church was instilled in our every day lives. My father was an electrical engineer for Motorola and we moved frequently while growing up. My parents would take us to the local church for education, social activities and as a connection to the new community. I know when I went into my parents’ bar with an empty gallon milk container (which I filled with all sorts of miscellaneous spirits and took to my sixth grade class), I did not think that this behavior would end up ruining my life. This was an isolated incident until I turned 16 and was able to drive. I quickly got into the habit of meeting my friends at the park with a six pack of beer and guzzling it until it was gone. We had innocent fun with no one noticeably getting hurt. I noticed that I was more outgoing and people thought I was pretty funny. I loved the attention. I was accepted to attend the University of Texas and Austin proved to be a very fun place. In between work and school I kept busy and did not have a lot of money. I kept drinking my beer on the weekends, but to me it seemed like I was on my way to a successful life. My grades were good and I got accepted into the School of Pharmacy. I was going places! Time went by quickly; I met a great girl and got married. I graduated the next year and got a job and was now making steady money at the wise old age of 23. I now thought I was God’s gift, everything was going my way. I thought it was common and ordinary behavior to have a few beers at the local pub when I got off of work. I had earned that privilege hadn’t I? I thought since I didn’t bring a bunch of booze home I was a great husband. In short time I was drinking a six pack every day while I was playing pool, shooting darts and goofing around with the guys. We had children quickly and I thought I was living the dream. We fought a little bit because I was starting to come home later as the years went by. I thought everyone had a beer in their hands doing chores or family activities. With this method of rationalization there was nothing I did without a beer except work, but I was great at that right? Time passes quickly and I am now 32, divorced with three kids. When I get a new job, instead of finding the local church, I find the best bars for my social activities and the stability in my life. I was cloaked in denial and blamed everyone else for things that happened. It’s 1994 and I get pulled over and taken in for a DUI. I wasn’t drunk of course and only got convicted of reckless driving. A normal person working themselves up to better positions

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at much better money would have curbed their appetite, but no, conventional rules do not apply to me. Now it is 2006. What is this policeman pulling me over for? I am an important man in town with lots of friends. Look, I buy them drinks all the time. How dare that judge actually convict me of DUI ? The truth be told you can set your watch by the time I get to the bar; it is my second office. I drink probably 10 to 12 beers plus assorted shots. Truthfully, drinking is not fun anymore; it is a habit. I pride myself on the fact that I do not use drugs or drink at work. Alcohol isn’t a drug, can’t you see. Well, I get a year probation and successfully complete it without drinking. I even go to a few AA meetings but they say the funniest things: “one day at a time”, “if you think you’re humble you are not”, “you will intuitively know”, “serenity prayer”… they must be brain dead or brain washed. I’ve graduated and my problems are gone, let’s have a drink! That didn’t last long. I got a letter from the Texas State Board of Pharmacy and I either strictly adhere to their PRN program (Texas equivalent to the PAPA program) or lose my license. I adhered to a dry drunk for nine months until I drank and failed one of those blasted random urinalysis tests. I got a call at work which instructed me to remove my pharmacy license from the wall, mail it to the State Board and all of a sudden the life I had known was over. This remains the saddest day of my life. My identity was gone. I had been practicing 25 years. There was no more respect, only shame. I had to wait 6 months but my license was suspended for 2 years. I was to begin the PRN program again but guess what? After sitting for 6 months drinking, I didn’t have a penny left which meant no program. In very little time I was homeless. No one would hire me, not even Taco Bell. I bounced from acquaintance to acquaintance constantly looking for work to no avail. My pharmacy license was revoked and I had hit bottom. My parents invited me to come to Sun City, Arizona in June 2010 after my license had been revoked. It took 5 months to find a job, but I eventually went to work at a recreational center in Sun City. I slowly got back on my feet, met a wonderful woman that I married the next year and began thinking life was great again. Sure enough I started drinking again. It did not take long for my wife to start suggesting that I hang up the bottle. I really did love this woman so I figured I just would not do it in front of her. Vodka became my new best friend. I started slamming first small, then larger amounts until I started blacking out. The night would supposedly be going great and then I would wake up in the morning to the disgusted look on her face. Normally she would greet me with this huge smile every morning. This happened many times, the last being on May 14th, 2012.

PAPA (continued from page 10) I woke up on what is now my anniversary date of May 15th, 2012 feeling horrible and looking at that scowl on her face. I knew I was in trouble but there was something different this morning. I looked into the bathroom mirror and felt God with me. He was not pleased. I was humbled and this was not a normal feeling for me. I knew I was done. I faced my wife who was not going to take anymore of me telling her I knew I needed help. I finally understood, I was powerless over alcohol and my life had become unmanageable. Unbeknownst to her I actually meant it. This was the beginning of Godsends which still have not stopped. We googled alcohol rehabilitation programs in the Phoenix area and God picked Calvary Addiction Recovery Center. Sue made me call (yes I wanted her to) and make an appointment for an interview. I had an interview with a counselor named Jim Corrington and we discussed my situation. He asked what I did for a living and I told him that I had been a pharmacist in Texas for almost 30 years and the State Board here wanted me to retake the Naplex exam. How’s that for honest and open? Keep in mind I had no idea who Jim was. We set up the details and I started the 8 week Intensive Outpatient Program. It only took one meeting before I learned who Jim really was so my first task was to fess up and begin being honest. I loved the program and Sue was with me every step of the way. I started going to AA meetings because I wanted to. I learned how it worked and what tools I had at my disposal to lead a happy, sober life. WHAT ! Happy and Sober in the same sentence, what a discovery. I went to all kinds of meetings and found a home group near my house that had early meetings seven days a week. I got a sponsor and began working the steps. I realized what it meant to have God back in my life and amazingly the 9th step promises do come true. I completed the Intensive Outpatient Program and felt like a new man. I could now openly discuss my problems with my peers without suffering the shame I felt I deserved. Although I completed the course, I realized that I would never graduate from AA. That it is a life long program that I really needed. Alcohol was merely a symptom of my disease, AA and the companionship that accompanies it have taught me how to handle life’s situations. It is funny, the more you delve in, the more defects it seems you actually have, and I thought I had been perfect. Instead of King Alcohol, I have returned to Christ my Lord in the only way I know I can be successful - one day at a time. I now have just over a year sobriety. I am in my home group’s rotation and lead the meeting every Tuesday morning. I am my home group’s Agua Fria Intergroup representative, and also have one sponsee. I am a formal member of Arizona’s PAPA program, and communication has begun with Texas’s PRN group. By the grace of God I will simultaneously do both programs. Life is good!

I would like to thank my God for not abandoning me through those decades where I turned my back on my spiritual life. I would like to tell my dear wife Sue and my mother that they are both saints I don’t know what I would have done without their unconditional love! I would like to thank Jim Corrington, whom I consider to be my mentor and my friend and whom I am fortunate to see every week as he is my Peer Group Counselor. I would also like to thank Lisa Yates and the entire staff of the PAPA program for accepting me and nurturing my quest to practice the career I love so much, but turned my back on. Last but surely not least my AA family, fellow peer group professionals, and fellow patients during rehab from whom I have shared my soul and learned immensely through our shared experiences. Don’t Drink, Go to Meetings!

If you or someone you care about is suffering from an alcohol and/or chemical dependency problem... ...help is available.

Pharmacists Assisting Pharmacists of Arizona “A Partnership in Caring”

Contact Lisa Yates, PAPA Program Administrator at 928.532.2293 or papa@azpharmacy.org All calls confidential. Caller remains anonymous.

PAPA

is a program of the Arizona Pharmacy Foundation

Summer 2013 • Arizona Journal of Pharmacy • 11

Legislative Update You should be proud to be a member of the Arizona Pharmacy Association! Our Executive Director Kelly Ridgway, President Michael Dietrich, and lobbyist Jeff Gray had a 100% success rate on the Bills they actively lobbied for on behalf of AzPA during the 2013 legislative session. AzPA supported the following Bills – all of which passed: • HB2045: Medicaid expansion/restoration • HB2327: Designer drugs • SB1188: Pharmacy board In addition, AzPA opposed SB1438 (substitution of biosimilars) because the legislation was premature. After numerous stakeholder meetings and hearings, this Bill was held waiting in the Committee of the Whole and was never brought to the floor for a vote. HB2045: Arizona’s five month long 2013 legislative session was one of the most contentious in recent memory between the legislative leadership and the governor, as well as between the Republican Party and Republican legislators. A big reason for this was some of the Governor’s key priorities impacting the Arizona Health Care Cost Containment System (AHCCCS), Arizona’s Medicaid program. In a surprise move after the House adjourned, Arizona Governor Jan Brewer called a special session to pass Medicaid expansion. After three days (and overnight negotiations) a bipartisan coalition approved Medicaid expansion.1 As a result of HB2045 passing we will see the following: • Expansion: Beginning January 1, 2014, the Bill will expand who is eligible for AHCCCS to include a person whose household’s modified adjusted gross income between 100% and 133% of the federal poverty level (FPL) guidelines. In the event that the Federal Medicaid Assistance Percentage (FMAP) is reduced to below 80%, then these people will no longer be eligible. • Hospital assessments: Beginning January 1, 2014, AHCCCS will collect an assessment on hospital revenues, discharges or by number of patient days. The purpose of the assessment is to fund the nonfederal share of certain costs. • Study committee: The Bill establishes a Medicaid Federal Circuit Breaker and Outcomes study committee through December 31, 2016. The committee is tasked with submitting several reports to the Governor and Legislature on potential impact of decreases in federal funding, restoring Medicaid coverage, and the hospital assessment. • Cost sharing: AHCCCS must pursue having enrollees pay a portion of the cost of their care. HB2327: This emergency measure became effective on April 3, 2013 immediately upon signature by the Governor. It expanded the definition of dangerous drugs to include specific chemical configurations that typically compose synthetic cannabinoids (aka “spice” or “K2”) and substituted cathinones (aka “bath salts”). In addition, it classifies these substances as Schedule I controlled substances. Prior to this, only compounds that were specifically listed in the statute were considered to be illegal, allowing enterprising bathtub chemists to slightly modify the molecule and sell these products on the street or in a smoke 12 • Arizona Journal of Pharmacy • Summer 2013

shop. HB2327 now allows law enforcement more leverage in taking these new designer drugs off the streets more quickly. SB1188: Senator Nancy Barto sponsored this Bill that was forwarded by the Board of Pharmacy. After submitting a sunrise application to clarify that pharmacists can sign prescription orders for immunizations and where the pharmacist is a party to a collaborative practice agreement, AzPA withdrew the sunrise application after coming to an agreement with stakeholders on language to address the concern. Upon working with the AZ Medical Association, AZ Osteopathic Medical Association, AZ Academy of Family Physicians, as well as the Board of Pharmacy, all parties agreed to an amendment to SB1188 that would include a corresponding change to the definition of a prescription order. SB1188 makes the following changes to the Pharmacy Act effective September 13, 2013: • Definition of prescription order: Amended the definition of “prescription order” in A.R.S. 32-1901(77) to include orders initiated by a pharmacist in two limited situations: (a) where the pharmacist was under a protocol-based drug therapy management agreement, or (b) when a pharmacist administered vaccines or immunizations. • Pharmacist licensing reciprocity: Clarifies that a pharmacist may obtain reciprocity if they have graduated from an ACPE-accredited pharmacy school (previous language required it to be on a list approved by the Board of Pharmacy). Requires applicants to have been licensed in good standing for at least one year and have passed the NAPLEX. • Disciplinary options: Allows the Board to discipline a pharmacist, pharmacy intern, graduate intern, pharmacy technician, or pharmacy technician trainee by requiring them to complete Board-designated continuing education classes. This additional type of sanction allows the Board to require additional education without having to place the individual’s license on probation. In addition, the Bill clarifies how pharmacist licenses can be summarily suspended. • DME permits: Currently, companies that distribute or dispense prescription durable medical equipment must hold either a wholesale permit (to distribute) or a pharmacy permit (to dispense). An amendment to A.R.S. 32-1930 allows the Board to promulgate rules to license these entities as a Durable Medical Equipment and Compressed Medical Gas Distributor Supplier permit. We expect the Board to begin work on these new rules within the next quarter. Proposed Board of Pharmacy Rules In addition to all of the changes coming from the legislature, you need to be aware of proposed rule changes. • Permits – General Provisions: Proposed revisions to A.A.C. R4-23-601 would ensure that wholesalers and pharmacies that engage in wholesale transactions ensure that all sellers and purchasers hold appropriate permits. In addition, it will require resident full-service wholesalers and resident pharmacies engaged in wholesale transactions to maintain a pedigree. • Limited-service Long-term Care Pharmacy: Proposed revisions to A.A.C. R4-23-701 to R4-23-704 would clarify the role of consultant pharmacists and the use of automated dispensing systems.

Legislative Update Legislative Update (continued from page 12) • Applications/ Licensure: The proposed changes would require pharmacies to verify new hires’ licenses. In addition, amendments would conform reciprocity and new license applications with the changes from SB1188. If you would like additional information, please contact Laura Carpenter, Legislative Committee Chair at legislative@ azpharmacy.org. In addition, the Arizona State Board of Pharmacy webpage at http://www.azpharmacy.gov/rules_and_ statutes/default.asp has links to each of the items discussed in this article. 1. See Arizona Legislature adjourns special session (Reinhart, Sanchez, Rau, & Pitzl, Arizona Republic, June 13, 2013) at: http://www.azcentral.com/news/ politics/articles/20130613house-approves-medicaid-expansion-billion-budget. html?nclick_check=1

Laura Carpenter AzPA Legislative Affairs Committee Chair legislative@azpharmacy.org

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Summer 2013 • Arizona Journal of Pharmacy • 13

Arizona State Board of Pharmacy Prescription Drug AbuseArizona’s Report Card submitted by Richard Cielinski, R.Ph.

In late June of this year, I was fortunate to be asked to represent the Arizona State Board of Pharmacy in a group conference to discuss policy options and other strategies for decreasing prescription drug abuse along with 3 other state partners. The 6 member Arizona team on which I participated represented a variety of governmental, non-profit, public health, and affiliated partners that were able to make effective decisions for policy development and changes within each of their organizations. The meeting was hosted by an organization called ASTHO, the Association of State and Territorial Health Officials. ASTHO is a national nonprofit organization representing public health agencies in the United States, the U.S. territories, and the District of Columbia, and over 100,000 public health professionals these agencies employ. ASTHO members, who are the chief health officials of the jurisdictions, create and determine sound public health policy and ensure the highest standards in statebased public health practice. Their primary function is to track, evaluate, and advise members on the impact and creation of public or private health policy that may affect them and to give guidance and technical assistance on improving the nation’s health. The purpose of the conference was to allow ASTHO to provide support to our state health officials, their leadership teams, or other partners in developing and implementing our state action plans to address prescription drug misuse, abuse, and drug diversion using a coordinated approach. The main principle is to help health officials identify sound policies and legal strategies that are successful in reducing deaths from overdosing through partnerships with traditional and nontraditional organizations. The conference allowed us to collaborate with other states facing similar issues and to identify the seriousness of the issue, determine political and resource barriers, evaluate partnerships, and summarize how the various organizations and systems could work together using a public health approach. For Arizona, key information about what’s happening to address prescription drug abuse was presented to ASTHO which included: Arizona’s Prescription Misuse and Abuse Initiative (https://www.azcjc.gov/acjc.web/rx/default.aspx), Arizona’s Controlled Substance Prescription Monitoring Program (https:// www.azpharmacy.gov/CS-Rx Monitoring/aboutpmp.asp), 2011 Poisonings in Arizona Report, Arizona Prescribing Guidelines for Emergency Rooms, (www.matforce.org), Arizona Poison and Drug Information Center, Tucson, Arizona, (https://www. pharmacy.arizona.edu/outreach/poison/index.php), Banner Good Samaritan Poison and Drug Information Center, Phoenix, Arizona, (https://www.bannerhealth.com/locations/arizona/ banner+poison+control+center/banner+poison+control+center. htm). From the information provided to ASTHO, a feasibility assessment was created for the State of Arizona and the 6 member team. Issues addressed were Maximizing Opportunities for Prevention within Healthcare Provider Education; Parent, Youth, and Patient Education; Community and Health Care Settings; and Proper Medication Disposal, Enhancing Treatment and Recovery Support Services within Better Access to 14 • Arizona Journal of Pharmacy • Summer 2013

Substance Abuse Treatment, Improved Prescription Monitoring and Surveillance within the Prescription Drug Monitoring Program; Patient Review and Restriction Programs; and, lastly, Reducing Drug Diversion and Partnering with Law Enforcement within Healthcare Provider Accountability; Laws to Prevent Drug Abuse and Diversion. Within each of these areas, existing state actions, strengths/ assets, barriers/challenges, needed stakeholders and resources, desired outcomes, timelines and applicable evaluation measures were discussed within each States’ group. From the feasibility assessment and the issues presented within all of the areas described, the Arizona team compiled 4 definitive domains needing to be addressed from a State health issue and drug abuse prevention perspective. Two key issues within those domains that will be worked on by each member of the Arizona Team within their area of expertise over the next year or so were identified. A. The 1st Domain to be worked on will be Prevention and Education and the 2 key issues are to: 1. coordinate disposal efforts across the state 2. create and disseminate educational materials for patients on the appropriate use and disposal of opioid pain relievers (Patient Education) B. The 2nd Domain to be worked on will be Monitoring and Surveillance (PDMP) and the 2 key issues are to: 1. focus on patients or areas at highest risk in terms of: prescription dosage, number of controlled substance scripts written, quantity of opioids (availability), prescribers who deviate from accepted medical practice and improve access 2. utilization of the existing PDMP data system by physicians and pharmacists for research or other beneficial purposes C. The 3rd Domain to be worked on will be Diversion Control and Law Enforcement and the 2 key issues are to: 1. use PDMP data to identify “doctor shoppers” by the number of discrete prescribers or pharmacies visited with the intent of receiving multiple prescriptions 2. promote collaborative efforts among law enforcement agencies to enforce prescription drug fraud statutes currently in effect D. The 4th Domain to be worked on will be Treatment and Recovery and the 2 key issues are to: 1. increase access to effective, accessible substance abuse treatment programs 2. leverage potential sources of funding for the efficient and effective delivery of substance abuse prevention programs The next challenge for our 6 member Arizona team will be how to address each key issue identified within each Domain and how to coordinate leadership, budget, and follow-through mechanisms. As the project progresses, more information will be provided regarding the progress of the Arizona team’s successes, barriers encountered, and emerging issues in future Arizona Pharmacy Association articles. Closer to home, the Arizona Substance Abuse Partnership (ASAP) was established by Executive Order in June of 2007. It serves as the single statewide council on substance abuse treatment, prevention, intervention/enforcement, and recovery

Arizona State Board of Pharmacy Arizona’s Report Card (continued from page 14) issues. Its mission is: “To ensure community-driven, agency supported outcomes to prevent and reduce the negative impacts of alcohol, tobacco, and other drugs by building and sustaining partnerships. Through coordination and collaboration among its members and their respective agencies and organizations, the ASAP strives to ensure that substance abuse is addressed in a comprehensive manner and that funding is spent efficaciously and efficiently.” To address the growing problem of prescription drug abuse and misuse in Arizona, the ASAP has endorsed a “Prescription Drug Reduction Initiative.” This initiative is currently under way in 3 pilot sites within Arizona, specifically Yavapai, Pinal and Graham counties. The implementation plan for this initiative includes strategies for reducing illicit acquisition and diversion of prescription medications, educating prescribers and pharmacists about “Rx drug best practices”, enhancing prescription drug practice and policies in law enforcement, increasing public awareness about the risks of prescription drug misuse, and building resilience in children and adults. Data gathered from our Prescription Monitoring Program between 2009 and 2011 shows that approximately 10 million Schedule II thru IV prescriptions were written each year in Arizona. Pain relievers accounted for over half of those medications dispensed. According to the ASAP, “In 2010, 13 percent of Arizona adults reported some type of Rx drug misuse in the past 30 days, with half of the misuse related to prescription pain relievers and 10.4 percent of Arizona youth reported some type of prescription drug misuse in the past 30 days, with 76.7 percent of the misuse involving prescription pain relievers.” The ability to participate in the ASTHO conference was a gratifying experience as it allowed me to meet my other Arizona team members who have already been successfully working to combat the drug abuse within the state, as well as our counterparts from the other participating states. The effort is great and there are a tremendous number of organizations involved in resolving this problem and participating together to help try and solve the issue both nationally and within the state. From the standpoint of ASTHO, various Arizona drug abuse prevention initiatives and multiple state partners, an increase in the Arizona Controlled Substances Prescription Monitoring Program sign up and usage needs to be achieved. More pharmacist, practitioner, and law enforcement participation is going to be needed to help manage this drug abuse/misuse problem. Are there barriers? Yes. The current system is not ‘Real-Time’, mandatory tutorial for practitioners is still cumbersome, and the request by practitioners to have their office designee gain access to the database, are among a few challenges currently being addressed in order to help increase usage. I would encourage every licensee to make sure that they are signed up for access to the Controlled Substances Prescription Monitoring Program and to use the database often.

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Featured Article The Golden Rule by Joe Rowan, R.Ph.

Rowan’s Flagstaff Pharmacy was located on US Route 66, right across from the Santa Fe Depot. A block down from the pharmacy were three lively bars known as Joe’s Place, Club 66, and the Rose Tree. Quite regularly one of our local residents would imbibe a little too much and make a trek to our front store steps before passing out. We would then assist them on continuing their journey up the street to yet another doorway. Three doors down from us was the Western Union office and we always had one or two down-and-outers at the soda fountain expecting that check from home or some money to be wired via Western Union any minute now. Sometimes the checks did arrive and sometimes they did not. We were never out much more than a cup of coffee and a sandwich, but since Route 66 provided the best means from Oklahoma and other Midwestern drought states to the promised land and bountiful jobs of California, we experienced a never-ending parade of broken down vehicles and down-on-their-luck families. The Greyhound and Trailways bus stations were two blocks away. Many of the bus drivers spent an overnight at the Weatherford Hotel across the street from the pharmacy. These fellows were interesting ones to chat with regarding their many and varied experiences traveling with the public. Directly across the street from the pharmacy was the railroad station for the Atchison Topeka and Santa Fe. The train stopped eight times a day: two eastbound engines traveling from Los Angeles and two from San Francisco through Flagstaff, and then four westbound traveling to Los Angeles and San Francisco from points east. Through passengers did not depart the train in Flagstaff, however we had some whose destination was our little burg and Rowan’s Pharmacy provided an opening greeting to them. Folks from Phoenix would drive to Flagstaff to pick up friends and relatives since there was no reliable rail service between Flagstaff and Phoenix. Our soda fountain always provided a handy meeting place. Occasionally, we were contacted to provide medication or oxygen for a railroad passenger who was in distress due to the 7000 foot elevation of Flagstaff. On occasions, some travelers would run out of tickets and money in Flagstaff. Depending on our impression of the individual we would provide a sandwich and a drink for the down-and-outers, and perhaps even lodging at the Grand Canyon Hotel across the street at the cost of $7.00 per night.

One traveling incident produced the most surprising result I could ever imagine. A gentleman came into the pharmacy looking very well-groomed and sharp of mind. He stated that he, his wife, and three kids were in the station wagon outside the pharmacy and he was on his way to Los Angeles for a great job. Apparently, he had been cut from work in Oklahoma and he found himself out of gas and money in Flagstaff. He inquired whether I knew someone who played golf and might have an interest in purchasing a brand new set of Jack Nicklaus golf clubs which he had just bought before losing his job. I said I played golf and would take a look at what he had to offer. True to his word they were excellent clubs with a very nifty leather bag. I asked how much he wanted for the set and he figured that $35.00 would get him and his family one more meal and into Los Angeles where he could secure help prior to his first paycheck. My impression of the gentleman and his family was so good that I told him I would give him the $35.00 and he could keep his clubs. I did this expecting full well that I would never see this person again but I still felt good about helping a seemingly nice guy and family get back on their feet. He assured me that someday he would repay this gesture. Two years later a gentleman walked into the pharmacy asking if I remembered him. While I was trying to place him, he reminded me that he was the fellow trying to sell me his golf clubs. He had lost my business card with my address on it but wanted to pay me back the $35.00 plus how much interest I would consider for the two year loan. I told him I was not in the business of collecting interest and the $35.00 sounded just right. The most wonderful feeling in the world came over me when I realized the honesty and integrity of this gentleman and that my first impression of him had been 100% correct. This is the tenth installment in a series of reflections from Joe Rowan, R.Ph., longtime Arizona pharmacist, and AzPA member. Follow Joe’s memoirs in future issues of the Arizona Journal of Pharmacy or catch up on past installments by visiting the Arizona Journal of Pharmacy archives on the AzPA website.

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Be Proactive. Be Protected. Be Prepared. Santa Fe Depot, Flagstaff, Arizona 16 • Arizona Journal of Pharmacy • Summer 2013

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Featured Article Super Bugs

by Tagg Daugherty, Pharm.D.; James Kultgen, Pharm.D., BCPS; Janet Cooley, Pharm.D., BCACP, University of Arizona College of Pharmacy

Background: In the mid 1900s penicillin was thought to be the miracle drug to cure all infections. Initially bacteria had little resistance to antibiotics; however, as use has increased, penicillin has become less effective. There are two theories concerning why resistance occurs: 1. selective pressure where genes for resistance are already present in a small portion of the population; and 2. random mutation where resistance to the antibioticsâ€™ mechanisms of action occurs by chance. Currently both of these theories play a role in the development of antibiotic resistance and we have discovered more mechanisms by which resistance occurs over the decades.1 Sulfonamides were in use before penicillin but they were far less potent than penicillin. After the discovery of penicillin, other antibiotics such as streptomycin and the tetracyclines were discovered. These new agents allowed for broader coverage of infecting organisms, but just like with penicillin, these organisms became more resistant as the drugs were used. Eventually multiple class antibiotic resistance occurred in some organisms and these harder to treat organisms became known as super bugs. Super bug outbreaks were reported as early as the 1950s and today nearly every species of bacteria has potential resistance to at least one type of antibiotic in the United States.2,3 One example is the Klebsiella pneumonia carbapenemase (KPC) outbreak in New York. This KPC super bug claimed a total of seven lives at the National Institute of Health (NIH) Clinical Center. The source of this particular outbreak was found to have originated overseas.4,5 The revolutionary method which the NIH used to track the spread of KPC through their patients was as much the reason for the headline coverage as was the pathogen, but super bugs are much more common than most would think. What are Super Bugs?: There is not one specific bacterial species that is known as the super bug,

nor is there a specific mechanism of resistance that classifies any bacteria as a super bug. As described above, super bugs are multi-drug resistant (MDR) bacteria that are very difficult to treat with conventional means and often only a few available antibiotics. Many common infecting organisms and natural flora have evolved to the point of being known as multi-drug resistant organisms. One of the most commonly known infecting organisms and which is part of the natural skin flora is Staphylococcus aureus. This particular organism has had several strains evolve into one of the most common super bugs known as methicillin-resistant Staphylococcus aureus (MRSA).6,7 Other super bugs are KPC, extended spectrum beta-lactamase (ESBL) Escherichia coli, vancomycin-resistant Enterococcus (VRE), MDR Pseudomonas aeruginosa, and MDR Acinetobacter baumanii. Genes for resistance are thought to be as old as naturally occurring antibiotics. Bacteria evolved to survive the harsh environment that antibiotics have created. One way MDR occurs is from the selective pressure that comes from widespread antibiotic use. This widespread use drives bacterial evolution from just natural random mutation. Bacteria are also capable of taking up genetic material from their environment and from neighboring bacteria through a process called plasmid conjugation, allowing resistance to cross species. Some good examples are the KPC and AmpC genes which are found in multiple species including Escherichia coli, Acinetobacter baumanii, and Klebsiella pneumonia.1,8,9 Resistance mechanisms can vary widely. Some of these resistance mechanisms include enzymes that will hydrolyze antibiotics, reduce porin channels in bacterial cell walls to limit drug exposure, altering of the target molecule to reduce drug binding affinity, produce proteinbinding molecules to block antibiotics, and efflux pumps to remove antibiotics from within the cell.8,9,10 Origins: Initial super bug outbreaks were often originally found to originate overseas and brought into the United States. For instance, KPC was first reported in Israel and the New York outbreak was thought to have originated from a patient who brought it over.8,10 Resistant organisms are also more common in places such as Asia,

18 â€˘ Arizona Journal of Pharmacy â€˘ Summer 2013

the Middle East, and Africa where there is less stringent use of antibiotics.2,8,9 The advancement of medicine has also led to better survival rates for immune suppressed patients such as those with HIV, cancer, and organ transplants. These patients are at times unable to clear infections and are put on extensive courses of antibiotics that can potentially provide an environment for the infecting organism to become a super bug. While these super bugs are generally isolated to these aforementioned patient populations, their increasing numbers cause concern for greater resource consumption which in turn opens up the possibility for more outbreaks that can originate locally. Impact: The Infectious Diseases Society of America (IDSA) reports that between $21 to $34 billion dollars is spent annually on combating antibiotic resistance.11 Patients in hospitals have a 1 in 20 chance of acquiring a hospital acquired infection (HAI) when admitted and in 2007, 16% of HAIs were caused by a MDR pathogen.3,12 The majority of these MDR infections were caused by MRSA, which has become a common nosocomial pathogen.10 Mortality rates from super bugs can be as high as 50% for infections from KPC producing bacteria, MDR Acinetobacter baumanii, as well as MRSA when compared to non-resistant Acinetobacter baumanii and Staphylococcus aureus.8,9,11 Counseling: Treatment failures have the potential to lead to resistant organisms and ultimately over time to become super bugs. With news headlines reporting super bug outbreaks, the IDSA and Center for Disease Control and Prevention (CDC) report antibiotic resistance as a primary concern, that the problem seems to be getting worse, and patients and healthcare workers may have fears of widespread epidemics. The problem of bacterial resistance is not new and has been well observed throughout infectious disease history. Today there are systems in place to help combat the problem. Pharmacists can play a key role in combating the development of super bugs by providing insight and guidance on this matter and also by counseling patients on responsible and appropriate use of antibiotics. Some information pharmacists may give when counseling patients is:

Featured Article Super Bugs (continued from page 18) • DO NOT try to self-treat an infection with antibiotics. • If prescribed antibiotics, take the full course. • Provide warnings of potential adverse drug event information and how to mitigate these effects to improve adherence. • Possible drug or food interactions that may reduce antibiotic effectiveness and how to mitigate these effects. • Instructions on how and when to seek medical attention if an infection is not clearing or worsening despite treatment. Pharmacists can also provide seasonal flu and pneumonia vaccinations to patients to prevent the need for antibiotics in the first place. Antimicrobial stewardship programs are often led by pharmacists and are an important part of hospitals’ infectious disease control teams. These pharmacists are trained to help assure that best practices, established by guidelines and peer-reviewed literature, are put into place. Pharmacists often limit the use of broad spectrum antibiotics (i.e. carbapenems) in hospitals. They do so by narrowing antibiotic therapy once the infecting organism has been identified and sensitivities to antibiotics are known.1 The IDSA provides numerous evidence based guidelines on their website for treating infections. Super bugs often affect hospitalized and immune suppressed patients the most. This is because in these two patient types, antibiotic use is common and often organisms colonize in the hospital’s infrastructure or within patients themselves. These resistant infections are taken seriously and hospitals have established patient isolation policies. There are also precautions and policies taken to prevent the spread of disease within hospitals. Examples include hand hygiene, isolating patients with suspected super bug infections, use of gowns, and specialized infection control rooms for high risk patients. Traveling abroad exposes people to infections that are not common in their homeland and this travel allows pathogens to come back with them. Sometimes these pathogens can be common local diseases like malaria and sometimes a super bug that could cause an outbreak. The CDC provides information to the public on foreign diseases, recommended vaccines

depending on destination, and guidance on how to stay healthy while traveling. Travelers should review the CDC website and research the diseases he/she could expect to encounter during travel.14 One recommendation worth mentioning here is that if a person is sick he/she should avoid traveling to prevent the spread of disease. Super bugs are a serious problem and people should know that super bugs are harder to treat with antibiotics, but not necessarily more communicable or resistant to our natural immune responses. A healthy person has little to fear from a super bug and a widespread epidemic within the public is unlikely to occur. However, not everyone can stay healthy forever and there is the fear that eventually no antibiotics will work against super bugs. Drug companies have also cut back on research and development for new antibiotics due to poor financial projections like return on investment since newer antibiotics are not usually used as a first line of defense against a super bug. This combined with increasing resistance to current antibiotics is why the CDC is pushing for the “10 by 20 program” which is a stated goal of 10 new antibiotics developed by 2020.15 References: 1. Shlaes, David M., et al. “Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals.” Clinical infectious diseases 25.3 (1997): 584-599. 2. Medical News Today. The Antibiotics Crisis: How Did We Get Here And Where Do We Go Next? Jan 10 2011. Accessed online 04/27/2013. http://www. medicalnewstoday.com/articles/213193.php. 3. Hidron, Alicia I., et al. “Antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007.” infection control and hospital epidemiology 29.11 (2008): 996-1011. 4. Vastag, B and Sun, LH. NIH superbug claims 7th victim. The Washington Post. Health & Science. Sep 15, 2012. Accessed online 04/27/2013. http://www.washingtonpost.com/ national/health-science/nih-superbug-claims-7thvictim/2012/09/14/09b3742e-fe9b-11e1-b153218509a954e1_story.html. 5. Szalavitz, M. Outbreak of NIH ‘superbug’ provides valuable lessons. Cable News Network. Turner Broadcasting System, Inc. Accessed online 04/27/2013. http://www.cnn.com/2012/08/30/health/ time-superbug-lessons/index.html/ 6. Jensen, AG, Wachmann CH, Poulsen KB, et al. Risk factors for hospital acquired Staphylococcus aureus bacteremia. Arch Intern Med. 1999; 159:1437–1444. 7. Zaoutis, Theoklis E., et al. “Clinical and

molecular epidemiology of community-acquired methicillin-resistant Staphylococcus aureus infections among children with risk factors for health care-associated infection: 2001-2003.” The Pediatric infectious disease journal 25.4 (2006): 343-348. 8. Lee, GC. Epidemiology and treatment of KPC’S…What’s the news? Pharmacotherapy Rounds 2012. 02/17/2012. Accessed online 04/27/2013. http://www.utexas.edu/pharmacy/divisions/ pharmaco/rounds/lee02-17-12.pdf. 9. Poirel, L and P, Nordmann. “Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology.” Clinical microbiology and infection 12.9 (2006): 826-836. 10. Gasink, Leanne B, et al. “Risk factors and clinical impact of Klebsiella pneumoniae carbapenemase–producing K. pneumoniae.” Infection control and hospital epidemiology: the official journal of the Society of Hospital Epidemiologists of America 30.12 (2009): 1180. 11. Infectious Diseases Society of America. Antimicrobial Resistance. Accessed online 04/27/2013. http://www.idsociety.org/Topic_ Antimicrobial_Resistance. 12. Center for Disease Control and Prevention. The Burden. Healthcare-associated Infections (HAIs). Accessed online 04/27/2013. http://www.cdc.gov/ HAI/burden.html. 13. Hanberger, Håkan, et al. “Increased mortality associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in the Intensive Care Unit: results from the EPIC II study.” International journal of antimicrobial agents 38.4 (2011): 331-335. 14. Center for Disease Control and Prevention. Traveler’s Health. Accessed online 04/27/2013. http://wwwnc.cdc.gov/travel/. 15. Center for Disease Control and Prevention. Antibiotic/Antimicrobial Resistance. Accessed online 04/27/2013. http://www.cdc.gov/drugresistance/ index.html. 16. Infectious Diseases Society of America. Antimicrobial Resistance. Accessed online 04/27/2013. http://www.idsociety.org/AR_Policy/

Summer 2013 • Arizona Journal of Pharmacy • 19

Featured Article Methylnaltrexone Bromide: Place in Therapy for OpioidInduced Constipation by Erin Bonelle, Pharm.D. Candidate Midwestern University College of Pharmacy-Glendale Class of 2013; Vickie Crouch, Pharm.D. Candidate, Midwestern University College of Pharmacy-Glendale Class of 2013; Mindy (Throm) Burnworth, Pharm.D., BCPS, Midwestern University College of Pharmacy-Glendale, AzPA Health-System Academy

Opioid analgesics are often used for the management of chronic pain; some of the side effects associated with opioid use subside as the body adjusts to the medication, but constipation (or opioidinduced constipation) is not one of the side effects that the body adjusts to (i.e. the body does not develop tolerance to).1,2 For patients that require chronic opioid use for the management of their pain, opioid-induced constipation (OIC) should be prevented by the prophylactic use of an over the counter stool softener and laxative combination.1,2 Unfortunately, even with the prophylaxis of a stool softener and laxative, some patients may still develop OIC.1,2 For this special patient population that is refractory to conventional treatment of constipation, newer agents are needed to specifically treat OIC. Methylnaltrexone Bromide (Relistor©) is a peripherally acting opioid antagonist approved by the Food and Drug Administration in April 2008. Methylnaltrexone is indicated for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy is insufficient. This agent is similar to the opioid antagonist naloxone in that it acts at the mu receptor to reverse the effects of opioid analgesics.3 Methylnaltrexone is a quaternary amine which has increased polarity when compared with the tertiary amine naloxone. The higher polarity of the methylnaltrexone molecule reduces lipid solubility and diminishes its capacity to cross the blood-brain-barrier.4 Methylnaltrexone produces a more rapid effect on the GI tract than other laxative agents commonly used and does not diminish opioid analgesic effects. Studies have shown methylnaltrexone is an effective agent to relieve opioid-induced

constipation without reducing pain control.3-9 Methylnaltrexone is dosed based on patient weight and is typically given as a subcutaneous injection every other day. It should not be given more than once in any 24 hour period and renal dose adjustments may be necessary in patients with decreased creatinine clearance. Patients that weigh 38 - 61 kg (84 - 135 lbs) should use the 8 mg prefilled syringe and patients that weigh 62 - 114 kg (136 - 251 lbs) should use the 12 mg pre-filled syringes; patients who weigh less than 38 kg or more than 114 kg should be given a dose based on 0.15 mg/kg.3 The cost of methylnaltrexone can be prohibitive, however, considering that a 12 mg singledose vial can cost more than fifty dollars (daily prophylaxis with docusate and sennokot is less than one dollar). When injected subcutaneously, methylnaltrexone is rapidly absorbed with an onset of action of about 30 - 60 minutes and the half-life is approximately eight hours.3 Most of the side effects that were reported in the trials were related to gastrointestinal issues with abdominal pain being the most frequently cited. Other common side effects included flatulence, nausea, diarrhea, and hyperhidrosis.5 Methylnaltrexone is contraindicated in patients with known or suspected gastrointestinal obstruction. It is also advised that if a patient experiences severe or persistent diarrhea or severe, persistent, or worsening abdominal symptoms, methylnaltrexone should be discontinued. Also, methylnaltrexone should be used with caution in patients with known or suspected lesions of the gastrointestinal tract due to the possibility of intestinal perforation.3 In in vitro drug metabolism studies, methylnaltrexone bromide did not significantly inhibit the activity of the cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2C19, or CYP3A4. It is considered a weak inhibitor of CYP2D6; however, in a clinical drug interaction study in healthy adult male subjects, a subcutaneous dose of 0.3 mg/kg of methylnaltrexone did not significantly affect the metabolism of dextromethorphan, a CYP2D6 substrate.3 Trials examining the efficacy of methylnaltrexone when given as a subcutaneous injection have demonstrated that it is efficacious in relieving opioid-induced constipation in both

20 • Arizona Journal of Pharmacy • Summer 2013

opioid naïve patients and in patients who were receiving long-term opioid therapy.4-9 These trials also show that methylnaltrexone is effective without causing withdrawal symptoms or loss of pain control. All six trials used either morphine or converted the dose of other opioids to their morphine equivalents. One of the three larger trials, conducted by Thomas J et al.,6 permitted study subjects to continue prophylactic bowel care regimens while the other two studied strictly the efficacy of methylnaltrexone bromide.5,7 Three of the trials administered methylnaltrexone doses based on the weight of the subject and used either 0.1, 0.15, 0.3, or 0.45 mg/kg per dose for the treatment arm of the study.4,6,9 Two trials used 12 mg doses given either daily or every other day.5,7 One trial varied the dose of methylnaltrexone giving 1 mg, 5 mg, 12.5 mg, and 20 mg doses to study subjects in different sessions.8 This study revealed that even at higher doses, patients did not experience any loss of pain control. The number of patients receiving methylnaltrexone that completed the studies was variable; minimum of 124,9 and maximum of 388.5 Methylnaltrexone is a pregnancy risk category ‘B’ agent that is excreted in breast milk based on studies done in rats. Because it has not been studied in pregnant women, use of methylnaltrexone should be limited to those occasions when the benefit outweighs the risk and used with caution in breast-feeding women. No dose adjustment is necessary based on age in adult patients and no safety studies have been conducted in pediatric patients.3 While methylnaltrexone is efficacious at relieving OIC without causing reversal of opioid analgesic effects, the cost of the agent may outweigh the benefit in most cases. Methylnaltrexone has been shown to be safe in studies conducted up to this point, with the majority of side effects being mild to moderate and mainly gastrointestinal in nature. There is a need for more large, doubleblind, comparison trials to examine the efficacy of methylnaltrexone against other conventional agents used to treat constipation. In conclusion, due to the cost of this agent, methylnaltrexone should be reserved for use in patients that are refractory to other more cost effective treatment options.

Featured Article Methylnaltrexone Bromide (continued from page 20)

References 1. McMillan SC. Assessing and managing opiateinduced constipation in adults with cancer. Cancer Control. 2004;11(3)S1:3-9. 2. Avila JG. Pharmacologic treatment of constipation in cancer patients. Cancer Control. 2004;11(3)S1:10-18. 3. Relistor [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals, Inc; April 2008. Updated: Relistor [package insert]. Raleigh, NC: Salix Pharmaceuticals; Feb 2012. 4. Yuan, C-S et al. Methylnaltrexone prevents morphine-induced delay in oral-cecal transit time without affecting analgesia: a double-blind randomized pacebo-controlled trial. Clinical Pharmacology & Therapeutics. 1996;59(4):469475. 5. Michna, E et al. Subcutaneous methylnaltrexone for treatment of opioid-induced constipation in patients with chronic, nonmalignant pain: a randomized controlled study. The Journal of Pain. 2011;12(5):554-562. 10.1016/j.jpain.2010.11.008 6. Thomas J et al. Methylnaltrexone for opioidinduced constipation in advanced illness. New England Journal of Medicine. 2008;358:2332-43. 7. Iyer, S et al. Effect of subcutaneous methylnaltrexone on patient-reported constipation symptoms. Value in Health. 2011;14:177-183. 10.1016/j.jval.2010.11.003 8. Portenoy, R et al. Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. Journal of Pain and Symptom Management. 2008;35(5):458-468. 9. Yuan, C-S et al. Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated side effecs: a double-blind randomized placebo-controlled trial. The Journal of Phamacology & Experimental Therapeutics. 2002;300(1):118-123.

Arizona Pharmacy Association

presents Arizona Pharmacy Law and Public Policy Course The ideal preparation for the MPJE!

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An Evaluation of Pharmacy Regulation Waivers Granted to Arizona Pharmacies from 2002 through 2012 by Steven C. Warren, Pharm.D., and Philip J. Schneider, MS, FASHP, FFIP, FASPEN, Associate Dean, University of Arizona College of Pharmacy

ABSTRACT Specific Aims: To compile and evaluate the impact of Arizona pharmacy rule waiver requests from 2002 through 2012 and to determine the current status of these waivers. Methods: Minutes of the Arizona State Board of Pharmacy (ASBP) meetings were reviewed to identify pharmacies which had sought waivers to Arizona state pharmacy regulations. Information was collected from these minutes and from the ASBP pharmacy permits database. Persons at the pharmacies were contacted regarding their operation, whether the waiver was still in use, and any perceived impact the waiver had made. Results: Fifty waivers were requested of the ASBP. Forty-seven of these requests were granted. Most waivers were requested by hospital and mail order pharmacies and the most common requests were for a smaller than required pharmacy floor plan area, no pharmacist final inspection or initialing, and fewer than the required hours of operation. One waiver was associated with a poor outcome and was subsequently rescinded. Three waivers were followed by rule changes. Some waivers improved pharmacy service to underserved or specialty patient groups and others increased patient convenience or eliminated unnecessary labor, facilities, or equipment. One waiver reduced product waste and another enabled training for pharmacy students. Several waivers allowed pharmacy technicians to work from home. About half the waivers are either no longer in use or were never used. Conclusions: The pharmacy regulation waiver process has helped pharmacy in Arizona evolve. The waiver process has also allowed health care entities to serve Arizona’s underserved populations and special patient groups. ACKNOWLEDGEMENTS Assistance provided by Hal Wand, Executive Director, Arizona State Board

of Pharmacy. The authors would like to thank the contact persons at the waiver recipients’ businesses for their participation in the survey. INTRODUCTION In the United States, State Boards of Pharmacy are charged with regulating the practice of pharmacy in the best interests of patients. These boards are empowered by law to promulgate regulations towards this end. As the fields of medicine, pharmacy, information technology and others evolve, these regulations are revised. To try changes to regulations on a small scale and to accommodate reasonable requests which are thought not to compromise patient safety, some states allow their Board of Pharmacy to grant waivers from these regulations to individual pharmacies. Arizona is one of these states. The authority for the Arizona State Board of Pharmacy (ASBP) to allow deviations from pharmacy regulations is written in Arizona Revised Statute 32-1904.B.6: “The board may grant permission to deviate from a state requirement for experimentation and technological advances.”1 The history of pharmacy regulation waivers in Arizona is reflected in the minutes of ASBP meetings.2 This report is a compilation of pharmacy rule waivers and the impact of these waivers. It summarizes these waivers by the types of waivers granted and the impact that these waivers have had on patient care, economics, and regulatory change. METHODS Design: This was a descriptive, crosssectional, telephone-based survey. The study was determined to not be human subjects research by the University of Arizona Institutional Review Board. Inclusion/exclusion criteria: All minutes available for ASBP meetings in calendar years 2002-2012 were reviewed. Only waivers granted to pharmacies were included. Data collection: Data from ASBP meeting minutes included the date of ASBP meeting, name of pharmacy, rule to be waived, name of person(s) representing the pharmacy at the ASBP meeting, ASBP action (grant or denial of the waiver request), waiver conditions, and other

Arizona Journal of Pharmacy • Summer 2013 • 21

Featured Article Pharmacy Regulation Waivers (continued from page 21) details. These data were entered into an Excel® spreadsheet. Data collection also involved a review of ASBP pharmacy permit application details by use of an ASBP database.3 These details included ASBP permit number, type of pharmacy operation, physical address and names/ phone numbers for pharmacy contact persons. The details of the specific regulations for which deviations were being requested were also recorded.4 Waiver recipients were contacted by telephone. The contact person was asked questions regarding their current usage of the waiver and any perceived impact the waiver may have had on patient care, or pharmacy or patient economics. A script was used to assure consistency and completeness in collecting information. Responses were entered into the spreadsheet. Other information collected included clarification of the nature of their waived activity where needed. Data analysis: The data are presented descriptively. Percentages and graphs are given where illustrative. RESULTS During the study period, 50 waivers were requested. The number of waiver requests per year is shown in Figure 1. Forty-seven requests were granted. Table I lists the number of waiver requests per operation type. Table II shows the number of waiver requests based on the ASBP regulation requested to be waived. The results of the telephone survey question regarding current waiver status are shown in Table III. Seven status categories were noted.

DISCUSSION Regarding the spikes in waiver requests shown in Figure I, it is thought that the increased number of waiver requests during 2009-2011 are due to a statewide rule-writing moratorium during that period.5 The reason for the spike in requests in 2004 was not investigated. The perceived impact of the pharmacy rule waivers are summarized below: • Deviation from R4-23-110 - This has allowed operation of remote dispensing machines and provides for quicker or more convenient medication by patients. This has been good for patient care and no negative impact has been reported. • Deviation from R4-23-402(A)(11) – Seven waivers of this rule allowed machine-checking of manufacturer unit-dosed medication, streamlining the process of automated mass filling as in for mail order. Theoretically this could have a positive impact on lowering prescription costs. The proven track record of these technologies has reduced pharmacist labor while preserving patient safety. One waiver of this rule allowed pharmacist final check using digital imaging. No negative impact was reported regarding these waivers. The same rule was waived once instead to allow a pharmacy technician to use a bar-code scanner for the final check. That facility was subsequently involved in a misfill which was associated with patient harm. Because of this, the waiver was rescinded. • Deviation from R4-23-407 - This has allowed pharmacies to transfer prescriptions electronically under special situations, allowing for improved patient convenience and reduced pharmacy labor. No negative impact was reported.

22 • Arizona Journal of Pharmacy • Summer 2013

Table I. Waiver requests per operation type

• Deviation from R4-23-409 - This has allowed a nursing-home service pharmacy to reuse pharmacy-unitdose packaged medications that are returned. This has reduced waste, reduced pollution and saved money. No negative patient care impact was reported. • Deviation from R4-23-609 - This has allowed a small compounding-only pharmacy to exist at an on-campus clinic that was also a site for pharmacy interns. This waiver was thought to be good for pharmacist training and convenient for on-campus patients. • Deviation from R4-23-611 and R4-23612 – This allowed a non-dispensing pharmacy to not have to have unneeded equipment and facilities. This waiver reduced investment and operating costs for the pharmacy and no negative impact was reported. • Deviation from R4-23-614(B)(2)(c) – This has allowed hospital night-shift employees to pick up prescriptions while at work. This improved patient convenience and no negative impact was reported. • Deviation from R4-23-653(B) and R423-655(B) - This has allowed operation of pharmacies in small hospitals serving rural areas or specialty patient groups. The waiver has been good for patient care and no negative impact was reported. • Deviation from R4-23-653(E) and R4-23-653(I) – This waiver will allow pharmacy technicians in a hospital to use a scanner to verify unit-dosed packaged medications when they are loaded into automated dispensing cabinets. This waiver will reduce pharmacist labor. • Deviation from R4-23-1104(A)(4) – Theoretically this waiver allows quicker response to surges in prescription orders. No negative impact was reported. One participant commented that work-from-home is the “direction the world is moving”. Two waived rules were subsequently revised to permit the activities allowed by the original waivers. These cases suggest that waiving rules has allowed the profession of pharmacy to respond to new technology on a small scale before allowing changes state-wide. Changes resulting from a positive experience with waivers include:

Featured Article Pharmacy Regulation Waivers (continued from page 22) • R4-23-402(A)(11) – Pharmacists no longer must initial the prescription label provided the pharmacy computer keeps track of which pharmacist was in charge at the time. • R4-23-402(E) – Electronic capture of patient declining an offer for consulting by a pharmacist is now allowed.

CONCLUSIONS The waiver process has helped pharmacy in Arizona evolve by allowing change quickly on a small scale before allowing these same changes statewide. The waiver process has also allowed marginally profitable health care businesses to serve Arizona’s underserved populations and special patient groups who might otherwise go unserved.

Limitations: This survey-based study was limited in that the honesty of the persons surveyed was not assessed. Another limitation is that these results should not be applied to states other than Arizona.

Table I. Waiver requests per operation type Operation type

Table II. Waiver requests by rule

Requests

Table I. Waiver requests per operation type

References 1. Arizona Revised Statutes, Title 32 - Professions and Occupations. Available at http://www.azleg.gov/ ArizonaRevisedStatutes.asp?Title=32 2. Arizona State Board of Pharmacy, Board Meeting Minutes, available at http://azpharmacy.gov/news/ board_meeting_minutes.asp 3. Arizona Board of Pharmacy Permit Applications Administration, secured access available via http:// az.gov/app/pharmacy_admin 4. Arizona Administrative Code, Title 4. Professions and Occupations, Chapter 23. Board of Pharmacy, available at http://azsos.gov/public_services/ Title_04/4-23.htm 5. Hal Wand, statement during the March 20, 2013, ASBP meeting

Requests Grants Rule requested to be waived 13

R4-23-655(B): The floorplan area of a hospital pharmacy must be 500 square ft.

R4-23-402(A)(11): Rule required a pharmacist to check and initial each prescription label. Initialing now not required if a computer identifies the verification pharmacist.

R4-23-653(B): A hospital pharmacy must be open 40 hours/week.

R4-23-110: "Supervision" means a pharmacist is present. Waiver requested to allow operation of remote automatic dispensing machines.

R4-23-1104(A)(4): Pharmacist must verify accuracy of technician order entry. Waiver requested to allow pharmacy technicians to perform order entry from home

R4-23-407: Rule specifies requirements for electronic prescription transfers.

Table III.Requests Waiver requests perstatus current status Waiver

R4-23-609(A) The floorplan area of a community pharmacy must be 300 square ft.

Requests Waiver status

R4-23-614(B)(2)(c): A medication dispensing machine must be no more than 20 feet from a pharmacy.

obsolete due to waived rule being changed 1

never used and will not use

R4-23-402(E): A pharmacist or pharmacy intern must accept and document patient refusal of consultation

R4-23-402(I): Written/printed patient information must be provided with refills.

no longer being used

Hospital

Operation type

Requests

Limited Service

Hospital

(mostly Mail Order)

Limited Service

(mostlyIndependent Mail Order)

Chain Independent

Chain Total

Total

Table III. Waiver requests per current status

denied

obsolete due to waived rule being changed

never used and will not use

no longer being used

R4-23-409: Returned medication cannot be re-dispensed.

3 beingnot being - will be used soon not used yet - used will beyet used soon

1 rescinded rescinded

R4-23-611: Pharmacy must include (1) a drug preparation sink and (2) toilet facilities within 50 feet of the pharmacy.

21 beingstill being used still used

R4-23-612: A pharmacy shall have graduates, a mortar and pestle, spatulas, a Class A balance and an ointment tile or equivalent.

Total 50 requests Total requests

R4-23-653(I): All technician activities must be supervised by a pharmacist. Waiver allowed verification of automated dispensing cabinets by pharmacy technicians utilizing a barcode scanner.

Total

Arizona Journal of Pharmacy • Summer 2013 • 23

Featured Pharmacist Caring for the Community on a Larger Scale by Asal Azizoddin, Pharm.D. Candidate, Midwestern University College of Pharmacy-Glendale, Class of 2014

Davey Lavergne, R.Ph. is the Regional Health & Wellness Director for Walmart. As a leader in community pharmacy, he is responsible for approximately 150 stores throughout Arizona and New Mexico. He hopes to achieve successful operations through determining strategic ways to meet the company goals, operating with compliance, meeting the expectations of share holders and most importantly, providing quality patient care. Mr. Lavergne went to the University of Louisiana at Monroe where he graduated in December of 1999, and began to work for Walmart as a pharmacist. He has held numerous positions within the company throughout these years, and his current position led him to move to Arizona this past November.

What is your intake on residencies? Does Walmart Pharmacy offer any? Residencies are great, however, I do not think they are for everyone. You need to look at what the residency has to offer and what you, as a pharmacist, will gain from it. Make sure the residency parallels and contributes to your career path and objectives. This past year Walmart started its first community practice residency in Bentonville, Arkansas. This residency focuses on the quality measure of how to improve patient care and outcomes through analysis, best practices and technologies. What changes do you foresee for the profession of pharmacy? I think that the profession of pharmacy is moving towards a greater focus of improving patient care. The industry will be driven by outcome measures for the patients we serve. What is your favorite part of your current position? I enjoy helping and developing other leaders within the company. There are opportunities for me to influence and make changes that can impact the entire industry to help better serve patients. I want to make sure the profession stays pure and true to patient care.

What motivated you to become a pharmacist? I knew I wanted to help people and I wanted to be in health care. Growing up, I looked up to our pharmacist and remember going to the local pharmacy with my mom. The pharmacist there helped my family on multiple occasions. He would stay open past closing Why is being a member of the Arizona Pharmacy Association hours to help out patients of the community. important to you? We, as pharmacists, should all be connected. The Arizona In your opinion, how has the pharmacy profession changed Pharmacy Association is our collective voice, and we should during your career? participate in the organization to try to lead by example and get The cost-plus model, where there is no scale or measure of other pharmacists involved. outcomes of patient care, has changed throughout the years. The primary focus now lies with patient care - an all-encompassing Do you have a mentor in your career? What was the best approach of improving different outcomes. The patient care advice he/she gave you? outcomes of successful pharmacies are based on how to improve I had several great mentors throughout my career. One of patient’s lives through improving health, decreasing the number my current mentors is Dr. John Agwunobi. He is the current of emergency department visits, decreasing potential drug-drug interactions, increasing patient adherence to their medications, and president of the Health & Wellness division of Walmart, where he has shared that being a successful leader in this industry highly more. relies on “doing the right thing,” and “striving for excellence.” Where do you find, or whom do you approach for innovative What advice do you have for new practitioners? ideas for the company? Choose an area of pharmacy where you will ultimately be happy I get the best ideas from the pharmacists who are practicing in and where you will make the greatest impact with patients. Do our stores. I carefully listen to what the pharmacists have to say, and I learn about what we (Walmart) can do better at the front line not base your career solely off your financial decisions. To be a good leader, you must practice honesty, integrity, transparency, for patients we serve. In addition to communicating with these authenticity, and staying true to these principles and serving pharmacists, I attend various pharmacy, optometry, and patientpatients will ultimately lead you to success. services conferences, I keep up with literature, CEs, and I consult my peers. What do you like to do on your free time? I like spending time with my family. I enjoy watching sports (I am a huge LSU fan!), playing golf and baseball, and attending baseball and football games. I also enjoy taking part in outdoor “Understanding healthcare activities.

in totality will lead to better continuity of care.” - Davey Lavergne

24 • Arizona Journal of Pharmacy • Summer 2013

Student Leadership, Where Will it Take You Next? By Asal Azizoddin, Pharm.D. Candidate, Midwestern University College of Pharmacy – Glendale, Class of 2014

On Saturday March 23, 2013 AzPA hosted its 3rd Annual Student Leadership conference at the Desert Willow Conference Center in Phoenix, Arizona where thirteen pharmacy students from Midwestern University College of Pharmacy-Glendale and the University of Arizona College of Pharmacy attended the informative event to gain leadership skills they can take with them throughout their pharmacy careers. Kelly Ridgway, AzPA CEO, and Mike Dietrich, AzPA President welcomed students, and they recognized the participants for their efforts of being involved through leadership and service in the field of pharmacy. Following the welcoming remarks, keynote speaker Metta Lou Henderson, Ph.D., Hon.D. shared her life journey of pharmacy and the active steps she took to advocate for the profession. Henderson educated students about leadership opportunities outside student organizations and how students should follow their vision to achieve any set of goals. She stated, “I define a leader as an individual who guides and directs others…They create ideas and follow up… This individual has vision and guides others towards that vision.” Her powerful remarks gave students insight on the idea that leadership opportunities are always available, and as advocates for the profession, students must take active steps to be involved and contribute to bettering the profession of pharmacy. Thomas Jaeger, Pharm.D., presented his financial tips for success. He spoke to students about making financial decisions for pharmacist professional liability, purchasing a home and life insurance, repaying back loans, tips for retirement, and other costs as part of a timeline of financial commitments. The “fortune building over a lifetime” concept gave students the opportunity to learn about how to appropriately allocate their money for different expenses throughout their lifetime. Jaeger also touched on the concept of building an appropriate budget and sticking to it. He opened the idea to students of how the average person divides his income to 70% for living expenses, 20% for life insurance and 10% for debt reduction. Following some financial tips, two other leaders in pharmacy - Keith Cook, R.Ph., President of Avella Specialty Pharmacy, and Crane Davis, Pharm.D., Assistant Pharmacy Director/Sales Manager Fry’s Pharmacy presented to students about their careers, mentorship, leadership, and tips for success. Keith Cook focused on the principle of integrity and how it is extremely important for pharmacists; he noted how pharmacists must work with integrity when serving patients and working behind the counter. He encouraged the students to strive to always exceed their customers’ expectations, in addition to excellent work habits and one’s commitment to the profession. He advised students to set 1, 5, and 10-year goals and to stay involved and up to date with the industry through attending meetings, networking with peers across the industry, and being connected throughout the community. Cook also highlighted how students should find a healthy balance in their lives “defining a life for you and your family.” Crane Davis delivered the concept of “branding” during his presentation, which enlightened students with the idea that the

Student Perspective Pharm.D. is a brand all pharmacists represent. He identified how certain brands continue to succeed, because they keep a promise to consistently produce the exact product or service to meet customers’ expectations; pharmacists must serve the community in an unwavering manner that defines the Pharm.D. Davis also incorporated the importance of being engaged, involved, and passionate throughout one’s career in order to keep that “spark” alive in areas such as the work setting, community, and conferences. Amanda Powell, a participant of the program expressed, “I liked how Dr. Davis shared his approach on the importance of being at eye-level with your co-workers and patients. He showed the group that simply getting down on one knee to be eye-to-eye with a person sitting on a chair makes a huge difference and gives that individual a sense of respect and trust when conversing with him or her.” Keeping an upbeat attitude and perception of the profession will enable people to continue embracing pharmacy throughout the course of time. Following the two presentations by Cook and Davis, students were able to interact in round table discussions. Round table discussions with Kelly Ridgway, Mike Dietrich, Crane Davis, and Keith Cook, gave this group of students the opportunity to not only discuss certain pharmacy related case studies, but also to speak to these pharmacy leaders. I was a participant of this conference, and I really enjoyed conversing with the speakers on a one-on-one basis. I learned various characteristics define what leadership entails, and I will strive to “pay it forward” in as many ways as possible once I am a practicing pharmacist in my community. As the day came to an end, the students were not only awarded with a certificate of completion for attending the program, but they walked away with a great deal of knowledge for broadening and practicing their leadership efforts in the field of pharmacy Lara Petrossian, a student participant of the program proclaimed, “It was great to hear from a variety of leaders in the pharmacy community, and to learn from them how to be the best leaders we could possibly be. I walked away from this conference with so much knowledge, confidence, and motivation to become a respectable pharmacist who guides and works well with others while achieving success.” Thank you to McKesson Corporation and Fry’s Pharmacy for their sponsorship of the 2013 AzPA Student Leadership Conference. Applications for the 2014 Student Leadership Conference will be available in January 2014.

SHOPPING ONLINE? PURCHASING TEXTBOOKS? SUPPORT AzPA! Access amazon.com through the AzPA home page and then bookmark the link. Each time you make a purchase on amazon.com a portion of your purchase price will be donated to AzPA.

Summer 2013 • Arizona Journal of Pharmacy • 25

Academy News Community Pharmacy Academy This is my final message as Community Pharmacy Academy Chair but I will continue to be active within AzPA as we address the need to recognize pharmacists as providers and keep up the fight against prescription drug abuse and misuse. I pass the baton to Betty Louton, Chair, and Grace Akoh-Arrey, Chair-Elect, and ask that you give them your total support as they represent community pharmacy in our association. I hope you were able to attend the 2013 AzPA Annual Convention in Tucson. The record-breaking attendance and fantastic programming made this the best convention I have attended. The Continuous Quality Assurance Workshop was particularly timely as the Arizona State Board of Pharmacy will begin actively enforcing the new requirements for community pharmacies to record all medication errors. Other noteworthy sessions presented were Innovations Across the Continuum of Care: The Affordable Care Act, Quality Improvement and the Role of Pharmacy in Improving Patient Care which featured a panel of pharmacists representing the wide spectrum of practice settings; and the Arizona Legislative Health Care Update with Senator Linda Lopez, Representative Bruce Wheeler, and Donald Hughes, Executive Director for the Arizona Health Insurance Exchange for the Office of the Governor. Save the date for the AzPA Fall Pharmacy Conference on Saturday, October 26, 2013. Location and agenda are pending. Watch your email and the AzPA website for updates. Thank you for the honor of serving our Academy on the AzPA Board of Directors.

SAVE THE DATE! Kristin Calabro, Pharm.D. Community Pharmacy Academy Chair cpa@azpharmacy.org

AzPA Fall Pharmacy Conference Saturday, October 26, 2013 Location to be announced.

Geriatric Care Academy The Geriatric Care Academy (GCA) leadership was excited to hold the GCA Conference on Friday, May 3, 2013 at Midwestern University in Glendale, Arizona. Many thanks to all of the facilitators who made this meeting a huge success: Michael Dietrich, Kip Raney, Jeffrey Barletta, Lisa Goldstone, and Amanda Reeve. The round-table, small-group format was well received and was a great experience for all. I would like to remind everyone of the ASCP Annual Meeting in Seattle, Washington November 20 - 22, 2013. Elizabeth Pogge will be presenting an educational session at the meeting entitled, “Beyond Flu Shots: Update on Immunizations for Older Adults” on November 21st. I encourage all members to attend to this very important meeting. Visit www.ascp.com for more information. Congratulations to Nicole Kitts on her election as the GCA Chair-Elect for the 2013 - 14 term on the Board of Directors. Elizabeth Pogge has ascended to the role of GCA Chair 2013- 14. Please support these two leaders as they work diligently to represent you and your colleagues on the AzPA Board of Directors. It has been a pleasure representing you this past year. I look forward to staying involved in the academy and helping whenever I can. I am excited to see where the future of this academy leads!

Tara Storjohann, Pharm.D., CGP, FASCP Geriatric Care Academy Chair gca@azpharmacy.org

26 • Arizona Journal of Pharmacy • Summer 2013

Academy News Health-System Academy News Our Academy has had a productive year and can be proud of its many accomplishments. I have enjoyed working with the Academy members and would like to give a special thanks to the HSA Executive Committee members for 2012 - 2013: Mindy Burnworth, Kristen Allison, Jon Merchen, Carol Rollins, Whitney Shields, Tina Smith, Stephen Perona, and Patricia Ritz. Without your dedication to our profession and the HSA we would not have been able to accomplish all that we have. This opportunity has allowed me to grow as a leader and communicator and I am certain that the knowledge and skills I bring away from my year as Chair will help me in my future endeavors – thank you all again for your passion and support. The Health-System Academy continues to grow and we are now over 330 members strong! Coming together to learn and support one another in our efforts to provide excellent patient care makes our profession stronger. On April 27, 2013 the HSA sponsored the AzPA Spring Clinical Conference which was held on the Banner Desert Medical Center campus. Our theme was “Team Healthcare: Collaboration for Improvement in Patient Outcomes.” Thanks to the efforts of the 14 planning committee members, chaired by Mindy Burthworth, this program was hugely successful! We had 94 attendees including pharmacists, students, and technicians. Our poster session allowed 15 pharmacy residents and students to present their scholarly efforts. The conference had 9 speakers and provided over 6 hours of CE credit including a special presentation by Joe Hill, Director of ASHP Federal Legislative affairs. Mindy Burnworth was awarded the AzPA Academy Service Award for her continued time, energy, and support of the HSA and pharmacy profession. Please plan ahead so that you can attend the 2014 AzPA Spring Clinical Conference – you won’t want to miss it! At the ASHP Summer Meeting this past June, our Arizona colleagues were a shining representation of the great work that is being done to promote and advance our profession. At least seven Arizona colleagues were speakers at the meeting, including Mindy Burnworth who provided an “ASHP State Affiliate Best Practice Pearl” on how our Academy meets the educational needs of our constituents. Serving this year as our Arizona representatives to the ASHP House of Delegates (HOD) were Carol Rollins, Mindy Burnworth and Christi Jen. Moving forward on a recommendation coming from 2012 Arizona HOD representatives, the motion to have an ASHP Professional Policy on Pharmacists as Healthcare Providers passed unanimously during the ASHP HOD session which was followed by an approval by the ASHP Board of Directors. To learn more about this and other professional policies approved by the ASHP HOD during the 2013 summer meeting, read the ASHP Press Release at http://www.ashp.org/menu/AboutUs/ForPress/ PressReleases/PressRelease.aspx?id=763. Even though we’ve had a great year, our work is not done. The HSA is planning to hold a Health-System Pharmacy Leadership Forum luncheon in the coming months with a theme of “Best Practices for Transitions of Care.” If you would like more information about this luncheon or have a best practice you would like to have showcased, please contact me at ldavis@midwestern.edu. Our Academy continues to be committed to advancing ASHP’s Pharmacy Practice Model Initiative (PPMI) through education and engagement of our Arizona Health-Systems. To learn more about PPMI, visit ASHP’s website at http://www.ashpmedia.org/ppmi/ index.html. If you are interested in helping our Academy meet this goal by serving on the AZ PPMI State Leadership Task Force, please contact our 2013 - 2014 Academy Chair, Kristen Allison at Kristen.Allison@va.gov. Finally, our Academy continues to strive to assist our future colleagues in their professional growth and development. One way we are meeting this goal is to be active in the AzPA Mentor Connection Program which pairs student pharmacists (mentees) to practicing pharmacists (mentors) for a 10-month mentoring cycle (October – July annually). If you would like to learn more about this mentoring program, please contact the AzPA Mentor Connection Program Standing Committee Chair Jon Merchen at merchen.jg@gmail.com. I hope that everyone is enjoying the summer and finding time to relax and soak up the sunshine!

Lindsay Davis, Pharm.D., BCPS Health-System Academy Chair hsa@azpharmacy.org The Health-System Academy of the Arizona Pharmacy Association is the Arizona affiliate of the American Society of Health-System Pharmacists (ASHP).

Summer 2013 • Arizona Journal of Pharmacy • 27

Academy News Managed Care Academy News Summer is in full swing and I hope this finds all of you enjoying some special times with family and friends. I am pleased to welcome our new MCA Chair, Eric Luecht and our new MCA Chair-elect, Paul Lynne. There is a lot of positive energy and we look forward to moving into a new year. I would like to say thank you to all of those that volunteered in our academy during the past year. We couldn’t do anything without our volunteers and leaders. Ideally we would love to have representation from all of the major managed care companies. Please reach out to Eric if you like to volunteer during this next year. We all had a great time at the AzPA Annual Convention in Tucson. There were lots of great CE opportunities, time to network, make new friends, and just have fun. Thank you to the AzPA staff for the great event and the long hours that you put in. During the convention, the Managed Care Academy had an open meeting and we had a lot of great discussions about the upcoming year. We once again are focused on quality CE, partnering with our pharmacy students, and participating with charitable organizations. Thank you for the opportunity to serve as your MCA Chair this year. It has been a wonderful experience. “What good is the warmth of summer, without the cold of winter to give it sweetness.”

― John Steinbeck

Ann Sears, R.Ph. Managed Care Academy Chair mca@azpharmacy.org

Technician Academy News The 2013 AzPA Annual Convention was a huge success offering valuable continuing education programming for technicians. Topics included diabetes, gout, obesity, women’s health, pain management, prescription drug abuse, and continuous quality improvement. Attending the annual convention is an excellent way to obtain CPE credits, connect with friends and colleagues, and network. Be sure to plan to attend the 2014 AzPA Annual Convention next June at the Wigwam in Litchfield Park, Arizona. Congratulations to Andrea Arellano, C.Ph.T., the AzPA Pharmacy Technician of the Year. Andrea is a technician with the Medication Management Center at the University of Arizona in Tucson. She received her award during the Awards Luncheon at the AzPA Annual Convention. Plans are underway for the AzPA Fall Pharmacy Conference to be held Saturday, October 26, 2013. The all-day conference will include CE for technicians, so save the date. Thank you for the privilege of serving as the Chair of the Technician Academy this past year. Our academy is in excellent hands with Judi Day, Chair, and Reg Roy, Chair-elect, at the helm. Please support them and their efforts on behalf of AzPA.

Joy Davis, C.Ph.T Technician Academy Chair tech@azpharmacy.org

28 • Arizona Journal of Pharmacy • Summer 2013

Academy News Student Pharmacist Academy News The AzPA Student Pharmacist Academy had a very successful conclusion to the year by reaching record-breaking student attendance at the 2013 AzPA Annual Convention at the Westin La Paloma Resort and Spa in Tucson, Arizona. Over 150 students attended the convention for at least one day, a new record for the Student Pharmacist Academies at Midwestern University and the University of Arizona who sent over 80 and over 60 students respectively. High attendance was partially due to the much anticipated Student Track, special programming designed for students that was held on Saturday, June 29th. Students participated in three separate Student Track sessions: “Lightning Rounds of Clinical Pearls” and “Finding your Pharma-niche: A Roundtable Discussion for Student Pharmacists,” as well as a mock interview and CV review session. For the clinical pearls session, five student pharmacists had the opportunity to speak in front of their peers for 15 minutes on a pharmacy topic of their choice. Presenters were: Steven Boyles (University of Arizona, Pharm.D. Candidate 2014), Marti Larriva (University of Arizona, Pharm.D. Candidate 2014), Karen Liu (Midwestern University, Pharm. D. Candidate 2014), Lara Petrossian (Midwestern University, Pharm.D. Candidate 2014), and Benjamin Thompson (Midwestern University Pharm. D. Candidate 2014). Each of the students did a phenomenal job presenting new and interesting topics on the forefront of pharmacy practice to of an audience of almost 100 students and pharmacists. Presenters gained valuable presentation experience while observers benefited by receiving valuable knowledge applicable to their future pharmacy practices. For the roundtable discussion session, students were able to talk to pharmacists from a variety of practice settings about their specific areas of pharmacy. Thank you to the following pharmacists that took the time to share valuable information and insight with the students: Sandra Leal (Ambulatory Care), Teresa Stickler (Community), Scott Hall (Hospital/ED), Mindy Burnworth (Political Advocacy), Mark Boesen (Pharmacy Law), Sid Patanwala (Academia/Research), Mark Harmon (Residency), Mary Lou Brubaker (Rural Health), and Rick Herrier (Indian Health Service). For the second year in a row, the mock interview/CV review session was a success. Over 50 students participated in the session, each receiving two mock interviews specific to their desired future practice setting. Thank you to the numerous pharmacists that volunteered to be interviewers; without you this session would not have been possible. In addition to the Student Track Sessions, students also participated in a variety of other events throughout the weekend including poster presentations, PharmOlympics, the NASPA OTC Challenge, and the Casino Royale Soiree. Thank you to Dr. Lindsay Davis and the AzPA Student Track Planning Committee for all of your hard work in making the event a success. This is our final message as Co-Chairs of the Student Pharmacist Academy. Please support the 2013 - 2014 Co-Chairs Pritesh Patel, U of A COP, and Sabrina Pennock, MWU-CPG, as they take over the leadership of the SPA. Sophia Galloway, SPA Co-Chair, Midwestern University College of Pharmacy Glendale sgalloway63@midwestern.edu Eric Wong, SPA Co-Chair, University of Arizona College of Pharmacy ewong@pharmacy.arizona.edu

Do you know someone who is not a member of the Arizona Pharmacy Association . . . and should be?! Invite them to join the only statewide organization that represents the pharmacy profession in Arizona. Annual dues for a pharmacist are just $20 per month! This equates to: • Approximately 2/10 of 1% of the annual wage for a new practitioner pharmacist • Less than 5 hours of work per year, after taxes • Less than 62 cents per day

Arizona Pharmacy Association

Visit the AzPA website at www.azpharmacy.org to join online or to download a printable Membership Investment Statement. AzPA values its members and recognizes that your time is valuable. Monthly payment plans are available for pharmacist membership categories, as well as an automatic annual renewal option, when you provide your credit card information.

Summer 2013 • Arizona Journal of Pharmacy • 29

Drug Information Question

Question: What evidence is available on controlled-release phentermine/ topiramate (Qsymia®) for obesity? by Tara Kalton, Pharm.D., and Stacy L. Haber, Pharm.D., Associate Professor, Midwestern University College of Pharmacy-Glendale

Answer: Introduction Obesity is a worsening epidemic, which currently affects over one-third of Americans. If the trend continues, over half of Americans will be obese by 2030. Obesity is associated with reduced life expectancy and increased comorbidities, including cardiovascular disease, diabetes, metabolic syndrome, and cancer.1 The first-line strategy for the treatment of obesity is achieving weight loss through lifestyle changes; however, these are difficult to accomplish without a supportive structure of family, friends, and an interdisciplinary healthcare team.2 Short-term pharmacological agents include phentermine, benzphetamine, diethylpropion, and phendimetrazine, and long-term options include orlistat, lorcaserin, and phentermine/ topiramate.3 Controlled-release phentermine/topiramate (Qsymia®) was approved by the FDA in July of 2012 as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with a body mass index of at least 30 kg/m2 or 27 kg/m2 and at least one comorbidity, such as hypertension, type 2 diabetes, or dyslipidemia.4 Alone, phentermine reduces appetite, but cardiovascular risks restricted it from being approved for long-term use.5 Topiramate reduces appetite and enhances satiety; however, dose-related adverse effects, including memory problems and depression, restricted it from being used as monotherapy.6 In a search of Medline, three randomized controlled trials were found that evaluated the safety and efficacy of phentermine/topiramate.7-9 Clinical Trials In a trial by Allison et al. (EQUIP), two strengths of controlledrelease phentermine/topiramate (PHEN/TPM) were compared to each other and placebo to test efficacy and tolerability in severely obese adults. After screening, all eligible patients underwent a blinded four-week titration period, then 52 weeks at the randomized dose. The primary endpoints were mean percentage of weight loss and proportion of patients achieving at least 5% weight loss. Secondary endpoints included waist circumference, blood pressure, fasting glucose, and lipid measures. Safety was evaluated through adverse effects and depression and suicidality assessments. In total, 1,267 patients were randomized (514 to placebo, 241 to PHEN/TPM 3.75/23 mg, and 512 to PHEN/ TPM 15/92 mg) and 40% discontinued the study drug (47% in placebo, 39% in the 3.75/23 mg group, and 34% in the 15/92 mg group). Patients in the 15/92 group lost significantly more weight than patients in the 3.75/23 group, who lost significantly more weight than patients in the placebo group (P < 0.0001 for all comparisons). In the intention-to-treat, last observation carried forward analysis, the mean weight loss was -1.55% for placebo, -5.10% for PHEN/TPM 3.75/23 mg, and -10.92% for PHEN/TPM 15/92 mg. The same trend occurred in the proportion of patients achieving at least 5% weight loss. Only 30 • Arizona Journal of Pharmacy • Summer 2013

17.3% of placebo patients, while 44.9% of the 3.75/23 group and 66.7% of the 15/92 group had at least 5% weight loss. The 15/92 group had significantly greater changes relative to placebo for waist circumference, blood pressure, fasting glucose, and lipid measures. The most common adverse effects in the 15/92 group were paresthesia (18.8%), dry mouth (17%), constipation (14.1%), dysguesia (8.4%), and insomnia (7.8%). The authors concluded that PHEN/TPM provided dose-dependent beneficial effects on weight and metabolic variables without serious adverse effects.7 In a similar trial by Gadde et al. (CONQUER), patients who were overweight or obese with two or more comorbidities were divided into three groups: placebo, PHEN/TPM 7.5/46 mg, and PHEN/TPM 15/92 mg. All patients had a dose titration during the initial four weeks, then the assigned doses were maintained for 52 weeks. The primary outcomes were mean percentage change in body weight and proportion of patients achieving at least 5% weight loss. Secondary outcomes were weight loss, proportion of patients achieving at least 10% weight loss, and change in waist circumference. Safety outcomes included blood pressure, heart rate, clinical and laboratory variables, adverse events, and depression and suicidality assessments. In total, 2,487 patients were randomized (994 to placebo, 498 to PHEN/ TPM 7.5/46 mg, and 995 to PHEN/TPM 15/92 mg) and 38% discontinued the study drug (43% in placebo, 31% in the 7.5/46 group, and 36% in the 15/92 group). The mean change in body weight was -1.2% for the placebo group, -7.8% for the 7.5/46 group, and -9.8% for the 15/92 group (P < 0.0001 for each PHEN/TPM group vs. placebo). The proportion of patients achieving at least 5% weight loss was 21% in the placebo group, 62% in the 7.5/46 group, and 70% in the 15/92 group. As in the previous study, the 15/92 group had significantly greater changes relative to placebo for weight loss, at least 10% weight loss, waist circumference, blood pressure, lipid measures, and fasting glucose. Dose-related trends in adverse events were noted; the 15/92 group experienced dry mouth (21%), paresthesia (21%), constipation (17%), dysgeusia (10%), insomnia (10%), dizziness (10%), anxiety (4%), disturbance in attention (4%), and irritability (3%). The authors concluded that both doses of PHEN/TPM were effective at reducing weight and improving metabolic variables in obese patients with two or more comorbidities.8 Garvey et al. conducted an extension study (SEQUEL) that followed patients from CONQUER for an additional 52 weeks. All patients were maintained on their randomized dosage. The two primary endpoints of CONQUER were retained and evaluated from baseline (week 0 of CONQUER) to week 108. Secondary endpoints were weight loss; percentage of patients achieving at least 10%, 15%, or 20% weight loss; and waist circumference. Other efficacy endpoints included changes in blood pressure, lipid variables, glycemic measures, and rate of progression to diabetes. Safety endpoints included

Drug Information Question (continued from page 30) adverse events, physical examination, clinical and laboratory measurements, vital signs, electrocardiography, and depression and suicidality assessments. In total, 676 patients were enrolled (227 taking placebo, 153 taking PHEN/TPM 7.5/46 mg, and 295 taking PHEN/TPM 15/92 mg) and 84% completed the additional year (86% in the placebo group, 83% in the 7.5/46 group, and 83% in the 15/92 group). The mean change in body weight for PHEN/TPM was significant at all time points; at week 108, it was -1.2% for placebo, -9.3% for the 7.5/46 group, and -10.7% for the 15/92 group (P < 0.0001 for each PHEN/TPM group vs. placebo). The proportion of patients achieving at least 5% weight loss at week 108 was 30.0% for placebo, 75.2% for the 7.5/46 group, and 79.3% for the 15/92 group. Patients treated with PHEN/TPM achieved greater changes compared to placebo for at least 10%, 15%, and 20% weight loss and waist circumference. PHEN/TPM was also associated with improvements in clinical manifestations of cardiometabolic disease, including hypertension, dyslipidemia, and hyperglycemia, and reduced use of concomitant medications. Interestingly, PHEN/TPM reduced both fasting glucose and insulin concentrations when compared to placebo, which is indicative of increased insulin sensitivity. There was a 54% reduction in the progression to diabetes in the 7.5/46 group and a 76% reduction in the 15/92 group when compared to placebo. The most commonly reported adverse events for the 15/92 group were upper respiratory tract infection (15.3%), sinusitis (9.5%), constipation (4.1%), paresthesia (3.4%), and dry mouth (1.4%). Overall, adverse events were similar to CONQUER, but markedly lower in incidence. The authors concluded that PHEN/ TPM produced significant and sustained weight loss over 108 weeks.9 The studies for PHEN/TPM present a few things to consider. EQUIP and CONQUER were associated with high dropout rates; the highest percentages were in the placebo groups, which may have been due to lack of efficacy. Both studies involved predominantly white and female patients, which may affect generalizability. EQUIP included severely obese patients, but excluded those with multiple comorbidities. CONQUER and SEQUEL included multiple comorbidities, but excluded severely obese patients. All three studies were funded by Vivus, the manufacturer of Qsymia®; however, no methodological concerns were noted. Discussion In all studies, the addition of PHEN/TPM to standardized lifestyle modifications led to substantial weight loss that coincides with the target of 10% recommended for overweight and obese individuals by the National Heart, Lung, and Blood Institute.2 Additionally, adverse effects were mild and welltolerated, and though PHEN/TPM has only been approved since July of 2012, phentermine has been used since 1973 and topiramate since 1996. Other issues to consider when evaluating PHEN/TPM involve comparative efficacy, cardiovascular risks, and precautions. The efficacy of PHEN/TPM was compared to other agents in a systematic review within CONQUER and to surgical treatments in the discussion of EQUIP.7,8 After subtracting weight loss from placebo, the average weight loss was 2.9% with orlistat from 13 trials, 3.3% with lorcaserin from 2 trials, and 8.6% with PHEN/TPM 15/92 from CONQUER.8 The average weight loss was 33% with bariatric surgery, 22% with lap band surgery,

and 14.4% with PHEN/TPM 15/92 in EQUIP.7 Based on this information, PHEN/TPM may be the drug with the greatest efficacy and a valuable therapeutic approach before patients consider surgical options. Sibutramine was used for long-term treatment of obesity, but withdrawn from the market in 2010 due to adverse cardiovascular events, which increased the safety concerns for all weight loss drugs. In clinical trials, sibutramine significantly increased heart rate (HR) and blood pressure (BP); however, PHEN/TPM only slightly increased HR and significantly decreased BP.7-9,10 In EQUIP, the PHEN/TPM 15/92 mg group experienced an increased HR of 1.2 beats/minute and a decreased systolic BP of 2.9 mm Hg and diastolic BP of 1.5 mm Hg.7 In SEQUEL, the PHEN/TPM 15/92 group experienced an increased HR of 0.9 beats/minute and a decreased systolic BP of 4.3 mm Hg and diastolic BP of 3.5 mm Hg, and over 15% of patients were also able to reduce their concomitant antihypertensive medications.9 Based on this information, PHEN/TPM may be a safer alternative in terms of cardiovascular risks. There are many dosing, drug interaction, and pregnancy risk considerations with PHEN/TPM. The dose must be titrated to avoid the risk of seizures. Due to the phentermine component, there are interactions with opioid analgesics, antihistamines, antacids, proton pump inhibitors, tricyclic antidepressants, antipsychotics, fat-soluble vitamins, folate, and iron; due to the topiramate component, there are interactions with azelastine, methadone, mirtazapine, amphetamines, anticonvulsants, CNS depressants, metformin, selective serotonin reuptake inhibitors, zolpidem, estrogen and progestin contraceptives, diuretics, and ketorolac. Additionally, topiramate is pregnancy category D due to an increased fetal risk of oral clefts following exposure in the first trimester. Because of the drug interaction with hormonal contraceptives and the fetal risk, PHEN/TPM should be used cautiously in women of childbearing age.3,4 In conclusion, PHEN/TPM is associated with many precautions, but provides the largest weight loss of the long-term pharmacologic agents. Thus, it is a reasonable option for obese patients if lifestyle changes and other agents have failed. References 1. Allison DB, Fontaine KR, Manson JE, et al. Annual deaths attributable to obesity in the United States. JAMA 1999;282:1530-38. 2. National Heart, Lung, and Blood Institute, NIH, US Department of Health and Human Services. Identification, evaluation, and treatment of overweight and obesity in adults. Washington, DC: National Heart, Lung, and Blood Institute, 2000. 3. Lexi-Comp, Inc. (Lexi-Drugs™). Lexi-Comp, Inc.; October 15, 2012. 4. Qsymia (product information). Vivus Inc USA: Mountain View, CA, 2012. 5. Adipex-P (product information). Teva Pharmaceuticals USA: Sellersville, PA, 2005. 6. Bray GA, Hollander P, Klein S, et al. A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 2003;11:72233. 7. Allison DB, Kishore MG, Garvey WT, et al. Controlled-release phentermine/ topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity 2011;20:330-42. 8. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomized, placebo-controlled, phase 3 trial. Lancet 2011;377:1341-52. 9. Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo—controlled, phase 3 extension study. Am J Clin Nutr 2012;95:297-308. 10. James WP, Caterson ID, Coutinho W, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 2010;363:905-17.

Summer 2013 • Arizona Journal of Pharmacy • 31

In Memoriam Thomas Allen Alspach, born on May 28, 1932 in Toledo, Ohio, passed into the Next Place on December 1, 2012 in Yuma. He is survived by his wife Nita (Carlson) and five children, David, Tim, Sarah Pfeiff, Andy, and Nancy Meadows, and eight grandchildren, He is also survived by brother Don David (Denny) Alspach Tom attended Pharmacy School at the University of Toledo and graduated with a degree in Pharmacy from the University of Arizona in 1958. Between those times he had served in the Army for 2 years, where he finished as a corporal and qualified as a Combat Medic. Tom and Nita were married in 1956 and after the U of A returned to Yuma, where his Dad and brother Jim, also pharmacists, had 2 stores. Over the years the family had Centre Drugs downtown, Frontier Drugs, The Pill Box Pharmacy, and Frontier Pharmacy, as well as a store in San Luis, Arizona. The last store, which closed in 1989, was Westmed Pharmacy. Tom then ran a pharmacy in the Grocery Store on Foothills Boulevard, and worked for Payless and Rite-Aid, retiring after working for Fry's Pharmacy in the Foothills, and Sant Drug. Pharmacists are noted as most trusted professionals, and Tom and his Dad and brother Jim personified that. Memorial services were held in Yuma. Donations can be made to a charity of your choice, or to the AWC Music Scholarship Program, c/o Prof. Deltrina Grimes, at 928-344-7574. Priyesh Patel, 26, born October 03, 1986. A pharmacy intern and student pharmacist enrolled at Midwestern University College of Pharmacy Glendale died Sunday, June 9, 2013. Services were held in Pryor, Oklahoma on June 14, 2013. Priyesh was a gentleman, scholar, and a great friend. He will truly be missed. My heartfelt condolences go out to his family and friends. – Quan Pham, CPG 2015

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www.azpharmacy.org/jobs AzPA Calendar of Events Friday, August 23, 2013 AzPA Immunization Training Program Friday, October 25, 2013 Anticoagulation Certificate Program Saturday, October 26, 2013 AzPA Fall Pharmacy Conference

A program designed to reduce medication errors.

Call toll free (866) 365-7472 or go to www.pqc.net for more information. PQC is brought to you by your state pharmacy association. 32 • Arizona Journal of Pharmacy • Summer 2013

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Visit www.azpharmacy.org for all upcoming events.

Continuing Education

Move Over Warfarin: A New Era of Treatment Options in Atrial Fibrillation

Elizabeth Pogge, Pharm.D., MPH, BCPS, FASCP, Assistant Professor, Pharmacy Practice, Midwestern University College of Pharmacy Glendale and Brittany Kaufman, Pharm.D. Candidate, Midwestern University College of Pharmacy Glendale, Class of 2013.

Table 1. CHADS2 Goal: Table 2. CHA2DS2VASc Table 2. CHA2DS2VASc 2 Risk Factor Table 1. CHADS Score Risk Factor Score This program has been developed to Risk Factor Score 1 S 1 CHF or LVEF < 40% Risk Factor update pharmacists and/or pharmacy CHF 1 1 Hypertension 1 CHF Hypertension technicians on the new oral anticoagulants CHF or LVEF < 40% Age > 75 Hypertension 1 2 Age ≥ 75 available to treat atrial fibrillation. 1 Hypertension 1 Diabetes Age > 75 D iabetes 1 Age ≥ 751 2 Hx of Stroke or TIA Hx of S troke, TIA or Objectives: 1 Diabetes Diabetes2 High risk = > 2, intermediate risk = 1, thromboembolism At the conclusion of this lesson, successful 2 low risk = 0 Hx of Stroke or TIA Hx of Stroke, TIA or 1 Vascular Disease participants should be able to: Table adapted from reference 3 High risk = > 2, intermediate risk = 1, thromboembolism 1 Age 65 – 74 1. Discuss the different stroke and low risk = 0 Vascular1Disease Female (Sex) bleeding risk assessment tools used in Table adapted from reference 3 High risk = > 2, intermediate Age risk 65 –= 1,74low atrial fibrillation. risk = 0 Table adapted from reference 4 2. Compare and contrast the three Female (Sex) category and thus requiring some which anticoagulation agent depends on recently FDA approved oral High risk = >form 2, intermediate risk of anticoagulation therapy. addition, patients’ risk factors for developing stroke risk = In 0 Table adapted from refe anticoagulants that can be used in because of the extended time period that and must also take into account their risk atrial fibrillation. Table 3. HASBLED most patients will be on therapy, some The primary method for 3. Describe some of the issues related to for bleeding. Risk Factor Score even1 lifelong, it is convenient to use oral determiningHypertension risk of stroke is the CHADS the new oral anticoagulants. (Uncontrolled, >1602mmHg 3 agents in these patients. For many years scoring system due to ease of 3. use. It systolic) Table HASBLED the gold in anticoagulation uses a patient’s history to differentiate a 1 or 2standard (1 pt for each) Introduction Abnormal renal/liver function Risk Factor Score therapy patient intoSlow, 1 was warfarin as it has been the In a field as dynamic as cardiology, it is troke intermediate or high risk Hypertension (Uncontrolled, >160 mmHg 1 , although easy to use only1 oral agent on the market. However, often difficult to stay on top of the updated for stroke. BCHADS leeding history or predisposition 2 systolic) 1 warfarin has many limitations, including and accurate, is not recommendations and guidelines. Major Labile INR sensitive enough to 1 or 2 (1 pt for each) function 1 interactions (e.g., drug-food, drug-disease stratify lowElderly risk patients. For this renal/liver reason changes occur frequently, new strategies (age > A 654bnormal years) 1 considerable Stroke 1 or 2 (1 pt for each)and and drug-drug) CHA2DS2VASc been created to further state, are evolving, older beliefs are challenged, Drugs has (ie concomitant antiplatelet/NSAID alcohol intra- and inter-patient1variability in explore lowuse) riskand/or patients anduse whether Bleeding history or predisposition new agents are developed and new score = 9 dose requirements that1result in frequent they requireMax anticoagulation The indications for old agents are approved. Labiletherapy. INR High risk = ≥ 3, moderate risk = 1 or 2, low risk = 0 normalized in scoring for CHADS and Pharmacists play a major role in managing differencesTable 1 ratio (INR) Elderly (age2 5> 65 years)international adapted from reference testing.3 The complexities CHA2DS2VASc are illustrated in Table 1 of warfarin anticoagulation therapy through agent Drugs (ie concomitant antiplatelet/NSAID 1 or 2 (1 pt for each) & 2. dosing and problems with interactions recommendations, monitoring outcomes use) and/or alcohol use Evidence isofconflicting on whichIndications scoring result in INR readings commonly out and education. It is important for Table 4. Mechanism Action and Approved Max score = 9 but both are useful of therapeutic range. Even in many pharmacists to be aware of new therapiesDrug system is superior Mechanism High risk = ≥ 3, moderate FDA Approved risk = 1 or 2, low risk = 0 aids in assessing a patient’s annual risk of specialized anticoagulation clinics, and to understand the differences between Dabigatran Direct Thrombin Inhibitor Stroke and embolism prevention in which Table adapted from reference 5systemic (Pradaxa®) AF stroke. Because the CHADS2 score has nonvalvular exist primarily to manage warfarin and the anticoagulant agents. Direct Factor Xa Inhibitor prophylaxis and treatment; been extensively validated and is easy DVT/PE other anticoagulant therapy,DVT time in Anticoagulant agents are indicated Rivaroxaban in orthopedics; stroke prevention in for clinicians to remember and use, the prophylaxis therapeutic INR range (TTR) is estimated for many disease states with the most (Xarelto®) nonvalvular AF Table 4. Mechanism of Action and Approved Indications 2012 CHEST guidelines recommend that to be only 50% – 60%, although some common being; venous thromboembolism/ Apixaban Drug Direct Factor Xa Inhibitor Stroke and systemicFDA embolism prevention in Mechanism Approved it be used as the principal approach for clinicsAF run by pharmacists have reported pulmonary embolism prophylaxis (Eliquis®) Dabigatran nonvalvular Direct Thrombin Inhibitor Stroke and systemic new embolism 3 6 Recently Recently, oral preventi assessing patients’ stroke risk. rates as high as 73%. and treatment, stoke prevention, atrial Warfarin Vitamin K Epoxide Reductase DVT/PE prophylaxis and treatment; stroke (Pradaxa®) nonvalvular AF a new scoring system has been developedprevention anticoagulant agents have been approved, fibrillation and acute coronary syndrome.(Coumadin®) Inhibitor in AF and/or cardiac valve Rivaroxaban Xa Inhibitor DVT/PE prophylaxis and replacement; reduction inprofessionals risk of death, MI, andtreatment; DVT to determine a patient’sDirect risk ofFactor bleeding, giving healthcare more Atrial fibrillation (AF) is the most 5 (Xarelto®) prophylaxis in orthopedics; stroke prev or systemic embolismyet after MI making termed HASBLED. It provides a modeststrokeoptions for therapy, also common sustained cardiac dysrhythmia nonvalvular AF fromofreferences 8 – 11 events. The prediction major bleeding optimal selection of therapy more in the United States; with an estimated Table adapted Apixaban DirectinFactor Stroke andmust systemic embolism preventi scoring system is illustrated TableXa Inhibitor complex. Pharmacists formulate prevalence between 2.7 and 6.1 million (Eliquis®) nonvalvularsuch AF that they fully 3. Even through all the scoring systems their recommendations adults (2010), resulting in approximately Warfarin Vitaminrisk K Epoxide prophylaxis treatment; stro are helpful tools for analyzing verse Reductase consider bothDVT/PE the patient’s risk ofand stroke 500,000 hospital discharges annually.1 (Coumadin®) prevention in by AF increasing and/or cardiac valve the decision forInhibitor anticoagulation and the potential for harm The primary adverse event associated with benefit, reduction in risk of death therapy must always be subjective and the bleeding replacement; risk. AF is the development of cardioembolic stroke or systemic embolism after MI patient-specific. ischemic stroke, which costs an estimated Table from references 8 – 11 New Oral Anticoagulant Agents The riskadapted of developing AF increases $53.9 billion per year (2010).2 significantly with age, combined with Before looking at the new AF increases the risk of stroke 4- to the high prevalence of diabetes and pharmacologic agents, figure 1 gives 5-fold and accounts for 5% – 20% of hypertension the majority of patients a simplified illustration of the clotting all ischemic strokes, therefore most with AF will receive scores of 2 or pathways and what factors each agent acts patients with AF will be on some form on. greater; putting them in the high risk of anticoagulation therapy.1 Selection of Summer 2013 • Arizona Journal of Pharmacy • 33

Table 3. HASBLED Risk Factor Continuing Education (continued from page 33) Hypertension (Uncontrolled, >160 mmHg Table 3. HASBLED systolic) Risk Factor Score Abnormal renal/liver function Hypertension (Uncontrolled, >160 mmHg 1 Stroke systolic) Bleeding history or1predisposition or 2 (1 pt for each) Abnormal renal/liver function Labile INR 1 Stroke 1 Bleeding history or predisposition Elderly (age > 65 years) 1 antiplatelet/NSAID Labile INR Drugs (ie concomitant Elderly (age > 65 years)use) and/or alcohol1 use 1 or 2 (1 pt for each) Drugs (ie concomitant antiplatelet/NSAID Max score = 9

Score 1 1 or 2 (1 pt for each) 1 1 1 1 1 or 2 (1 pt for each)

use) and/or alcohol useHigh risk = ≥ 3, moderate risk = 1 or 2, low risk = 0 Max score = 9 Table adapted from reference 5 High risk = ≥ 3, moderate risk = 1 or 2, low risk = 0 Table adapted from reference 5

Figure 1

Adapted from reference 7

he risk of developing AF increases significantly withApproved age, combined with the high prevalence of Table 4. Mechanism of Action and Indications and hypertension patients with AF will receive scores of 2FDA or greater; putting Drug the majority ofMechanism Approved he high riskDabigatran category and thus requiring some form Inhibitor of anticoagulation therapy. addition, Direct Thrombin StrokeInand systemic embolism prevention in of the extended time period that most patients will be on therapy, some even lifelong, it is (Pradaxa®) nonvalvular AF nt to use oral agents in these patients. manyXa years the gold standardDVT/PE in anticoagulation Rivaroxaban DirectFor Factor Inhibitor prophylaxis and treatment; DVT was warfarin(Xarelto®) as it has been the only oral agent on the market. However, warfarin has prophylaxismany in orthopedics; stroke prevention in s, including interactions (e.g., drug-food, drug-disease state, and drug-drug) and considerable nonvalvular AF inter-patient variability in dose requirements that result in frequent international normalized Apixaban Direct Factor Xa Inhibitor Stroke and systemic embolism prevention in ) testing.3 The complexities of warfarin dosing and problems with interactions result inAF INR (Eliquis®) nonvalvular commonly out of therapeutic range. EvenKinEpoxide many specialized anticoagulation clinics, which Warfarin Vitamin Reductase DVT/PE prophylaxis and treatment; stroke arily to manage warfarin and other anticoagulant therapy, time in therapeutic INR range (TTR) (Coumadin®) Inhibitor prevention in AF and/or cardiac valve ed to be only 50% – 60%, although some clinics run by pharmacists havereplacement; reported rates reduction as high in risk of death, MI, and Recently, new oral anticoagulant agents have been approved, giving healthcare stroke professionals or systemic embolism after MI ons for therapy, also making selection of therapy more complex. Pharmacists must Tableyet adapted fromoptimal references 8 – 11 e their recommendations such that they fully consider both the patient’s risk of stroke and the for harm byTable increasing the bleeding risk. 5. Characteristics of Oral Anticoagulants

Agent

Dabigatran

Rivaroxaban

Standard dose

150 mg twice daily

20 mg daily

Alternative dose

CrCl 15 – 30 mL/min: 75 mg twice daily CrCl 30 – 50 m/min with dronadrone or ketoconazole: 75 mg twice daily 3 – 7%

CrCl 15 – 50 mL/min: 15 mg daily

Bioavailability Hepatic elimination Renal elimination Half-life

Glucuronidation P-gp substrate 80% as unchanged drug

Protein binding

35%

12 – 17 hours

34 • Arizona Journal of Pharmacy • Summer 2013

Apixaban 2

66% (80 - 100% with food) CYP3A4/5 and CYP2J2 P-gp substrate 66% (36% as unchanged drug) 5 – 9 hours (11 – 13 hours in geriatrics) 92 – 95%

5 mg twice daily 2.5 mg twice daily: 2+: age>80 yrs; wt<60 kg; serum Cr > 1.5 mg/dL OR with strong CYP3A4 and P-gp inhibitors 50% CYP3A4/5 P-gp substrate 25% as unchanged drug 12 hours 87%

Continuing Education (continued from page 34) Only within the last three years have new oral anticoagulants been made available; dabigatran (2010), rivaroxaban (2011) and apixaban (2012). Table 4 outlines each agent’s mechanism of action and Food and Drug Administration (FDA) approved indications for use. It is important to note that all agents are approved for use in nonvalvular AF, but warfarin is the only agent with approval for use in patients with AF in the setting of rheumatic heart disease, mitral stenosis, or prosthetic heart valves. Dabigatran (Pradaxa®) Dabigatran is a prodrug that received FDA approval for prevention of stroke and systemic embolism in nonvalvular AF.8 Dabigatran is usually dosed at 150 mg twice daily, but has a reduced dosage of 75 mg twice daily recommended for patients with CrCl of 15 to 30 mL/ min. It is important to note that this FDA approved dose of 75 mg had not been studied in clinical trials but was instead based on pharmacokinetic extrapolations. Dabigatran use is contraindicated in patients with CrCl < 15 mL/min and those with CrCl < 30 mL/min who are also taking strong P-glycoprotein (Pgp) inhibitors (e.g. dronedarone or oral ketoconazole). It is also recommended to consider a reduced dose of 75 mg twice daily in patients with CrCl 30 to 50 mL/min who are on concomitant p-gp inhibitors. It is recommended to avoid concomitant use of p-gp inducers (e.g. rifampin) and dabigatran as it may reduce dabigatran efficacy. The American Geriatric Society has listed dabigatran in the 2012 Beers criteria.12 Due to a greater risk of bleeding as compared to warfarin in those who are over 75 years of age as well as a lack of evidence for efficacy and safety in those with CrCl < 30 mL/min, the Beers criteria expert panel recommends that dabigatran be used with caution in those who are < 75 years of age or have a CrCl <30 mL/min. Table 5 details the pharmacology of dabigatran. The most common adverse effects associated with dabigatran are generally gastrointestinal (GI) related, bleeding, gastritis, dyspepsia, and are thought to be due to the coating. The pellet coating of dabigatran is formulated with tartaric acid that is specially designed to acidify the stomach environment and increase dabigatran absorption. It should be noted that the use of proton pump inhibitors in

clinical trials did not affect the efficacy of dabigatran compared with warfarin.13 However, given the over-the-counter availability of both histamine antagonists and proton pump inhibitors, the potential exists for higher doses than those that were clinically evaluated in clinical trials. It remains to be seen if these higher doses will affect dabigatran efficacy. The Randomized Evaluation of LongTerm Anticoagulation Therapy (RE-LY) trial was a phase III study that compared dabigatran with warfarin for stroke prevention in patients with AF.13 Table 6 summarizes the details from the RE-LY trial. The trial found that the dabigatran 110 mg group was noninferior to warfarin in regards to the primary endpoint of stroke or systemic embolism (annual rate 1.53% vs. 1.69%, hazard ratio, 0.91 (0.74-1.11); noninferiority p<0.001) while the 150 mg group was superior to warfarin (1.11% vs. 1.69%, hazard ratio, 0.66 (0.53-0.82); superiority p < 0.001). Bleeding rates were similar between warfarin and the 150 mg group, while the 110 mg group had fewer major and nonmajor bleeding events. In the 150 mg group, the incidence of GI bleeding was higher when compared to warfarin (annual rate 1.51 vs. 1.02, p < 0.001), while intracranial bleeding was lower (annual rate 0.30 vs. 0.75, p<0.001). The rate of myocardial infarction (MI) was higher with the dabigatran 110 mg group (annual rate 0.72% vs. 0.53%, p=0.07) and 150 mg group (annual rate 0.74% vs. 0.53%, p=0.048) compared to warfarin. It is noteworthy to mention that warfarin management in the trial produced an overall mean TTR of 64%.14 However, in patients with a mean TTR greater than 65.5%, there was no significant difference in the risk of stroke or systemic embolism compared with the 110 mg or 150 mg dabigatran groups, and rates of major bleeding events were similar. Rivaroxaban (Xarelto®) Rivaroxaban has FDA approval for use in DVT/PE prophylaxis and treatment, DVT prophylaxis in orthopedics and stroke prevention in nonvalvular AF. Rivaroxaban for the prevention of stroke in AF is dosed 20 mg daily with a dose reduction to 15 mg daily if CrCl is 15 – 50 mL/min. Rivaroxaban use is contraindicated in patients with CrCl < 15 mL/min and in patients with moderate to severe hepatic impairment (Child-

Pugh class B and C). Rivaroxaban doses ≥ 15 mg per day should be taken with food as it increases bioavailability.9 Table 5 details the pharmacology of rivaroxaban. Rivaroxaban should not be used concurrently with strong cytochrome P450 (CYP) 3A4 and P-gp inducers or inhibitors. The most common adverse effects associated with rivaroxaban are bleeding events. The Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial was a phase III study that ultimately led to rivaroxaban approval for stroke prevention in AF.15 Table 6 summarizes the details from the ROCKET-AF trial. The trial found that rivaroxaban was noninferior to warfarin in stroke or systemic embolism prevention (annual rate 2.1% vs. 2.4%, hazard ratio, 0.88 (0.74 - 1.03); noninferiority p<0.001). Both rivaroxaban and warfarin had similar major and nonmajor clinically relevant bleeding rates, with less intracerebral hemorrhage (0.5% vs. 0.7%, p=0.02) and fatal bleeding (0.2% vs. 0.5%, p=0.003) with rivaroxaban. Of note warfarin management in this trial produced an overall mean TTR of 55%, which is lower than in other trials with new oral anticoagulants. The trial also observed an increased rate of stroke or systemic embolism following discontinuation of rivaroxaban (81 events vs. 66 events in warfarin, p=0.58), which led to a black box warning and a recommendation to bridge patients with alternative anticoagulation upon discontinuation of rivaroxaban. Apixaban (Eliquis®) Apixaban, the most recently FDA approved oral anticoagulant, is approved for stroke and systemic embolism prevention in nonvalvular AF.10 The approved dose of apixaban is 5 mg twice daily with a dose reduction to 2.5 mg twice daily in patients with any two of the following: weight ≤ 60kg, Scr ≥ 1.5 mg/ dL or ≥ 80 years old. Also recommended is a dose of 2.5 mg twice daily when used concomitantly with strong CYP3A4 and p-gp inhibitors. It is not recommended in severe hepatic impairment (Child-Pugh class C) or in patients with CrCl < 15 mL/ min. Table 5 details the pharmacology of apixaban. The most common adverse

Summer 2013 • Arizona Journal of Pharmacy • 35

Continuing Education (continued from page 35) Table 6: Summary of Clinical Trials Trial RE-LY (n = 18,113) Drug Dabigatran Dose 150 mg twice daily and 110 mg twice daily Compared to Patient Population

Warfarin INR target 2 – 3 Nonvalvular AF

ROCKET-AF (n = 14,264) Rivaroxaban 20 mg daily (15 mg daily was used in those with CrCl 30-50 mL/min) Warfarin INR target 2 – 3 Nonvalvular AF

Median duration of follow up Additional requirements

2 years

1.9 years

Warfarin INR target 2 – 3 Nonvalvular AF or atrial flutter 1.8 years

Hx stroke, TIA, LVEF < 40%; NYHA ≥ class II PLUS Age ≥ 75 OR age 65 – 74 PLUS DM, HTN or CAD Open label

Hx stroke, TIA, or systemic embolism OR At least 2 of the following: CHF; HTN; DM; age ≥ 75

At least 1 of the following: Age ≥ 75 yo; hx of stroke, TIA or systemic embolism; HF or LVEF < 40%; DM; HTN

Double-blind, doubledummy Noninferiority 3.48 ± 0.94

Double-blind, doubledummy Noninferiority 2.1 ± 1.1

Trial design Trial type CHADS2 tx group (mean ± SD) Annual rate of stroke or systemic embolism vs. warfarina TTR warfarin Annual rate of major and nonmajor clinically relevant bleeding vs. warfarinb Annual rate of major bleeding vs. warfarinb

Noninferiority 150 mg: 2.2 ± 1.2 110 mg: 2.1 ± 1.1 150 mg: 1.11% 110 mg: 1.53% vs. 1.69% 64% 150 mg: 16.42% (p=0.002) 110 mg: 14.62% (p<0.001) vs. 18.15%

150 mg: 3.11% (p=0.31) 110 mg: 2.71% (p=0.003) vs. 3.36% Table adapted from references 13-16 a Data is from the intent to treat population b Bleeding definitions were variable

effects associated with apixaban are bleeding events similar to all other anticoagulants. The Apixaban Versus Warfarin In Patients with Atrial Fibrillation (ARISTOTLE) trial ultimately led to the approval of apixaban in the United States.16 Table 6 summarizes the details from the ARISTOTLE trial. The trial found that apixaban was noninferior and superior to warfarin in stroke or systemic embolism prevention (annual rate 1.27% vs. 1.60%, hazard ratio, 0.79 (0.66-0.95); noninferiority p<0.001, superiority p =0.01). Apixaban was found to have lower major bleeding rates than warfarin. Similar to rivaroxaban, an increased rate of stroke following discontinuation of apixaban was observed during the transition from apixaban to warfarin in clinical trials.10 This has led to a black box warning and a recommendation to bridge patients with alternative anticoagulation upon discontinuation of apixaban. Discontinuation of therapy As with other anticoagulants, these new

ARISTOTLE (n = 18,201) Apixaban 5 mg twice daily

2.1% vs. 2.4%

1.27% vs. 1.6%

55% 14.9% vs. 14.5% (p=0.44)

62.2% 4.07% vs. 6.01% (p<0.001)

3.6% vs. 3.4% (p=0.58)

2.13% vs. 3.09% (p<0.001)

oral anticoagulants must be discontinued prior to invasive procedures to decrease the risk of bleeding. Due to the short half life of these agents and several box warnings about an increased risk of stroke upon discontinuation, it is recommended to minimize lapses in therapy whenever possible. Table 7 lists current recommendations for procedural management. Conversion between anticoagulants The advertising of these new agents may alert patients to the different options and patients may request to be switched to another agent. This is another area where pharmacist should be knowledgeable and able to safely and effectively switch patients between anticoagulant agents. The recommendations for switching between agents are summarized in Table 8. Issues related to new anticoagulants Although the new agents are well tolerated and equally efficacious compared to warfarin, they are not without issues of their own. Their short half-life presents

36 • Arizona Journal of Pharmacy • Summer 2013

the problem of no anticoagulant effect with missed doses. Compliance is of utmost importance and missing doses can put a patient at risk of have a stroke. Additionally, there is no way to monitor the drug levels in patients and therefore doses cannot be customized for elderly patients or patients with hepatic or renal dysfunction. Unlike vitamin K for warfarin, the new anticoagulant agents have no specific antidotes for bleeding events and reversal is dependent on the elimination process. Due to low protein binding dabigatran can be removed via hemodialysis, but rivaroxaban and apixaban cannot. Since all of the agents have kidney and/or liver metabolism, the elimination of each agent can be prolonged in the present of organ insufficiency. For these reasons, warfarin remains the drug of choice for patients with severe renal or hepatic dysfunction. Furthermore, the RE-LY trial produced the hypothesis that warfarin may be protective against MI; as the dabigatran group had an increase rate of MI.13 It is important to note that this increased risk of MI was not seen in the ROCKET-AF or ARISTOTLE trial.15-16 There are several drug-drug interactions that are possible with the new oral anticoagulants. Although they are fewer than the drug-drug interactions with warfarin, they may be of more concern due to the inability to monitor a therapeutic effect and adjust therapy accordingly. Due to the vast history of warfarin the list of confirmed drug interactions is long and detailed, while the short history of the new anticoagulants lacks this knowledge. Conclusion In conclusion, the prevalence of AF and resulting risk of stroke creates a need for anticoagulant agents. The decision for anticoagulant therapy will remain subjective and patient-specific with the need to balance risk of stroke against risk of bleeding. CHADS2, CHA2DS2VASc and HASBLED have given us modest assistance for determining a patient’s risk of stroke and bleeding, respectively. Overall, the new oral anticoagulants have many advantages compared with warfarin. These include the lack of drug-food interactions, the lack of need for routine monitoring, and the use of fixed dosing. Furthermore, clinical trials have shown that each agent is either noninferior or superior to warfarin with similar bleeding

Continuing Education (continued from page 36) Table 7. Procedural Management Agent Pre-procedure Dabigatran

Rivaroxaban Apixiban

Post procedure

Discontinue 1-2 days (CrCl > 50 mL/min) Discontinue 3-5 days (CrCl 15-50 mL/min) Consider longer time for patients undergoing major surgery, spinal puncture, or placement of spinal or epidural catheter or port Discontinue at least 24 hours prior to invasive procedure Discontinue at least 48 hours prior if procedure has moderate or high risk of bleeding Discontinue at least 24 hours prior if a procedure has a low risk of bleeding

Restart after adequate hemostasis has been established. If oral medication cannot be given during or after surgical intervention, consider administration of a parenteral anticoagulant

Table 8. Conversion between Anticoagulant Agents Switching Dabigatran Rivaroxaban From Discontinue warfarin, start Discontinue warfarin, start warfarin dabigatran when INR < 2.0 rivaroxaban when INR < 3.0 To CrCl ≥ 50: start warfarin 3 No clinical data available. warfarin days before discontinuing Discontinue rivaroxaban and dabigatran begin a parenteral CrCl 30 – 50: start warfarin 2 anticoagulant and warfarin days before at the time of the next CrCl 15 – 30: start warfarin 1 scheduled dose. Discontinue day before the parenteral anticoagulant when INR reaches an acceptable range. From Start dabigatran 0 – 2 hours Start rivaroxaban 0 – 2 hours other before the next scheduled before the next scheduled agents dose of the other dose of the other anticoagulant. anticoagulant. If a continuously If a continuously administered parenteral administered parenteral drug, stop infusion and start drug, stop infusion and start dabigatran at the same time. rivaroxaban at the same time. To other Wait 12 hours if CrCl ≥ 30 or For patients switching to an agents 24 hours if CrCl < 30 after anticoagulant with rapid the last dose of dabigatran onset, discontinue before starting an rivaroxaban and give the alternative anticoagulant first dose of the other with a rapid onset. anticoagulant (oral or parenteral) at the time of the next scheduled dose. Dabigatran may increase INR, Rivaroxaban may affect INR, INR Notes measure warfarin’s effect on INR at least 2 days after dabigatran had been stopped

Table adapted from references 8-10

measurements may not be useful for determining maintenance dose of warfarin

Apixaban Discontinue warfarin, start apixaban when INR < 2.0 Discontinue apixaban and begin a parenteral anticoagulant and warfarin at the time of the next scheduled dose. Discontinue the parenteral anticoagulant when INR reaches an acceptable range. Discontinue the anticoagulant being taken and begin apixaban at the next scheduled dose.

Discontinue apixaban and begin the other anticoagulant at the next scheduled dose.

Apixaban may affect INR, INR measurements may not be useful for determining maintenance dose of warfarin

rates.13,15-16 Although warfarin’s cost, efficacy and proven track record will prolong its use, it is important to fully consider all agents when selecting one for individual patients. References 1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation. 2013;127:e6-e225. 2 Heidenreich PA, Trogdon JG, Khavjou OA, et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011;123(8):933–44. 3. You JJ, Singer DE, Howard PA, et al. Antithrombotic Therapy for Atrial Fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2):e531S-e575S. 4. Lip GY, Nieuwlaat R, Pisters R, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro heart survey on atrial fibrillation. Chest. 2010b;137:263-72. 5 Lip GY, Frison L, Halperin JL, et al. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED score. J Am Coll Cardiol.2011;57:173-80. 6. Young S, Bishop L, Twells L, et al. Comparison of pharmacist managed anticoagulation with usual medical care in a family medicine clinic. BMC Fam Pract. 2011;12:88. 7. Pathophysiology and Natural History of Venous Thromboembolism. Figure 2. The coagulation cascade. Assessed March 5th, 2013 via http://www. cancerthrombosis.org/moduleArticle?id=2. 8 Product Information: Pradaxa®, dabigatran etexilate mesylate. Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT. Revised: December 2012. 9. Product Information: Xarelto®, rivaroxaban. Janssen Pharmaceuticals, Titusville, NJ. Revised: March 2013. 10. Product Information: Eliquis®, apixaban. Bristol-Myers Squibb Company, Princeton, NJ. Revised: December 2012. 11. Product Information: Coumadin®, warfarin. Bristol-Myers Squibb Company, Princeton, NJ. Revised: October 2011. 12. American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society Update Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60(4):616-31. 13. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51. 14. Wallentin L, Tusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalized ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010;376:975-83. 15 Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-91. 16. Granger CB, Alexander JH, McMurray JV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-92.

Summer 2013 • Arizona Journal of Pharmacy • 37

Continuing Education

Variceal Bleeding from Cirrhosis: A Clinical Review of Causes and Pharmacotherapy Options

by Hillary Aphaisuwan, Pharm.D. Candidate, Midwestern University College of Pharmacy-Glendale Class of 2014, Ibrahim Lala, Pharm.D. Candidate Midwestern University College of Pharmacy-Glendale Class of 2014, and Laura Tsu, Pharm.D., BCPS, Assistant Professor, Pharmacy Practice, Midwestern University College of Pharmacy-Glendale Goal: Systemic Complications Pathophysiology This home-study CPE activity has been Stemming from the vascular changes Cirrhosis is characterized histologically developed to educate pharmacists on the and the resultant increase in intrahepatic by the presence of fibrotic lesions in prevention and treatment of hemorrhagic resistance, cirrhosis results in systemic the liver. Due to chronic offense to the esophageal varices resulting from complications. These complications liver, inflammation and tissue injury cirrhosis. include: portal hypertension, esophageal persist. Abnormal wound healing leads varices, ascites, spontaneous bacterial to the replacement of normal hepatocytes Objectives: peritonitis (SBP), hepatic encephalopathy, At the conclusion of this lesson, successful with collagenous scar tissue, which can hepatorenal syndrome, and then be encapsulated by a fibrotic cap. participants should be able to: coagulopathies. 1. Explain which systemic complications Eventually, the fibrosis accumulates to The primary complication, nearly such a degree that the scar tissue disrupts are commonly seen in cirrhotic hepatic vasculature, compromising hepatic universal among cirrhotic patients, is patients portal hypertension. It is defined as an circulation and resulting in a reduction of 2. Compare the mechanism of action of increased resistance to hepatic circulation. liver function. Once hepatic circulation is the medications used to prevent and compromised and vasculature is damaged, Due to altered morphology of the liver treat hemorrhagic varices caused by fibrosis, the liver is unable to liver fibrosis is classified as cirrhosis. 3. Select an appropriate dose of efficiently circulate blood through the The end result of this excess fibrosis is medication for the prevention and portal vein, hepatic sinusoids, and in poor liver function, increased intrahepatic treatment of hemorrhagic varices resistance (leading to portal hypertension), hepatic venous outflow. Quantitatively, 4. Formulate an appropriate therapeutic portal hypertension is defined as a pressure regimen for a patient given the current and an increased risk for the development gradient between the portal and central of hepatocellular carcinoma.3,5 state of the varices veins of more than 5mmHg. This gradient is called the hepatic venous pressure Signs and Symptoms Introduction: gradient (HVPG).3,5 Signs and symptoms of cirrhosis vary Epidemiology and Etiology A primary consequence of portal Cirrhosis is an irreversible, chronic liver widely, depending on the degree of liver hypertension is the development of damage that has occurred. Typically, disease which affects slightly more than varices. Due to an increase in portal early damage shows few unique signs 100,000 individuals and caused 31,000 resistance, blood flow backs up into the and symptoms, and as a result goes deaths in 2009.1 This represents a 30% left gastric vein, which drains much of the undetected and undiagnosed. Symptoms mortality rate, which is significantly blood leaving the esophagus. As a result of nonspecific liver damage, which may higher than more prevalent disease of back-up, the left gastic vein and its present in the early stage of cirrhosis, states. The high rate of death due to tributaries become dilated. These swollen include jaundice, bleeding and bruising, cirrhosis indicates the importance of esophageal veins are called varices, which fatigue, and nausea.3,6,7 As cirrhosis pharmacotherapeutic interventions, which are prone to twisting and rupture, leading progresses, the signs and symptoms can readily prevent complications and to internal hemorrhage. Qualitatively, become progressively more serious. reduce mortality. Educating pharmacists hemorrhagic varices typically present These systemic complications are often on proper treatment options allows them as hematemesis and abdominal pain. the reason a patient gets evaluated and make recommendations and ensure that Quantitatively, varices develop when the diagnosed in the first place. Advanced patients are receiving optimal therapy cirrhotic patients present with the hallmark HVPG rises to 8 - 10mmHg. When the based on the most current evidence HVPG further rises to >12mmHg, these systemic complications described below. available. varices can rupture, resulting in variceal In addition to the described signs There are multiple etiologies of bleeding into the abdomen. Variceal and symptoms, certain lab findings are cirrhosis, including metabolic diseases, consistent with cirrhosis. In both the early bleeding occurs in up to 40% of cirrhotic autoimmune diseases, and non-alcoholic patients, and has a 33% fatality rate.3,5 and advanced stages of cirrhosis, a patient fatty liver disease/non-alcoholic In addition to causing varices, portal steatohepatitis. The most common causes, may present with elevated liver enzymes hypertension results in ascites, which (with AST > ALT), elevated bilirubin, however, are chronic alcohol abuse is the accumulation of fluid within the hypoalbunemia, thrombocytopenia, and (defined as two to three drinks per day peritoneal cavity. Ascites occurs in leukopenia.3,7 As with external signs for women, and three to four drinks per approximately 50% of cirrhotic patients. and symptoms, these laboratory findings day for men) and chronic infection with It is a result of three factors: persistent Hepatitis B, C or D viruses.2,3 In addition, progress as the disease progresses, and water retention (due to a drop in arterial may not become apparent until a patient certain medications can lead to cirrhosis blood pressure), increased splanchnic has a more advanced case of the disease. due to hepatotoxicity, the most commonly vascular permeability (due to persistent used of which is acetaminophen.4 38 â€˘ Arizona Journal of Pharmacy â€˘ Summer 2013

are essential in improving quality of life and preventing morbidity and mortality. The most commonly seen complication is an acute variceal hemorrhage, which has a complicated, but well-defined treatment protocol involving vasoactive agents, beta-blockers, antimicrobials and surgical procedures. Continuing Education (continued from page 38) A last line-treatment option when complications cannot be managed is a liver transplant.

vasodilation as a result of intrahepatic Table 1 – Child-Pugh Classification of Cirrhosis10 resistance) and lymph leakage into the 3,5 peritoneum. Another common, and often fatal, complication of cirrhosis is spontaneous bacterial peritonitis (SBP). In cirrhotic patients, enteric bacteria undergo bacterial translocation into abdominal lymph nodes. When cirrhotic patients become ascitic, these bacteria move along with lymphatic fluid into the peritoneum, resulting in Table 2 – Primary Prophylaxis of Variceal Bleeding SBP.8 In the presence of ascites, patients are often treated prophylactically to Child-Pugh Class A Child-Pugh Class B or C prevent SBP. The American Association for the Study of Liver Diseases (AASLD) Initiate NSBB therapy Small Varices Annual upper endoscopy guidelines recommend treating patients prophylactically for SBP when they Initiate NSBB therapy or treat with endoscopic Medium or present with hemorrhagic varices, as N/A ligation (EBL/EVL) Large Varices studies have shown that this reduces infectious complications and reduces the patient's bilirubin level, serum prevention of first incident of bleeding, mortality.9,10 Hepatic encephalopathy (HE) is the treatment of acute variceal hemorrhages,  albumin, prothrombin time, and whether result of the liver's inability to process encephalopathy is present. Based on the and prevention of rebleeding. It is nitrogenous wastes, resulting in an patient's lab values and the severity of recommended that all patients undergo increased ammonia load in the blood. encephalopathy and ascites (if present), esophagogastroduodenoscopy (EGD) These wastes can enter the CNS, altering point values are assigned to each regularly to screen for the presences neurotransmission and resulting in an characteristic. The points are then added of varices. The AASLD guidelines altered mental status, typically confusion. recommends an EGD every three years up, and the patient is then classified as While HE does not correlate directly with if no diagnosis of varices is made upon Child A, B, or C, in order of increasing a specific blood ammonia level, treatments severity of cirrhosis. See Table 1 for initial examination. After a diagnosis of focus on removal of ammonia from the varices is made, preventive measures of the numerical scores assigned to each blood.3 variceal hemorrhages are dependent on the characteristic.12 A Child A patient has As a result of splanchnic vasodilation, a 100% 1-year survival rate, whereas a patient’s Child-Pugh Score.13 there is decreased renal blood flow, and Child C patient only has a 40% 1-year thus, a decreased glomerular filtration survival rate.3 Prevention of Variceal Hemmorhages rate. These factors present as hepatorenal Varices are categorized based on Patients with Small Varices syndrome, which is functional renal their appearance and size. Per AASLD AASLD guidelines state that patients failure in the absence of renal disease. guidelines, varices should be classified with small varices that have not bled who Hepatorenal syndrome occurs in about into one of two categories: small or large. have a Child-Pugh score of B/C should 20% of patients within 1 year of being Small varices are those that are <5mm in use nonselective β-blockers (NSBB), diagnosed, and approximately 40% of diameter, while large varices are those that such as propranolol or nadolol, for the patients after 5 years.11 are >5mm in diameter. Some institutions prevention of a first variceal bleeding The last commonly seen systemic utilize a three category classification based event. These agents can also be used complication of cirrhosis is a set of on morphological assessment. In these for patients with no increased risk of coagulopathies. Due to the fact that institutions, small varices are minimally bleeding but benefits are inconclusive.13 the liver is responsible for producing elevated above the lumen, medium varices NSBB can significantly reduce the risk the proteins responsible for hemostasis, are torutous veins occupying less than of bleeding by reducing portal pressure damage to the liver disrupts this delicate one-third of the esophageal lumen, and by two mechanisms. These medications balance. Hemostatic substances, such as large varices occupy more than onecan decrease cardiac output by blocking clotting factors and platelets, are decreased third of the esophageal lumen. AASLD adrenergic β1 receptors and reduce in cirrhotic patients. The net result of this guidelines recommend treating medium portal blood flow through splanchnic hemostatic disruption is the development varices the same as large varices.10 vasoconstriction by blocking adrenergic of bleeding, which results in an elevated A combination of the Child-Pugh score β2 receptors. For this reason, NSBB must prothrombin time.3 and variceal categorization is used to be used over selective beta-blockers in the determine the treatment for varices, as case of primary prophylaxis. According Classification of Cirrhosis and Varices described below. to the AASLD guidelines, propranolol 20 The Child-Pugh scoring system is a mg orally twice daily or nadolol 40 mg numerical measurement of the severity Variceal Management: orally once daily can be given. Doses of of a patient's cirrhosis. It takes into There are three main components to these agents are titrated to decrease the account whether the patient has ascites, management of variceal hemorrhages: heart rate 25% from baseline. However, Summer 2013 • Arizona Journal of Pharmacy • 39

Continuing Education (continued from page 39) reducing heart rate has not been found to reduce HVPG so maximal tolerated doses are commonly used.13,14 Heart rate and blood pressure should be monitored in patients on this medication. Patients should be cautioned against the side effects of NSBB which include, but are not limited to syncope, fatigue, dizziness and impotence.15,16 Although direct comparison trials have not been completed with propranolol and nadolol, propranolol showed higher rates of side effects13. If patients are to discontinue their use of NSBB, the medication must be tapered over 2 weeks to avoid hypertension, acute tachycardia and/or ischemia.15,16 Patients receiving beta-blockers do not require an EGD but those who are not should obtain an EGD every 2 years.13 Patients with Medium/Large Varices AASLD guidelines state that patients with medium/large varices that have not bled (Child-Pugh score of B/C) should receive NSBB. The same recommendations can be considered in patients who are not at a high risk of bleeding. Propranolol 20mg orally twice daily or nadolol 40 mg orally once daily can also be given to patients who fall under this category. Monitoring parameters for safety and efficacy for these medications follow those described previously.13 Endoscopic variceal ligation (EVL) can also be used for patients with medium/large varices and has showed a small, significant lower incidence of bleeding in comparison to NSBB use.14 EVL involves the use of rubber bands attached to varices. After 48 - 72 hours, the varix will slough off and leave a mucosal ulceration that will heal. The procedure is repeated every 1 - 2 weeks until complete resolution of the varices.17 Repeat examinations are also recommended in 1 - 3 months, then every 6 - 12 months. AASLD guidelines do not recommend the use of nitrates in the prevention of first event variceal hemorrhage. Nitrates, such as isosorbide mononitrate, are effective in comparison to NSBB but were found to increase mortality rates in a long-term follow up study. In addition, shunt therapy or sclerotherapy is also not recommended for use in primary prevention.13 Treatment of Variceal Hemmorhages The treatment of cirrhosis includes resolving acute complications that

arise from the condition and preventing further ones from occurring. Variceal hemorrhage is a dangerous complication of cirrhosis that warrants immediate treatment requiring general stabilization of the patient and controlling the bleeding.3 According to the AASLD guidelines, the treatment of variceal hemorrhage include pharmacotherapy and endoscopic intervention. Drug therapy typically includes a vasoactive agent to assist in the reduction of bleeding and an antibiotic to prevent SBP. Endoscopic treatments such as sclerotherapy and variceal band litigation is also necessary to inhibit bleeding.13 Acute Management of Variceal Bleeding Variceal hemorrhage requires intensive care and hemodynamic stability of airway, breathing and circulation of the patient. Goals of treatment include systolic blood pressure of 90-100 mmHg, heart rate less than 100 beats per minute, and a stabilization of blood volume for a target hemoglobin level of 7-8 g/dL. In addition, a transfusion of fresh frozen plasma and platelets can be given for severe coagulopathy or thrombocytopenia Excessive fluids are typically avoided to prevent complications of ascites. Recombinant factor VIIa is also not recommended.3, 14 Vasoactive Drug Therapy Common vasoactive medications used for the treatment of variceal hemorrhages include octreotide and vasopressin.3 Octreotide is a splachnic vasoconstrictor that assists in the reduction of portal blood flow and pressure. This agent works by inhibiting vasodilatory agents in the body with effects localized to the splanchnic vasculature, causing fewer side effects than vasopressin. Although octreotide is available as subcutaneous and intravenous injections, it is recommended to be used intravenously for this treatment. The recommended dose for the use of octreotide is a 50 mcg bolus followed by 50 mcg/hr continuous infusion. The guidelines recommend continuing the use of octreotide for 5 days after an incident of variceal hemorrhaging to prevent the reoccurrence of bleeding, since this complication commonly occurs 3 - 5 days after an initial incident.13,14 Patients on octreotide should be monitored for safety for dyspnea, hypothyroidism, cardiovascular issues, GI disturbances and

40 â€˘ Arizona Journal of Pharmacy â€˘ Summer 2013

CNS changes. It should also be used in caution with patients currently on insulin therapy for hyper/hypoglycemia. Patients should also be educated on side effects of dyspepsia, flatulence, nausea, and headache.18 Vasopressin (also known as antidiuretic hormone) can also be used for the treatment of acute variceal hemorrhages. This agent is also a splachnic vasoconstrictor that causes a reduction of portal blood flow and pressure, however, unlike octreotide, vasopressin is a nonselective agent so its effects are not localized to the splanchnic vasculature bed. Because of its systemic effects, vasopressin can cause a reduction of cardiac output, heart rate and coronary blood flow which can cause further complications of myocardial infarction, arrthymias and other cardiovascular effects. The recommended dose for vasopressin is a 0.2 - 0.4 unit/minute (maximum of 0.8 unit/minute) by continuous infusion for a maximum of 24 hours. It must be administered along with intravenous nitroglycerin (40 â€“ 400 mcg/ minute adjusted to maintain SBP of over 90 mmHg) to reduce the risk of adverse events.3,13,14 Serum and urine sodium, serum and urine osmolality, fluid input and output, blood pressure and heart rate should be monitored for safety in the use of vasopressin.19 Common side effects of vasopressin include nausea, vomiting, vertigo and chest pains. The use of vasopressin is undesirable in comparison to octreotide due to its systemic side effects and risk for complications. Because of this, octreotide has been more commonly used for the treatment of acute variceal hemorrhage than vasopressin.13 Terlipressin, a common agent used in Europe, is a synthetic analogue of vasopressin. Although it is quite similar to vasopressin, it has a longer duration of action. More importantly, terlipressin has fewer side effects compared to vasopressin and has a lower risk for serious complications.3 Spontaneous bacterial peritonitis (SBP) is a serious complication that can arise due to an acute variceal hemorrhage. Active bleeding in patients can increase the risk of bacterial infections such as SBP. As described previously, enteric bacteria undergo bacterial translocation into abdominal lymph nodes which can lead to SBP. According to AASLD guidelines, all patients should receive

Continuing Education (continued from page 40) a short course of antibiotic therapy to reduce these risks. Antibiotic therapy can also prevent bleeding reoccurrences and decrease mortality in cirrhosis patients. Common pathogens of SBP include Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, and Enterococcus species. Over 90% of these cases are monomicrobrial and most are caused by E. coli and Klebsiella sp.3, 13, 20, 21 Norfloxacin 400mg BID can be used for oral administration of antibiotic prophylaxis to cover E. coli, K pneumonia, S. pneumonia over a course of 7 days maximum. Norfloxacin should be taken on an empty stomach either one hour before or two hours after meal. Adequate hydration is also recommended in norfloxacin use. Patients should be informed of common side effects including dizziness, lightheadedness, headache, nausea, vomiting and photosensitivity. Patients on norfloxacin should also be monitored for tendon inflammation or pain.21 For prolonged therapy, CBC, renal and hepatic function must be monitored. If oral administration is contraindicated, ceftriaxone 1g/day or ciprofloxacin IV can be used. Endoscopic Interventions Endoscopy should be performed as soon as possible to inhibit active variceal bleeding. Although endoscopy is used to diagnose the variceal bleeding, it can also be used to assist in the inhibition of active hemorrhaging. EVL, as described above, can be completed in the event of active variceal hemorrhage and the procedure is repeated in 7 - 10 days to ensure complete resolution of the varices. Repeat examinations are also recommended in one month, then every three months, after the procedure.13, 17 Endoscopic sclerotherapy involves the injection of a sclerosing agent to cause thrombosis of varices and subsequently inhibit blood flow. There are many sclerosing agents that can be used and none have been proven to be superior over another agent. Commonly, 1 - 2 mL of 5% sodium morrhuate per injection for a total of 12 - 20 mL per session has been used. Ethanolamine is an alternative sclerosing agent using the same dosing regimen. In regard to endoscopic interventions, sclerotherapy has shown inferiority over EVL and should be used in the treatment of variceal hemorrhages. In comparison to EVL, endoscopic sclerotherapy can result

in less control of the hemorrhage, higher risks of adverse events and higher risks for rebleeding occurrences.3,13 Alternative Treatments In the case of failure from previous treatments, balloon tamponade can be used. Although this method can assist in the short-term treatment of variceal hemorrhage, it can lead to further complications and a high risk of rebleeding.13 The Sengstaken-Blakemore tube, the Minnesota tube, and the LintonNachlas tube have been used to stop variceal bleeding. Surgery can also be used to control variceal bleeding in the failure of other treatments. Two types of procedures exist for surgical options: shunt and nonshunt procedures. A common surgical procedure for the treatment of variceal hemorrhage includes a transjugular intrahepatic portosystemic shunt (TIPS) which involves the widening of a portal vein branch and a hepatic vein stent with a cylindrical wire mesh. This allows the blood to bypass high pressure vessels which subsequently decreases pressure in the portal veins.23 Prevention of Rebleeding In addition to treatment of an active variceal hemorrhage, it is also important to prevent bleeding reoccurrences in the future. Rebleeding can occur in 60% of patients within 1 - 2 years after an initial complication and holds a 33% mortality rate. Secondary prophylaxis does not have to be initiated in patients who have undergone shunt surgery for treatment. Patients with a Child-Pugh score equal to or greater than 7 should begin secondary prophylaxis for rebleeding.3 According to AASLD guidelines, the best option for secondary prophylaxis includes a combination of NSBB and EVL. As in the prevention of first event bleeding, NSBB should be adjusted to a tolerated dose for each patient. Also similar to first prophylaxis, EVL should be repeated every 1 - 2 weeks. If EVL is contraindicated, the combination of NSBB and isosorbide mononitrate has shown slight benefits. Guidelines also state that TIPS can be considered in patients with a Child-Pugh Score of A or B who have experienced an acute variceal hemorrhage on multiple occasions. In the event of extreme situations and the failure of aforementioned treatments, liver transplant should be considered.13,14

Role of the Pharmacist and Conclusion: In a community setting, pharmacists may deal with long-term management of cirrhosis and prevention of exacerbations. While the acute complications, such as variceal hemorrhage, can be fatal, proper long-term management of the disease state is essential to prevent those acute complications from occurring. Patients with cirrhosis may be on many medications concomitantly, and the pharmacist should always screen for drug-drug interactions. It would not be uncommon to see an advanced stage cirrhosis patient on a beta-blocker for variceal management, a loop diuretic for ascites prevention, and warfarin for coagulopathy management. When combined with medications for other disease states, it is easy to see where medication therapy management can have a large impact and optimize outcomes. In an acute care setting, pharmacists can also have a large impact. The acute management of variceal hemorrhage is a complicated one involving many medications and procedures. The pharmacist can ensure that proper antibiotics are being selected, and assist in the management of adverse effects from the myriad medications that a patient will be on while in the hospital. Overall, cirrhosis is a dangerous disease state with a high mortality rate. There are a host of systemic complications that can arise as a result, and the acute and chronic management of these complications are essential in improving quality of life and preventing morbidity and mortality. The most commonly seen complication is an acute variceal hemorrhage, which has a complicated, but well-defined treatment protocol involving vasoactive agents, beta-blockers, antimicrobials and surgical procedures. A last line-treatment option when complications cannot be managed is a liver transplant.

CPE MONITOR INSTRUCTIONS: Beginning January 1, 2013 Statements of Credit for home-study activities will no longer be provided. All activities will be reported to the NABP CPE Monitor system as mandated by ACPE. Licensees may obtain additional information and set up their NABP e-Profile at www.MyCPEmonitor.net.

Summer 2013 â€˘ Arizona Journal of Pharmacy â€˘ 41

Continuing Education (continued from page 41) References: 1. FASTSTATS – Chronic Liver Disease or Cirrhosis [Internet]. Atlanta, GA: Centers for Disease Control and Prevention. http://www.cdc.gov/nchs/ fastats/liverdis.htm (accessed 2013 Jan 14). 2. Cirrhosis – National Digestive Diseases Information Clearinghouse [Internet]. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases. http://digestive.niddk.nih.gov/ddiseases/pubs/ cirrhosis/ (accessed 2013 January 17). 3. Sease JM. Portal Hypertension and Cirrhosis. In: Talbert RL, DiPiro JT, Matzke GR, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011 4. Drugs that may cause liver dysfunction or damage [Internet]. Akron, OH: Hepatitis C Resouces & Support. http://www.hepcnet.net/ drugsandliverdamage.html (accessed 2013 Jan 14) 5. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008;371(9615):838-51. 6. Cirrhosis: Symptoms – Mayoclinic.com [Internet]. Rochester, MN: Mayo Clinic. http://www.mayoclinic.com/health/cirrhosis/ DS00373/DSECTION=symptoms (accessed 14 March 2013).

7. Udell JA, Wang CS, Tinmouth J, et al. Does this patient with liver disease have cirrhosis?. JAMA. 2012;307(8):832-42. 8. Koulaouzidis A, Bhat S, Saeed AA. Spontaneous bacterial peritonitis. World J Gastroenterol. 2009;15(9):1042-9. 9. Soares-weiser K, Brezis M, Tur-kaspa R, et al. Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding. Cochrane Database Syst Rev. 2002;(2):CD002907. 10. Runyon BA. Management of adult patients with ascites due to cirrhosis: an update. Hepatology.2009;49(6):2087-107. 11. Heidelbaugh JJ, Sherbondy M. Cirrhosis and chronic liver failure: part II. Complications and treatment. Am Fam Physician. 2006;74(5):767-76. 12. Pugh RN, Murray-lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60(8):646-9. 13. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46:922-938. 14. Bari K, Garcia-Tsao G.. Treatment of portal hypertension. World J Gastroenterol. 2012;18(11):116-1175. 15. Propranolol. In: Lexi-Drugs Online [Internet Database]. Hudson, OH: Lexi-Comp, Inc. Updated 2013 Mar 26.

16. Nadolol. In: Lexi-Drugs Online [Internet Database]. Hudson, OH: Lexi-Comp, Inc. Updated 2013 Mar 13. 17. Goff JS. Endoscopic variceal ligation. In: UpToDate [Internet Database]. DS, Basow, eds. Waltham, MA: UpToDate. Updated 2012 Jun 4. 18. Octreotide. In: Lexi-Drugs Online [Internet Database]. Hudson, OH: Lexi-Comp, Inc. Updated 2013 Mar 25. 19. Vasopressin. In: Lexi-Drugs Online [Internet Database]. Hudson, OH: Lexi-Comp, Inc. Updated 2013 Mar 4. 20. Runyon BA. Treatment and prophylaxis of spontaneous bacterial peritonitis. In: UpToDate [Internet Database]. DS, Basow, eds. Waltham, MA: UpToDate. Updated 2013 Jan 23. 21. Parsi MA, Atreja A, Zein N. Spontaneous bacterial peritonitis: Recent data on incidence and treatment. Cleve Clin J Med. 2004;71(7):569-576. 22. Norfloxacin. In: Lexi-Drugs Online [Internet Database]. Hudson, OH: Lexi-Comp, Inc. Updated 2013 Mar 13. 23. Sanyal AJ. Indications for the use of transjugular intrahepatic portosystemic shunts. In: UpToDate [Internet Database]. DS, Basow, eds. Waltham, MA: UpToDate. Updated 2012 Nov 13.

Table 3 – Medication Summary for Cirrhosis Management Medication

Dose

Monitoring Parameters

Side Effects

Prevention of Variceal Hemorrhage

Propranolol

20 mg twice daily orally

heart rate, blood pressure

syncope, fatigue, dizziness

Nadolol

40 mg twice daily orally

heart rate, blood pressure

drowsiness, insomnia

dyspnea, hypothyroidism, cardiovascular issues, GI disturbances and CNS changes

nausea, headache, flatulence, dyspepsia

Treatment of Variceal Hemorrhage Octreotide

50 mcg bolus followed by 50 mcg/hr continuous infusion for 2-5 days

0.2 - 0.4 unit/minute heart rate, blood pressure, (maximum of 0.8 serum and urine sodium, unit/minute) continuous Vasopressin serum and urine osmolality, infusion for a maximum fluid input and output of 24 hours Prophylaxis of Spontaneous Bacterial Peritonitis Norfloxacin

400 mg twice daily orally

42 • Arizona Journal of Pharmacy • Summer 2013

CBC, renal and hepatic function for prolonged therapy

nausea, vomitting, vertigo, chest pains

dizziness, lightheadedness, headache, nausea, vomiting and photosensitivity

Continuing Education

Obesity and Lifestyle Modification

Shrouq Qaisi, Pharm.D., PGY2 Resident, The University of Arizona Medication Management Center, Tucson, Arizona Goal: This self-study continuing education activity has been developed to educate pharmacists on managing obesity and counseling patients on life-style modification. Objectives: At the conclusion of this lesson, successful participants should be able to: 1. Identify health consequences of being overweight/obese 2. Categorize patients based on body mass index calculations 3. Create a caloric deficit Prevalence: The prevalence of obesity overall has been dramatically increasing around the world; the World Health Organization (WHO) has classified it as an epidemic. Furthermore, the WHO estimates that by 2015, 2.3 billion and 700 million adults will be overweight and obese.1 According to the 2010 data collected by the Center for Disease Control (CDC), roughly 68% of Americans are either overweight or obese in the United States. 35.7% of adults and 17% of children and adolescents are obese. The prevalence of obesity has leveled off between men and women; whereas at the beginning of 2000, obesity was more common in women than it was in men.2 The incidence of obesity in Arizona is slightly below the national average at 24.7%.3 Problems Associated With Obesity: The American Heart Association (AHA) states that obesity causes other problems as well, like psychological (depression), social (discrimination), economic (increased spending), and health distress.4 It is the second cause of preventable death in the United States and it is an associated risk factor for several disease states including but not limited to the following: coronary heart disease (CHD), stroke, hypertension, hyperlipidemia, diabetes, osteoarthritis, certain cancers, and sleep apnea.5 If obesity rates continue increasing at the same rate, it is expected that diabetes, CHD, stroke, hypertension, and arthritis will increase by 10 times between 2010-2020 and then increase again twofold by 2030.6 There are also financial implications associated

with obesity. Some experts state that there Hence, obesity is usually linked to poor is a link between obesity prevalence and life-style choices. In general, people have medical cost. Medical costs associated been moving or exercising less and eating with obesity have been estimated at $147 more. Food portion sizes have increased billion in 2008. Healthcare cost for an dramatically. In the 1990s the average Adult Obesity Rates in 2011 obese patient is 42% higher than it is for muffin was 1.5 ounces and about 210 7 a normal weight patient. The Trust for calories. In a period of 20 years the size increased by 138% to 4 ounces and 500 America’s Health states that the medicals calories. cost of obesity range anywhere between Of course, there are other contributing $147-210 per year. They estimate that by factors to obesity which include genetics, 2030, greater than 60% of the population in 13 states will be obese and that in all 50 family history, smoking, health conditions (hypothyroidism, Cushing’s disease, states the obese population will be greater polycystic ovarian syndrome, and than 44%; this will lead to a greater than 20% increase in obesity-related healthcare mental health conditions), medications (corticosteroids, certain antidepressants, costs in at least nine states.6 seizure medications) age, and emotional factors.8,9,10,11 Causes of Obesity: Weight gain is multifactorial; however, essentially it is an imbalance of energy. Defining overweight and obesity: This means that the intake of energy is Both overweight and obesity are greater than the energy expended. Energy measurements of ranges of weight that are intake is described using the amount greater than what is considered healthy of calories received through eating or for a specified height. The body mass drinking; whereas the energy expended is index (BMI) is one of the most common the amount of calories the body burns, for assessment measures used. Others include example during breathing, exercise, and waist circumference, waist to height ratio, digestion. and fat percentages. The body mass index is calculated using the following equation:

Energy intake = Energy expenditure-- sustains current weight Energy intake > Energy expenditure  weight gain Energy intake < Energy expenditure  weight-loss

BMI = Weight (Kg) Height squared (m^2) OR BMI = Weight (lbs.) *703 Height squared (inches ^2) People can be classified as underweight, normal, overweight, obese, and extremely obese based on their calculated BMI.12,13

Summer 2013 • Arizona Journal of Pharmacy • 43

Continuing Education (continued from page 43) Classification of BMI Classification Underweight Normal Overweight Obese Class I Obese Class II Obese Class III

BMI <18.5 18.5-24.9 25-29.9 30-34.9 35-39.9 >40

Why Should Pharmacists Get Involved? Since pharmacists are the most accessible and trusted healthcare professionals, they can be a tremendous aid in a path that leads to the solution. They come in contact with patients on a daily basis that could benefit from counseling on life-style modifications, whether they are picking up a prescription or asking a question about an over the counter product. According to the CDC roughly 75% of healthcare costs are attributed to chronic disease states many of which are linked to obesity. Health experts state that weight loss of as little as 5-10% of total body weight decreases the obesity related risks and is correlated with improved health benefits. A small amount of weight loss has been shown to decrease blood pressure in those with hypertension, lower blood glucose in diabetics and lower total cholesterol, LDL and triglycerides and increase HDL in patients with dyslipidemia. Therefore, it is extremely important that as healthcare professionals we educate ourselves on obesity and strategies for weight-loss.13 Some pharmacists have recognized the need for weight-loss counseling and have implemented it in both clinical and community settings. The “Take Charge Program” was initially started by an independent pharmacist who now franchises the program to other independent pharmacies. It is based on a pharmacist counseling patients on healthy eating habits and physical activity; the pharmacist acts as a life coach.14 Two other programs for weight loss include the “Healthy Habits” program, started at Auburn University Pharmaceutical Care Center and the “Healthy Sharks Program,” started at Nova Southeastern University.15,16 In these programs, clinical pharmacists and fourth year pharmacy students counsel patients on healthy eating habits and implementing exercise. In busier community settings where time is

a barrier, referring patients to an online weight-loss program could potentially be beneficial.4 There are a vast array of free and fee based online weight loss programs. Some of the popular fee based programs include but are not limited to Weight Watchers, Jenny Craig, and Nutrisystem;17,18,19 free programs include My Fitness Pal, SparkPeople, and LiveStrong.20,21,22 Participants can read about appropriate healthy eating habits and can track their calorie intake and calories burned. Participants can also calculate their BMI, basal metabolic rate (BMR), and the amount of weight needed to be lost each week in order to reach their target weight. Managing Weight-loss: Weight is a sensitive topic. It is imperative to be to supportive and empathetic. Terms like “weight” and “excess weight” are preferred. On the other hand, “obesity”, “fatness”, and “excess fat” are socially insensitive. The US Preventative Task Force recommends using the same motivational counseling techniques used in smoking cessation, known as the 5A’s (ask, advise, assess, assist, and arrange). Patients believe that it is the healthcare provider’s duty to ask and counsel on weight-loss. As a matter of fact, patients advised on weightloss were 3 times more likely to attempt making changes. It has been shown that even counseling as brief as 2-3 minutes in additional to written information can make a difference.4,23,24 When assessing a patient, the BMI should be calculated. If the patient needs

44 • Arizona Journal of Pharmacy • Summer 2013

to lose weight, it is important to set realistic expectations. Healthy weight loss should be done at a rate of 5-10% of total body weight-loss over a period of 6 months; which is approximately 1-2 pounds per week. In order to track calories for successful weight-loss, it is important to calculate the basal metabolic rate (BMR) using the Harris Benedict Equation, which is the amount of calories needed to sustain life.13,25 Women: BMR = {655 + ( 4.35 x weight in pounds ) + ( 4.7 x height in inches ) - ( 4.7 x age in years )} * activity factor Men: BMR ={ 66 + ( 6.23 x weight in pounds ) + ( 12.7 x height in inches ) - ( 6.8 x age in year )} * activity factor Activity factors • Sedentary: 1.2 • Lightly active: 1.375 • Moderately active: 1.55 • Very active: 1.725 • Extra active: 1.9 Once the basal metabolic rate is calculated, it is important to relay to the patient that if his/her caloric intake is equal to the BMR, there will be no weight gain or weight loss. In order, to lose weight, a caloric deficit needs to be created. This can be done by a combination of decreasing the caloric intake and increasing physical activity. A 3500 caloric deficit per week will lead to a one-pound weight loss. Thus, if a patient needs to lose one pound at the end of the week, a daily caloric deficit of 500 calories

Adult Obesity Rates in 2011

Continuing Education (continued from page 44) (500 calories *7 days/week =3500 calories which leads to a one pound loss) should be created. If the aim is to lose one-half of a pound each week, a daily caloric deficit of 250 calories is needed (250 calories * 7days/week = 1750 calories). Once the daily caloric intake decreases below 1200 calories, metabolism decreases and weight-loss will not be sustainable. It is imperative to remind patients to keep their daily caloric intake above 1200. Physical activity should be an integral part of a weight loss plan. It burns calories, prevents decrease in muscle mass, boosts energy, increases metabolism, and improves self-image. To reduce health risks and maintain weight, 30 minutes of moderate physical activity is recommended; whereas for weightloss, 60 minutes of moderate physical activity on most days of the week is recommended. However, any physical activity is better than no exercise. The National Institute of Health (NIH) states that people can actually gain health benefits from as little as 60 minutes of physical activity per week.26,27 Calories Burned Through Physical Activity Weight-loss pharmacotherapy can be used; however, it is important to assess side-effect profiles and comorbidities for individual patients. Pharmacotherapy for weight-loss can be combined with calorie reduction and physical activity in those who have a BMI ≥ 30 or in those with BMI ≥ 27 with obesity related risk factors. Risk factors include the following: cigarette smoking, hypertension or the use of anti-hypertensives, LDL≥ 160 mg/dl, HDL ≤ 35, fasting glucose between 110-125 mg/dl, family history of CHD, and age ( ≥45 for males and ≥55 for females). If weight is regained, then so are the risks related to obesity. Some medications can be used longterm. The following drugs are approved for long-term use: orlistat (pancreatic lipase inhibitor), lorcaserin (serotonin-2C receptor agonist), Phentermine-topiramate (sympathomimetic amine-antiepileptic). Weight-loss attributed to medications is 2-10 kg. Patients who are considered severely obese with a BMI ≥ 40 or ≥ 35 with comorbidities have the option to pursue weight-loss surgery. Surgery should only be pursued after failing to achieve

appropriate weight-loss through calorie reduction, physical activity, and other treatments. Weight-loss surgeries seem to be effective and have been shown to sustain weight loss for ≥ 5 years. Healthcare providers must remember that patients who undergo weight-loss surgery will require a lifelong medical monitoring and that medications might require dose adjustments.13,28 It is essential for health-care providers to counsel patients on weight-loss and life-style modifications. As with many other interventions (smoking cessation, adherence), a few minutes can make a difference. Some of the complaints constantly revisited as to why weightloss counseling does not take place are lack of time/ reimbursements and lack of knowledge. The government has realized the importance of counseling. Medicare has been reimbursing primary care physicians and practitioners (nurse and physician assistant) for weightloss counseling. This could also be a reimbursement opportunity for pharmacists to pursue. Both medicine and pharmacy schools have been trying to incorporate life-style modifications into their curriculums. One quick, targeted way to counsel patients on weight loss is to go over the important points below and refer them to a weight-loss website.29 Important Points: • Keep a food and exercise log • Technological resources can aid in the weight-loss process • Initial weight loss goal should be 5-10% of body weight-loss over 6 months • Drink at least eight cups of water per day • Cutout sweetened/sugary beverages • Increase fiber intake slowly to 20-30 grams/day • Read the nutrition label • Use smaller cups and plates • Eat smaller meals frequently and slowly to prevent starvation mode • Protein satisfies hunger than other caloric sources • Reducing dietary fat without reducing calories will not produce weight loss • Physical activity is an integral part of any weight-loss program • Weight-loss medications should only be used in patients with a BMI ≥ 27 who have failed to lose weight after six months with two or more

cardiovascular risk factors and/ or in patients with a BMI ≥ 30. References 1. Who.int (2013) WHO | Obesity. [online] Available at: http://www.who.int/topics/obesity/en/ [Accessed: 7 Mar 2013]. 2. Cdc.gov Unknown. (2013) Prevalence of Obesity in the United States, 2009–2010. [online] Available at: http://www.cdc.gov/nchs/data/databriefs/db82.pdf [Accessed: 7 Mar 2013]. 3. Cdc.gov (2011) Obesity and Overweight for Professionals: Data and Statistics: Adult Obesity DNPAO - CDC. [online] Available at: http://www. cdc.gov/obesity/data/adult.html [Accessed: 7 Mar 2013]. 4. Circ.ahajournals.org (2011) New and Emerging Weight Management Strategies for Busy Ambulatory Settings. [online] Available at: http://circ. ahajournals.org/content/124/10/1182 [Accessed: 7 Mar 2013]. 5. Cdc.gov (2001) Obesity and Overweight for Professionals: Adult: Causes - DNPAO - CDC. [online] Available at: http://www.cdc.gov/obesity/ adult/causes/index.html [Accessed: 7 Mar 2013]. 6. RWJF (2012) F as in Fat: How Obesity Threatens America’s Future 2012. [online] Available at: http:// www.rwjf.org/en/research-publications/find-rwjfresearch/2012/09/f-as-in-fat--how-obesity-threatensamerica-s-future-2012.html [Accessed: 7 Mar 2013]. 7. Ncbi.nlm.nih.gov (2009) Annual medical spending attributable to obesity: payer-and service-specific estimates.. [online] Available at: http://www.ncbi. nlm.nih.gov/pubmed/19635784 [Accessed: 7 Mar 2013]. 8. Nhlbi.nih.gov (2012) What Causes Overweight and Obesity? - NHLBI, NIH. [online] Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/ obe/causes.html [Accessed: 7 Mar 2013]. 9. Hp2010.nhlbihin.net (n.d.) NHLBI-Portion Distortion Quiz. [online] Available at: http://hp2010. nhlbihin.net/portion/ [Accessed: 7 Mar 2013]. 10. Nhs.uk (n.d.) Obesity - Causes - NHS Choices. [online] Available at: http://www.nhs.uk/Conditions/ Obesity/Pages/Causes.aspx [Accessed: 7 Mar 2013]. 11. jessicawithers (2013) hope4health. [online] Available at: http://hope4health.wordpress.com [Accessed: 7 Mar 2013]. 12. Cdc.gov (2002) Healthy Weight: Assessing Your Weight: BMI: About Adult BMI | DNPAO | CDC. [online] Available at: http://www.cdc.gov/ healthyweight/assessing/bmi/adult_bmi/index.html [Accessed: 7 Mar 2013]. 13. Nhlbi.nih.gov (1900) Obesity GuidelinesPractical Guide, NHLBI - NIH. [online] Available at: http://www.nhlbi.nih.gov/guidelines/obesity/ practgde.htm [Accessed: 7 Mar 2013]. 14. Takecharge.info (2006) Take Charge Professional Weight Loss & Healthy Lifestyle Strategies - Home. [online] Available at: http://www. takecharge.info/cms/ [Accessed: 7 Mar 2013]. 15. Pharmacy.auburn.edu (n.d.) HSOP - AU Pharmaceutical Care Center. [online] Available at: http://pharmacy.auburn.edu/aupcc/health_habits.htm [Accessed: 7 Mar 2013]. 16. NSU, I. (2008) About Healthy Sharks | NSU Health and Wellness. [online] Available at: http:// www.nova.edu/wellness/about_healthysharks.html [Accessed: 7 Mar 2013]. 17. Weightwatchers.com (2001) Weight Watchers Online - Lose Weight Completely Online with Our Plan. [online] Available at: http://www. weightwatchers.com/plan/www/online_01.aspx

Summer 2013 • Arizona Journal of Pharmacy • 45

Continuing Education (continued from page 45) [Accessed: 7 Mar 2013]. 18. Jenny Craig | Official Site (n.d.) Jenny Craig. [online] Available at: http://www.jennycraig.com/ [Accessed: 7 Mar 2013]. 19. Nutrisystem.com (2012) Nutrisystem® Official Site – Weight Loss and Diet Programs. [online] Available at: http://www.nutrisystem.com/jsps_hmr/ home/index.jsp?_requestid=9721 [Accessed: 7 Mar 2013]. 20. Myfitnesspal.com (2012) Free Calorie Counter, Diet & Exercise Journal | MyFitnessPal.com. [online] Available at: http://www.myfitnesspal.com/ [Accessed: 7 Mar 2013]. 21. SparkPeople (2012) Free Diet Plans at SparkPeople. [online] Available at: http://www. sparkpeople.com/ [Accessed: 7 Mar 2013].

22. LIVESTRONG.COM (2013) WEIGHT LOSS: Healthy Diet and Exercise Regimens | LIVESTRONG.COM. [online] Available at: http:// www.livestrong.com/weight-loss/ [Accessed: 7 Mar 2013]. 23. Healthysd (n.d.) Talking to Patients About Weight Issues. [online] Available at: http://www. healthysd.gov/Documents/Obesity/talking.pdf [Accessed: 7 Mar 2013]. 24. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES (2005) Talking With Patients About Weight Loss: Tips for Primary Care Professionals. [online] Available at: http://open. umich.edu/sites/default/files/EOral-obesity-NIHWIN.pdf [Accessed: 7 Mar 2013]. 25. Bmi-calculator.net (n.d.) Harris Benedict Equation. [online] Available at: http://www. bmi-calculator.net/bmr-calculator/harris-benedictequation/ [Accessed: 7 Mar 2013].

26. Nhlbi.nih.gov (2012) Recommendations for Physical Activity - NHLBI, NIH. [online] Available at: http://www.nhlbi.nih.gov/ health/health-topics/topics/phys/recommend. html [Accessed: 7 Mar 2013].

27. Caloriecontrol.org (2012) Let’s Get Physical: Calorie chart showing calories burned through exercise and activity | The Calorie Control Council. [online] Available at: http://www.caloriecontrol.org/ articles-and-video/lets-get-physical [Accessed: 7 Mar 2013]. 28. Uptodate.com (2013) Drug therapy of obesity. [online] Available at: http://www.uptodate.com/ contents/drug-therapy-of-obesity?topicKey=ENDO %2F5376&elapsedTimeMs=0&source=search_res ult&searchTerm=weight+loss+medications&selec tedTitle=1~150&view=print&displayedView=full [Accessed: 3 Apr 2013]. 29. Trent (1999) Physician Reimbursement for Obesity Counseling. [online] Available at: http:// solutions4mds.com/intensive-behavioral-therapy-forobesity/ [Accessed: 3 Apr 2013].

Calories Burned Through Physical Activity

3500 Calories = 1 pound lost

To achieve a healthy 10% loss in 6 months: 

3500 Calories = 1 pound lost

To achieve a healthy 10% loss in 6 months:  

BMI 27-35  Deficit of 300-500 Calories/day BMI >35  Deficit of 500-1,000 Calories/day

46 • Arizona Journal of Pharmacy • Summer 2013



BMI 27-35 of 300-500 Calories/day  Deficit Calories Burned Through Physical BMI >35  Deficit of 500-1,000 Calories/day

Activity

Continuing Education Quiz Move Over Warfarin: A New Era of Treatment Options in Atrial Fibrillation Answer the questions one through four in regard to DP, a 68 year old male, 5’6”, 100 kg, who presents with atrial fibrillation. His past medical history is significant for high blood pressure and peripheral vascular disease. He does not drink or smoke. His medications include lisinopril and a multiple vitamin. Scr = 1.0 mg/dL 1. What is DP’s estimated stroke risk according to his CHADS2 and CHA2DS2VASc scores, respectfully? a. intermediate and intermediate b. low and intermediate c. intermediate and high d. high and high e. intermediate and low 2. What is DP’s bleeding risk according to his HASBLED score? a. low risk b. moderate risk c. high risk 3. DP is started on dabigatran for atrial fibrillation. What dose do you recommend? a. 150 mg twice a day b. 75 mg twice a day c. 20 mg once a day d. 150 mg once a day e. 5 mg twice a day

This activity was developed by the Arizona Pharmacy Association for pharmacists as a knowledgebased learning activity. The Arizona Pharmacy Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

4. DP is having a low bleeding risk procedure done in which he needs to stop his dabigatran. What do you recommend? a. stop dabigatran 1-2 days prior to his procedure b. stop dabigatran 3-5 days prior to his procedure c. stop dabigatran 5 days prior to his procedure and “bridge” with an injectable anticoagulant d. stop dabigatran 7 days prior to his procedure and “bridge” with an injectable anticoagulant 5. Which of the following is a true statement in regards to the results of the RE-LY trial? a. dabigatran 110 mg twice daily was superior to warfarin in terms of the primary endpoint of stroke or systemic embolism prevention b. dabigatran 150 mg twice daily produced more overall bleeding when compared to warfarin c. dabigatran 150 mg twice daily produced a higher rate of myocardial infarction when compared to warfarin d. dabigatran 150 mg twice daily produced less GI bleeding when compared to warfarin e. dabigatran 150 mg twice daily produced more intracranial bleeding when compared to warfarin. 6. Which of the following agents has a high incidence of GI side effects, including bleeding, dyspepsia, and gastritis that are thought to be due to its pellet coating? a. dabigatran b. rivaroxaban c. apixaban d. warfarin

7. Which of the following agents is (are) substrates for CYP3A4? a. dabigatran b. rivaroxaban c. apixaban d. A and B e. B and C 8. SP is currently on warfarin and the decision has been made to switch her to apixaban. When do you recommend she take her first dose of apixaban once stopping the warfarin? a. start apixaban 3 days after stopping warfarin b. start apixaban 5 days after stopping warfarin c. stop warfarin, monitor INR and start apixaban once the INR falls below 3.0 d. stop warfarin, monitor INR and start apixaban once the INR falls below 2.0 e. stop warfarin, monitor INR and start apixaban once the INR falls below 1.5 9. Which of the following agents has low protein binding and is therefore removed by hemodialysis? a. dabigatran b. rivaroxaban c. apixaban d. A and B e. B and C 10. Which of the following is a benefit to using apixaban? a. it has an antidote b. therapeutic drug monitoring can be done to assess safety and efficacy c. it has fixed twice daily dosing d. it can be used in severe renal dysfunction e. it is not a substrate for the cytochrome P450 enzyme system

Move Over Warfarin: A New Era of Treatment Options in Atrial Fibrillation

ACPE UAN#0100-0000-13-051-H01-P This activity is accredited for 1.0 hours of CPE credit (CEUs 0.10) This activity is a benefit to AzPA members. Non-members of AzPA must enclose a $25.00 check payable to the Arizona Pharmacy Association. In order to qualify for ACPE credit, participants must achieve a grade of 70% or above on the quiz and submit a completed activity evaluation. ACTIVITY EVALUATION – Please indicate if the activity met the stated learning objectives: 1. Discuss the different stroke and bleeding risk assessment tools used in atrial fibrillation. 2. Compare and contrast the three recently FDA approved oral anticoagulants that can be used in atrial fibrillation. 3. Describe some of the issues related to the new oral anticoagulants.

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Will the information presented cause you to make any changes to your style or method? Yes No If you answered “yes” please list one or two things you will do differently: _________________________________________________________________________________________________________________________________ _________________________________________________________________________________________________________________________________ Overall evaluation of the article content: (please circle one)

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Activity accredited date: 08-01-2013 Expiration date: 08-01-2016. Name __________________________________________________________ Send this page to: AzPA, 1845 E. Southern Ave., Tempe, AZ 85282 Address ________________________________________________________

Email ________________________________________________________

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Continuing Education Quiz Variceal Bleeding from Cirrhosis: A Clinical Review of Causes and Pharmacotherapy Options 1. Which of the following is a systemic complication commonly seen in cirrhosis? a. Immunocompromise due to the liver’s inability to synthesize proteins for immune function b. Congestive heart failure due to an increased intravascular fluid load c. Hyperglycemia due to the liver’s inability to properly store glycogen d. Portal hypertension due to increased intrahepatic resistance, stemming from hepatic fibrosis 2. Which of the following is FALSE regarding systemic complications arising from cirrhosis? a. Hepatorenal syndrome arises, in part, from a decreased glomerular filtration rate. b. Hepatic encephalopathy is due to the accumulation of ammonia in the CNS. c. Cirrhotic patients are hypercoagulable due to thrombocytosis. d. Ascites is an accumulation of fluid in the peritoneum and may result in peritonitis. 3. Which of the following is true regarding the use of NSBB in the prevention of variceal hemorrhage? a. NSBB are as equally efficacious as cardioselective beta-blockers. b. A reduction in heart rate is essential in the prevention of variceal hemorrhage . c. NSBB function, in part, by inducing splanchnic vasoconstriction via β2 receptors. d. The use of NSBB has demonstrable benefits in all cirrhotic patients, regardless of bleeding risk.

4. NSBB, octreotide, and vasopressin all function, in part, by increasing portal blood flow, thereby maintaining hepatic perfusion and function. a. True b. False 5. Which of the following is FALSE regarding octreotide? a. Octreotide inhibits vasdoilatory agents in the body, thereby inducing vasoconstriction. b. Octreotide should be administered initially as a bolus, then as a continuous infusion. c. Octreotide is preferred over vasopressin due to fewer systemic side effects. d. Octreotide use should be limited to 3 days, due to concerns of cardiovascular complications. 6. Which of the following is FALSE in regard to the use of vasopressin? a. Vasopressin causes a reduction of portal blood flow. b. Vasopressin effects localize in the splanchnic vasculature bed. c. Octreotide is preferred over vasopressin. d. Vasopressin is used in the treatment of variceal hemorrhages. 7. Which can be used for the prevention of variceal hemorrhage in a patient with small varices? a. Vasopressin b. Endoscopic variceal ligation c. Nadolol d. Isosorbide mononitrate

8. The typical dose for propranolol for prevention of variceal hemorrhage is: a. 40 mg twice daily orally b. 20 mg twice daily orally c. 20 mg once daily orally d. 40 mg once daily orally 9. Which of the following should not be used in the treatment of variceal hemorrhage? a. Nonselective beta blockers b. Vasopressin c. Endoscopic band ligation d. Transjugular intrahepatic portosystemic shunt 10. After an EGD, a patient was found to have large varices. Which of the following is true in regard to prophylaxis of variceal hemorrhage in this patient? a. The patient should begin propranolol and follow up with an EGD every 2 years. b. Isosorbide nitrate are not recommended per AASLD guidelines for prophylaxis use. c. After an initial EVL procedure, the patient must follow up in 3 months to confirm the resolution of the varices. d. Patient should start norfloxacin 400 mg twice daily orally for prophylaxis. This activity was developed by the Arizona Pharmacy Association for pharmacists as a knowledgebased learning activity. The Arizona Pharmacy Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

Variceal Bleeding from Cirrhosis: A Clinical Review of Causes and Pharmacotherapy Options

ACPE UAN#0100-0000-13-049-H01-P This activity is accredited for 1.0 hours of CPE credit (CEUs 0.10) This activity is a benefit to AzPA members. Non-members of AzPA must enclose a $25.00 check payable to the Arizona Pharmacy Association. In order to qualify for ACPE credit, participants must achieve a grade of 70% or above on the quiz and submit a completed activity evaluation. ACTIVITY EVALUATION – Please indicate if the activity met the stated learning objectives: 1. Explain which systemic complications are commonly seen in cirrhotic patients 2. Compare the mechanism of action of the medications used to prevent and treat hemorrhagic varices 3. Select an appropriate dose of medication for the prevention and treatment of hemorrhagic varices 4. Formulate an appropriate therapeutic regimen for a patient given the current state of the varices

AGREE AGREE AGREE AGREE

DISAGREE DISAGREE. DISAGREE DISAGREE

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Email ________________________________________________________

City, State, Zip ___________________________________________________ Birthdate (MM/DD only) ______________ NABP e-Profile ID# ________________

48 • Arizona Journal of Pharmacy • Summer 2013

Continuing Education Quiz Obesity and Lifestyle Modification 1. Obesity is classified as having BMI of: A. >25 B. > 18 C. > 27 D. > 30 2. Calculating the BMR depends on which of the following: A. Gender B. Age C. Activity factor D. All the above

4. Why should pharmacists be involved in life-style modifications counseling? A. Obesity is a risk factor for several chronic diseases B. Pharmacists are the most accessible healthcare providers C. Patients are not be properly educated on healthy dietary decisions

3. A pound of fat is equivalent to how many calories? A. 2500 B. 6500 C. 3500 D. 4000

Obesity and Lifestyle Modification

ACPE UAN#0100-0000-13-050-H01-P This activity is accredited for 0.50 hours of CPE credit (CEUs 0.05) This activity is a benefit to AzPA members. Non-members of AzPA must enclose a $25.00 check payable to the Arizona Pharmacy Association. In order to qualify for ACPE credit, participants must achieve a grade of 70% or above on the quiz and submit a completed activity evaluation. ACTIVITY EVALUATION – Please indicate if the activity met the stated learning objectives: 1. Identify health consequences of being overweight/obese 2. Categorize patients based on body mass index calculations 3. Create a caloric deficit

AGREE AGREE AGREE

DISAGREE DISAGREE. DISAGREE

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Email ________________________________________________________

City, State, Zip ___________________________________________________ Birthdate (MM/DD only) ______________ NABP e-Profile ID# ________________ Summer 2013 • Arizona Journal of Pharmacy • 49

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