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NEW DRUG REVIEW FLIBANSERIN>TO TRE AT SE XUAL DESIRE DISORDER pg. 37 ® Drug Topics® DrugTopics.com February February 2016 2016 || Vol. Vol. 160 160 No. No. 22 Feb r u a r y 2016 SPECIAL ANNIVERSARY ISSUE 1856-2016 C P E: T H E PH AR M AC IS T ’S RO L E IN M AN AG IN G O PIO ID US E D IS O R D ER , PAR T 1 r O T C : O RA L CA R E From Apothecary to PharmD VOICES 2 CPE CREDITS VO L . 1 60 N O. 2 Recognition & referral to enhance recovery: The pharmacist’s role in managing opioid use disorder pg. 39 Part 1: Working together for the greater good: MD versus RPh 6 Can pharmacists be sued for doing their jobs? 38 A pharmacy pioneer of the 20th century bounds into the 21st 51 Recommend Nexium® 24HR for stronger, longer acid control vs omeprazole 20 mg1* Now you can print up to 30 coupons per day right from your office. Help your patients with frequent heartburn save on the most powerful OTC acid blocker available.1,2 To print coupons and order samples, sign in at StartNexium24HR.com *Acid control (pH >4) does not imply symptom relief. The correlation of pH data to clinical outcome has not been directly established. References: 1. Lind T, Rydberg L, Kylebäck A, et al. Esomeprazole provides improved acid control vs. omeprazole in patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2000;14(7):861-867. 2. Data on file. Pfizer Inc, New York, NY. ©2016 Pfizer Inc. NXM011608 2/16 StartNexium24HR.com EDITORIAL ADVISORY BOARD Philip P. Burgess, RPh, MBA Mary E. Inguanti, RPh, MPH, FASCP Chairman Community Pharmacy Foundation Illinois Board of Pharmacy Chicago, Ill. Marvin R. Moore, PharmD Strategic Customer Vice President BD South Windsor, Conn. Pharmacy manager and co-owner The Medicine Shoppe/ Pharmacy Solutions Inc. Two Rivers, Wisc. Perry Cohen, PharmD, FAMCP Debbie Mack, BS Pharm, RPh David D. Pope, PharmD, CDE The Pharmacy Group LLC Glastonbury, Conn. Director Pharmacy Regulatory Affairs Wal-Mart Health and Wellness Bentonville, Ark. Chief of Innovation, Co-Founder Creative Pharmacist Augusta, Ga. David J. Fong, PharmD Frederick S. Mayer, RPh, MPH Brian Romig, RPh, MBA Former community chain store senior pharmacy executive Danville, Calif. President Pharmacists Planning Service Inc. San Rafael, Calif. Vice President Corporate Pharmacy Director, Supply Chain Adventist Health System Altamonte Springs, Fla. Anna Garrett, PharmD, BCPS Gene Memoli Jr., RPh, FASCP Jack Rosenberg, PharmD, PhD President Dr. Anna Garrett Asheville, N.C. Director Customer Development, Omnicare Cheshire, Conn. Professor Emeritus Pharmacy Practice and Pharmacology Long Island University Brooklyn, N.Y. Salvatore J. Giorgianni, Jr., PharmD, BSc, CMHE Ned Milenkovich, PharmD, JD Stephen W. Schondelmeyer, PharmD, PhD Partner Health, Drug, and Pharmacy Practice Much Shelist PC Chicago, Ill. Consultant Pharmacist Griffon Consulting Group, Inc. Chair, Men’s Health Caucus, American Public Health Association Advisory Board, Pharmacist Partners, LLC and The Men’s Health Network Editorial Mission: Drug Topics is the top-ranked pharmacy resource for community and healthsystem professionals. Since 1857, readers have turned to Drug Topics for coverage of issues and trends important to the practice of pharmacy, and for a forum in which they can share viewpoints and practical ideas for better pharmacy management and patient care. ACCOUNT MANAGER, RECRUITMENT Joanna Shippoli UBM LIFE SCIENCES 440-891-2615 / [email protected] SALES DIRECTOR,DIGITAL MEDIA Don Berman SPECIAL PROJECTS DIRECTOR Meg Benson VP, MARKETING Amy Erdman EVP & SENIOR MANAGING DIRECTOR, LIFE SCIENCES DIRECTOR, MARKETING & RESEARCH SERVICES Gail Kaye LIST ACCOUNT EXECUTIVE Renee Schuster CONTENT VP, CONTENT & STRATEGY Sara Michael GROUP EDITORIAL DIRECTOR Susan Kweskin CONTENT CHANNEL DIRECTOR Julia Talsma 440-891-2792 / [email protected] CONTENT CHANNEL MANAGER Julianne Stein 440-826-2834 / [email protected] CONTENT EDITOR Mark Lowery 440-891-2705 / [email protected] PUBLISHING AND SALES EVP, MANAGING DIRECTOR Georgiann DeCenzo VICE PRESIDENT, GROUP PUBLISHER Ken Sylvia NATIONAL ACCOUNT MANAGER Mark Hildebrand 732-346-3006 / [email protected] SALES MANAGER CLASSIFIED/DISPLAY ADVERTISING Tod McCloskey 440-891-2739 / [email protected] ACCOUNT MANAGER,CLASSIFIED/DISPLAY Patrick Carmody 440-891-2621 / [email protected] Director, PRIME Institute College of Pharmacy University of Minnesota Minneapolis, Minn. 440-891-2613 / [email protected] PERMISSIONS Maureen Cannon 440-891-2742 / [email protected] REPRINTS 877-652-5295, ext. 121 bkolb@wrightsmedia. com Outside US, UK, direct dial: 281-419-5725, ext. 121 Tom Ehardt SENIOR VP, FINANCE Tom Mahon EVP & MANAGING DIRECTOR, UBM MEDICA Georgiann DeCenzo EVP, STRATEGY & BUSINESS DEVELOPMENT Mike Alic VP & MANAGING DIRECTOR, PHARM/SCIENCE GROUP Dave Esola VP & MANAGING DIRECTOR, CBI/IVT Johanna Morse VP & MANAGING DIRECTOR, VETERINARY GROUP Becky Turner Chapman VP, MARKETING & AUDIENCE DEVELOPMENT Joy Puzzo DESIGN VP, MEDIA OPERATIONS Francis Heid DIRECTOR, DESIGN AND DIGITAL PRODUCTION DIRECTOR, HUMAN RESOURCES Jamie Scott Durling Nancy Bitteker ART DIRECTOR Lecia Landis UBM AMERICAS CHIEF EXECUTIVE OFFICER Simon Foster PRODUCTION CHIEF FINANCIAL OFFICER David Cox PRODUCTION DIRECTOR Karen Lenzen CHIEF OPERATING OFFICER Brian Field 218-740-6371 [email protected] AUDIENCE DEVELOPMENT VP, MARKETING & AUDIENCE DEVELOPMENT Joy Puzzo DIRECTOR, AUDIENCE DEVELOPMENT Christine Shappell AUDIENCE DEVELOPMENT MANAGER Jamie Vidales 218-740-7285 / [email protected] HEAD OF LEGAL Michael Bernstein UBM PLC CHIEF EXECUTIVE OFFICER Tim Cobbold GROUP OPERATIONS DIRECTOR Andy Crow CHIEF FINANCIAL OFFICER Marina Wyatt CHAIRMAN Dame Helen Alexander DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 1 TABLE OF CONTENTS FEBRUARY 2016 | Vol. 160 | 02 Celebrating Our 160th Anniversary Anniver sary Issue COVER STORY This special anniversary issue provides glimpses into Drug Topics’ past and celebrates how the practice of pharmacy has advanced. Stay tuned for more 160th coverage throughout the year. 14 PRESCRIBED RE ADING WORKING TOGETHER FOR THE GREATER GOOD: MD VERSUS RPH 6 All it took was a simple phone call, right? MCK & R DRUG TOPICS CAN PHARMACISTS GET SUED FOR DOING THEIR JOB? THROUGH THE DECADES Columnist Ken Baker’s answer may surprise you 1910-1920: A house organ 23 38 A PHARMACY PIONEER OF THE 20TH CENTURY BOUNDS INTO THE 21ST 51 One of the founding fathers of public health shares what keeps him juiced HEALTH-SYSTEM PHARMACISTS NEW CPE MINI - SERIES: AND February 2016 and March 2016 Embracing new roles 8 KASEY K. THOMPSON, PHARMD, MS, MBA Drug Topics and The University of Connecticut School of Pharmacy present a new CPE series for pharmacists...and they’re FREE. Earn up to 2 hours of CPE credit with each online activity. A PHARMACY PIONEER FEBRUARY 2016: Part 1: Recognition and referral to enhance recovery: The pharmacists’ role in managing opioid use disorder Champion of public health 51 MARCH 2016: Part 2: Law: Educating and empowering patients and caregivers: The pharmacist’s role in reducing the risk of opioid overdose 2 CPE CREDITS 2 Earn 2 CPE Credits. Go Online to > www.drugtopics.com/cpe DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM FRED MAYER, RPH, MPH TABLE OF CONTENTS CONTINUED ON PAGE 4 > Put the MAGIC Back in Your MOUTHWASH Humco’s NEW Mouthwash base line is designed to SIMPLIFY the process of extemporaneous compounding of active ingredients for delivery to the oral cavity. It contains a combination of excipients that are suitable for dissolving and suspending drugs to treat ORAL PAIN, MOUTH SORES, and ORAL INFECTIONS. Humco mouthwash bases are PACKAGED in a container allowing for mixing of actives, labeling and dispensing in the ORIGINAL container ;: Ō-B;>10w<.AŊ1>10wE1>11 !>-8;5?@A>5F1>w;-@?@41;A@4 MOUTHWASH-GP is a general purpose mouthwash base for the dissolution and/or suspension of the common active ingredients used in magic mouthwash MOUTHWASH-OM is a mouthwash base for Oral Mucositis for dissolution of high levels of watersoluble active ingredients MOUTHWASH-AF is an alcohol free mouthwash base containing solubilizers to allow the incorporation of high levels of hydrophobic active ingredients Wholesaler Mouthwash GP NDC 00395-6030-98 Mouthwash OM NDC 00395-6040-98 Mouthwash AF NDC 00395-6050-98 AmerisourceBergen 6 468041 468049 468037 AmerisourceBergen 8 10158041 10157957 10158040 Cardinal Health 5202486 5202510 5202528 185827 185843 185850 3510963 3510989 3510997 471748 471896 471904 Dakota Drug McKesson Morris Dickson Smith Drug 746156 746164 746172 Value Drug 147242 147244 147246 Humco | 512 E 11th St, Austin, TX 78701 855.925.4736 | www.humcocompounding.com TABLE OF CONTENTS FEBRUARY 2016 | Vol. 160 | 02 2 CPE CREDITS C O N T I N U I N G E D U C AT I O N Part 1: The pharmacist’s role in managing opioid use disorder With an epidemic of patients with opioid use disorder, myths and stereotypes about this patient population inhibit entry into treatment and recovery. Pharmacists can make a difference. 39 6 VIEW FROM THE ZOO Working together for the greater good: MD vs. RPh ISSUES & TRENDS 7 REMINGTON HONOR MEDAL Leslie Z. Benet, PhD, to receive at APhA Annual Meeting next month 13 GOOD USE OF PHARMACY CLAIMS DATA Primary nonadherence to meds identified through EHRs 16 0 T H A N N I V E R S A R Y 8 HEALTH-SYSTEM PHARMACISTS Integral members of the healthcare team 14 COMMUNITY PHARMACISTS Patient care still top priority 5 STATES FAVOR “DEATH WITH DIGNITY” Movement to affect RPHs 50 51 A PHARMACY PIONEER Fred Mayer, RPH, MPH: No better time than now to practice public health pharmacy CLINICAL 32 ANTICOAGULATION THERAPIES Pre-op anticoagulation reduces VTE risk in cancer patients 37 CLINICAL NEW DRUG Flibanserin for sexual desire disorder R E G U L AT O R Y & L E G A L 38 INCREASED LIABILITY Will doing your job increase your risk of being sued? 50 “DEATH WITH DIGNITY” LAWS Five states recognize assisted suicide for terminally ill patients 23 THROUGH THE DECADES 1910-1920: Drug Topics is magazine for the druggist, drug clerk, and drug trade P R O D U C T U P D AT E S 27 NEW PRODUCTS Elbasvir/grazoprevir (Zepatier) for chronic HCV genotypes 1 and 4 26 PHARMACY EDUCATION Specialized training puts RPhs front & center 30 ORAL CARE Proper oral hygiene for kids, adults ANNA D. GARRETT, PHARMD, BCPS VTE RISK REDUCTION IN CANCER PTS Pre-op anticoagulation key 32 Corrections Drug Topics should have added attribution to a statement that appeared in the January 2016 Regulatory & Legal column (“Valeant business practices embroiled in controversy,” page 50). The corrected version is as follows: “After this, in September 2015, Valeant came under severe criticism for exponentially increasing the prices of drugs it sent to the marketplace. According to a Deutsche Bank analyst, in 2015 alone, the company increased prices on its brand-name drugs by an average of 66%, five times more than increases set by its closest industry competitor.” In the same issue, Drug Topics incorrectedly identified Sen. Gayle Manning as a physician in the January Innovations column (“Ohio pharmacists gain ground with expanded CPAs,” page 68). Rep. Stephen Huffman is a physician. Drug Topics regrets the errors. Drug Topics (ISSN# 0012-6616) is published monthly and Drug Topics Digital Edition (ISSN# 1937-8157) is issued every week by UBM Medica 131 West First St., Duluth, MN 55806-2065. One-year subscription rates: $61 in the United States & Possessions; $109 in Canada and Mexico; all other countries, $109. Single copies (prepaid only) $10 in the United States; $10 in Canada and Mexico; all other countries, $15. Include $6 per copy for U.S. postage and handling. Periodicals postage paid at Duluth, MN 55806 and additional mailing offices. POSTMASTER: Please send address changes to Drug Topics, P.O. Box 6079, Duluth, MN 55806-6079. Canadian G.S.T. number: R-124213133RT001. Publications Mail Agreement Number 40612608. Return undeliverable Canadian addresses to: IMEX Global Solutions PO Box 25542 London, ON N6C 6B2 CANADA. Printed in the U.S.A. ©2016 Advanstar Communications Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical including by photocopy, recording, or information storage and retrieval without permission in writing from the publisher. Authorization to photocopy items for internal/educational or personal use, or the internal/educational or personal use of specific clients is granted by Advanstar Communications Inc. for libraries and other users registered with the Copyright Clearance Center, 222 Rosewood Dr. Danvers, MA 01923, 978-750-8400 fax 978-646-8700 or visit http://www.copyright.com online. For uses beyond those listed above, please direct your written request to Permission Dept. fax 440-756-5255 or email: [email protected]. Microfilm or microfiche copies of issues are available through Advanstar Marketing Services, (800) 225-4569, Ext. 839. Unsolicited manuscripts, photographs, art, and other material will not be returned. Publisher assumes no responsibility for unsolicited manuscripts, photographs, art, and other material. Drug Topics provides certain customer contact data (such as customers’ names, addresses, phone numbers, and e-mail addresses) to third parties who wish to promote relevant products, services, and other opportunities that may be of interest to you. If you do not want UBM Medica to make your contact information available to third parties for marketing purposes, simply call toll-free 866-529-2922 between the hours of 7:30 a.m. and 5 p.m. CST and a customer service representative will assist you in removing your name from UBM Medica’s lists. Outside the U.S., please phone 218-740-6477. Drug Topics does not verify any claims or other information appearing in any of the advertisements contained in the publication, and cannot take responsibility for any losses or other damages incurred by readers in reliance on such content. Drug Topics welcomes unsolicited articles, manuscripts, photographs and other materials but cannot be held responsible for their safekeeping or return. LIBRARY ACCESS Libraries offer online access to current and back issues of Drug Topics through the EBSCO host databases. TO SUBSCRIBE, call toll-free 888-527-7008. Outside the U.S. call 218-740-6477. 4 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM IMAGE: GETTY IMAGES / DESIGN PICS/HAMMOND HSN COUNTER POINTS 5 DISPENSED AS WRITTEN Drug Topics: 160 years strong NED MILENKOVICH, PHARMD, JD DISPENSED AS WRITTEN Anniver sary Issue Julia Talsma, Content Channel Director Drug Topics: 160 years strong Drug Topics celebrates its 160th anniversary this year, and we want to provide you with some perspective to demonstrate how far your profession has developed. With the advances in technology, drug therapy, and healthcare reform, the practice of community and health-system pharmacy continues to evolve dramatically. Yet your role as providers has not really changed that much. The patient still comes first. Retail pharmacists In this month’s cover story, Contributing Editor Fred Gebhart takes you on a historical journey through community pharmacy, from the first apothecary Louis Hébert, who set up shop in 1605 in the vicinity of today’s Nova Scotia, through the end of the 18th century, when apothecaries were in almost every U.S. city, most physicians mixed and dispensed medications, and most pharmacists treated patients. The 19th century marked the beginning of formal pharmacy education with the opening of the Philadelphia College of Pharmacy in 1821; then came the establishment of the American Pharmaceutical Association (today’s American Pharmacists Association) in 1888. In addition, drug companies and chemical companies began to expand their research and development, and to commercialize standardized pharmaceutical products. By the early 20th century, the market for manufactured medicine and the growing urbanization of America gave rise to the drugstore chains. But don’t count out the independents, according to Justin Wilson, PharmD. While a number of independents have disappeared, those with business acumen will survive. Health-system pharmacists Health-system pharmacy has continued to evolve over the last half century. Journalist Anthony Vecchione covers pharmacists’ important role on the interprofessional healthcare team as they participate in physician rounds, develop pharmaceutical care plans, and create medication therapy management strategies for patients. Over time the role of the pharmacist has evolved into a more clinically focused position. For example, healthsystem pharmacists have made great inroads in emergency medicine, following the Institute of Medicine’s landmark 1999 report on medical errors. In the area of clinical ambulatory care pharmacy, pharmacists gained ground during the 1970s when the Indian Health Service developed the Pharmacy Practitioner Training Program, positioning pharmacists as patient care providers for those with chronic diseases. Critical care pharmacy has been a recognized concern for only about 35 years. Today, ICU patient safety has been greatly enhanced through the efforts of pharmacists in the reduction of preventable adverse events. Pharmacy education In this issue, Lucinda L. Maine, PhD, RPh, executive vice president and CEO of the American Association of Colleges of Pharmacy, reviews the evolution of pharmacy education since the mid-19th century. Did you know that from 1929 until 1969, pharmacists were not permitted to discuss a physician’s prescription with a patient? Maine reminds us how challenging it was to practice pharmacy during those years, in light of this onerous restriction. By 1969, the role of the pharmacist had shifted from strictly dispensing medications to a focus on patient care. Pharmacy educators began to reimagine the profession and adjust the curriculum to expand the role of the pharmacist. By the 1970s, pharmacy institutions started the transition from the BS to the PharmD degree, hiring clinical faculty members to teach the enriched, expanded curriculum. Today, the PharmD degree is a requirement for all students who want to practice pharmacy. Our archives Starting this month and continuing through the year, we plan to offer some glimpses into Drug Topics’ past, decade by decade. In the early 1900s, Drug Topics was the house organ of drug wholesaler McKesson & Robbins, boasting a circulation of more than 12,000 at an annual subscription rate of 25 cents. During that time, Drug Topics’ primary mission was to “educate, improve, and entertain the druggist, drug clerk, and drug trade” in general. We hope these interesting tidbits will do just that. Also, don’t miss Drug Topics’ 160th Anniversary Quiz (inside). Good luck! We want to hear from you. Post a comment at > www.drugtopics.com or e-mail us at > [email protected] DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 5 COUNTER POINTS VIEW FROM THE ZOO David Stanley, RPh Working together for the greater good: MD vs. RPh It started the way so many of these things do, with a phone call to get the ball rolling on a prior auth. “I’m not sure that’s the strength the doctor meant to prescribe,” the lady at the group medical practice said. “I’ll have to check and call you back.” That was on Friday morning. On Saturday morning a friend of the patient — who was seriously ill and having trouble breathing — came in to get the prescription. No one from the group practice had called us back. You know exactly how this goes. through another lengthy session on hold — which I suspected the staff made longer than necessary to penalize me for being a pain in the neck — before the doctor got on the line. Our conversation went something like this: Step 1: The doctor is out Step 3: Work with me here First, a test claim. The far-more-common strength of this nebulizer solution would go through the patient’s insurance just fine. Actually, it would also be easier to use; the only difference between what we were told “was probably wrong” and what was covered was that the paid-for med didn’t require predilution. The solution to this problem was in sight. You can guess what happened next. “Well that doctor’s not in today. If the patient’s really ill, they should go to the emergency room.” This, of course, was delivered after a lengthy hold. Evidently the concept of paging a physician was long forgotten at this practice, along with asking the doctor on duty for his opinion. Me: “Can we do the commonsense thing here that everyone knows is best for the patient, and give her the easier-to-use, far-more-common strength of this nebulizer solution, which most likely was what was meant to be prescribed in the first place?” Doctor: “Absolutely.” The end was in sight. Just some quick phone counseling with the patient, who was at home and gasping with every word, to make sure that the original prescription wasn’t what the original, unwilling-to-be-reached doctor really wanted. Step 2: My life on hold One thing they can’t teach you in pharmacy school is when not to take no for an answer. Fortunately, I knew the doctor on duty this day had a good helping of common sense in his head. It took a while, and I had to sit Step 5: Calling around Back to the phones to call around, until I located one at the independent drugstore in the next town. It was the best I could do, as I didn’t have a nebulizer in stock. I gave the friend directions to the store and came to grips with the fact that this was the best solution I could engineer. Not perfect I thought, but not all bad. Now it was on to the next crisis. Mid-morning on Monday someone from the group medical practice called. Step 6: Count to 10 “We just wanted to let you know the oncall doctor took care of that nebulizer prescription with the strength issue.” They were probably lucky that my technician took that phone call instead of me. Not that this was anything special. Things like this happen every day, in every pharmacy, in every corner of the country. Step 4: What machine? “When they were going over how to use your nebulizer machine, did they say you would have to dilute this medicine first?” “What machine?” They had sent this woman out the door with a prescription for medication to go into a nebulizer without ever mentioning that she would need a nebulizer. Replaced by what? Really? Feel free to tear this page out and give it to the next person who says that pharmacists are soon destined to be replaced with machines. David Stanley is a pharmacy owner, blogger, and professional writer in northern California. Contact him at [email protected]. We want to hear from you. Post a comment at > www.drugtopics.com or e-mail us at > [email protected] 6 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM ISSUES & TRENDS Up front Industry News & Analysis PHOTO BY CHRISTINE KRIEG Benet to receive Remington Honor Medal Leslie Z. Benet, PhD, professor and former chair of the Department of Bioengineering & Therapeutic Sciences, a joint department of the pharmacy and medicine schools at University of California – San Francisco, is this year’s recipient of the American Pharmacists Association (APhA) Remington Medal of Honor. Official recognition will occur at the APhA Annual Meeting and Exposition in Baltimore, Md., March 4-7. “Dr. Benet touches the lives of every practitioner who makes decisions about the dosing of any drug. He is a master of pharmacokinetics. His lifelong work as a pharmacist and scientist has provided all pharmacists with the ability to translate LESLIE Z. BENET bench pharmacology into clinical drug application for improved patient care,” one of his colleagues said when nominating Benet for the award. Benet was selected for the medal, the highest award that APhA bestows, in recognition of his numerous substantial scientific and public service contributions to the REIMBURSEMENT Medication adherence: How to get paid for helping patients An insurance executive recently revealed top ways pharmacists can obtain reimbursement for helping their patients with medication adherence. During a recent Wolters Kluwer Clinical Drug Information webinar, Alexandra Tungol Lin, clinical manager of health outcomes and pharmacy care manageALEXANDRA LIN ment for Blue Cross Blue Shield of Michigan, provided pharmacists with some new information. Here are her top tips: 1. Metrics. Participate in the Medicare Star Ratings program as well as the Quality Rating System (QRS) from the Centers for Medicare & Medicaid (CMS), which informs consumers about the quality of healthcare services in healthcare plans purchased on the Marketplace. pharmacy profession. His work has been published in 540 publications, he has received 12 patents, and he has edited six books. In fact, he is one of the most widely cited pharmaceutical scientists in the world. He also has mentored 54 PhD graduates and an additional 122 post-doctoral and visiting scientists in his laboratory. Benet “blends deep passion for pharmaceutical practice and science with vision, energy, and boldness in advancing the stature of the pharmaceutical profession,” one of his nominators said. Benet has served as president of the APhA Academy of Pharmaceutical Sciences, the American Association of Pharmaceutical Scientists, and the American Association of Colleges of Pharmacy, as well as chair of the FIP Board of Pharmaceutical Sciences. In 1987, he was elected to membership in the Institute of Medicine of the U.S. National Academy of Sciences. He received his pharmacy degree from the University of Michigan and his PhD in pharmaceutical chemistry from the University of California – San Francisco. “Pay-for-performance programs for pharmacy can really move the needle,” Lin said. “Currently, there are no payments tied to QRS. But many of us anticipate that payments will be tied to QRS,” Lin said. 2. Pay for performance. When possible, take part in health plans’ pay-forperformance programs. Although it is one of the few insurers offering such a program, an example from Blue Cross Blue Shield of Michigan and the University of Michigan is the Michigan Pharmacists Transforming Care and Quality (MPTCQ) program. Starting with 10 participating physician organizations across the state, clinical pharmacists review patients’ medication plans, collaborate with physicians to make necessary medication changes, and work with patients to help them understand how to safely and properly use the medications. 3. In the community. Host health fairs in the community, giving individuals knowledge about their conditions. — CHRISTINE BLANK, CONTRIBUTING EDITOR “Especially with the Marketplace population, it is probably the first time for many patients to have insurance. Terms like ‘formulary’ are very foreign to them,” Lin said. 4. Empathy. Express empathy, using statements such as “Your doctor and I can work together to help you,” Lin said. Patients might then become less defensive and admit that they are splitting their statin tablets, for example. “Patients might be experiencing muscle aches that they associate with statins. We should really use our medication expertise and address whether there should be an alternative statin, whether a dose increase is necessary, whether there is a vitamin D deficiency causing the muscle ache, or if exercise is causing the pain,” Lin said. 5. Outreach. Call patients to find out the barriers to medication adherence they are experiencing. — CHRISTINE BLANK, CONTRIBUTING EDITOR C O N T I N U E D O N P A G E 13 > DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 7 HEALTH SYSTEMS Anniver sary Issue Anthony Vecchione Health-system pharmacists empower the team The role of health-system pharmacists has evolved considerably over the last half-century. No longer responsible only for compounding drugs and dispensing prescriptions, today’s health system pharmacists are an integral part of an enterprise-wide healthcare team. Many-sided expertise As they participate in rounding teams, develop pharmaceutical care plans, and create medication therapy management (MTM) strategies, health-system pharmacists are involved in patient care and interact regularly with physicians, nurses, and other caregivers. With the establishment of residency programs, antimicrobial stewardship programs, specialties in emergency medicine and ambulatory care, and board certification, health-system pharmacists have established themselves as essential healthcare professionals. They evaluate trends in medication use and physician prescribing, develop that control drug distribution. In collaboration with nursing, they help to ensure that patients receive the right medication, in the correct form and dosage, at the right time, in order to prevent adverse events. Standards and certification “Hospital pharmacists have long embraced the roles that practice standards, residency training, credentialing and privileging, and specialty certification play in achieving optimal patient care outcomes,” said Kasey K. Thompson, PharmD, MS, MBA. Thompson is vice president of the Office of Policy, Planning, and Communications, ASHP. It’s really wonderful to see how much the medical community, patients, and other providers have embraced the vital roles pharmacists play.” KASEY THOMPSON guidelines for medication use, educate patients and healthcare professionals, and implement and maintain drug distribution systems. In some hospitals, they provide specialized services in areas such as pediatrics, oncology, infectious diseases, nutrition support, and drug information. As patient safety experts, they are responsible for the automation systems 8 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM Thompson noted that pharmacy technician education, training, and certification, along with the enhanced use of information technology, have also played important roles. “These advancements and others in hospitals have served as examples for other practice settings, many of which are now seeking to adopt similar pharmacy practice models,” Thompson said. Residency programs According to the American Society of Health-System Pharmacists (ASHP), pharmacy residencies date back to the early 1930s. Originally referred to as internships, the main goal of residencies was to train pharmacists in hospital pharmacy management. ASHP got involved in 1948 with the development of standards for pharmacy internships. In 1962, ASHP established an accreditation process and accreditation standards for residencies in hospital pharmacy. Fast forward to the 1970s. Residencies in clinical practice increased, which led to the establishment of accreditation standards for clinical pharmacy and specialized residency training. According to ASHP, at that juncture, most programs were conducted in colleges of pharmacy, and general and clinical residencies were recognized separately. By the early 1990s, the two types of residency programs, general and clinical, were replaced by pharmacy practice residencies that placed a greater focus on pharmaceutical care. By the late 1990s, ASHP had developed accreditation standards that recognized 15 specialized areas of practice. Partnerships Recently, ASHP has forged partnerships with other pharmacy associations, including the Academy of C O N T I N U E D O N P A G E 11 > “Ever since Dad was in the hospital last year, I go to work with a real purpose. I want to help people just like my father. It’s that kind of commitment that guides us in everything we do.” Amneal Manufacturing Supervisor Amneal applies the “Family Business” model across the full span of its operations. Every department is driven by the belief that each patient is a family member, and every business partner should be treated like a guest in our home. At Amneal we understand that to do good things we must first ensure we are good people. We are led by visionary scientists and entrepreneurs focused on a grander purpose that is more important than simply making money. We believe that doing the right thing is its own reward, far more valuable than a glowing quarterly report. We have a resourceful spirit that allows us to remain nimble and to meet every opportunity. We build trusted relationships that improve our business and help create a better world for future generations. We take enormous pride in working hard and in truly collaborating in order to succeed together. We are empowered from front line to founder. We ALL take the initiative to build an organization known for superior execution in every aspect of our operation. We are humble and refuse to let any amount of success change our core beliefs. And we will never stop trying to make ourselves, and Amneal, better. Generic’s New Generation a m n e a l. co m Copyright © 2016 Amneal Pharmaceuticals, All Rights Reserved - AMN-DT 02/16 160TH < CONTINUED FROM PAGE 8 Managed Care Pharmacy (AMCP), the American College of Clinical Pharmacy (ACCP), and the American Pharmacists Association (APhA), for accreditation of residencies. In 2005, ASHP established new residency accreditation standards that replace pharmacy practice residencies with postgraduate year one (PGY1) pharmacy residencies and specialized residencies with postgraduate year two (PGY2) pharmacy residencies. Health-system pharmacists, according to ASHP, can achieve board certification in a variety of specialty areas: ambulatory care, critical care, nuclear pharmacy, nutrition support pharmacy, oncology, pediatrics, pharmacotherapy, and psychiatric pharmacy. Numerous studies have indicated that expanding the role of pharmacists in the hospital setting can have a positive impact on the quality of patient care and can provide cost savings. Board certification Established in 1976, the Board of Pharmacy Specialties (BPS) was created as an independent division of APhA. The goals of BPS certification aim to: t(SBOUSFDPHOJUJPOPGBQQSPQSJBUF pharmacy practice specialties on the basis of criteria established by BPS t&TUBCMJTITUBOEBSETGPSDFSUJåDBUJPO and recertification of pharmacists in recognized pharmacy practice specialties t(SBOUUPRVBMJåFEQIBSNBDJTUTDFS tification and recertification in recognized pharmacy practice specialties t4FSWFBTBDPPSEJOBUJOHBHFODZBOE information clearinghouse for organizations and pharmacists in recognized pharmacy practice specialties t&OIBODFQVCMJDDPOTVNFSQSPUFD tion by developing effective certification programs for specialty practices in pharmacy More than 20,000 pharmacists worldwide are board-certified by BPS in the eight specialties already men- tioned. Data have shown that when specialty-trained pharmacists are part of the collaborative care team, patient satisfaction is enhanced and there are fewer complications in drug treatment; laboratory monitoring improves; use of unnecessary medications is reduced; and hospital stays are shorter, resulting in lower treatment costs. Emergency medicine It wasn’t until the early 1970s that hospital pharmacists became involved in emergency departments (ED). In those early years, they dealt mostly with cost containment, inventory control, and dispensing. In the December 1, 2015 issue of the American Journal of Health-System Pharmacy (AJHP), “Emergency medicine pharmacy: Still a new clinical frontier,” an article by co-authors Nicole macists in the ED setting could help reduce error rates. But for that goal to be achieved, Aquisto and Hays noted, this new area of practice for pharmacists would require validation, accreditation, and new practice guidelines. Initially, clinical pharmacy services focused on drug procurement during cardiac arrest, adverse drug event surveillance, and identification of medication-related ADEs in the ED. Clinical pharmacy services in the ED began to escalate in the early 2000s. ASHP has been instrumental in supporting the growth of EM pharmacy practice. EM physicians and nurses value the pharmacists’ role in the ED. In 2014, pharmacists involved with ASHP’s Section Advisory Group on Emergency Care drafted a resolution document asking that the American College of Data have shown that when specialty-trained pharmacists are part of the collaborative care team, patient satisfaction is enhanced and there are fewer complications in drug treatment; laboratory monitoring improves; use of unnecessary medications is reduced; and hospital stays are shorter, resulting in lower treatment costs.” M. Aquisto, PharmD, and Daniel P. Hays, PharmD, noted: “As hospital distribution practices changed, the role of the pharmacist developed into one that was more clinically focused.” The development of emergency medicine (EM) pharmacy services was sluggish in the early years, according to Aquisto and Hays, until the Institute of Medicine’s landmark 1999 report on medical errors revealed that EDs had high rates of preventable adverse drug events. Then it was recognized that the inclusion of phar- Emergency Physicians (ACEP) create a policy statement to support clinical pharmacy services in the ED. In 2015, ACEP adopted the resolution, and the American Academy of Emergency Medicine (AAEM) accepted pharmacists as members of the organization’s Allied Health Professionals membership category. Ambulatory care Throughout the 1960s and 1970s, ambulatory care pharmacy practice C O N T I N U E D O N P A G E 12 > DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 11 Anniver sary Issue < C O N T I N U E D F R O M P A G E 11 in the United States was the domain of stand-alone independent community pharmacists. In “Evolution of ambulatory care pharmacy practice in the past 50 years,” an article published in the December 1, 2015 issue of AJHP, co-authors Jannet M. Carmichael, PharmD, and Deanne L. Hall, PharmD, noted that while hospitals and clinics operated outpatient pharmacies that allowed patients to fi ll prescriptions before being discharged from the hospital, those facilities were not intended to fill prescriptions for medications used for chronic conditions. In the early 1950s, APhA prohibited pharmacists from discussing therapeutic effects of a prescription drug with a patient. That counseling prohibition was removed in 1969. The policy shift, according to Carmichael and Hall, enabled pharmacists to begin offering patients verbal consultations. During the 1970s and 1980s, pharmacists started getting involved with clinical ambulatory care pharmacy. In 1972, the Indian Health Service years between 1990 a nd 2000, increased “focus on chronic disease state management and disease prevention positioned the ambulatory care pharmacist to become a vital member of the healthcare team by improving patient outcomes.” In 1990, ASHP created an accreditation standard for residencies in primary care that was revised as a standard for PGY2 residencies in ambulatory care pharmacy in 2006. hospital and clinical pharmacy standards, and on specialized residency standards, in the 1980s. The Ninth-Floor Pharmacy Project paved the way for pharmacists to engage directly with physicians in the management of patients. Benedict and Hess cite a landmark 1999 study by Leape and colleagues “describing the major impact pharmacists can have on ICU patient safety through the reduction of preventable adverse events.” Critical care Antimicrobial stewardship Critical care pharmacy has been in existence only for about 35 years. Clinically oriented pharmacy practice came about as a result of changes in industry processes, education standards, laws, and coordination of views through professional organizations, according to Neal Benedict, PharmD, and Mary M. Hess, PharmD. In their article “History and future of critical care pharmacy practice,” published in the December 1, 2015 issue of AJHP, the notion of moving pharmacists into patient care areas began in the mid-1960s. An ASHP position paper promoting the pharmacist’s role in antimicrobial stewardship and infection control states, “Pharmacists have a responsibility to take prominent roles in antimicrobial stewardship and infection prevention and control programs in health systems.” The association contends that pharmacists should participate in antimicrobial stewardship and infection prevention and control efforts through clinical endeavors that concentrate on correct antimicrobial use and membership on appropriate multidisciplinary work groups and committees in health systems. According to ASHP, antimicrobial stewardship is employed in practice settings of health systems to improve patient outcomes and minimize the unintended consequences of antimicrobial use. The goals of antimicrobial stewardship programs include attenuating or reversing antimicrobial resistance, preventing antimicrobial-related toxicity, and reducing the costs resulting from inappropriate antimicrobial use and healthcare-associated infections. At an antimicrobial stewardship forum convened by the White House in June 2015, a top official at the Department of Health and Human Services (HHS) suggested that hospitals would eventually be required to improve the way they use antimicrobial drugs. Clinically oriented pharmacy practice came about as a result of changes in industry processes, education standards, laws, and coordination of views.” developed the Pharmacy Practitioner Training Program, which was designed to position ambulatory care pharmacists as patient care providers in the area of chronic disease management. Carmichael and Hall reported that in the 1990s, the Department of Veterans Affairs (VA) established guidelines for deployment of “clinical pharmacy specialists” within the ambulatory care environment, which paved the way for the use of pharmacists to provide direct patient care in the management of anticoagulation therapy and chronic diseases. According to the authors, in the In the “Ninth-Floor Pharmacy Project” at the University of California, San Francisco (UCSF), pharmacists were responsible for distributing drugs and gathering drug histories from patients at Moffitt Hospital. Ultimately, according to Benedict and Hess, the pharmacist’s role expanded to include participation on resuscitation teams and responsibility for parenteral nutrition calculations. In 1962, ASHP developed formal pharmacy post-graduate training program standards that focused on hospital pharmacy administration. This evolved into a greater emphasis on We want to hear from you. Post a comment at > www.drugtopics.com or e-mail us at > [email protected] 12 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM 160TH Paul W. Abramowitz, ASHP’s executive vice president and CEO, applauded the Obama Administration’s initiative in making antibiotic stewardship a PAUL ABRAMOWITZ national priority and in recognizing the vital roles that pharmacists play in improving stewardship and antibiotic use. Chief pharmacy officer As the role of the health-system pharmacist continues to expand beyond clinical duties, the pharmacy executive, a relatively new position, is also gaining ground. According to ASHP, hospitals and health systems would benefit greatly from having a pharmacy executive responsible for the strategic planning, design, operation, and improvement of the organization’s medication management system. Widespread use of the title “chief pharmacy officer” was first proposed in 2000 in an effort to enhance the contribution of pharmacy by creating organizational parity between the pharmacy executive and other C-suite executives, including chief nursing, medical, and information officers. In its position statement titled “Roles and Responsibilities of the Pharmacy Executive,” ASHP asserted that “when the pharmacy executive works collaboratively with others at this executive level, the pharmacy department is better positioned to effectively contribute to the organization’s strategic initiatives and address system-wide issues regarding medications and medication management.” The future Going forward, how will the evolving role of the health-system pharmacist continue to benefit the patient? For some industry experts, the answer to that question is clear. “Pharmacists improve patient outcomes as members of interprofessional teams,” said ASHP’s Thompson. When a pharmacist is on the team, patients are safer, medication therapy is optimized, and healthcare costs are lower, he said. “As healthcare, science, and pharmacy practice continue to evolve, pharmacists will continue to take on enhanced roles in areas such as pharmacogenomics, personalized medicine, and many others,” said Thompson. “It’s really wonderful to see how much the medical community, patients, and other providers have embraced the vital roles pharmacists play as direct patient care providers.” The clear benefits shown by teambased practice models have demonstrated the important and necessary roles pharmacists already play for patients and will continue to play in the future, said Thompson. Anthony Vecchione is a healthcare journalist based in New Jersey. < UP FRONT C O N T I N U E D F R O M P A G E 7 DATA MINING Pharmacy claims data can help adherence Pharmacy claims data may be useful in cases of nonadherence to antihypertensive medications, suggested a study published in the January 4 online edition of the American Journal of Managed Care. To better understand nonadherence, the research team of pharmacists and physicians reviewed pharmacy claims data available through electronic health DOMINIQUE COMER records (EHRs) . “Primary nonadherence is an increasingly identified barrier to optimal hypertension management. However, the ability to intervene has been limited by the lack of pharmacy claims records available in clinical practice in nonintegrated delivery systems,” wrote Dominique Comer, PharmD, MS, senior clinical researcher, Christiana Care Value Institute, Philadelphia, Penn. After reviewing EHRs in the Surescripts network, the researchers found no evidence that one-third of patients prescribed a new antihypertensive medication had filled the Rx within 30 days. “This is consistent with Fischer et al, who identified a 28.4% incidence of primary nonadherence in a similar cohort. Lower rates of primary nonadherence have been found in studies within integrated delivery systems, perhaps reflecting the ability of an integrated delivery system to capture more complete medication refill history,” Comer wrote. History not available Only 791 of 3,284 patients who were prescribed an antihypertensive drug met the study requirements. “This was largely due to the fact that the pharmacy fill history was not available because the provider had not accessed the medication history after the new prescription.” However, the researchers did fi nd that primary nonadherence was associated with increasing medication burden, age, and noncardiovascular comorbidities. “This is consistent with previous literature suggesting that medication nonadherence may increase as competing comorbidities, particularly with active symptoms, take precedence over asymptomatic conditions such as hypertension,” Comer wrote. “Our results showed that the majority of patients who do fill their medications do so on the day it is prescribed, suggesting that interventions could be applied in the first few days following prescription. This approach has been used to improve the proportion of patients who fill statin prescriptions,” Comer wrote. — CHRISTINE BLANK, CONTRIBUTING EDITOR DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 13 BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR GRANIX® (tbo-filgrastim) injection, for subcutaneous use SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE GRANIX is indicated to reduce the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Splenic Rupture Splenic rupture, including fatal cases, can occur following administration of human granulocyte colony-stimulating factors. In patients who report upper abdominal or shoulder pain after receiving GRANIX, discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture. 5.2 Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) can occur in patients receiving human granulocyte colony-stimulating factors. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS. 5.3 Allergic Reactions Serious allergic reactions including anaphylaxis can occur in patients receiving human granulocyte colony-stimulating factors. Reactions can occur on initial exposure. The administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine may reduce the severity of the reactions. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim. 5.4 Use in Patients with Sickle Cell Disease Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving human granulocyte colony-stimulating factors. Consider the potential risks and benefits prior to the administration of human granulocyte colony-stimulating factors in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis. 5.5 Capillary Leak Syndrome Capillary leak syndrome (CLS) can occur in patients receiving human granulocyte colonystimulating factors and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. 5.6 Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte colony-stimulating factor (G-CSF) receptor through which GRANIX acts has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded. 6 ADVERSE REACTIONS The following potential serious adverse reactions are discussed in greater detail in other sections of the labeling: UÊ -«iVÊ,Õ«ÌÕÀiÊQsee Warnings and Precautions (5.1)] UÊ VÕÌiÊ,iëÀ>ÌÀÞÊÃÌÀiÃÃÊ-Þ`ÀiÊQsee Warnings and Precautions (5.2)] UÊ -iÀÕÃÊiÀ}VÊ,i>VÌÃÊQsee Warnings and Precautions (5.3)] UÊ 1ÃiÊÊ*>ÌiÌÃÊÜÌÊ-V iÊ iÊÃi>ÃiÊQsee Warnings and Precautions (5.4)] UÊ >«>ÀÞÊi> Ê-Þ`ÀiÊ[see Warnings and Precautions (5.5)] UÊ *ÌiÌ>ÊvÀÊ/ÕÀÊÀÜÌÊ-ÌÕ>ÌÀÞÊvviVÌÃÊÊ>}>ÌÊ iÃÊQsee Warnings and Precautions (5.6)] The most common treatment-emergent adverse reaction that occurred at an incidence of at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group was bone pain. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. GRANIX clinical trials safety data are based upon the results of three randomized clinical trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of patients were female, the median age was 50 years, and 86% of patients were Caucasian. In the lung cancer study, 80% of patients were male, the median age was 58 years, and 95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients were male, the median age was 55 years, and 88% of patients were Caucasian. In all three studies a placebo (Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim product were administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy for at least five days and continued to a maximum of 14 days or until an ANC of *10,000 x 106/L after nadir was reached. Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-USapproved filgrastim product). Leukocytosis In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than 1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies. Additional Adverse Reactions Other adverse reactions known to occur following administration of human granulocyte colony-stimulating factors include myalgia, headache, vomiting, Sweet’s syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis and thrombocytopenia. 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody development in patients receiving GRANIX has not been adequately determined. 7 DRUG INTERACTIONS No formal drug interaction studies between GRANIX and other drugs have been performed. Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution. Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C Risk Summary There are no adequate and well-controlled studies of GRANIX in pregnant women. In animal reproduction studies, treatment of pregnant rabbits with tbo-filgrastim resulted in increased spontaneous abortion and fetal malformations at systemic exposures substantially higher than the human exposure. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data In an embryofetal developmental study, pregnant rabbits were administered subcutaneous doses of tbo-filgrastim during the period of organogenesis at 1, 10 and 100 mcg/kg/day. Increased abortions were evident in rabbits treated with tbo-filgrastim at 100 mcg/kg/day. This dose was maternally toxic as demonstrated by reduced body weight. Other embryofetal findings at this dose level consisted of post-implantation loss‚ decrease in mean live litter size and fetal weight, and fetal malformations such as malformed hindlimbs and cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic exposure (AUC) of approximately 50-90 times the exposures observed in patients treated with the clinical tbo-filgrastim dose of 5 mcg/kg/day. 8.3 Nursing Mothers It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GRANIX is administered to a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. 8.4 Pediatric Use The safety and effectiveness of GRANIX in pediatric patients have not been established. 8.5 Geriatric Use Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients were 65 years of age and older. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients. 8.6 Renal Impairment The safety and efficacy of GRANIX have not been studied in patients with moderate or severe renal impairment. No dose adjustment is recommended for patients with mild renal impairment. 8.7 Hepatic Impairment The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment. 10 OVERDOSAGE No case of overdose has been reported. ©2014 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. GRANIX is a registered trademark of Teva Pharmaceutical Industries Ltd. Manufactured by: Distributed by: Sicor Biotech UAB Teva Pharmaceuticals USA, Inc. Vilnius, Lithuania North Wales, PA 19454 U.S. License No. 1803 Product of Israel GRX-40580 January 2015 This brief summary is based on TBO-004 GRANIX full Prescribing Information. Anniver sary Issue From the Past to the Present Care for patients’ everyday needs still top priority Fred Gebhart, Contributing Editor America’s first pharmacist would be lost in a retail pharmacy today. With the advances in retail technology, new drugs and delivery systems, and online adjudication and payment, the practice of pharmacy has changed dramatically since Parisian apothecary Louis Hébert set up shop in 1605 in what would later become Nova Scotia. But the role of the retail pharmacist has changed remarkably little. Hébert was the sole medical provider for what was then France’s only settlement in North America. He grew medicinal plants, bought and sold botanicals, and supervised the colony’s gardens. Retail pharmacy wasn’t much different in America’s first recorded pharmacy, opened in Wildwyck, New Netherland, in 1663. Gysbert Van Imbroch 14 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM launched a general store that sold drugs along with coal, pots, pans, and cast-iron stoves in what is now Kingston, N.Y. Fast-forward to 1912 and the opening of Morgan’s Pharmacy in the Washington, D.C., suburb of Georgetown. While pharmacy remains the core business today, OTC and front-end sales are key elements. One of c ur rent ow ner Ba r r y Deutschman’s prize artefacts is a copy of a receipt for a delivery to the White House in the early 1960s. The customer was famous, Jacqueline Kennedy; the delivery list includes staples such as aspirin, “Almay Face,” Revlon nail polish, and “spot strips.” A focus on healthcare, customers “Pharmacy has always been a retailoriented segment in the healthcare industry,” said Chuck Wilson, PharmD, COVER STORY CA R E FOR PAT I E N TS ’ E V E RY DAY N E E DS ST I L L T OP P R IOR I T Y vice president of operations for Health Mart, the independent pharmacy brand owned by McKesson. “ T he bu s i ne s s model has always focused on healthCHUCK WILSON care, but pharmacists have been business people as much as they have been healthcare providers. In some cases, the pharmacy has become almost a convenience store. People talk about the growing economic importance of the front end, but retail pharmacists have always looked after the whole person by helping them get well and stay healthy, as well as by taking care of everyday needs,” Wilson said. The business model That basic business model, which focused on drugs and catered to customers’ every need, first appeared in 754 AD in Baghdad and developed along with the disciplines of medicine and pharmacology in the centuries that followed. The endlessly flexible retail pharmacist model was soon adopted by Europe and then North America. By 1721, there were at least 14 apothecary shops in Boston. But it was Spain that licensed the first pharmacist in the Americas in New Orleans in 1769. And it was a 1770 edict from the Spanish governor of New Orleans, Don Alexandre O’Reilly, that first recognized pharmacy as a profession distinct from medicine and surgery in what would become the United States. Newspaper advertisements suggest that there were apothecaries in virtually every U.S. city by the end of the 18th century. Most physicians mixed and dispensed medications, and most pharmacists treated patients. In 1808, the Massachusetts Medical Society published its Massachusetts Pharmacopoeia, the nation’s first. The first US Pharmacopoeia appeared in 1820. When pharmacy changed forever The Philadelphia College of Pharmacy, created in 1821, changed pharmacy forever. The College published its first dispensatory in 1824, a cookbook of previously secret recipes for medications imported from England. Generic competition had arrived, and pharmacists across the growing country began concocting a growing stream of medications. American pharmacists couldn’t have asked for a better business model. About 170 different plant-based drugs from North America and another 50 from Latin America appeared on the 1820 USP or the National Formulary, published in 1888 by the American Pharmaceutical Association, now the American Pharmacists Association (APhA). But compounded botanical drugs varied widely in potency, even when made by expert pharmacists from the same recipe. The active ingredients in botanicals differ based on the specific variety, growing conditions, processing, storage, and other variables. Parke, Davis & Company transformed the practice and business of pharmacy with its first standardized pharmaceutical extract, Liquor Erogtae Purificatus, in 1879. Dupont, Lilly, Bayer, Pfizer, and a growing list of chemical companies rapidly expanded research and development programs to create and commercialize an ever-growing list of standardized pharmaceutical products and medication delivery systems. Gelatin capsules were first produced on a large scale in 1875, and then tablets and enteric-coated tablets in 1884. By 1900, most pharmacies carried manufactured medications and compounding was on the wane. William Procter, APhA’s first corresponding secretary, worried about this. “If the preparation of medicines is taken from the apothecary and he becomes merely the dispenser of them … he relapses into a simple shopkeeper,” Procter wrote. The rise of chain pharmacy For many retail pharmacists, that is exactly what happened. The growing availability of standardized, manufactured medicines and the growing ur- banization of America helped fuel the growth of drugstore chains. In 1901, Charles Walgreen Sr. bought a Chicago drugstore where he had worked as a pharmacist. By 1916 he had nine stores and the Walgreen Co. was born. Walgreen was as much a business innovator as he was a pharmacist. The merchandising and sales concepts that were fueling the rise of retail giants such as Sears and Montgomery Ward also fueled pharmacy growth and product innovation, although not always in the pharmacy department. In 1922, Walgreens introduced the malted milkshake and customers lined up three and four deep at the soda fountain. The chain opened four storefronts at the Chicago World Fair in 1933. Experiments in novel fixtures, layout, lighting techniques, and colors transformed pharmacy design across the industry. In 1950, Walgreen opened its first self-service store and became the largest self-service retailer in the country within three years. CVS, Rite Aid, Thrifty, Happy Harry’s, and other chains soon joined the fray. Retail pharmacists had the option to become part of the chain world or remain independent and compete with chains. Or they could go out of business. The retail pharmacist prospers “I’m a second-generation pharmacist, and I’ve been hearing about the imminent demise of the independent pharmacist for as long as I can remember,” said Justin Wilson, PharmD, who owns three pharmacies in Oklahoma. “Yes, we have lost some independents. A lot of that is pharmacy owners aging out of the business. And a lot is pharmacists who didn’t have the business acumen to JUSTIN WILSON survive. Not only do we take care of our patients, we do it in ways that pay the bills and lets us keep the doors open.” C O N T I N U E D O N P A G E 16 > DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 15 F ROM T H E PA ST T O T H E P R E SE N T Anniver sary Issue Competing with chains can be challenging, said Bradley Arthur, PharmD, owner of the Buffalo, N.Y.-based independent Black Rock Pharmacy. Competition also suggests other business opportunities. “We are starting to hear of pharmacists who are working in traditional physician office settings,” said Arthur, president of the National Community PharBRADLEY ARTHUR macists Association. “Progressive practices recognize that as healthcare reform continues to develop, they are going to be measured on outcomes — not on the quantity of activity they engage in, but the quality of that activity. A pharmacist is perfectly situated to help them improve quality. That is why, in a nutshell, I am a believer in moving pharmacy from the dispensing function to more comprehensive clinical services.” Health Mart’s Chuck Wilson has identified two key drivers that are influencing retail pharmacists. One driver is economic. Payers have been cutting dispensing fees for decades. Chains can compensate by increasing prescription volume and front-end sales. Independents can become more efficient in their dispensing operations and add clinical services. The other driver is the shift to valuebased payments. The Centers for Medicare and Medicaid Services (CMS) is leading the shift from payment for services to payment for outcomes. State Medicaid agencies are following their lead, and commercial payers are moving in similar directions. “Pharmacists are playing a much larger role in helping patients stay out of the hospital and out of the emergency room, but payment for those new roles isn’t keeping up,” Wilson said. “Pharmacists are being forced to create a much more efficient model at the point of care, so they can deliver all those services and still keep the doors open.” to look for [drug] interactions, examine adherence, educate patients, and deal with other potential problems before they happen. We are getting away from a commodity-based practice to one where we are part of the healthcare team and actively working with patients to improve their outcomes.” The first step is to redesign dispensing workflows using many of the tools chains have developed. Assembly-line workflows, robotics, and other tools can dramatically improve dispensing efficiency. Interactive voice response can handle up to 60% of phone calls, he said, which frees up clerks, technicians, and pharmacists. The extra time let him open a travel immunization service for patients who need special immunizations for overseas missions and other travel. He also expanded a basic diabetes care clinic to include insulin pumps and pump training. A hormone replacement therapy (HRT) program includes compounding. Medication therapy management can be an important contributor to cash flow. So can medication synchronization, which can dramatically improve adherence, cash flow, inventory turns, and patient outcomes. New avenues The University of California San Francisco created the first six-year PharmD program in 1955. Sixty years later, clinical services are a profitable reality. “We want our pharmacists out front, talking with patients,” said Justin Wilson. “We want them to have the time 1700 1800 Pharmacy Through the Years 1770 Spanish governor of New Orleans, Don Alexandre O’Reilly, recognizes pharmacy as a profession distinct from medicine/surgery 1721 1605 At least 14 apothecary shops established Parisian apothecary Louis Hébert opens first shop in Nova Scotia 1663 Dutch physician, Gysbert Van Imbroch, opens first pharmacy in Wildwyck, New Netherland 1824 1820 First US Pharmacopoeia 1769 First licensed pharmacist in the Americas in New Orleans 1821 1808 Massachussetts Medical Society produces the Massachussetts Pharmacopoeia 16 Philadelphia College of Pharmacy publishes first dispensatory DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM Philadelphia College of Pharmacy created 1833 First Dispensatory of the United States COVER STORY CA R E FOR PAT I E N TS ’ E V E RY DAY N E E DS ST I L L T OP P R IOR I T Y Into the future Regulatory change has boosted the movement toward clinical services. Twenty-five years ago, pharmacists rarely gave injections. Today, pharmacists routinely administer immunizations in all 50 states. “Immunization by pharmacists is really about access to healthcare,” said Stacie Maass, BS, JD, senior vice president of Pharmacy Practice and Government AfSTACIE MAASS fairs at the American Pharmacists Association (APhA). “Pharmacists are educated and trained to provide multiple clinical services that used to be available only in physician offices. The specific services you might want to provide depend on your business plan and the needs in your community.” Healthcare reform has created even more opportunities, including the growing acceptance of pharmacists as healthcare providers with direct reimbursement. Washington State has the most pharmacist-friendly provider regulations. Starting January 1, 2016, commercial 1879 Gelatin capsules produced on a large scale First standardized pharmaceutical extract scription drug measures for other providers are heavily weighted. Pharmacyrelated measures account for 48% of STAR ratings for stand-alone Part D Prescription Drug Plans (PDPs) and 17% for Medicare Advantage PDPs. Medication-related measures also count heavily for physician and healthsystem ratings. “My PSAO, my contracting entity, gives me my STAR rating report card every month,” Arthur said. “I can challenge our pharmacy staff to improve our quality performance. It’s just a matter of repurposing your assets in the store.” Justin Wilson is equally upbeat. Payers are moving toward pharmacist reimbursement as they recognize the true value of retail pharmacists. “As a pharmacist and a business owner, I just keep doing the things that are best for my patients,” he said. “If I make business decisions with that mindset, everything else seems to work itself out. If I’m doing what is right for my patients, I’m doing what’s right for my business. That’s how you make retail pharmacy successful.” Contributing Editor Fred Gebhart is based in Oregon. 1900 1875 health plans are required to cover services provided by a clinic-based pharmacist operating within their scope of practice if the same service is covered when provided by other healthcare professionals. Provider status rolls out to community pharmacists in 2017. “Washington is one of the broadest examples of pharmacists being paid for services within the commercial sector,” said Anne Burns, RPh, APhA’s vice president of Professional Affairs. “With immunizations as a model, we can see pharmacists providing a variety of patient services and being reimbursed for those services. There are even pilot programs on the horizon where pharmacists are helping to treat minor ailments under collaborative practice agreements or protocols [with physicians].” ANNE BURNS CMS is also boosting pharmacy services and reimbursement through its STAR ratings program that evaluates Part C and Part D health plan quality, access, and services for Medicaid recipients. Not only do pharmacies get STAR ratings; pre- 1963 CVS opens first store in Lowell, Mass. 1950 Walgreen opens first self-service store 1916 Walgreen Company consists of nine stores 1884 Tablets and entericcoated tablets produced 1888 American Pharmaceutical Association develops a National Formulary 1962 Rite Aid’s first store, Thrift D Discount Center, opens in Scranton, Penn. 1901 Charles Walgreen Sr. buys Chicago, Ill., drugstore where he had worked as a pharmacist 1922 Walgreens introduces malted milkshake DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 17 An Insulin of Today A stable activity profilea to last beyond 24 hours1 Once-daily Toujeo® should be injected at the same time each day. A different distribution profile than an equivalent dose of Lantus® (insulin glargine injection) 100 Units/mL1 1/3 the injection volume of standard insulin (100 Units/mL)1 3 Gradual release and consistent insulin levels1,2 2 1 GIR=glucose infusion rate. The pharmacodynamics of Toujeo® at steady state after 8 days of daily injections was evaluated against Lantus® in a euglycemic clamp study of patients with type 1 diabetes mellitus (T1DM) (N=30). The dose on day 8 was followed by a 36-hour euglycemic clamp.1,3 a 0 0 6 12 18 24 30 36 7 Toujeo® at steady state had a different activity profile than an equivalent dose of Lantus®, with a 27% lower GIR as measured by the 24-hour area under the curve1 7 Steady-state levels are reached by at least 5 days of once-daily injections1 7 Patients on Toujeo® may require a 10%-18% higher dose than patients on Lantus®1 Indications and Usage for Toujeo® Important Safety Information for (insulin glargine injection) 300 Units/mL Toujeo® (insulin glargine injection) 300 Units/mL Toujeo® is a long-acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus. Limitations of Use: Toujeo® is not recommended for treating diabetic ketoacidosis. Please see additional Important Safety Information for Toujeo® on the following pages. Please see brief summary of full Prescribing Information for Toujeo® on the following pages. Contraindications Toujeo® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to insulin glargine or any of its excipients. Warnings and Precautions Toujeo® contains the same active ingredient, insulin glargine, as Lantus®. The concentration of insulin glargine in Toujeo® is 300 units per mL. Insulin pens and needles must never be shared between patients. Do NOT reuse needles. Toujeo® offers today’s adult patients who require basal insulin: A1C Small precipitate and gradual release1,2 Reductions in a broad range of adult patients with diabetes1,b Proven safety profile1 Toujeo® COACH— tailored, integrated patient support Redesigned pen b Based on their previous anti-hyperglycemic therapy. Toujeo® provides consistent and significant A1C reductions in a once-daily dose1,c EDITION 3: T2DM insulin-naive EDITION 2: T2DM, previously treated with insulin and OADs EDITION 1: T2DM, previously treated with basal and mealtime insulin ± metformin A1C reduction A1C reduction A1C reduction -1.42% -1.46% Lantus® Toujeo® -0.73% -0.70% -0.90% Lantus® Toujeo® -0.87% Lantus® Toujeo® 7 In all studies Toujeo® met the primary endpoint (prespecified noninferiority margin of 0.4% and a 95% CI)1,4 c All studies were 26-week, open-label, controlled, titrate-to-target, noninferiority studies in adults with diabetes not at A1C goal (range: 7% to 10% or 11%), randomized to Toujeo® or Lantus® once daily. All patients were titrated to an FPG goal of 80-100 mg/dL. In EDITION 1, patients used Toujeo® with mealtime insulin analog ± metformin. In EDITION 2 and 3, patients used Toujeo® with OADs. T2DM=type 2 diabetes mellitus; OAD=oral antidiabetes drugs; FPG=fasting plasma glucose. d Severe hypoglycemia: event requiring assistance of another person to actively administer a resuscitative action. 1 Incidence of hypoglycemia in T2DM studies Severe,d Toujeo® with OADs regimen 0.9% to 1.0% e Severe,d Toujeo® with mealtime insulin regimen Documented symptomatic hypoglycemia in multiple studiese,f 8% to 37% 7 Most common adverse events with Toujeo® in T2DM patients: 7.1% nasopharyngitis, 5.7% upper respiratory infection Visit www.toujeopro.com for more information. References 1. Toujeo® Prescribing Information. May 2015. 2. Maiorino MI, et al. Expert Opin Biol Ther. 2014; 14(6):799-808. 3. Becker RHA, Dahmen R, et al. Diabetes Care. 2015;38(4):637-643. 4. Data on file, Sanofi US. kVDQRƓDYHQWLV86//&$OOULJKWVUHVHUYHG Documented symptomatic hypoglycemia: an event with typical symptoms of hypoglycemia accompanied by a self-monitored plasma glucose value ≤54 mg/dL. 5% 86*/7 f Toujeo® with OADs or with mealtime insulin regimen with or without metformin. Important Safety Information for Toujeo® (insulin glargine injection) 300 Units/mL Warnings and Precautions (cont’d) Monitor blood glucose in all patients treated with insulin. Modify insulin regimens cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral antidiabetic treatment. Changes in insulin regimen may result in hyperglycemia or hypoglycemia. Unit for unit, patients started on, or changed to,Toujeo® required a higher dose than patients controlled with Lantus®. When changing from another basal insulin to Toujeo®, patients experienced higher average fasting plasma glucose levels in the first few weeks of therapy until titrated to their individualized fasting plasma glucose targets. Higher doses were required in titrate-to-target studies to achieve glucose control similar to Lantus®. Hypoglycemia is the most common adverse reaction of insulin therapy, including Toujeo®, and may be life-threatening. Medication errors such as accidental mix-ups between basal insulin products and other insulins, particularly rapid-acting insulins, have been reported. Patients should be instructed to always verify the insulin label before each injection. Do not dilute or mix Toujeo® with any other insulin or solution. If mixed or diluted, the solution may become cloudy, and the onset of action/time to peak effect may be altered in an unpredictable manner. Do not administer Toujeo® via an insulin pump or intravenously because severe hypoglycemia can occur. Severe life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue Toujeo®, monitor and treat if indicated. A reduction in the Toujeo® dose may be required in patients with renal or hepatic impairment. As with all insulins,Toujeo® use can lead to life-threatening hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Closely monitor potassium levels in patients at risk of hypokalemia and treat if indicated. Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) with insulin.These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of TZD must be considered. Drug Interactions Certain drugs may affect glucose metabolism, requiring insulin dose adjustment and close monitoring of blood glucose. The signs of hypoglycemia may be reduced in patients taking anti-adrenergic drugs (eg, beta-blockers, clonidine, guanethidine, and reserpine). Adverse Reactions Adverse reactions commonly associated with Toujeo® include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema and weight gain. Important Safety Information for Toujeo® SoloStar® Toujeo® SoloStar® is a disposable prefilled insulin pen.To help ensure an accurate dose each time, patients should follow all steps in the Instruction Leaflet accompanying the pen; otherwise they may not get the correct amount of insulin, which may affect their blood glucose levels. Do not withdraw Toujeo® from the SoloStar® disposable prefilled pen with a syringe. Please see Brief Summary of Prescribing Information on the following pages. References: 1. Toujeo Prescribing Information. May 2015. 2. Becker RHA, Dahmen R, Bergmann K, Lehmann A, Jax T, Heise T. Diabetes Care. 2015;38(4):637-643. 3.'DWDRQ¿OH6DQR¿86 Brief Summary TOUJEO® (insulin glargine injection) U-300, for subcutaneous use Rx Only Brief Summary of Prescribing Information 1. INDICATIONS AND USAGE TOUJEO is indicated to improve glycemic control in adults with diabetes mellitus. Limitations of Use TOUJEO is not recommended for the treatment of diabetic ketoacidosis. 2. DOSAGE AND ADMINISTRATION 2.1 General Dosing Instructions Inject TOUJEO subcutaneously once a day into the abdominal area, thigh, or deltoid at the same time each day. Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy [See Adverse Reactions (6.1)]. Individualize and titrate the dosage of TOUJEO based on the individual’s metabolic needs, blood glucose monitoring results, and glycemic control goal. The dosage of TOUJEO ranges from 1 to 80 units per one injection. To minimize the risk of hypoglycemia titrate the dose of TOUJEO no more frequently than every 3 to 4 days. Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness to minimize the risk of hypoglycemia or hyperglycemia [see Warnings and Precautions (5.2), and Use in Specific Populations (8.5, 8.6)]. To minimize the risk of hypoglycemia, do not administer TOUJEO intravenously, intramuscularly or in an insulin pump. To minimize the risk of hypoglycemia, do not dilute or mix TOUJEO with any other insulin products or solutions. 2.2 Starting Dose in Insulin-Naïve Patients Type 1 Diabetes: The recommended starting dose of TOUJEO in insulin naïve patients with type 1 diabetes is approximately one-third to one-half of the total daily insulin dose. The remainder of the total daily insulin dose should be given as a short-acting insulin and divided between each daily meal. As a general rule, 0.2 to 0.4 units of insulin per kilogram of body weight can be used to calculate the initial total daily insulin dose in insulin naïve patients with type 1 diabetes. The maximum glucose lowering effect of a dose of TOUJEO may take five days to fully d il i li d i i li ï ti t ith t 1 di b t manifest and the first TOUJEO dose may be insufficient to cover metabolic needs in the first 24 hours of use [See Clinical Pharmacology (12.2) in the full prescribing information]. To minimize risks associated with insufficient insulinization when initiating TOUJEO, monitor glucose daily, titrate TOUJEO per instructions, and adjust co-administered glucose lowering therapies per standard of care. Type 2 Diabetes: The recommended starting dose of TOUJEO in insulin naïve patients with type 2 diabetes is 0.2 units per kilogram of body weight once daily. The dosage of other anti-diabetic drugs may need to be adjusted when starting TOUJEO to minimize the risk of hypoglycemia [See Warnings and Precautions (5.3)]. 2.3 Starting Dose in Patients with either Type 1 or Type 2 Diabetes Already on Insulin Therapy To minimize the risk of hypoglycemia when changing patients from a once daily long-acting or intermediate acting insulin product to TOUJEO, the starting dose of TOUJEO can be the same as the once daily long-acting dose. For patients controlled on LANTUS (insulin glargine, 100 units/mL) expect that a higher daily dose of TOUJEO will be needed to maintain the same level of glycemic control [see Clinical Pharmacology (12.2) in the full prescribing information and Clinical Studies (14.1) in the full prescribing information]. To minimize the risk of hypoglycemia when changing patients from twice-daily NPH insulin to once-daily TOUJEO, the recommended starting TOUJEO dose is 80% of the total daily NPH dosage. To minimize the risk of hyperglycemia when changing patients to TOUJEO, monitor glucose frequently in the first weeks of therapy titrate the dose of TOUJEO per instructions and the dose of other glucose lowering therapies per standard of care. [See Warning and Precautions (5.2) and Clinical Pharmacology Section (12.2) in the full prescribing information]. 2.4 Important Administration Instructions Prior to initiation of TOUJEO, patients should be trained by their healthcare professional on proper use and injection technique. Training reduces the risk of administration errors such as needle sticks and incomplete dosing. Patient should follow the Instructions for Use to correctly use the pen device and administer TOUJEO. Please see Brief Summary of full Prescribing Information for Toujeo® on the following pages. TOUJEO® (insulin glargine injection) U-300, for subcutaneous use Patients should be informed that the dose counter of the TOUJEO SoloStar disposable prefilled Patients pen should be the informed counter toof be theinjected. TOUJEO shows numberthatof the unitsdose of TOUJEO TheSoloStar TOUJEOdisposable SoloStar shows thespecifically number of designed units of TOUJEO to be injected. TOUJEO SoloStar prefilled pen has been for TOUJEO, thereforeThe no dose conversion is prefilled pen has been specifically designed therefore no dose conversion is required [Patient counseling information (17)forinTOUJEO, the full prescribing information]. required should [Patientbecounseling (17) inthe theTOUJEO full prescribing Patients instructed information to visually inspect solutioninformation]. for particulate matter and Patients should beprior instructed to visually inspect TOUJEO solutionisforclear particulate matter discoloration to administration and onlytheuse if the solution and colorless and discoloration prior to administration and only use if the solution is clear and colorless with no visible particles. with single no visible particles. For patient use only [see Warnings and Precautions (5.1)]. For single patient only [seeTOUJEO WarningsSoloStar and Precautions (5.1)]. Refrigerate unuseduse (unopened) prefilled pens. unused (unopened) TOUJEO SoloStar prefilled pens. 4. Refrigerate CONTRAINDICATIONS 4. CONTRAINDICATIONS TOUJEO is contraindicated: TOUJEO contraindicated: Duringis episodes of hypoglycemia [See Warnings and Precautions (5.3)]. During episodes of hypoglycemiato [See Precautions (5.3)]. [See Warnings In patients with hypersensitivity insulinWarnings glargine and or one of its excipients and In patients with hypersensitivity to insulin glargine or one of its excipients [See Warnings Precautions (5.5)]. and Precautions (5.5)]. 5. WARNINGS AND PRECAUTIONS 5. Never WARNINGS PRECAUTIONS 5.1 ShareAND a TOUJEO SoloStar pen Between Patients 5.1 Never Sharedisposable a TOUJEO SoloStar TOUJEO SoloStar prefilled penspen mustBetween never bePatients shared between patients, even if the TOUJEOis SoloStar prefilled must be shared patients, even if the needle changed.disposable Pen sharing posespens a risk for never transmission of between blood-borne pathogens. needleHyperglycemia is changed. Penorsharing poses a with risk for transmission of blood-borne 5.2 Hypoglycemia Changes in Insulin Regimen pathogens. 5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic Changes insulin strength, manufacturer, type, or method administration affect glycemic control andin predispose to hypoglycemia [see Warnings andofPrecautions (5.3)]may or hyperglycemia. control changes and predispose [seeand Warnings and Precautions (5.3)] or hyperglycemia. These should tobehypoglycemia made cautiously only under close medical supervision, and the These changes should be made cautiously andbeonly under close medical with supervision, and the frequency of blood glucose monitoring should increased. For patients type 2 diabetes, frequency of blood glucose monitoring be increased. Formay patients with type 2 diabetes, dosage adjustments of concomitant oralshould anti-diabetic products be needed. dosage concomitant anti-diabetic productseffect maythan be needed. On a unitadjustments to unit basis,ofTOUJEO has aoral lower glucose lowering LANTUS [See Clinical On a unit to unit(12.2) basis,inTOUJEO has a lowerinformation]. glucose lowering effecttrials, than patients LANTUSwho [Seechanged Clinical Pharmacology the full prescribing In clinical Pharmacology the full prescribing information]. clinicalfasting trials, patients who changed to TOUJEO from(12.2) otherinbasal insulins experienced higher In average plasma glucose levels to the TOUJEO from other basalcompared insulins experienced average fasting plasma glucose levels in first weeks of therapy to patients higher who were changed to LANTUS. To minimize in theriskfirstofweeks of therapy when compared to patients who monitor were changed LANTUS. minimize the hyperglycemia initiating TOUJEO glucoseto daily, titrateTo TOUJEO the risk oftohyperglycemia when initiating monitor glucose lowering daily, titrate TOUJEO according labeling instructions, and adjustTOUJEO co-administered therapies per accordingoftocare labeling adjust co-administered glucosedoses lowering therapieswere per standard [Seeinstructions, Dosage andand Administration (2.2, 2.3)]. Higher of TOUJEO standard of care [See Dosage and Administration (2.2, 2.3)]. Higher doses of TOUJEO were required to achieve similar levels of glucose control compared to LANTUS in clinical trials [see requiredStudies to achieve similar levels of glucose control compared to LANTUS in clinical trials [see Clinical (14.1) in the full prescribing information]. Clinical Studies (14.1) in the fulldevelops prescribing The onset of action of TOUJEO overinformation]. 6 hours following an injection. In type 1 diabetes The onsettreated of action developsthe over 6 hours following anofinjection. type 1 stopping diabetes patients withofIVTOUJEO insulin, consider longer onset of action TOUJEOIn before patients IV insulin, consider longer onset of action TOUJEO before IV insulin.treated The fullwith glucose lowering effectthe may not be apparent for atof least 5 days [Seestopping Dosage IV insulin. The full glucose lowering may not be(12.2) apparent for full at least 5 days [See Dosage and Administration (2.2) and Clinicaleffect Pharmacology in the prescribing information]. and Administration (2.2) and Clinical Pharmacology (12.2) in the full prescribing information]. 5.3 Hypoglycemia 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction associated with insulin, including TOUJEO. Hypoglycemia is the most adverse reaction with insulin, including Severe hypoglycemia cancommon cause seizures, may be associated life-threatening or cause death. TOUJEO. HypoglySeverecan hypoglycemia can cause seizures, may betime; life-threatening or an cause death.and Hypoglycemia impair concentration ability and reaction this may place individual others cemia concentration abilityabilities and reaction time; this may an individual and others at riskcan in impair situations where these are important (e.g.,place driving, or operating other at risk in situations wherecanthese abilities are important (e.g., may driving, other machinery). Hypoglycemia happen suddenly and symptoms differorin operating each individual machinery). Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, lesspatients pronounced patients with diabetes, innervous patients system with diabetic disease, in using inmedications thatlongstanding block the sympathetic (e.g., nerve beta-blockers) in patients using medications block thewho sympathetic system (e.g., beta-blockers) [See Drug Interactions (7)], orthat in patients experiencenervous recurrent hypoglycemia. [See Factors Drug Interactions (7)], or in patients who experience recurrent hypoglycemia. Risk for Hypoglycemia Risk timing Factorsof for Hypoglycemia The hypoglycemia usually reflects the time-action profile of the administered insulin The timing ofAshypoglycemia reflectsthe theglucose time-action profile of the insulin formulation. with all insulinusually preparations, lowering effect timeadministered course of TOUJEO formulation. As with all insulin preparations, glucose effect time of TOUJEO may vary in different individuals or at differentthe times in thelowering same individual andcourse depends on many may vary in different different times in the individualsite andblood depends on many conditions, includingindividuals the area orofatinjection as well as same the injection supply and conditions, including the Pharmacology area of injection as prescribing the injection site bloodOther supply and temperature [see Clinical (12.2)asinwell the full information]. factors temperature [see Clinical Pharmacology (12.2) ininclude the fullchanges prescribing information]. Other macrofactors which may increase the risk of hypoglycemia in meal pattern (e.g., which may increase the riskof ofmeals), hypoglycemia in meal patternor(e.g., macronutrient content or timing changesinclude in levelchanges of physical activity, changes to nutrient content medication or timing [see of meals), changes in(7)].level of physical or changes to co-administered Drug Interactions Patients with renalactivity, or hepatic impairment co-administered [see Drug Interactions (7)].Specific PatientsPopulations with renal or(8.5, hepatic may be at highermedication risk of hypoglycemia [see Use in 8.6)].impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.5, 8.6)]. Risk Mitigation Strategies for Hypoglycemia Risk Mitigation Strategiesmust for Hypoglycemia Patients and caregivers be educated to recognize and manage hypoglycemia. SelfPatients and mustplays be educated to recognize manage and hypoglycemia. monitoring of caregivers blood glucose an essential role in theand prevention managementSelfof monitoring of blood glucoseat plays role in the and prevention of hypoglycemia. In patients higheranriskessential for hypoglycemia patientsand whomanagement have reduced hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring recommended. To minimize the risk of hypoglycemia do not administer TOUJEO intravenously,is recommended. To minimize the pump risk oforhypoglycemia not administer intravenously, intramuscularly or in an insulin dilute or mixdo TOUJEO with anyTOUJEO other insulin products intramuscularly or solutions. or in an insulin pump or dilute or mix TOUJEO with any other insulin products or solutions. 5.4 Medication Errors 5.4 Medication Accidental mix-upsErrors between basal insulin products and other insulins, particularly rapid-acting Accidental mix-ups insulin productserrors and other insulins, particularly rapid-acting insulins, have been between reported.basal To avoid medication between TOUJEO and other insulins, insulins,patients have been reported. To avoid medication TOUJEO and other insulins, instruct to always check the insulin label errors beforebetween each injection. instructHypersensitivity patients to always the insulin label before each injection. 5.5 andcheck Allergic Reactions 5.5 Hypersensitivity Allergic Reactions Severe, life-threatening,and generalized allergy, including anaphylaxis, can occur with insulin Severe, life-threatening, generalized allergy, including anaphylaxis, can TOUJEO; occur withtreat insulin products, including TOUJEO. If hypersensitivity reactions occur, discontinue per products, ofincluding TOUJEO. hypersensitivity reactions occur, discontinue TOUJEO; treat(6)]. per standard care and monitor Ifuntil symptoms and signs resolve [See Adverse Reactions standard ofis care and monitorinuntil symptoms [See Adverse Reactions (6)]. TOUJEO contraindicated patients who and havesigns had resolve hypersensitivity reactions to insulin TOUJEO is contraindicated in patients who have had hypersensitivity reactions to insulin glargine or other of the excipients [See Contraindications (4)]. glargine or other of the excipients [See Contraindications (4)]. 5.6 Hypokalemia 5.6 insulin Hypokalemia All products, including TOUJEO, cause a shift in potassium from the extracellular to All insulin products, including leading TOUJEO,to cause a shift inUntreated potassiumhypokalemia from the extracellular to intracellular space, possibly hypokalemia. may cause intracellular space, possibly to hypokalemia. Untreated hypokalemia cause respiratory paralysis, ventricularleading arrhythmia, and death. Monitor potassium levels inmay patients at respiratory paralysis, ifventricular andusing death. Monitor potassiummedications, levels in patients at risk for hypokalemia indicated arrhythmia, (e.g., patients potassium-lowering patients risk formedications hypokalemiasensitive if indicated (e.g., patients using potassium-lowering medications, patients taking to serum potassium concentrations). taking Fluid medications sensitive to serum potassium concentrations). 5.7 Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists 5.7 Fluid Retention andwhich Heartare Failure with Concomitant Use of PPAR-gamma Agonists Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor (PPAR)-gamma Thiazolidinediones (TZDs), whichare peroxisome proliferator-activated receptor (PPAR)-gamma agonists, cancause dose-related fluid retention,particularly whenused in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including TOUJEO, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered. 6. ADVERSE REACTIONS The following adverse reactions are discussed elsewhere: Hypoglycemia [See Warnings and Precautions (5.3)] Hypersensitivity and allergic reactions [See Warnings and Precautions (5.5)] Hypokalemia [See Warnings and Precautions (5.6)] 6.1 Clinical trial experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates actually observed in clinical practice. The data in Table 1 reflect the exposure of 304 patients with type 1 diabetes to TOUJEO with mean exposure duration of 23 weeks. The type 1 diabetes population had the following characteristics: Mean age was 46 years and mean duration of diabetes was 21 years. Fifty five percent were male, 86% were Caucasian, 5 % were Black or African American and 5 % were Hispanic. At baseline, the mean eGFR was 82 mL/min/1.73m2 and 35% of patients had eGFR≥90 mL/min/1.73m2. The mean BMI was 28 kg/m2. HbA1c at baseline was greater or equal to 8% in 58% of patients. The data in Table 2 reflect the exposure of 1242 patients with type 2 diabetes to TOUJEO with mean exposure duration of 25 weeks. The type 2 diabetes population had the following characteristics: Mean age was 59 years and mean duration of diabetes was 13 years. Fifty three percent were male, 88% were Caucasian, 7% were Black or African American and 17% were Hispanic. At baseline, mean eGFR was 79 mL/min/1.73m2 and 27% of patients had an eGFR≥90 mL/min/1.73m2. The mean BMI was 35 kg/m2. HbA1c at baseline was greater or equal to 8% in 66% of patients. Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Common adverse reactions occurring for TOUJEO-treated subjects during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in Table 1 and Table 2, respectively. Hypoglycemia is discussed in a dedicated subsection below. Table 1: Adverse reactions in two pooled clinical trials of 26 weeks and 16 weeks duration in adults with type 1 diabetes (with incidence ≥5%) TOUJEO + mealtime insulin*, % (n=304) Nasopharyngitis 12.8 Upper respiratory tract infection 9.5 *″mealtime insulin″ refers to insulin glulisine, insulin lispro, or insulin aspart Table 2: Adverse reactions in three pooled clinical trials of 26 weeks duration in adults with type 2 diabetes (with incidence ≥5%) TOUJEO*, % (n=1,242) Nasopharyngitis 7.1 Upper respiratory tract infection 5.7 *one of the trials in type 2 diabetes included mealtime insulin Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including TOUJEO [See Warnings and Precautions (5.3)]. In the TOUJEO program, severe hypoglycemia was defined as an event requiring assistance of another person to administer a resuscitative action and documented symptomatic hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by a self-monitored or plasma glucose value equal to or less than 54 mg/dL. The incidence of severe hypoglycemia in patients with type 1 diabetes receiving TOUJEO as part of a multiple daily injection regimen was 6.6% at 26 weeks. The incidence of documented symptomatic hypoglycemia was 69% at 26 weeks. There were no clinically important differences in hypoglycemia between TOUJEO and LANTUS among type 1 diabetes patients. The incidence of severe hypoglycemia in patients with type 2 diabetes was 5% at 26 weeks in patients receiving TOUJEO as part of a multiple daily injection regimen, and 1.0% and 0.9% respectively at 26 weeks in the two studies where patients received TOUJEO as part of a basal-insulin only regimen. The incidence of documented symptomatic hypoglycemia in patients with type 2 diabetes receiving TOUJEO ranged from 8% to 37% at 26 weeks and the highest risk was again seen in patients receiving TOUJEO as part of a multiple daily injection regimen. Insulin initiation and intensification of glucose control Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy. Peripheral Edema Insulin, including TOUJEO, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Lipodystrophy Long-term use of insulin, including TOUJEO, can cause lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients and may affect insulin absorption [see Dosage and Administration (2.1)]. Weight gain Weight gain has occurred with some insulin therapies including TOUJEO and has been attributed to the anabolic effects of insulin and the decrease in glucosuria. Allergic Reactions Some patients taking insulin therapy, including TOUJEO have experienced erythema, local edema, and pruritus at the site of injection. These conditions were usually self-limiting. Severe cases of generalized allergy (anaphylaxis) have been reported [See Warnings and Precautions (5.5)]. Cardiovascular Safety No clinical studies to establish the cardiovascular safety of TOUJEO have been conducted. A cardiovascular outcomes trial, ORIGIN, has been conducted with LANTUS. It is unknown whether the results of ORIGIN can be applied to TOUJEO. The Outcome Reduction with Initial Glargine Intervention trial (i.e., ORIGIN) was an open-label, randomized, 12,537 patient study that compared LANTUS to standard care on the time to first occurrence of a major adverse cardiovascular event (MACE). MACE was defined as the composite of CV death, nonfatal myocardial infarction and nonfatal stroke. The incidence of MACE was similar between LANTUS and standard care in ORIGIN [Hazard Ratio (95% CI) for MACE; 1.02 (0.94, 1.11)]. In the ORIGIN trial, the overall incidence of cancer (all types combined) [Hazard Ratio (95% CI); 0.99 (0.88, 1.11)] or death from cancer [Hazard Ratio (95% CI); 0.94 (0.77, 1.15)] was also similar between treatment groups. 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. In a 6-month study of type 1 diabetes patients, 79% of patients who received TOUJEO once daily were positive for anti-insulin antibodies (AIA) at least once during the study, including 62% that were positive at baseline and 44% of patients who developed anti-drug antibody [i.e., anti-insulin glargine antibody (ADA)] during the study. Eighty percent of the AIA positive patients on TOUJEO with antibody test at baseline, remained AIA positive at month 6. In two 6-month studies in type 2 diabetes patients, 25% of patients who received TOUJEO once daily were positive for AIA at least once during the study, including 42% who were positive at baseline and 20% of patients who developed ADA during the study. Ninety percent of the AIA positive patients on TOUJEO with antibody test at baseline, remained AIA positive at month 6. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to TOUJEO with the incidence of antibodies in other studies or to other products, may be misleading. 7. DRUG INTERACTIONS 7.1 Drugs That May Increase the Risk of Hypoglycemia The risk of hypoglycemia associated with TOUJEO use may be increased with antidiabetic agents, (ACE) inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics. Dose adjustment and increased frequency of glucose monitoring may be required when TOUJEO is co-administered with these drugs. 7.2 Drugs That May Decrease the Blood Glucose Lowering Effect of TOUJEO The glucose lowering effect of TOUJEO may be decreased when co-administered with atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isonazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline) and thyroid hormones. Dose adjustment and increased frequency of glucose monitoring may be required when TOUJEO is co-administered with these drugs. 7.3 Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of TOUJEO The glucose lowering effect of TOUJEO may be increased or decreased when co-administered with alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Dose adjustment and increased frequency of glucose monitoring may be required when TOUJEO is co-administered with these drugs. 7.4 Drugs That May Affect Signs and Symptoms of Hypoglycemia The signs and symptoms of hypoglycemia [see Warnings and Precautions (5.3)] may be blunted when beta-blockers, clonidine, guanethidine, and reserpine are co-administered with TOUJEO. 8. USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control. It is essential for patients with diabetes or a history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. In patients with diabetes or gestational diabetes, insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential in these patients. Therefore, female patients should be advised to tell their physicians if they intend to become, or if they become pregnant while taking TOUJEO. Human data There are no clinical studies of the use of TOUJEO in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal data Subcutaneous reproduction and teratology studies have been performed with insulin glargine and regular human insulin in rats and Himalayan rabbits. Insulin glargine was given to female rats before mating, during mating, and throughout pregnancy at doses up to 0.36 mg/kg/day, which is approximately 50 times the recommended human subcutaneous starting dose of 0.2 Units/kg/day (0.007 mg/kg/day). In rabbits, doses of 0.072 mg/kg/day, which is approximately 10 times the recommended human subcutaneous starting dose of 0.2 Units/kg/day (0.007 mg/kg/day), were administered during organogenesis. The effects of insulin glargine did not generally differ from those observed with regular human insulin in rats or rabbits. However, in rabbits, five fetuses from two litters of the high-dose group exhibited dilation of the cerebral TOUJEO® (insulin glargine injection) U-300, for subcutaneous use ventricles. Fertility and early embryonic development appeared normal. 8.3 Nursing Mothers Endogenous insulin is present in human milk; it is unknown whether insulin glargine is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when TOUJEO is administered to a nursing woman. Use of TOUJEO is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses. 8.4 Pediatric Use The safety and effectiveness of TOUJEO have not been established in pediatric patients. 8.5 Geriatric Use In controlled clinical studies, 30 of 304 (9.8%) TOUJEO treated patients with type 1 diabetes and 327 of 1242 (26.3%) TOUJEO treated patients with type 2 diabetes were ≥65 years of age, among them 2.0 % of the patients with type 1 and 3.0% of the patients with type 2 diabetes were ≥75 years of age. No overall differences in effectiveness and safety were observed in the subgroup analyses across the age groups. Nevertheless, caution should be exercised when TOUJEO is administered to geriatric patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia [See Warnings and Precautions (5.3), Adverse reactions (6) and Clinical Studies (14) in the full prescribing information]. 8.6 Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of TOUJEO has not been studied. Frequent glucose monitoring and dose adjustment may be necessary for TOUJEO in patients with hepatic impairment [See Warnings and Precautions (5.3)]. 8.7 Renal Impairment The effect of renal impairment on the pharmacokinetics of TOUJEO has not been studied. Some studies with human insulin have shown increased circulating levels of insulin in patients with renal failure. Frequent glucose monitoring and dose adjustment may be necessary for TOUJEO in patients with renal impairment [See Warnings and Precautions (5.3)]. 8.8 Obesity No overall differences in effectiveness and safety were observed in subgroup analyses based on BMI. 10. OVERDOSAGE Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.6)]. Mild episodes of hypoglycemia can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or physical activity level may be needed. More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately. sanofi-aventis U.S. LLC Bridgewater, NJ 08807 A SANOFI COMPANY ©2015 sanofi-aventis U.S. LLC LANTUS, TOUJEO and SoloStar are registered trademarks of sanofi-aventis U.S. LLC. GLR-BPLR-SA-SEP15 Revised: September 2015 Anniver sary Issue Through the Decades 1910-1920: A magazine for the druggist, drug clerk, and drug trade Julia Talsma, Content Channel Director In the early part of the 20th century, drug wholesaler McKesson & Robbins published Drug Topics as a pocket-sized magazine boasting a monthly circulation of more than 12,000. It retailed at an annual subscription cost of 25 cents. With a primary mission to educate, improve, and entertain the druggist, drug clerk, and drug trade in general, Drug Topics’ tidbits of advice for the retailer were timely and practical approaches for boosting drugstore sales, including sales of products manufactured by publisher McKesson & Robbins. Making the most of the weather For example, in a 1919 feature, Drug Topics lauded February as the druggist’s bonanza month. Even though “February is a dour month” because of the weather, the editor noted, “it could be a grand month for the druggist if he is alive to its opportunities in a business way,” with customers celebrating its various anniversaries and holidays — Groundhog Day, Lincoln’s and Washington’s birthdays, Longfellow’s birthday, and of course, Valentine’s Day. In addition to the sale of souvenirs and novelties, the editor advised, druggists should C O N T I N U E D O N P A G E 24 > A HOUSE ORGAN: During the early part of the 20th century, McK & R Drug Topics, published as a house organ by drug wholesaler McKesson and Robbins until 1922, peppered its pages with advertisements of its own offerings, such as the Clean-OPore Vacuum Massage Outfit (above). Druggists also were introduced to products still around today, such as Listerine and licorice. (Images from Drug Topics archives). DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 23 Anniver sary Issue prominently display seasonable items for soothing “coughs, colds, sore throats, chilblains, chapped hands, grippe, and many other severe and minor ailments.” Pushing the product Inside the issue, McKesson & Robbins cleverly ran advertisements designed to drive druggists to its own offerings, like Strickly Pure Old-Fashioned Horehound Drops, Horehound Herb Tea, Pure Granulated Sugar, and Wild Cherry Drops to “tickle the palate and ease a tickle in the throat.” The Great War Drug Topics also followed the events leading up to America’s participation in World War I, also known as the Great War, and its impact on drug and chemical imports with “The Market Report.” In this column, the editor warned that with few suppliers of chemicals in the United States in 1917 and the impending U.S. participation in the war effort, the price of imported materials would increase. Scare items in early April 1917 included citric acid, phosphoric acid, salicylic acid, antipyrine, arsenic, soap bark, ergot, licorice root, and sulphur. Business advice Despite these hardships, Drug Topics’ editor had plenty of advice to offer enterprising drugstore businesses seeking to boost trade, with features on subjects such as how to win the patronage of a soldier’s family; why the well-managed store makes an ideal place for a business education; and ways to save money by “Making a Drug Store Pay.” The editor also suggested ways for drugstores to achieve larger profits through such practices as publishing weekly advertising circulars, offering charge accounts, soliciting business from manufacturing plants, and remembering customers’ birthdays — all still good advice today. 24 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM 160th Anniversary Quiz Calling all history buffs To commemorate the 160th anniversary of Drug Topics, we have created the following contest for you pharmacy history buffs. Hint: The answers to the quiz can be found within the Special Anniversary issue. Go to www.drugtopics. com/160quiz to take the quiz and enter to win one of three $50 VISA cards. Next month, we will publish the answers and the names of the lucky winners. (Winners will be chosen randomly from the group of correct entries.) 1. The first American apothecary set up shop in 1605. This medical provider came from which European country? A. England B. The Netherlands C. France D. Spain 2. In 1769, the fi rst pharmacist in the Americas was licensed in what U.S. city? A. Boston, Mass. B. Kingston, N.Y. C. Philadelphia, Penn. D. New Orleans, La. 3. Which company transformed the practice and business of pharmacy with its fi rst standardized pharmaceutical extract, Liquor Erogtae Purificatus? A. Parke, Davis & Company B. E. I. du Pont de Nemours and Company C. Eli Lilly and Company D. Pfizer Inc. 4. Which drugstore introduced the malted milkshake? A. Happy Harry’s B. Black Rock Pharmacy C. Walgreens D. CVS 5. In 1955, which academic institution created the fi rst 6-year PharmD program? A. Philadelphia College of Pharmacy B. The University of California, San Francisco C. The Ohio State University College of Pharmacy D. University of North Carolina–Chapel Hill Good luck! Take the Quiz at NEW DRUG REVIEW DISORDER AT SE XUAL DESIRE FLIBANSERIN> TO TRE pg. 37 ® www.drugtopics.com/160QUIZ DrugTopics.com 160 Vol. 160 2016 || Vol. February February 2016 No. No. 22 Y ISSUE 1856-2016 SPECIAL ANNIVERSAR D From Apothecary to Pharm VOICES Download the Free App to Take the Quiz and for More of Our Legacy Images and stories. www.drugtopics.com/drugtopicsapp d MD ersus RPh 6 DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 25 ISSUES & TRENDS Anniver sary Issue Lucinda L. Maine, RPh, PhD Specialized training puts pharmacists front and center As we consider how the profession of pharmacy has changed over the past 160 years — and how much it might change in the near future — I want to note the profound changes made in pharmacy education over these 16 decades. Elements of our history seem to be coming full circle. Physicians played a key role in formalizing pharmacy education in the mid-19th century, because they were concerned with the quality of drug products. They recognized the importance of ensuring the integrity of medicines, and they took the initiative in molding a profession with the skills and knowledge needed to prepare and distribute high-quality medications. Today, physicians increasingly recognize the need to take advantage of pharmacists’ expertise when faced with the complexity of medication management — especially for patients with multiple chronic conditions. Transition and change The changes in education over just the last 60 years underscore that we have, indeed, advanced as a profession. This becomes clear in the context of the APhA Code of Ethics, which from 1929 until 1969 stated: “Pharmacists should never discuss the therapeutic effect of a physician’s prescription with a patron or disclose details of the composition which the physician has withheld.” After decades on the front lines of patient care, pharmacists were told to stop “counterprescribing” — and state law even prohibited placement of drug names on the prescription labels. This was a challenging time in pharmacy practice, a time when more prefabricated medications were coming to market and when the effectiveness and actions of many medicinal products were often unclear. 26 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM Reimagining the profession As pharmacists found their compounding duties shrinking, pharmacy educators began to reimagine the curriculum. And education and practice leaders began to accumulate evidence indicating that medication errors could harm patients when pharmacists’ roles were limited. A multiyear study of the profession, released in 1949, represented a turning point in thought leadership about pharmacy education and practice. The report recommended increasing the prepharmacy coursework to increase both scientific rigor and general education requirements. It also encouraged an evolution of the core pharmacy curriculum in keeping with changes in other professions. By the early 1960s, the degree advanced from a four-year BS to a fiveyear degree. In 1969, the APhA Code of Ethics revision markedly changed the profession’s ethical commitment to patients and society, stating, “A pharmacist should always strive to perfect and enlarge his knowledge. He should utilize and make available this knowledge as may be required in accordance with his best judgment.” The change from “should never discuss” to “should make available” was a 180-degree shift for the pharmacist and patient care. Fortunately, pharmacy education had begun to introduce important changes that would help prepare graduates for their new role. year Doctor of Pharmacy curriculum, thereby ushering in the clinical pharmacy movement. In the 1970s, fueled by federal funds to stimulate enrollments across the health professions, schools of pharmacy hired the first clinical faculty members and began to expand the focus on therapeutics within the curriculum. Many schools began to offer post-baccalaureate PharmD degrees as well. In the late 1990s, the issue of credentialing that had been raised in 1949 was finally resolved. A single degree standard affirmed that a doctoral level of education was necessary for 21st century pharmacy professionals. A more proactive patient management role for pharmacists was beginning. Healthier, better Doctor of Pharmacy The last revision of the APhA Code of Ethics, released in 1994, stressed the evolution in education and practice: “Considering the patient-pharmacist relationship as a covenant means that a pharmacist has moral obligations in response to the gift of trust received from society. In return for this gift, a pharmacist promises to help individuals achieve optimum benefit from their medications, to be committed to their welfare, and to maintain their trust.” Contemporary pharmacy education is grounded in this relationship and in the role of the pharmacist as a patient advocate. As we say, “Pharmacists help people live healthier, better lives.” California schools did not make the fouryear-to-five-year BS transition; instead, in the late 1950s they introduced the six- Lucinda Maine is executive V.P. and CEO, American Association of Colleges of Pharmacy. PRODUCT UPDATES NEW PRODUCTS Julianne Stein, Content Channel Manager 1 PRODUCT IMAGES COURTESY OF NOVO NORDISK / NOVARTIS / ALLERGAN RX CARE: New drugs Late in January, FDA approved Merck’s once-a-day combo pill elbasvir/grazoprevir (Zepatier), to be used with or without ribavirin for treatment of chronic hepatitis C (HCV) genotypes 1 and 4. Zepatier was granted breakthrough-therapy designation for treatment of chronic HCV genotype 1 infection in hemodialysis patients with end-stage renal disease and for treatment of chronic HCV genotype 4 infection. The most common side effects were fatigue, headache, and nausea when taken without ribavirin and anemia and headache with ribavirin. This product carries a warning about elevated liver enzymes. Liver-related blood tests should be performed before therapy begins and continue through treatment. Patients with moderate or severe liver impairment should not take this drug. (www.zepatier.com) Toward the end of January, Novo Nordisk announced the nationwide availability of its newest insulin injection, insulin degludec injection 200 units/mL 1 (Tresiba), approved by FDA in September 2015 to improve glycemic control in adults with diabetes. Tresiba will be available in the FlexTouch pen device in 100 units/mL or 200 units/mL. It is designed to last at least 42 hours after 2 3 once-a-day injection, enabling patients to schedule doses at their convenience. Novo Nordisk is offering a Tresiba Instant Savings Card that can lower co-pays to as little as $15 for 24 months for qualifying patients with commercial insurance. (www.tresibapro.com) Eisai’s chemotherapy drug eribulin mesylate (Halaven) was approved in late January. Described as the first drug to show survival benefit in liposarcoma, a soft-tissue sarcoma appearing in fat cells, it is indicated to treat unresectable or metastatic conditions in patients who have already been treated with an anthracycline drug. In clinical trials, this therapy extended survival an additional seven months beyond the comparative treatment. Halaven was given orphan drug status and priority review. (www.halaven.com) available in a single-use pen, prefilled syringes, and vials of lyophilized powder for subcutaneous injection. A Medication Guide accompanies this product. The Cosentyx Connect Personal Support Program provides assistance to eligible patients experiencing financial hardship. (www.cosentyx.com) Allergan has announced recent FDA approval of onabotulinumtoxinA injection 3 (Botox) to treat ankle and toe spasticity in adult stroke patients. Botox was first approved in 2010 for treatment of spastic muscle groups in the elbow, wrist, fingers, and in April 2015 for treatment of two thumb muscles. A boxed warning cites problems with swallowing, speaking, or breathing, and spread of toxin effects beyond the injection site. It also carries a Medication Guide. (www.botoxinfo.com) New Indications New Formulations FDA has approved two new indications for Novartis’ secukinumab 2 (Cosentyx), a human interleukin-17A antagonist first approved in January 2015 for treatment of adult patients with moderate-to severe-plaque psoriasis. The new indications are for treatment of adult patients with active ankylosing spondylitis and active psoriatic arthritis. Cosentyx is Impax Laboratories has announced FDA approval of its chewable 100-mg tablet formulation of the anthelmintic mebendazole (Emverm) for treatment of pinworm, whipworm, common roundworm, common hookworm, and American hookworm. The product is said to have a clinical cure rate of 95%. Organ system functions, including hemato- DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 27 PRODUCT UPDATES NEW PRODUCTS poietic and hepatic, should be assessed periodically during prolonged therapy. Release is scheduled for the second quarter of 2016. (www.impaxlabs.com) FDA has approved Takeda’s Dexilant SoluTab 4 , a delayed-release orally disintegrating dexlansoprazole tablet indicated to treat heartburn associated with gastroesophageal reflux disease. Dexilant SoluTab is a proton pump inhibitor (PPI) designed to provide two separate releases of medication with its dual delayed release (DDR) technology. Dexilant is also available in 30-mg and 60-mg delayed-release capsules. (www.takeda.com) New Generics FDA has approved Neos Therapeutics’ once-daily Adzenys XR-ODT, the first and only orally disintegrating extendedrelease tablet, for treatment of ADHD in patients six years of age and older. Bioequivalent to Shire’s amphetamine Adderall XR, the product will be available in six dosage strengths of 5, 10, 15, 20, 25, and 30 mg. A boxed warning cites high potential for abuse and dependence. (www.neostx.com) In January, FDA approved Aurobindo’s norethindrone acetate tablets 5 mg, a generic equivalent of Duramed Phar- 28 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM 5 maceuticals’ Aygestin tablets, indicated to treat secondary amenorrhea, endometriosis, and abnormal uterine bleeding. (www.aurobindo.com) In the same week in January, FDA approved Aurobindo’s famotidine tablets 20 mg and 40 mg, a generic version of Valeant’s Pepcid tablets, used to treat an active duodenal ulcer, an active benign gastric ulcer, and gastroesophageal reflux disease (GERD). It is also is used as maintenance therapy for duodenal ulcer patients after an active ulcer heals and as treatment of certain other hypersecretory conditions. (www.aurobindo.com) FDA also has approved Aurobindo’s paricalcitol capsules, described as bioequivalent and therapeutically equivalent to Abbvie’s Zemplar capsules, used to treat high levels of parathyroid hormone in certain patients with chronic kidney disease. The drug will be available in dosage strengths of 1, 2, and 4 mcg. (www.aurobindo.com) Greenstone has launched colestipol hydrochloride granules for oral suspension, its authorized generic version of Pfizer’s Colestid, for treatment of high cholesterol. The product will be available in cartons containing 30 5-g foils, 90 5-g foils, and in 500-g bottles that come with a scoop. (www.greenstonellc.com) Greenstone also has launched linezolid tablets 600 mg 5 , its authorized generic version of Pfizer’s Zyvox. The drug is indicated to treat certain infections caused by susceptible Gram-positive bacteria in adults and children. (www.greenstonellc.com) Mylan too is launching linezolid tablets in the 600-mg strength, to treat bacterial infections. (www.mylan.com) Mylan also is launching felbamate tablets 400 mg and 600 mg, generic for Meda’s Felbatol, indicated to treat seizures. (www.mylan.com) Lupin has launched its norgestimate/ ethinyl estradiol tablets (Tri-Lo-Marzia), generic for Janssen’s Ortho Tri-Cyclen Lo contraceptive product. (www. lupinpharmaceuticals.com) Teva has launched Tri-Lo-Sprintec, its own generic norgestimate/ethinyl estradiol version of Janssen’s Ortho Tri-Cyclen Lo. (www.tevapharm.com) Dr. Reddy’s has announced the U.S. relaunch of its esomeprazole magnesium delayed-release capsules, generic for AstraZeneca’s Nexium delayedrelease capsules for treatment of GERD and ulcers. The relaunch is due to a change in capsule color. (www.drreddys.com) PRODUCT IMAGES COURTESY OF TAKEDA / GREENSTONE 4 Your lifeline for quality, integrity and value in generics From discovery to delivery, Camber is dedicated to providing the highest quality generics, at the most affordable prices. ® Camber Pharmaceuticals, Inc. | Phone 732.529.0430 | camberpharma.com PRODUCT UPDATES ORAL CARE Mark Lowery, Content Editor 1 2 OTC Proper oral care, including toothbrushing and other practices designed to reduce plaque and bacteria, is aesthetically important. Even more important, it helps prevent ailments that start in the mouth and move elsewhere throughout the body. That’s true for both children and adults. However, getting children to practice proper oral hygiene can be challenging at times. According to the Centers for Disease Control and Prevention, tooth decay is four times more common than asthma among adolescents aged 14 to 17 years. Amid the multitude of oral-care products for children and adults to be found on pharmacy shelves are numerous items designed to help parents teach children proper oral care. Toothbrushes and more tKolibree’s smart sonic toothbrush with 3D motion sensors uses games to 30 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM teach young children how to brush their teeth properly. With four new games that show children where they brushed and where they missed, Kolibree’s sonic toothbrush only weighs 2.5 ounces. t%FTJHOFEFTQFDJBMMZGPSDIJMESFOXJUI braces, Kolibree’s orthodontic brush head helps them brush more easily, safely, and gently around the brackets to help prevent post-orthodontia cavities. “The Kolibree platform strengthens the dentist-patient relationship by allowing parents to digitally share family brushing habits with their dentist as part of a personalized approach to preventive dental care,” said Thomas Serval, Kolibree’s founder and CEO. t5IFPhilips Sonicare for Kids is a rechargeable toothbrush equipped with Bluetooth wireless technology. Connected to a free coaching app that helps children learn proper brushing techniques, the toothbrush encourages them to brush for two minutes and allow parents to monitor progress. According to Philips, 98% of the parents whose children used Sonicare for Kids said the toothbrush made it easier for their children to brush longer and better. tBrush Buddies’ Soniclean Pro One 1 features sonic technology that offers 30,000 vibrations per minute. Used properly, it promises to remove more plaque than a manual toothbrush would do and provide a fresh, clean feeling. Its end-rounded nylon bristles are specially designed to clean the outer layers of the teeth, while the rubberized polishing cups in the middle are made to polish teeth. “The Soniclean Pro One will get your teeth whiter and help you keep them cleaner than ever before,” said Anish Patel, CEO of Brush Buddies. t#SVTI#VEEJFTBMTPPGGFSTShopkins 2 , a line of character-based toothbrushes and oral care products PRODUCT IMAGES COURTESY OF BRUSH BUDDIES Through the teeth, over the gums: Pastes, whiteners, and more PRODUCT UPDATES 3 created just for children. The product line includes powered and manual toothbrushes, travel kits, light-up brushes, singing brushes, bandages, hand sanitizers, and facial tissues. “Shopkins is one of the most exciting and fastest growing brands out there,” Patel said. “We’re excited to add these fun-loving characters to our portfolio of licensed products.” PRODUCT IMAGES COURTESY OF PAULA’S CHOICE / TOM’S OF MAINE Whiteners, pastes, and rinses Once the exclusive domain of the dentist, numerous tooth-whitening products now line OTC shelves. tPaula’s Choice Brighten Up 2-Minute Teeth Whitener 3 is a portable way to whiten teeth and eliminate stains from wine, berries, and coffee almost instantaneously. Recommended for travel and quick touch-ups, Paula’s is a balm-like formula designed to improve stability and block sensitivity. It can be used to maintain or prolong professional whitening results. tTom’s of Maine offers natural toothpaste and mouthwash products, including Clean & Gentle Toothpaste. It promises to leave your mouth feeling clean and fresh without sodium lauryl sulfate (SLS). Instead of SLS, its 4 formula uses glycyrrhizin (derived from licorice root). It also contains naturally sourced fluoride for cavity prevention and natural flavor oils to freshen breath. t"MTPGSPN5PNTJTWicked Fresh! Mouthwash, with zinc to neutralize odor caused by bad-breath germs. It promises to provide long-lasting fresh breath without the burn. tTom’s Children’s Silly Strawberry Fluoride-free Toothpaste 4 uses calcium and silica to clean teeth. tTom’s Silly Strawberry Anticavity Fluoride Toothpaste features an all-natural strawberry taste. According to Tom’s, it is the only natural children’s fluoride toothpaste approved by the American Dental Association. tTom’s Simply White Toothpaste 5 uses naturally sourced silicas for clinically proven whitening without bleaching chemicals. Product literature states that this is the only natural whitening toothpaste to earn the ADA Seal. tTheraBreath Oral Rinses promise to eliminate bad breath. The mintflavored rinse uses the oxygenating power of OXYD-8 to destroy the bacteria that cause bad breath and eliminate sour, bitter, and metallic tastes in the mouth. The oral rinses, which are 5 available in different flavors and strength levels, also promise to help with dry mouth and tonsil stones. tACT Anticavity Fluoride Rinse is clinically proven to strengthen teeth and prevent tooth decay. It contains the maximum amount of fluoride available in mouthwash form without a prescription and a dosage meter to make sure the proper amount is used. Advertiser Index Brand Name Advertiser Name Page Corporate Amneal Pharmaceuticals 9A* Corporate Camber Pharmaceuticals 29A* Corporate Epic Pharma Corporate Humco Corporate Mylan Inc. CV4 Florajen American Lifeline CV3 Granix Teva Oncology Nexium Pfizer Toujeo Sanofi Aventis 18-22 Viberzi Allergan 33-36 25 3 9B-10B* CV2 *Indicates a demographic advertisement. DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 31 CLINICAL ANTICOAGULATION THERAPIES Anna D. Garrett, PharmD, BCPS Pre-op anticoagulation reduces VTE risk in cancer patients Venous thromboembolism (VTE) is a frequent cause of morbidity during cancer treatment, and although a number of studies have found that postoperative anticoagulation decreases rates of VTE in surgical oncology patients, the effect of adding preoperative anticoagulation to postoperative VTE prophylaxis is largely unknown. Now researchers at Memorial Sloan Kettering Cancer Center in New York have found that rates of deep venous thrombosis and pulmonary embolism were significantly lower among patients who received preoperative chemoprophylaxis than in those who did not. Investigators selected 2,058 patients who were undergoing major cancer surgery to receive preoperative VTE prophylaxis of either low-molecular-weight heparin (LMWH) (40 mg enoxaparin) or unfractionated heparin (5,000 units). Anticoagulation was administered in the preoperative holding area by the nursing staff within two hours of surgery. Bleeding, transfusion, and VTE rates were compared with those of 4,960 historical controls who did not receive preoperative VTE chemoprophylaxis. Patients who received the intervention did not have a statistically significant difference in the rate of major bleeding events. They also had lower rates of both documented bleeding and blood transfusion, as well as statistically significant lower rates of documented DVT and pulmonary embolism. Source: Selby LV, Sovel M, Sjoberg DD, et al. Preoperative chemoprophylaxis is safe in major oncology operations and effective at preventing venous thromboembolism. J Am Coll Surg. 2015. Published online December 14, 2015. http://www.journalacs.org/ article/S1072-7515(15)01712-3/abstract. Meta-analysis: Heart failure raises VTE risk Among hospitalized patients, heart failure appears to be an independent risk 32 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM factor for VTE, according to a recently published meta-analysis. The analysis included 71 studies reporting absolute or relative risks for VTE among hospitalized heart failure patients. Overall, the VTE rate was 1.5% among heart failure patients who received thromboprophylaxis and 3.7% for those who did not. The rate was highest among patients with both heart failure and cancer (6.6%). After multivariable adjustment, heart failure was associated with a 50% increased risk for VTE. The authors concluded that heart failure is an independent risk factor for VTE and that thromboprophylaxis should be considered in clinical practice for highrisk patients. Source: Tang L, Wu Y, Lip GYH, et al. Heart failure and risk of venous thromboembolism: A systematic review and meta-analysis. Lancet Haematology. Published online December 3, 2015. http://www.thelancet. com/journals/lanhae/article/PIIS23523026(15)00228-8/abstract. LMWH/warfarin switch appears safe in cancer patients Switching to warfarin after six months of anticoagulant treatment with LMWH appears to be safe in patients with cancer-associated thrombosis. LMWH is considered to be the treatment of choice for anticoagulation therapy for cancer-associated thrombosis, with treatment for at least three to six months after diagnosis. However, the data regarding LMWH treatment beyond six months are unclear. Researchers compared the two options in a retrospective registry study. The cohort included 1,502 patients who were enrolled in the RIETE Registry and who had already completed six months’ treatment with a LMWH. About half of the patients continued receiving LMWH (n=763); for the other half, therapy was changed to warfarin (n=739). The primary outcome was time to recurrence of VTE. The secondary outcome was major bleeding, defi ned as bleeding associated with a decrease in hemoglobin of 20 g/L or more requiring at least 2 units of red blood cell transfusion; bleeding into a critical organ; fatal bleeding; or nonmajor bleeding. There were no significant differences in the two groups with regard to recurrent VTE or major or nonmajor bleeding. Results suggest that switching to warfarin after initial treatment with LMWH is safe. Source: Chai-Adisaksopha C, Iorio A, Crowther MA. Switching to warfarin after 6-month completion of anticoagulant treatment for cancer-associated thrombosis. American Society of Hematology (ASH) 57th Annual Meeting. Abstract 430. Presented December 7, 2015. https://ash. confex.com/ash/2015/webprogram/ Paper81374.html. Anna D. Garrett is a clinical pharmacist and president of Dr. Anna Garrett (www. drannagarrett.com). Her mission is to help women in midlife maximize their mojo! Contact her [email protected] CLINICAL NEW DRUG REVIEW Kathryn Wheeler, PharmD, BCPS Flibanserin: Risk vs. benefit On August 19, 2015, FDA approved flibanserin (Addyi; Sprout Pharmaceuticals) for the treatment of premenopausal women experiencing distress resulting from acquired generalized hypoactive sexual desire disorder (HSDD) not caused by a medical or psychiatric condition, relationship problems, or the effects of medications or other substances. In October 2015, the manufacturer made the drug available for prescribing and appropriate use. Because of concerns about adverse effects, training through the Addyi REMS program is required for prescribers and pharmacies that want to participate in the medication use process for this drug. Prescribers also must complete the Addyi REMS provider-patient agreement form with each patient before prescribing Addyi. Efficacy Flibanserin is a 5-HT1A receptor agonist and a 5-HT2A receptor antagonist: As such, through unknown mechanisms it affects pleasure pathways of the brain and affects a woman’s sense of sexual desire. The drug’s efficacy, which led to its FDA approval, was based primarily on three 24-week, randomized, doubleblind, placebo-controlled clinical trials. Participants in these trials were premenopausal women experiencing significant distress or relationship difficulties due to acquired, generalized HSDD for at least six months and who previously had no concerns with sexual desire. Participants received either 100 mg flibanserin (1,227 participants) at bedtime or placebo (1,238 participants). Change in monthly satisfying sexual events (SSEs) from baseline to week 24 and in sexual desire as calculated by participant diary responses (studies 1 and 2) or the Female Sexual Function Index (FSFI) (study 3) served as co-primary endpoints in the studies. The FSFI was assessed as a secondary endpoint in stud- ies 1 and 2. All three trials assessed the degree of bother, an aspect of distress, experienced in relation to low sexual desire as a secondary endpoint. Participants taking flibanserin had an average increase of 0.5 to 1.0 SSE per month compared to participants taking placebo. Measures of distress demonstrated that participants taking flibanserin “frequently” to “always” experienced distress related to low desire at baseline; by week 24, they experienced distress “occasionally” to “frequently.” Safety Flibanserin is not indicated for treatment of HSDD in postmenopausal women, for use in men, or for enhancement of sexual performance. The drug carries a boxed warning citing severe hypotension and syncope, particularly when used by patients with hepatic impairment or when taken in combination with alcohol, moderate to strong CYP3A4 inhibitors, or certain herbal supplements. Flibanserin use is contraindicated in these circumstances. Certified pharmacies may dispense flibanserin only pursuant to a prescription from a certified prescriber. Every patient must be counseled to abstain from alcohol during treatment with flibanserin to avoid the increased risk of syncope associated with concomitant use. In trials, the most common adverse effects associated with flibanserin included dizziness, nausea, tiredness, difficulty sleeping, and dry mouth. A simulated driving impairment and cognition study was performed to evalu- ate the residual effects of bedtime flibanserin dosing on awakening the next day. In these tests, flibanserin demonstrated effects similar to placebo after seven hours of sleep. In light of these results, it might be prudent to counsel patients not to drive or perform tasks requiring attention within seven hours of taking flibanserin — at least until the patient knows how she will react to the medication. Dosage Flibanserin 100 mg is administered as a single bedtime dose. Bedtime administration is intended to mitigate the drug’s hypotensive and CNS depressive effects. Pharmacokinetic studies of flibanserin used at a dose of 50 mg daily in patients with renal impairment (n=16) indicate minimal change in exposure to flibanserin compared to responses of healthy participants. Patients should be instructed to skip any missed dose and to take their next scheduled dose at the appropriate time to avoid increased levels of flibanserin, which could increase the risk of syncope and fall-related injury. Patients who experience lightheadedness or dizziness should be advised to lie down and to report any loss of consciousness to their prescriber. Patients should discontinue treatment with flibanserin after eight weeks if no symptom improvement has been detected. Kathryn Wheeler is associate clinical professor, Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Conn. DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 37 REGULATORY & LEGAL ETHICAL DECISION-MAKING Kenneth R. Baker, BS Pharm, JD Can pharmacists be sued for doing their jobs? I was speaking with Don McGuire, BS Pharm, JD, when he brought up a question he had received from a pharmacist. Don is general counsel and senior vice president of risk management with Pharmacists Mutual Insurance Company, so he receives many questions about legal liability. This question was particularly interesting, because it encompassed changes in pharmacists’ standards of care that have occurred over the last few decades. ing a patient or physician of contraindications, allergies, overdoses, and other conditions connected with medications.3 Today courts are finding more pharmacists liable of more professional duties.3 Not so long ago A generation ago, a short time in the study of a profession’s legal standards of practice, if a pharmacist filled a prescription correctly — meaning that it contained the right drug, had the right directions on the label, and was delivered to the right patient — the pharmacist generally would not be liable for injuries to the patient caused by the drug. In 1993 an Illinois court, finding that the pharmacist had no duty to warn in the case of a patient who died as a result of an overdose of imipramine, said, “To impose a duty to warn on the pharmacist would be to place the pharmacist in the middle of the doctor-patient relationship, without the physician’s knowledge of the patient.”1 In a similar circumstance, an earlier court noted, “Such a duty would compel the pharmacist to second-guess every prescription a doctor orders in an attempt to escape liability.”2 These courts perhaps did not understand the pharmacist’s expertise and direct duty to the patient. Changing times While today, courts have been reluctant to find a generalized duty to warn in all cases, they have found more exceptions.3 A pharmacist is likely to be held to a higher standard when it comes to warn- 38 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM Increased liability The question asked of Mr. McGuire was, “If I make a specific recommendation to a physician of the drug to be used in a particular case, am I increasing my liability?” The answer is yes. The more duties we take on and the more specific our recommendations and advice, the more we may be held liable if our advice is wrong. Legal duty may be imposed by law, or by court decision, or by community standards. Duty may also be taken on by a volunteer who assumes a duty.4 The real question The real question is, are there times that we as pharmacists should assume professional duties, such as when a physician asks for professional knowledge, experience, and training? Pharmacists are the foremost experts in drugs. What good is that expertise if we are unwilling to use it to benefit a colleague or a patient? Under the Pharmacists’ Code of Eth- ics, pharmacists promise to help patients get the most from their medications; to be committed to patients’ welfare; and to maintain their trust.5 As part of that covenantal relationship, pharmacists’ use of their knowledge, experience, and training for the benefit of the patient may include helping physicians make critical decisions involving risk assessment. In essence, the question sent to Mr. McGuire was: If I do my job, might I get sued? The answer is yes. Protections As we do our jobs, there are ways we can protect ourselves. First, we can ensure that we give professional advice only in areas in which we are competent. We can follow the ethical principal that a pharmacist has a duty to maintain knowledge and abilities.5 Second, when we give advice, we can document what we said and under what circumstances. Third, we can maintain our professional liability insurance, both commercial and individual. What we cannot do is shirk our duty as professionals. References available at www.drugtopics.com. Ken Baker is a pharmacist and an attorney. He teaches ethics at the Glendale, Arizona, campus of Midwestern University, and risk management for the University of Florida, and consults in the areas of pharmacy error reduction, communication, and risk management. He is an attorney of counsel with the Arizona law firm of Renaud Cook Drury Mesaros, PA. E-mail [email protected]. These articles are not intended as legal advice and should not be used as such. When a legal question arises, the pharmacist should consult with an attorney familiar with pharmacy law in his or her state. AND AN ONGOING CE PROGRAM OF THE UNIVERSITY OF CONNECTICUT SCHOOL OF PHARMACY AND DRUG TOPICS 2 CPE CREDITS EARN CE CREDIT FOR THIS ACTIVITY AT WWW.DRUGTOPICS.COM Educational Objectives GOAL: To enhance knowledge and awareness of opioid use disorder in order to identify and effectively manage patients at risk of overdose After participating in this activity, pharmacists will be able to: > Describe the scope of opioid use disorder in the United States to dispel myths and stereotypes regarding patients who misuse prescription or illicit opioids > Recognize risk factors for and symptoms of opioid use disorder, withdrawal, and overdose > Explain evidence-based pharmacologic and nonpharmacologic treatment strategies for opioid use disorder > Discuss communication strategies for engaging patients about potential opioid misuse or overdose risk and effectively triaging them to appropriate recovery options After participating in this activity, pharmacy technicians will be able to: > Describe the scope of opioid use disorder in the United States to dispel myths and stereotypes regarding patients who misuse prescription or illicit opioids > Recall indicators of potential opioid use disorder and recognize when to refer patients to the pharmacist for additional counseling Part 1: Recognition and referral to enhance recovery The pharmacist’s role in managing opioid use disorder Anita N. Jackson, PharmD CLINICAL ASSOCIATE PROFESSOR, UNIVERSITY OF RHODE ISLAND, COLLEGE OF PHARMACY, KINGSTON, RI Pharmacists and pharmacy technicians are eligible to participate in the knowledge-based activity, and will receive up to 0.2 CEUs (2 contact hours) for completing the activity, passing the quiz with a grade of 70% or better, and completing an online evaluation. Statements of credit are available via the CPE Monitor online system and your participation will be recorded with CPE Monitor within 72 hours of submission. ACPE# 0009-9999-16-002-H01-P ACPE# 0009-9999-16-002-H01-T Grant funding: None Activity Fee: There is no fee for this activity. Jeffrey P. Bratberg, PharmD, BCPS CLINICAL PROFESSOR OF PHARMACY PRACTICE, UNIVERSITY OF RHODE ISLAND, COLLEGE OF PHARMACY, KINGSTON, RI Abstract The United States is in an unrelenting epidemic of patients with opioid use disorder, yet myths and stereotypes among pharmacy staff and the public about this patient population inhibit entry into treatment and recovery, leading to overdoses and deaths. Pharmacists are essential frontline partners who can not only recognize risk factors for and symptoms of opioid use disorder, withdrawal, and overdose, but can also communicate with patients in an engaging fashion so that patients are aware of the pharmacologic and nonpharmacologic options for treatment. INITIAL RELEASE DATE: FEBRUARY 10, 2016 EXPIRATION DATE: FEBRUARY 10, 2018 To obtain CPE credit, visit www.drugtopics.com/cpe and click on the “Take a Quiz” link. This will direct you to the UConn/Drug Topics website, where you will click on the Online CE Center. Use your NABP E-Profile ID and the session code: 16DT02-XTK28 for pharmacists or the session code: 16DT02-JCT39 for pharmacy technicians to access the online quiz and evaluation. First-time users must pre-register in the Online CE Center. Test results will be displayed immediately and your participation will be recorded with CPE Monitor within 72 hours of completing the requirements. For questions concerning the online CPE activities, e-mail: [email protected]. Faculty: Anita N. Jackson, PharmD and Jeffrey P. Bratberg, PharmD, BCPS Dr. Jackson is a clinical associate professor at the University of Rhode Island, College of Pharmacy, Kingston, RI. Dr. Bratberg is a clinical professor of Pharmacy Practice at the University of Rhode Island, College of Pharmacy, Kingston, RI. Faculty Disclosure: Dr. Jackson and Dr. Bratberg have no actual or potential conflict of interest associated with this article. Disclosure of Discussions of Off-Label and Investigational Uses of Drugs: This activity may contain discussion of unlabeled/unapproved use of drugs in the United States and will be noted if it occurs. The content and views presented in this educational program are those of the faculty and do not necessarily represent those of Drug Topics or University of Connecticut School of Pharmacy. Please refer to the official information for each product for discussion of approved indications, contraindications, and warnings. DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 39 IMAGE: GETTY IMAGES / DESIGN PICS/HAMMOND HSN The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. CONTINUING EDUCATION T H E P H A R M ACIST ’S ROL E I N M A NAG I NG OP IOI D USE DISOR DE R Introduction A November 2015 national poll by the Kaiser Family Foundation revealed that 56% of those surveyed personally knew someone who had taken a prescription painkiller that was not prescribed to him or her, been addicted to prescription painkillers, or died from a prescription overdose.1 A recent survey report of 1,111 nationally sampled Americans revealed that more than 28% of Americans have used a prescription opioid pain reliever in the last year, and almost 70% have used a prescription opioid pain reliever within their lifetime; of these, 17.3% reported using a prescription opioid that was not prescribed for them.2 Prescription opioids are an important class of medications that are highly effective for relieving the suffering associated with some types of acute and chronic pain. Patients may be prescribed opioids for legitimate medical purposes or they may first misuse opioids through recreational exposure.3 Patients who misuse alcohol, opioids, or other drugs were previously classified as having substance abuse or substance dependence disorders. These categories were combined in the fifth version of the Diagnostic and Statistical Manual (DSM-5) into one category called “Substance Use Disorder,” which is measured on a continuum from mild to severe.4 Each of the substances has a separate disorder classification (e.g. alcohol use disorder, opioid use disorder), however the diagnostic criteria used have overarching similarities.4 In 2012, 289 million opioid pain relievers were dispensed in the United States, enough for every American adult to have obtained a prescription. This represents 6.8% of the 4.2 billion prescriptions dispensed in 2012. From 2007 to 2012, the rate of opioid prescribing outpaced the increase in total prescription volume in the United States and the overall U.S. population growth. Primary care providers are prescribing 50% of the opioids dispensed, although the largest increase was observed among physical/rehabilitation specialists.5 Ten of the states with the highest rates of opioid prescribing are located in the Southern part of the United States, with the high- 40 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM FIGURE 1 Opioid pain reliever sales and overdose death rate States with more opioid pain reliever sales tend to have more drug overdose deaths Kg of Opioid Pain Relievers sold per 10,000 3.5 - 5.6 5.7 - 7.5 7.6 - 9.4 9.5 - 13.3 Drug overdose death rate* per 100, 000 Death rate, 2013, National Vital Statistics System. Opioid pain reliever sales rate, 2013, DEA’s Automation of Reports and Consolidated Orders System 7.1 - 11.2 11.3 - 14.3 14.4 - 19.4 19.5 - 36.3 *age-adjusted rates Source: Ref 9 est rates (more than 135 prescriptions per 100 persons) reported in Alabama, Tennessee, and West Virginia.6 According to an analysis of an IMS Health database, Every day in the United States, 46 people die from overdose associated with prescription opioids.” states vary in opioid and benzodiazepine prescribing/dispensing rates, particularly for high-dose opioids, long-acting opioid formulations, and benzodiazepines; however, differences in prescribing rates do not reflect differences in the incidence of corresponding pain conditions in these states.6 As rates of opioid prescribing increase, a parallel increase in the number of opioid-related hospital admissions, emergency department (ED) visits, and deaths has been observed. In 2011, more than 488,000 ED visits were related to opioid misuse. Opioid-related ED visits are commonly associated with the concurrent use of opioids with benzodiazepines and/or other substances, including alcohol.7 The most recent morbidity and mortality analysis of drug overdose among eight states from the Prescription Behavioral Surveillance System (PBSS) indicated that prescribing rates approach one opioid prescription per state resident.8 This study also found that nearly a quarter of opioid prescriptions overlapped by seven or more days without clinical rationale and that benzodiazepine prescribing is highest among patients aged more than 65 years despite known adverse events in this population. The PBSS analysis found that patients who seek controlled substances from multiple prescribers are more likely to pay with cash and that 10% of prescribers account for 50% to 66% of opioid prescribing across the eight states studied.8 Research has also demonstrated a link between the number of opioid sales and the number of drug overdose deaths across states (Fig. 1).9 From 1999 to 2013, the number of prescription opioid pain relievers dispensed in the United States has quadrupled, and CONTINUING EDUCATION PA RT 1: R E COG N I T ION A N D R E F E R R A L T O E N H A NCE R ECOV E RY this significant increase in opioid prescribing cannot be attributed to an increased incidence of conditions associated with pain.10 This is happening despite the lack of evidence supporting the efficacy of opioid use for chronic pain, with moderately strong evidence for harmful effects.11,12 Researchers have noted that dysfunctional regulation of promotional campaigns by pharmaceutical companies fueled the rise in oxycodone prescribing.13, 14 Opioid overdose can occur at any point in time during opioid use or misuse, in those who are opioid naïve and in those with chronic exposure. In 2009, the direct medical cost of opioid overdose was estimated at $2.2 billion; indirect costs, including absenteeism and loss of future earnings due to mortality, were estimated at more than $18.2 billion.1 5 Every day in the United States, 46 people die from overdose associated 33%, respectively) for years. This is particularly important when considering that rates of neonatal abstinence syndrome have increased nearly 400% in the last decade.19,20 In 2014, an estimated 4.3 million people in the United States had misused prescription opioid pain relievers in the last month.21 Some examples of misuse of prescription opioids include taking a higher dosage than prescribed, altering the route of administration, taking a drug prescribed for another individual, or obtaining a drug without a legal prescription.7 Although the overall trend in nonmedical use of prescription opioids decreased from 5.4% to 4.9% from 2003 to 2013, opioid use disorders increased over the same time period, from 0.6% to 0.9%.22 A recent meta-analysis of 38 studies assessing patients with chronic pain who were taking opioids showed that PAUSE AND PONDER What negative comments regarding patients and their misuse of opioids or treatments for opioid use disorder have you encountered in your role as a healthcare professional? How have you addressed them? What language have you used? with prescription opioids,16 and in 2013, drug overdose was the leading cause of unintentional injury death.17 Although the majority of opioid overdose deaths between 1999 and 2013 occurred in white non-Hispanic men aged 25 to 54 years,17 opioid use disorder and overdose are national problems that cut across all races, ethnicities, socioeconomic classes, ages, and sexes. White non-Hispanic middleaged men in the United States are dying at increased rates versus their counterparts in similar countries and versus other ethnicities, races, and age groups within the United States. Poisonings are a principle reason for this increase in mortality, surpassing lung cancer, suicide, liver disease, and diabetes.18 Rates of opioid use among women of childbearing age with private insurance or Medicaid have remained stable (25% and approximately 25% of patients were using medications not as prescribed (misuse), and approximately one in 10 patients reported use associated with a high potential for harm.23 Research has suggested that increasing nonmedical use of prescription pain relievers may lead to subsequent heroin abuse.24 Heroin users are 40 times more likely than the general population to have a history of prescription opioid misuse. The percentage of heroin users misusing opioid pain relievers more than doubled from 2002 to 2013, and concurrent opioid pain reliever misuse was more common among heroin users than the concurrent use of alcohol, marijuana, or cocaine.25 While prescription opioid overdose deaths have skyrocketed and then leveled out, heroin overdose deaths have nearly quadrupled from 2002 to 2013.25 In Rhode Island, nearly There is recent evidence showing a significant level of public awareness of the severity of the opioid epidemic and support of public policy aimed at reducing opioid pain reliever misuse.” 80% of opioid-related unintentional deaths in 2015 involved heroin, a 15% increase from past years. Even more concerning, 50% of these deaths involved heroin combined with nonpharmaceutical fentanyl, an exponential increase from 5% of overdose deaths in previous years. Nonpharmaceutical fentanyl is a synthetic opioid that is 50 to 100 times more potent than morphine, is more rapidly acting, and is considered a threat to health and safety by the Drug Enforcement Administration (DEA), particular for overdose.26–28 Promisingly, some states have been effective in curtailing opioid prescribing, resulting in a plateau or decrease in opioid diversion and misuse.29 A study of drug overdose deaths from 28 states showed that in the seven states where opioid overdose death rates declined heroin overdose death rates did not increase, indicating that efforts to curb opioid prescribing do not result in increased heroin use.30 However, the introduction of abuse-deterrent extendedrelease oxycodone has resulted in an increase in the use of heroin due to ease of use, lower cost, and increased availability of illicit heroin.31 Heroin use has increased among most demographic groups, including those with historically low rates of use such as women and those with higher income. The highest rates of heroin use are seen among 18- to 25-year-olds, nonHispanic white men, those living in urban areas, and those without insurance or who are enrolled in Medicaid.32 DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 41 CONTINUING EDUCATION T H E P H A R M ACIST ’S ROL E I N M A NAG I NG OP IOI D USE DISOR DE R Stigma associated with substance use disorders Despite increasing scientific evidence that substance use disorders are complex brain disorders, it is a common public misconception that drug misuse is a deficit in moral principle or willpower and that patients can simply choose to stop use through strength of will.33 Biases against patients with substance use disorder and those who misuse drugs are pervasive, and health professionals have been shown to share societal perceptions and prejudices.34 Because of these biases, patients may be denied access to effective treatments, and the development of new treatments for substance use disorder may be compromised.35 The stigmatization of persons with substance use disorders and subsequent discriminatory treatment may create chronic stress among patients and result in serious mental and physical repercussions. Patients in need may avoid seeking treatment because of fears about further discrimination and/or legal consequences.36 Although negative perception toward individuals with opioid use disorders is higher than for individuals with other mental illnesses, recent evidence shows a significant level of public awareness of the severity of the opioid epidemic and support of public policy aimed at reducing opioid pain reliever misuse. One author suggests that the public needs to see more positive portrayals of substance use and mental health disorders.37 A study on the portrayal of substance use disorder as a treatable disease yielded significantly decreased stigma when patients in vignettes were identified as treated versus untreated.38 Another study showed decreased stigma toward people with mental health disorders when student pharmacists interacted with someone with the disease.39 Factors that contribute to stigma and lack of effective treatment for opioid use disorder include the lack of understanding of addiction as a medical illness, lack of integration of treatment into the standard healthcare system, use of derogatory language to describe individuals with substance use disorder, and failure of the criminal justice system to include treatment 42 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM TABLE 1 Dispelling myths regarding substance (opioid) use disorder MYTHS AND STEREOTYPES EVIDENCE Substance use disorder is voluntary. Ì Chemical and physical changes in the brain occur with use in susceptible individuals. Substance use disorder is a character flaw. Ì Genetic and environmental components account for more than half of a patient’s inherent risk of substance use disorder. Patients with substance use disorder have to hit “rock bottom.” Ì Patients seek treatment for a variety of reasons, including self-motivation and a desire to protect family and career. Treatment for substance use disorder is not effective. Ì The majority of patients who quit using drugs successfully received assistance through treatment programs. Relapse indicates treatment failure. Ì Substance use disorder is a chronic condition and successful cessation of use frequently requires multiple attempts. Source: Adapted with permission from Ref 43 for substance use disorder throughout an incarceration or parole.40 Common language regarding substance use disorder and recovery that is used by the public and healthcare providers further stigmatizes individuals with opioid use disorder. Descriptions of opioid use disorder as a “habit,” a person with an opioid use disor- Some states have been effective in curtailing opioid prescribing, resulting in a plateau or decrease in opioid diversion and misuse. der as a “junkie,” “addict,” or “abuser,” and a person who has successfully stopped using opioids as “clean” are examples of stigmatizing language that is often encountered.41,42 Other common misunderstandings about substance use disorder are summarized in Table 1.43 Neurobiology of opioids The term “opioid” refers to the class of drugs derived from opium, which originates from the poppy plant, as well as synthetically manufactured drugs with a similar chemical structure and activity. While often used interchangeably with opioid, the term “opiate” refers to codeine and morphine, the naturally occurring derivatives of opium.44 Examples of opioids include the illicit street drug heroin and the semisynthetic and synthetic prescription opioid analgesics (including oxycodone, hydrocodone, fentanyl, hydromorphone, buprenorphine, methadone, tapentadol, and oxymorphone). Opioids interact with mu-, delta- and kappa-opioid receptors in the gastrointestinal tract and the peripheral and central nervous systems. Opioids bind to receptors located in the reward and pain pathways. The reward pathway is activated by pleasurable stimuli and results in the release of dopamine from the ventral tegmental area to the nucleus accumbens and prefrontal cortex.45 Prescription opioids may result in opioid use disorder due to activation of the reward pathway and the subsequent euphoric effects. Additionally, patients with a genetic predisposition to opioid use disorder may have alterations in receptor sensitivity or drug metabolism that result in permanent changes to the brain with chronic misuse.34 Although patients taking opioid pain relievers as prescribed may develop an opioid use disorder, risk is in- CONTINUING EDUCATION PA RT 1: R E COG N I T ION A N D R E F E R R A L T O E N H A NCE R ECOV E RY TABLE 2 Spectrum of symptoms associated with opioid use, overdose, and withdrawal OPIOID INTOXICATION Bradycardia Miosis (pinpoint pupils) Drowsy, but arousable (responds to sternal rub) Slurred speech Slowed breathing (8+ breaths/min) OPIOID OVERDOSE OPIOID WITHDRAWAL Ì Tachycardia Ì Bradycardia Ì Tremor Ì Hypotension Ì Anxiety Ì Miosis Ì Hypertension Ì Breathing slow or stopped (<8 breaths/min) Ì Diaphoresis Ì Choking/gurgling breathing noises Ì Restlessness Ì Not speaking Ì Mydriasis Ì Not arousable (no sternal rub response) Ì Rhinorrhea/lacrimation Ì Blue/gray lips and nails Ì Muscle/abdominal cramps Ì Nausea/vomiting Ì Diarrhea Source: Adapted from Refs 50-52 that pharmacists can promote; this initiative will be detailed in Part 2 of this continuing education program.47 Patients may become tolerant to the effects of opioid agonists over time, resulting in a requirement for higher doses of drug to elicit the same response (euphoria or analgesia). Patients may also become dependent physically on opioid agonists to avoid withdrawal symptoms and may experience withdrawal if they decrease the dose, attempt to discontinue use, or are given an opioid antagonist, such as naloxone. Tolerance and dependence can develop with opioid use for legitimate medical purposes or in patients who are misusing opioids. Opioid use disorder PAUSE AND PONDER may include Reflect on the criteria in Table 2. How can you features of tolerand physiidentify patients who exhibit these symptoms? ance cal dependence, and may be acsituations or may be combined with opioid companied by intense cravings for opioids agonists to deter abuse and alteration of with maladaptive behavior related to obtainthe dosage form. The peripherally acting ing the drugs and an inability to control use mu-opioid receptor antagonists methylnal- despite negative consequences.48,49 trexone, alvimopan, and naloxegol are useThe symptoms associated with use of, ful for preventing constipation associated withdrawal from and overdose with opioids with opioids without reducing their effect are summarized in Table 2.50–52 In patients on pain. Distribution of naloxone for the re- with chronic opioid use disorder, imaging versal of opioid activity during an overdose can show changes in the areas of the situation is a critical public health initiative brain that are critical to decision-making, creased through misuse, including altering the mode of administration to increase the euphoric effects (such as crushing and injecting or insufflating [“snorting”] tablets).46 Available opioids differ in their affinity for the opioid receptors, which are primarily responsible for the euphoric and analgesic effects of opioids. Some opioids exhibit full agonist activity, whereas others possess partial agonist activity. Mu-opioid receptor antagonists are available and may be administered to block or reduce the activity of the opioid agonists. The centrally and peripherally acting mu-opioid receptor antagonists naloxone and naltrexone are used to reverse opioid activity in overdose learning, memory, and impulse control, and these changes likely play a role in the compulsive cycle of misuse.53,54 Opioid withdrawal in individuals with physical dependence typically occurs within six to 12 hours of discontinuing the use of short-acting opioids or 24 to 36 hours for long-acting opioids.52 Although opioid withdrawal is not life threatening, it may result in severe flu-like symptoms that are significantly uncomfortable and distressing to the patient. Patients going through withdrawal often feel anxiety, insomnia, and low energy that may last for several weeks to months. Hallmark symptoms of opioid withdrawal include piloerection, tachycardia, diaphoresis, restlessness, mydriasis, yawning, rhinorrhea, lacrimation, muscle cramps, nausea, abdominal cramps, vomiting, and diarrhea.55 Complications of opioid withdrawal can include aspiration, dehydration, and electrolyte disturbances from vomiting and/or diarrhea. Patients with dependence on other substances in addition to opioids (such as benzodiazepines or alcohol) may be at risk for other serious complications, including seizures or death, with concomitant discontinuation of those agents. Withdrawal from alcohol use disorder can result in death, however resumption of alcohol use after withdrawal does not. In contrast, because opioid tolerance fades in hours to days, resumption of use, particularly at prewithdrawal doses, significantly increases the risk of fatal overdose.56,57 Periods of abstinence because of prison stays, hospital stays, or detoxification are the biggest risk factors for fatal overdose.52,58 Various treatment regimens for the relief of opioid withdrawal symptoms can be found online. These products are not without risk of side effects or dependence and have not demonstrated efficacy in randomized controlled trials. Products ranging from legal herbal supplements to illegal hallucinogens, including kratom, phenibut, marijuana, and ibogaine root, may be available to patients for purchase and differ in legality from state to state.59 Risk factors for opioid use disorder and overdose Chronic use of opioids may lead to physical DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 43 CONTINUING EDUCATION T H E P H A R M ACIST ’S ROL E I N M A NAG I NG OP IOI D USE DISOR DE R tolerance/dependence, but no single factor can predict if a patient will develop an opioid use disorder over time. The main factors related to opioid use disorder are a personal or family history of alcohol or substance use disorder, a history of physical or sexual abuse, or concomitant psychiatric conditions.60 Genetics and environmental influences account for approximately half of a patient’s vulnerability for developing a substance use disorder. The age at which a patient begins using opioids (early onset of use) and the method of administration— crushing for injection or insufflating—may also increase the risk of substance use disorder (Table 3).62 A number of screening tools are available to assess a patient’s risk for developing an opioid use disorder; these should ideally be administered before a patient begins chronic opioid therapy. Some validated risk assessment tools include the opioid risk tool (ORT); National Institute on Drug Abuse Quick Screen; CAGE alcohol screening questionnaire adapted to include drug use (CAGE-AID); Diagnosis, Intractability, Risk, Efficacy (DIRE) tool; Rapid Opioid De- TABLE 3 Risk factors and protective factors for substance use disorder RISK FACTORS PROTECTIVE FACTORS Aggressive behavior in childhood Ì Good self-control Lack of parental supervision Ì Parental monitoring and support Poor social skills Ì Positive relationships Drug experimentation Ì Academic competence Availability of drugs at school Ì School anti-drug policies Community poverty Ì Neighborhood pride Source: Adapted from Ref 62 monitoring program (PDMP), urine drug screening, opioid therapy agreements, behavioral interventions, and tamperresistant opioid formulations.47 Caution is warranted, as researchers still haven’t linked PMP and opioid use agreements to improvements in opioid overdose incidence.64,65 One study that linked abusedeterrent formulations to decreases in prescription drug overdose reported increases in heroin-related overdose PAUSE AND PONDER What local community groups are you aware of that are active in substance use disorder treatment and recovery? Which of these could you contact for information on referring patients for opioid use disorder treatment and recovery? pendence Screen (RODS); and Drug Abuse Screening Test (DAST).60,62 Pharmacists may also use these screening tools to identify patients with active substance use disorders to refer for treatment and recovery. The RODS may be particularly beneficial for pharmacists in the community pharmacy setting, as this validated eight-item tool takes less than two minutes to complete. The questions correspond directly to the criteria for substance use disorder in the DSM-5 and inquire about opioid use within the past 12 months.63 In addition to utilizing available screening tools, clinicians can ensure appropriate adherence to opioid pain reliever treatment by using a prescription drug 44 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM deaths.66 Clinicians should consider any tool used to enhance adherence and reduce misuse as only part of a comprehensive strategy.67 Although patients can overdose from opioids at any point during use or misuse, there are additional risk factors that increase the likelihood of experiencing accidental fatal or nonfatal overdose; these factors are summarized in Table 4.61,68–88 Treatment of opioid use disorder Discontinuation of long-term opioid use should be attempted for patients who are not able to attain pain relief despite escalating doses of opioids, those experiencing intolerable side effects, those misusing opioids, those with functional deterioration secondary to opioid use, and those with resolution of the underlying pain condition.89 Patients undergoing discontinuation may be only physically dependent on opioids or they may meet the criteria for an opioid use disorder. Preventing and/ or relieving the physical symptoms of withdrawal is more easily managed than treating an opioid use disorder.90 Discontinuation of opioids may be achieved by switching patients to an alternative agent (particularly from shorter- to longer-acting), initiating a rapid or slow taper of the opioid dose (over days to months), and/or administering an opioid receptor antagonist.91 Symptoms of withdrawal may be prevented by a slow taper of the opioid alone or may be managed with adjunctive medications. The minimum dose required to prevent acute withdrawal is 25% of the previous daily dose (eg, 30 mg of morphine for a patient taking 120 mg daily); however, gradual tapering of 10% to 50% of the dose every 5 to 7 days until a threshold of 30% of the original dose is achieved followed by a slower taper to discontinuation over weeks to months is recommended in those with long-term dependence.89 For a rapid reversal of opioid dependence, patients may require administration of naloxone in conjunction with general anesthesia to prevent intolerable withdrawal symptoms. The alpha-2 adrenergic agonist clonidine may be useful to ameliorate the noradrenergic symptoms of withdrawal and may increase the chance of successful CONTINUING EDUCATION PA RT 1: R E COG N I T ION A N D R E F E R R A L T O E N H A NCE R ECOV E RY TABLE 4 Risk factors for opioid overdose RISK FACTOR CATEGORY EVIDENCE Drug regimen Ì Administered through nonmedical routes (injection or snorting)61 Ì High dose68,69 Ì Coprescribed benzodiazepines70-74 Ì Coprescribed antidepressants or sedatives/hypnotics75 Ì Use of long-acting opioid formulations76 Ì Use of buprenorphine for medication-assisted therapy77 Ì Longer durations of use69,78 Ì Use of oxycodone or methadone for pain79-81 Disease Ì Chronic pain82,83 Ì Mental illness or a history of alcohol or other substance abuse78,79 Social history Ì Relapsing to opioid misuse after a period of abstinence58,84,85 Ì Living in rural area and having low income69,71 Ì Receiving Medicaid69,71 Ì Obtaining opioid prescriptions from multiple providers and pharmacies86,87 Ì Using alcohol88 Source: Refs 61, 68-88 withdrawal. Benzodiazepines may also be administered to reduce anxiety, though caution should be used in patients who also have anxiolytic use disorder.52 Opioid withdrawal symptom severity can be assessed with the Clinical Opioid Withdrawal Scale (COWS) or the Subjective Opioid Withdrawal Scale (SOWS). Collaborative tapering agreements are recommended to outline patient and provider responsibilities throughout the process.89 Opioid use disorder management extends beyond detoxification/tapering alone and requires caring for the whole patient, including medical, psychological, vocational, social, and legal issues. Patients with opioid use disorder experience intense cravings for opioids in addition to experiencing the symptoms of withdrawal when opioid use is decreased or stopped. Substance use disorder is a chronic condition; long-term treatment after withdrawal/discontinuation is needed to support recovery. Treatment options need to be multifaceted and incorporate various modalities of care, including individual and group counseling, inpatient and residential treatment, inten- sive outpatient treatment, partial hospital programs, case or care management, medication-assisted treatment (MAT), recovery support services, 12-step fellowship programs, and peer support.92 Understanding Methadone maintenance studies have shown higher rates of abstinence from heroin and increased patient retention in OTPs. substance use disorder is as important for pharmacists as understanding any other chronic disease state. Pharmacists are uniquely positioned to inquire about opioid use and overdose risk, and to gather a list of local resources to make referrals for treatment/recovery services.93 MAT using methadone, buprenorphine, and/or short- or long-acting naltrexone is an important part of the recovery process. MAT has consistently been proven to be the most effective treatment for opioid use disorder in both short- and long-term studies and has been shown to decrease the incidence of drug-related poisonings.94,95 The U.S. Department of Health and Human Services has recommended expanding access to MAT and is making strides to loosen current regulations that restrict the prescribing of medications for managing opioid use disorder.96 Patients using MAT may require maintenance therapy for weeks or months to years as part of an opioid treatment program (OTP). OTPs are overseen, certified, and accredited by the Substance Abuse and Mental Health Services Administration (SAMHSA).97 Methadone maintenance therapy administered in a clinic setting has been used for several decades in patients suffering with opioid use disorder. Methadone is usually the least costly medication available for use by OTPs and can improve patient quality of life and health outcomes.98 Studies of methadone maintenance therapy have shown higher rates of abstinence from heroin and increased patient retention in OTPs (relative RR, 0.34; 95% CI, 0.22 - 0.44).99 Methadone maintenance in some studies has also been associated with lower rates of experiencing depression, contracting infectious diseases/HIV, committing crimes, and developing work/financial/family difficulties.91 Because of the potential for misuse and to avoid diversion, methadone is usually provided to patients under direct observation in a clinic setting as a single daily dose (duration of methadone activity is 2436 hours) but may also be prescribed for between-visit use at home once patients have demonstrated adherence to therapy.100 Higher doses of methadone (60-100 mg/day) are associated with higher rates of retention and lower rates of relapse to illicit drug use.101 Outpatient oral buprenorphine therapy with or without concomitant naloxone has demonstrated success in helping patients to abstain from opioid misuse. Buprenorphine acts as a partial agonist on opioid receptors and possesses a lower potential for misuse, induces less euphoria and DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 45 CONTINUING EDUCATION T H E P H A R M ACIST ’S ROL E I N M A NAG I NG OP IOI D USE DISOR DE R physical dependence, and exhibits a milder withdrawal profile compared with full opioid agonists. Buprenorphine also exhibits a ceiling effect, meaning that additional doses do not elicit an increased effect; this reduces the risk of overdose.102 In an analysis of opioid overdose deaths in New York, only 2% of patients had toxicologic evidence of buprenorphine use.103 Naloxone inclusion deters alteration of the prescribed dosage form by activating the release of the opioid receptor antagonist and precipitating withdrawal if injection is attempted after crushing or dissolving buprenorphine/naloxone. Buprenorphine is available as a generic agent in a sublingual tablet (with or without naloxone) and as a branded sublingual tablet (Zubsolv), sublingual film (Suboxone), and buccal film (Bunavail), all coformulated with naloxone to deter misuse.104 Buprenorphine may be prescribed by a qualified, trained outpatient physician (not a nurse practitioner or physician assistant) and dispensed to the patient for at-home use. While use of buprenorphine for pain is not limited, at this time providers wishing to treat patients for opioid use disorder outside of opioid treatment centers are limited in the number of patients they can treat with buprenorphine: 30 patients the first year and 100 (with permission) thereafter. Since patients use these medications longterm, this further limits the ability of physicians to care for new patients. Physicians must also complete an eight-hour course to be able to prescribe buprenorphine under the Drug Addiction Treatment Act (DATA) of 2000.105 Despite increased use of buprenorphine among Medicaid patients and in rural areas (because of availability of prescribing in physician offices), the overall number of patients treated with opioid agonist therapy did not change from 2007 to 2009, indicating a need for further education about buprenorphine availability.106 Therapy with buprenorphine may be maintained for long periods of time before tapering or attempting complete cessation. Buprenorphine tapering over four weeks with subsequent naltrexone therapy may offer advantages such as improved treatment response and retention over faster tapering regimens (one or two weeks).107 46 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM Buprenorphine at fixed or low doses is less effective at retaining patients in remission compared with methadone; however, the resolution of withdrawal symptoms is sistance untreated. Although the data demonstrated an increase in outpatient and physician office-based treatment, the largest increase was observed among inpatient facili- Because opioid tolerance fades in hours to days, resumption of use, particularly at prewithdrawal doses, significantly increases the risk of fatal overdose.” faster with buprenorphine.99 The first study comparing the efficacy of methadone and buprenorphine indicated similar positive long-term outcomes (minimum follow-up 2 years; mean 4.5 years) in terms of reduction in opioid use and mortality. However, buprenorphine users demonstrated significantly higher use of opioids within the first 22 months of the follow-up period versus methadone users and had lower long-term treatment participation rates.94 In a pilot study, a regimen of screening, brief intervention, and emergency department (ED)-supplied buprenorphine/naloxone plus referral to DATA-waived primary care physicians for continued buprenorphine for 10 weeks was compared with a regimen of screening, brief intervention, and referral for treatment and with a regimen of screening and referral for treatment alone. This study did not demonstrate decreased positive urine tests for opioids in ED-supplied buprenorphine/naloxone-treated patients, but did demonstrate increased patient engagement in care, fewer inpatient admissions for addiction, and decreased self-reports of illicit opioid use. These results indicate that ED-supplied buprenorphine is potentially cost-saving and emphasizes that treatment with MAT should be offered whenever and wherever opioid use disorder screening and diagnosis occur.108 Expansion of access to opioid agonist therapy has been shown to result in significant decreases in heroin overdose deaths.109 The National Survey of Drug Use and Health performed from 2004 to 2013 indicated that approximately 20% of people with an opioid use disorder were receiving any treatment, leaving four of five people who needed as- ties where buprenorphine may not be available, highlighting the need for expanded MAT programs across all settings.110 Pharmacists may play a key role in expanding access to buprenorphine. Survey results from the United States indicate that the majority of pharmacists and technicians support buprenorphine use for opioid use disorder and are not concerned about theft, diversion, or forgery compared with other controlled substances.111 Pharmacies in Australia, the United Kingdom, and Finland dispense opioid agonist therapy to stable patients to expand access to therapy, particularly in rural areas, and often at a lower cost than is available at publicly funded clinics. These pharmacybased services are generally well supported by the public and pharmacists. Problems cited in surveys of pharmacists in these countries include a lack of pharmacist training, increased potential for diversion, stigmatization of patients, lack of pharmacist reimbursement, inability of customers to pay dispensing fees, and need for increased communication between pharmacists and providers.112,113 A small study examining a collaborative pharmacist-physician approach to increase access to buprenorphine treatment demonstrated high program retention rates and adherence to buprenorphine therapy. Pharmacists conducted intake and follow-up assessments of patients and were responsible for providing medication adherence education, monitoring medication outcomes, and assisting in diversion prevention. The positive pilot study results led to the establishment of a permanent program and the first state-approved collaborative practice agreement related to opioid agonist therapy.114 CONTINUING EDUCATION PA RT 1: R E COG N I T ION A N D R E F E R R A L T O E N H A NCE R ECOV E RY TABLE 5 Assessment of patient readiness to quit STAGE OF CHANGE PATIENT THOUGHTS AND BEHAVIORS STRATEGIES TO AFFECT CHANGE Precontemplation Ì Patients not considering changing the behavior Ì Patients may be unaware of risk or unwilling to acknowledge risk Ì Strongly advise to quit Ì Provide information regarding health risks and concerns Ì Express empathy, foster communication, and offer support Contemplation Ì Patients are aware of risk Ì Patients may be considering change but are not ready to commit to change Ì Strongly advise to quit Ì Encourage self-reevaluation of concerns Ì Identify reasons for continuing use and reasons for stopping Ì Express empathy, foster communication, and offer support Preparation Ì Patients are actively considering change and are willing to take steps to change within the next 30 days Ì Facilitate the process of initiating change Ì Discuss coping strategies (cognitive and behavioral) Ì Identify potential triggers for relapse Ì Refer to available recovery and treatment programs with MAT and comprehensive care Action Ì Patients have made a change in the behavior within the past six months Ì Praise success Ì Assess and discuss status of the quit attempt Ì Encourage adherence to medication-assisted treatment and other recovery programs Ì Discuss coping strategies (cognitive and behavioral) Ì Identify ongoing triggers for relapse Maintenance Ì Patients have made a change and maintained the change for the past six months or longer Ì Praise success and reinforce health behaviors Ì Encourage continued adherence to medication-assisted treatment and other recovery programs Abbreviations: MAT, medication-assisted treatment. The opioid receptor antagonist naltrexone has long been considered for use as maintenance therapy to block the subjective effects of opioids, and long-acting formulations of naltrexone have increased efficacy for treatment and decreased risk of hepatic toxicity versus short-acting products.115,116 Injectable extended-release (ER) naltrexone helps to control cravings for opioids and maintain abstinence from opioid use. This agent may be particularly useful for those patients in whom opioid agonists are not appropriate or those returning to their usual environment after a period of enforced abstinence (such as incarceration or hospitalization).92 Monthly injectable ER naltrexone (Vivitrol) has been found to be an effective treatment strategy for patients after opioid detoxification and complete discontinuation of opioid maintenance therapy (seven or more days off opioid therapy). In one study, patients randomized to inject- Source: Adapted with permission from Ref 129 able ER naltrexone versus placebo dem- portant and easily implementable role for onstrated a significantly higher proportion pharmacists. Statewide prescription drug of weeks of confirmed abstinence, median monitoring programs (PDMP) can facilitate opioid-free days, and number of days of retention.117 Unconventional and controversial treatments for chronic opioid use disorder are also being studied. One study in the United Kingdom showed greater success with supervised injectable heroin-assisted therapy (HAT) versus oral methadone treatment in maintaining abstinence from illicit street heroin. Denmark and Switzerland regularly operate HAT programs. Several European countries have conducted trials with HAT and have shown reductions in crime rates and illicit drug and alcohol use, with improvements in patients’ mental and physical health.118,119 pharmacist recognition of patients who may be excessively filling prescriptions for conApproach to the patient Identifying patients at risk for or actively trolled substances and therefore may be suffering from opioid use disorder is an im- at risk for overdose.120 Patients with prescrip- Pharmacists are uniquely positioned to have critical conversations with patients who they suspect may be misusing opioids.” DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 47 CONTINUING EDUCATION T H E P H A R M ACIST ’S ROL E I N M A NAG I NG OP IOI D USE DISOR DE R tion opioid use may be taking the agents as prescribed, or they may be prescribed misusers, medically healthy misusers, or illicit users.121 Persons with opioid use disorder are more likely to be young men, have a history of multiple opioid prescriptions, have a higher-day supply of medication, fill prescriptions at multiple pharmacies, have a that improving pharmacist-patient communication would deter misuse.124 Pharmacists should have readily accessible educational resources available to give to patients and should be prepared to make referrals to local treatment and recovery programs. Factors shown to be positively associated with pharmacist provision of Opioid use disorder management extends beyond detoxification/tapering alone and requires caring for the whole patient, including medical, psychological, vocational, social, and legal issues.” concomitant psychiatric disorder, pay higher copays for opioids, use short-acting opioids, and have a higher rate of health service use.122 In Part 2 of this continuing education program, we will outline the utility of the PDMP in detail and focus on the identification of patients at risk of opioid overdose who may benefit from naloxone therapy for emergent reversal. Pharmacists are uniquely positioned to have critical conversations with patients who they suspect may be misusing opioids. The goal of these conversations is to increase patient awareness of the risks of opioid use disorder and provide information regarding options for recovery. A recent survey of 739 pharmacists from Texas and Utah found that just under half of pharmacists are currently screening for misuse of prescription opioids and/or discussing opioid misuse with patients. Pharmacists conducting screening were more likely to be employed by a chain pharmacy, have more years in practice, and/or be interested in conducting research related to prescription opioid misuse. Pharmacists who conducted screenings were also more likely to subsequently discuss opioid misuse with patients than those who did not.123A survey of pharmacists from Tennessee indicated that the majority (87.5%) of pharmacists perceive that prescription opioid misuse is an issue in their pharmacy setting, and approximately half said substance use disorder treatment and recovery information to patients include having treatment facility information available in the pharmacy, having confidence in their ability to discuss available treatment facility options, having participated in continuing education related to opioid use disorder, being male, and working more hours per week in the practice setting.125 Pharmacy and substance use disorder experts recommend building off pharmacists’ experience with medication therapy management, knowledge of adverse drug events, and skill in promoting adherence to prescribed regimens as a framework to identify opioid misuse and coordinate interventions in the community pharmacy setting.126 Health behavior change is a widely researched area of study that pharmacists may draw from to communicate with patients about opioid use disorder. The Transtheoretical Model (TTM) of health behavior change is widely used in helping patients to change unhealthy behaviors such as smoking, physical inactivity, and substance misuse. Important components of the TTM include assessing a patient’s readiness to change, helping to create a decisional balance (pros and cons of change), and building patient self-efficacy.127 Patients may present anywhere along the continuum of readiness to change. Research has shown that matching messages to the stage of readiness to change is important to build- ing rapport and making progress toward change (Table 5).128,129 Adequate communication with patients in the community pharmacy setting regarding opioid misuse is hindered by a focus on processing and dispensing prescriptions over clinical operations. By prioritizing the identification of patients at highest risk of opioid misuse and scheduling extensive counseling and follow-up, pharmacists can advance the profession of pharmacy, improve job satisfaction, and improve patient-centered care.130 The education and training of pharmacists tend to focus on understanding pharmacology and therapeutics, so pharmacists may miss opportunities to offer care that is focused on individual patient needs and experiences.131 Pharmacists can use motivational interviewing when communicating with patients with an opioid use disorder to maximize the chances that patients will consider and implement a health behavior change. Motivational interviewing is a “collaborative, person-centered form of information exchange to facilitate constructive patient sense-making about health.”132 Patient readiness, assessment of the importance of the problem, and confidence that a change can be made are critical to the likelihood of an attempt.133 Pharmacists can facilitate patient behavior change by building rapport and trust with the patient, exploring the patient’s resistance or ambivalence to change, and providing information that helps the patient make sense of the disorder and benefits of change.132 Conclusion Pharmacists can build rapport with patients by approaching suspected opioid use disorder with empathy in a nonjudgmental manner. By facilitating a patient’s understanding of opioid use disorder, including risks of misuse, benefits of stopping, and availability of different treatment programs, pharmacists can effectively participate in assisting patients with opioid use disorder. References are available online at www.drugtopics.com/cpe. r For immediate CPE credit, take the test now online at > www.drugtopics/cpe Once there, click on the link below Free CPE Activities 48 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM CONTINUING EDUCATION T E ST QU E ST ION S For Pharmacists 1. Which of the following regarding the increase in opioid prescribing is FALSE? a. It cannot be accounted for by an increase in pain-related conditions. b. It has coincided with an increase in opioid overdoses and deaths. c. It is predominately related to an increase in pain specialty clinics. d. It has been influenced by promotional advertising by pharmaceutical companies. 4. 5. 2. 3. Which of the following factors can pharmacists AVOID to decrease the stigmatization of patients with an opioid use disorder? a. Using derogatory language such as “junkie,” “addict,” or “abuser” to describe patients b. Using the Prescription Drug Monitoring Program to identify patients with potential opioid dependence or opioid use disorder c. Strongly advising patients who have developed an opioid use disorder to quit and explaining the risks of continued use d. Counseling patients on the risks of long-acting opioids Which of the following is a symptom of opioid withdrawal? a. Diaphoresis b. Miosis c. Bradycardia d. Constipation 6. 7. Which of the following is an important criterion for differentiating between opioid use disorder versus physical dependence? a. Experiencing withdrawal symptoms upon discontinuation of use b. Experiencing withdrawal symptoms upon administration of an opioid antagonist c. Using opioids at higher doses to control pain d. Using opioids to avoid symptoms of withdrawal Which of the following is an important risk factor for opioid overdose? a. Use of buprenorphine maintenance therapy for physical dependence b. Resumption of opioid use after recent withdrawal from opioid dependence c. Co-prescribed antidepressant therapy d. All of the above Which of the following has been demonstrated to increase the efficacy of methadone for relapse prevention? a. Combination with naloxone b. Higher doses (60-100 mg/day) c. Shorter duration of use (less than 8 weeks) d. Concomitant benzodiazepine use Which of the following is fastest for the resolution of withdrawal symptoms? a. Naloxone b. Methadone c. Naltrexone d. Buprenorphine 8. Which of the following is associated with the use of buprenorphine? a. Higher retention rates versus methadone b. Higher risk of overdose versus methadone c. Similar long-term outcomes versus methadone d. Similar rates of continued heroin use as methadone 9. Which of the following factors is associated with increased pharmacist provision of opioid use disorder treatment and recovery information? a. Female sex b. Lower number of hours worked per week c. Availability of treatment facility information d. The pharmacist being in recovery 10. Pharmacists who provide more extensive opioid use disorder counseling and follow-up enjoy which of the following? a. Improved patient-centered care b. Increased job satisfaction c. Advancement of the pharmacy profession d. All of the above For Pharmacy Technicians 1. 2. 3. 4. Which of the following BEST represents the scope of prescription opioid use in the United States? a. More than a quarter of Americans have used a prescription opioid within the past year. b. More than half of Americans have used a prescription opioid within the past year. c. More than three-quarters of Americans have used a prescription opioid within the past year. d. None of the above Approximately what percentage of patients taking prescription opioids for chronic pain report misuse or high-risk use? a. 5% b. 10% c. 25% d. 50% Which of the following describes complications that may occur as a result of stigmatization of persons with opioid use disorder? a. Increased chronic patient stress b. Decreased access to treatments c. Decreased development of new treatments d. All of the above The risk of opioid overdose is highest in which of the following patient populations? a. Black or African American men b. Hispanic women c. White non-Hispanic men d. Asian women 5. Which of the following regarding opioid use disorder is FALSE? a. Opioid use disorder involves chemical changes in the brain of patients. b. Opioid use disorder is a voluntary disorder. c. Opioid use disorder treatment increases the likelihood of successful quitting. d. Opioid use disorder is influenced by genetic and environmental factors. 6. Which of the following factors in a patient’s history puts him or her at the highest risk for opioid use disorder? a. Alcohol use disorder b. Psychiatric disorders c. Sexual abuse d. All of the above 7. Which of the following is a potential indicator of opioid misuse and risk of opioid overdose? a. Use of hydrocodone for pain b. Younger patient age c. Use of oral pain medications d. Filling prescriptions on time 8. A patient presents a new prescription for Oxycontin and one of the following medication classes to be refilled. In which of the following scenarios would you alert the pharmacist that a patient may be at higher risk of opioid overdose than if she filled just the Oxycontin prescription? a. Benzodiazepines (eg, lorazepam, alprazolam) b. Quinolone antibiotics (eg, moxifloxacin, levofloxacin) c. Laxatives (eg, senna, polyethylene glycol) d. Antiseizure medications (eg, levetiracetam, lamotrigine) 9. Which of the following patient behaviors indicates a risk for an opioid use disorder and should be referred to the pharmacist for counseling? a. Filling multiple opioid prescriptions b. Paying higher copays for opioids c. Having a higher-day supply of opioids d. All of the above 10. True or false: Because a majority of pharmacists surveyed feel that prescription misuse is a problem in pharmacy settings, patients at risk should be referred to pharmacists to help address this problem. a. True. b. False. DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 49 REGULATORY & LEGAL LEGAL COMPLIANCE Ned Milenkovich, PharmD, JD “Death with dignity” laws gain traction in several states “Death with dignity” laws are on the rise around the nation. Today, five states legally recognize assisted suicide in the face of terminal illness. They include Oregon, Washington, Montana, Vermont, and most recently, the country’s most populous state, California. It is estimated that in 2016 one in 10 Americans will live in jurisdictions in which it is legal for a physician to prescribe a lethal drug to a terminally ill patient who, under a variety of safeguards, may commit suicide. While only five states currently allow individuals to choose this option, more than 25 other states have introduced bills that discuss the legalization of some form of “right-to-die” measures. death within six months. The act goes on to require that the individual be a resident of California, be physically and mentally capable of self-administering the aid-in-dying drug, and that the application process for the medication include two verbal requests, submitted a minimum of 15 days apart, and a written request, all addressed to the patient’s attending physician. Many patients still excluded The End-of-Life Option Act California’s “End of Life Option Act” serves as a good touchstone in understanding the death with dignity landscape, particularly in regard to how far it has come and in what direction it may expand in the future. The act, which became effective in January 2016, authorizes adults to request a drug for the purpose of ending their lives if they meet certain qualifications and their physicians determine that they suffer from a defined terminal disease. While the act creates an avenue for individuals to make right-to-die choices, its restrictions and qualifications create limits on who may avail themselves of this option. In California, the act requires that the individual suffer from a “terminal disease,” which is defined as an incurable and irreversible disease that has been medically confirmed and will, within reasonable medical judgment, result in California’s End of Life Option Act still excludes a considerable range of patients who may want to be covered. This includes people with progressive debilitating diseases who don’t have a clear six-months-to-live prognosis, as well as people with dementia, one of the fastest-growing health threats in the United States. There are similar restrictions in the other four states that currently allow this practice. Moreover, there are medical conditions that are unpredictable in terms of life expectancy, as well as in terms of how, when, and in what order bodily functions are lost. Examples of these include progressive neurological diseases such as multiple sclerosis and ALS; patients with these conditions who want to avoid the most debilitating final stages might end their lives prematurely, afraid that their ability to self-administer the life-ending medication may become impossible. Utah’s death with dignity bill proposed that individuals could seek lifeending medication if they were suffering from an “intractable and unbearable disease,” meaning a bodily disorder that cannot be cured or successfully palliated, and that caused suffering severe enough to cause patients to prefer death. This bill was put on hold for further review; however, State Representative Rebecca Chavez-Houck plans to reintroduce the bill again in the 2016 session. National conversation only beginning The death with dignity discussion is only beginning, as there are more than 25 states considering bills that concern death with dignity laws. This movement will affect not only individuals who choose this option, but also physicians and pharmacists who may be asked to play a role in a patient’s end-of-life decision. There will certainly be legal implications, and equally important, there will be moral and social issues to be debated in our society. Ned Milenkovich is a partner in the health, drug, and pharmacy practice at Much Shelist PC, and vice chair of the Illinois State Board of Pharmacy. Contact him at 312-521-2482 or nmilenkovich@ muchshelist.com. This article is not intended as legal advice and should not be used as such. When legal questions arise, pharmacists should consult with attorneys familiar with the relevant drug and pharmacy laws. We want to hear from you. Post your comments at > www.drugtopics or e-mail them to > [email protected] 50 DrugTopics | FEBRUARY 2016 | DRUGTOPICS.COM PROFILE Anniver sary Issue Christine Blank, Contributing Editor A pharmacy pioneer of the 20th century bounds into the 21st Fred Mayer, RPh, MPH, Drug Topics’ longtime editorial advisor and CEO of Pharmacy Planning Services Inc., is known to almost everyone in pharmacy as both an advocate for the profession and a champion of public health causes such as The Great American Smokeout, National Condom Week, and the Medication Take Back Day sponsored by the Drug Enforcement Administration (DEA). While some people might think of retirement at Mayer’s age — he’s 84 — he acts like he’s just getting started. Drug Topics recently spoke with Mayer about his accomplishments and the important issues facing pharmacists. DT: You are a working pharmacist. Why is that important to you? Mayer: If you’re going to lead pharmacy into the future, FRED MAYER I think it’s very, very important to have a firsthand awareness and understanding of how the profession works, its problems and issues, in order to solve our many, many problems. Causes and challenges DT: What are the greatest challenges facing pharmacy? Mayer: Leadership. Like Moses, we need to get out of the desert of counting, pouring, and typing to better utilization of pharmacists’ education and skills to improve patient care. In order to do this, we must document successes that pharmacists have had — such as the fact that last year, pharmacists immunized 42% of all U.S. citizens for the flu. We must also recognize the successes of pharmacists all over the United States who are changing and reforming the pharmacy practice acts in their states. DT: Why has it been so important to you to lead and participate in causes such as the Great American Smokeout and DEA’s Take Back Day? Mayer: I have found that the No. 1 problem in the pharmacy profession is lack of a take-charge attitude. Most pharmacists are introverted, not outspoken. We need to be more like nurses in our thinking and attitudes and ability to think outside the box. What makes nurses so effective is that they are organized as unified healthcare professionals. My No. 1 priority would be to unify all pharmacy organizations so they could speak with a single voice. Impact DT: Out of all the causes you have been involved in, which ones have made the strongest impact on public health and/or pharmacy? What do you consider your greatest career accomplishments? Mayer (counting): One, being a father of public health pharmacy in the U.S.A. Two, instigating the Great American Smokeout; 50 million Americans stopped smoking through this simple campaign. Three, safety caps on prescription vials: The lives of 7,230 kids have been saved each year through Poison Prevention Month. Four, increased awareness of reproductive health and reduction of unplanned pregnancies, especially teen pregnancy in the U.S. Five, reduction of sexually transmitted diseases and sexually transmitted infections, condom awareness cam- paigns, sex education in the schools, and working with Planned Parenthood and PTAs in school districts. DT: Why have PPSI’s public health campaigns been so successful? Mayer: The reason we have been so successful is that we get our message out to the public through the consumer networks of our 6.4 millionstrong organizations California Alliance for Retired Americans (CARA) and Alliance for Retired Americans (ARA), as well as the press we have received over the past 50 years through Drug Topics magazine. We could not motivate, educate, and communicate our 55 public health campaigns without their great assistance. Enthusiasm DT: Do you love pharmacy now as much as when you first started? Mayer: Yes. I love it more than I did 60 years ago, when I first graduated from UCSF, the No. 1 school of pharmacy in the country. One of the things they taught us at UCSF — and at UC Berkeley, where I obtained my Masters of Public Health in 1970 — was to think outside the box. It’s time for pharmacists to think outside the box. With a shortage of 16,000 physicians in the U.S., there is no better time than now to go out and practice public health pharmacy. DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 51 PRODUCTS & SERVICES SHOWCASE T BUY-SELL-BROKER Contemplating the Sale of Your Pharmacy? 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DRUGTOPICS.COM | FEBRUARY 2016 | DrugTopics 55 Anniver sary Issue Remember When Mark Lowery, Content Editor One “bitter ender” holds out against corporate pharmacy ownership Back in 1974, Drug Topics examined the issue of pharmacy ownership. That is, the restrictions individual states had once placed on who could own pharmacies within their borders. That article noted that “drug chains, supermarkets, and mass merchandisers will fight pharmacy ownership regulation to the bitter end, state by state.” And so they did. For the most part, corporate America fought and won that battle, and chain pharmacies such as Walgreens, CVS, and Walmart now dominate the industry. However, in one state that’s not the case. In 2014, North Dakota residents rejected a ballot measure that would have eliminated pharmacy-ownership restrictions. Today North Dakota remains the only state that prevents big-box retailers from providing medications to consumers. According to the Center for Public Integrity, Walmart spent $9.3 million to convince North Dakota residents to shoot down the state law that requires majority ownership of pharmacies in the state to be held by pharmacists. Despite that influx of corporate dollars, nearly 60% of the state’s residents rejected the effort to change North Dakota’s pharmacy-ownership rules. “I would hope the people of North Dakota have spoken,” Steve Boehning, president of the North Dakota Pharmacists Association, said following the ballot measure. “It’s been defeated legally and legislatively, and now by the public.” NEW DRUG REVIEW DISORDER AT SE XUAL DESIRE FLIBANSERIN> TO TRE pg. 37 ® DrugTopics.com 160 Vol. 160 2016 || Vol. February February 2016 No. No. 22 ISSUE 1856-2016 SPECIAL ANNIVERSARY Download the Free APP for More of Our Legacy Images and Stories. >www.drugtopics.com/drugtopicsapp D From Apothecary to Pharm VOICES 2 CPE Recognition & referral to enhance 56 Working together for the greater good: MD versus RPh 6 i jb? 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