Vol. 8, No. 6 November 2013 T T HE HE K K ENTUCKY ENTUCKY P P HARMACIST HARMACIST Marriott Griffin Gate Resort, Lexington, KY November 15-16, 2013 KPhA Open House Celebrating Kentucky and American Pharmacists Month More Photos inside on Page 5. Video of the proclamation presentation is on the KPhA YouTube channel. http://www.youtube.com/user/KyPharmAssoc News & Information for Members of the Kentucky Pharmacists Association Above: Lee Cruse, from LEX 18 discusses the Mobile Pharmacy Unit with ED Robert McFalls and Dir. of Pharmacy Emergency Preparedness Leah Tolliver on sunrise. Right: President-Elect Bob Oakley and President Duane Parsons with Mr. Froggy and Roamey. 2013 CE Deadline: We know Your CE is important to you. To help us help you, all CE quizzes from The Kentucky Pharmacist must be received in the KPhA office no later than noon on December 30 to be counted for 2013!
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Transcript
Vol. 8, No. 6
November 2013
TTHEHE KKENTUCKYENTUCKY
PPHARMACISTHARMACIST
Marriott Griffin Gate Resort, Lexington, KY
November 15-16, 2013
KPhA
Open House
Celebrating Kentucky and
American Pharmacists Month
More Photos inside on Page 5.
Video of the proclamation
presentation is on the KPhA YouTube channel.
http://www.youtube.com/user/KyPharmAssoc
News & Information for Members of the Kentucky Pharmacists Association
Table of Contents— Oath— Mission Statement 2 President’s Perspective 3 2013 KPhA Mid-Year Conference 4 Pharmacists Month Open House 5 From your Executive Director 6 APSC 8 KPhA in the Political Arena 9 Saving the Bowl of Hygeia 12 November 2013 CE: Prevention and Treatment of Venous Thromboembolism 13 November Pharmacist/Pharmacy Tech Quiz 20 KPhA Emergency Preparedness Initiative 21
Technician Review 22 December 2013 CE: Cocoa 23 December Pharmacist/Pharmacy Tech Quiz 30 Kentucky Renaissance Pharmacy Museum 31 KPhA New and Returning Members 32 Pharmacy Law Brief 36 UK College of Pharmacy White Coat Ceremony 37 Pharmacy Policy Issues 38 Pharmacy Time Capsules 39 Pharmacists Mutual 40 Cardinal Health 41 KPhA Board of Directors 42 50 Years Ago/Frequently Called and Contacted 43
Oath of a Pharmacist
At this time, I vow to devote my professional life to the service of all humankind through the profession of phar-
macy.
I will consider the welfare of humanity and relief of human suffering my primary concerns.
I will apply my knowledge, experience, and skills to the best of my ability to assure optimal drug therapy out-
comes for the patients I serve.
I will keep abreast of developments and maintain professional competency in my profession of pharmacy.
I will embrace and advocate change in the profession of pharmacy that improves patient care.
I take these vows voluntarily with the full realization of the responsibility with which I am entrusted by the public.
Kentucky Pharmacists Association
The mission of the Kentucky Pharmacists Associa-
tion is to promote the profession of pharmacy, en-
hance the practice standards of the profession, and
demonstrate the value of pharmacist services within the
National Legislative Update—Matthew J. DiLoreto, Director – State Government Affairs, National Community Pharmacists Association (NCPA)
10:45-11:14 a.m. Hazardous Waste in a Pharmacy (0143-0000-13-073-L03-P&T)
Mike Burleson, Executive Director, Kentucky Board of Pharmacy
11:50 a.m. Lunch & Advancing Pharmacy Practice in Kentucky Coalition Update
12:45-2:00 p.m. Legislative Presentations
2:15-3:45 p.m. Effective Legislative Involvement Part 2 (0143-0000-13-072-L03-P&T)
Jan Gould, Senior Vice President - Government Affairs, Kentucky Retail Federation; Trish Freeman, RPh, PhD, Associate Professor and Director, Center for the Advancement of Pharmacy Practice, UKCOP
4:00-5:00 p.m. Legislative Issues Briefing and House of Delegates
Saturday, November 16, 2013 7:30 a.m. Registration Opens
8:00-8:30 a.m. Breakfast
8:45-10:15 a.m. Pharmacy’s Role in Emergency Preparedness: How YOU Can Become Involved
(0143-0000-13-065-L04-P&T)
Leah Tolliver, KPhA Director of Pharmacy Emergency Preparedness
10:30-11:30 a.m. New HIPAA Rules: Key Implications For Your Organization
(0143-0000-13-074-L03-P&T)
Christopher Shaughnessy, Esq., McBrayer, McGinnis, Leslie & Kirkland PLLC
Noon-6:00 p.m. Adult Immunization Training Program (0143-0000-13-015-L04-P&T) (includes lunch)
Cathy Hanna, PharmD, Director of Research and Education, APSC
Watch for the January 2014
issue of The Kentucky Pharmacist
for a report on the event.
November 2013
THE KENTUCKY PHARMACIST 5
2013 KPhA Pharmacists Month Open House
Open
House
2013
KPhA welcomed members, partners and guests to the
KPhA headquarters on Oct. 30, 2013 to celebrate
Kentucky and American Pharmacists Month. Lee Cruse,
from WLEX18 in Lexington, came out for live updates
during Sunrise and Froggy 104.9 & 101.7 broadcast live
during the event, which showcased the state’s Mobile
Pharmacy Unit and displays from the Kentucky
Renaissance Pharmacy Museum. RIGHT: Eric
Friedlander, Deputy Secretary of the Cabinet for Health
and Family Services, presents President Duane Parsons
with a proclamation from Gov. Steve Beshear proclaiming
October as Pharmacists Month.
November 2013
THE KENTUCKY PHARMACIST 6
From Your Executive Director
MESSAGE FROM YOUR
EXECUTIVE DIRECTOR
Robert “Bob” McFalls
We were all excited recently to learn about California’s pro-
gress in advancing their profession through the passage of
Provider Status legislation. We sincerely congratulate the
California Pharmacists Association (CPA) and our pharma-
cist colleagues in The Golden State, and it has been my
pleasure to extend our collective accolades in person to
CPA’s CEO, Jon Roth. California’s action has captured the
attention of the media, and that represents a victory for all of
us in advancing this critical conversation in Kentucky.
Built upon a solid tradition of dispensing medication and car-
ing for the health care needs of patients, those of us within
the pharmacy family readily recognize how services by phar-
macists are expanding and continue to grow over time. To-
day, we are learning about new models of care by pharma-
cists who work in a variety of practice settings who are
providing advanced services to patients in a number of ways,
e.g., coordination of medications during periods of transitions
of care, chronic disease management, medication monitor-
ing, as well as wellness services, among others.
Pharmacists throughout Kentucky are doing really great
work, and in recognition of your innovative practice, I have
had the privilege of being invited to participate in three meet-
ings with APhA on the topic of Provider Status during the
past year. KPhA has established Provider Status as a top
legislative priority as did the Advancing Pharmacy Practice
Coalition in Kentucky when we met at Summit II on April 13.
We are on a winning track, but this effort will certainly require
a long-term commitment of energy, collaboration and pas-
sionate engagement. There are several encouraging signs
on the horizon. In December 2012, JCPP CEOs agreed to
collaborate on Provider Status Principles. Consequently, a
coalition of 14 national organizations have been working
since mid-January at the federal level on Provider Status
principles; these partners include APhA, AACP, ACCP,
AMCP, ASCP, ASHP, CPNP, FMI, IACP, NACDS, NASPA,
NCPA, Rite Aid and Walgreens. And through NASPA—the
National Alliance of State Pharmacy Associations, we are
working closely with our sister state pharmacy associations
on this strategic initiative.
For purposes of this column, I decided to informally term the
resource and report, Improving Patient and Health System
Outcomes through Advanced Pharmacy Practice: A Report
to the U.S. Surgeon General 2011 as “The Provider Status
Guidebook” (or The P.S. Guidebook for short). In this re-
spect, The P.S. Guidebook provides a great treatise on Pro-
vider Status, and I want to once again encourage everyone
to read or review this report periodically as we continue to
work together on this priority. The P.S. Guidebook clearly
outlines how pharmacists have been and are continuing to
be integrated into primary care as contributing health care
providers by managing disease and delivering patient care
services following diagnosis. This is especially true within the
federal health delivery system and infrastructure. The report
further notes that the pharmacist’s collaboration with the phy-
sician provides for higher quality, safer and better patient
outcomes as s/he collaborates with the prescriber as an inte-
gral contributor to the comprehensive healthcare team.
The P.S. Guidebook strongly encourages policy makers to
more effectively review and utilize evidence-based, pharma-
cist-delivered models of patient care. Citing the impact that
chronic disease management is having on our healthcare
system, The P.S. Guidebook documents that chronic diseas-
es currently affect 45 percent of the population while ac-
counting for some 81 percent of all hospital admissions, 91
percent of all prescriptions filled and 76 percent of all physi-
cian visits. Alarmingly, the report reminds us that 99 percent
P.S. …I will apply my knowledge, experience, and skills to the best of my ability to assure
optimal outcomes for my patients….
November 2013
THE KENTUCKY PHARMACIST 7
From Your Executive Director
of all Medicare spending goes to beneficiaries with chronic
disease. Turning more locally, chronic diseases (especially
cancer and heart disease) account for 70 percent of our
state’s total mortality and are the most costly of all health
problems according to the KY Institute of Medicine (The
Health of Kentucky: A County Assessment, 2007). Further,
the Institute reports that many of these chronic diseases
are highly preventable and/or treatable through changes in
personal behaviors and/or primary healthcare interven-
tions. The P.S. Guidebook denotes that the pharmacist is
equipped to serve as “the clinical chronic disease manag-
er” in working with the physician to address such chronic
disease management challenges as well as providing oth-
er cognitive and clinical services. In fact, the pharmacist
has been doing so for more than 40 years (Fisher et al,
Pharmacy in History, 1995, cited).
Our collective efforts to advance Provider Status come at
a time when there are more clinically trained pharmacists
and many others who are willing to be trained. Some 79 of
Kentucky’s counties already are above the national aver-
age in terms of their percentage of elders. Given the
state’s aging demographic imperative and the increasing
shortage of primary care doctors in the Commonwealth
(currently projected at 1,917 and growing: KY Rural Medi-
cal Educators Conference, May 2013), we find ourselves
at a crossroads of patient need and pharmacist expertise.
We are strategically aligned, and we must unite to make
the case for our patients.
With respect to the physician’s perspective, The P.S.
Guidebook also reports on a respondent-driven survey
developed by the U.S. Public Health Service to seek the
input of HIS physicians on the clinical and administrative
impact of pharmacists in delivering primary care services,
including but not limited to disease management. With
respect to results, the report cites that “76.8 percent of
physicians surveyed ‘agreed’ or ‘strongly agreed’ that from
their experiences, the services provided by pharmacists
provide adequate evidence to recognize them as billable
non-physician practitioners.”
In reading the sections of the Social Security Act which
determines eligibility for Medicare Part B and related
health care programs, it is amazing that the word
“provider” appears more than 70 times while recognition of
the role of the pharmacist is conspicuously absent. There
are several potential pathways to achieving Provider Sta-
tus, and the SSA is only one. Part B, Part D, the CMS
Center for Medicare and Medicaid Innovation, ACOs,
HRSA, Medicaid, the Kentucky Health Insurance Ex-
change, Medical Homes, Private Payers—all or any one of
these represents an opportunity for us to advance the role
of the pharmacist in serving the needs of the patient at a
reasonable reimbursement level. In August, CMS released
Medication Therapy Management in Chronically Ill Popula-
tions: Final Report, concluding among other findings that
“Poor medication adherence has been associated with
adverse health outcomes and increased risk of mortality
across multiple disease conditions, particularly among pa-
tients with chronic conditions.” CMMI has also declared its
intent to fund one or more demonstrations in 2014 to ad-
dress medication adherence. YOUR KPhA developed and
submitted a proposal to participate in this initiative, and we
will keep our members informed about CMS’ funding deci-
sion. I am pleased to report that the level of collaboration
was strong, and we will continue to explore funding oppor-
tunities to advance Provider Status with CMMI and others.
All parties involved in Provider Status discussions quickly
acknowledge that additional work is going to be needed to
shift the paradigm from uncompensated clinical and cogni-
tive services to billable service activities that pharmacists
provide or can provide. We can use the experience and
lessons learned by Rx Therapy Management with MTM
services for state retirees, along with other services that
pharmacists are currently providing. Health care reform is
a driver and will be on our side as we continue to explore
these opportunities. Staff from former HHS Secretary Mike
Leavitt’s firm, Leavitt Partners, challenged us at our Sep-
tember meeting at APhA headquarters to recognize that
health care reform (with or without The Affordable Care
Act) will continue to drive health care cost containment
and focus on improved health care and outcomes. Those
sentiments were echoed again at the NCPA Convention in
October in remarks offered by former President Bill Clinton
in terms of the pharmacist’s role in improving care while
helping to contain costs. Pharmacists can and should be a
critical part of the health care reform solution.
I titled this column, P.S., in the spirit of post scriptus from
the Latin with its literal meaning of “after having been writ-
ten.” Provider Status should not be viewed as an “after
fact.” As illustrated by the inclusion of a portion of the Oath
of a Pharmacist in the heading, we can and should think
about Provider Status as another volume in the practice of
pharmacy as we continue to build upon the myriad contri-
butions that pharmacists, pharmacy technicians and phar-
macies contribute to your patients.
I look forward to hearing from you as we work together to
advance Provider Status. Share your stories. Drop me a
note. Let’s chat at one of our meetings. Give me a call.
Send me an email. Meanwhile, on behalf of YOUR KPhA
staff, we wish you and yours a happy and joyous holiday
season.
November 2013
THE KENTUCKY PHARMACIST 8
APSC
November 2013
THE KENTUCKY PHARMACIST 9
KPhA in the Political Arena
KPhA IN THE POLITICAL ARENA
Guardian of the Profession
Throughout its history, the Kentucky Pharmacists Associa-tion (KPhA) has maintained a positive and respected posi-tion in the Commonwealth’s political arena. To Kentucky legislators and executive branch officials, KPhA is the voice of Kentucky pharmacy concerning legislative and regulatory matters and has served as the Guardian of the Profession of Pharmacy since its inception in 1879.
Maintaining KPhA’s presence in the Capitol is a high priori-ty for the Association. Political advocacy for the profession of pharmacy is vital to preserve a favorable and progres-sive environment for the practice of pharmacy in the Com-monwealth.
Over the years KPhA, through its political activities, has been instrumental in shaping public policy to the benefit of pharmacists in all practice settings. KPhA’s accomplish-ments have benefited both the professional practice of pharmacists and the health care delivery system in which they practice. Below is a brief summary of KPhA’s major legislative and regulatory successes in recent years:
The 1990s
The early nineties saw the beginning of a serious debate on health care reform both at a national and state level. KPhA stepped to the forefront representing the profession in the debate. In 1991, KPhA worked with the legislature and state Medicaid officials on HB 21, the original provider tax bill, and successfully lobbied for a significant increase
in the dispensing fee.
The 1994 session has sometimes been dubbed the “health care session.” KPhA’s work during the interim paid off as pharmacy fared well under the KY Health Care Reform Act. KPhA scored a major victory in the health care reform de-bate with the passage of an “any willing provider” provi-
sion in state law.
In 1995, KPhA along with other pharmacy organizations, laid the groundwork for a major revision in the Pharmacy Practice Act. The consensus-building process resulted in widespread agreement in the profession and a cross-professional coalition to advance its passage. HB 467 re-ceived nearly unanimous approval of the Kentucky General Assembly and was signed into law by Governor Patton in April 1996. The passage of the Pharmacy Practice Act ush-ered in a new era for Kentucky’s pharmacists. Its progres-sive provisions including collaborative care agreements, the recognition of pharmacists as health care professionals, and many other sections set the stage for the practice of pharmacy in the next century.
The Pharmacy Practice Act was further amended by an initiative brought forth by KPhA in the 1998 General As-sembly. The bill, which ultimately passed the legislature, allowed pharmacists to perform CLIA-waived tests
vastly broadening the scope of the practice. HB 649 also created an “impaired pharmacists committee,” a long-time goal of KPhA. Finally, in a major victory for pharmacy,
the provider tax on prescription drugs was repealed.
KPhA was actively involved in a number of key regulations during 1999. The Association worked with the Board of Pharmacy to create a Charitable Pharmacy Permit by regulation, which allowed pharmacists seeking to provide critical pharmacy care to the indigent to operate in a less restrictive environment. Also, on the regulatory front, KPhA worked on regulatory changes to authorize centralized dispensing and to recognize the certification of Nuclear
Pharmacist Technicians.
The 2000s
The 2000 legislature saw activity on both the mail order pharmacy front and Medicaid where KPhA took a leading role to protect the interests of Kentucky pharmacists. KPhA successfully opposed legislation to allow ARNPs’ unlim-ited dispensing authority and supported legislation add-ing a pharmacist to the End of Life Health Care Task Force.
The first ever “annual session” of the Kentucky General Assembly in 2001 saw an important victory for the profes-sion. A KPhA-supported proposal to eliminate the an-nual HIV/AIDS continuing education requirement passed the legislature. The statutory change was in line with KPhA’s long-standing opposition to subject-specific CE requirements. The “short” session also saw another attempt to allow ARNPs to dispense prescription drugs which was again defeated. On the regulatory front, KPhA battled re-ductions in the Medicaid dispensing fee including the elimination of the “unit dose” add-on and worked with the Board of Pharmacy to rewrite the regulations dealing with reference materials and equipment and the electronic transfer of prescription information.
The 2002 Session was characterized by massive financial problems in Medicaid and KPhA spent countless hours bat-tling fee reductions in the program. Also in 2002, KPhA worked with the state Public Health Department to resolve the issue of dispensing activities by health department per-sonnel. HB 67 which ultimate passed the General Assem-bly gives pharmacists oversight of drug distribution at local health departments by mandating that each health de-partment have a pharmacist on its governing board. The involvement of pharmacists in public health programs was applauded by the state’s Commissioner of Public Health Dr. Rice Leach. According to Leach, “The bottom line (is) pharmacists are an asset.” KPhA was also suc-cessful in helping pass legislation to regulate prescrip-tion discount cards and to allow the Board of Pharmacy to expunge minor violations from a pharmacist’s permanent record.
November 2013
THE KENTUCKY PHARMACIST 10
KPhA in the Political Arena
In 2003 KPhA passed legislation to recognize the validi-ty of prescriptions written by out-of-state practitioners. The Association also successfully opposed legislation to mandate mail order for Medicaid maintenance medi-
cations.
2004 was another busy year for pharmacy. KPhA again championed a major change to the Pharmacy Practice Act allowing pharmacists to administer immunizations via a prescriber-approved protocol. This change opened the door for pharmacists to play an even more important role in preventive care. KPhA also was instrumental in the pas-sage of legislation implementing the recommendations of the Prescription Drug Abuse Task Force. KPhA’s efforts with the Task Force and the legislature averted passage of a requirement that pharmacists obtain additional identification from patients obtaining controlled sub-stances. KPhA also worked with the Board of Pharmacy to pass a bill increasing the terms of members of the
Board from three to four years.
In 2005, KPhA faced a major Medicaid reimbursement bat-tle as the Cabinet for Health and Family Services proposed dramatic reductions in pharmacy reimbursement. KPhA filed a lawsuit to stop the reimbursement reductions and ultimately appealed to Governor Fletcher to signifi-cantly pare the cuts. The result was a compromise that restored a major portion of the cuts totaling tens of millions of dollars. The 2005 legislative session saw the passage of one of the nation’s toughest Internet phar-macy laws. SB 63 required that out-of-state pharmacies have a pharmacist-in-charge who is licensed in Kentucky, a long-time legislative goal of KPhA. The bill also contained a KPhA-backed provision restricting the sale of pseudoephederine products to pharmacies only. In 2005, KPhA also defeated legislation to require drug pedigrees and supported funding for a new College of
Pharmacy building at the University of Kentucky.
KPhA launched a significant initiative to expand the prac-tice of pharmacy in 2006. The Association backed legisla-tion to allow pharmacists to prescribe under a collabo-rative practice agreement with a physician. While the legislation did not pass, its introduction fundamentally changed the debate on pharmacy and allowed the profes-sion to show the many ways pharmacists can improve ac-cess to health care and patient care. KPhA scored two ma-jor victories in the 2006 Session. The organization passed legislation to include an “any willing provider” provi-sion and a mail order parity provision in the state’s self-insured health plan. These provisions ensure that Ken-tucky’s pharmacists can continue to provide prescription services to state employees and teachers. KPhA also suc-cessfully added language to the state budget to allow pharmacists to refuse service to Medicaid recipients who fail to pay required copayments for drugs. Finally, KPhA supported the remaining state funding for the
new pharmacy college building at UK.
In the 2007 session, KPhA continued to push for an expan-sion of the role pharmacists play in the health care system. Legislation allowing limited prescriptive author-
ity for pharmacists was again introduced. That year’s version of the bill included language granting pharmacists more flexibility in the use of collaborative care agree-ments. Pharmacists again emphasized the role that they can play in the delivery of health care as the bill received a hearing by the House Health and Welfare Committee. Dur-ing 2007, KPhA also helped strengthen the rules for out-of-state and Internet pharmacies and successfully fought against legislation to weaken Kentucky’s gener-ic drug law. KPhA also worked closely with state Medicaid officials to petition Congress to delay the implementation of a federal law mandating the use of tamper resistant pre-scriptions for Medicaid. In late 2007, KPhA led the charge to stop a proposed Board of Pharmacy regulation that would have significantly weakened the state’s pharmacist licensing law.
KPhA scored a major success in the 2008 session with the passage of HB 538, exempting over-the-counter drugs dispensed pursuant to a prescription from the state sales tax. The bill reduced the financial exposure of pharmacies by millions of dollars in the years ahead. KPhA also continued to focus on the advancement of the profession. The 2008 Session also saw the passage of a KPhA-endorsed bill to require the registration of pharmacy technicians and a pharmacy-friendly drug pedigree bill. On the regulatory front, KPhA worked closely with the Ken-tucky Board of Pharmacy to advance a regulatory change allowing the use of common prescription databases.
In 2009, KPhA launched a major legislative initiative to address the abusive audit practices by pharmacy bene-fit managers. The bill passed the General Assembly and was signed into law by Governor Beshear. Its pas-sage gave Kentucky one of the most comprehensive audit laws in the country and gave pharmacists ammunition in fighting the aggressive audit tactics employed by PBMs. Also that year, KPhA sought and won a sales tax exemp-tion for durable medical equipment that significantly helped pharmacies that sold DME.
2010 to Today
After a devastating ice storm in the winter of 2009, KPhA began setting the stage for legislation to grant expanded powers to pharmacists during emergencies. That effort culminated in the passage of legislation in 2010 that gave pharmacists additional tools in order to serve their patients during natural and man-made disasters. The law allows the Governor to grant expanded powers to pharmacists in the event of a declared state of emergency. It has been invoked numerous times since 2010—including the 2012 disaster that impacted West Liberty and other af-fected communities—and has dramatically helped pharma-cists meet patient needs during disasters. 2010 also saw the passage of a KPhA-backed proposal to significant-ly expand immunization authority for pharmacists. The legislation allowed pharmacists the ability to provide the full range of immunization to individuals 14-17 years of age. Before its passage pharmacists were limited to providing immunizations to adults only.
November 2013
THE KENTUCKY PHARMACIST 11
Donate online to the Kentucky Pharmacists
Political Advocacy Council!
Go to www.kphanet.org and click on the Advocacy tab for
more information about KPPAC and the donation form.
KPhA in the Political Arena
The 2011 legislative session provided KPhA with an-other opportunity to expand immunization authority. The Association was successful in passing a bill to allow pharmacists to administer influenza vaccines to individuals down to the age of 9 years old. That session also saw KPhA working with drug control officials to establish a framework for allowing the electronic prescribing of
controlled substances.
In 2012 KPhA built on the foundation of the pharmacy audit bill that was passed in 2009 and passed legisla-tion adding further protections for pharmacies. The legislation also expanded the scope of the law to cover managed care organizations serving the Medicaid popula-tion. KPhA was also in the forefront in the debate over prescription drug abuse. The Association was successful in amending what became known as HB 1 to remove provi-sions requiring pharmacists to run KASPER reports before dispensing a controlled substance. KPhA was very active in a work group assisting in the implementation of HB 1 after it passed the General Assembly in a Special Session, in-cluding a much-needed exemption for hospitals and long term care facilities having to run KASPER reports before administering pain medication to patients. The Associa-tion also worked throughout the year in addressing problems associated with a new law licensing individu-als that fit therapeutic shoes for diabetics. KPhA’s ef-forts resulted in an agreement with the board regulating these individuals that allowed pharmacy technicians to as-
sist pharmacists in fitting therapeutic shoes without addi-tional licensure requirements.
In 2013, YOUR KPhA led efforts to pass the first PBM transparency bill in the country. SB 107 put KPhA on the national stage as it became one of the very few phar-macy organizations to successfully fight back against the PBM industry. The bill addressed the issue of MAC pricing and provided Kentucky pharmacies with a way to counter the aggressive pricing practices of PBMs. KPhA continues to work with pharmacists to monitor the effective-ness of this legislation as it evolves into practice.
The Future
KPhA’s past legislative showing has created a solid foun-dation to help move the profession into the future. The As-sociation continues to shape the evolution of pharmacy practice and is active in the legislative and regulatory pro-cess to affect positive change. The Association continues to promote the expansion of the role of the pharmacist in the health care delivery system and continues to publicize the many ways pharmacists can add to the value and quali-ty of health care. The changing nature of Medicaid remains a constant concern to the Association and continues to be a focus of its government affairs plan.
KPhA remains committed to being the voice and
guardian of the profession for Kentucky’s pharmacists.
SUPPORT KPHA’S EFFORTS IN SERVING THE PROFESSION OF PHARMACY
YOU CAN PARTICIPATE BY:
CONTRIBUTING TO THE GOVERNMENT AFFAIRS FUND
CONTRIBUTING TO THE KENTUCKY PHARMACISTS PAC
GETTING TO KNOW YOUR STATE SENATOR AND REPRESENTATIVE
ENGAGING WITH YOUR KPhA ON GRASSROOTS ALERTS
November 2013
THE KENTUCKY PHARMACIST 12
Bowl of Hygeia
Vote for Kentucky to be #1! Vote with your contribution for Kentucky to be #1 with the “Bowl of Hygeia State Association
Challenge 2.0.”
Every dollar you donate will double as a result of our 2013 Bowl of Hygeia recipient Leon Clay-
well’s pledge to match donations up to $5,000. You can help Kentucky earn Leon’s Pledge!
The APhA Foundation will award cash prizes to the state raising the most funds for the Bowl of
Hygeia Endowment. The Endowment is at 75 percent of its goal.
To qualify for Kentucky’s “win,” your donation has to be received by the APhA Foundation no
Funds contributed to KPhA Government Affairs are ap-
plied directly to our lobbying efforts in terms of staffing
and contracted lobbying services. Company donations are
acceptable for Government Affairs contributions, unlike contributions to
Political Advocacy Funds, like KPPAC.
Go to www.kphanet.org and click on the Advocacy tab for more infor-
mation about the KPhA Government Affairs fund and the donation form.
For more information on the Bowl Of Hygeia, visit:
http://www.aphafoundation.org/bowl-hygeia-award.
November 2013
THE KENTUCKY PHARMACIST 13
Nov. 2013 CE-Venous Thromboembolism
Prevention and Treatment of Venous Thromboembolism - New Medications and Recommendations By: Thomas Pressley, PharmD; Bradley Wagner, PharmD and Debbie Minor, PharmD,
The University of Mississippi Medical Center Department of Medicine; Jackson, MS
Reprinted with permission of the authors and the Mississippi Pharmacists Association where this
article originally appeared. This activity may appear in other state pharmacy association journals.
There are no financial relationships that could be perceived as real or apparent conflicts of interest.
Universal Activity # 0143-9999-13-011-H01-P&T
2.0 Contact Hours (0.2 CEU)
Goal
To review anticoagulant agents and their place in therapy for the treatment and prevention of thromboembolism.
Objectives
At the conclusion of this article, the reader should be able to:
1. Review the coagulation pathway, in reference to the need for antithrobotic therapy and the pharmacology of available agents.
2. Discuss the historical, current and potential future use of anticoagulants. 3. Describe the advantages and disadvantages of specific anticoagulants, with a focus on new oral agents. 4. Highlight recent guideline updates and implications for antithrombotic treatment and management.
KPERF offers all
CE articles to
members online at
www.kphanet.org
INTRODUCTION
The risk of clot formation, or venous thromboembolism (VTE), is increased in many individuals. Common condi-tions that increase the risk for abnormal coagulation and complications include trauma, surgery, immobility, hyperco-agulable disorders, previous VTE, arrhythmias, obesity, smoking and older age. These conditions or risk factors are additive and are often criteria for the recommendation of temporary or chronic anticoagulant therapy to prevent or treat VTE and to avoid adverse complications.
1 For exam-
ple, both major hip and knee surgery increase the risk for developing deep vein thrombosis (DVT) and justify the use of anticoagulants following surgery.
Patients who are at risk for developing or have an acute VTE often require appropriate anticoagulation for preven-tion or treatment of thromboembolic events and adverse outcomes. Atrial fibrillation (AF), DVT and pulmonary em-bolism (PE) are disease states or conditions that often re-quire anticoagulant treatment. AF is a common arrhythmia that significantly increases the risk of ischemic stroke by four to five-fold. With an overall prevalence of 0.4 to 1 per-cent, approximately 2.2 million Americans have AF. The prevalence increases with age, affecting approximately 8 percent of those aged 80 and older.
1 Fifteen percent of
strokes in all individuals and 30 percent of those in persons over the age of 80 years are attributable to AF.
Depending
on the thromboembolic level of risk, anticoagulation is rec-ommended for many individuals with nonvalvular AF to pre-vent the occurrence of stroke.
2
Among Americans, the annual incidence of first time VTE,
including DVT and PE, is approximately 1 to 2 per 1,000 persons.
3 Two-thirds of VTE occurrences are DVTs with
one-third progressing to PE. Mortality rates for patients one month post-VTE are 6 percent with DVT and 12 percent after PE.
2 Following an initial VTE, the risk of recurrent VTE
is high, estimated at 25 percent during the first 6 to 12 months without appropriate anticoagulation.
3
VTE occurs as a result of activation of the body’s coagula-tion cascade. The coagulation cascade consists of intrinsic and extrinsic pathways which converge forming a common pathway. The intrinsic and extrinsic pathways are activated in response to active bleeding and tissue injury. Once ei-ther pathway is activated, it terminates at the common pathway, producing thrombin (IIa) and fibrin to form a sta-ble clot and prevent further bleeding. Thrombin can exist as free thrombin which can facilitate clot formation or as fibrin-bound thrombin that is capable of triggering clot growth. Some medications affect only free thrombin, while others affect both free and bound thrombin. Each anticoagulant inhibits one or more components of the coagulation cas-cade to reduce the risk of VTE occurrence or complica-tions.
1
The purpose of this article is to review the currently availa-ble anticoagulant agents and their place in therapy for the treatment and prevention of thrombosis. The included table provides a summary of these agents as well as potential advantages and disadvantages of each.
WARFARIN
Warfarin is a vitamin K antagonist (VKA) used for the pre-
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vention and treatment of thromboses, including those asso-ciated with AF, DVT/PE and cardiac valve replacement. Coumarin, warfarin’s predecessor, was discovered fortui-tously by a farmer who noticed his cattle dying from inges-tion of sweet clover hay. Wisconsin Alumni Research Foun-dation (WARF) biochemist Karl Paul Link then isolated the coumarin compound from the deceased cow’s anticoagu-lated blood in 1941.
By inhibiting the vitamin K dependent
clotting factors II, VII, IX, and X, as well as natural antico-agulant proteins C and S, warfarin reduces the likelihood of thrombi development.
4,5
The lack of alternative anticoagulants has perpetuated the use of warfarin since 1954.
Years of clinical experience,
once-daily oral dosing, no dosage adjustment requirements with renal dysfunction and the availability of clear antidotes (i.e., vitamin K, four-factor prothrombin complex concen-trates [PCC]) are advantages for the use of warfarin.
4 In
contrast, disadvantages of warfarin use include a slow on-set of therapeutic effect, numerous drug-drug and drug-food interactions, a narrow therapeutic index, and the need for routine monitoring of prothrombin time (PT) and interna-tional normalized ratio (INR).
Warfarin is primarily metabolized via liver enzyme CYP2C9.
4 Though warfarin is relatively
safe, through inhibi-
tion or induction of this enzyme or other mechanisms, many medications can increase (e.g., antibiotics, NSAIDs, amiodarone) or decrease (e.g., estrogens, carbamazepine, St. John’s Wort) the effects. Polymorphisms of CYP2C9 decrease warfarin’s clearance approximately 30 percent to 90 percent and may necessitate a lower dose; however, there are no current recommendations for genetic screen-ing.
6 A consistent diet is also necessary to minimize INR
fluctuations, as vitamin K rich foods (e.g., spinach, broccoli, mayonnaise) antagonize the anticoagulant effects of warfa-rin.
A meta-analysis including 67 studies of 50,208 patients on warfarin highlighted the difficulty of maintaining therapeutic INRs. Though the amount of time within the therapeutic INR range is strongly correlated with fewer thrombi and bleeding complications, patients achieved a therapeutic time in range (TTR) only 63.6 percent of the time.
7 The re-
cent 2012 CHEST guidelines provide updates in the areas of anticoagulant dosing, VTE prophylaxis and treatment and atrial fibrillation.
8 The levels of evidence for each of
these recommendations are delineated within the guide-lines. New recommendations for warfarin suggest that the patient’s current dose of warfarin be continued if the INR is ≤ 0.5 above or below target, with reassessment within 1 to 2 weeks. In addition, the frequency of INR monitoring may be extended from 4 to 12 weeks in selected patients on warfarin with stable INRs and dosing. In reference to acute VTE treatment, the guidelines suggest starting warfarin 1 to 2 days after initiating therapy with low molecular weight heparins (LMWH), fondaparinux, or unfractionated heparin (UFH).
8
HEPARINS AND FONDAPARINUX
UFH, enoxaparin (Lovenox®), dalteparin (Fragmin
®) and
tinzaparin (Innohep®) are injectable heparins that are avail-
able for use in the United States. These medications bind
antithrombin III (AT), resulting in inhibition of factors Xa and IIa. LMWHs have more anti-Xa activity compared to the approximately equal anti-Xa and anti IIa activities of UFH. Heparins only inhibit free thrombin which is capable of forming a new thrombus. Fondaparinux (Arixtra
®) is non-
heparin anticoagulant that shares similarities with the hepa-rins, including mechanism of action. Also administered by injection, fondaparinux binds AT, but inhibits factor Xa on-ly.
1 Each of the LMWHs and fondaparinux differ by indica-
tion and pharmacodynamic and pharmacokinetic proper-ties. Use of a particular agent should be based on specific patient considerations and proven efficacy and safety for each indication.
9-13
UFH, LMWHs, and fondaparinux are commonly used to provide prompt anticoagulation when bridging to VKA ther-apy for long-term use. LMWHs and fondaparinux provide benefits over UFH including improved subcutaneous (SC) bioavailability, predictable anticoagulation response, lower incidence of thrombocytopenia, less frequent administration and a reduced need for laboratory monitoring.
9-14 When
used for VTE treatment, the antithrombotic effect of UFH should be monitored by activated partial thromboplastin time (aPTT) or anti-Xa activity to ensure efficacy and safe-ty.
10,15 LMWHs and fondaparinux generally do not require
routine monitoring, however, some patients may be at risk for efficacy or safety concerns and may benefit from moni-toring anti-Xa levels (approximately 4 hours after dosing).
10-14 At risk patients include those that are obese,
underweight, renally impaired, elderly, undergoing surgery or pregnant.
11-14
Advantages of treatment with UFH, LMWHs and fondapari-nux are the rapid onset of anticoagulation and few drug interactions. The anticoagulant effects of LMWH, and more so UFH, can be mostly reversed by protamine sulfate. Alt-hough fondaparinux has no approved agent for reversal, recombinant factor VIIa may be effective at normalizing coagulation times.
16 Because enoxaparin has no maximum
dose recommendation, the risk of bleeding may be in-creased in obese individuals when dosed by weight. Fondaparinux may be preferred over LMWHs for obese patients because of a set dosage recommendation of 10 mg for those > 100 kg.
11,14 Tinzaparin and dalteparin are
dosed based on weights up to 165 kg and 190 kg, respec-tively, and may have less risk.
12,13 Fondaparinux is contra-
indicated for DVT prophylaxis and has a recommendation for caution in treatment of VTE in patients < 50 kg because of an increased bleeding risk.
14 UFH, tinzaparin and dalte-
parin do not require dosage adjustments for renal impair-ment. Because of renal clearance, both enoxaparin and fondaparinux require baseline and periodic assessments of renal function.
10-14 In patients with a CrCl < 30 mL/minute,
enoxaparin should be dosed once daily and fondaparinux is contraindicated.
8,14
Heparin induced thrombocytopenia (HIT), a prothrombotic complication mediated by an immune response to heparin-induced immune complexes, is a risk of using heparin-based products. As a result, baseline and periodic monitor-ing of platelets is necessary when using heparins to deter-mine if use is appropriate or to diagnose the presence of HIT.
10-13 Fondaparinux is thought to have a lower risk of
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HIT associated with its use, but evidence supporting fondaparinux’s use in HIT is limited and controversial.
8
Consequently, fondaparinux also requires monitoring of platelets at baseline and during therapy.
14
Recent guideline updates recommend 10 to 14 days of DVT prophylaxis with LMWH, UFH, fondaparinux, dabigatran, rivaroxaban, VKA or aspirin following major hip and knee surgery. LMWH is the treatment of choice due to increased bleeding risk with other agents and lack of long-term safety data with newer agents. Recommendations for LMWH use before and after surgery also have been updat-ed to increase efficacy and reduce bleeding complications. LMWHs should be stopped 24 hours before elective sur-gery (48 to 72 hours before high risk surgery) and started 12 hours or more following surgery. Updated recommenda-tions for acute VTE treatment note that LMWHs, UFH and fondaparinux are acceptable for bridge therapy to a VKA, with LMWHs and fondaparinux recommended over UFH. Of note, at the time of release, post-marketing safety data were unavailable for dabigatran and rivaroxaban, and apix-aban was not yet marketed. This lack of data and availabil-ity prevented stronger recommendations in favor or opposi-tion of these agents for certain indications.
8
DABIGATRAN
Approved in 2010, dabigatran (Pradaxa®) is an oral, re-
versible, direct thrombin inhibitor that inhibits both free and fibrin-bound thrombin, unlike UFH and LMWH which only inhibit free thrombin. By inhibiting fibrin-bound thrombin, dabigatran halts the continued expansion of the fibrin clot whereas other anticoagulants do not.
9,17 Dabigatran pro-
longs both thrombin and ecarin clotting time, two plasma markers for thrombin inhibition. Dabigatran etexilate, the prodrug of dabigatran, is metabolized to its active form by gut, plasma and liver esterases. Anticoagulant effects oc-cur approximately 1.5 hours after administration and reach steady state in about 3 days.
17
There are no requirements for routine monitoring of dabigatran and there is no approved antidote, though prac-titioners have used packed red blood cells, plasma, and PCC.
17,18 Clinical trials are seeking clarification of
dabigatran reversibility with PCC and factor VIIa. Since me-
tabolism is independent of the CYP450 system, dabigatran has few drug interactions. It is a substrate of P-glycoprotein (P-gp) and may have potential interactions (e.g., rifampin, quinidine, amiodarone) through this pathway. Dabigatran is primarily excreted renally (80 percent), requiring dose ad-justments at CrCl levels < 30 mL/minute. It is approved for prevention of stroke and systemic embolism in patients with nonvalvular AF at a twice daily dose of 150 mg or 75 mg with renal impairment.
17
The RE-LY trial investigated the incidence of stroke or sys-temic embolism in 18,113 patients with nonvalvular AF and moderate risk for stroke (mean CHADS2 2.1, mnemonic for major stroke risk factors: congestive heart failure, hyperten-sion, age > 75 years, diabetes mellitus and prior stroke or transient ischemic attack). This non-inferiority trial random-ized patients to dabigatran 110 mg or 150 mg twice daily or warfarin titrated to an INR of 2 to 3. Dabigatran 150 mg was superior to warfarin in reduction of stroke or systemic
embolism (1.11 percent vs. 1.69 percent; p < 0.001) and non-inferior to warfarin in major bleeding (3.11 percent vs. 3.36 percent; p = 0.31). Dabigatran 110 mg was non-inferior to warfarin in stroke or systemic embolism (1.53 percent vs. 1.69 percent) and superior to warfarin in major bleeding (2.71 percent vs. 3.36 percent; p = 0.003).
19
Dabigatran is available as 75 mg and 150 mg capsules in the United States and Europe. A 110 mg dose also is avail-able in Europe, though our FDA failed to approve this dose because a subgroup of benefit could not be identified. The 75 mg dose, approved based on pharmacokinetic and pharmacodynamic modeling, is reserved for patients with renal impairment.
20 Because of the RE-LY results, recent
guideline updates recommend dabigatran over warfarin in patients with nonvalvular AF with a CHADS2 score of 1 or 2 and in patients with previous ischemic stroke or transient ischemic attack.
8
In a reanalysis of the elderly subpopulation (≥ 75 years) of RE-LY, the safety benefit of dabigatran over warfarin was less evident. This subgroup maintained lower rates of intra-cranial bleeding with dabigatran at both doses (RR = 0.37, 110 mg, RR = 0.42, 150 mg) and similar extracranial bleed-ing with dabigatran 110 mg; however, the 150 mg dose was 39 percent more likely to cause extracranial bleed-ing.
21 The RE-LY extension trial (RELY-ABLE) enrolled 32
percent of patients from the original trial, to provide long-term safety and efficacy data for dabigatran. After 28 months, stroke, systemic embolism and major bleeding rates remained similar to the initial reports, though follow-up data was available for only 12 percent of the original trial participants.
22
Since approval, the safety profile of dabigatran demonstrat-ed in industry-sponsored trials has been questioned. Using post-marketing data, the Institute for Safe Medication Prac-tices reported 856 suspected cases of serious, disabling or fatal injury associated with dabigatran use. This represents more than any other regularly monitored medication and includes reports of 511 hemorrhages and 117 patient deaths. The median patient age for hemorrhage was 80 years old, supporting vulnerability in elderly populations.
23
Though there are no new indications, completed and ongo-ing studies have explored the use of dabigatran for VTE prophylaxis following major hip and knee surgeries, long-term prevention of recurrent VTE and prevention of new ischemic events following an acute coronary syndrome (ACS).
RIVAROXABAN
Rivaroxaban (Xarelto®) is an oral, direct factor Xa inhibitor
that provides prompt and predictable anticoagulation in 2 to 4 hours. No routine monitoring is required or recommended with rivaroxaban, though PT can be measured to estimate the degree of anticoagulation.
9,24
As with dabigatran, there is no approved agent to reverse the anticoagulant effects of rivaroxaban. Trials with PCC and recombinant factor VIIa are ongoing and have shown some benefit.
9 Oral bioavailability decreases with increas-
ing doses of rivaroxaban, however, administration of doses ≥ 15 mg with food improves bioavailability. Rivaroxaban is
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Anticoagulant Comparisons
Anticoagulant Mechanism of
Action Advantages Disadvantages Monitoring
Warfarin
(Coumadin®)
Vitamin
K antagonist
- Clinical experience
- Once daily dosing
- Oral administration
- Antidote
- Inexpensive
- Slow onset
- Routine INR monitoring
- Numerous drug-drug and drug-food interactions
INR
CBC (Hb/Hct*)
UFH Indirect inhibition of clotting factors Xa and IIa
- Rapid onset
- Clinical experience
- Antidote
- Limited drug interactions
- aPTT or anti-Xa monitoring (VTE treatment)
- Variable SC bioavailability
- Dose-dependent response/clearance
- HIT
- Parenteral administration
aPTT or anti-Xa
CBC (Hb/Hct/Platelets)
LMWHs Indirect inhibition of clotting factors Xa and IIa
- Rapid onset
- No routine monitoring
- Antidote
- Limited drug interactions
- Renal dosing (enoxaparin)
- No maximum dose (enoxaparin)
- HIT
- Parenteral administration
Renal function
CBC (Hb/Hct/Platelets)
Anti-Xa
Fondaparinux
(Arixtra®)
Indirect inhibition of clotting factor Xa
- Rapid onset
- No routine monitoring
- Once daily dosing
- Limited drug interactions
- Possible use in HIT
- Stratified, weight-based dosing
- Contraindicated with:
CrCl < 30 mL/min
Weight < 50 kg (prophylaxis)
Bacterial endocarditis
Thrombocytopenia with platelet antibodies
- Increased bleeding in elderly (> 75 years)
- Parenteral administration
- No antidote
Renal function
CBC (Hb/Hct/Platelets)
Anti-Xa
Dabigatran
(Pradaxa®)
Direct thrombin inhibitor
- Rapid onset
- No routine monitoring
- Oral administration
- Few drug interactions
- Intracranial bleeding
< warfarin
- P-gp substrate
- Twice daily dosing
- Renal dose adjustments
- Avoid if CrCl < 15 mL/min
- Extracranial bleeding > warfarin
- No antidote
Renal function
CBC (Hb/Hct)
Rivaroxaban
(Xarelto®)
Direct factor Xa inhibitor
- Rapid onset
- No routine monitoring
- Oral administration
- Predictable dose-response
- CYP3A4 & P-gp substrate
- Avoid in moderate/severe hepatic impairment
- Avoid if CrCl < 15 mL/min
- Abrupt discontinuation increases risk for thromboembolism
- Administer with food (≥ 15 mg)
- Elderly/ underweight have slightly increased levels/ response
- GI bleeds > warfarin
- No antidote
Renal function
CBC (Hb/Hct)
Apixaban
(Eliquis®)
Direct factor Xa inhibitor
- Rapid onset
- No routine monitoring
- Oral administration
- Predictable dose-response
- CYP3A4 & P-gp substrate
- Twice daily dosing
- Avoid in severe hepatic impairment
- Dosage adjustment if at least 2:
- Age ≥ 80
- Body weight ≤ 60 kg
- Serum creatinine ≥ 1.5 mg/dL
- Abrupt discontinuation increases risk for thromboembolism
- No antidote
Renal function
CBC (Hb/Hct)
*Hb/Hct – Hemoglobin/hematocrit
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metabolized by CYP3A4 and is a substrate of P-gp, likely interacting with inducers (e.g., rifampin, phenytoin) and in-hibitors (e.g., azole antifungals, macrolide antibiotics, prote-ase inhibitors) of these pathways. Strong inhibitors and in-ducers of CYP3A4 and P-gp should be avoided with riva-roxaban. Because approximately two-thirds of rivaroxaban is cleared renally, patients with renal insufficiency require dosage adjustments if they are receiving rivaroxaban for AF.
9,24 Rivaroxaban should be avoided in patients with a
CrCl < 30 mL/minute or < 15 mL/minute in patients with DVT or AF, respectively. Patients with moderate or severe hepatic insufficiency should not receive rivaroxaban. The elderly have an increased overall exposure to rivaroxaban, but no dosage adjustment is recommended.
24
Because rivaroxaban has a relatively short half-life (5 to 9 hours), there is an increased risk of stroke or systemic em-bolism with abrupt discontinuation. This includes an in-creased risk for patients who are noncompliant with the dosing schedule. A black box warning recommends alter-nate anticoagulation if rivaroxaban needs to be discontin-ued for reasons other than bleeding.
9,24 After an initial ap-
proval for DVT prophylaxis, rivaroxaban now also is ap-proved for acute VTE treatment, secondary prevention of VTE, and stroke and systemic embolus prevention in pa-tients with nonvalvular AF.
24
Rivaroxaban was studied for the prevention of DVT in > 14,000 patients undergoing elective hip or knee replace-ments in the RECORD 1, 2, 3 and 4 trials. Patients were randomized to rivaroxaban 10 mg once daily starting 6 to 8 hours after surgery or enoxaparin at various doses, sched-ules and timing around surgery for each trial. The occur-rence of DVT, PE or death was significantly lower with riva-roxaban in each trial. Major VTEs occurred significantly more often with enoxaparin in all trials, except RECORD 4 which showed similar results to rivaroxaban. Although not significantly different between groups, bleeding events trended higher in patients receiving rivaroxaban.
25-28
The efficacy and safety of rivaroxaban in patients with non-valvular AF was derived from ROCKET AF, a multicenter, double-blinded trial. Over 14,000 patients were randomized to rivaroxaban 20 mg taken daily with the evening meal (15 mg if CrCl 30-50 mL/minute) or warfarin (adjusted to INR, 2 to 3). The primary efficacy endpoint, time to first occurrence of stroke or non-central nervous system embolism, was not significantly different between the groups, demonstrating non-inferiority of rivaroxaban to warfarin (1.7 percent vs. 2.2 percent; p < 0.001). The primary safety endpoint, major and non-major clinically relevant bleeding, was similar be-tween groups (14.9 percent vs. 14.5 percent; p = 0.44). Intracranial hemorrhage (0.5 percent vs. 0.7 percent; p = 0.02) and fatal bleeding (0.2 percent vs. 0.5 percent; p = 0.003) occurred significantly less in those receiving rivarox-aban though more patients developed gastrointestinal (GI) bleeds with rivaroxaban. In an initial 28-day post-study fol-low-up, there were significantly more strokes in patients that had received rivaroxaban as the study medication compared to those that had received warfarin. Investigators attribute this to the study closeout protocol, as those that were on rivaroxaban were changed to warfarin with no in-terim or bridge therapy.
2
The clinical trials supporting rivaroxaban’s approval for the treatment and secondary prevention of DVT and PE were EINSTEIN-DVT and EINSTEIN-PE. These trials included over 8,200 patients randomized to rivaroxaban 15 mg twice daily for 3 weeks followed by 20 mg daily thereafter or standard therapy (enoxaparin, VKA) for the same duration. The primary endpoint for both trials, recurrent VTE, oc-curred in 2.1 percent of those treated with rivaroxaban and 3.0 percent and 1.8 percent of those treated with standard therapy, respectively (p < 0.001, p = 0.003 for non-inferiority, respectively).
3,29 The principle safety outcome,
major bleeding or clinically relevant non-major bleeding, occurred at similar rates between the groups in both tri-als.
3,29 In a continued-treatment study, patients received
rivaroxaban 20 mg daily or placebo for the prevention of a recurrent DVT. Rivaroxaban reduced the recurrence of DVT significantly (1.3 percent vs. 7.1 percent; p < 0.001), but increased the occurrence of bleeding events compared to placebo (6.0 percent vs. 1.2 percent; p < 0.001).
3
Rivaroxaban has been studied in phase III trials in patients with ACS and acutely ill medical patients, but no indications have been approved for these populations.
Recent guide-
line updates reported that limited post-marketing safety data was available for rivaroxaban at the time of release. This lack of data prevented stronger recommendations in favor or opposition of rivaroxaban.
8
APIXABAN
Like rivaroxaban, apixaban (Eliquis®) is an oral, direct fac-
tor Xa inhibitor with a predictable dose response. It has a quick onset of anticoagulation (1 to 3 hours), short half-life (12 hours) and rapid elimination, requiring twice daily dos-ing.
9,30 There are no recommendations for routine monitor-
ing of apixaban and there is no approved agent for antico-agulation reversal.
30
Apixaban is a substrate of P-gp and is metabolized by CYP3A4. Inhibitors of CYP3A4 and P-gp (e.g., azole anti-fungals, macrolide antibiotics, protease inhibitors) can in-crease exposure to apixaban and should be avoided if pos-sible. If these medications are necessary, apixaban should be avoided or the dose decreased by 50 percent. Strong inducers of CYP3A4 and P-gp (e.g., phenytoin, rifampin) can decrease apixaban’s effectiveness and increase the risk for thromboembolism and should be avoided with apix-aban.
30
Similar to rivaroxaban, apixaban discontinuation for any reason other than bleeding requires coverage with another anticoagulant to decrease the risk of thromboembolism. Due to apixaban’s short half-life, the risk of thromboembo-lism is increased in patients who are noncompliant with the dosing schedule.
Apixaban is indicated for the prevention of
stroke and systemic embolism in patients with nonvalvular AF at a dose of 5 mg twice daily. A lower dose of 2.5 mg twice daily is recommended for individuals with at least 2 of the following: age ≥ 80 years, body weight ≤ 60 kg, or se-rum creatinine ≥ 1.5 mg/dL.
30
The clinical trials AVERROES and ARISTOTLE support the use of apixaban in AF. The AVERROES trial compared apixaban to aspirin for incidence of stroke or systemic em-
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bolism in patients who were not suitable for or unwilling to take warfarin therapy. The study was terminated early due to the clear benefit in favor of apixaban.
31 The ARISTOTLE trial
compared stroke or systemic embolism incidence in 18,201 patients with nonvalvular AF and moderate stroke risk (CHADS2 score, 2.1). This non-inferiority trial randomized patients to apixaban 5 mg twice daily or warfarin titrated to an INR of 2 to 3 (TTR = 62.2 percent). Apixaban was superi-or to warfarin in rates of stroke or systemic embolism (1.27 percent vs. 1.60 percent; p = 0.01), major bleeding (2.13 per-cent vs. 3.09 percent; p < 0.001) and death from any cause (3.52 percent vs. 3.94 percent; p = 0.047).
32
Apixaban has been studied for VTE treatment and prophy-laxis as well as recent ACS but no other indications have been approved at this time. Because apixaban was not mar-keted in the United States at the time of the CHEST guide-line updates, there were no recommendations for use.
POTENTIAL FUTURE AGENTS
RB006, a factor IXa inhibitor, is currently in phase II trials. Its antidote, RB007, a complementary oligonucleotide, has shown immediate anticoagulation reversal in patients under-going percutaneous coronary intervention. Ideally, RB006 and RB007 would replace heparin and its reversal agent, protamine sulfate, in stent placement and cardiac bypass surgeries. RB006 is particularly useful in kidney dysfunction as it is not renally cleared.
33
CONCLUSION
The use of warfarin has clearly improved clinical outcomes for many patients for over 50 years. The advent of new anti-coagulants affords the advantage of less burdensome drug profiles - in regard to the need for routine monitoring and often drug interactions - in addition to more rapid onset of anticoagulation. The oral agents, apixaban, dabigatran and rivaroxaban, also eliminate the need for injections, but their lack of clear antidotes and long-term safety data require fur-ther considerations. Selection of an anticoagulant remains highly patient specific, considering indication, risk of adverse effects, dosing compliance, previous anticoagulant use and cost. Regardless of the agent used, appropriate patient edu-cation is essential to ensure both medication efficacy and avoidance of adverse effects at all stages of treatment.
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27. Kakkar AK, Brenner B, Dahl OE, et al. Extended dura-tion rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled tri-al. Lancet 2008;372(9632):31-9.
28. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 26;358(26):2776-86.
29. Turpie AG, Lassen MR, Davidson BL, et al. Rivaroxa-ban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009;373(9676):1673-80.
30. Büller HR, Prins MH, Lensin AW, et al. Oral rivaroxa-ban for the treatment of symptomatic pulmonary embo-lism. N Engl J Med 2012;366(14):1287-97.
32. Connlly SJ, Eikelblood J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806-17.
33. Granger CB, Alexander JH, McMurray JJ, et al. Apixa-ban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365(11):981-92.
34. Cohen MG, Purdy DA, Rossi JS, et al. First clinical ap-plication of an actively reversible direct factor IXa inhib-itor as an anticoagulation strategy in patients undergo-ing percutaneous coronary intervention. Circulation 2010;122(6):614-22.
November 2013 — Prevention and Treatment of Venous Thromboembolism - New Medications and Recommendations
1. Each of the following are risk factors for VTE except: A. immobility. B. younger age. C. cancer. D. surgery. 2. In selected patients, current guidelines suggest that the frequency of INR monitoring may be extended up to: A. 4 weeks. B. 12 weeks. C. 16 weeks. 3. Advantages of treatment with LMWHs and fondaparinux in comparison to warfarin include: A. rapid onset of anticoagulation. B. few drug interactions. C. less frequent monitoring. D. all of the above. 4. Enoxaparin should be dosed once daily if CrCl is < 30 mL/minute. A. True B. False 5. Dabigatran is a substrate at which protein transporter? A. CYP2C9 B. CYP3A4 C. P-glycoprotein 6. Dabigatran is approved for prevention of stroke and sys-temic embolism in patients with: A. nonvalvular atrial fibrillation. B. DVT prophylaxis. C. prevention of recurrent VTE. D. all of the above.
7. According to recent guidelines, the best option for throm-boembolic prophylaxis in a 65-year old patient with AF that has recently had an ischemic stroke is: A. enoxaparin. B. dabigatran. C. rivaroxaban. D. warfarin. 8. Rivaroxaban is FDA approved for use in: A. DVT prophylaxis after major surgery. B. acute treatment and secondary prevention of VTE. C. stroke and systemic embolus prevention in patients with
nonvalvular AF. D. all of the above. 9. Of the following patients with AF, which would be the best candidate for anticoagulation with rivaroxaban? A. 70-year-old who does not like the frequent visits for moni-
toring B. 65-year-old with chronic kidney disease (CrCl < 15 mL/
minute) C. 48-year-old who requires chronic phenytoin therapy D. 57-year-old on warfarin for 6 months and frequently miss-
es daily doses 10. The new oral anticoagulants have specific warnings about discontinuation and the recommendation for use of alternate anticoagulation because of their: A. rapid onset. B. drug and food interactions. C. short duration of action. D. expense.
November 2013
THE KENTUCKY PHARMACIST 20
Nov. 2013 CE-Venous Thromboembolism
This activity is a FREE service to members of the Kentucky Pharmacists Association. The
fee for non-members is $30. Mail completed forms to: KPERF, 1228 US 127 South,
Frankfort, KY 40601. Credit will be applied to your CPE Monitor Profile.
The Kentucky Pharmacy Education & Research Foundation is
accredited by The Accreditation Council for Pharmacy
Education as a provider of continuing Pharmacy education.
Quizzes submitted without NABP eProfile
ID # and Birthdate cannot be accepted.
PHARMACISTS ANSWER SHEET November 2013 — Prevention and Treatment of Venous Thromboembolism - New Medications and Recommendations Universal Activity # 0143-9999-13-011-H01-P Name ________________________________________________ KY Lic. # __________________________________ Address ______________________________________________Email_____________________________________ PLEASE CIRCLE THE APPROPRIATE ANSWERS: 1. A B C D 3. A B C D 5. A B C 7. A B C D 9. A B C D 2. A B C 4. A B 6. A B C D 8. A B C D 10. A B C D Information presented in the activity: Met my educational needs ___Yes ___No Figures and tables were useful ___Yes ___No Achieve the stated objectives ___Yes ___No Posttest was appropriate ___Yes ___No Was well written ___Yes ___No Commercial bias was present ___Yes ___No Is relevant to my practice ___Yes ___No Unmet Objectives:______________________________________________________________________________ I hereby certify that I completed this self-study program independently and without assistance from any other party. Signature _________________________________________________ Date _________________________________
NABP eProfile ID #_____________________________ Birthdate ___________________(MM/DD)
Expiration Date: November 1, 2016 Successful Completion: Score of 80% will result in 2.0 contact hour or 0.2 CEU.
Participants who score less than 80% will be notified and permitted one re-examination.
TECHNICIANS ANSWER SHEET. November 2013 — Prevention and Treatment of Venous Thromboembolism - New Medications and Recommendations Universal Activity # 0143-9999-13-011-H01-T Name _______________________________________________KY Cert. # __________________________________ Address ______________________________________________Email_____________________________________ PLEASE CIRCLE THE APPROPRIATE ANSWERS: 1. A B C D 3. A B C D 5. A B C 7. A B C D 9. A B C D 2. A B C 4. A B 6. A B C D 8. A B C D 10. A B C D Met my educational needs ___Yes ___No Figures and tables were useful ___Yes ___No Achieve the stated objectives ___Yes ___No Posttest was appropriate ___Yes ___No Was well written ___Yes ___No Commercial bias was present ___Yes ___No Is relevant to my practice ___Yes ___No I hereby certify that I completed this self-study program independently and without assistance from any other party. Signature _________________________________________________ Date _________________________________
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November 2013
THE KENTUCKY PHARMACIST 21
Pharmacy Health Screening Provide state of the art health screenings to help improve
YOUR patients’ health and your bottom line.
Schedule a Health Screening Day at your pharmacy to offer YOUR patients a
service to improve their health and potentially catch dangerous issues early!
The health screenings offer multiple advantages for your business including
immediate profit from the screening process and the early recognition of diseases
that are usually treated with medications as well as increase the health and longevity
of your patients.
The process is a partnership between the Kentucky Pharmacists Association and Xcel
Diagnostics and YOUR pharmacy to bring state of the art health screenings to your patients.
The net profit is divided among the partners, including your pharmacy.
Call Xcel Diagnostics today to schedule your screening day.
(606) 218-5483
For more information on how you can be involved in the KPhA Pharmacy Emergency Preparedness Initiative, contact
Leah Tolliver, KPhA Director of Pharmacy Emergency Preparedness at 502-227-2303 or by email at
[email protected]. KPhA is a partner with the Kentucky Department of Public Health for emergency preparedness
and disaster response.
For more resources, visit YOUR www.kphanet.org and
click on Resources—Emergency Preparedness.
KPhA Pharmacy Emergency Preparedness
Pharmacist and Pharmacy Technician
Recruitment
As KPhA representatives continue to roam the state, meet-
ing with pharmacists and pharmacy technicians at various
events, many of you have contacted KPhA about volunteer-
ing with the Medical Reserve Corp. In doing so, this gives
you the opportunity to work on the mobile pharmacy if it's
deployed in the event of a disaster. Thank you!
The process to volunteer is filling out the application on
https://www.kentuckyhelps.com. Once this step is complet-
ed, the MRC Coordinator for your county will contact you to
schedule your training and verify your credentials.
IF YOU ARE NOT CONTACTED WITHIN 2 WEEKS OF
COMPLETING THE APPLICATION ON https://
www.kentuckyhelps.com. PLEASE CONTACT KPHA IM-
MEDIATELY SO WE CAN EXPEDITE YOUR REGISTRA-
TION AS A VOLUNTEER.
As always, if you have any questions or would like to learn
more about the KPhA emergency preparedness program,
Cocoa – Potential Benefits in Cardiovascular Disease By: Laura Latham, PharmD and Deborah Minor, PharmD, University of Mississippi Medical Center, Departments of Pharmacy, Pharmacy Practice and Medicine Reprinted with permission of the authors and the Mississippi Pharmacists Association where this article originally ap-peared. This activity may appear in other state pharmacy association journals. There are no financial relationships that could be perceived as real or apparent conflicts of interest. Universal Activity # 0143-9999-13-012-H01-P&T 1.5 Contact Hours (0.15 CEUs)
Goal: To evaluate the effects and potential benefits of cocoa on risk factors for cardiovascular disease.
Objectives: At the conclusion of this lesson, the reader should be able to:
1. Discuss the associations of cocoa intake with blood pressure (BP) and other risk factors for cardiovascular disease (CVD).
2. Describe the possible mechanisms for the beneficial effects of flavanol-rich cocoa. 3. Highlight considerations for the use of cocoa as a dietary supplement as supported by the medical literature.
KPERF offers all
CE articles to
members online at
www.kphanet.org
Introduction
As pharmacists, we commonly receive questions about
nutritional and dietary supplements. An admirable number
of people seek methods to address or enhance some as-
pect of their health, with many having a preference for a
“natural” approach. For centuries, cocoa has been recog-
nized not only for its delectable taste but also for its pro-
posed health benefits. Dark chocolate and cocoa products
have garnered recent attention specifically as a potential
dietary approach to lower blood pressure and other risk
factors for cardio vascular disease.1-3
Regular dietary in-
take of plant-derived foods and beverages is routinely rec-
ommended to decrease the risk of CVD among the general
population.1,3,4
For many, dietary changes and other nec-
essary lifestyle modifications are effective for the primary
prevention and treatment of hypertension and are critical
for management of CVD risk factors.4
The addition of chocolate to the diet may be a desirable
and pleasurable way to approach health for many people.
Both consumers and health care providers should be
aware of the issues surrounding cocoa as a supplement
and factors influencing both possible benefits and product
selection. The goal of this review is to highlight considera-
tions for use and evaluate the effects and potential benefits
of cocoa on risk factors for CVD.
Flavanols
An extract from beans of the Theobroma cacao tree, cocoa
is a rich source of plant polyphenols, a heterogeneous
group of molecules found primarily in fruits and vegetables.
Cocoa is especially rich in flavanols, the specific polyphe-
nol subtype proposed as the mediator for cardiovascular
benefits.2,3
Flavanols are also found in varying amounts in
other plant-based foods (Table 1).1,3
Structurally, flavanols
exist either as lower molecular weight monomeric com-
pounds [e.g., (−) and (+) epicatechin, (−) and (+) catechin],
of which epicatechin exerts more effects on the vascular
endothelium,5 or as complex higher molecular weight oligo-
meric and polymeric compounds (e.g., procyanidins), which
are less vasoactive.2,6
The profile and ratio of flavanols in
cocoa as well as other food products can be altered at
many stages of growth, development and production.5,6
Many factors can potentially influence the flavanol content
of cocoa and products vary considerably.1,5
Flavanol con-
tent in cocoa and chocolate products is largely dependent
on the crop cultivar type, post-harvest handling practices
and manufacturer processing techniques.2
Fresh and fer-
mented cocoa beans contain approximately 10 percent fla-
vanols (100 mg/g) prior to processing. In contrast, cocoa-
rich dark chocolate consumed by Western populations typi-
cally contains approximately 0.5 percent flavanols. Milk and
white chocolate have lower flavanol content or even fla-
vanol-free composition, respectively.1 Because flavanols
are often bitter and considered unpalatable, different pro-
cesses are used to enrich the flavor and improve the taste.
Fermentation, roasting up to 120°C, and alkalizing to a pH
of 7 to 8 (i.e., “dutching”), as well as the addition of sugar,
milk, vanilla and emulsifiers are all techniques that have
been used to improve the palatability of cocoa.5,7
Unfortu-
nately, these processes can virtually eliminate flavanols
from the finished product, with concentrations decreased
to less than 0.001 percent.7 The percent of cocoa identified
November 2013
THE KENTUCKY PHARMACIST 24
Dec. 2013 CE — Cocoa
on a given product is likewise not a reliable indicator of the
flavanol content or the flavanol-isomer profile. Because of
these many factors, one cocoa product may contain an en-
tirely different flavanol composition than a similarly identi-
fied product.1
Associations of Cocoa Intake and Cardiovascular
Disease Risk Factors
Numerous observational studies support the association
between high cocoa intake and reduced CVD risk and mor-
tality.8,9
Initial interest in the effect of cocoa on CVD risk
factors began with observations among the Kuna Indian
population on the San Blas Islands of Panama. Distinctively
low rates of hypertension and CVD, coupled with an ab-
sence of the age-related increases in BP found in other
populations, were
observed across
this population.1,10
Environmental fac-
tors, rather than
genetic, appeared
to confer this pro-
tective role.1,10
Unique to this pop-
ulation was their
cocoa intake. On
average, traditional
island-dwelling Kuna Indians consumed approximately four,
8-ounce cups of unprocessed cocoa beverages per day
(containing about 3.6 percent flavanols).10,11
Even in those
over 65 years of age, the population-wide mean BP was
110/70 mm Hg.10,11
Conversely, migrant Kuna Indians con-
sumed up to 10 times less cocoa and experienced a BP
increase with age and hypertension prevalence similar to
Western populations.1,10,11
Salt consumption among the
island-dwelling population was equivalent or greater com-
pared to the migrant Indians and there were no significant
differences in body mass index.1,10
Independent of cocoa,
sodium intake and weight, it should be noted that additional
lifestyle factors and changes in physical activity, smoking
status, stress level and diet, may be related to the CVD risk
factor modifications experienced with the migrant Kuna
population.10
Based on the Kuna Indian observations and others, investi-
gational trials were designed to further define the cardio-
vascular and antihypertensive effects of cocoa consump-
tion in various populations. Although a variety of mecha-
nisms have been proposed for these cardiovascular bene-
fits, many of the findings involve improvements in endothe-
lial function. The vascular endothelium plays a key role in
the regulation of vascular homeostasis and alterations con-
tribute to the pathogenesis and clinical expression of CVD.
Prospective studies have demonstrated an association be-
tween endothelial dysfunction and an increased risk of
CVD events. Endothelial function, most commonly quanti-
fied by flow-mediated vasodilation, may improve following
the consumption of flavanol-rich cocoa. Subsequently, clini-
cal or physiological benefits may be realized in hyperten-
sion, platelet aggregation and adhesion, insulin resistance
and hypercholesterolemia.12
Mechanisms and Effects on Blood Pressure
The relationship between BP and CVD risk is continuous
and independent of other risk factors.4 Even small reduc-
tions in BP can lead to substantial decreases in cardiovas-
cular risk.4 Suggested pathways for the effects of cocoa on
BP and other cardio-
vascular risk factors
include an increase
in endothelial nitric
oxide (NO) and a
strong antioxidant
effect. The increased
NO generation asso-
ciated with cocoa
intake is thought to
be triggered by up-
regulation of endo-
thelial NO synthase
(eNOS), responsible for the synthesis of NO from L-
arginine. Enhancement of NO by cocoa flavanols leads to
vasodilation and decreased BP, as well as prevention of
leukocyte adhesion and migration, smooth muscle cell pro-
liferation and platelet adhesion and aggregation.3,13
Heiss
et al reported that in patients with cardiovascular risk fac-
tors including smoking, a cocoa drink high in flavanol con-
tent (176 to 185 mg) rapidly increased circulating levels of
bioactive NO by more than a third and augmented flow-
mediated vasodilation.14
Furthermore, the associated im-
provements in peripheral vasodilation and endothelial func-
tion are reversed by L-NG-monomethyl arginine, a competi-
tive eNOS inhibitor.3,14
Given the reversal of cocoa’s effects
following eNOS inhibition, it can be argued that the reduced
BP and cardiovascular risk in individuals who consume fla-
vanol-rich foods is due to the favorable effect on eNOS ac-
tivity.15
Consumption of 40 g of commercially available dark
chocolate (74 percent cocoa) also significantly improves
plasma antioxidant status two hours after ingestion.16
It is
likely that not only eNOS induction and elevated NO con-
centrations occur, but also a reduction in oxidative stress.
NO breakdown by reactive oxidant species is reduced,
which contributes to enhanced endothelial function, espe-
cially under conditions with a high oxidative stress burden
(e.g., smoking).16
The antioxidant effect may prevent NO
Table 1. Flavanol Content in Foods3
Source Flavanol Content (mg/kg or mg/L)
Apples 20–120
Apricots 100–250
Blackberries 130
Black tea 60–500
Chocolate 460–610
Grapes 30-175
Green tea 100–800
Legume-type Beans 350–550
Red wine 80–300
November 2013
THE KENTUCKY PHARMACIST 25
Dec. 2013 CE — Cocoa
transformation into peroxynitrite, a powerful oxidant, and
thus provide additional protection against vasoconstriction
and vascular damage.3
Another possible mechanism by which polyphenols may
lower BP is by direct inhibition of angiotensin-converting
enzyme (ACE). Through the renin-angiotensin-
aldosterone system (RAAS) pathway for regulation of BP,
ACE transforms angiotensin I to angiotensin II, a potent
vasopressor.2 In vitro and in vivo
studies both support the
occurrence of ACE inhibition by flavanols.17,18
Three hours
after intake of 75 g of dark chocolate, the average inhibi-
tion of ACE activity in healthy volunteers was 18 percent.
This is a level consistent with the magnitude of inhibition
achieved with the ACE inhibitor class of medications.18
This study supports ACE inhibition by flavanol-rich cocoa
as a potential mechanism contributing to BP reduction and
other CVD benefits.
Several randomized controlled trials have investigated the
effects of dark chocolate on BP in patients with hyperten-
sion. Similar designs were used in trials published in 2003
and 2005. Patients were randomized to receive either 100
g of dark chocolate or 90 g of flavanol-free white chocolate
daily for two weeks, then the alternative treatment after a
7-day washout period. In both studies, systolic BP (SBP)
and diastolic BP (DBP) (mean ± S.D.) decreased signifi-
cantly in the dark chocolate arm, while white chocolate
consumption did not reduce BP. In 2003, SBP and DBP
decreased by 5.1 ± 2.4 mm Hg and 1.8 ± 2.0 mm Hg, re-
spectively, and by 11.9 ± 7.7 mm Hg and 8.5 ± 5.0 mm Hg
in 2005.19,20
In 2007, Taubert and associates assessed the
effects of lower doses of dark chocolate (6.3 g of chocolate
containing 30 mg of flavanols) and white chocolate (5.6 g
of flavanol-free chocolate) over a longer period of time (18
weeks).13
SBP was significantly reduced by 2.9 ± 1.6 mm
Hg and DBP by 1.9 ± 1.0 mm Hg in the dark chocolate
group, while white chocolate had no significant effect on
BP compared with baseline. This study suggests that ha-
bitual intake of low doses of dark chocolate may have a
sustained effect on BP.13
Contrary to these findings, other
studies have shown no effect of dark chocolate ingestion
on BP. Muniyappa et al found that consumption of a fla-
vanol-rich cocoa drink for two weeks did not significantly
reduce BP in patients with primary hypertension.21
Addi-
tionally, Engler and colleagues observed no significant
changes in BP following flavanol-rich cocoa intake by
healthy adults during a randomized controlled trial over this
same period of time.22
Because of conflicting results and the small sample sizes
of these and other studies, several meta-analyses have
been conducted. A 2012 meta-analysis of twenty studies
revealed a statistically significant BP reducing effect of fla-
vanol-rich cocoa products compared to controls.1 This me-
ta-analysis identified mean reductions of 2.77 mm Hg and
2.20 mm Hg in SBP and DBP, respectively, providing addi-
tional support that dark chocolate may have a small, but
clinically significant BP-lowering effect.1 In general, a 3 mm
Hg reduction in SBP is estimated to reduce the relative risk
of stroke mortality by 8 percent, coronary artery disease
mortality by 5 percent and all-cause mortality by 4 per-
cent.2
BP is clearly influenced by diet.4 As documented by the
Dietary Approaches to Stop Hypertension (DASH) eating
plan, adoption of a diet rich in fruits, vegetables, and low-
fat dairy products, with a reduced content of saturated and
total fat, is associated with an 8 to 14 mm Hg reduction in
SBP and 5 mm Hg or greater decrease in DBP.23
Certain
dietary supplements (Coenzyme Q-10, fish oil, garlic and
vitamin C) also have evidence of antihypertensive ef-
fects.24
The BP reduction observed in the studies of cocoa
intake is not as robust as that exhibited by the DASH diet
or these specific dietary supplements.23,24
Although cocoa
may be consumed as a part of a healthy DASH-type diet,
there is insufficient evidence to recommend it as a supple-
ment for, or approach to, BP management.
Mechanisms and Effects on Platelets
Platelet dysfunction is another hallmark of CVD. Conse-
quently, the ability of flavanols to reduce platelet activity
might explain, in part, the observed beneficial effects of
these compounds on CVD risk.25
Cocoa diminishes platelet
aggregation and adhesion by reducing adenosine diphos-
duces LDL oxidative susceptibility and has beneficial
effects on plasma HDL-cholesterol concentrations in
humans. Am J Clin Nutr. 2007 Mar;85(3):709-17.
34.Neufingerl N, Zebregs YE, Schuring EA, et al. Effect of
cocoa and theobromine consumption on serum HDL-
cholesterol concentrations: a randomized controlled
trial. Am J Clin Nutr. 2013 Jun;97(6):1201-9.
35.Desch S, Schmidt J, Kobler, D et al. Effect of cocoa
products on blood pressure: systematic review and
meta-analysis. Am J Hypertens. 2010 Jan;23(1):97-
103.
36.Pearson DA, Holt RR, Rein D, et al. Flavanols and
platelet reactivity. Clin Dev Immunol. 2005 Mar;12(1):1-
9.
37.Caffeine. In: DRUGDEX [intranet database]. Version
5.1. Greenwood Village (CO): Thomas Reuters
(Healthcare) Inc. 2013 Oct 17.
38.Zomer E, Owen A, Magliano DJ, et al. The effectiveness
and cost effectiveness of dark chocolate consumption
as prevention therapy in people at high risk of cardio-
vascular disease: best case scenario analysis using a
Markov model. BMJ. 2012 May 30;344:e3657.
December 2013 — Cocoa – Potential Benefits in Cardiovascular Disease
1. Which of the following food sources has the highest total flavanol content? A. Black tea B. Chocolate C. Apricots D. Red wine 2. Which flavanol compound exerts the strongest effects on the vascular endothelium? A. Epicatechin B. Catechin C. Procyanidin D. Proanthocyanidin 3. Dark chocolate typically consumed by the Western population contains approximately: A. 70 percent flavanols. B. 10 percent flavanols. C. 3 percent flavanols. D. 0.5 percent flavanols. 4. Possible mechanisms by which chocolate may lower blood pressure include: A. Antioxidant properties. B. Direct inhibition of angiotensin-converting enzyme (ACE). C. Increased nitric oxide (NO). D. All the above. 5. A 2012 meta-analysis revealed that flavanol-rich cocoa products reduced BP by approximately: A. 8 mm Hg SBP; 5 mm Hg DBP. B. 3 mm Hg SBP; 2 mm Hg DBP. C. 2 mm Hg SBP; 3 mm Hg DBP. D. 1 mm Hg SBP; 1 mm Hg DBP.
6. The BP reduction following cocoa intake is as robust as that exhibited by the DASH diet. A. True B. False 7. Which of the following are true regarding the effect of flavanol-rich dark chocolate on platelets? A. Cocoa increases adenosine diphosphate (ADP)/collagen-
activated hemostasis. B. Effects appear to be the same in both sexes. C. Flavanols reduce glycoprotein IIb/IIIa expression. D. Milk and white chocolates exhibit similar effects as dark
chocolate. 8. By decreasing insulin resistance, chocolate may im-prove not only cardiovascular health but also cognitive function. A. True B. False 9. Flavanol compounds lower LDL-C by all of the follow-ing mechanisms EXCEPT: A. Inhibiting cholesterol absorption in the digestive tract. B. Decreasing expression of LDL-C receptors in the liver. C. Inhibiting LDL-C biosynthesis. D. Suppressing hepatic secretion of apolipoprotein B. 10. Which of the following are precautions that should be considered before recommending dark chocolate for health benefits? A. Excess caloric intake B. Elevations in blood glucose concentrations C. Lack of standardization and content inconsistencies D. All the above
November 2013
THE KENTUCKY PHARMACIST 30
This activity is a FREE service to members of the Kentucky Pharmacists Association. The
fee for non-members is $30. Mail completed forms to: KPERF, 1228 US 127 South,
Frankfort, KY 40601. Credit will be applied to your CPE Monitor Profile.
The Kentucky Pharmacy Education & Research Foundation is
accredited by The Accreditation Council for Pharmacy
Education as a provider of continuing Pharmacy education.
Quizzes submitted without NABP eProfile
ID # and Birthdate cannot be accepted.
Dec. 2013 CE — Cocoa
PHARMACISTS ANSWER SHEET December 2013 — Cocoa – Potential Benefits in Cardiovascular Disease Universal Activity # 0143-9999-13-012-H01-P Name ________________________________________________ KY Lic. # __________________________________ Address ______________________________________________Email_____________________________________ PLEASE CIRCLE THE APPROPRIATE ANSWERS: 1. A B C D 3. A B C D 5. A B C D 7. A B C D 9. A B C D 2. A B C D 4. A B C D 6. A B 8. A B 10. A B C D Information presented in the activity: Met my educational needs ___Yes ___No Figures and tables were useful ___Yes ___No Achieve the stated objectives ___Yes ___No Posttest was appropriate ___Yes ___No Was well written ___Yes ___No Commercial bias was present ___Yes ___No Is relevant to my practice ___Yes ___No Unmet Objectives:______________________________________________________________________________ I hereby certify that I completed this self-study program independently and without assistance from any other party. Signature _________________________________________________ Date _________________________________
NABP eProfile ID #_____________________________ Birthdate ___________________(MM/DD)
TECHNICIANS ANSWER SHEET. December 2013 — Cocoa – Potential Benefits in Cardiovascular Disease Universal Activity # 0143-9999-13-012-H01-T Name _______________________________________________KY Cert. # __________________________________ Address ______________________________________________Email_____________________________________ PLEASE CIRCLE THE APPROPRIATE ANSWERS: 1. A B C D 3. A B C D 5. A B C D 7. A B C D 9. A B C D 2. A B C D 4. A B C D 6. A B 8. A B 10. A B C D Met my educational needs ___Yes ___No Figures and tables were useful ___Yes ___No Achieve the stated objectives ___Yes ___No Posttest was appropriate ___Yes ___No Was well written ___Yes ___No Commercial bias was present ___Yes ___No Is relevant to my practice ___Yes ___No I hereby certify that I completed this self-study program independently and without assistance from any other party. Signature _________________________________________________ Date _________________________________
NABP eProfile ID #_____________________________ Birthdate ___________________(MM/DD)
Expiration Date: November 13, 2016 Successful Completion: Score of 80% will result in 1.5 contact hour or 0.2 CEU.
Participants who score less than 80% will be notified and permitted one re-examination.
November 2013
THE KENTUCKY PHARMACIST 31
Kentucky Renaissance Pharmacy Museum
Reflections of a pharmacy museum founder By: Gloria Doughty
Chairperson and Founder
Kentucky Renaissance Pharmacy Museum
When a box filled with ‘treasures’ from an old Kentucky
Pharmacy arrives at the Kentucky Renaissance Pharmacy
Museum, I can hardly wait to open it. The amber glass bot-
tles, the clear glass apothecary bottles with ground glass
tops and gold and black reverse painted glass labels, the
brass mortars and pestles and fine brass balances are all
symbols of the professional practice of Pharmacy in days
gone by. We can feel the fine porcelain of a pill tile made in
the early 1700’s and envision it being used in the Bard-
stown Pharmacy next to the Tavern where Louis Phillipe
and his group were in exile in 1790.
Now that a major portion of our collection is in storage at
the Kentucky Pharmacists Association buildings in Frank-
fort, we have carefully chosen unique pieces to share with
visitors. At the same time it gives us the opportunity to
delve into the written history of Pharmacy in Kentucky. We
have discovered some amazing facts that make me proud
to be a Kentucky Pharmacist.
It has made me aware of how many ‘firsts’ have occurred
since our state was part of Virginia. Kentucky was the sec-
ond state to join the Union after the original 13, which are
represented by the red and white stripes the United States
flag. That was in 1792. By that time Stanford, Harrodsburg,
Danville and Lexington were growing communities, and
Lexington was known as the “Athens” of the West.
In 1787, Lexington records show that a pharmacy was es-
tablished by ‘Lord’ Morton and Robert Barr in the stockade
at the location now known as Main and Upper Streets. In
1789 Andrew McCalla’s pharmacy was at Short and Market
Streets. In 1795, the “Kentucky Gazette” advertised that
McCalla “carries an assortment of drugs and 167 patent
medicines.” In 1797, the “Gazette” announced the addition
of French Brandy, Gin and cordials along with drugs owned
by Semple and Cox to the pharmacy. The Kentucky Phar-
macy Museum has an imprinted bottle from the McCalla
Pharmacy.
Andrew McCalla was a leader in the community. He was a
member of the city council, the town librarian, a curator of
Transylvania University and Director of “The Kentucky
Vineyard,” the first commercial vineyard in America. Mr.
McCalla was the father of General John McCalla whose
home was built in 1812. He sold his home to Bernard
Gratz. The historic area in Lexington now is known as
Gratz Park. In 1817, McCalla was the
principal leader in establishing the
Eastern Lunatic Asylum, the second in
America.
The first Asylum was in Bethlehem,
Penn., my home town. The Kentucky
Renaissance Pharmacy Museum has
bottles and pharmacy artifacts from
the Rau Drug Company in Bethlehem.
In the 1960s it was the oldest continu-
ously operating pharmacy in the Unit-
ed States, having been established 1743.
With the founding of the first Medical School West of the
Appalachians by Transylvania in 1799, Lexington became
a mecca for chemists, pharmacologists, botanists and sur-
geons. In 1802, Lexington was the first community in the
world to use a vaccination for smallpox. Dr. Samuel Brown,
at the Medical College, had studied
about Jenner’s use of cowpox vaccination to prevent the
spread of the disease. Dr. Brown organized the treatment
for Lexington residents when smallpox had ravaged other
towns. More amazing was the fact that this was before Jen-
ner was permitted use of it in Great Britain.
At that same time Ephraim McDowell, in Danville, was op-
erating his Apothecary Shop, established in 1795, in con-
nection with his medical practice. Later, 1860, Dr. McDow-
ell distinguished himself and Kentucky by performing the
first laporatomy in the world.
Another little known fact involving firsts and medicinal
plants of Kentucky is that sassafras helped to colonize
America. In the 17th Century, sassafras was second only to
tobacco in volume of export to England. Parcels of land
were given to colonists who agreed to come to ‘The New
World’ to grow sassafras. The largest sassafras tree in the
United States was in Owensboro, Ky. It was 100 feet high
with a trunk diameter of 12 feet. Today sassafras root ex-
tracts in which safrole has been removed are permissible
Jamal Aboulhosn Louisville, Ky Donna Adams Sebree, Ky Jennifer Anderson Morehead, Ky Thomas L Arnold Lexington, Ky John E Ausenbaugh Dawson Springs, Ky Charles V. Bailey Union City, Tn Donald R Baker London, Ky Chester Baltenberger Louisville, Ky Verlon Banks Whitesburg, Ky Nancy Horn Barker Winchester, Ky Kerri L Barman Scottsville, Ky Jim R Bell Sebree, Ky Justin Bell Lexington, Ky Richard B Bergman Sarasota, Fla Robert Michael Bero Sanford, N.C. Kristina Dianne Blanton Lexington, Ky Bryan Boelyn Prestonsburg, Ky Bradley Boone Marion, Ky Charlotte Lanae Bowling London, Ky Chris Bowling Barbourville, Ky Lanny G Branstetter Horse Cave, Ky
Jackson Mac Bray Frankfort, Ky Deborah Lee Brewer Sandy Hook, Ky Tyler E Bright Frankfort, Ky James C Brown Bowling Green, Ky Sam Brown Murray, Ky William Brown Mayfield, Ky Scott E Burris Partridge, Ky Robert Burton Hazard, Ky Wendell Doug Butler Burkesville, Ky Kenneth D Calvert Glasgow, Ky Don A Carpenter Olive Hill, Ky Joseph Carr Owensboro, Ky Michelle Casto-Litton Zionsville, In Mashawna Caudill Isom, Ky John Chaney Hazard, Ky Vickie Chaudry Corbin, Ky Rebecca Cheek London, Ky Leanne Clark Richmond, Ky Richard Clement Cadiz, Ky Virginia Clements Morganfield, Ky Charles R. Clifton Fort Thomas, Ky
Rhonda Cochran Liberty, Ky Adam Coffman Nortonville, Ky Samuel Joseph Coletta Cincinnati, Oh Stephanie Sue Collins Corbin, Ky Kimberly Lynn Corley Owensboro, Ky Charlotte Cornett London, Ky Chad Corum Manchester, Ky Anna B Cox Louisville, Ky Melvin R Croley Park City, Ky Marcelle R Curtis Shelbyville, Ky William E Danhauer Owensboro, Ky Kimberly Daugherty Louisville, Ky Marshall Davis Paducah, Ky Alicia Dawson Mcdowell, Ky Kecia Dawson Prospect, Ky Laura Dehart Paducah, Ky James Denton Georgetown, Ky Marie Denton Georgetown, Ky John Dickerson Olive Hill, Ky Alfred L Diebold Louisville, Ky Kenneth Dove Winchester, Ky
Derek Downing Alexandria, Ky David Dubrock Arlington, Ky Michael Durbin Mckee, Ky Hank Edelenbos Louisville, Ky Cathy Edwards Richmond, Ky Mark Edwards Richmond, Ky Joseph Max Eiler Louisville, Ky Rita Etter Williamson, W.Virg. Frank Facione Louisville, Ky William Farmer Henderson, Ky Brian E Fingerson Louisville, Ky Peggy A Fishburn Scottsville, Ky Jennifer L Fitch Lexington, Ky Michael Fitch Lexington, Ky Laura H Fleener Leitchfield, Ky William K Fleming Prospect, Ky Charles R Fletcher Monticello, Ky Shane Fogle Central City, Ky Sherri Forrest Brentwood, Tn Larry T Fortenberry Pikeville, Ky Julian Simms Frank Paris, Ky
November 2013
THE KENTUCKY PHARMACIST 33
KPhA New and Returning Members
Tom G Frazier Salyersville, Ky Milton Dale Frizzell Murray, Ky Barry N Frost Columbia, Ky Judy Gallagher Madisonville, Ky Timothy L Gallagher Madisonville, Ky Joyce M Gardner Hodgenville, Ky Milton E Gardner Jeffersontown, Ky Gale M Garner Paducah, Ky Nevin Goebel Winchester, Ky Eddie Gordon Frankfort, Ky Rebecca Gordon Frankfort, Ky Linda L Gormley Villa Hills, Ky Daniel K Gray London, Ky Marsha Greer-Arnold Louisville, Ky Richard E Griffieth Lexington, Ky Jack B Gross Louisville, Ky Erik Grove Madison, In Patty Guinn Somerset, Ky Julie Hagan Paducah, Ky Cara Hale Inez, Ky James Wayne Hall Owensboro, Ky Jennifer Hall Martin, Ky Michael Hall Danville, Ky
Philip S Hamilton Ludlow, Ky Kyle Harris London, Ky Ellen Harrison Tompkinsville, Ky Phillip Layne Hatcher Pikeville, Ky Clara Herrell Lexington, Ky Whitney Herringshaw Winchester, Ky Linette Hieneman Flatwoods, Ky Jody Holland Pikeville, Ky Michael D Horne Georgetown, Ky Jerry J Horwitz Cincinnati, Oh Marylou Hoskins Hawesville, Ky Marylou Hoskins Owensboro, Ky H. Harper Housman Paducah, Ky Bryan Howze St. Augustine, Fla James Howze St. Augustine, Fla Travis Hudnall Smiths Grove, Ky John Hutchinson Lexington, Ky Gerard Hyland Manchester, Ky Arthur Jacob Louisville, Ky Patrick James Louisville, Ky Phillip Johnson Georgetown, Ky Constance H. Jones Russell Springs, Ky Helen Jones Columbia, Ky
Kimberly Jones Williamsburg, Ky Misty Jones Aurora, Ill Megan Kappes Independence, Ky Michael Keller Salem, Ky Anita King Richmond, Ky Jerry Knifley Columbia, Ky James Knight Berea, Ky Kerry Knochenmus Louisville, Ky John Knoop Louisville, Ky Robert Knott Paducah, Ky Michael Kupper Louisville, Ky Richard S. Lacefield Bowling Green, Ky Kevin Lamping Lexington, Ky Randall Lange Butler, Ky Judith B Lawson Monticello, Ky Teresa Leslie Prestonsburg, Ky Robert Lester Elkhorn City, Ky Donna Lile Campbellsville, Ky Douglas Linger Georgetown, Ky Cheryl Little Prestonsburg, Ky Aaron Lohnes Stanville, Ky Robert Long Louisville, Ky Sheri Lucas Millstone, Ky
W Lusk Betsy Layne, Ky John Lutz Louisville, Ky Carolyn Mallory Russellville, Ky Terry Manley Mount Sterling, Ky Laura Maples Villa Hills, Ky Nicholas Maroudas Williamson, Wv John Marshall Henderson, Ky William Mattingly Lebanon, Ky Charlene McCown Grayson, Ky Jennifer McCreary Louisa, Ky Sheldon McCreary Louisa, Ky Sheldon McCreary Louisa, Ky John McDaniel Lexington, Ky Leeann McDonald Dunnville, Ky Christopher McGlone Vanceburg, Ky William I. McMakin La Grange, Ky John McMeans Ashland, Ky Nicole Maroudas McNamee Forest Hills, Ky Paula Miller Fort Thomas, Ky Jesica Mills Louisville, Ky Boyd Minnich Mount Sterling, Ky Jason Moore Corbin, Ky Emily Morton Hardinsburg, Ky
November 2013
THE KENTUCKY PHARMACIST 34
KPhA New and Returning Members
Amy Mueller Louisville, Ky Steven J Mueller Petersburg, Ky Sherri Muha Hazard, Ky Daniel Nall Louisville, Ky David Nation Owensboro, Ky Troy Neagle Glasgow, Ky James Rodney Neat Louisville, Ky William Nebel Kuttawa, Ky Clarinda Newell Greenup, Ky Edwin Nickell Eddyville, Ky Johnny P Nixon Tompkinsville, Ky Paul Nixon Tompkinsville, Ky Donald Noble Garrison, Ky Jamie Norman Russellville, Ky Kenneth Norwood Louisville, Ky Fred Nowak Independence, Ky Jeff O'connor Frankfort, Ky Wendy Oliver Allensville, Ky Staci Overby Paducah, Ky Christopher Palutis Richmond, Ky Dennis Parker Glasgow, Ky Jennifer D Parker Florence, Ky Vincent Peak Louisville, Ky
Charles Peal Lexington, Ky Alfred Pence Stanford, Ky Robert Perkins Clinton, Ky David Peyton West Liberty, Ky Ronald Poole Central City, Ky Gary T Preece Prestonsburg, Ky John Russell Prine Bowling Green, Ky Jonathon Ratley Henderson, Ky Christi Ratliff Pikeville, Ky Nicholas Rawe Bellevue, Ky James Ray Hopkinsville, Ky Fran Reasor Pikeville, Ky Wendy Renfrow Barlow, Ky Levi Rice Beaver Dam, Ky Jerry Rickard Madisonville, Ky Donald Glenn Riley Russellville, Ky Eugene Carroll Riley Russellville, Ky Stewart Riley Elkton, Ky Kristie Roark Whitesburg, Ky James Robinette London, Ky Richard L Roeding Lakeside Park, Ky Elizabeth Routh Louisville, Ky Jesse L. Rudd Salyersville, Ky
Denise Rueff Louisville, Ky Bonnie Russell Elizabethtown, Ky Gary Russell Madisonville, Ky Larry Russell Elizabethtown, Ky Paul Ruwe Covington, Ky Wanda Salyer Flat Gap, Ky Gregory John Sanders Lexington, Ky Angela Sandlin Louisville, Ky Phillip Sandlin Louisville, Ky Stanley Scates Lexington, Ky Ellen Louise Schueler Franklin, Ky Alyson Schwartz Bardstown, Ky Aron Schwartz Louisville, Ky Benjamin Scott Lexington, Ky Terrence Seiter Burlington, Ky George Shackleford Corbin, Ky Charles Shannon Louisville, Ky William Shely Morehead, Ky Nancy K Shepherd Paducah, Ky Jarrod Shirley Glasgow, Ky Kelli Shirley Glasgow, Ky Thomas Shively Owensboro, Ky Melisa Sigley Charleston, W.Virg.
Michael Sizemore London, Ky Angela Slaughter Covington, Ky William Smallwood Independence, Ky George Snider Bardstown, Ky Linda F Soper Carlisle, Ky John Sorrell Cynthiana, Ky Francis Southall Lebanon, Ky Larry Spears Crittenden, Ky Kelley Spencer Versailles, Ky Glenn Stark Frankfort, Ky Sandra Staton Albany, Ky Cheryl Steiner Hopkinsville, Ky Martha Stepp Harlan, Ky Jack Stone Mayfield, Ky Laura W Stone Louisville, Ky Leslie Stultz Flatwoods, Ky Amanda Sublett Lexington, Ky Clarence Sullivan Richmond, Ky Tracy Sullivan Paducah, Ky Richard Sutton Paducah, Ky Brittany A Taylor Lancaster, Ky Carolyn Taylor Crestwood, Ky David Taylor Crestwood, Ky
November 2013
THE KENTUCKY PHARMACIST 35
@KyPharmAssoc
@KPhAGrassroots
Facebook.com/KyPharmAssoc
KPhA Company Page Are you connected
to KPhA?
Join us online!
KPhA New and Returning Members
KPhA MEMBERSHIP BENEFIT
Discounts on Safety Supply Kits
YOUR KPhA negotiated a discount with SafetyNET for disaster
survival kits. These kits are stored in backpacks and have
supplies to last a three days in case of a disaster.
Go to www.kphanet.org and click on Membership—Benefits for
more information and to find out how to order your kit.
Gloria J Taylor Louisville, Ky Mark Taylor Danville, Ky Mary L. Thacker Louisville, Ky Deborah B Thorn Bowling Green, Ky Joel Thornbury Pikeville, Ky Patricia Thornbury Lexington, Ky Sandra Thornbury Dorton, Ky Rick Timmons Paducah, Ky Charles Turk Williamson, W.Virg. Brenda Turner Jackson, Ky Steven Wagers London, Ky Kelly Walker Philpot, Ky
Rebecca A Walker Hyden, Ky Robert Wallace Dry Ridge, Ky Anthony Warford Clay, Ky Rob Warford Goshen, Ky Jeffrey Warner Jamestown, Ky Julie Warren Gamaliel, Ky L Dwayne Watson Paducah, Ky Stacy Wedeking Metropolis, Ill Clayton Wells Inez, Ky Leslie Joe Wells Mt. Sterling, Ky Kim Wheately Bardstown, Ky William Wheeler Lexington, Ky
Angela G Whetstone Tiline, Ky Jerrold White Russellville, Ky Marcia White Richmond, Ky David Whitley Russellville, Ky Ronald Whitmore Alvaton, Ky Denis Wiggins Louisville, Ky William Wiley Glasgow, Ky Donald Wilkerson Morgantown, Ky Karin Williamson Louisville, Ky Lisa Williamson Louisville, Ky James Wilson Paducah, Ky Carol Wishnia Louisville, Ky
Jacob Wishnia Louisville, Ky Denton M Wood Grand Rivers, Ky Glenn B Wooden Leitchfield, Ky William D Wooden Leitchfield, Ky Dachea Wooten Hazard, Ky Greg Wright Paducah, Ky Joseph M Wright Lucasville, Oh Barbara Sue Yates Horse Cave, Ky Navas Yoonus Elizabethtown, Ky Timothy Young Mount Vernon, Ky Arnold Zegart Prospect, Ky
November 2013
THE KENTUCKY PHARMACIST 36
Pharmacy Law Brief
Pharmacy Law Brief: Pharmacy Law Exam for Licensure Author: Joseph L. Fink III, B.S.Pharm., J.D., Professor of Pharmacy Law and Policy and Kentucky Pharmacists Associ-
ation Professor of Leadership, Department of Pharmacy Practice and Science, UK College of Pharmacy
Question: When I graduated from pharmacy school
quite some time ago, I took a pharmacy law exam as part of
the licensure process, and I’m fairly certain that this exami-
nation was composed locally by the members and staff of
the Board of Pharmacy. The focus was principally on local
state laws. I understand that has changed quite a bit and
that now there is a national pharmacy law exam for those
seeking licensure. Can you describe what contemporary
graduates will be facing?
Response: You are correct – there have been sub-
stantial changes since you (and I) went through this portion
of the licensure process. The National Association of
Boards of Pharmacy administers the Multistate Pharmacy
Jurisprudence Examination (MPJE) to accompany the
North American Pharmacist Licensure Examination
(NAPLEX) in a two pronged approach to assessing the
readiness of nascent pharmacists to become licensed pro-
fessionals. While you may have taken a paper-and-pencil
examination back then, the MPJE, and the NAPLEX, is a
computer based exam.
The exam consists of 90 questions of which 75 “count”, that
is, the responses to those questions will be used to calcu-
late the candidate’s score. What about the other 15 ques-
tions? Those are test items being evaluated for possible
future use. It should be noted, however, that the examinee
does not know which are the “real” questions and which are
included for validation and assessment for possible future
use.
How are the test items vetted to assure their relevance to
practice and propriety for use in assessment of knowledge
and competence? Initial preparation of possible questions
is done by those designated as “Item Writers.” Those who
devise the questions to be considered are drawn from the
ranks of academicians who teach in this area (Your author
pleads guilty! I was an Item Writer way back when the
MPJE was first devised decades ago.) as well as from
among officials affiliated with administrative and regulatory
agencies of relevance to pharmacy such as officials with
boards of pharmacy. There is an MPJE Review Committee
that also weighs in on whether a particular question has
clarity and addresses a relevant area of legal knowledge for
pharmacists. A final step involves review of the proposed
questions by the state board of pharmacy of the jurisdiction
where exam will be used. That step assures that unique
elements of the pharmacy laws of that state are adequately
addressed.
Because the exam administered in State A has questions
specific to the law of that jurisdiction a recent graduate who
takes the MPJE for State A and who then later decides to
also pursue licensure in State B will need to take a sepa-
rate examination for State B. These scores cannot be trans-
ferred from state to state as can be done with NAPLEX ex-
am scores.
Having a computer-based administration of the exam
means that the examination can be assembled using
“adaptive technology.” This means that the upcoming ques-
tions to be posed to the examinee are selected based on
how that individual responded to prior questions. This is
designed to enhance the precision of the examination
based on the test-taker’s performance on prior questions.
One outcome of this process is that each pharmacy gradu-
ate sitting for the exam receives a quite different, perhaps
even unique, test. Test administrators then use something
known as “item response theory” to assure that the various
versions of the exam being administered were equitable.
Another prominent national, even international, exam that
uses this computer adaptive technology approach is the
Kentucky Pharmacists Association 1228 US 127 South Frankfort, KY 40601 (502) 227-2303 www.kphanet.org Kentucky Board of Pharmacy State Office Building Annex, Ste. 300 125 Holmes Street Frankfort, KY 40601 (502) 564-7910 www.pharmacy.ky.gov Pharmacy Technician Certification Board 2215 Constitution Avenue Washington, DC 20037-2985 (800) 363-8012 www.ptcb.org
Kentucky Society of Health-System Pharmacists P.O. Box 4961 Louisville, KY 40204 (502) 456-1851 x2 (502) 456-1821 (fax) www.kshp.org [email protected]
American Pharmacists Associa-tion (APhA) 2215 Constitution Avenue NW Washington, DC 20037-2985 (800) 237-2742 www.aphanet.org
National Community Pharmacists Association (NCPA) 100 Daingerfield Road Alexandria, VA 22314 (703) 683-8200 [email protected]
Drug Information Center Sullivan University College of Pharmacy 2100 Gardiner Lane Louisville, KY 40205 (502) 413-8638 www.sullivan.edu Kentucky Regional Poison Center (800) 222-1222
Frequently Called and Contacted
50 Years Ago/Frequently Called and Contacted
KPhA Remembers KPhA desires to honor members who are no longer with us. Please keep KPhA informed by sending this information to
[email protected]. Deceased members for each year will be honored permanently
at the KPhA office.
50 Years Ago at KPhA CRAWFORD MEYER ELECTED VICE-PRESIDENT AT N.A.R.D. CONVENTION
Crawford Meyer, R.Ph., Louisville, past president of the Kentucky Pharmaceutical Associa-
tion, was elected fifth vice president of the National Association of Retail Druggists at the
67th annual convention of the N.A.R.D. in Chicago Thursday, October 10th. There was
only one vacancy in the N.A.R.D.’s official family and it is quite an honor for Crawford and
Kentucky to be selected for that opening.
Mrs. Alvin L. Schulte, South Fort Mitchell, who served as treasurer the past year, was re-
elected treasurer of the women’s organization of the National Association of Chain Druggists. Mrs. Schulte appeared on
the program at the women’s organization on both Tuesday and Wednesday.
- From The Kentucky Pharmacist, November 1963, Volume XXVI, Number 11.
November 2013
THE KENTUCKY PHARMACIST 44
THE
Kentucky PHARMACIST
1228 US 127 South
Frankfort, KY 40601
KPhA EVENTS
KPhA Mid-Year Conference
on Legislative Priorities
November 15-16, 2013 Marriott Griffin Gate Resort and Spa
Lexington, KY
136th KPhA Annual Meeting and
Convention
June 5-8, 2014 Marriott Griffin Gate Resort and Spa