ARIZONA JOURNAL OF PHARMACY THE OFFICIAL PUBLICATION OF THE ARIZONA PHARMACY ASSOCIATION BROUGHT TO YOU BY PHARMACY NETWORK OF ARIZONA
Spring 2016
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2016 Annual Convention June 9-12th Sheraton Wild Horse Pass Resort & Spa, Chandler
Spring 2016 • Arizona Journal of Pharmacy • 1
Run to Support Pharmacy Education
APF 5K Fun Run Join us Saturday June 11th @6:30am Sheraton Wild Horse Pass Resort & Spa (Chandler) $25 to participate
Proceeds benefit the Arizona Pharmacy Foundation
Visit the Calendar of Events for details and a course map
2nd Annual Southwestern States Residency Conference June 10, 2016
@Sheraton Wild Horse Pass Resort & Spa Chandler, AZ Present research & network with colleagues. Pharmacy residents, preceptors and pharmacy directors are welcome.
Learn More azpharmacy.org/Residency2016
Arizona Journal of Pharmacy
THE OFFICIAL PUBLICATION OF THE ARIZONA PHARMACY ASSOCIATION Brought to you by Pharmacy Network of Arizona
Vol. 8, No. 1
Spring 2016
In This Issue .... Message from Leadership Special contributions
Time Capsule Understanding DSCSA and How it Impacts You Rx and the Law Disclosures of PHI
4 16 17 18
Features Proton pump inhibitors for acute upper gastrointestinal bleeds: To drip or not to drip? 19 Departments Association News New Members PAPA Legislative Update Technician Spotlight: J.R. Gill Pharmacist Spotlight: Jessica DiLeo
5 8 10 12 14 15
Academy News: • Community Pharmacy Academy • Geriatric Care Academy • Health-System Academy • Managed Care Academy • Student Pharmacist Academy • Technician Academy
22 22 23 23 24 24
Continuing Education: Chlamydia, Gonorrhea, and Trichomoniasis: A Guide to Prevention, Diagnosis, and Treatment 25 Venus Thromboembolism: A Review of Prevention and Treatment Options 36
Advertisers
Med Pro PAAS Pharmacy Quality Commitment Pharmacists Life Insurance PTCB Rx Armory
2 44 11 47 11 16
Managing Editor
Editor
Kelly Fine (Ridgway), R.Ph. Rachel Jimenez Marketing & Communications Chief Executive Officer
www.azpharmacy.org/ajp
Editorial Board
Whitney Rice, Pharm.D. Christi Jen, Pharm.D. Kalani Anderson, C.Ph.T.
Andrea Burns, Pharm.D. Jaime Bailey, Pharm.D
Spring 2016 • Arizona Journal of Pharmacy • 3
Leadership Dear AzPA Members, I was getting ready to write this letter, and it dawned on me that I only had one more of these to write after this one. It was a bittersweet moment. This year is flying by, and we have had so many wonderful and successful events, and many more on the horizon. The AzPA Staff and our Executive Board hosted a Holiday Open House in December. We had a great time greeting about 30-40 members who stopped by throughout the evening. The Staff and your Executive Board provided finger food, sweets, hot chocolate and hot apple cider to drink. It was nice to see the turnout, and was an enjoyable social event. After the holiday break, we started the year off with our quarterly Board of Directors Meeting on January 20th. We had good attendance, many via phone. I appreciate your Board of Directors dedication by attending the Board Meetings and through the valuable support and guidance the Board members provide to ensure AzPA events are a success. Our next Board of Directors meeting will be in April; we will be in the final planning stages of the Annual Convention, and your input is important. Please contact the office or any Board Member if you have suggestions for programs or speakers that are wanting to present. On January 23rd, we had an Immunization Training Certificate Program at Midwestern University College of Pharmacy. We had more than 50 in attendance. We appreciate the support that we get from the universities in the state. We had a great turn out at the Southwestern Clinical Pharmacy Seminar. It was held at the JW Marriott Starr Pass Resort & Spa, February 20th and 21st. Prior to the Seminar, we hosted the NACDS Community Pharmacy-Based Point-of-Care Testing Certificate Program, and the Psychiatric Certificate Training Program on February 19th. On Sunday the 21st, we held the APhA Pharmacist & Patient-Centered Diabetes Care Certificate Program. We had wonderful groups of lifelong learners at all of our certificate programs. It is so rewarding to see the continued attendance at these educational programs. Thank you to those who participated in February’s APF Fun Run. We were able to raise some additional funds by creating a new ticket category for this event. It was the new Sleep in Option for the Fun Run. Watch for it at the Annual Convention as well; it is a great opportunity to support the Foundation and get to sleep in. We are in the final planning stages of Pharmacy Day at the Capitol on March 22nd. We hope it will be a productive event to show our legislative representative the scope of services pharmacy professionals bring to public healthcare. This year, we need plenty of support as we are working on multiple bills and initiatives this legislative session. Volunteer to join us in our lobbying efforts during this event. Nominations have started for 2016-2017 Board of Directors positions and Pharmacy Awards. Please complete your nominations before March 11th. Links can be found at the AzPA website under the Member Center tab. This year, we ask that you please first notify the individual you are nominating for a Board position to ensure he / she would be willing to accept the position. Please put on your calendar the upcoming Annual Convention on June 9th through the 12th. This year the event is being held at the Sheraton Wild Horse Pass Resort & Spa in Chandler, AZ. Registration is now available. It is a new and exciting venue. We look forward to seeing you all in June.
Arizona Pharmacy Association
Advancing Pharmacy to Improve Healthcare
Betty Louton, PharmD President AzPA Board of Directors 2015-2016
Kelly Fine (Ridgway), R.Ph., FAzPA Chief Executive Officer Arizona Pharmacy Association
ASSOCIATION NEWS
Arizona Pharmacy Association Events Tuesday, March 22nd, 2016
2016 Pharmacy Day at the Capitol - Phoenix
Meet with state legislators and their staffs. Promote the clinical services pharmacists provide to our community. Discuss current issues relating to pharmacy and health care.
Friday, June 10th, 2016
2nd Annual Southwestern States Residency Conference - Sheraton Wild Horse Pass Resort & Spa
A platform for residents and fellows to present their research. This conference also offers residents and preceptors a forum to network with colleagues.
Friday, June 10th, 2016 APF Golf Tournament Play 18 holes with colleagues to support the Arizona Pharmacy Foundation.
June 10th -12th, 2016 AzPA 2016 Annual Convention - Sheraton Wild Horse Pass Resort & Spa, Chandler
AzPA’s annual event offering CPEs, awards, networking, exhibit hall receptions and more. This 3-day conference typically offers CPE sessions for all practice settings, accredited for both pharmacists and pharmacy technicians.
CALL FOR NOMINATIONS
2016-2017 azPA board of directors nominations
A membership privilege of the Arizona Pharmacy Association is the ability to participate in the election of the Board of Directors and Officers. Your voice is important to the future of our profession and AzPA! Please consider running for a position on the 20162017 AzPA Board of Directors. Open Positions AzPA Board of Directors: • • • • • • • • • • • •
•
President-Elect Treasurer Secretary Community Pharmacy Academy Chair-Elect Geriatric Care Academy Chair-Elect Health-System Academy Chair-Elect Managed Care Academy Chair-Elect Technician Academy Chair-Elect ACCP Chapter Chair-Elect Northwest District Director Southeast District Director Southwest District Director
awards nominations
Honor your peers and colleagues by nominating them to receive an award. These awards are presented during the Annual Convention. • • • • • • • •
Bowl of Hygeia Award AzPA Pharmacist of the Year Award AzPA Technician of the Year Award AzPA Hall of Fame Awards Elias Schlossberg Award Distinguished Young Pharmacist of the Year Award Excellence in Innovation Award Exemplary Patient Care Award
Access Award Nominations at www.azpharmacy.org/2016Awards
Industry Representative
Access Board Nominations at www.azpharmacy.org/2016BODNom Spring 2016 • Arizona Journal of Pharmacy • 5
2016 Annual Convention REGISTRATION FORM OR REGISTER ONLINE TODAY AT azpharmacy.org/Convention2016 First Name: __________________________ Last Name: _______________________________ Organization/Pharmacy:__________________________Professional Designation ______________ Preferred First Name (for name badge): ____________________ Address: ___________________________________________________________________________________ City/State/Zip:_______________________________________________________________________________ Daytime Phone: ____________________ E-mail address: __________________________________ Date of Birth (MMDD only) __________ NABP eProfile ID # ___________ NPI _________________ (Date of Birth and NABP eProfile ID# required to receive continuing pharmacy education credit.) AzPA Member? Yes__ No __ Dietary Need: ___ Vegetarian ___ Gluten-Free I. Early Registration Fees until 05/08/2016
Special Needs/Disabilities: ___________ Section I Total
AzPA Member Pharmacist
NonMember Pharmacist
AzPA Member Allied Pharmacy*
NonMember Allied Pharmacy*
AzPA Member Student
FULL: 3-DAY REGISTRATION
$375
$575
$225
$300
$100
$150
SINGLE DAY __FRI __SAT __SUN
$150
$200
$100
$125
$40
$50
SPOUSE/GUEST : 3-DAY
$200
$250
$200
$250
$200
$250
II. Standard Registration Fees between 05/30/2015 and 6/22/2015
AzPA Member Pharmacist
NonMember Pharmacist
AzPA Member Allied Pharmacy*
NonMember Allied Pharmacy*
AzPA Member Student
FULL: 3-DAY REGISTRATION
$385
$585
$235
$310
$110
$160
SINGLE DAY __FRI __SAT __SUN
$175
$225
$125
$150
$50
$60
SPOUSE/GUEST : 3-DAY
$250
$300
$250
$300
$250
$300
AzPA Member Pharmacist
NonMember Pharmacist
AzPA Member Allied Pharmacy*
NonMember Allied Pharmacy*
AzPA Member Student
FULL: 3-DAY REGISTRATION
$395
$595
$245
$320
$120
$170
SINGLE DAY __FRI __SAT __SUN
$175
$225
$125
$150
$50
$75
SPouse / Guest: 3 DAY
$250
$300
$250
$300
$250
$300
II. ON-SITE
Section II Total
Section II Total
*For AzPA Annual Convention Registration, Allied Pharmacy category includes associate, pharmacy technician, PGY resident, nurse, industry representative, and other non-pharmacist attendees. Federal Commissioned Pharmacists: Please contact the AzPA office at 480.838.3385 for available discounts.
SEPARATE REGISTRATION IS REQUIRED FOR THE THURSDAY, JUNE 9, 2016 OPTIONAL CERTIFICATE TRAINING PROGRAMS. III. Multiple AzPA Certificate Programs will be offered Thursday 6/09/16
EARLY - UNTIL 05/08/16 STANDARD - Between 5/09/16 &
6/03/16
AzPA Member Pharmacist
Non-Member Pharmacist
AzPA Member Resident or Student
Non-Member Resident or Student
$350
$450
$250
$350
$400
$500
$300
$400
Section III Total
Visit the azpharmacy.org/events for a current list of the certificate programs offered June 9th. All certificate programs will run with the program fees listed above.
AzPA 2016 Annual Convention REGISTRATION FORM PAGE TWO Section IV. CONVENTION HANDOUTS
NUMBER
All convention handouts will be available for electronic downloading prior to and after the annual convention. If you wish to pre-order handouts, please make your selection and these will be included in your registration packet.
Pre-loaded Flash Drive
PRICE
Section VI Total
$ 10.00
Section V.
Section VII Total
DONATION
The Arizona Pharmacy Foundation (APF) is a 501 (c) (3) charitable organization. All donations are tax deductible.
Fun Run Participant 06/11/16
$25
APF Golf Tournament 06/10/16
$125 Individual
Section VI. Additional Optional Purchases
$450 Team of 4 PRICE
Friday, June 10, 2016 Exhibit Hall Reception - Adult
$50.00
Friday, June 10, 2016 Exhibit Hall Reception - Child (ages 5-12)
$15.00
Saturday, June 11, 2016 Exhibit Hall Lunch - Adult
$50.00
Saturday, June 11, 2016 Exhibit Hall Lunch - Child (ages 5-12)
$15.00
Friday, June 10, 2016 Awards Luncheon - Single Ticket
$55.00
Friday, June 10, 2016 Awards Luncheon - Table of 10
$500.00
Adopt-A-Technician - includes AzPA Technician Dues
$225.00
Adopt-A-Student - student must be an AzPA member
$100.00
NUMBER
Section VIII Total
Name(s) of Registered Guest(s)/Spouse: Name(s) of Child(ren) Attending Events: Names(s) of Student(s)/Technician(s) [optional]:
PAYMENT SUMMARY Total Due (Sections I, II, III, IV, V)
$
Charge Card: Visa ___ MasterCard ___ Amex ____ Discover ____
Check # _____________
Card Number ______ - ______ - ______ - ______ Exp. Date _______ Security Code _______ Signature ________________________________________________________________________ Make checks payable to Arizona Pharmacy Association Return this form to Arizona Pharmacy Association Office (Mail) 1845 E. Southern Ave., Tempe, AZ 85282 (Fax) 480 838-3557 (Email Scanned Copy) web@azpharmacy.org Or Register Online at www.azpharmacy.org/Convention2016 ALL TIMES AND PROGRAMS SUBJECT TO CHANGE.
Spring 2016 • Arizona Journal of Pharmacy • 7
WELCOME NEW MEMBERS October 1 - December 31st 2015
PHARMACISTS Kellie Smith RESIDENTS Ndidi Alino Gregory Spake Jason Barca Lisa Bailey Pranitha Toom Mardoqueo Martinez Wendell Bernier Cuong Truong Judith Bodor Paul Walicke TECHNICIANS Shamama Burney Megan Woods April Aguirre Mark Carlson Robin Woodward Udit Bakshi Janet Clark Sirintip De La Rosa STUDENTS Pieter Doubell Saul Diaz Michelle Abou-Eid John Ginniman Kassandra Figueroa Elizabeth Alanis Melissa Golladay Brianna Galvan Jason Albright Niru Gupta Erica Lloyd Michael Alexander Stephanie Kehle Monica Orozco Tiba Alsagheer Robert Lawson Scott O’Shaughnessy Krizol Alvarez Timothy Lindgren Margaret Rochon Cody Benson Roberto Sambrano Carlos Jeffrey Low Esau Calderon Cindy Maciak Ashley Stockton Grace Chang Joy Minks Victoria Teague Briana Choi Christine Morgan Bethany Conn Lisa Muth ASSOCIATES Justin Cushing CANG NGUYEN Holly Lloyd Sarina Dhaliwal Jade Nguyen Thien-Huong Nguyen Debra Droopad NEW PRACTITIONER Spencer Duckworth Peter Niedzwecki Jelyn Egan Candice Eastman Karyn Ott Richard Korb Yi Fan Paula Parker Ae Ri Lee Jacob Frazier Heath Randall Belinda Mikic Kimberly Remblake Thomas Hanson Hope Nakazato Marcus Harding Travis Shelton Carolyn Dewart Jennifer Hendricks Marie Belle Herrera Hannah Hertzig Jimmy Stevens Sara Ho Kristin Hoffman NEW MEMBERS: Visit your Member Meghan Hoogervorst Center to learn how to get more Brooke Howard involved with AzPA. Located at www.azpharmacy.org
Tiffany Jomoc Kianaz Kamangar Lauren Kile Pawel Kojs Alisa Lee Bryan Leung Benjamin Liang Dania Lopez Megan Malott Rianne Michael Gina Milazzo Shawn Morse Yvonne Ng Sidharth Patel Sidhi Patel Sarah Penny Christine Phung Joel Pina Tania Pourshams-Manzouri Ana Ramirez KoanHee Rim Eric Rollender Melissa Romero-Aleshire Lauren Rosa Haley Rounsaville Allie Schapker David Seto Isha Shah Eric Smith Rebecca Smith Angel Soto Haley Stenquist Chongwoo Sun Katie Tam Karen Tsui Nichole Uribe
MISSION STATEMENT The Arizona Pharmacy Association is committed to serving and representing all practice settings. AzPA will foster safe and effective medication therapy, promote innovative practice, and empower its members to serve the health care needs of the public.
Stay connected! Arizona Pharmacy Association
Association News
*** Available On-Demand *** Pick Your Poison Current Trends in Toxicology This on-demand program includes 12 video modules covering envenomation, drug abuse, anticoagulants, analgesics, acetaminophen, pediatric ingestions and more. Earn up to 12 contact hours (1.2 CEUs). Accredited for pharmacists only. ACPE UAN# 0100-0000-15-085-H04-P
On-Demand CPE Sessions Purchase a bundle of 6 diverse pre-recorded accredited sessions or select individual sessions of interest. Sessions include: • Pharmacy Law • Pain Management • Immunization Update • Assessing for Gluten in Medication • ABCDs of E-Cigarettes • HIV PrEP
See webpage for accreditation information
azpharmacy.org/OnDemand NEW Virtual Learning Take a virtual lunch break with AzPA every 4th Wednesday of the month to earn LIVE continuing pharmacy education. azpharmacy.org/virtual
Cheers for Volunteers!
We acknowledge the contributions of the volunteers who have made a difference for our organization. Advancing Pharmacy to Ali McBride Denise Atwood Improve Healthcare Katherine Murphy Aisha Badr Hanna Phan Nancy Balch Carol Rollins Jasmin Brantley Michael Rupp Lou Caldwell Candace Thompson Richard Haftmann Lisa Tonrey David Hewlett Hannah Vanderpool Alexa Jane Jaime Holly Van Lew Adrijana Kekic Marti Larriva Jeannie Kim Lee Robert Lipsy Lynne Mascarella
AzPA Academies & Committees ACCP Academy Officers Chair: R. Michelle Baker Meetings held 2nd Tues of the month at 12pm Communications Committee Chair: Whitney Rice Meetings held 3rd Wed of the month at 12pm Community Pharmacy Academy Chair: Valerie Richards Meetings held 3rd Wed of the month at 12pm Community Outreach Committee Chairs: Reginald Roy and Kelee Smith Meetings held 2nd Tues of the month at 3pm Continuing Education Committee Chairs: Nicole Scovis & Lindsay Davis Meetings held 2nd Thurs of the month at 2pm Geriatric Care Academy Chair: Jessica DiLeo Meetings held 2nd Wed of the month at 12:30pm Health-Systems Academy Chair: Lisa Tonrey Meetings held every other 2nd Wed of the month at 12pm Legislative Committee Chair: Mark Boesen Meetings held 1st Wed of the month at 12pm Managed Care Academy Chair: Susan Halterman Meetings held 3rd Wed of the month at 7am Membership Committee Chair: Amy Leung Meetings held 3rd Tues of the month at 12pm Mentor Connection Program Committee Chair: Marcella Honkonen Meetings held 2nd Wed of the month at 2pm Technician Academy Chair: Kalani Anderson Meetings held 2nd Wed of the month at 7pm
Association News
Spring 2016 • Arizona Journal of Pharmacy • 9
Pharmacists Assisting Pharmacists of Arizona (PAPA) Born to be an Addict Anonymous Submission
I was born to a single young mother. My biological father wasn’t ready for children, so he wasn’t in the picture. A couple years later she found a man was soon married and had my brother. My stepfather turned in to a mean addict and alcoholic always in and out of jail. He used to dumpster dive behind hospitals to get his drugs. My earliest memories are of my stepfather telling me I was stupid. Deep down I knew I was smart and I would tell him that my dad was going to save me from him. He made sure to tell me that my real father didn’t want me, in fact, he wanted me dead. He would leave me with men that couldn’t keep their hands to themselves. The first time I was five, later a babysitter, then an old guy that I used to help clean his house. I tried so hard to make him love me, I was cleaning and taking care of my younger brother at age 8. I walked around on my tip toes so he wouldn’t get mad. If it was a Friday, and he had a job and just got paid things here good and there was going to be a party. If it was a Monday and his car was parked out front when I came home from school it meant I needed to stay out front and wait till mom came home. I was always a fighter and stood up to him when I thought he was hurting my brother, this one time my brother snuck-ate something of his , he started hitting my brother. So, I ran into the room and started yelling at him to not hit my brother. He threw my brother on the bed, then locked the door so my mom couldn’t get in and I got the beating of a lifetime. We were so poor, the school nurse used to take pity on us and that is how we got our shoes and jackets. When he was in jail things were good, it meant we got to live with grandma and grandpa. Then he would get out and he would be on his best behavior, then slowing he would start drinking again. Then when I was 11 he brought me into my bedroom and told me he was going to make me ready for men. He was so nice to me and was finally paying attention to me. I told a friend and was devastated that she told her mother. I ultimately had to tell my mom. When, my mom found out she believed me and called the police. He tried to come back and did for a while, the last time I talked to him it was on the phone I told him that I hated him and we would be better off without him. My mom kept picking these terrible men and I continued to grow up. A huge turning point in my life was when I was 15 and my mom just had another baby and still single. I was pregnant and absolutely didn’t want to be like my mom. I vowed from that point on I was going to go to school and become something. During a consult for birth control with a very kind compassionate pharmacist that’s when I knew what I wanted to be. I worked two jobs and went to school full time. I soon started dating my husband and was mar-
ried. We continued going to school then I started having dental problems and female problems. The doctors kept giving me pain medication and for the first time, I felt all was good. We had a baby, then another, then I finally graduated from pharmacy school. I loved my new job, my children and my husband but I felt like something was missing. I would stress over silly things like she doesn’t like working with me or omg I made a mistake or maybe I really am stupid. I couldn’t stay in my head. Then, I hurt my knee and the doctor gave me pain pills, it didn’t help so much with the pain. But, what it did do is help me stop the constant thinking. So, I turned to pain pills for every ailment. A hang nail…I defiantly needed a Vicodin. Soon, the doctors stopped giving me prescriptions. So, I started stealing them, telling myself every time that this was the last time. My husband was laid off from work about the same time my partner started noticing that the counts didn’t add up on the hydrocodone. So, I got a prescription for Xanax and then started stealing that too. I couldn’t sleep so I started taking Ambien. I was a human garbage disposal for prescription medications. When I finally got caught, I was so relieved that all the lying was over. I was completely broken, I and my husband had no job, I was being charged with 3 felonies and I lost everything that I worked so hard to achieve. I called Hal, at the state board of pharmacy and told him what I had done and he had PAPA contact me and she set me up an appointment with a phycologist a week later. My husband was so worried about me that he called the phycologist and dragged me down to his office that day. He recommend that I go into treatment that day, so my husband took me that was 12-16-2010. I spent Christmas in rehab, without my children, my husband, and my pills, I was so devastated, and I felt like my life was over. While in treatment I meant some of the most wonderful people that didn’t care what I had done they just cared about me. They made me go to these silly meetings and talk about my feelings and my past. I could not even look at a Christmas tree, but they still made me. I missed my family and this was the first time I had ever been away from them. They made me carry around a duck and made me tell complete strangers that I loved them and had them tell me that they loved me. When I got out of rehab, I started going to the PAPAs meetings. There I meant some real characters that were completely open about being a thief and a liar and how they sometimes struggle. I slowly came to the realiza-
tion that I wasn’t alone and this addiction that I have is really a disease. I still had problems talking and I still wanted to say I am fine, but the counselor would not let me. I did listen to what he was saying and got a sponsor and started going to meetings. My sponsor made me get a service commitment, so I became a greeter and I called out the ticket numbers for people to speak. I kept doing the suggestions that were made by the PAPA counselor and my sponsor. They recommended I go to Utah for Alcoholism and Drug addiction for health care professionals. I went to Utah by MYSELF, there I meant some of the most amazing people and learned even more about the disease of addiction. I learned that this is a brain disease and I have a thinking problem and for the first time I prayed to God for a spiritual awaking and to take away all the pain that I was in and that I had caused. After the convention was over I was eager to get home so I drove all day and night. Just outside of Flagstaff something happened to me my cruise control wasn’t on. There was a deer in the road and I certainly would have hit had I been traveling the normal 85-90mph. Ever since then, I know God is with me. I used to be mad at God and sometimes thought he wasn’t there because he let bad things happen, but now that I’m older I realize that he gave me the power to fight and he stuck key people in my life to help me stand on my own. I am his miracle-born to be an addict in recovery.
Pharmacists Say it Best … “PTCB Certified Pharmacy Technicians continually demonstrate the highest excellence of professional performance across practice settings. I’ve had the pleasure to work with PTCB CPhTs and rely on their support to my pharmacist activities in providing patient care. They are among the best qualified to participate in operational functions of dispensing and inventory management. Our pharmacy simply couldn’t function without our team of PTCB CPhTs.” —Jeanie Barkett, RPh, Long Term Care Pharmacy Lead Pharmacist, Providence Specialty Pharmacy Services, Portland, OR
Certification Excellence
Do it for your pharmacy. Do it for your patients. Do it for you. Encourage your technicians to become PTCB certified today! Candidates may apply to take the Pharmacy Technician Certification Exam online at www.ptcb.org.
Since 1995, the Pharmacy Technician Certification Board (PTCB) has certified over 400,000 technicians nationwide and is the only pharmacy technician certification program endorsed by the American Pharmacists Association, the American Society of Health-System Pharmacists, and the National Association of Boards of Pharmacy.
CONNECT ONLINE:
If you or someone you care about is suffering from an alcohol and/or chemical dependency problem... ...help is available.
Pharmacists Assisting Pharmacists of Arizona “A Partnership in Caring”
Contact the AzPA Office at 480.207.7869 or papa@azpharmacy.org All calls confidential. Caller remains anonymous.
PAPA
is a program of the Arizona Pharmacy Foundation
Spring 2016 • Arizona Journal of Pharmacy • 11
LEGISLATIVE UPDATE 2016 AzPA Legislative Priorities H2109: PHARMACISTS; LICENSURE
The Board of Pharmacy is authorized to license as a pharmacist, without a pharmacist licensure examination, a person who is licensed as a pharmacist by a pharmacist licensure examination in another jurisdiction if the person holds the license in good standing for any period of time, instead of for at least one year. (First sponsor: Rep. Boyer)
S1112: PHARMACISTS; SCOPE OF PRACTICE
Licensed pharmacists are authorized to administer influenza vaccines to a person who is at least three years of age, booster doses for the primary adolescent series as recommended by the U.S. Centers for Disease Control and Prevention (CDC) and to administer immunizations or vaccines recommended by the CDC to a person who is at least 13 years of age. Previously, a licensed pharmacist could administer only influenza vaccines or immunizations or vaccines in response to a public health emergency to a person who is at least six years of age. A pharmacist who administers an immunization or vaccine is required to report the administration to the person’s identified primary care provider or physician within 48 hours, and failure to report is unprofessional conduct. Establishes a list of methods a pharmacist must use to make a reasonable effort to identify the person’s primary care provider or physician. (First Sponsor: Sen. Barto)
FAIR AUDIT INTEGRITY (Passed in 34+ states):
• There is currently no statutory oversight or procedural requirements in place for pharmacy prescription claims audits in Arizona. While audits are necessary to prevent fraud, waste, and abuse, they should be performed in a fair manner and not be designed to simply take back money. In addition, there should be a written appeals process that allows me to dispute disagreements with audit findings. This bill does not prohibit audits or prevent the recoupment of money or enactment of other penalties where fraud, waste, and abuse have occurred.
PATIENT ACCESS-PHARMACY CHOICE (Passed in 20 states):
• This bill allows AHCCCS members to use the pharmacy of their choice as long as that pharmacy is willing to accept the terms and conditions of the contract. This bill ensures seniors and patients living in our rural communities can utilize the services of my local community pharmacy. Please note: the 2016 legislative session is currently in progress. This means there will be constant updates to bill verbiage and process. For specific inquiries please contact the AzPA Office at 480-838-3385 or legislative@azpharmacy.org
Support these Legislative Initiatives Contribute to the Pharmacists Political Action Committee of Arizona (PharmPAC) www.azpharmacy.org/PharmPAC
All AzPA members are welcome to attend the monthly meetings. If you are interested in joining the discussions, contact Mark Boesen and Kenneth Bykowski, Legislative Committee Chairs at legislative@azpharmacy.org or Kelly Fine, AzPA CEO at kelly@azpharmacy.org
Mark Boesen & Kenneth Bykowski AzPA Legislative Affairs Committee Co-Chair legislative@azpharmacy.org Jeff Gray, R & R Partners AzPA Lobbyist
Bill Tracking Bill Number / Short Title
Summary
Sponsors
H2264: INSURANCE; PRESCRIPTION EYE DROPS; REFILLS
Health and disability insurance contracts and policies issued, delivered or renewed on or after the effective date of this legislation that provide coverage for prescription eye drops are prohibited from denying coverage for a refill of a prescription for eye drops if the subscriber requests the refill within specified time periods, the prescription eye drops are a covered benefit, the prescribing provider indicates on the original prescription that additional quantities are needed, and the refill requested does not exceed the number of additional quantities prescribed.
First sponsor: Rep. Brophy McGee
H2265: EPINEPHRINE AUTO-INJECTORS
Health care practitioners are authorized to prescribe epinephrine auto-injectors in the name of an “authorized entity” (defined as any entity or organization other than a school at which allergens capable of causing anaphylaxis may be present). Authorized entities are permitted to acquire and stock a supply of epinephrine auto-injectors and designate employees or agents who are trained to be responsible for the injectors. Trained employees or agents are authorized to provide or administer an epinephrine auto-injector to any individual s/he believes in good faith is experiencing anaphylaxis. Training requirements are specified.
First sponsor: Rep. Cobb
A “durable medical equipment supplier” (defined) that has a permit to do business in Arizona is required to submit to the Board of Pharmacy a notarized affidavit attesting that the supplier has at least one accredited physical facility that is staffed during reasonable business hours, has sufficient inventory and staff to service or repair products, and is accredited by an accrediting organization that is recognized and accepted by the Centers for Medicare and Medicaid Services.
First sponsor: Rep. Cobb
A licensed physician is authorized to prescribe or dispense naloxone hydrochloride or any other opioid antagonist that is approved by the U.S. Food and Drug Administration to a person who is at risk of experiencing an opioid-related overdose or a family member or community organization that may be in a position to assist that person. A pharmacist is authorized to dispense without a prescription, according to Board of Pharmacy protocols, naloxone hydrochloride or any other opioid antagonist that is approved by the U.S. Food and Drug Administration to a person who is at risk of experiencing an opioid-related overdose or a family member who is in a position to assist that person. A person is authorized to administer an opioid antagonist that is prescribed or dispensed in accordance with the protocol specified by the physician or pharmacist to a person who is experiencing an opioid-related overdose. Physicians, pharmacists and persons who take these actions in good faith are immune from specified liability.
First sponsor: Rep. Carter
H2266: DURABLE MEDICAL EQUIPMENT SUPPLIERS; REQUIREMENTS
H2355: OPIOID ANTAGONISTS; PRESCRIPTION; DISPENSING; ADMINISTRATION
Spring 2016 • Arizona Journal of Pharmacy • 13
TECHNICIAN SPOTLIGHT J.R. Gill: Family Man, Sailor, Educator, Social Worker, Pharmacy Technician by Kalani Anderson, C.Ph.T
Shortly after the end of the Vietnam War, new high school graduate and 18 year-old, Joseph (“J.R.”) Gill wanted to serve his country, see the world, and receive medical training. The Navy offered him the perfect opportunity to fulfill all three desires, so he enlisted and later completed a program at the U.S. Naval School of Health Sciences in Portsmouth, VA in 1981 becoming a pharmacy technician. As a Navy Pharmacy Technician, J.R. worked in a hospital setting, independently aboard a ship, and in a clinical setting. He prepared sterile and nonsterile compounds, worked with controlled medications, unit dosing, and pre-packaging medications, and managed inventory. He served in leadership roles in many of these settings supervising other technicians. During his 20 years of service in the Navy, he fulfilled his desire to see the world traveling to nearly every continent. While in Greece in 1991, he received a letter of recognition from the White House during a visit by then President of the United States, George H. W. Bush for his service to the country. While stationed at a Branch Medical Clinic in Bangor, Washington in 1995, he was recognized as Sailor of the Year. Upon retiring from the Navy, J.R. continued pursuing his education and serving his country and others. In 1997, he completed a Bachelor of Science Degree from the University of New York, Albany. Upon completion of this degree, he embarked on a career in social work and later in correctional health where he had innumerable experience working closely with people from all walks of life and helping them work their way through tough situations. Despite leaving the pharmacy profession for a time, the profession of pharmacy didn’t leave him. Director of Education at Brookline College, Meryl Krich says “J.R. eats, breathes, and lives pharmacy,” and he found a way to combine all his experiences as a pharmacy technician educator. In 2010, he moved to Arizona and has worked as a Program Director for a technician training program, first at the Bryman School of Arizona and for the last year at Brookline College – Phoenix, AZ. He loves taking “real world” scenarios and applying them to lessons and seeing the “a-ha” moments when a concept is understood. He helps students and new pharmacy technicians to succeed by mentoring and offering consistent and personalized encouragement and relishes the excitement students express when they share their successes with him. Todd Wells, Store Manager at a Walgreens location that works closely with J.R. in placing externs underscores the emphasis J.R. places on individually mentoring and working with students in the following statement: “J.R.’s strength for Walgreens is also in the fact he knows his students very well. If he has a student who isn’t strong in certain areas, he is very good at communicating those issues so the student can be placed in a store that can improve those weaknesses and continue their training schedule.” Michael Cochran, who knew J.R. in the Navy, as well as through Brookline College, describes J.R.’s influence at Brookline by saying, “In an incredibly short time, J.R. seemed to have a full grasp of where the program was at and the direction it needed to go to remain both relevant and competitive…[H]e was able to commence a number of large projects, such as initiating an online component to Brookline’s P.T. Program, as well as preparing the program for ASHP accreditation, all while simultaneously instructing students and re-writing and implementing syllabi!” J.R. joined AzPA in 2010 to network with other members of the pharmacy profession and sees it as a great opportunity to serve the community. His goals are to be an active member in forming policy and affecting positive change in the training and education of pharmacy technicians on the state and national level and values membership in AzPA for the work done in this same direction. He currently serves as a Technician Academy CE Committee representative helping with the newly formed Technician CE Task Force helping to ensure technicians have relevant and worthwhile continuing education offerings through AzPA. J.R. seems to have boundless, energy which is visible as he discusses issues within the industry. His eight children (aged 33 all the way down to seven), some of whom have special needs, provide more than a second full time job for him and his wife, but they also fill them with purpose and zeal for life. Their family can often be seen participating in local food banks’ efforts and Operation Santa Claus during the holidays and regular efforts to support St. Mary’s Food Bank. If you want to contact J.R. for networking or to ask him about his work, he recommends connecting on Linkedin, emailing him at joseph.gill@brookline.edu, or chatting with him on the “Arizona Pharmacy Technician – Facilitated by AzPA’s Technician Academy” Facebook group where he is a regular participant and voice.
PHARMACIST SPOTLIGHT Profile: Jessica DiLeo, PharmD
by Zachary Segerman, PharmD candidate 2016
Dr. Jessica DiLeo is, in no uncertain terms, a pharmacist. At the same time we were chatting on the telephone, she was also busy at work, while answering my questions without losing pace, or dropping characters from her impressive 100 words-per-minute typing ability. Observing this level of skill and productivity, it is clear why she was recently named the Distinguished Young Pharmacist of 2015 at the Arizona Pharmacy Association’s Annual Convention. An award given to young pharmacists (those graduated within the last 5 years) who have shown outstanding leadership. She received her Doctorate of Pharmacy from the University of Arizona in 2013, which she described as a logical continuation of her experience as a pharmacy technician where she handled disparate duties including scheduling and even auditing. During her pharmacy education she interned at a hospital, but noted, “The [hospital] setting did not have the level of patient interaction I wanted.” Following that experience, she joined the Medication Management Center at the University of Arizona. This was providential; it became her career where she is currently a Medication Management Specialist and was where she developed a close relationship with her mentor Kevin Boesen (founder of the Medication Management Center). Her job description as a Medication Management Specialist is lengthy. “I wear many hats here,” she jokes, which quickly becomes an understatement as our conversation continued. She provides counseling on correct and appropriate use of medication to patients across the country, with a focus on the Medicare beneficiary patient population. In addition to that, she develops processes used throughout the Center that guide, systematize and consubstantiate the medication counseling given out to patients. Often pharmacy interns do not know what they do not know, and Dr. DiLeos has algorithms in place known as “Red Flag Process Guides” that can direct an intern to escalate the medication management session to a registered pharmacist so that s/he can evaluate that patient further and provide most medically prudent advice regarding serious medication side effects, interactions or clinical markers such as high blood pressure. This work has given her the opportunity to shepherd pharmacy interns during their formative early practice years as well. Dr DiLeo comments, “I am in a better position than I was. Now, I am comfortable enough in my practice style and still close enough to my educational training to guide students through pharmacy education and prepare them for the challenges of actually being a professional.” Despite the transformative nature of the necessary student-to-professional change, Dr DiLeo enjoys preceptorship immensely and sharing her experience with others to help mentor and develop capable, involved professionals. Involvement is something near to Dr DiLeo’s heart. She long had a spirit of volunteerism, but does counsel that getting involved in an organization is again an exercise in reducing unconscious ignorance. “You may not necessarily find the right organization first and that’s OK. You start your didactic education with an idea of what you want to do,” going on to add that the idea may (and probably will) fall apart. The AzPA offers an opportunity to start generally and branch into specific specialties, where Dr DiLeo has become the Chair of the Geriatric academy as her practice setting became focused on the elderly. She also has helped organize the student track at the AzPA annual convention and currently helps organize new practitioner monthly social gatherings. While, Dr DiLeo’s contributions have been tremendous, she notes that, “Everyone should be involved, but involvement will look different for different people,” if it’s just a little bit, that’s fine. She wants the profession to develop a voice, and helping to build a voice that speaks for pharmacy may not need a huge commitment, but a small amount of mentorship and advice from pharmacist to pharmacist, tech to tech or any combination would go a long way to tuning that voice so it speaks with a clear timber and pitch about how pharmacists can improve patient health.
Spring 2016 • Arizona Journal of Pharmacy • 15
SPECIAL CONTRIBUTIONS Pharmacy Time Capsules 1st Quarter 2016 1991 - Twenty-five Years ago: • The Joint Commission of Pharmacy Practitioners developed that mission statement for pharmacy that would be embraced by most pharmacy organizations: To help people make the best use of their medications. 1966 - Fifty Years ago: • 9th Floor project at Moffitt Hospital at University of California San Francisco put pharmacists on the floor to provide 24/7 unit dose dispensing and admixture program. • First ASHP Midyear Clinical Meeting held in Washington, DC attended by 250 individuals. 1941 - Seventy-five Years ago: • Japanese sneak attack on Pearl Harbor on Sunday, December 7 leads to a declaration of war on December 8. • On February 12 English Constable Albert Alexander becomes the first patient treated with intravenous penicillin. His condition improves initially but there is insufficient supply to stop the fatal infection. 1916 - One hundred Years ago: • Margaret Sanger opens the first U.S. birth control clinic in Brooklyn. By: Dennis B. Worthen, PhD, Cincinnati, OH One of a series contributed by the American Institute of the History of Pharmacy, a unique non-profit society dedicated to assuring that the contributions of your profession endure as a part of America’s history. Membership offers the satisfaction of helping continue this work on behalf of pharmacy, and brings five or more historical publications to your door each year. To learn more, check out www.aihp.org.
Promote Your Company to Arizona’s Pharmacy Professionals! Connect with AzPA The following opportunities are available: • Become a VIP by sponsoring an upcoming event • Advertise in this journal, event program, AzPA website, job board or weekly e-newsletter • Participate in the Annual Convention exhibit hall to meet around 500 pharmacy professionals
For more information visit azpharmacy.org/sponsor or contact Rachel Jimenez, AzPA Marketing at rachel@azpharmacy.org, 480-838-3385
Understanding DSCSA and How it Impacts YOU! Arizona Pharmacy Association
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Spring 2016 • Arizona Journal of Pharmacy • 17
Rx AND THE LAW
This series, Pharmacy and the Law, is presented by Pharmacists Mutual Insurance Company and your State Pharmacy Association through Pharmacy Marketing Group, Inc., a company dedicated to providing quality products and services to the pharmacy community.
DICLOSURES OF PHI
By Don R. McGuire, Jr., R.Ph., J.D. Uses and disclosures of Protected Health Information (PHI) are allowed under the Health Insurance Portability and Accountability Act (HIPAA) as needed to perform transactions for treatment, payment, or healthcare operations (TPO). This is well known to pharmacists, but not always by patients. Patients are aware of HIPAA and some of them think that HIPAA prohibits all use and disclosure of PHI. Patients have reported claims alleging that the pharmacists violated HIPAA by contacting the prescriber to clarify a prescription. Pharmacists know that they can disclose PHI to another treating health professional under TPO. Pharmacists may be less aware of other uses and disclosures permitted under HIPAA that are not included under TPO. These can be found in the Code of Federal Regulations at 45 CFR 164.512. These uses and disclosures are not absolute. Many have conditions that must be met prior to the use or disclosure being made. The length of this article won’t allow a complete listing of all the conditions for each. The regulations may also restrict the parties to whom the disclosure may be made. The first permitted use and disclosure is for public health activities. This allows disclosures to public health authorities, FDA and other persons in certain circumstances. One of these is an agency authorized to receive reports of child abuse or neglect. This connects to a second permitted disclosure about victims of abuse, neglect, or domestic violence. There is some overlap in these permitted uses, so caution is needed to make sure your situation fits into the parameters. There are three related disclosures that involve law enforcement. The first allows disclosures to law enforcement officials about victims of crime or about criminal conduct. Disclosure is also permitted to avert serious threats to health or safety, either to a person or to the public. This could even include disclosing PHI that would help police identify or apprehend escapees. The third permitted use here is disclosures to a coroner or medical examiner to help identify a person or help determine the cause of death. Regulations also permit disclosures for cadaveric organ, eye or tissue donations; or for research purposes. There are a number of specific conditions regarding disclosures for research purposes. There are two exceptions involving the legal and regulatory system. The regulation provides for disclosures to a health oversight agency if the agency is performing their oversight activities. This would include audits, inspections, investigations or disciplinary actions. These are not audits conducted by third party payers. There is also an exception for court orders and subpoenas. There are conditions to be met for the subpoena exception to be valid, so use caution when responding to a subpoena. The last two exceptions are in specialized areas. The first is for specialized government functions. These include uses and disclosures for military and veterans activities, national security activities, protective services for the President, correctional institutions or to the National Instant Criminal Background Check System. The last exception is the disclosure of PHI to workers compensation programs as required by law. Workers compensation is a statutorily-created system that regulates the care of injured workers. The lesson for pharmacists is that there are many situations other than TPO where use or disclosure of PHI is permitted without the patient’s authorization. All of the exceptions are subject to conditions and are not absolute. Also, the pharmacist should remember that they are only allowed to disclose the minimum amount of information necessary to fulfill the purpose of the disclosure. These exceptions are not authorizations to disclose all PHI concerning an individual. When presented with a request for PHI, the pharmacist should investigate if the request is permissible under TPO or some other exception. If the request is permissible, the pharmacist should verify that all conditions have been met. The Department of Health and Human Services has a useful page on its website to help the pharmacist navigate rules and conditions. It can be found at: http://www.hhs.gov/hipaa/for-professionals/faq. As always, the pharmacist should reach out to their local attorney if they need assistance in navigating the HIPAA waters. © Don R. McGuire Jr., R.Ph., J.D., is General Counsel, Senior Vice President, Risk Management & Compliance at Pharmacists Mutual Insurance Company. This article discusses general principles of law and risk management. It is not intended as legal advice. Pharmacists should consult their own attorneys and insurance companies for specific advice. Pharmacists should be familiar with policies and procedures of their employers and insurance companies, and act accordingly.
FEATURES Proton pump inhibitors for acute upper gastrointestinal bleeds: To drip or not to drip?
By: Georgina Rubal-Peace, PharmD, BCPS, PGY1 Pharmacy Residency Director, Banner - University Medical Center South; Jamie Natkowski, PharmD, BCPS, Critical Care Pharmacist, Banner - University Medical Center South; and Melissa L. Nelson, PharmD Candidate 2016, University of Arizona College of Pharmacy
Introduction: An acute upper gastrointestinal (GI) bleed is a serious but common medical emergency. One of the most common causes of acute upper GI bleeds is peptic ulcer disease (PUD), which can be precipitated by a number of conditions including Helicobacter pylori infection, excess use of non-steroidal anti-inflammatory drugs (NSAIDs), and stress-related ulcers.1-2 Each of these conditions impairs the GI mucosa, increasing cell membrane permeability, which causes hydrogen ions to diffuse back over the membrane further increasing acidity, leading to membrane cell death and ulceration.3 The International Consensus Upper Gastrointestinal Bleeding Conference Group and the American College of Gastroenterology have published guidelines for acute upper GI bleeds under these conditions. Both guidelines recommend the use of endoscopic hemostatic therapy (EHT) followed by a proton pump inhibitor (PPI).1,4 Treatment with a PPI will raise gastric pH levels, which promotes clot formation, decreases risk of rebleed, and enables healing.3 In the acute care setting, PPI therapy is usually delivered intravenously in patients with high-risk findings on endoscopy (e.g., active bleeding, adherent clots and visible vessels). The guidelines recommend an intravenous (IV) bolus of a PPI dosed at 80mg followed by a continuous infusion (8mg/ hr for 72 hours). This is based on the hypothesis that a continuous gastric pH > 6 will minimize recurrent bleeding by stabilizing clot formation.1,4 However, delivery by continuous infusion is associated with higher costs and increased resource utilization prompting researchers to conduct studies examining the effectiveness of various PPI regimens (e.g., continuous infusion vs. intermittent IV bolus vs. oral dosing). Both guidelines acknowledge that there is evidence directly comparing high-dose IV therapy with intermittent IV or oral PPI dosing. However, due to issues related to trial weaknesses, they do not make a recommendation for alternative PPI regimens. The international guidelines do state that for patients in whom high-dose IV therapy is not available or feasible, lower IV doses or high-dose oral therapy are effective, particularly in the Asian population which has more data to support intermittent oral or IV therapy.4
FEATURES
Clinical Trials:
Several studies have been conducted to compare the efficacy of intermittent IV bolus PPI dosing or oral dosing versus the standard continuous infusion regimen utilized for acute upper GI bleeds. The published studies are mostly small in number and underpowered. They also include a variety of dosing regimens using different PPIs. This makes it necessary to rely on meta-analyses to assess the available data and whether or not adequate evidence is available to support alternative dosing regimens. In order to assess noninferiority of intermittent PPI dosing, a recent systematic review and meta-analysis was conducted by Sachar et al. to evaluate 13 randomized controlled trials (RCTs) that included 1691 patients.5 RCTs were included if patients had an upper GI bleed with a high risk stigmata (HRS) and underwent successful EHT. Since the degree of acid suppression required to reduce rebleeding is currently unknown, studies that included any dose of boluses were included in addition to studies that used either oral or IV routes. The primary hypothesis was that intermittent PPI dosing (oral or IV) would be found to be noninferior to the standard continuous infusion regimen for recurrent bleeding, and a noninferiority margin was defined a priori as an absolute risk difference of 3% or less. The primary outcome selected (rebleed within 7 days) was recorded in ten of the trials included in the meta-analysis. The absolute risk difference for this outcome was -0.28% (much less than the 3% margin for noninferiority). The authors concluded this demonstrated that intermittent PPI dosing is noninferior to continuous infusion with regards to the primary outcome. Post-hoc intent-to-treat sensitivity analysis provided nearly identical results for the primary outcome (0% absolute risk difference) further supporting the conclusion that intermittent dosing is not inferior to continuous infusion. Only one trial included in this analysis reported a statistically significant difference in rebleed between the two dosing regimens, and it actually favored intermittent dosing over the standard continuous infusion regimen.6 Noninferiority was also demonstrated for the secondary outcome measures (e.g., rebleed within 3 days, rebleed within 30 days, mortality, and hospital length of stay). Thus, the authors concluded that since similar clinical outcomes can be Spring 2016 • Arizona Journal of Pharmacy • 19
obtained with intermittent IV dosing versus the current recommended regimen (bolus plus continuous infusion), guidelines should be revised to support use of intermittent PPI dosing.5 Sachar et al. also performed a subgroup analysis on studies that included oral PPI administration. Results of this analysis showed that oral administration provided a similar effect on gastric pH compared to intermittent IV dosing.5 However, current treatment guidelines do not recommend the use of oral medications as a first line choice in acute upper GI bleed as there are no well-designed studies providing evidence of similar efficacy with oral dosage forms.1,4 Further studies are needed prior to recommending oral therapy for acute GI bleeds. This meta-analysis provided significant evidence to support the use of intermittent PPI therapy; however, it also prompted some questions. A limitation to these studies is that there were neither restrictions on doses, frequencies, nor routes of the PPIs. In the studies evaluated, intermittent PPI dosing regimens varied. Different agents were used and frequency of administration varied across the studies. To provide information to fill the gap for which intermittent regimen is best, the authors performed a subgroup analysis in an attempt to determine if there were differences in efficacy among the various intermittent IV PPI regimens. Although one would expect that increased dosing frequency and higher doses would improve efficacy, since larger doses administered more frequently are associated with a more continuous increase in gastric pH, the subgroup analysis did not reveal improved efficacy in those groups as expected. Instead, the treatment effects were similar across all dosing regimens. Therefore, the authors recommend using an intravenous PPI (whichever agent is available at the organization) at least twice daily given the pharmacodynamics associated with PPIs.5 Further limitations of the meta-analysis exist in the form of bias and heterogeneity. As previously stated, the reviewed studies were of variable quality and had risks for bias. This was mostly because 8 of the 13 studies were not blinded and therefore were prone to a lack of allocation concealment. However, subgroup analysis was able to rule out significant study heterogeneity related to bias. A meta-analysis performed by Tsoi et al. compared six randomized studies that examined the efficacy of oral versus IV PPI administration in patients with peptic ulcer disease specifically.7 The characteristics of the individual studies and results are noted in Table 1. The primary outcome was recurrent bleeding at 30 days in four trials and at 15 days in the other two trials.8-13 Transfusion requirements, length of hospital stay, surgical intervention, and mortality were also evaluated. The analysis revealed that there was no significant difference in efficacy between the FEATURES
two dosage forms. Additionally, no statistical difference was found between oral and IV PPIs for volume of blood transfusion (mean difference, -0.02 units; 95% CI, -0.29 to 0.24 units), mortality (RR, 0.88; 95% CI, 0.29 to 2.71), and surgical intervention (RR, 0.82; 95% CI, 0.19 to 3.61). The length of hospital stay was slightly lower for those receiving oral PPI therapy (mean difference, -0.74 days; 95% CI, -1.10 to -0.39 days). However, the sample sizes were small (total of 615 patients included), and there was a lack of blinding in the oral versus intermittent IV PPI trials. In addition, one trial employed poor randomization and allocation techniques.7 Overall, Tsoi et al. concluded that there were no differences between IV and oral PPI therapy in recurrent bleeding and mortality in patients with peptic ulcer bleeding. The authors acknowledged that their analysis was likely underpowered and called for further investigation with larger RCTs.
Discussion:
With the higher costs and increased resource utilization associated with the continuous infusion PPI regimen recommended in current treatment guidelines, research is focusing on alternate regimens to treat acute upper GI bleeds. Current treatment guidelines recommend a high dose PPI starting with an 80 mg IV bolus followed by 8 mg/hr IV infusion for 72 hours. 1,4-5 One specific PPI is not preferred over the other. However, the meta-analysis by Sachar et al. provided evidence to support the use of high dose PPI given at least twice daily, PO or IV, as an effective alternative to continuous infusion. Despite the need for larger, double-blind, randomized control trials, intermittent PPI therapy may be a reasonable alternative for lower risk patients and/or those in whom a continuous infusion is not possible. Providers should take into consideration the provided data and use caution when selecting intermittent PPI therapy over a continuous infusion.
References:
1. Laine L and Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107(3):345-60. 2. Dickman R, Mattek N, Holub J, Peters D, Fass R. Prevalence of upper gastrointestinal tract findings in patients with noncardiac chest pain versus those with gastroesophageal reflux disease (GERD)-related symptoms: results from a national endoscopic database. Am J Gastroenterol. 2007;102(6):1173-9. 3. Shin JM and Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10(6):528-34. 4. Barkun AN, Bardou M, Kuipers EJ et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152(2):101. 5. Sachar H, Vaidya K, and Laine L. Intermittent vs continuous
proton pump inhibitor therapy for highrisk bleeding ulcers: a systematic review and meta-analysis. JAMA Intern Med. 2014;174(11):1755-62. 6. Ucbilek E, Sezgin O, Altintas E. Low dose bolus pantoprazole following successful endoscopic treatment for acute peptic ulcer bleeding is effective: a randomized, prospective, double blind, double dummy pilot study [abstract] Gastroenterology. 2013;144(suppl 1):S506. Full article in Acta Mediterranea, 2015;31:91-96. 7. Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-8 8. Jae YJ, Kwang RJ, Young H, et al. A comparison of the effect of high-dose oral and intravenous proton pump inhibitor on the prevention of rebleeding after endoscopic treatment of bleeding peptic ulcers. Korean J Gastrointest Endosc 2006; 22: 6–11. 9. Yilmaz S, Bayan K, Tuzun Y, Dursun M, Canoruc F. A head to head comparison of oral vs intravenous omeprazole for patients with bleeding peptic ulcers with a clean base, flat spots and adherent clots. World J Gastroenterol 2006;12(48): 7837–43. 10. Bajaj JS, Dua KS, Hanson K, Presberg K. Prospective, randomized trial comparing effect of oral versus intravenous pantoprazole on rebleeding after nonvariceal upper gastrointestinal bleeding: a pilot study. Dig Dis Sci 2007; 52(9): 2190–4. 11. Tsai JJ, Hsu YC, Perng CL, Lin HJ. Oral or intravenous proton pump inhibitor in patients with peptic ulcer bleeding after successful endoscopic epinephrine injection. Br J Clin Pharmacol 2008; 67(3):326–32. 12. Mostaghi AA, Hashemi SA, Heydari ST. Comparison of oral and intravenous proton pump inhibitor on patients with high risk bleeding peptic ulcers: a prospective, randomized, controlled clinical trial. Iran Red Crescent Med J 2011; 13: 458–63. 13. Yen HH, Yang CW, Su WW, et al. Oral versus intravenous proton pump inhibitors in preventing re-bleeding for patients with peptic ulcer bleeding after successful endoscopic therapy. BMC Gastroenterol 2012; 12: 66.
Table 1 Study Name
Study design
N
Intervention
Jae et al. 20068
Single Center Prospective RCT
38
211
20069
Single Center Prospective RCT
Bajaj el al. 200710
Single Center Prospective RCT
25
Tsai et al. 200811
Single Center Prospective RCT
156
Pantoprazole 40mg PO BID x 5days vs 80mg bolus + 8mg/hr infusion x 3 days Both followed by 40mg PO daily x 8 weeks Omeprazole 80mg IV bolus followed by 8mg/hr x 72 hr vs omeprazole 40mg PO q12 x 72 hr Both followed by omperazole 40mg PO daily Pantoprazole 80 mg PO BID x 3days vs 80mg IV bolus + 8mg/hr infusion x 3 days. Both followed by pantoprazole 40 mg PO BID x30 days Rabeprazole 20mg PO BID x 3days vs omeprazole 40mg IV q12 h x 3days. Then oral PPI x 2 months (rabeprazole 20 mg or esomeprazole 40 mg once daily)
Mostaghi et
Single Center Prospective RCT
106
Single Center Prospective RCT
100
Yilmaz et al.
al. 201112
Yen et al. 201213
Total
Omeprazole 80mg PO BID x 3 days vs pantoprazole 80 mg IV bolus + 8 mg/hr infusion x 3 days followed by omeprazole 20 mg PO daily x 30days Esomeprazole 40mg continuous infusion q6h x 3days, then 40mg PO daily x 2 months vs lansoprazole 30mg PO QID x 3days followed by once daily for 2months
Recurrent Bleed Events (IV group) 2/19
Recurrent Bleed Events (PO group) 1/19
RR, 95% CI
0.5 [0.05, 5.06]
7/112
5/99
0.81 [0.26, 2.47]
2/13
0/12
0.22 [0.01, 4.08]
12/78
13/78
1.08 [0.53, 2.22]
4/41
5/44
1.16 [0.34, 4.04]
2/50
2/50
1.00 [0.15, 6.82]
29/313
26/302
0.92 [0.56, 1.50]
(95% CI)
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Spring 2016 • Arizona Journal of Pharmacy • 21
Academy News Community Pharmacy Academy News
Geriatric Care Academy News
It has been a wonderful past couple months! We collaborated with the new practitioners and held a meet and greet at Postino in downtown Gilbert. There were a few members and even a few puppies! It is always delightful to hear from current members about their thoughts on the academy. Thank you to all who came out. Coming up, there are plenty of opportunities for CE and AzPA is constantly working to prepare new and exciting events for you. Please take a moment to head over to the website and look at the upcoming CE calendar. Over the next couple of months we will be gearing up for the Annual Convention, located this year at Wild Horse Pass. We look forward to seeing every one there and establishing a pronounced path for next year. Thank you for being a part of AzPA. As always, please do not hesitate to contact us.
We are off to a great start for 2016 and we closed out 2015 strong. Several members of the Geriatric Care Academy presented at the Southwestern Clinical Pharmacy Seminar. Topics included OTC and dietary herbal supplement in the elderly and pharmacologic and non-pharmacologic strategies for sleep in the elderly. Our second newsletter was released, spotlighting a geriatric pharmacist. Thanks to all GCA members who contributed to making these past events a success. As we continue through the year, our focus remains committed to increasing membership involvement. I encourage all pharmacists, students, and technicians to become involved with the GCA. Geriatrics is a topic that can arise in a majority of pharmacy settings and will become more prevalent as the baby boomers population ages. Don’t forget, conference calls for the GCA are held on the second Wednesday of every month, from 12:30pm to 1pm. Follow up emails will be sent with additional information. We have a couple of opportunities for Precepting Health Fairs for spring 2016. Additional emails will be sent with details, but feel free to contact me if you have any questions or concerns. I look forward to seeing you all at the Annual Convention!
Valerie Richards, PharmD Community Pharmacy Academy Chair
us! You tell r copy of ou y prefer rnal of Do you J ona ou r print? iz r A e h t ital o cy in dig Pharma us know at Let news g /azpar .o y c a azpharm
JOIN AN ACADEMY TODAY! • • • • • • •
Visit azpharmacy.org Login on the right hand side of website Select Manage Profile (on right) Select Edit Bio Scroll to ‘AzPA Academy Affiliation’ field Select the appropriate academy You may also choose a secondary academy
Once you have selected an academy, you will begin to receive academy meeting emails / invites. Questions? Please contact the AzPA Office 480.838.3385
Jessica DiLeo PharmD Geriatric Care Academy Chair
Academy Meeting Calendar
• ACCP Officer Meeting: TBD • Community Pharmacy Academy: 3rd Thurs of the month at 7am • Geriatric Care Academy: 2nd Wed of the month at 12:30pm • HSA Executive Committee: 2nd Wed of the month at 12pm • Managed Care Academy: 3rd Wed of the month at 7am • Student Pharmacy Academy: Contact Academy Chairs • Technician Academy: 2nd Wed at 7pm
Health-System Academy News Our first quarter of 2016 has been successful. The Health-Systems Academy selected our ASHP House of Delegates representatives for 2016-2017. Delegates include: Carol Rollins serving her 3rd year; Christi Jen serving her 2nd year, newly re-elected Mindy Burnworth serving her first year and Thomas Van Hassel will serve as an Alternate. There are a couple legislative issues this session that will impact health-systems pharmacists. Biosimilars: I am looking for HSA members with subject matter expertise in the area of Biosimilars to help with a proposed legislation regarding the substituion of a “biosimilar” prescription product to replace an original biologic product. This bill is continously evolving, so please contact me, or connect with the AzPA Legislative Committee for up to date information. PGY and License Reciprocity: Currently PGY2 residents coming to Arizona can only apply for reciprocity after being licensed in another state for one year. This causes a delay in their ability to participate in direct patient care, which is definitely a concern for Health System pharmacists that accept Pharmacy Residents. AzPA is working to change the requirement to allow the Arizona State Board of Pharmacy the ability to authorize licensure as long as the pharmacist holds a license in good standing from another jurisdiction for any period of time. Pharmacists; Scope of Practice: AzPA is supporting a legislative initiative to expand Arizona pharmacists’ ability to immunize children. The bill would allow pharmacists to administer influenza vaccines to children at least three years of age, and booster doses as recommended by the CDC. It would also enable pharmacists to administer immunizations or vaccines recommended by the CDC to teenagers at least 13 years of age. Get involved. Contact me or join our Health-System Academy calls the 2nd Wednesday every other month at 12pm to find out how you can help. The Health-System Academy of the Arizona Pharmacy Association is the Arizona affiliate of the American Society of Health-System Pharmacists (ASHP).
Arizona
Lisa Tonrey, RPh, FAPhA Health-System Academy Chair hsa@azpharmacy.org
Managed Care Academy News Hello and Happy New Year to our members, Managed Care for most of us who came from a retail setting was filling prescriptions in a closed door facility where these prescriptions were shipped to the patients instead of patients coming in for them. Now after over 15 years in this field, this is not only the role a pharmacist or technician have in the managed care setting. Managed Care now has many different opportunities for both the pharmacist and the technician. There are many facets this academy provides. To name a few, there is Drug Informatics, Prior Authorizations, Drug Utilization, MTMs, Specialty and Specialized Disease specialists. Each of these departments incorporate not only the pharmacist but also the technicians along with personal care advocates. Growth is emerging within the practice of pharmacy to many different aspects, so please get involved and join our academy here in Managed Care. We have monthly phone meetings every 3rd Wednesday where we discuss the newest legislative issues being brought forth to help us in the field of pharmacy as well as activities that each academy has planned for social events. This includes up coming conferences, social gatherings, webinars and even cycling fundraising events to fight for a diabetes cure. These next few months include some of these events. Just in this month of March, we have the Tour de Cure bike ride, Saturday, March 19th to help fight Diabetes. The following Tuesday, March 22nd, we have Pharmacy Day at the Capitol where we will meet with the legislators and their representatives to talk about important issues in healthcare and pharmacy. In June, the weekend of the 10th-12th, AzPA will be hosting the Annual Convention at the Sheraton Wild Horse Pass Resort & Spa in Chandler. I would like to invite you to become involved in the academy as a volunteer, committee member, Susan Halterman, RPh academy chair and even a board member. Nominate yourself or a coworker for the upcoming elections. Hope to hear from you. Join us on the road as we and come and Managed Care Academy Chair enjoy the ride for Diabetes with the Managed Care Academy’s Team AzPA. ACADEMY NEWS
Spring 2016 • Arizona Journal of Pharmacy • 23
Student Pharmacist Academy News This past Winter quarter has been a busy one for Midwestern University’s Student Pharmacist Academy. With the help of Dr. Sophia Galloway, we welcomed Detective Keith Yingling, the City of Phoenix’s only Prescription Drug Investigator, to our school in December where he talked to our students about the police side of fraudulent prescriptions and investigations. Detective Yingling’s website is located at http://phoenixpddeb.com and includes many resources available for pharmacists. Also in December, SPA helped organize and recruit pharmacy student volunteers for Central Arizona Dental Mission of Mercy where they counseled patients on antibiotic and other medication use after dental procedures. In our upcoming Spring quarter, SPA has many exciting events planned! Both MWU and UofA students will come together for AzPA’s Pharmacy Day at the Capitol on March 22nd where we will talk to legislators about important pharmacy legislation. In April, MWU will be hosting our annual Spring Health Fair at the Glendale Adult Center where students will provide blood pressure, blood glucose, and cholesterol screenings to the community with the help of Dr. Whitney Rice, her resident, and community partners. We will also have informational booths on topics such as sodium, tobacco cessation, the DASH diet, aspirin use, and others. Our students are working hard to make these events a success, and we appreciate the support of our all of our members, professors, and community partners in making these possible! Paris Cook, SPA Co-Chair, Midwestern University of College of Pharmacy Glendale Mika Jankowski, SPA Co-Chair University of Arizona College of Pharmacy
Technician Academy News The past three months have been full of visits to technician training programs, discussions in the Arizona Pharmacy Technicians group on Facebook, and working to develop various initiatives for the benefit of members and the profession in Arizona. We recently had a great meeting at the SW Clinical Conference in Tucson and were able to meet in person as an academy to plan future efforts. We recently established a Technician CE Task Force that acts as an extension of the CE Committee. This permanent task force is a group of technicians and pharmacists that works with the CE Committee to ensure that tech-specific continuing education offerings are regularly developed for AzPA conferences, the journal, online, and elsewhere. This group is actively working on some great projects relative to the Annual Convention and on into the coming year. If you would like to help with CEs for technicians or have suggestions, reach out to me or Angela Schlett (angela@azpharmacy.org). The Technician Academy will again take part in AzPA’s Pharmacy Day at the Capitol on March 22. We will be out to support AzPA’s legislative efforts and educate legislators regarding the work of all members of the pharmacy team. If you are interested in joining us on March 22, please reach out to me and we will include you in our preparations. Make sure you put the Annual Convention on your calendars for June 10-12 in Chandler. There will be plenty of great CEs and training programs and some very remarkable speakers. You won’t want to miss this one! Lastly, Elections for next year’s Chair Kalani Anderson, C.Ph.T. Elect will be coming soon, so keep checking your emails and make sure you exercise your Technician Academy Chair rights as members to vote. If you are interested in playing a leadership role in the Academy, you can nominate yourself for the Chair-Elect position and start to get involved now. Make sure you take advantage of this opportunity. We look forward to hearing from you!
ACADEMY NEWS
CONTINUING EDUCATION Chlamydia, Gonorrhea, and Trichomoniasis: A Guide to Prevention, Diagnosis, and Treatment by Adrianna Im, Pharm.D. Candidate, Midwestern University College of Pharmacy-Glendale Class of 2016; Courtney Deshauer Pharm.D. Candidate, Midwestern University College of Pharmacy-Glendale Class of 2016; Thien Tran, Pharm.D.; and Christi Jen, Pharm.D., BCPS
Goal:
This home-study CPE activity has been developed to educate pharmacists and pharmacy technicians on the prevention and treatment of three common sexually transmitted infections (STIs) - chlamydia, gonorrhea, and trichomoniasis.
Objectives
At the conclusion of this CPE activity, participants should be able to: 1. Identify and differentiate the symptoms of chlamydia, gonorrhea, and trichomoniasis. 2. Select the appropriate medication and dosing regimen for a patient infected with chlamydia, gonorrhea, or trichomoniasis. 3. Discuss important counseling points an infected patient must know to prevent reinfection, transmission of the STI to his or her partner(s), complications, or worsening of symptoms. 4. Describe the potential benefits of Expedited Partner Therapy (EPT) and how to implement it in practice.
Introduction
There are currently more than 30 sexually transmitted infections (STIs) of viral, bacterial, and parasitic origin that affect many people worldwide. Some of these STIs represent opportunities for research and humanitarian aid to third-world countries. It is estimated that there are more than 448 million new cases of chlamydia, gonorrhea, or trichomoniasis each year.1 These three STIs are currently curable and are also present in high numbers even in developed countries, such as the United States (U.S.). This is a realm in which pharmacists can play an important role to ensure appropriate treatment and decrease the risk of transmission and reinfection.
Chlamydia
Epidemiology and Etiology Chlamydia is the most common and frequently reported bacterial STI in the U.S..2 There are an estimated 3-4 million new cases of chlamydial infections that occur each year in the U.S., and the number of people infected is increasing each year.3,4 The actual number of cases may be much greater than what has been reported by routine surveillance data because initial infections are mostly
asymptomatic.5 The highest prevalence of chlamydia is in persons ≤ 25 years, especially young sexually active women, non-Hispanic blacks, men who have sex with men (MSM), and people with multiple sex partners or with high turnover rate of new sexual partners.6 According to the Centers for Disease Control and Prevention (CDC), in 2012, there were higher rates of chlamydia in women than men as well as a great number of people infected in southern states of the U.S..4 Among all the states and U.S. colonies, Alaska and the Virgin Islands have the highest rates of chlamydia.4 Chlamydia infection occurs by a gram-negative bacterium known as Chlamydia trachomatis. Co-infection with gonorrhea is common in which case dual-therapy may be needed. Chlamydia can be contracted by having oral, vaginal, or anal sex with an infected partner. This STI is known as the “silent infection” because many of the patients are asymptomatic due to the slow replication cycle of the organism.2 An infection can go unnoticed for some time since it takes several weeks for symptoms to appear, which may be a contributing factor in the increase in infection rates each year. If left untreated, C. trachomatis can spread to the upper reproductive tract and cause complications in women such as scarring of the fallopian tubes, blockage of the tubes, ectopic pregnancy, pelvic inflammatory disease (PID), infertility, and chronic pelvic pain. Early diagnosis and treatment are very important to prevent sequelae, transmission, and reinfection.2,3 Presentation It is very common for persons with chlamydia to be asymptomatic.5 Approximately 50% of men and 80% of women with chlamydia are asymptomatic.3 Therefore, screening tests are important for early detection, mainly in young women and populations that are at high risk. If symptoms are present in men, they are generally mild compared to those in women. Urethritis is the most common symptom in men who have urethral infection of C. trachomatis. Infection further into the genital tract may lead to epididymitis, which is the inflammation of the testicle where sperm is stored. Epididymitis occurs in a minority of men with chlamydia, but symptoms can include unilateral swelling, pain, and tenderness in the testicle. Moreover, studies did not find conclusive evidence of infertility in men from chlamydia.2,3 Spring 2016 • Arizona Journal of Pharmacy • 25
Women are at higher risk for severe complications and repeated infections than men. Therefore, annual screening for young women ≤ 25 years is recommended to detect asymptomatic infections and prevent permanent damage to the reproductive tract.6,7 In a study of 11,000 women, those who had more than three chlamydial infections were 6 times more likely to be diagnosed with PID.3 A symptomatic female may experience urethritis, lower abdominal pain, cervicitis, and bleeding between periods and after sex. Both men and women can have painful urination and mucopurulent discharge from the penis or vagina.8 PID in women can cause scarring of the fallopian tubes, which may lead to tubal blockage and ultimately infertility. Other issues can arise from progression of multiple sequelae from chlamydia such as ectopic pregnancy and chronic abdominal pain from persistent inflammation. Scarring and injury to the reproductive tracts are irreversible even after treatment. Therefore, early screening, diagnosis, and treatment are crucial to prevent progressive damage. Chlamydia can be transmitted to infants during childbirth from an infected mother. Chlamydial conjunctivitis, also known as ophthalmia neonatorum, occurs in 18-44% and chlamydial pneumonia in 3-16% of infants born to untreated women during delivery.2 Other orifices, rectal or genital, can be infected with C. trachomatis for up to a year or longer. Ophthalmic conjunctivitis can also occur in both adult men and women who are exposed to infected genital secretions.2,9 Diagnosis Annual screening is recommended for all sexually active women ≤ 25 years and populations with increased risk per CDC 2010 STI and United States Preventative Services Task Force (USPSTF) screening guidelines.6,7 Men are only tested if they show signs at the time of their visit to the office or if they are within a high risk population such as MSM. There is little supporting evidence that indicates that annual screening is cost-effective for males. Screenings are most cost-effective in sexually active young adolescents who have multiple sexual partners and in young women. Resources are saved for women because sequalae that occur from the infection can be more complicated and severe than for men.3 There are a number of ways to diagnose patients with chlamydia, such as cell cultures and nucleic acid amplification tests (NAATs). The CDC recommends NAATs for C. trachomatis testing because they are the most sensitive tests for detecting the bacteria, while providing a rapid response.10 Interestingly, NAATs do not require viable organisms because their mechanism is simply DNA or RNA detection. NAATs amplify and detect targeted nucleic acid sequences that are present in the bacteria. A positive CONTINUING EDUCATION
test can occur from just one single copy of DNA or RNA.10 Other tests are not recommended by the CDC due to their lack of sensitivity in detecting the bacteria.10 In men, urine samples are commonly utilized for diagnosis and NAAT testing. In women, vaginal swabs can be done by the clinician or by the patient, by obtaining the swab independently in the comfort of her home and then mailing it to the laboratory.10 A study in Denmark reported that self-sampling at home increased the number of women tested by 11-fold compared to sampling at the doctor’s office.3 Different tests vary in the amount of time it takes to receive the results, but, on average, test results should be available within two to three days.11 A rectal swab can be done if the person engages in receptive anal intercourse, but this method is not Food and Drug Administration (FDA)-cleared. Oropharyngeal infections are also not FDAcleared for NAAT.10 There is no current test to detect PID.9 PID can be difficult to detect in early stages if asymptomatic. Similarly, infertility can be difficult to diagnose unless the female is trying to actively conceive.3 These factors are imperative as to why annual screening is recommended in young women and high risk women who are sexually active or exercising risky sexual behavior. Once the patient is screened and diagnosed with chlamydia, the goal is to treat the patient to avoid these complications and to prevent transmission to others. Treatment Chlamydia can be easily treated with antibiotics. Azithromycin 1 g orally in a single dose or doxycycline 100 mg orally twice a day for 7 days are the recommended drug regimens for chlamydia.3,12 Azithromycin and doxycycline are similar in efficacy and have similar cure rates of 97% and 98%, respectively.12 Azithromycin may be more cost-effective because of its ease of use and single dose treatment, particularly for those who are noncompliant, have unpredictable follow-up rates, are of low socioeconomic status, or are adolescents.12 To maximize compliance, the single dose of azithromycin or the first dose of doxycycline should be directly observed if administered at a healthcare provider’s office.3,12 Alternative regimens include erythromycin base, erythromycin ethylsuccinate, levofloxacin, and ofloxacin, as seen in Table 1.3,12 Erythromycin may be less effective than the other treatment options because of adverse gastrointestinal effects from the drug, which lead to decreased compliance.3,12 Levofloxacin and ofloxacin are effective alternative treatments but are more expensive than other available alternatives.3,12 Neither provide any advantage over the other regimens, while other fluoroquinolones have not been adequately evaluated or have not shown to be reliably effective in treating chlamydia.12 Erythromycin base or ethylsuccinate is recommended for
STIs children under 45 kg. A child who weighs at least 45 kg may take either azithromycin or doxycycline, depending on his or her age.12 Current treatment for chlamydia infections will not reverse any permanent damage to the reproductive system due to PID in women.9 It is crucial to initiate antibacterial treatment to eradicate chlamydia from the body, prevent damage, and avoid infertility, which can be devastating if a woman is considering pregnancy in the future. Chlamydia-infected men and women should follow up in three months after treatment to be retested.12 If unable to test in three months, a retest should be scheduled within the 12 months of initial treatment. A test-of-cure, a repeat testing after three to four weeks of completing therapy, is only advised in pregnant women, if noncompliance is in question, if symptoms persist, or if possible reinfection is suspected.3 A diagnostic test less than three to four weeks after treatment can lead to false results and validity for testing sooner has not been established.12 High prevalence of reinfection is observed in men and women who have already received treatment for chlamydia.13 Reinfection often occurs due to the failure of the sex partners to receive treatment or because of initiation of sexual activity with a new infected partner.13 Patients should refer their sex partners to get evaluated, tested, and treated as soon as possible.13 If the patient finds it difficult to refer a sex partner, another option is available. Expedited Patient Therapy (EPT) is a new patient-led strategy to get the patient’s partners treated more quickly for STIs.14 EPT was developed in the 1990s and is an approach that was derived from the 1970s patient referral method in which health care providers encouraged patients to refer partners for treatment due to the increase in gonorrhea infections in the U.S.14 EPT allows patients to deliver antibiotics to partners along with condoms and written information such as a monograph and an STI Fact Sheet.13 This strategy may be beneficial in increasing the number of patients treated, reducing the number of patients lost to follow-up, and reducing reinfection rates.13,14 However, there are disadvantages as well. There are missed opportunities for counseling, testing for other STIs including human immunodeficiency virus (HIV), and for evaluating other underlying disease states.13,14 Adverse drug reactions may also occur without knowing the patients’ medical history or allergies.13,14 Also, EPT can be a potential liability for providers. Providers may feel reluctant to prescribe an antibiotic for a patient’s partner without performing a proper medical examination. HIPAA liability is another concern because providers may need to contact the patient’s partner without revealing patient’s identity. In addition, not every state allows EPT to be practiced, thus clinicians should consult or refer to the laws on EPT. 14 CONTINUING EDUCATION
EPT needs ongoing evaluation to define when and how it should be utilized. Nevertheless, EPT is still available to clinicians as an option for partner treatment. Provider-assisted referral utilizes third party health specialists, also called disease intervention specialists (DIS), to contact possible infected partners through the explicit consent of the index patient, who is the patient newly diagnosed with an STI.14 Provider Referral is the best option to optimize therapy in possible infected partners but is not available to most gonorrhea and chlamydia patients due to resource limitations.14 EPT may be a useful option in treating male partners of women infected with chlamydia or gonorrhea, especially when the benefits outweigh the risks.13,14 Pregnancy All pregnant women should be screened at their first prenatal visit. Screening and treatment is the best method to prevent perinatal infection.2 It is recommended to be treated during pregnancy if chlamydia diagnosis is definite.2 The goals of treatment are to prevent preterm delivery, transmission of the infection to the baby during birth, and other severe complications for the mother and infant.2 Azithromycin has been studied extensively and is a safe and effective medication to treat pregnant women with the infection.2,12 Azithromycin 1 g orally in a single dose or amoxicillin 500 mg orally 3 times a day for 7 days are two different recommended options. Alternative choices are erythromycin base or erythromycin ethylsuccinate, as seen in Table 1. Other antimicrobials usually utilized to treat chlamydia, such as ofloxacin, doxycycline, levofloxacin, and erythromycin estolate, are all contraindicated in pregnant women.12,15 Erythromycin estolate can cause hepatotoxicity in all populations who are on this medication for >10 days or is a repeated course of therapy.15 Generally, the occurrence of this adverse side effect is rare and reversible once the medication is discontinued. However, due to its potential risks, the CDC recommends avoiding this medication in this unique population.15 Pregnant women should receive a test-for-cure three weeks after the regimen is completed and then retest again three months after treatment, considering the severe sequelae that can occur in mothers and neonates.12 Women less than 25 years of age need to be retested once more during their 3rd trimester to prevent postnatal complications.12 Chlamydia infections can transfer to neonates during childbirth and can cause postnatal complications to both the mother and infant.12 Due to the mother’s cervix being lined with C. trachomatis, the infection transfers to the infant during labor through mucus membranes such as the eyes, mouth, urogenital tract, and rectum.12 However, the child can be asymptomatic for some time.12 Chlamydia infection in babies is most frequently recognized by ocular conjunctivitis that develops 5-12 days after birth.12 Tissue culture and non-culture tests are both utilized for sensitivity Spring 2016 • Arizona Journal of Pharmacy • 27
STIs and specific methods to diagnose C. trachomatis, but most non-culture tests are not FDA-cleared for detection of the bacteria. Everted eye specimens are obtained using a Dacron-tipped swab or a manufacturer’s swab kit. The specimen must contain both conjunctival cells and exudate in order for it to be appropriately tested.12 A test for gonococcal conjunctivitis should also be done as co-infection with chlamydia is common.12 Silver nitrate and antibiotic ointments do not prevent transmission of C. trachomatis from mother to infant but are effective in ocular prophylaxis of preventing gonococcal ophthalmia and, therefore, should be administered.12 Chlamydia can also cause sub-acute afebrile pneumonia in infants starting at one to three months of age. Signs and symptoms of pneumonia include repetitive staccato cough with tachypnea, hyperinflation and bilateral diffuse infiltrates on chest radiograph, and peripheral eosinophilia (≥400 cells/mm3), which occurs most frequently.12 Therefore, the recommended choice of therapy is erythromycin base or ethylsuccinate 50 mg/kg/ day orally divided into 4 doses daily for 14 days for chlamydia infection or chlamydial pneumonia.12 Infantile hypertrophic pyloric stenosis (IHPS) has been reported in infants less than 6 years old who have been administered erythromycin.12 Erythromycin is approximately 80% effective and may require a second course of drug therapy.12 Therefore, follow-up is recommended to determine if the initial treatment was successful. During follow-up, the infant should also be examined for IHPS.12
Gonorrhea
Epidemiology and Etiology Gonorrhea is the second most common STI in the U.S..16 According to the CDC, an estimated 820,000 new cases occur in the U.S. each year, although only half are detected or reported.16 It has a higher occurrence among sexually active teens and young adults, as well as in African Americans. Gonorrhea is a bacterial infection caused by a gram-negative cocci known as Neisseria gonorrhoeae. This bacterium spreads through sexual contact via the penis, vagina, mouth, or anus of an infected partner with or without ejaculation. It infects mucous membranes of the reproductive tract in men and women, as well as the mouth, throat, eyes, and anus.16 Another mode of transmission is perinatal spread from an infected mother to her baby.16 CONTINUING EDUCATION
Table 1: Recommended Regimens for Chlamydia Recommended Regimens
Clinical Pearls and Counseling Points
Adults and Children ≥ 8 years Alternative Regimens: Azithromycin 1 g orally in Erythromycin base 500 mg orally a single dose four times daily for 7 days OR OR Erythromycin ethylsuccinate 800 mg orally four times daily for 7 Doxycycline 100 mg orally days twice daily for 7 days OR Levofloxacin 500 mg orally once daily for 7 days OR Ofloxacin 300 mg orally twice daily for 7 days
May take azithromycin without regards to food If GI effects, take with meals.15 Ofloxacin, doxycycline, levofloxacin contraindicated in pregnant women.15 Erythromycin may irritate the GI, increase noncompliance.12 Levofloxacin is equally as effective as ofloxacin, but more expensive.12
Infants and Children <45 kg Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into 4 doses daily for 14 days
Children <6 yrs of age are at risk for IHPS.12
Children ≥45 kg and <8 Years Azithromycin 1 g orally in a single dose Pregnant women Azithromycin 1 g orally in a single dose OR Amoxicillin 500 mg orally three times daily for 7 days
Alternative Regimens: Erythromycin base 500 mg orally four times daily for 7 days OR Erythromycin base 250 mg orally four times daily for 14 days OR Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days OR Erythromycin ethylsuccinate 400 mg orally four times daily for 14 days
If GI effects are unbearable, patients should be administered on a low dose, 250 erythromycin base or 400 mg erythromycin ethylsuccinate, for extended 14 day duration.12 Avoid erythromycin estolate due to hepatotoxicity concerns.15
Adapted from the 2010 CDC Treatment Guidelines.12
Presentation Men infected with N. gonorrhoeae are mostly asymptomatic. However, the most common symptomatic presentation in men is urethritis.16 Urethral infection can cause dysuria and white, yellow, or green urethral discharge 1-14 days after infection.16 Epididymitis and scrotal pain may also occur. Women infected with N. gonorrhoeae are often asymptomatic until complications occur.16 When symptoms do occur, they are often mistaken for a bladder or vaginal infection because of the similar symptoms of dysuria and increased vaginal discharge.16 A more specific symptom of gonorrhea is vaginal bleeding between periods.16 If an infected mother passes N. gonorrhoeae to her child, the baby may suffer from blindness, joint infection, life-threatening blood infection, conjunctivitis, or pneumonia within 5-12 days after birth.16 Rectal and pharyngeal gonococcal infections are usually asymptomatic.16 However, if rectal symptoms are present, the patient may experience discharge, itching, soreness, bleeding, and painful bowel movement.16 A sore throat may accompany a pharyngeal infection.16 Infection with N. gonorrhoeae increases an individual’s risk of contracting other STIs, including HIV.16 Diagnosis Gonorrhea infections are very similar to chlamydia infections. Moreover, chlamydia is commonly a co-infection; therefore, the
STIs patient with gonorrhea should also be tested for chlamydia.17 Depending on the test, the turnaround time for result can vary. Typically, results are readily available in two to three days.11 As in chlamydia diagnostic testing, gonorrhea is diagnostically tested using NAAT because of its high specificity and sensitivity.10,17 NAATs can be used with a variety of specimens including urine in both men and women, vaginal and endocervical swabs in women, and urethral swabs in men,.10,17 NAATs are not FDA-cleared for pharyngeal or rectal swab specimens.10 However, some laboratories have established performance specifications for NAATs to be tested using pharyngeal or rectal swabs, allowing results to be used for management in the clinical setting.10 Non-culture tests cannot provide antimicrobial susceptibility results.17 Therefore, clinicians should perform both culture and antimicrobial susceptibility testing in cases where treatment failure is suspected or documented.17 A gram stain has > 99% specificity and > 95% sensitivity.17 For male urethral specimens, a gram stain can be considered for diagnostic testing for N. gonorrhoeae in symptomatic men if polymorphonuclear leukocytes with intracellular gram-negative diplococci are present.17 In asymptomatic males, a negative gram-stain is not sufficient in ruling out the infection because of lower sensitivity in detecting the infection; therefore, further tests should be done.17 Also, a gram stain alone cannot be used to test endocervical, pharyngeal, and rectal specimens.17 Patients who have gonorrhea are commonly co-infected with chlamydia.16 High risk populations such as MSM, individuals 15-24 years of age, older women who have multiple sex partners or who rapidly change partners, and those not utilizing contraceptive methods should get tested annually for gonorrhea and chlamydia.16 Patients should also be tested for other STIs such as HIV because gonorrhea can increase the risk of acquiring HIV.16 Treatment The CDC recommends that patients who test positive for gonorrhea should be on ceftriaxone plus an additional regimen CONTINUING EDUCATION
Table 2: Recommended Regimens for Gonorrhea Recommended Regimens Adults and Children >45 kg Ceftriaxone 250 mg in a Alternative Regimens single intramuscular dose If ceftriaxone not available: PLUS Cefixime 400 mg in a single oral dose Azithromycin 1 g orally in a single dose OR Doxycycline 100 mg orally twice a day for 7 days*
Clinical Pearls and Counseling Points
The use of azithromycin as the second antimicrobial is preferred due to high PLUS prevalence of resistance to tetracyclines. Azithromycin 1 g orally in a single Test-of-cure in one dose week should follow OR Doxycycline 100 mg orally twice daily alternative regimens. Pregnant women for 7 days* should not take doxycycline due to its If severe cephalosporin allergy: 15 Azithromycin 2 g in a single oral dose teratogenic effects.
Children ≤45 kg and with Uncomplicated gonococcal Vulvovaginitis, Cervicitis, Urethritis, Pharyngitis, or Proctitis Children <6 yrs of age Ceftriaxone 125 mg IM in a single dose are at risk for IHPS12 Children with Bacteremia or Arthritis Ceftriaxone 50 mg/kg IM or IV in a single dose daily for 7 days
Maximum dose 1 g in children ≤45 kg
Adapted from the 2010 CDC Treatment Guidelines.12
to also treat chlamydia.17 As shown in Table 2, the patient should be administered ceftriaxone 250 mg in a single intramuscular dose plus doxycycline or azithromycin for uncomplicated gonococcal infections of the cervix, urethra, and rectum.17 A combination therapy of two different antibiotics with different mechanisms is used to ensure the treatment is effective and to prevent further resistance to antimicrobials. If a patient has severe allergies (i.e. Stevens Johnson Syndrome, anaphylaxis) to penicillins, they may have cross-reactivity reactions to cephalosporins.18 Therefore, these patient populations should not be administered ceftriaxone and can instead be prescribed azithromycin 2 g in a single oral dose.17 In addition, doxycycline, a tetracycline, has been reported to have high prevalence of gonococcal resistance.18 Doxycycline alone does not cover gonorrhea, but does cover chlamydia. Furthermore, oral cephalosporins are no longer recommended in treatment for gonococcal infections due to the spread of resistance.17 Treatment failures have been reported with oral cephalosporins in Asian countries.17 To provide appropriate therapy, clinicians should ask patients of their recent travel and sexual activity to these countries. If suspected treatment failure to cephalosporins is observed, clinicians should perform a culture and susceptibility test, consult with a specialist for clinical management, and report to the CDC through local and state health authorities.17 N. gonorrhea treatment is becoming very difficult as antibiotic resistance is increasing. As of 2007, fluoroquinolones are no longer recommended for treatment of gonorrhea and gonorrhea-associated conditions such as PID due to resistance.17,18 If ceftriaxone is not available, the alternative regimen is cefixime 400 mg in a single oral dose plus azithromycin 1 g orally in a single dose and test-of-cure in one week.17 Doxycycline 100 mg orally twice daily for 7 days can be substituted for azithromycin, but azithromycin as the second antimicrobial is preferred due to convenience, higher compliance rates from single dose administration, and high prevalence of tetracycline resistance.17,18 Ceftriaxone 250 mg provides a higher sustained bactericidal level Spring 2016 • Arizona Journal of Pharmacy • 29
STIs than cefixime 400 mg.17,18 In published clinical trials, cefixime 400 mg dose has a cure rate of 97.5% of uncomplicated urogenital and anorectal and 92.3% of pharyngeal gonococcal infections whereas ceftriaxone has cure rates of 99.2% and 98.9%, respectively.17 Although cefixime may be available in a more preferred dosage form, because of its oral formulation compared to an intramuscular injection for ceftriaxone, ceftriaxone has higher efficacy in treating pharyngeal gonococcal infections than cefixime.17 Therefore, the provider should inquire about oral sexual exposure to ensure appropriate drug therapy that will target the bacteria effectively.17 If a patient confirms oral sexual exposure, ceftriaxone should be the antibiotic of choice.17 Due to extensive clinical experience, the use of ceftriaxone is known to be safe and effective in treating uncomplicated gonorrhea.17 If the STI is left untreated, then women may develop permanent damage and severe complications such as PID.16 Similarly to chlamydia, complications from PID include ectopic pregnancy, scar tissue that can lead to blockage of the fallopian tubes, chronic pelvic or abdominal pain, and possibly infertility,.16 Different from chlamydial infection, men can become sterile from gonococcal infection.16 Painful conditions can also occur in the tubes attached to the testicles such as epididymitis, swelling, and tenderness. In severe and rare cases for both men and women, gonorrhea can spread into the blood and joints and can be life-threatening.16 It is important for patients and their partners to get tested if infection is suspected and if they are at high risk for an STI infection.16 If gonococcal conjunctivitis is present in adults, wash or perform a lavage to the infected eye with sodium chloride 0.9% solution, and ceftriaxone 1 g intramuscularly in a single dose should be administered.17 In a published study, the treatment of all 12 study participants with gonococcal conjunctivitis responded to a single dose of 1g intramuscular injection of ceftriaxone.17 Gonococcal conjunctivitis requires more aggressive antibiotic therapy due to penicillinase-producing N. gonorrhoeae.19 The effects on the eye can be severe from pus formation to the possibility of the bacteria perforating the cornea which can lead to corneal ulcers.20 Therefore, a high dose of ceftriaxone 1 g intramuscularly should be administered for these reasons and especially because studies have shown efficacy. EPT is an option for partners of patients who test positive for gonorrhea.21 Since ceftriaxone intramuscular injection is not possible for EPT, dual therapy with orally-administered cefixime plus azithromycin is the recommended option.21 Even though the CDC no longer recommends the routine use of cefixime as a treatment of gonorrhea, it is more important to treat the patients’ partners rather than leave them untreated.21 Therefore, cefixime and azithromycin should still be administered.21 CONTINUING EDUCATION
Instructions and appropriate warnings about taking the medication such as allergies, pregnancy, gonorrhea health education fact and counseling sheets, and a statement advising patients to seek medical evaluation should be included along with the medications.21 Information for the partner to follow-up and test-for-cure in one week after completing the medication should also be provided.21 Every effort should be made to treat and evaluate the patients’ sex partners within the last 60 days.21 Sexual abuse is the most frequent cause of gonorrhea infections in prepubescent children.17 Due to the nature of the incidence and legality issues, obtaining cultures is the preferred method of diagnosing N. gonorrhoeae although NAATs may be utilized in certain circumstances.17 Gram stains are inadequate in determining diagnosis and should not be used.17 If ceftriaxone is used, follow-up cultures are not necessary.17 Pregnancy Pregnant women diagnosed with gonorrhea should follow the same treatment options as recommended for non-pregnant patients but should not take doxycycline due to its teratogenic effects.17 If allergies to cephalosporins or penicillins are known or if the patient cannot tolerate the medication, then azithromycin 2 g orally can be considered.17 An infected pregnant mother who was not treated for gonococcal infection may transmit the infection to the infant during delivery, similarly to neonatal infection in chlamydia.17 The infant is exposed to the mother’s infected cervix, and the illness manifests 2-5 days after birth.17 Severe cases of N. gonorrhoeae infection may cause conjunctivitis and sepsis that can lead to arthritis and meningitis in the infant.17 Less severe symptoms include rhinitis, vaginitis, and urethritis.17 Detecting and treating ophthalmia neonatorum early is especially important because perforation of the globe of the eye can occur, resulting in blindness.17 Antibiotic susceptibility should be tested to ensure definitive diagnosis of gonorrhea in all neonatal conjunctivitis because there are other nongonococcal organisms that cause neonatal conjunctivitis such as Moraxella catarrhalis and other Neisseria species.17 The recommended regimen is ceftriaxone 25-50 mg/kg IV or IM in a single dose and not to exceed 125 mg.17 The recommended dose for ceftriaxone can also be given for prophylactic treatment to asymptomatic infants whose mothers are infected.17 Ceftriaxone should be administered carefully to hyperbilirubinemic infants, particularly those who were born prematurely.17 Erythromycin 0.5% ophthalmic ointment is the only recommended ophthalmic antibiotic ointment for neonate ocular prophylaxis.17 Erythromycin 0.5% ophthalmic ointment should be administered to prevent sight-threatening ophthalmia neonatorum.17 This procedure is required by law in most states.17 Erythromycin 0.5% ophthalmic ointment should
STIs be administered immediately after delivery, regardless of delivery method.17 Single use tubes of ointment should be used instead of multiple-use tubes.17 If erythromycin 0.5% ophthalmic ointment is not available, then ceftriaxone injection can be given. Both the mother and infant should be tested for chlamydia.17 In addition, silver nitrate and tetracycline ophthalmic ointments are no longer manufactured in the U.S.17 Bacitracin is not effective and iodine use and efficacy has not been established.17
Trichomoniasis
Epidemiology and Etiology Trichomoniasis is the most common curable STI, 22 affecting more than 3.7 million people in the U.S.22 Trichomoniasis is caused by the flagellated, motile protozoa Trichomonas vaginalis.23 The attachment of T. vaginalis to the mucosa elicits an inflammatory response, which then causes the discharge of leukocytes.23 It most commonly spreads to an uninfected partner’s lower genital tract during sexual intercourse. Like many STIs, infected people without any visible symptoms can still spread it to others.22 Although it is extremely rare, T. vaginalis could theoretically spread via contact with inanimate objects, since it can survive up to 45 minutes on moist surfaces.23 This could potentially be a concern in public spas and bathing areas. Trichomoniasis is more common in women than men. Part of this difference between genders may be due to a lower detection rate. For one, it is less likely that a male will seek medical treatment for trichomoniasis because men have a higher spontaneous cure rate.23 It is also more difficult to detect T. vaginalis in an infected male urethra than a female urethra because of the substantially lower number of organisms.23 Among women, it occurs most often in older women.22 This could be due to unsafe sex practices later in life as well as changes in the vaginal pH and flora in postmenopausal women. Although it is rare, it is also possible for an infected mother to transmit T. vaginalis during delivery. Presentation Approximately 30% of individuals with trichomoniasis have signs or symptoms,22 which normally occur after the incubation period of 3-28 days.23 Symptoms may persist or may oscillate with periods of apparent remission to varying levels of irritation and inflammation.22 The most common site of infection for women is the endocervical canal.23 Other less common sites include the urethra, rectum, eye, and oropharynx.23 More than half of infected women present with a malodorous vaginal discharge that may be clear, white, yellow, or green.22,23 Other symptoms include itching, painful urination, painful sex, urethritis, a vaginal pH of 4.5-6, as well as inflammation and redness CONTINUING EDUCATION
of the vulva, vagina, or cervix.23 For men, the most common site of infection with trichomoniasis is the urethra.23 Other possible sites include the rectum, oropharynx, and eye.23 Men are more likely than women to be asymptomatic.23 If they do present with symptoms, they may have a clear to mucopurulent urethral discharge as well as itching, painful urination, and pain upon ejaculation.22,23 Both women and men may experience severe complications from trichomoniasis. Women with trichomoniasis are at an increased risk for premature labor, low-birthweight infants, and PID, which can increase the risk for infertility and ectopic pregnancy.23 Trichomoniasis may also increase a woman’s risk for cervical neoplasia,23 which may or may not lead to cervical cancer. Males may also experience infertility due to trichomoniasis as well as epididymitis and chronic prostatitis.23 Along with these potentially life-altering complications, an infection with T. vaginalis can increase an individual’s risk for contracting other STIs. Infected women are three times more likely to have gonorrhea, whereas 20% of men with gonococcal urethritis also have trichomoniasis.23 Inflammation from trichomoniasis may facilitate HIV entry and infection.24 Diagnosis A laboratory diagnosis is required for trichomoniasis since the pruritus, inflammation, discharge, and other symptoms associated with it are similar to those of bacterial vaginosis. A vaginal pH > 5.0 usually indicates T. vaginalis or Gardnerella vaginalis.23 Currently, the diagnosis is most often done via microscopy; T. vaginalis can be confirmed with 60-80% sensitivity by the presence of pear-shaped, flagellated organisms on a wet-mount examination of vaginal discharge.23 There are two other FDA-approved point-of-care diagnostic tools that can be used to test vaginal discharge, which are OSOM Trichomonas Rapid Test and Affirm VP III. These techniques use an immunochromatographic capillary flow dipstick and a nucleic acid probe test to reveal results in about 10 minutes and in 45 minutes, respectively. These two tests have similar sensitivities of greater than 83% and specificities greater than 97%; however, false positives can still occur.25 Culture techniques, PCR assays, and DNA/RNA probes are other methods with high specificity and sensitivity.23 The turnaround time, unfortunately, makes them not ideal for rapid diagnosis. However, they may be helpful in verifying results and in determining antimicrobial susceptibility.23,25 They also hold an important place in the diagnosis of males for whom there are no approved point-of-care tests available. Cultures and PCR assays using a urethral swab, urine, or semen are possible. If a urethral swab is being taken, then males should avoid voiding prior to the sample being taken.23 Spring 2016 • Arizona Journal of Pharmacy • 31
STIs Treatment Some T. vaginalis infections are cured spontaneously without treatment. However, an infection may last for months to years without treatment.22 Metronidazole has been the drug of choice since the 1960s.26 Oral, systemic metronidazole treatment is better than local treatment because it guarantees that therapeutic drug levels are reached and protects against reinfection from other body sites.23 Most cases may be treated by a single, oral dose of metronidazole 2 g or tinidazole 2 g as shown in Table 3. There are several advantages to this single-dose treatment. It provides for increased patient adherence, lower cost, and a decreased risk of pseudomembranous colitis or symptomatic candidal vulvovaginitis.23 Alcohol should be avoided during the course of therapy and for at least 24 hours after metronidazole or 72 hours after tinidazole is completed because of the potential for a disulfiram-like reaction.15 Discomfort aside, this is a potential concern because the patient may fail treatment if the medication is lost due to vomiting. Although topical vaginal therapy is not usually recommended, it may be used in combination with the oral, systemic metronidazole or tinidazole.23 There are two alternative treatment regimens for treatment failures: metronidazole 500 mg by mouth twice daily for 7 days or tinidazole 2 g by mouth in a single dose (if failed single-dose metronidazole). The longer dosing regimen of metronidazole may be beneficial for HIV positive individuals, as it has been seen to result in higher cures and lower rates of reinfection.24 A higher dose of metronidazole, such as 2-3 g for 7-14 days, may be used if the second course of therapy is not successful.23 Metronidazole and tinidazole are very similar structurally, which presents a problem with cross-reactivity for allergic reactions and a dilemma when resistance occurs. Although it has yet to gain widespread commercial availability in the U.S., pentamycin, a polyene macrolide, now provides an option for these cases and has been approved for intravaginal use. Pentamycin has been successful in vitro26 and in a small in vivo study,27 as well as case CONTINUING EDUCATION
Table 3. Recommended Regimens for Trichomoniasis for Adult Men and Women Clinical Pearls and Counseling Alternative Regimens Points Metronidazole 2 g PO in a Metronidazole 500 mg PO Disulfram reaction with single dose twice daily for 7 days metronidazole and tinidazole can occur; avoid concomitant use of OR OR alcohol during treatment and 48-72 hours, respectively, after Tinidazole 2 g PO in a Tinidazole 2 g PO in a completion of treatment.15 single dose single dose (if failed single Metronidazole has been shown to be carcinogenic in animal studies, dose metronidazole) but available studies show no link to infant cancer.15 Metronidazole and tinidazole are contraindicated during 1st trimester of pregnancy, but may be used with caution. Cleft lip with or without palate has been reported in infants of mothers on metronidazole during 1st trimester.15 Pregnancy Category B for metronidazole Pregnancy Category C for tinidazole because of lack of studies Administer tinidazole with food and may administer metronidazole with food.15
Recommended Regimens
Adapted from the 2010 CDC Treatment Guidelines.12
studies.28 It has been used intravaginally with 6 mg daily for 5 days or 3 mg daily for up to 10 days with mainly mild local side effects.27,28 These dosing regimens may change as pentamycin is used more frequently for T. vaginalis and as resistance increases, so it is important to stay abreast of any developments in order to provide the most appropriate patient care. Regardless of the chosen therapy, infected individuals should avoid sexual intercourse for at least one week and until they are asymptomatic.22,29 There appears to be some disagreement on whether or not asymptomatic partners should be tested and if treated asymptomatic individuals should be retested. This likely follows from the fact that some cases are spontaneously cured without treatment. However, there are many asymptomatic individuals who may still transmit T. vaginalis to others or who may be reinfected themselves. About 20% of individuals are reinfected within three months of their first infection.22 Consequently, it is recommended that populations at risk, especially sexually active women and HIV positive individuals, are considered for retesting three months after the initial infection.24,25 In fact, some studies suggest that all individuals should receive follow up care within three months of treatment.30 The reasoning is that these patients are at a high risk for developing other asymptomatic STIs even if their original infection is treated. Cure rates of up to 95% are reported when both partners are treated,23 making this the ideal option when possible. EPT appears to have potential benefit in reaching more individuals for treatment and decreasing reinfection,14 but the most beneficial protocol for this is unclear and not specified by the current CDC guidelines.25 Pregnancy Untreated trichomoniasis can increase the risk for a low birth weight of less than 5.5 lbs22 and a preterm delivery, which can have a large impact on general development and health. The increase in
STIs preterm delivery is similar to that caused by maternal smoking, making this quite a significant association.31 T. vaginalis can also be transmitted to the neonate during delivery, leading to urinary tract infection, genital infection, and sometimes respiratory infection.23,32 Because of this, it appears to be beneficial for pregnant women to be screened for trichomoniasis.32 Metronidazole and tinidazole, the mainstays of trichomoniasis therapy, are pregnancy category B and C, respectively. They are both contraindicated during the first trimester of pregnancy, but a single 2 g dose of metronidazole has not been associated with teratogenicity.31 The CDC makes the general recommendation that pregnant women should be treated.22 However, it is sometimes recommended that asymptomatic pregnant women wait to receive metronidazole until they are past 37 weeks of gestation.23 If neonatal infection does occur, there are no guidelines on the appropriate dosing regimen. However, a case study reported that two doses of metronidazole (15 mg/kg and then 7.5 mg/kg) was successful in curing an asymptomatic neonate.33 The CDC recommends that women avoid breastfeeding during treatment and 12-24 hours after the last dose of metronidazole or three days after the last dose of tinidazole.25
Prevention
Complete abstinence is the only way to entirely avoid STIs, such as chlamydia, gonorrhea, and trichomoniasis. In addition, being in a long-term and monogamous relationship can decrease an individual’s risk, and the CDC gives the suggestion of speaking with a potential partner about STIs before having sex.22 This discussion may prompt both individuals to be tested for common STIs before moving on in the relationship. This would be beneficial for the discussed curable STIs and for more serious and incurable STIs, such as HIV. If an individual is positive for one of these curable STIs, he/she can receive and complete treatment before passing it on to any partners. The consistent and correct use of latex condoms can help reduce the risk of spreading many STIs, including the three discussed in this article. However, condoms do not cover all the genitalia and may still break despite being used correctly, making transmission possible. An important aspect of secondary prevention is that of screening. Screening not only reduces the chance of transmitting the STI to new partners, but also allows for treatment before an asymptomatic individual develops symptoms or more severe complications. Annual screening for gonorrhea and chlamydia is recommended for women 25 years old and younger, MSM, African Americans, those who have multiple sex partners, and individuals not using barrier contraceptives.6,7,16 Screening for trichomoniasis is recommended for high risk populations, such as sexually
CONTINUING EDUCATION
active women and HIV positive patients.22
Counseling Points
Pharmacists can interact with STI patients in a variety of settings. In the case of an undiagnosed patient experiencing symptoms, a pharmacist serves as an important resource in referring patients to seek evaluation and receive a laboratory diagnosis. Pharmacists also provide important counseling points such as avoiding douching, as this could worsen an infection. When a patient is diagnosed and receiving therapy, he/she should be counseled to abstain from sexual intercourse while on the medication, for at least 7 days after treatment completion, and until symptoms are resolved. His/her partners should be treated, either after being diagnosed themselves or through EPT. The importance of finishing the entire course of medication should be stressed to the patient. He/she should be educated on the simple administration details for each medication. For example, alcohol should be avoided with metronidazole and tinidazole during treatment and 24 or 72 hours after treatment, respectively.15 Tinidazole should be taken with food and metronidazole may be taken with food to reduce stomach upset.15 Photosensitivity may occur with some antibiotics, including doxycycline, ofloxacin, and levofloxacin.15 Doxycycline, ofloxacin, and levofloxacin are contraindicated in pregnant women.15 When a female patient finishes an antibiotic, it is possible that a vaginal yeast infection may develop. Patients may like to take a probiotic in an attempt to ward off such an occurrence, but it is also important that they know the symptoms of a yeast infection. They should seek treatment if they experience any new or continuing symptoms.
Conclusion
Chlamydia, gonorrhea, and trichomoniasis affect individuals of all races and socioeconomic classes in the U.S. Their prevalence may be daunting, but these are treatable STIs. Pharmacists can provide a helpful service through patient interaction in recognizing possible symptoms and encouraging patients to be evaluated by clinicians. Pharmacists can play a major role in ensuring appropriate pharmacological treatment and counseling for patients in order to decrease the prevalence of these conditions.
Acknowledgements
Thank you to Laura Tsu, PharmD., BCPS, CGP for her support and assistance throughout the process of creating this CE. References
1. World Health Organization, Department of Reproductive Health and Research. Prevalence and incidence of selected Spring 2016 • Arizona Journal of Pharmacy • 33
STIs sexually transmitted diseases. Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, and Trichomonas vaginalis. Methods and results used by WHO to generate 2005 estimates. Geneva, Switzerland: WHO; 2011. <http://www.who.int/reproductivehealth/ publications/rtis/9789241502450/en> Accessed March 2015. 2. Centers for Disease Control and Prevention. Chlamydia - CDC Fact Sheet (Detailed). Dec 2014. <http://www.cdc.gov/std/chlamydia/stdfact-chlamydia-detailed.htm> Accessed March 2015. 3. Taylor BD, Haggerty CL. Management of Chlamydia trachomatis genital tract infection: screening and treatment challenges. Infect Drug Resist. 2011;4:19-29. 4. CDC Division of Sexually Transmitted Disease Prevention. 2012 Sexually Transmitted Disease Surveillance. Feb 2014. <http:// www.cdc.gov/std/stats12/slides.htm> Accessed March 2015. 5. Horner P. Chlamydia (uncomplicated, genital). BMJ Clin Evid. 2010 Apr 22;2010. 6. Torrone E, Papp J, Weinstock H. Prevalence of Chlamydia trachomatis genital infection among persons aged 14-39 years- United States, 2007-2012. MMWR 2014;63(38):834-838. 7. USPSTF Recommendations for STI Screening. U.S. Preventive Services Task Force. February 2014. <http://www.uspreventiveservicestaskforce.org/Page/Name/uspstf-recommendations-for-sti-screening> Accessed March 2015. 8. Diseases and Conditions: Chlamydia. Mayo Clinic. April 2014. <http://www.mayoclinic.org/diseasesconditions/chlamydia/basics/definition/CON-20020807?p=1> Accessed March 2015. 9. Centers for Disease Control and Prevention. Pelvic Inflammatory Disease (PID) - CDC Fact Sheet. July 2014. <http://www.cdc.gov/ std/pid/stdfact-pid.htm> Accessed March 2015. 10. Papp J, Schachter J, Gaydos C, et al. Recommendations for the Laboratory Based Detection of Chlamydia trachomatis and Neisseria gonorrhoeae - 2014. MMWR 2014;63(2):1-19. 11. Summit Medical Group. Gonorrhea and Chlamydia Tests. RelayHealth. 2014. <http://www.summitmedicalgroup.com/library/ adult_health/aha_gonorrhea_and_chlamydia_tests> Accessed March 2015. 12. Centers for Disease Control and Prevention. 2010 STD Treatment Guidelines: Chlamydial Infections. August 2014. <http:// www.cdc.gov/std/treatment/2010/chlamydial-infections.htm > Accessed March 2015. 13. Centers for Disease Control and Prevention. Expedited Partner Therapy. January 2015. <http://www.cdc.gov/std/ept/> Accessed March 2015. 14. Ferreira A, Young T, Mathews C, et al. Strategies for partner notification for sexually transmitted infections, including HIV. Cochrane Database Syst Rev. 2013 Oct 3;10:CD002843. 15. Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc.; March 2015. 16. Centers for Disease Control and Prevention. Gonorrhea – CDC Fact Sheet (Detailed Version). December 2014. <http://www.cdc. gov/std/gonorrhea/stdfact-gonorrhea-detailed.htm> Accessed March 2015. 17. Centers for Disease Control and Prevention. 2010 STD Treatment Guidelines: Gonococcal Infections. August 2014. <http:// www.cdc.gov/std/treatment/2010/gonococcal-infections.htm> Accessed March 2015. 18. Rio C, Hall G, Holmes K, et al. Update to CDC’s Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections. MMWR August 2012; 61(31);590-594. CONTINUING EDUCATION
19. Haimovici R, Roussel TJ. Treatment of gonococcal conjunctivitis with single-dose intramuscular ceftriaxone. Am J Ophthalmol. 1989 May 15;107(5):511-4. 20. Gupta MP. Conjunctivitis. American Foundation for the Blind. <http://www.visionaware.org/info/your-eye-condition/ guide-to-eye-conditions/conjunctivitis/125>. Accessed March 2015. 21. Centers for Disease Control and Prevention. Guidance on the Use of Expedited Partner Therapy in the Treatment of Gonorrhea. July 2013. <http://www.cdc.gov/std/ept/gc-guidance.htm>. Accessed March 2015. 22. Centers for Disease Control and Prevention. Trichomoniasis - CDC Fact Sheet. August 2012. <http://www.cdc.gov/std/ trichomonas/stdfact-trichomoniasis.htm>. 23. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th ed. McGraw-Hill Companies, Inc. 2014. 24. Kissinger P, Adamski A. Trichomoniasis and HIV interactions: a review. Sex Transm Infect. 2013 Sep;89(6):426-33. 25. Centers for Disease Control and Prevention. Disease Characterized by Vaginal Discharge: Sexually Transmitted Diseases Treatment Guidelines, 2010. 26. Kranzler M, Syrowatka M, Leitsch D, Winnips C, Walochnik J. Pentamycin shows high efficacy against Trichomonas vaginalis. Int J Antimicrob Agents. 2015 Feb 2. pii: S09248579(15)00047-3. 27. Balmer JA. Treatment of vaginal infections with intravaginal pentamycin in clinical practice. Internet J Gynecol Obstret 2009;11. 28. Goldman LM, Upcroft JA, Workowski K, Rapkin A. Treatment of metronidazole- resistant Trichomonas vaginalis. Sex Health 2009;6:345–7. 29. Sherrard J, Ison C, Moody J, et al. United Kingdom National Guideline on the Management of Trichomonas vaginalis 2014. Int J STD AIDS. 2014 Mar 10;25(8):541-549. 30. Peterman TA, Tian LH, Metcalf CA, et al. RESPECT-2 Study Group. High incidence of new sexually transmitted infections in the year following a sexually transmitted infection: a case for rescreening. Ann Intern Med. 2006 Oct 17;145(8):564-72. 31. Silver BJ, Guy RJ, Kaldor JM, Jamil MS, Rumbold AR. Trichomonas vaginalis as a cause of perinatal morbidity: a systematic review and meta-analysis. Sex Transm Dis. 2014 Jun;41(6):36976. 32. Sangkomkamhang US, Lumbiganon P, Prasertcharoensuk W, et al. Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery. Cochrane Database Syst Rev. 2015 Feb 1;2:CD006178. 33. Trintis J, Epie N, Boss R, Riedel S. Neonatal Trichomonas vaginalis infection: a case report and review of literature. Int J STD AIDS. 2010 Aug;21(8):606-7.
To receive CPE credit you must complete the quiz and evaluations on page 37 & 38.
ACPE UAN# 0100-0000-16-003-H04-P; 0100-0000-16-003-H04-T This activity has been approved for 2.0 contact hours or (0.20 CEUs) of continuing pharmacy education.
The Arizona Pharmacy Association is accredited by the Accreditation council for Pharmacy Education as a provider of continuing pharmacy education.
CONTINUING EDUCATION QUIZ QUESTIONS
Chlamydia, Gonorrhea, and Trichomoniasis: A Guide to Prevention, Diagnosis, and Treatment ACPE UAN# 0100-0000-16-003-H04-P; 0100-0000-16-003-H04-T This activity has been approved for 2.0 contact hours or (0.20 CEUs) of continuing pharmacy education. 1. Which of the following organisms is a protozoan? a. Chlamydia trachomatis b. Neisseria gonorrhoeae c. Trichomonas vaginalis d. A and B e. All of the above
7. Which class of medications is no longer used for gonorrhea or gonorrhea associated conditions? a. Cephalosporins b. Macrolides c. Quinolones d. Penicillins
2. SM, a 22 year-old female, presents to the pharmacy with complaints of painful urination and excessive vaginal discharge, along with some spotting between her periods. What is your advice for SM? a. Buy phenazopyridine over the counter for UTI pain. b. See a provider and possibly be tested for gonorrhea at the provider’s discretion c. Use miconazole OTC if she has previously been diagnosed with a yeast infection d. Wait a couple weeks as trichomoniasis infections have a high spontaneous cure rate
8. When a laboratory test is done for a patient with chlamydia or gonorrhea, how long would it take for the test to come back positive? a. 24 hours b. 2-3 days c. 5 days d. 1 week
3. Which of these is NOT an acceptable primary treatment regimen for trichomoniasis? a. Tinidazole 2 g by mouth in a single dose b. Metronidazole 2 g by mouth in a single dose c. Metronidazole 0.75% gel intravaginally once daily for 5 days d. Metronidazole 500 mg by mouth twice daily for 7 days 4. Which of the following medications are correctly matched with corresponding counseling points to share with patients? a. Azithromycin: never take with food because of increased risk for acid reflux b. Metronidazole: avoid alcohol for 24 hours c. Doxycycline: wear sunscreen and avoid unnecessary sun exposure due to possible photosensitivity d. A and B e. B and C 5. JT, a 19 year-old male, has completed his azithromycin regimen for chlamydia and is now symptom free. What can he do to avoid reinfection? a. Ensure all partners are treated b. Limit his number of sexual partners c. Always use a latex condom for every sexual act d. All of the above 6. Which medications are contraindicated for pregnant women? a. Levofloxacin b. Ofloxacin c. Doxycline d. Erythromycin estolate e. All of the above
To receive CPE credit you must complete the quiz and evaluations on page 38.
9. Which of the following is NOT true about EPT? a. It is a new patient-led strategy to get patient’s partner treated more quickly for STIs b. It allows patients to deliver antibiotics to their partner along with condoms and written information c. It stands for Enhanced Partner Therapy. d. It can increase the number of patients treated and reduce infection rates 10. What is the recommended regimen for chlamydia for adult men and women? a. Azithromycin 1 g single oral dose b. Doxycycline100 mg by mouth 2 times a day for 7 days c. Ceftriaxone 250 mg single IM dose + azithromycin 1g single oral dose d. Ceftriaxone 250 mg single IM dose + doxycycline 100 mg by mouth twice a day for 7 days e. A & B 11. True or False: Compared to women, men are at a higher risk for complications if chlamydia is left untreated. a. True b. False 12. What is (are) the complication(s) that women can experience if an STI is left untreated? a. PID b. Ectopic pregnancy c. Infertility d. A & B e. All of the above 13. What is the most common side effect of erythromycin? a. Gastrointestinal discomfort b. Dizziness c. Somnolence d. Vaginal discharge e. Sore mouth
Spring 2016 • Arizona Journal of Pharmacy • 35
Venous Thromboembolism: A Review of Prevention and Treatment Options by Kristine Carrasco, Pharm.D. Candidate, Midwestern University College of Pharmacy-Glendale Class of 2016, Christie H. Kim, Pharm.D. Candidate Midwestern University College of Pharmacy-Glendale Class of 2016, Jane Lee, Pharm.D. Candidate Midwestern University College of Pharmacy-Glendale Class of 2016, and Jaime Bailey BSPharm. Purdue University This continuing education activity is accredited for pharmacists only. Goal: This home-study CPE activity has been developed to educate pharmacists on the prevention and treatment of venous thromboembolism. Objectives 1. Explain the need for prophylactic anticoagulation in hospitalized patients with restricted mobility. 2. Formulate a medication regimen for a patient in need of anticoagulation therapy. 3. Identify the drug of choice for cancer patients, pregnant patients, and children. 4. Identify the target INR for warfarin therapy. 5. Summarize the oral medications that require a parenteral agent during initiation and list the plan. 6. Discuss the use of non-pharmacologic therapy in VTE prophylaxis and treatment. 7. Recognize important drug interactions of warfarin. Introduction Venous thromboembolism (VTE) is a condition that affects over 300,000 individuals in the United States each year.1 Deep vein thrombosis (DVT) and pulmonary embolism (PE) are two conditions categorized as VTE. Two-thirds of VTE cases are classified as DVT while a third are PE cases.1 VTE is the leading cause of preventable hospital deaths in the United States.1 Physiology Mechanism of Blood Coagulation The process of blood coagulation is a complex mechanism involving a balance of coagulation and anticoagulation factors. Under normal conditions, the intact endothelial layer separates blood contents from extravascular collagen and tissue factor inhibiting hemostasis.2 Upon injury, matrix proteins such as collagen and von Willebrand factor are exposed and cause platelet aggregation and activation along with the release of vasoconstrictors and other platelet-recruiting molecules such as thromboxane A2 (TXA2), adenosine diphosphate (ADP), and serotonin (5-HT). Activated platelets undergo a conformational change in the glycoprotein IIb/IIIa receptors, allowing them to bind fibrinogen resulting in platelet plug formation. Fibrinogen must be cleaved by thrombin to create fibrin, its active form.
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Table 1. Coagulation Cascade
The Coagulation Cascade The formation of thrombin and the initiation of the coagulation cascade is started largely by exposure of the normally extravascularly expressed protein tissue factor (TF) to the blood. This results in a TF-factor VIIa complex that activates factors IX and X. Activated factors VIIIa and factor IXa then form the tenase complex that activates additional Factor X. Activated Factor Xa and Va subsequently form the prothrombinase complex on activated cell surfaces which catalyzes the conversion of factor II (prothrombin) to its active form factor IIa (thrombin). Thrombin then converts fibrinogen to its active form fibrin, further perpetuating an active fibrin clot while also amplifying its production by influencing upstream factors VIII and IX causing continued clot formation.3 Antithrombin & Anticoagulation Thrombin also acts as an anticoagulant by activating protein C with the help of a thrombomodulin cofactor. Activated protein C (APC) then binds to protein S on cell membranes where it inactivates factors Va and VIIIa, leading to inhibition of thrombin generation by inhibiting the actions of prothrombinase and tenase complex-
VTE es.4 Antithrombin (AT) is an endogenous anticoagulant that inactivates proteases IIa, IXa, Xa, XIa, and XIIa. The clotting mechanism is a complex and carefully modulated mechanism that adjusts the amount of response in proportion to the injury during normal function. Fibrinolysis After an injury, endothelial cells release tissue plasminogen activator (t-PA) which cleaves plasminogen into its active form plasmin. Plasmin is a fibrin specific enzyme protease which cleaves fibrin into fibrin degradation products such as D-dimer. Plasminogen and plasmin are both selective for fibrin clots, thereby adding clot specificity to the fibrinolytic process. However, fibrin clot specificity only exists at physiologic levels of t-PA. At pharmacologic levels of t-PA used in therapy, specificity disappears and the body enters a systemic lytic state resulting in an overall increased risk of bleeding.3 Pathophysiology VTE is a pathological clotting disorder that includes DVT and PE. Damage to the valves of the veins in combination with reduced flow of oxygenated blood in the veins put the endothelium in an oxygen-deprived state. This hypoxemic state attracts leukocytes to bring tissue factor to the endothelium, resulting in activated factor VII triggering the extrinsic coagulation pathway. This results in the formation of a fibrin-rich thrombus. DVT is defined as a thrombus that originates in the deep veins of the lower extremities. The initial thrombus can become detached from its original site and embolize throughout the blood circulation, eventually blocking a smaller vessel. A serious consequence of embolism is PE, in which the thrombus travels to the lungs and blocks central vessels and peripheral vessels. As a result of the blockage, parts of the lungs are not receiving blood flow leading to arterial hypoxemia. Increased ventilation compensates for the hypoxemia; however, overcompensation may result in hypocapnia. Blockage of the blood vessels in the lungs leads to consequences such as increased right ventricular overload and decreased filling of the left ventricle, resulting in right-sided and left-sided heart failure. At the same time, the lodged thrombus secretes chemical mediators that cause bronchoconstriction and vasoconstriction, resulting in alveolar hypoxemia.5, 6 Etiology Virchow’s triad describes the three risk factors that may contribute to the pathology of venous thrombus formation: hypercoagulable state, venous stasis, and vascular endothelial damage.6 A hypercoagulable state can be caused by inherited and acquired risk factors. Inherited factors include Factor V Leiden, Prothrombin G20210A mutation, and deficienCONTINUING EDUCATION
cies in antithrombin, protein C, protein S and plasminogen. These inherited factors can place patients at a higher risk of developing an initial VTE. Acquired factors include cancer, chemotherapy, oral contraceptives, hormone replacement therapy (HRT), pregnancy, postpartum period and central obesity. Cancer cells express procoagulant proteins such as tissue factor and cancer procoagulant, which activates factor X. Chemotherapy drugs have been shown to induce tissue factor, down regulate protein C and protein S, damage the endothelial wall, and activate platelets. High estrogen levels in the blood from oral contraceptives, HRT, pregnancy, and postpartum period cause the liver to synthesize procoagulant proteins and decrease synthesis of anticoagulant and fibrinolytic proteins. Cytokines from adipocytes can cause procoagulant effects and increased activity of the coagulation cascade. Obesity can also cause increased inflammation, oxidative stress, and endothelial dysfunction, which can lead to a hypercoagulable state.2,6 Venous stasis or the slowing of blood flow through the venous circulation can be caused by a variety of factors such as reduced mobility (e.g., long air travel, hospitalizations), excessive overproduction of red blood cells, and congestive heart failure (CHF).6 Endothelial damage caused by long term central venous catheters, major surgery, and trauma exposes the subendothelial layer containing tissue factor and collagen. The exposed tissue factor and collagen bind and activate circulating platelets, leading to aggregation and clot formation. Other causes such as hypertension and cigarette smoking decrease nitric oxide and prostacyclin synthesis and increase endothelin-1, causing endothelial dysfunction and an imbalance between clot formation and clot breakdown.6 Risk Factors Genetic Several genetic risk factors have been elucidated for VTE. Antithrombin deficiency was one of the first risk factors discovered for risk of venous thrombosis. Antithrombin (AT) inhibits thrombin and many of the enzymes involved in the coagulation pathway. Decreased amounts of AT result in decreased control of the coagulation cascade leading to increased clot formation. Protein S deficiencies also incur a risk for VTE due to its stimulatory action as a cofactor for APC, a potent endogenous anticoagulant which exerts its effects by inhibiting FVIIIa and FVa. Protein C deficiencies are also associated with thrombosis, but is regarded as a mild risk factor compared to other genetic mutations. The most common genetic alteration observed in patients with thrombosis is APC Resistance incurred by a FV Leiden mutation. With a single point mutation on the FV gene, FV and also FVIIIa degradation by APC is impaired resulting in APC resistance and decreased inhibition of coagulation. The most prevalent manifestaSpring 2016 • Arizona Journal of Pharmacy • 37
VTE tions of the FV Leiden mutation are venous thrombosis and pulmonary embolisms. Another single point mutation located in the 3’ untranslated region of the prothrombin gene is associated with increased concentrations of prothrombin, resulting in a 3-4 fold increased lifetime risk for venous thrombosis.7 Increased concentrations of factors VIII, IX, XI, or fibrinogen also incur risk for VTE.8 Patients with antiphospholipid antibodies are also at an increased risk for VTE and are most commonly seen in those with autoimmune disorders such as systemic lupus erythematosus and inflammatory bowel disease.9 Physiologic The rate of blood flow in the venous circulation is relatively slow, particularly in the deep veins of the lower extremities. Muscle contractions in the calf and thigh, along with venous valves, aid to propel blood flow back to the heart and lungs. Damage to the venous valves or physiologic states predisposing low blood flow in the veins such as bed rest during hospitalization, use of a plaster cast, or orthopedic surgery can result in an increased risk of VTE.2 Due to the lack of muscle movement, blood pools in the veins, causing lowered oxygen tension. This results in oxidative stress, which can lead to the recruitment of pro-inflammatory factors such as monocytes, granulocytes and platelets. The presence of these factors can subsequently lead to exposure of tissue factor (TF) and initiation of the extrinsic coagulation pathway.10 Cancer also increases the presence of pro-coagulant substances which puts the body in a hypercoagulable state. Furthermore, cancer patients have decreased levels of protein C, protein S, and antithrombin.11 Estrogen in contraceptives, hormone replacement therapy, and selective estrogen receptor modulators are all associated with an increased risk of VTE. Estrogen increases the presence of coagulation factors and induces APC resistance.12 Clinical Presentation VTE is a disorder of inappropriate blood clotting, leading to many complications, including death.2 Patients with DVT present with unilateral pain and swelling in the lower extremities while patients with PE typically present with chest pain and shortness of breath.2 Diagnosis The gold standard for diagnosing VTE is a radiographic contrast study such as a venography or pulmonary angiography. However, contrast studies are not commonly used in clinical practice due to their limitations.13 They are expensive, invasive, and difficult to perform. The radiocontrast dyes can cause damage to the kidneys and vessel walls, which may then cause a VTE. Therefore, less invasive procedures such as compression ultrasound (CUS), computed tomography (CT) scans, and the ventilaCONTINUING EDUCATION
tion-perfusion (V/Q) scan are used for the initial diagnosis. D-dimer tests may also be used to diagnose a suspected VTE.13 D-dimer is a fragment of fibrin clot that is present in the blood and is a sensitive marker of clot formation. Patients with a VTE usually have elevated levels of D-dimer concentration in their blood.13 However, D-dimer elevations are not used as a definitive diagnosis for VTE because there are many other causes of elevated D-dimer, such as recent surgery or trauma, pregnancy, increasing age, and cancer. Therefore, D-dimer tests are used to rule out VTE when the probability is low.13
Anticoagulant Therapy
Table 2. Coagulation cascade with medication targets
Heparin Unfractionated heparin (UFH) Heparin sodium is a heterogeneous group of mucopolysaccharides called glycosaminoglycans which have anticoagulant effects. Heparin binds antithrombin III resulting in inhibition of Factor X activation and prothrombin to thrombin conversion. If thrombosis has developed, increased doses of heparin can hamper additional coagulation by inhibiting the conversion of fibrinogen to fibrin. Heparin is indicated for use in prophylaxis in high-risk medical patients such as hospitalized patients who are not fully ambulatory and treatment of VTE and PE.14 Heparin is administered by intravenous injection, infusion, or deep subcutaneous injection. Intramuscular administration should be avoided due to the possibility of hematoma development at the injection site. For intravenous infusion, therapeutic dosing starts with an initial dose of 80 units/kg or 5,000 units IV push, followed by a continuous infusion of 18 units/kg/hr. For patients undergoing surgery, prophylactic dosing is typically 5,000
VTE units subcutaneously 2 hours before surgery and 5,000 units every 8 to 12 hours for 7 days or until the patient is fully ambulatory. Dosing should be adjusted based on the patient’s activated partial thromboplastin time (aPTT) and should be avoided in patients with severe thrombocytopenia or uncontrolled bleeding states. There is an increased risk of hemorrhage in all patients receiving heparin. Up to 30% of patients receiving heparin have reported incidences of thrombocytopenia. Platelet counts should be collected at baseline and periodically while on heparin. If the count falls below 100,000/mm3 or a drop of greater than 50% from baseline is observed, Heparin-induced Thrombocytopenia (HIT) should be considered and all forms of heparin should be discontinued while further workup is in process. Reversal of heparin toxicity can be accomplished with prompt discontinuation of the drug and administration of the antidote protamine sulfate. Interpretation of increased liver function tests (LFTs) should be exercised with caution as use of heparin is associated with temporary increases in AST and ALT levels. Local irritation can also occur at injection sites. Periodic platelet counts, hematocrit, and occult blood samples should be collected during the course of therapy. Use of heparin should be cautioned when used concomitantly with other oral anticoagulants and platelet inhibitors due to an increased risk of bleeding. Careful monitoring is required during administration of these drugs together. Heparin is pregnancy category C and should only be used when deemed medically necessary. If available, preservative-free Heparin Sodium Injection is recommended. In nursing mothers, preservative-free Heparin Sodium Injection should be used as opposed to non-preservative free heparin.15 Since the effects of unfractionated heparin (UFH) are less predictable than low molecular weight heparins (LMWH’s), its place in therapy is typically in acute treatment for VTE in patients with severe renal insufficiency (creatinine clearance <30 mL/min).16 Low Molecular Weight Heparin (LMWH) (Lovenox/enoxaparin, Fragmin/dalteparin) Unlike unfractionated heparin, low molecular weight heparin (LMWH) consists of shorter-chain fractions of heparin that exert more predictable effects than UFH. LMWH is prescribed in a fixed, weight-based dosing and generally has predictable pharmacokinetics in patients with normal renal function. For patients undergoing abdominal surgery and those with restricted mobility, enoxaparin is dosed at 40 mg once daily for prophylaxis of VTE for 7-10 days or until risk of VTE has diminished. For patients undergoing hip or knee replacement, VTE prophylactic treatment is enoxaparin 30 mg subcutaneously every 12 hours given 12-24 hours after surgery for 7-10 days. An alternative dose for patients unCONTINUING EDUCATION
dergoing hip replacement surgery is 40 mg subcutaneously given 12 hours before surgery and continuing for at least 10 days up to 4 weeks. For inpatient treatment of DVT, an enoxaparin dose of either 1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg once daily can be used. Outpatient treatment can only utilize the dosing regimen of 1 mg/kg subcutaneously every 12 hours. Therapy should be continued for a minimum of 5 days until an INR of 2-3 is reached along with concomitant warfarin therapy.3 The prophylactic dose of dalteparin for hip replacement surgery can vary depending on whether it is first given pre-operatively or post-operatively. If started post-operatively, 2,500 units are given SQ 4-8 hours after surgery, then 5,000 units SQ q24h. If it is first given pre-operatively, the dose is 5,000 units SQ 10-14 hours before surgery, 5,000 units SQ 4-8 hours after surgery, and then 5,000 units SQ q24h thereafter. For VTE prophylaxis in abdominal surgery, 2,500 units are given SQ q24h, initiated 1-2 hours prior to surgery.2 Therapeutic dosing of dalteparin for DVT (with or without PE) is 200 units/kg daily. LMWH should be given with caution in patients with renal dysfunction or a body weight of greater than 150 kg. Monitoring of anti-factor Xa levels is not necessary unless the patient presents with other comorbidities such as renal insufficiency or pregnancy. The occurrence of HIT is also notably lower in LMWH than in UFH. Protamine sulfate can be used in cases of LMWH overdose, but the reversal is incomplete. An increased risk for bleed exists with the use of LMWH, as with all anticoagulants.3 Factor Xa Inhibitors Fondaparinux Fondaparinux sodium (Arixtra) depends on anti-thrombin III (ATIII) as a substrate and indirectly inactivates Factor Xa, resulting in inhibition of thrombus formation from prothrombin. Fondaparinux does not inactivate thrombin, has no known effect on platelet activity, and is not fibrinolytic.19 The CHEST 2012 Guidelines (CHEST 2012) suggest SC fondaparinux as an alternative to LMWH over IV and SC UFH for the treatment of acute DVT of the leg and acute PE.16 It can be used for VTE prophylaxis in patients undergoing hip fracture surgery, hip or knee replacement surgery, abdominal surgery, or in patients who are at risk for thromboembolism. For VTE prophylaxis, it is dosed as 2.5 mg SC injection once every 24 hours. For VTE treatment, fondaparinux is an actual body weight-based SC injection given once every 24 hours: 5 mg if less than 50 kg, 7.5 mg if 50 to 100 kg, and 10 mg if greater than 100 kg. Fondaparinux is avoided if CrCl is less than 30 mL/min. Other contraindications include active major bleeding, Spring 2016 • Arizona Journal of Pharmacy • 39
VTE bacterial endocarditis, and thrombocytopenia in the presence of the drug. If the body weight is less than 50 kg, fondaparinux should not be used for VTE prophylaxis. A common side effect with fondaparinux is bleeding complications. Agents that increase the risk of bleeding should be discontinued prior to treatment with fondaparinux unless they are deemed medically necessary. Monitoring parameters include evaluating for signs and symptoms of bleeding, CBC, serum creatinine level, and stool occult blood tests.16 Direct Factor Xa Inhibitors The direct acting Factor Xa inhibitors are oral agents: rivaroxaban (Xarelto ®), apixaban (Eliquis®), and newly approved edoxaban (Savaysa®). Unlike fondapariux, the direct Factor Xa inhibitors can inactivate unbound and clot-bound Factor Xa without depending on anti-thrombin as a substrate. CHEST 2012 guidelines mention the use of oral rivaroxaban as an option for the initial treatment of DVT without initial warfarin and initial parenteral therapy. VTE treatment with rivaroxaban has less monitoring and may be demonstrate better clinical outcomes over LMWH and warfarin. However, postmarketing studies of safety were not available during the creation of the guidelines. Therefore, warfarin or LMWH are recommended over rivaroxaban for long-term therapy in patients with VTE. Apixaban and edoxaban are not mentioned because they were not FDA-approved when the CHEST 2012 guidelines were created.16 However, randomized controlled trials show that both apixaban and edoxaban were noninferior to the standard treatment with enoxaparin and warfarin for the primary efficacy outcome of symptomatic venous thromboembolism and primary safety outcome of major and nonmajor bleeding.17,18 For the VTE treatment, rivaroxaban 15 mg is given orally every 12 hours with food for 21 days, then 20 mg once every 24 hours with food for the remainder of therapy. For VTE prophylaxis during hip and knee replacement surgery, rivaroxaban 10 mg is given orally once every 24 hours with or without food. Rivaroxaban is avoided if CrCl is less than 30 mL/min. Patients with prosthetic heart valves and/or active pathological bleeding should avoid rivaroxaban. The most common side effects are related to bleeding.20 For VTE treatment, apixaban 10 mg is given orally twice daily for 7 days, followed by 5 mg twice daily for the remainder of therapy. For VTE prophylaxis following hip or knee replacement surgery and reduction in the risk of recurrent VTE following initial therapy, 2.5 mg is given twice daily. Renal dose adjustments are not listed in the package insert and trials did not include patients with a CrCl less than 30 mL/min. Similar to rivaroxaban, patients with prosthetic heart valves and/or active pathological bleeding should avoid apixaban. The most common side CONTINUING EDUCATION
effects are related to bleeding.21 For VTE treatment following 5 to 10 days of initial therapy with a parenteral anticoagulant, edoxaban 60 mg is given once daily. For patients with CrCl 15 to 50 mL/min, body weight less than or equal to 60 kg, or patients who use certain P-glycoprotein (P-gp) inhibitors, the edoxaban dose should be decreased to 30 mg. Unlike rivaroxaban and apixaban, edoxaban is not currently indicated for VTE prophylaxis. Contraindications include patients with mechanical heart valves or moderate to severe mitral stenosis, and active pathological bleeding. The most common side effects are bleeding, rash, abnormal liver function, and anemia.22 Monitoring parameters for the direct Factor Xa inhibitors include evaluating for signs and symptoms of blood loss, CBC, and serum creatinine. CBC and SCr should be evaluated at baseline and every 3-6 months. Monitoring of coagulation tests are not required for the direct Factor Xa inhibitors, which can be less burdensome for patients. However, there is no antidote available to reverse serious bleeding. These drugs have interactions with P-gp inducers and inhibitors.20,21,22 Andexanet alfa may become the first approved agent to reverse the bleeding caused by apixaban and rivaroxaban. In a randomized controlled study, andexanet alfa 400 mg IV bolus (30 mg/min), or 400 mg IV bolus plus a continuous infusion of 4mg/min for 120 min was given to patients three hours after their last dose of apixaban 5 mg orally twice daily. Andexanet alfa 800 mg IV bolus (30 mg/ min), or 800 mg IV bolus plus a continuous infusion of 8 mg/min for 120 min was given to patients four hour after their last dose of rivaroxaban 20 mg orally once daily for 4 days. The study found that andexanet alfa reversed the factor Xa inhibitor activity of apixaban and rivaroxaban within minutes. Andexanet alfa has been given orphan drug designation by the FDA.23 Vitamin K Antagonist (Warfarin) Vitamin K antagonists such as warfarin work by preventing the recycling of vitamin K to and from its oxidized and reduced state.2 Vitamin K is a critical cofactor for the activation for coagulation proteins prothrombin (factor II), factor VII, IX, X and anticoagulant proteins C and S.2 By preventing the enzymatic carboxylation of these proteins, warfarin can prevent the formation of fully active coagulation proteins.2 Vitamin K antagonists, however, will not affect already activated clotting factors or thrombi that have already formed.2 The extent a patient is anticoagulated can be monitored using prothrombin time (PT). While taking a vitamin K antagonist, frequent monitoring of a patient’s PT or International Normalized Ratio (INR), a more standardized way to monitor a patient’s response to warfarin, is required.24 For the treatment of VTE, the target INR is
VTE between 2.0 – 3.0.2, 24 In the treatment of acute DVT of the leg, vitamin K antagonists should be started the same day as a parenteral anticoagulant.16 According to the Chest 2012 guidelines, the recommended outpatient warfarin dose is 5 – 10 mg daily for the first two days then dosing based on INR.24 Doses < 5 mg may be indicated for the elderly, patients with impaired nutrition, liver disease, congestive heart failure, or patients with a high bleed risk.24 Doses between 2 to 3 mg may be appropriate for patients who have undergone valve replacement.24 The parenteral anticoagulant, such as heparin or enoxaparin, should be used for a minimum of 5 days and until the INR is 2.0 or greater for more than 24 hours.16 For long-term therapy, vitamin K antagonists are the preferred agent for patients who suffered DVT of the leg with no cancer.16 To treat an acute first episode of VTE, warfarin therapy should be continued for three months.16 Extending warfarin use in patients should be considered carefully. Patients who suffer from an unprovoked proximal DVT of the leg or PE, whether a first or subsequent event, with low to moderate bleeding risk may be on extended anticoagulant therapy (over three months).24 Patients with high bleed risk, three months of anticoagulant therapy is recommended.24 For patients without cancer requiring extended therapy for proximal DVT of the leg or PE, vitamin K antagonist therapy is preferred over LMWH.24 When discontinuing vitamin K antagonist therapy, no tapering is required.24 Warfarin has a black box warning for major or fatal bleeding.25 Side effects include hemorrhage and necrosis of the skin.25 Skin necrosis usually occurs soon after starting warfarin therapy.25 If skin necrosis occurs, discontinue warfarin immediately and administer warfarin antidote vitamin K and fresh frozen plasma.2, 24 Purple toe syndrome, a rare but serious side effect, may also occur.2 Warfarin is classified as pregnancy category X for most pregnant women but is considered pregnancy category B for pregnant women with mechanical heart valves.25 The Chest Guidelines also recommend against the use of NSAIDs, including COX-2 selective drugs.26 Warfarin has numerous drug interactions. Vitamin K can reverse warfarin’s effects and is often used as an antidote when INR levels are too high.2 Patients should be counseled to eat a normal balanced diet and keep vitamin K consumption consistent in their diet.25 Drugs that affect CYP2C9, CYP1A2, and CYP3A4 can greatly affect warfarin’s effects.2 All in all, there are over 200 agents that may interfere with warfarin.25 When a patient’s INR is supratherapeutic, vitamin K can be used to reverse warfarin’s effects. For patients whose INR is between 4.5 and 10 and are currently not bleeding, the CHEST 2012 guidelines recommend against the use of vitamin K.26 At an INR greater 10, the guidelines CONTINUING EDUCATION
recommend the use of oral vitamin K to reverse warfarin’s effects.26 If patients on warfarin experience major bleeding, the guidelines recommend rapid reversal with four-factor prothrombin complex concentrate and the additional use of vitamin k 5 to 10 mg via slow IV injection.26 Table 3. Some Common Drug Interactions with Warfarin24 Effect on Warfarin Drug Highly probable to increase warfarin’s effects Ciprofloxacin Erythromycin Fluconazole Diltiazem Propranolol Citalopram Sertraline Cimetidine Omeprazole Probable to increase warfarin’s effects Amoxicillin/clavulanate Azithromycin Clarithromycin Aspirin Simvastatin Acetaminophen Celecoxib Tramadol Grapefruit Highly probable to decrease warfarin’s effects Nafcillin Rifampin Barbiturates Carbamazepine High vitamin K content foods Large amounts of avocado Probable to decrease warfarin’s effects Terbinafine Telmisartan Sulfasalazine
Direct Thrombin Inhibitors (argatroban, bivalirudin, dabigatran) Direct thrombin inhibitors such as argatroban, bivalirudin (Angiomax®), and dabigatran (Pradaxa®) work by directly binding to thrombin, blocking its active site and preventing its downstream effects.3 Argatroban and bivalirudin is administered intravenously.27,28 In the United States, dabigatran is available orally as a 75 mg or 150 mg capsule and is dosed as 150 mg twice daily for the treatment of DVT and PE; however, use of a parenteral anticoagulant before dabigatran initiation for 5-10 days is required.29 Argatroban is indicated for patients who develop HIT while on heparin or LMWH.27 If a patient who cannot be on warfarin develops HIT, the Chest Guidelines recommend the use of argatroban, lepirudin, or danaparoid over the continued use of heparin or LMWH.26 Bivalirudin is indicated as an anticoagulant for patients undergoing percutaneous coronary intervention (PCI), or with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA), or for patients at high risk of HIT undergoing PCI.28 The Chest Guidelines recommend the use of bivalirudin for patients with acute HIT who require cardiac surgery.26 Side effects of direct thrombin inhibitors were related to bleeding events.27, 28, 29 Contraindications to dabigatran use include the presence of a mechanical prosthetic heart valve, history of hypersensitivity reaction to dabigatran, and patients with active pathological bleeding.26, 29 Dabigatran should be avoided in patients with severe Spring 2016 • Arizona Journal of Pharmacy • 41
VTE renal impairment (creatinine clearance < 30 mL/min).26, 29 Contraindications to bivalirudin use include active major bleeding and hypersensitivity to bivalirudin.28 Contraindications to argatroban include active major bleeding and hypersensitivity to argatroban.27 Unlike warfarin, therapeutic INR levels for argatroban have not been established but activated partial thromboplastin times (aPTT) have been shown to correlate with its anticoagulation effects.27 Idarucizumab (Praxbind), a monoclonal antibody fragment, is an antidote that can be used to reverse the effects of dabigatran. In a prospective cohort study, idarucizumab 5 grams IV was given to patients on dabigatran who were experiencing overt, uncontrollable, or life-threatening bleeding or patients who required procedures that could not be delayed.28 The study found that idarucizumab rapidly and completely reversed the anticoagulant effects of dabigatran in 88-98% of patients.28 Thrombolytics Anticoagulants decrease the chance of forming further clots, prevent the clots from becoming larger, and prevent extension of the clots to the lungs. Anticoagulants do not breakdown or dissolve the clots that are already formed in the blood. The body has a natural mechanism to dissolve the fibrin clots. Thrombolytic drugs such as alteplase, streptokinase, and urokinase can be injected directly at the site of the clot to break it down. These agents convert plasminogen to plasmin which breaks down the thrombus.2 Limitations of using thrombolytics include active internal bleeding, recent intracranial or intraspinal surgery, serious head trauma, intracranial conditions that may increase the risk of bleeding, bleeding diathesis, and current severe uncontrolled hypertension.29 For acute proximal DVT of the leg, the CHEST 2012 guidelines recommend anticoagulant therapy alone over thrombolytics. If thrombolysis is used for acute DVT, a catheter-directed thrombolysis (CDT) is recommended over systemic thrombolytic therapy. A CDT will result in faster lysis of the thrombus using lower doses and reduce the risk of serious bleeding. For acute PE, thrombolytics are recommended if the PE is associated with systolic BP less than 90 mm Hg and if the patient is not at high risk for bleeding. Thrombolytics are not recommended in acute PE without hypotension. If a thrombolytic agent is used in acute PE, short infusion times of 2 hours are preferred and administration through the peripheral vein is recommended over a pulmonary artery catheter.2 IV alteplase is given as 10 mg over 10 min, then 90 mg over 2 hours for a total of 100 mg. IV streptokinase is given as 250,000 units over 30 minutes, then 100,000 units per hour for 24 hours. IV urokinase is given as 4,400 units per kg over 10 minutes, then 4,400 units per kg for 12 to 24 hours.31 CONTINUING EDUCATION
Non-Pharmacologic Treatment Some non-pharmacological treatments for VTE include graduated compression stockings (GCS), sequential compression devices (SCD), and the use of inferior vena cava (IVC) filters. According to the 2012 Chest Guidelines, for patients with increased risk of VTE intending to travel long distances, it is recommended that they ambulate often, perform calf-muscle exercises or use properly-fitted, below-theknee graduated compression stockings (GCS) that provide 15 to 30 mmHg of pressure at the ankle.32 IVC filters can also be used, although there are no clear long-term benefits.32 The 2012 Chest Guidelines generally do not recommend IVC filters for primary VTE prophylaxis.32 Use of an IVC filter may be warranted for patients who suffered from an acute PE with a contraindication to anticoagulant therapy.16 Special Populations Cancer Cancer patients are at an increased risk for VTE and VTE recurrence due to the strong association between cancer cells and thrombus formation.33 The risk of recurrence depends on whether the cancer is metastatic, persistent, rapidly progressing, or being treated with chemotherapy within the past 6 months. Cancer patients should be assessed on an individual basis when it comes to choosing appropriate treatment for VTE, such as tolerance to injections, need for therapeutic and safety laboratory monitoring, and treatment costs. In patients with DVT of the leg/PE and cancer, CHEST 2012 recommends LMWH over warfarin. If LMWH is not being used, warfarin is recommended over dabigatran or rivaroxaban for long-term therapy. If active cancer patients with DVT of the leg/PE are at a low to moderate risk of bleeding, extended anticoagulant treatment is recommended. If the bleeding risk is high, extended anticoagulant therapy is suggested.16 Pregnancy LMWH is recommended over UFH for the prevention and treatment of VTE in pregnant women. For acute VTE, CHEST 2012 suggests that anticoagulants should be continued for at least 6 weeks after childbirth (for a minimum treatment duration of 3 months.) Women with a history of pregnancy complications (e.g., two or more miscarriages) should not use antithrombotic prophylaxis.13 Children There is weak evidence that supports the use of antithrombotic agents in children and neonates. CHEST 2012 recommends that experienced pediatric hematologists manage VTE in the pediatric population. UFH and LMWH are the drugs of choice. UFH should be titrated to a target anti-Xa level (i.e., 0.35 to 0.7 units/mL) or an aPTT/PT that
VTE correlates to this range. LMWH should be monitored to a target range (i.e., 0.5 to 10 units/mL) 4 to 6 hours after SC injection.35 Role of the Pharmacist and Conclusion: Pharmacists in the acute care setting can have a huge impact on managing and preventing VTE. They can ensure that all patients at risk for a VTE are on appropriate antithrombotic prophylaxis. If patients are contraindicated to antithrombotic therapy due to bleeding risks, pharmacists can ensure that non-pharmacologic interventions such as graduated compression stockings or sequential compression devices are being utilized. Pharmacists can also manage VTE by recommending appropriate treatment regimens, screening for contraindications, and assisting in the management of adverse effects while patients are in the hospital. In the community setting, pharmacists can help triage patients to the appropriate type of care they should receive by asking important questions on the type of symptoms a patient is experiencing. Not only can community pharmacists assist in this manner, but pharmacists in a dispensing role can also ensure a patient is adherent to their medication and help guide patients on the appropriate way to take their medication. In an ambulatory care setting, pharmacists can help manage warfarin dosing by doing INR point-of-care. In conclusion, VTE prophylaxis is one of the most important measures that pharmacists can implement as providers to prevent unnecessary mortality from complications associated with a VTE. It is the responsibility of providers to be aware of the various environmental and genetic risk factors that can contribute to a VTE and to ensure patients are on the appropriate preventative therapy. In the case of unprovoked VTE events, it is important that patients remain on anticoagulant therapy for the appropriate duration to minimize the risk of a recurring event. Pharmacists can play a vital role in both the acute care and community setting by ensuring the proper implementation of both preventative and treatment medication regimens for VTE. References 1. Beckman MG, Hooper WC, Critchley SE et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010 Apr;38(4 Suppl):S495-501. 2. Witt DM, Clark NP. Chapter 9. Venous Thromboembolism. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.http://accesspharmacy.mhmedical.com/ content.aspx?bookid=689&Sectionid=48811458. Accessed March 02, 2015. 3. Zehnder JL. Drugs Used in Disorders of Coagulation. In: Katzung BG, Trevor AJ. eds. Basic & Clinical Pharmacology, 13e. New York, NY: McGraw-Hill; 2015. http://0-accessmedicine.mhmedical.com. millennium.midwestern.edu/content.aspx?bookid=1193&Sectionid=69108955. Accessed March 02, 2015. 4. Esmon, CT. The protein C pathway. Chest. 2003 Sep;124(3 SupCONTINUING EDUCATION
pl):26S-32S. 5. Saha P, Humphries J, Modarai B et al. Leukocytes and the natural history of deep vein thrombosis: current concepts and future directions. Arterioscler Thromb Vasc Biol. 2011;31(3):506-12. 6. Tapson VF. Acute pulmonary embolism. N Engl J Med. 2008 Mar 6;358(10):1037-52. 7. Dahlback, B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood. July 2008:112(1). 8. Rosendaal FR, Reitsma PH. Genetics of venous thrombosis. J Thromb Haemost. 2009;7(Suppl 1):301–304. 9. Giannakopoulos B, Passam F, Rahgozar S, Krilis SA. Current concepts on the pathogenesis of the antiphospholipid syndrome. Blood. 2007;109(2):422–430. 10. Reitsma, P., Versteeg, H., Middeldorp, S. Mechanistic View of Risk Factors for Venous Thromboembolism. Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32:563-568. 11. Buller HR, van Doormaal FF, van Sluis GL, Kamphuisen PW. Cancer and thrombosis: From molecular mechanisms to clinical presentations. J Thromb Haemost. 2007;5(Suppl 1): 246–254. 12. Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Female hormones and thrombosis. Arterioscler Thromb Vasc Biol. 2002;22(2):201–210. 13. Bates SM, Jaeschke R, Stevens SM et al. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141 (2 Suppl):e351S– e418S. 14. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e195S–e226S 15. Heparin sodium package insert. Lakeforest, IL: Hospira, Inc.; 2013 Aug. 16. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e419S–e494S 17. Agnelli G, Buller HR, Cohen A et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799-808. 18. Büller HR, Décousus H, Grosso MA et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406-15. 19. Atrixtra (fondaparinux sodium) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2013 Sept. 20. Xarelto (rivaroxaban) package insert. Titusville, NJ: Janssen Pharmaceuticals; 2014 Dec. 21. Eliquis (apixaban) package insert. Princeton, NJ: Bristol-Myers Squibb; 2014 Aug. 22. Savaysa (edoxaban) package insert. Parsippany, NJ : Daiichi Sankyo; 2015. 23. Siegal D, Curnutte J, Connolly S et al. Andexanet alfa for the reversal of Factor Xa Inhibitor activity. N Engl J Med. 2015;373:2413-2424. 24. Ageno W, Gallus AS, Wittkowsky A et al. Oral anticoaguSpring 2016 • Arizona Journal of Pharmacy • 43
VTE lant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e44S–e88S. 25. Coumadin (warfarin) package insert. Bristol-Myers Squibb Pharma Company; 2014 Aug. 26. Guyatt GH, Akl EA, Crowther M et al. American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):7S-47S. 27. Argatroban package insert. Research Triangle Park, NC: GlaxoSmithKline; 2014 March. 28. Pollack C, Reilly P, Eikelboom J et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015;373(6):511-20. 29. Angiomax (bivalirudin) package insert. The Medicines Company; 2013 May. 30. Pradaxa (dabigatran) package insert. Boehringer Ingelheim Pharmaceuticals, Inc.; 2015 Jan. 31. Activase (alteplase) package insert. San Francisco, CA: Genentech, Inc; 2015 Feb. 32. Watson LI , Armon MP . Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev. 2004;(4):CD002783 . 33. Gould MK, Garcia DA, Wren SM et al. American College of Chest Physicians. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e227S-77S. 34. Stricker H. Venous thromboembolism and cancer: pathophysiology and incidence. Vasa. 2014;43(4):239-43. 35. Monagle P, Chan AKC, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2) (suppl):e737S-e801S.
To receive CPE credit you must complete the quiz and evaluations on page 46 ACPE UAN# 0100-0000-16-004-H04-P; This activity has been approved for 2.0 contact hours or (0.20 CEUs) of continuing pharmacy education.
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CONTINUING EDUCATION QUIZ QUESTIONS
Venous Thromboembolism: A Review of Prevention and Treatment Options ACPE UAN# 0100-0000-16-004-H04-P This continuing education activity is accredited for pharmacists only.
This activity has been approved for 2.0 contact hours or (0.20 CEUs) of continuing pharmacy education. 1. Which of the following anticoagulant agents require a parenteral anticoagulant before initiation? a. Unfractionated Heparin b. Fondaparinux c. Dabigatran d. Bivalirudin 2. What is the target INR for patients on warfarin for the treatment of VTE? a. 4.0 – 5.0 b. 1.0 – 3.0 c. 2.0 – 3.5 d. 2.0 – 3.0 3. Which of the following drugs will lead to an increased bleed risk for patients on warfarin? a. Cimetidine b. Carbamazepine c. Nafcillin d. Rifampin 4. When starting warfarin for the treatment of acute DVT of the leg, how should a parenteral anticoagulant be used? a. Parenteral anticoagulant should be started 5 days after initiation of warfarin until the INR is 2.0 for a minimum of 24 hours b. Parenteral anticoagulant should be started on the same day as warfarin and continued for a minimum of 5 days and until the INR is 2.0 for more than 24 hours c. Parenteral anticoagulant should be started 24 hours before starting warfarin and should be continued until the INR reaches 2.0 d. Parenteral anticoagulant should not be used at the same time as warfarin 5. Which of the following is not a recommendation for non-pharmacologic prophylaxis of VTE? a. Ambulating often for long distance traveling b. Below-the-knee graduated compression stockings that provide 15 to 30 mmHg pressure at the ankle c. IVC filters for patients with no contraindication to anticoagulant therapy d. Calf-muscle exercises 6. Which oral anticoagulants require 5-10 days of initial therapy with parenteral anticoagulation? a. Apixaban b. Rivaroxaban c. Edoxaban d. Warfarin
7. Which of the following statements is incorrect? a. Rivaroxaban is given with food during VTE treatment b. The VTE treatment dose for apixaban is 10 mg by mouth every 12 hours for 7 days, then 5 mg by mouth every 12 hours for the remainder of therapy c. The VTE prophylaxis dose for edoxaban is 15 mg PO q24 hours d. All of the statements above are correct 8. What is the drug of choice for cancer patients, pregnant patients, and children? a. Enoxaparin b. Fondaparinux c. Dabigatran d. Rivaroxaban 9. Which of the following statements are/is correct regarding VTE diagnosis? a. Contrast venography is commonly used because it is accurate and reliable b. Less invasive procedures such as compression ultrasound (CUS), computed tomography (CT) scans, and the ventilation-perfusion (V/Q) scan are commonly used for the initial diagnosis of VTE c. D-dimer elevations are preferred for diagnosing VTE d. All of the statements above are correct 10. The most common genetic alteration found in patients with thrombosis is: a. Antithrombin deficiency b. Protein S deficiency c. Protein C deficiency d. APC resistance by a FV Leiden mutation 11. The following are all risk factors for VTE except: a. Hospitalized patients with restricted mobility b. Patients taking estrogen contraceptives, hormone replacement therapy, or selective estrogen receptor modulators c. Orthopedic surgery d. Patients with hypercholesterolemia 12. Choose the correct dosing for VTE prophylaxis in patients undergoing hip/knee replacement surgery: a. 40 mg SQ q12h given 12-24 hours after surgery for 7-10 days b. 30 mg SQ q12 h given 12-24 hours after surgery for 7-10 days c. 1 mg/kg dose SQ q12h or 1.5 mg/kg daily for a minimum of 5 days until an INR of 2-3 is reached along with concomitant warfarin therapy. d. 20 mg SQ q24h given 12-24 hours after surgery for 7-10 days Spring 2016 • Arizona Journal of Pharmacy • 45
Continuing Education Answer Sheet:
I.
Chlamydia, Gonorrhea, and Trichomoniasis: A Guide to Prevention, Diagnosis, and Treatment ACPE UAN# 0100-0000-16-003-H04-P; 0100-0000-16-003-H04-T
Activity accredited date: 02/29/2016 Expiration date: 03/01/2019. This activity has been approved for 2.0 contact hours (0.2 CEUs) of continuing pharmacy education. In order to qualify for ACPE credit, participants must achieve a grade of 70% or above on the quiz and submit a completed activity evaluation.
CE Assessment Answers - Please circle your answers (one answer per question.) 1. a. b. c. d. e. 8. a. 2. a. b. c. d. 9. a. 3. a. b. c. d. 10. a. 4. a. b. c. d. e. 11. a. 5. 6. 7.
a. a. a.
b. b. b.
c. c. c.
d. d. d.
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12. 13.
Questions on page 40. b. c. d. b. c. d. b. c. d. e. b.
a. a.
b. b.
c. c.
d. d.
e. e.
ACTIVITY EVALUATION – Must be completed to receive credit. 1. The activity met the stated learning objectives. (Full list of learning objectives in article.) AGREE DISAGREE 2. Please rate the activity based on the following (please circle one): • Overall evaluation of the article content: Poor 1 2 3 4 5 Excellent • Relevance to pharmacy practice Poor 1 2 3 4 5 Excellent • Value of the content Poor 1 2 3 4 5 Excellent 3. The information presented (check all that apply): Reinforce my current practice/treatment habits Will improve my practice/patient outcomes Provided new ideas or information I expect to use Adds to my knowledge 4. Will the information presented cause you to make any changes to your style or method? Yes No 5. Will the information presented cause you to make any changes in your practice? Yes No 6. How committed are you to making these changes? Not committed 1 2 3 4 5 Very committed 7. Do you feel future activities on this subject matter are necessary and/or important? Yes No
II. Venous Thromboembolism: A Review of Prevention and Treatment Options
ACPE UAN# 0100-0000-16-004-H04-P. Accredited for pharmacists only. Activity accredited date: 03/01/2016 Expiration date: 03/01/2019. This activity has been approved for 2.0 contact hours (0.2 CEUs) of continuing pharmacy education. In order to qualify for ACPE credit, participants must achieve a grade of 70% or above on the quiz and submit a completed activity evaluation. \ C
CE Assessment Answers - Please circle your answers (one answer per question.) 1. a. b. c. d. 6. a. 2. a. b. c. d. 7. a. 3. a. b. c. d. 8. a. 4. a. b. c. d. 9. a. 5. 11.
a. a.
b. b.
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d. d.
10. 12. 13.
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Questions on page 41 b. c. d. b. c. d. b. c. d. b. c. d. b. b. b.
c. c.
d. d.
ACTIVITY EVALUATION – Must be completed to receive credit. 1. The activity met the stated learning objectives. (Full list of learning objectives in article.) AGREE DISAGREE 2. Please rate the activity based on the following (please circle one): • Overall evaluation of the article content: Poor 1 2 3 4 5 Excellent • Relevance to pharmacy practice Poor 1 2 3 4 5 Excellent • Value of the content Poor 1 2 3 4 5 Excellent 3. The information presented (check all that apply): Reinforce my current practice/treatment habits Will improve my practice/patient outcomes Provided new ideas or information I expect to use Adds to my knowledge 4. Will the information presented cause you to make any changes to your style or method? Yes No 5. Will the information presented cause you to make any changes in your practice? Yes No 6. How committed are you to making these changes? Not committed 1 2 3 4 5 Very committed 7. Do you feel future activities on this subject matter are necessary and/or important? Yes No PARTICIPANT INFORMATION: Name ________________________________________ Phone _______________________________________
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