AJP Winter 2015

ARIZONA JOURNAL OF PHARMACY THE OFFICIAL PUBLICATION OF THE ARIZONA PHARMACY ASSOCIATION BROUGHT TO YOU BY PHARMACY NETWORK OF ARIZONA

Winter 2015

Advancing Pharmacy to Improve Healthcare

Sneak Peak:

1.5 contact hours of CE Upcoming AzPA Events 2016 AzPA Legislative Priorities Winter 2015 • ArizonA JournAl of PhArmAcy • 1

YOUR HOLIDAY SHOPPING CAN Support Pharmacy Education

Visit azpharmacy.org/holidays

SAVE THE DATE 49th Annual Southwestern Clinical Pharmacy Seminar February 19-22nd 2016 Tucson Saturday & Sunday Earn CE credits!

Arizona Pharmacy Association

ARIZONA JOURNAL OF PHARMACY

THE OFFICIAL PUBLICATION OF THE ARIZONA PHARMACY ASSOCIATION BROUGHT TO YOU BY PHARMACY NETWORK OF ARIZONA

Vol. 7, no. 4

WINTER 2015

IN THIS ISSUE ....

Message from Leadership SPECIAL CONTRIBUTIONS

Clinical Implications of Latex Allergies in Vaccination Time Capsule Student Perspective: Ambulatory Care Pharmacy

4

13 14 16

FEATURES Review of Hypersensitivity Reactions with Classic Cytotoxic Agents 17 DEPARTMENTS Association News New Members PAPA Legislative Update Technician Spotlight: Christopher Fuentes Pharmacist Spotlight: Hal Wand

5 6 8 10 11 12

Academy News: • ACCP Arizona Academy • Community Pharmacy Academy • Geriatric Care Academy • Health-System Academy • Managed Care Academy • Student Pharmacist Academy • Technician Academy

24 24 24 25 25 25 26

Continuing Education: From A to Z: Clinical Pearls Part 2

27

ADVERTISERS MED PRO PAAS PHARMACY QUALITY COMMITMENT PHARMACISTS LIFE INSURANCE PTCB RX ARMORY RX RELIEF

EDITOR

2 23 23 39 11 23 40

MANAGING EDITOR

Kelly Fine (Ridgway), R.Ph. Rachel Jimenez Chief Executive Officer Marketing & Communications

EDITORIAL BOARD www.azpharmacy.org/ajp

Whitney Rice, Pharm.D. Christi Jen, Pharm.D. Kalani Anderson, C.Ph.T.

Andrea Burns, Pharm.D. Jaime Bailey, Pharm.D

Winter 2015 • ArizonA JournAl of PhArmAcy • 3

Leadership Dear AzPA Members, The year got off to a good start with the Annual Board of Directors Retreat. It was held at the Sheraton Wild Horse Pass Resort & Spa. The location was wonderful giving us a preview for the 2016 Annual Convention. I would like to give credit to Ann Sears; she organized several fun events that helped all of us work on team building and communication.

We appreciate the effort that all of the Board Members made to get to the retreat, recognizing the importance of knowing how their Association conducts business. I would like to extend a special thanks to the AzPA staff for all of their hard work in making the retreat a success.

The next event that we hosted was the Annual Fall Conference on the 26th of September. It was held in Chandler, where we had 83 attendees and a very dynamic group of speakers. Again, our AzPA Staff did an outstanding job making sure we had a successful conference. Their many hours of hard work and dedication are always appreciated. All of the attendees had a good time and enjoyed the educational sessions.

Our first Board of Directors Meeting was held on October 21st. It was good to see all of the new faces around the Board Room. We have a strong, motivated group of leaders that you elected; it is sure to be a great year. The energy within our Association is what makes this an incredible organization.

AzPA held the APhA Pharmacy-Based Cardiovascular Disease Risk Management Program on November 6th. This event was hosted by Midwestern University, and we are appreciative of their support. It is because of these programs that we can continue providing Professional Development opportunities for our members.

As the end of the year quickly approaches, please keep in mind, if you are willing to work with the Community Outreach Committee there are many opportunities available during the Holiday Season. It would be wonderful if AzPA could host an Outreach Event. If you have any specific ideas, please let us know. For the committee’s first year, let’s create an event that could become a yearly tradition.

We still have our Volunteer Tree at the AzPA Office. If you have some spare time and want to help, please call the AzPA Office and let them know what you would like to help with, or how much time you would like to donate. We are also looking for two more Pharmacists to fill Board positions for District Directors in the Southwest and Southeast areas of the state.

We have had a busy quarter, and have more events planned for next quarter as well. We have the Southwest Clinical Pharmacy Seminar in February that will be held in Tucson in partnership with the University of Arizona and the American Society of Health-System Pharmacists (ASHP). Please save the date: March 22, 2016 - Pharmacy Day at the Capital where we meet with Arizona legislators and their representatives to discuss important issues to healthcare and pharmacy. We are always in need of pharmacist volunteers to represent AzPA at this event. Check our website often for new information. I hope you all have a safe and happy Holiday Season.

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

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February 19-21st, 2016

49th Annual Southwestern Clincial Pharmacy Seminar - Tucson

A two-day CPE seminar presented in partnership by The University of Arizona College of Pharmacy, the Arizona Pharmacy Association, and the AzPA Health-System Academy - the Arizona affiliate of ASHP. Dates and location to be announced soon.

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.

Saturday, April 23rd, 2016

APhA Pharmacy-Based Cardiovascular Disease Risk Management Program - Flagstaff

This certificate training program explores that pharmacist’s role in cardiovascular disease risk management. The programs teaches pharmacists the essential skills to successfully assess risk, promote cardiovascular disease prevention, and encourage patient adherence to therapy.

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.

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.

*** 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

Fall 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

Check Calendar for Updates azpharmacy.org/events View the Calendar page by category (CE events, on-demand programs, socials, committee meetings, etc).

Use the selection menu at the top of the page.

The Arizona Pharmacy Association is accredited by the Accreditation Council for Pharmacy Education as providers of continuing education.

Winter 2015 • ArizonA JournAl of PhArmAcy • 5

WELCOME NEW MEMBERS July 1 - September 31st 2015) RESIDENTS Elena Almada-Quijada Issouf Diallo Sylvia Do Stephanie Hart Helen Hwang Diana Tamer Juan Villanueva-Quirino Dominique Werge Silu Zuo TECHNICIANS

Dana Gross Shawn Hamon Shraddha Hungund Danielle Klise Julie Kosden Elizabeth Planeta Rebecca Reiter

ASSOCIATES Michael Corbitt Dan Day Jack Kain Geetha Kumaraswamy Bryan Martinka

PHARMACISTS Sara Badaglialacqua Brenda Benally Shelly Brown Alissa Carter Steve Firman Tiffany Gutierrez Kalie Heideman Joseph Hinton Michael Katz John Kraft Milva Malapo Mallory Minahan Elizabeth Nelson Dalys O’Connor Ethel Odiakosa Lilian Parisotto Rajal Patel Carol San Vicente Ray Wilson NEW PRACTITIONER Jenna Bittner Bibina Fonjong Lynn Koester Marti Larriva Keysha Ray Hector Roman Irina Yermolovich

NEW MEMBERS: Visit your Member Center to learn how to get more involved with AzPA. Located at www.azpharmacy.org

STUDENTS Jordyn Abrego Sarah Allen Edmund Antone Ranna Ardebili Paulina Belosludtsev Brianna Beluscak Kimberly Briones Timothy Celaya Gavin Chiles Cindy Cho Michael Choi Kindra Dao Catherine Duong Haider Faris Randall Flores Tyler Freed Jennifer Gutierrez Dennis Hawxby Robert Hernandez Mark Hoffman Jonah Horn Joseph Howdeshell Jamie Hudgens Dorothy Huynh Jan Jimenez Megan Johnson-Bacon Aaron Julien Tiffany Kim Xenia Kleinschmidt Maria Kovac Courtney Kruse Omema Kulsoom

Heather Lee Justin Lee Kyle Lee Ryan Lowe Tanya Luc Terra Lundgren Michael Luu Wendy Luu Megan Lychwick Rebecca May Stephen Merchant Andrea Miller Christen Nguyen Jessica Nicewonder Joanne Park Anthony Raviele Jenna Reynolds Corissa Roman Kyle Schaetzle Danica Serrano Neda Shirazi Sabrina Simrin Haleigh Slinker Megan Spragg Hannah Throckmorton Tan Tien Melanie Tschida Kristina Veloz Dylan Vo Keith Wiegand Lisa Winghart Kevin Wong Nicole Woods Alysse Wortmann Kelly Yiu

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

MESSAGE MEMBERS VIA AZPA PROFILE PAGE www.azpharmacy.org/messaging

Connect with your fellow AzPA members.

We encourage you to take advantage of in-person social events and conferences to meet and network with members. You may also send a fellow member a message via your AzPA profile. Login, then select Messages on the right hand side of our website (or go to azpharmacy.org/messaging). Click on Message a Member. This will allow you to search for the individual to send him/her a private message.

Use this tool to contact your Academy / Committee Chairs, network with others in your practice, etc.

Note: This option is limited to dues-paying members only.

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

Arizona Pharmacy Association

Advancing Pharmacy to Improve Healthcare

cheerS for VolunteerS!

We acknowledge the contributions of the volunteers who have made a difference for our organization.

Advancing Pharmacy to Georgina Rubal-Peace Grace Akoh-Arrey Improve Healthcare Thanes J. Vanig Kenneth Baker Holly Van Lew Lindsay Davis Kathleen Vest Jessica DiLeo Silu Zuo Shareen El-Ibiary Sophia Galloway Brooke Griffin Samantha Karr Kayla Kloc Robert Kronenberg Kate Murphy Elizabeth Pogge Erin Raney

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 2nd Wed of the month at 3pm 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

Winter 2015 • ArizonA JournAl of PhArmAcy • 7

Pharmacists Assisting Pharmacists of Arizona (PAPA) A Recipe for Sobriety

(originally published in TogetherAZ)

By Jim Corrington, Jr. LCSW, Director of Outpatient Services, Meadows Outpatient Center Having worked in the field of addiction treatment and behavioral health as a therapist and Director for 30 years, it has been my experience that everyone who follows the suggestions in the AA Big Book gets better, everyone. They are suggestions, similar to when I went skydiving. I jumped out of a plane at 10,500 feet and after one minute of freefall, the instructors, tugging on my side, “suggested” that I pull the ripcord. We all have choices.

A metaphor I like to use is the Tollhouse Cookie Recipe. Back in the ‘30’s Ruth Wakefield, living in a Cape Cod style house on the outskirts of Whitman, MA. in the “Tollhouse Inn,” (the original house built in 1709 charged passengers tolls for changing horses, meals, etc.) decided to add bits of chocolate to a cookie dough from an old Colonial Day recipe for Butter Drop Do cookies.

She thought the chocolate would just melt out of the cookie, but it didn’t — and they turned out delicious. In 1939 the Nestles Tollhouse cookie recipe was published and printed on all the bags of chocolate chips. Today, 76 years later, if we buy the ingredients listed on the bag of chocolate chips, and follow the directions exactly as they are written, we get great cookies every time.

That’s why I say there is a 100% recovery rate for people who follow the directions.

In the same year, 1939, the book Alcoholics Anonymous first edition was published. The AA Big Book says, “Clear cut directions are given showing how we recovered.” Page 29. It is simple. It is straightforward and “it works, it really does.”

This article is about how to get and stay clean and sober the rest of your life, one day at a time. Relapse does not have to be part of recovery. The problem arises when we hear, “But you don’t understand, my case is different.” If one believes this, the “recipe” doesn’t apply or work to them.

I always say to those who feel they’re different, “surely in the millions of people in long-term successful recovery in the world (23 million people in the U.S. alone in “long term successful recovery”) – (Anonymous People movie) there are people who have gone through nearly exact circumstances as yourself, applied the program of recovery outlined in the Big Book to their lives, received any outside help needed, and had the promises come true for them (each and every promise..pg.83).

I also remind folks of the Herbert Spencer quote in the Spiritual Experience Appendix of the AA Big Book: “There is a principle which is a bar against information, proof against all arguments, and cannot fail to keep a man in everlasting ignorance; that principle is contempt prior to investigation.”

In nearly every AA meeting in the world we read, “Rarely have we seen a person fail who has thoroughly followed our path. Those who do not recover are people who cannot or will not completely give themselves to this simple program.”

In addition to the Big Book of AA, there are many tools and skills required, (trauma work, family of origin work, psychiatric services) if practiced and utilized can guarantee great results in sobriety. The following is my interpretation of the “Recipe for Sobriety.”

Total Abstinence Most people who think they’re chronic relapsers are not. They simply have not given up their right to a chemical peace of mind. The first step means, I can’t have anymore — ever, one day at a time. And, no switching to another addictive drug. I get a sobriety or clean date, meaning I’m clean and sober.

The good news is one only has to do this a day at a time. This is AA’s most well-known slogan for a reason. I always say, “Just don’t drink or use before you go to sleep.” If you do that, you’ll die clean and sober at the end of a long run of sobriety.

The trick is, it appears difficult to stay clean and sober one day at a time, if one hasn’t given up their “right” to do a “little sumpin’ sumpin’ “ for life. The AA Big Book states, “We have seen the truth demonstrated again and again: “Once an alcoholic, always an alcoholic. Commencing to drink after a period of sobriety, we are in a short time as bad as ever. If we are planning to stop drinking, there must be no reservation of any kind, nor any lurking notion that someday we will be immune to alcohol.” (p.33) The most important ingredient in this recipe is to give up your right to drink and drug— for life….and then, immediately snap back in to just doing it One Day at a Time.

Don’t worry about the whole day, focus on this hour or minute, don’t drink or drug right now. If you not drink or drug

right now, you’ll stay sober the rest of your life, as it is always now.

There is a sign behind some bars that reads, “Free Drinks Tomorrow!” That’s the idea, give up your right to do it today — just for today. This is doable, isn’t it?

The common denominator that makes all alcoholics and addicts the same — is they think they’re unique. It’s the voice in your head saying your case is different — this kind of thinking can lead to disaster.

Here’s how it is explained in the AA Big Book, “Most of us have been unwilling to admit that we were real alcoholics. No person likes to think he is bodily and mentally different from his fellows.

Therefore, it is not surprising that our drinking careers are characterized by countless vain attempts to prove we could drink like other people. The idea that somehow, someday, he will control and enjoy his drinking is the great obsession of every abnormal drinker. The persistence of this illusion is astonishing. Many pursue it into the gates of insanity or death. We learned that we had to fully concede to our innermost selves that we were alcoholics. This is the first step in recovery. The delusion that we are like other people, or presently may be, has to be smashed.” (p.30) The Switches Switching from one thing to another. Many people get into trouble in early recovery because they reserve the right to take something, other than their drug of choice, to deal

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

with whatever is going on in their lives. There are hundreds of switches that have been tried: whiskey to beer, beer to wine, alcohol to marijuana, oxycontin to percoset, percoset to heroin, shooting cocaine to smoking it, smoking heroin to snorting it, pot to ambien, whiskey to soma, methamphetamine to Ritalin, Ritalin to Adderall, and Lunesta to marijuana. (A need to medicate feelings can manifest in process addictions as well).

There is a pamphlet: AA Members, Medications and Other Drugs. It is highly recommended to read. In the summary it states, “No AA member plays doctor,” and “consult a physician with demonstrated experience in the treatment of alcoholism.” Consult an addiction medicine MD (www.abam.net) American Board of Addiction Medicine Board Certified to treat addiction, and who is committed to the total abstinence model about what medications are safe to take. Some medications are lifesaving; others will change your sobriety date.

As far as products containing alcohol (C2H5OH), I say 0.000% is how much I can have in my body. There are many products that contain alcohol.

One also simultaneously recognizes that we don’t have the “power” to stay away from alcohol/other drugs on our own…..we are “powerless” against the first drink/drug alone. That power must come from a “Higher Power” (God).

Find the Right Meeting There are numerous 12 step groups (AA, PA, NA, CA, HA, etc.). When people tell me they didn’t like a meeting they tried I believe them. There are meetings that aren’t right for everyone. It is imperative to search them out until one feels right. We should feel a sense of hope, and experienced a solution to our problem. Keep attending until one fits. It is important, eventually to attend meetings where you will find identification.

READ THE FULL ARTICLE www.azpharmacy.org/recipeforsobriety Reprinted with permission togetheraz, October 2015 Jim’s personal recovery from addiction and trauma began 30 years ago, and he brings strong passion to the process. He is very active in his personal 12step program. Jim earned his Master’s Degree in Social Work at The University of Maryland. He has been in the recovery field as a Director/Therapist for outpatient programs for 28 years during which time thousands of patients and families have been treated in his IOP programs. He has also spent 15 years working with the Arizona Medical Board and Arizona Board of Pharmacy monitoring programs running weekly Relapse Prevention groups for impaired professionals. In addition, as a former athlete, Jim also has extensive experience working with impaired professional athletes. Jim believes recovery and miracles happen every single day. For more information about programs offered at The Meadows, visit www. themeadows.com or call 800-244-4949.

Winter 2015 • ArizonA JournAl of PhArmAcy • 9

LEGISLATIVE UPDATE 2016 Legislative Session Immunization Expansion:

In 2009, legislation was enacted permitting pharmacists to immunize adults 18 years and older without a prescription. However, Arizona pharmacists are still limited in their ability to immunize children ages 6-17, requiring a prescription order for all vaccinations except influenza. The need for children ages 6-17 to have a prescription order for any vaccination, other than influenza, is a significant barrier to improving vaccination rates. AzPA is supporting a legislative initiative to expand Arizona pharmacists’ immunization abilities.

Help support the Immunization Expansion Initiative. Contribute to the Pharmacists Political Action Committee of Arizona (PharmPAC). www.azpharmacy.org/PharmPAC Fair Audit & Generic Pricing

Well over 30 states have passed legislation to create standards for pharmacy audits. These statues create, among other things: notice requirements; establish periods of time such audits can go back; prohibit “extrapolation” (assuming an error rate for a small audit sample applies across all prescriptions and thus rescinding payment). Maximum Allowable Cost (MAC) pricing is the methodology payers use to reimburse network pharmacies for generic drugs. Payers often times do not use uniform methods or criteria for updating MAC prices.

Residency PGY2 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. AzPA is looking to change the requirement of reciprocity to six months instead of one year.

All AzPA members are welcome to attend the monthly meetings. If you are interested in joining the discussions, contact Mark Boesen, Legislative Committee Chair at legislative@azpharmacy.org or Kelly Fine (Ridgway), AzPA CEO at kelly@azpharmacy.org

1 ADMISSION

P������� D�� �� ��� C������ March 22nd, 2016 Arizona State Capitol Senate Lawn

Meet with AZ legislators and discuss healthcare issues in the state.

RSVP azpharmacy.org/PDAC2016

AzPA Federal & State Law Review (Bundle) Available on-demand Federal Pharmacy Law Part 1 (0.45 CEUs) Arizona Pharmacy Law Review Part II (0.45 CEUs) Registration is available online only at: azpharmacy.org/ Pharmacy_Law $200 for AzPA members

Pharmacy Law Update On-Demand Webinar

Presented by Kenneth R. Baker, BS Pharm, J.D. $15 AzPA members

Review areas of federal and state pharmacy law and risk management. Accredited for pharmacists and pharmacy technicians.

ACPE accredited for 1.5 hours (0.15 CEUs) 0100-0000-15-079-H03-P; 0100-0000-15-079-H03-T Initial release date: 09/26/2015 Planned expiration date: 09/26/2018

azpharmacy.org/event/LawWebinar Mark Boesen AzPA Legislative Affairs Committee Chair legislative@azpharmacy.org Jeff Gray, R & R Partners AzPA Lobbyist

TECHNICIAN SPOTLIGHT A Case Study in Realized Potential: Christopher Fuentes

by Kalani Anderson, C.Ph.T

Case study: A 13 year old Hispanic male, who has always excelled at math and the sciences, enters 8th grade at the beginning of a new school year.

His aptitude and interest in the subject is apparent from the first day. No one in his family has ever attended college, which can be a challenge when embarking on a career in the sciences.

Christopher Fuentes started out on a process of exploration that opened his eyes to the possibilities of his future. He soon discovered pharmacy and has never looked back as he moves toward his goal of becoming a pharmacist and potentially owning his own pharmacy.

Chris now works as a technician-in-training at the Medication Management Center (MMC), at the University of Arizona in Tucson, where he is learning the ins and outs of the work of a pharmacy technician and gaining exposure to other roles and the work that goes on in a pharmacy. He is preparing to sit for the Pharmacy Technician Certification Board Exam, studying on his own and learning from his colleagues and experiences at work. He plans to sit for the exam and become certified in 2016. Besides simply enjoying the science behind his work, he finds it fulfilling because of the variety of ways he is able to help people, from updating a medication list to simply listening to a patient. Early in his time at the MMC he recalls speaking to an older woman who was clearly going through a hard time in her life. By the sound of her voice he recognized a sense of sadness and a need to be heard. So he listened to her. By the end of the call, her voice was more upbeat, and he knew he had made a difference just by listening and being polite.

His work provides valuable practical experience that complements his continued studies. As an essential step in his goal to becoming a pharmacist, Chris successfully became the first in his family to attend college when he joined the University of Arizona’s Public Health program in 2014. Along with rigorous academic work, he is actively involved in extracurricular activities; participating in the Pre-Pharmacy Club, the Spanish Heritage Club, and even intramural basketball.

This last summer he participated in the Global Student Embassy’s volunteer program and spent 12 days in Nicaragua, volunteering in community gardens as well as shadowing doctors and pharmacists at a local clinic

called Clínica Verde. Experiences like this have expanded his perspective and deepened his understanding of people he may serve as a pharmacist.

His ability to listen and work well with patients is highly valued by his employer. Martin Pelger, lead pharmacist at the MMC, says that “Chris is able to quickly develop a great rapport with the many patients he speaks to throughout the day. This is vital because our business model is built upon great customer service.” Chris recognizes that communication (both listening and speaking up) is critical to creating a positive work environment. It helps keep people on the same page and makes everyday operations run smoothly. He appreciates the monthly staff meetings at his work where each voice is heard and everyone has a chance to evaluate together the things that have and have not been working.

Along with such formal methods for communication, he has found that simply getting to know your co-workers is valuable in helping the flow of communication. To this end, he can occasionally be found playing softball and according to Martin Pelger makes a “slick third baseman.”

Whether on the softball diamond, in a science class, or in the pharmacy, Chris is a class act and a trailblazer that will go far. Contact Chris at fuentes@pharmacy.arizona.edu.

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

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.

Certification Excellence 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:

Winter 2015 • ArizonA JournAl of PhArmAcy • 11

PHARMACIST SPOTLIGHT Profile: Hal Wand, RPh

by Carl Labbe, RPh

Pharmacists have many different ideas of what retirement should look like. There may be time for new and old hobbies, domestic and foreign travel, checking off bucket list items, and plenty of leisure. For Hal Wand, retirement from the Arizona Board of Pharmacy after 26 years of service means continued dedication to our profession, with many of those retirement goals still possible, including fun times rolling along in the Airstream. In 2003, Hal became the Executive Director of the Arizona State Board of Pharmacy (ASBP) and his leadership has created one of the best pharmacy practice environments in the world.

Always true to the mission of protecting the patients, Hal’s positive and progressive vision has always forged partnerships that include patients, pharmacists, other health care providers and the ASBP. That vision maintains the public safety aspect of the Board’s mission, while its enforcement is reasonable and judicious. Hal has said many times, “We want results that are a win for everybody.” That attitude has helped make Arizona a leader in pharmacy practice and has attracted many companies that appreciate a regulatory climate that fosters innovation.

In his “retirement”, Hal continues to serve the profession as President-elect of the National Association of Boards of Pharmacy (NABP). Some readers might not realize that the NABP is international, with member boards from Canada, Australia, New Zealand, and US territories. As President, Hal will continue to work with other boards to ensure safe and effective models for pharmacy in a wide variety of practice settings in many parts of the world. As more pharmacy businesses expand globally, it is essential that NABP continues to be a lead regulatory architect of patient-focused pharmaceutical care.

Carmen Catizone, Executive Director of the NABP, who has known and worked with Hal for over 20 years, has a deep appreciation for Hal’s thoughtful approach to leadership. Director Catizone indicated that he relies on Hal and his “open and innovative approach to finding solutions,” and looks forward to Hal’s year as President of NABP when he will be “the face of the NABP” in this important time for pharmacy here at home and around the world. Carmen believes that he has convinced Hal that there is another worthy baseball team in Chicago other than his beloved Cubs, but that was not confirmed by Hal. Hal’s continuing journey has been one of significant accomplishments beginning with a degree in Biology from Cal State Northridge followed by graduation from the University of Arizona pharmacy program in 1979. Choosing the U of A College of Pharmacy (COP) was fortuitous for Hal, the college, and the state of Arizona. It was there that Hal discovered that being director of the ASBP was his career goal and where he became a true Wildcat, strong supporter of the University as a sports fan, and the COP as a pharmacy advocate. Love blossomed between Hal and, U of A alumna and pharmacist, Marilyn Fruth, when working together at Phoenix Baptist. They married in 1977 and are living happily ever after.

Hal Wand loves pharmacy and continues to serve the profession with his wisdom, compassion, integrity, and leadership. He is truly one of pharmacy’s pioneers and his dedication and love are demonstrated in words and deeds.

Hal Wand and family outside of the Westin La Paloma Resort & Spa in Tucson, AZ during the AzPA 2015 Annual Convention.

SPECIAL CONTRIBUTIONS Clinical implications of latex allergies in vaccination

By: Megan Handley, Pharm.D.

The role of pharmacists in preventive medicine is continuously expanding; this expansion is largely due to pharmacists’ ability to administer vaccinations. Pharmacists are easily accessible to patients interested in obtaining vaccines and/or learning more about available vaccinations. A common topic of discussion in regards to vaccination is latex allergies. The American Latex Allergy Association reports less than 1% of the general population in the United States has a sensitivity to natural rubber latex (about 3 million people); additionally, 8-17% of health care workers have this sensitivity. Latex gloves are utilized less frequently in health care settings due to increasing prevalence of latex allergies in patients and health care professionals; however, gloves are not the only concern when it comes to vaccinating latex-allergic patients. Latex derivatives are often used to make products such as medication vial stoppers and syringe plungers of vaccinations.

Latex is the milky fluid obtained from tapping the rubber tree, Hevea brasiliensis. Substances made with latex or its derivatives are often labeled as containing: natural rubber latex, dry natural rubber, synthetic latex, or synthetic rubber; these are all forms of natural rubber and may cause an allergic reaction in those with a latex-sensitivity. A full spectrum of symptoms may manifest in an IgE-mediated reaction to latex including: localized pruritus and urticaria after skin contact, rhinitis and conjunctivitis from aerosol exposure or direct facial contact, systemic reactions such as bronchospasm and hypotension after significant exposure or in extremely sensitive individuals, or even shock leading to fatal cardiovascular events. Avoiding exposure is the cornerstone of treatment for latex allergies. Latex-allergic individuals and their health care providers must be continuously vigilant for hidden sources of exposure; such as components of vaccines. Those with a history of a systemic reaction to latex should not be given vaccinations that have been in contact with any form of natural rubber.

All patients being administered vaccinations should be asked if they have an allergy to latex. If a latex allergy is reported, the nature of the allergy should be documented.

There are several references that can be utilized to determine if a vaccination contains a derivative of latex.

The packaging, for instance, is required by the FDA to state: “Caution: This Product Contains Natural Rubber Latex Which May Cause Allergic Reactions” if there is latex in any component of the product. In addition, the package insert can be referenced. The necessary information can be found in the insert in multiple sections including: the “Warnings and Precautions” section, the section regarding prevention and management of allergic reactions, and the description of the components present in the product. Another source to determine whether a vaccine has come into contact with a latex derivative is the Center for Disease Control and Prevention website. They have a list titled “Latex in Vaccine Packaging” that identifies which vaccination brands and formulations contain latex. The list is updated regularly and is a quick reference source. The package insert should still be checked if doubt remains. During administration of any vaccine, providers should be prepared to recognize and treat an allergic reaction. Epinephrine should be readily available in case it is needed. *The following are directly from the Fluvirin package insert to demonstrate where readers may look to find the necessary information regarding the latex content of the product.

WARNINGS AND PRECAUTIONS • If Guillain-Barré syndrome has occurred within 6 weeks of receipt of prior influenza vaccine, the decision to give FLUVIRIN® should be based on careful consideration of the potential benefits and risks. (5.1) • Immunocompromised persons may have a reduced immune response to FLUVIRIN®. (5.2) • The tip caps of the FLUVIRIN® prefilled syringes may contain natural rubber latex which may cause allergic reactions in latex sensitive individuals.

5.3 Preventing and Managing Allergic Reactions Winter 2015 • ArizonA JournAl of PhArmAcy • 13

Latex allergies continued...

Prior to administration of any dose of FLUVIRIN®, the healthcare provider should review the patient’s prior

immunization history to identify possible adverse events, to determine the existence of any contraindication to immunization with FLUVIRIN®, and to allow an assessment of benefits and risks.

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine. The tip caps of the FLUVIRIN® prefilled syringes may contain natural rubber latex which may cause allergic reactions in latex sensitive individuals.

Carton Fluvirin Product Presentations Presentation NDC Number Pre-filled syringe 66521-117-02

Multi-dose vial

66521-117-10

Components 0.5 mL single dose pre-filled syringe, package of 10 syringes per carton (may contain latex) [NDC 66521-117-12] 5.0 mL multi-dose vial, individually packaged in a carton (contains no latex) [NDC 66521-117-11]

Acknowledgement: Courtney Pawula, Pharm.D., BCPS Clinical Pharmacist, Phoenix VA Health Care System

501(c)3 charitable non-profit supporting Pharmacy Awareness & Education

Pharmacy Time Capsules Fourth Quarter 2015

1990 - Twenty-five Years ago: • There were 174,000 pharmacists in US • 31% of actively practicing pharmacists are women according to a study in JAPhA 1965 - Fifty Years ago: • The average cost for a prescription was around $3.50 according to 1965 Lilly Digest ($26.34 in 2015) • Older American Act passed. Services to the aged include disease prevention/ health promotion services 1940 - Seventy-five Years ago: • Lilly Digest reported that 13% of pharmacies in the 1940 survey were operating at a loss. An additional 12% had less than 2% net profit • Woodruff and Waksman isolated and purified actinomycin from Actinomyces griseus

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.

Spot the giving hand at an upcoming AzPA event and donate unwanted gift cards to the Arizona Pharmacy Foundation.

Or send gift cards in the mail.

1845 E. Southern Ave, Tempe, AZ 85282 Learn more azpharmacy.org/giveagiftcard

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.

Delivering the Prescription

By Don R. McGuire, Jr., R.Ph., J.D. A lot has been written about quality processes in the dispensing function and many good ideas are out there; the Two Dosage Unit rule, shelf talkers, NDC checks, etc. But one thing that isn’t often talked about is getting the right prescription to the right patient. All of the safety and quality processes go for naught if the prescription is given to the incorrect patient. Consider these two examples.

Tom Smith comes into Anytown Pharmacy to pick up his wife’s prescription. In the will-call bin with her prescription was also one for Ron Smith. The technician thought Tom had said Ron and assumed that the second prescription was his.

She gave Tom both prescriptions. The error was discovered when Tom returned home.

Paul was making a delivery for City Pharmacy one afternoon and pulled into a driveway shared by 101 and 103 Main Street. Mary was standing in the driveway. “You got here just in time; I’m headed out for my doctor’s appointment.”

Paul ignored his normal protocol at the insistence of the patient. He gave the prescriptions to Mary who left for her appointment. Paul discovered later that the prescriptions were for a patient who lived at 103, but Mary lived at 101.

Many times pharmacists don’t think about the actual hand-off to patients. They would be surprised to learn what happens at the delivery point. For example; patients step forward when someone else’s name is called, patients or staff hear names incorrectly, patients with the same or similar names appear at the pharmacy at the same time, or patients in the same extended family with the same name utilize the same pharmacy. Unfortunately, claims history tells us that these patients are very likely to take the medications that they go home with or get delivered to them. This occurs even when their name isn’t on the label, they have never heard of the drug or their own doctor’s name is not on the prescription. Also unfortunately, juries are less inclined to place blame on the patient for these sorts of mishaps. Fair or not, the responsibility falls on the pharmacy to get the right medication to the right patient. A number of solutions are available.

Previous articles have extolled the value, to both the patient and the pharmacist, of patient counseling. This article won’t repeat all of those benefits, but patient counseling is an effective tool to discover errors at the time of delivery.

But patient counseling is not always needed or required, so we need other tools. Asking the patient to produce identification and requiring the staff to review prior to handing over the medications is one method. Others have asked the patient for a second identifier to differentiate patients with similar names; address, phone number or social security number. This has to be done as discreetly as possible to protect the patient’s privacy. It is also helpful to ask additional questions of persons picking up others’ prescriptions; what is their relationship to the patient or ask some of the secondary identifiers above. Delivery drivers should never deviate from their protocols and should verify the address and identity of the patient when delivering medications. Date, time and to whom the medications were delivered should all be documented.

Most of the time, delivery to the patient is not a problem, so little attention is paid to it. But, ignoring this step of the dispensing process creates a weak point in the pharmacy’s overall quality initiative. History shows us that patients will take whatever medication is given to them, even when it makes no rational sense to do so. It is essential that this final step in the dispensing process gets the same attention as other steps in the process. Once the medication is in the wrong hands, it is impossible to predict the outcome. © 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.

Winter 2015 • ArizonA JournAl of PhArmAcy • 15

STUDENT PERSPECTIVE: Ambulatory Care Pharmacy

By Omema Sultan, Pharm.D. Candidate 2016, Concordia University Wisconsin Ambulatory care pharmacy, which has been expanding and making health care more convenient for patients, is a relatively new addition in the field of pharmacy. According to the Report of the Role Delineation Study of Ambulatory Care Pharmacists, ambulatory care has five domains of practice including: direct patient care, practice management, public health, medical informatics and professional development and patient advocacy. Pharmacists are now playing a larger role in providing direct patient care, medication management, and patient education. Ambulatory care pharmacists work in a variety of environments, each with its unique practice style, including clinics, hospitals, accountable care organizations, and medical homes.

Before starting my ambulatory care rotation, I was not aware of the pharmacist’s role and their impact on patient care in this particular setting. On my ambulatory care rotation with Dr.Virginia Boomershine at the Palomino Health Center, I learned how the combination of evidence- based diabetes care, knowledge of current diabetes concepts and the standards of care, compassion, and dedication make a difference in patients’ lives. Palomino’s medical team includes a nurse practitioner, pharmacist, dentist, care coordinator, behavioral health consultant, and medical assistants. Together they provide affordable healthcare to individuals and families who have little to no access to basic medical needs.

Palomino is one of the NOAH (Neighborhood Outreach Access to Health) clinics. NOAH, founded in 1997, is a non-profit organization affiliated with Honor Health dedicated to improving health and quality of life through a wide range of disease prevention and management programs and services addressing the medical, dental and behavioral health of their communities. This rotation was an excellent opportunity to apply my clinical knowledge of the guidelines, pharmacology and pharmacotherapy, which I learned in pharmacy school, to direct patient care.

Evidence-based care, including the use of the most up to date guidelines, and relevant clinical trials when applied to patient care, has demonstrated improved clinical outcomes in ambulatory practice. The thoughtful, systematic approach to patient care is most exemplified by the example of Dr. Boomershine’s approach to looking for other causes for increased blood glucose rather than reflexively increasing a patient’s insulin dose. This includes evaluating patient adherence, access to medications, nutrition, and understanding of blood glucose goals. In this way, the ambulatory practice acts to help manage patients as a whole. A multidisciplinary team is employed at the ambulatory clinic to assist in patient care, and help patients with nutrition management, behavioral health, adherence and access to medications.

Another example of using a team-based approach to carry out evidence-based medicine in a compassionate, thoughtful manner was of an anxious patient with family issues. Dr. Boomershine identified the patient’s anxiety and social problems as barriers to optimal diabetes management. She confronted the adherence barrier by referring the patient to behavioral health, in addition to counseling the patient on the importance of medication adherence. Patient education provided by Dr. Boomershine is unique to each patient and tailored to their individual needs and habits. The therapeutic recommendations are based on guidelines (ADA or AACE/ACE), but it requires taking smaller steps over the span of multiple patient encounters to reach the goals of therapy. Another strategy used by the clinic to help increase medication adherence includes, providing weekly pillboxes to patients thereby, simplifying their medication administration, or prescribing medication based on patient’s preferred route.

Comprehensive pharmacy visits at Palomino also include preventative health such as monitoring lipids, ensuring foot, eye, and dental exams, and immunizations are up to date. This ensures that the patient is achieving healthcare standards for improved health. This being said, although the clinic employs multiple techniques to ensure superior healthcare for their patients, it is ultimately up to the patient to accept and follow through with treatment recommendations. I believe this is not only a limitation to this ambulatory practice but to any healthcare practice in the world.

Our healthcare system places an increased focus on chronic disease management, and prevention, and this ambulatory care practice provides a unique and fulfilling opportunity for pharmacy students and PGY1 residents that would like to provide this kind of care to patients, not only at Palomino, but in the multiple ambulatory clinics that comprise NOAH. As a fourth year pharmacy student, I would like to see our profession advance in this field of practice, providing superior, meaningful care to patients. It was truly an amazing experience to see Dr. Boomershine and her pharmacy staff making a huge advancement in this field of practice for pharmacists by improving accessibility to quality healthcare for the underserved population of Phoenix. Using this model, the health care services that ambulatory care pharmacists provide can relieve the burden on primary care physicians, save our healthcare system billions of dollars, and most important improve our patients’ health.

FEATURES Review of Hypersensitivity Reactions with Classic Cytotoxic Agents

By: Andrew Garcia, Pharm.D. Candidate 2016, University of Arizona College of Pharmacy; and Ali McBride, PharmD, MS, BCPS, Clinical Coordinatory Hematology / Oncology for the University of Arizona Cancer Center

Introduction:

Hypersensitivity reactions (HSRs) can occur during the infusion of chemotherapy agents. These reactions can be immediate, often starting within minutes of administration, but may also have delayed consequences with latent reactions. Several classical chemotherapy groups such as taxanes, platinum agents and epipodophyllotoxins, are known to be commonly associated with these reactions (Table 1).1 Symptoms that present during an infusion reaction may have similar manifestations within classes, but may also differ based on variability among patients. Common symptoms range from mild or moderate severity, such as flushing, itching, fever, and chills, to more severe reactions such as respiratory arrest, cardiogenic shock, seizures, and others that can ultimately lead to death. Management tactics depend upon the severity of the reaction and the administered chemotherapy agent. Strategies for managing reactions often include altering premedication, adding additional agents and adjusting infusion rates. In this review we will outline the most common hypersensitivity reactions, their incidence, clinical features, etiology (if known), and management of reactions.

Taxanes: Overview and Incidence: The taxanes are a chemotherapeutic class that inhibit microtubular disassembly, and thus prevent mitotic turnover in a variety of solid tumor cancers, including breast, ovarian, lung, bladder, prostate.1 Notable agents that are associated with HSRs include paclitaxel and docetaxel. Ranges in the literature suggest that incidence of reactions for patients receiving taxanes is 0.7-10.6% for paclitaxel and 0.8-25.3% for docetaxel.1–6 Clinical Features: Clinical features of HSRs to taxanes include flushing, chest, back or abdominal pain, respiratory symptoms, abdominal symptoms (i.e., diarrhea and/or vomiting), and cardiovascular symptoms such as acute hypertension or hypotension.2 Studies have found some reactions to be more common with certain agents, such as desquamative rash (shedding of the outermost layer of the skin) with use of paclitaxel, and plaque-like erythrodysesthesia (tingling sensation of palms and soles progressing to severe tenderness with erythema and edema) with use of docetaxel. Delayed-type FEATURES

hypersensitivity reactions such as Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson’s Syndrome (SJS) have also been reported.2 Table 1: Incidence of patients experiencing HSR

Drug Taxanes Paclitaxel Docetaxel Platinums Cisplatin Carboplatin Oxaliplatin Epidophyllotoxins Etoposide Teniposide L- Asparaginase

% Incidence reported 0.7 – 10.63,6 0.8 – 25.36 0 – 246 0.8 – 506 0.7 – 246

1 – 516 6.5 – 521 3 – 4528–30

Etiology: The mechanism of taxane induced HSRs remains to be established, although different etiologies have been suggested for each agent. For paclitaxel, there are three proposed mechanisms by which HSRs develop: (1) complement activation induced by cremophor, a common formulation vehicle used for poorly water soluble drugs, (2) histamine release through a direct but undefined effect of paclitaxel on basophil cells or (3) an IgE/IgG-mediated mechanism directed against either the taxane or cremophor EL, a surfactant used in many taxane compounds such as paclitaxel. The surfactant has been shown to cause histamine release from mast cells upon exposure, prompting the use of histamine H1 and H2 antagonists as a premedication combined with glucocorticoids for the prevention of HSRs prior to the administration of paclitaxel.4,7 For docetaxel, studies have pointed towards elements in the injectable formulation, specifically the surfactant vehicle polysorbate-80 and ethanol, as the main factors contributing to development of HSRs, which has prompted the development of non-injection delivery systems to limit the necessity for the polysorbate-80 based formula.8 Prevention: Due to insufficient knowledge regarding pathogenesis of taxane HSRs, a greater array of management strateWinter 2015 • ArizonA JournAl of PhArmAcy • 17

Platinum compounds: Overview and Incidence The platinum compounds include the agents cisplatin, carboplatin, and oxaliplatin. These drugs are commonly used in the treatment of testicular, ovarian, lung, breast, cervical, stomach, colon, rectal, and prostate cancers, with oxaliplatin specifically being used for treatment of metastatic colorectal cancer, breast cancer, melanoma, and non-Hodgkin’s lymphoma.1 Cisplatin has numerous adverse events that are characterized by neurotoxicity, nephrotoxicity, ototoxicity, and emetogenicity.12 Carboplatin has a smaller adverse event profile overall in comparison to cisplatin, yet does have increased thrombocytopenia compared to cisplatin.

Oxaliplatin has adverse events such as myelotoxicity, nausea and vomiting, diarrhea, paresthesias, and dysesthesias.

Severe anaphylaxis has been observed with use of these drugs, but in case reports rather than in trials.12 HSRs to the platinum compounds have been reported to be between 0-24% for cisplatin, and 0.8-50% for carboplatin, and 0.724%% for oxaliplatin.6 Cisplatin HSRs typically start within minutes of infusion, mostly between the 4th and 8th course, and increased FEATURES

severity with concomitant radiation. Oxaliplatin HSRs occurs within minutes to hours from infusion, mostly after the 6th course, and low incidence of grade 3-4 reactions.

Characteristics of carboplatin adverse reactions warrant a larger explanation, since this typically has the highest incidence of the three. Incidence is approximately 44% in scenarios where it is used as a 3rd line option for treatment, such as after a patient has failed treatment with PCV (lomustine/procarbazine/ vincristine) or temozolamide.12 Carboplatin HSR is rarely observed during the first course of treatment, with a reported incidence of 1%. The incidence of HSRs increases during the sixth cycle of treatment, at 6.5%, and has been seen to be as high as 27% in patients that receive more than seven cycles of treatment.12,13 The most common incidence occurs after eight infusions, but these are usually mild grade 1 and 2 reactions.12 The more severe grade 3 and 4 reactions often are seen after the sixth infusion cycle, but these types of reactions are more rare, occurring in about 1.6% of patients (Table 2).12 Table 2: Incidence of Carboplatin/Taxane HSR per Reaction Cycle47

Percent of Patients

gies exist for this chemotherapeutic group. Chemotherapy regimens that are taxane-based require premedication prior to administration of the drug, including corticosteroids such as dexamethasone, and histamine H1/H2 antagonists such as diphenhydramine and famotidine.1,2 One widely adopted method is to modify the regimen to allow a single intravenous or oral 10mg dexamethasone dose 30 minutes prior to administration of paclitaxel. The utilization of premedication has resulted in a marked decrease of immediate HSRs versus the standard two-dose dexamethasone protocol that was used prior to the infusion and with steroids 30 minutes before administration.2,9 One study of 183 patients pretreated with single-dose intravenous dexamethasone found this strategy to be particularly useful to deal with hypersensitivity.9 Studies examining docetaxel management protocols have further supported the benefit of premedication such as dexamethasone to reduce the incidence of edema and/ or HSRs.10 Some clinicians have attempted to rechallenge patients with initial infusion reactions against taxanes with moderate success. A recent phase I trial of paclitaxel sponsored by the National Cancer Institute, in which a cohort of 27 patients were retreated after experiencing immediate HSRs demonstrated this strategy. Outcomes included seven cases in which subsequent paclitaxel infusions were tolerated, eleven cases of recurrent HSRs, and one death.11 Generally, any severe non-immediate HSRs such as SJS/TEN should warrant discontinuation of the drug, although some data defend that safe reintroduction might be possible with the use of desensitization protocols.2

70% 60%

50% 40%

Carboplatin

30% 20% 10% 0%

Taxanes 1

2

3

4

5 6 Cycle Number

7

8

9

10+

Risk factors for platinum HSRs should be reviewed prior to drug administration. Such factors include prior history of allergy to drugs, female gender, and environmental exposure to platinum-containing compounds.12 Risk factors noted in the literature have also included combination chemotherapy regimens that may cause development HSRs. HSRs reported in combination most commonly occur with carboplatin/paclitaxel compounds rather than with pegylated liposomal doxorubicin (PLD).12 In oxaliplatin regimens, young age, female sex, and use of the platinum compound for salvage therapy have been recognized as risk factors.12 Clinical Features: Clinical features for platinum HSRs vary, with mild to more severe symptoms having been reported. Many of these reactions develop acutely, during the infusion or within minutes, hours, or days following infusion. Mild HSRs can include development of a rash. More severe reactions can include urticaria, flushing, palmar itching, burning, peripheral edema of the face and hands, abdominal cramping, diarrhea, back pain, and pruritis.12 The most severe manifestations include bronchospasm, tachycardia, hypotension, hypertension, seizures, and chest pain.12 1

Etiology: Although it is currently unclear regarding which mechanism of hypersensitivity is attributed to platinum HSRs, many sources point toward an IgE-mediated mechanism. This is in part defended by the occurrence of early-onset symptoms such as itching, chest pain, rash, and anaphylactic reactions in reports of exposed refinery workers.14,15 Other HSRs have also been observed, such as type IV delayed HSRs due to reactions occurring hours or even days after administration of chemotherapy and type-II HSRs due to the presence of thrombocytopenia and hemolysis in oxaliplatin treatments.12 Type III HSRs have also been implicated, due to the presence of chronic urticarial symptoms, joint pain, and proteinuria following oxaliplatin administration.12 Prevention: Classic strategies to reduce frequency and severity of platinum-mediated HSRs include lowering infusion rate and premedicating with dexamethasone, chlorpheniramine, and ranitidine. These strategies have allowed successful readministration of the platinum agent in some cases. In several studies of patients with relapsed ovarian, fallopian tube, or primary peritoneal cancer being retreated with platinum compounds, it has been shown that slowly increasing the infusion rate by 1%, 9%, and 100% at hours 1, 2, and 3 respectively, along with appropriate premedication, may reduce hypersensitivity reactions in comparison to standard 30-minute infusions.12,16

Epipodophyllotoxins: Overview and Incidence The epipodophyllotoxins include the agents teniposide and etoposide. Etoposide is often used for treatment of testicular, bladder, prostate, lung, stomach, uterine, and brain cancers, and teniposide for acute lymphocytic leukemia and neurological malignincies.1 Incidence of HSRs with use of epipodophyllotoxins has been cited as 1-51% for etoposide and 6.5-52% for teniposide.1,6 One study involving 108 children with acute lymphoblastic leukemia found HSRs incidence to be around 46% with these two drugs.17 Between cancers, incidence of teniposide HSRs has been determined to range from 6.5% in brain cancer patients to 41% in children with leukemia.18 The official incidence of hypersensitivity from the Food and Drug Administration’s insert for Vumon (teniposide for injection) however, is around 5%, though this may be due to conflicting data about what is considered a true HSR to teniposide as opposed to another type of infusion reaction.19 Clinical Features: Most reactions associated with teniposide are of grade 1 or 2 severity, appearing within the first few minutes of infusion to hours after administration. The clinical characteristics

for the two drugs are similar, with reactions such as urticaria, flushing, and chills being most common, with severe reactions such as bronchospasm and hypotension occurring less commonly in a rate dependent fasion.1,17,20,21 Etiology: The cause of infusion reactions is not well understood, but many studies point towards Cremophor EL or polysorbate 80, the two intravenous solvents for teniposide and etoposide respectively, as the causative agent.22,23 Oral etoposide has not been associated with HSRs, indicating that the solvent may be what causes HSR to these agents.20,24 It is important to note that some studies suggest that epipodophyllotoxins may cause HSRs independent of solvent. In one study, Nolte et al demonstrated that in sensitized individuals exposed to teniposide and Cremophor EL, teniposide caused basophil degranulation, while Cremophor did not.25 In addition, cross-sensitivity between teniposide and etoposide have been reported, despite being dissolved in different solvents.26 There is debate regarding the mechanism of HSR to epipodophyllotoxins, with acute reactions being suggestive of a non-antibody mediated, while reactions after several doses are consistent with an antibody-mediated allergic reaction.20 This later observation was noted in a study by Kellie et al, where patients being treated for acute leukemia were more often seen to develop HSRs to teniposide when cumulative dose increased.17 Prevention: Intensified premedication with histamine blockers and slow infusion rates have been shown to decrease the risk of further hypersensitivity reactions upon rechallenge with epipodophyllotoxins.22 Slow infusion is particularly important in reducing the chance of severe hypotension.20 Previous exposure is an important risk factor for increasing the likelihood for developing HSR, so this should also be considered in determining a course of treatment.20 Due to the higher incidence of HSRs to teniposide than with etoposide, switching to teniposide is not recommended for people who experience HSRs to etoposide.22,27

Asparaginase: Overview and Incidence: L-asparaginase is an antineoplastic agent used in the treatment of acute lymphoblastic leukemia (ALL). There are three types currently approved for ALL treatment: Native E. coli asparaginase and Polyethylene glycol (PEG)-asparaginase, which are both derived from the same bacteria, and asparaginase Erwinia chysanthemi, Winter 2015 • ArizonA JournAl of PhArmAcy • 19

which is derived from an alternate bacterial source.28 Overall incidence of HSRs to L-asparaginase is reported to be around 3-45% of patients after intravenous infusion.28–30 Some sources have even reported it to be as high as 75%.31 Native E. coli asparaginase has the highest incidence between the three, with around a 5-60% incidence. This is followed by PEG-asparaginase, from around 3-24%, and then asparaginase Erwinia chysanthemi at 6-33%.28 Clinical Features: Immune reactions to L-asparaginase are classified into two general categories: clinical hypersensitivity and subclinical hypersensitivity.28 HSRs to L-asparaginase typically include a variety of mild to severe symptoms. Mild to moderate grade 1 and 2 reactions include flushing fever, chills, rash, pain around the injection site, and dyspnea.28 Severe grade 3 and 4 reactions typically include bronchospasm and acute anaphylaxis.28 Etiology: Asparaginase is derived from bacterial origin, so an immune response may be initiated based on the foreign nature of the enzyme.28 Polyethylene glycol (PEG) conjugated form of L-asparaginase has greatly reduced the likelihood of reactions compared to administration of native L-asparaginase, do occur.28 The mechanism is thought to be IgE-mediated, though this has not been fully established. Some researchers have also discovered increases in IgG-specific L-asparaginase antibodies in children experiencing hypersensitivity reactions, which may explain the development of clinical allergy following asparaginase administration in patients.1,28,31,32 The occurrence of these anti-asparaginase antibodies can result in reduced asparaginase activity, necessitating the importance of quick management for the development of HSRs.33,34 Prevention: Since reactions can be sudden, patients are usually observed within the first hour of chemotherapy to identify any signs of hypersensitivity.28 Due to the differences in half-life between L-asparaginase and PEG-asparaginase, reactions may occur hours after infusion.28 Performing an intradermal skin test is common to perform before initial administration of L-asparaginase, to identify allergy, however, a negative skin test does not preclude the possibility of hypersensitivity from developing.28 Premedication with corticosteroids is possible, although it has shown limited effectiveness for asparaginase HSRs and may even mask subclinical hypersensitivity.28 For example, a study by Woo et al attempted rechallenge of E. coli asparaginase in 12 patients who had prior HSRs to E. coli derived asparaginase by premedicating them with diphenhydramine or corticosteroids, only to find that a surprising 83% of

these patients experienced a second HSR and had to be switched to asparaginase Erwinia chysanthemi.35

Management of Infusion Reactions: Taxanes One management strategy that has gained large support over the last decade is rapid desensitization, in which a premedication protocol along with slower infusion times helps drug-sensitive patients tolerate their regimens more effectively.1,2,36,37 In 2005, Feldweg et al. reported use of a 6- to 7-hour rapid desensitization protocol for patients with HSRs to paclitaxel and/or docetaxel, with only 4 of 77 patients experiencing HSRs upon retreatment with this protocol.38 Platinum Compounds Several strategies for management of platinum-derived HSRs are similar to those for the taxane compounds, such as desensitization protocols to allow for continued therapy. Other strategies include decreasing the infusion rate and adding additional premedication prior to the infusion. Substituting with a different platinum agent in the event of an HSR may work as well, as there are several documented cases of successfully lowering the incidence of HSRs in women with gynecological malignancies by switching carboplatin with cisplatin. Lastly, skin testing has been used in an effort to predict HSRs in patients prior to readministration of platinum salts.12 Epipodophyllotoxins: Switching patients to etoposide phosphate following development of HSRs to intravenous etoposide has been shown to be successful in some cases.39 This is likely due to the fact that etoposide phosphate does not contain the solvent polysorbate 80, which has been postulated as a potential cause of hypersensitivity reactions as mentioned before.22,23 Switching to oral etoposide may also be a viable management strategy, as this form has not been associated with HSRs.22,24 Asparaginase: If HSRs to PEG-asparaginase occurs, there are typically three treatment options. The first is termination of all asparaginase treatment. The second is to attempt to continue treatment through a desensitization protocol, or to use a combination of acetaminophen, diphenhydramine, and steroids. The third is to switch the patient to Erwinia chrysanthemi derived asparaginase.28 An important reason for this final option is that while PEG-asparaginase appears to have the least incidence between the three, there is a significant amount of immunologic overlap between this type and the native E. coli asparaginase. In fact, those who are switched from the native form to the pegylated form

usually show a greater incidence of hypersensitivity to PEG-asparaginase compared to those who receive PEG-asparaginase during the induction period.28 Limited cross-reactivity between native E. coli or PEG-asparaginase and Erwinia derived asparaginase has been observed in practice, defending the benefit of this management strategy.40–43 Given the clarity of inferior outcomes for ALL patients who stop asparaginase therapy completely, this is usually the best possible approach if access to alternative asparaginase is available. A notable study at the Dana Farber Cancer Institute found that when 42 patients with HSRs to native E coli asparaginase were switched to Erwinia asparaginase, 81% of the patients were able to finish > 26 weeks of their therapies, as well as report a 5.4-year event-free survival.42 Another more recent study by Tong et al. also found very high success, with 97% of patients that had experienced HSRs and been switched to Erwinia asparaginase being able to complete their treatments.43 Anaphylaxis Anaphylaxis may have varied incidence of occurrence, dependent on the infusion agent and patient risk factors.

Anaphylaxis during an infusion may lead to generalizable or systemic symptoms. Symptoms often include anxiety, change in airway status and circulatory changes. Additional symptoms may include stridor, wheezing, fatigue, hypoxia and progression to a loss of consciousness. Anaphylaxis must be treated promptly following the reaction.

Immediate cessation of the infusion is required, and the patient should be assessed based on symptoms and side effects. Treatment criteria should be readily available at infusion sites to expedite measures to manage symptoms.

Guidelines for the management of anaphylaxis have been developed by the American Heart Association and the Oncology Nursing Society.44–46 Content for institutional anaphylaxis protocols should be available on chemotherapy protocols or electronic health care records (Table 3).

Summary HSRs occur with numerous chemotherapy agents in a wide variety of treatment regimens. HSRs may be specific to drug classes and even between the drugs themselves. Patients who exhibit infusion-related reactions to the agents discussed here are able to be managed most effectively through a variety of different means depending on the drug class, such as through desensitization protocols and premedication in the case of the taxanes and platinum compounds, intensified premedication with the epipodophyllotoxins, and through switching agents in the case of L-asparaginase. The next decade should bring new biologic and non-biologic antineoplastic agents that will need to be continually evaluated for infusion reactions. The expected increase in survival of cancer patients and those being

Table 3: Summary of Treatments for Managing Infusion Reactions48 Cessation of chemotherapy Administer high-flow oxygen (>10 L/min).

Administer epinephrine 1:1,000 (weight-based) (adults: 0.01 mL per kg, up to a maximum of 0.2 mL to 0.5 mL every 10 to 15 minutes as needed; children: 0.01 mL per kg, up to a maximum dose of 0.2 mL to 0.5 mL) by SC or IM route and, if necessary, repeat every 15 minutes, up to two doses. If unresponsive to epinephrine for maintaining hemodynamic stability, dopamine 400mg in 500ml of 5% dextrose can be given at a rate of 2-20mg/kg per minute and titrated to maintain systolic blood pressure >90 mm Hg. If the patient is taking a β-

adrenergic blocker that complicates treatment, a glucagon infusion (1-5mg) can be given IV over 5 minutes.

Administer fluid hydration (adults 500 mL to 1000 mL; children crystalloid 20 mL/kg) over the first five minutes. A maximum of 50ml/kg over the first 30 minutes can be given. Colloids should be stopped, as they may be the triggers for the reaction. Patients with with comorbidities such as congestive heart failure or chronic renal dysfunction should be observed carefully for signs of fluid overload.

Administer H1/H2 slowly IV/IM. These can counteract some of the activity of circulating histamine from the mast cells. Diphenhydramine 25-250mg may be given slowly via IV, though oral doses can also be considered for mild reactions.

Ranitidine 50mg with diphenhydramine 50mg diluted in 5% dextrose to 20ml are seen as superior to diphenhydramine given alone, especially in cases where tachycardia and cutaneous symptoms are present.

Administer inhaled albuterol/ipratropium for bronchospasms not responding to epinephrine administration Give hydrocortisone sodium succinate 100 mg to 200 mg by slow IV injection (choose the lower dose if steroid has already been given as antiemetic or premedication). Hydrocortisone has an onset of action that is delayed for up to 4 to 6 hours. However, it may shorten or prevent a protracted reaction.

IM indicates intramuscular; IV, intravenous; SC, subcutaneous

diagnosed with cancer for the first time will surely increase the number of patients needing treatment with current and future chemotherapy. Developing a plan that prevents infusion-related reactions at your institution requires developing a process that educates healthcare staff to the signs and symptoms of these reactions (Table 4), counseling patients on the adverse effects of therapy, and creating protocol guidelines for managing reactions when they occur. Implementation of these procedures for infusion centers can provide proper management to prevent and treat reactions in a timely manner.

References: 1. Syrigou, E., Makrilia, N., Koti, I., Saif, M. W. & Syrigos, K. N. Hypersensitivity reactions to antineoplastic agents: an overview. Anticancer.

Drugs 20, 1–6 (2009).

2. Picard, M. & Castells, M. C. Re-visiting Hypersensitivity Reactions to Taxanes: A Comprehensive Review. Clin. Rev. Allergy Immunol. (2014). doi:10.1007/s12016-014-8416-0 3. Colwell, H. H. et al. The Impact of Infusion Reactions on Oncology Patients and Clinicians in the Inpatient and Outpatient Practice Settings.

30, 153–160 (2007).

4. Sendo, T. et al. Incidence and risk factors for paclitaxel hypersensitivity during ovarian cancer chemotherapy. Cancer Chemother. Pharmacol.

56, 91–6 (2005).

Winter 2015 • ArizonA JournAl of PhArmAcy • 21

5. Gennari A, Salvadori B, Tognoni A, C. P. Rapid intravenous premedication with dexamethasone prevents hypersensitivity reactions to paclitaxel. Ann. Oncol. 7, 978–979 (1995).

6. Demoor PA, Matusov Y, Kelly C, Kolan S, Barnachea L, B. LA. A retrospective review of the frequency and nature of acute hypersensitivity reactions at a medium-sized infusion center: comparison to reported values and inconsistencies found in literature. J. Cancer 2, 153 – 164 (2011).

7. Decorti G, Bartoli KF, Candussio L, et al.

Effect of paclitaxel and Cremophor EL on mast cell histamine secretion and their interaction with Adriamycin. Anticancer Res. 16, 317–320 (1996).

8. Zhang H, Dou J, Z. G. Advances in the formulations of non-injection administration of docetaxel. J. Drug Target. 22, 87–94 (2014).

9. Micha, J. P. et al. Single-dose dexamethasone paclitaxel premedication.

Gynecol. Oncol. 69, 122–4 (1998).

10. Kato A, et al. Effect of oral dexamethasone given 24 hours previously on docetaxel-induced edema: a retrospective study. Gan to Kagaku Ryoho 41, 211–214 (2014).

11. Weiss, B. R. B. et al. Hypersensitivity Reactions From Taxol. 8, 1263–1268 (1990).

12. Makrilia N, Syrigou E, Kaklamanos I, Manolopoulos L, S. M. Hypersensitivity reactions associated with platinum antineoplastic agents: A systematic review.

Met. Based Drugs 2010, 1–11 (2010).

13. Hoekstra, A. V, Hurteau, J. a, Kirschner, C. V & Rodriguez, G. C. The combination of monthly carboplatin and weekly paclitaxel is highly active for the treatment of recurrent ovarian cancer.

Gynecol. Oncol. 115, 377–81 (2009).

14. Sliesoraitis S, C. P. Carboplatin hypersensitivity. Int. J. Gynecol. Cancer 15, 13–18 (2005).

15. Joerger, M. Prevention and handling of acute allergic and infusion reactions in oncology. Ann. Oncol. 23 Suppl 1, x313–9 (2012).

16. O’Cearbhaill, R. et al. The prophylactic conversion to an extended infusion schedule and use of premedication to prevent hypersensitivity reactions in ovarian cancer patients during carboplatin retreatment. Gynecol. Oncol. 116, 326–31 (2010).

17. Kellie, S. J. et al. Hypersensitivity Reactions to Epipodophyllotoxins in Children With Acute LymphobIastic Leukemia.

1070–1075 (2000).

18. Lee, C., Gianos, M. & Klaustermeyer, W. B. Diagnosis and management of hypersensitivity reactions related to common cancer chemotherapy agents. Ann. Allergy. Asthma Immunol. 102, 179–87;

Table 4: CTCAE Criteria v3.0 for Hypersensitivity Grades49

Grade 1 = Mild adverse event; Grade 2 = Moderate adverse event; Grade 3= Severe adverse event; Grade 4 = life threatening or disabling adverse event; Grade 5 = Death related to adverse event

quiz 187–9, 222 (2009).

19. Vumon, Teniposide for injection (Warning).

(2011). at <http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020119s010s011lbl.pdf> 20. Zanotti, K. M. & Markman, M. Prevention and Management of Hypersensitivity Reactions. 24, 767–779 (2001).

21. Hoetelmans RMW, Schornagel JH, Bokkeel HWW, B. J. Hypersensitivity reactions to etoposide.

Ann. Pharmacother. 30, 367–371 (1996).

22. Pagani, M. The complex clinical picture of presumably allergic side effects to cytostatic drugs: symptoms, pathomechanism, reexposure, and desensitization. Med. Clin. North Am. 94, 835–52, xiii (2010).

23. Shepherd, G. M. Hypersensitivity Reactions to Chemotherapeutic Drugs Index Entries : 24, 253–262 (2003).

24. RB, W. Hypersensitivity reactions. Semin. Oncol.

19, 458–477 (1992).

25. Nolte H, Carstensen H, H. H. VM-26 (teniposide)-iduced hypersensitivity and degranulation of basophils in children. Am. J. Pediatr. Hematol. Oncol.

10, 308–312 (1988).

26. Carstensen H, Nolte H, Hertz H, J. T. Hypersensitivity reactions to teniposide in children. J. Clin.

Oncol. 5, 1491–1492 (1987).

27. Hudson, B. M. M. et al. Acute Hypersensitivity Reactions to Etoposide in a VEPA Regimen for Hodgkin ’ s Disease. 11, 1080–1084 (2015).

28. Burke, M. J. How to manage asparaginase hypersensitivity in acute lymphoblastic leukemia.

Future Oncol. 10, 2615–27 (2014).

29. Pieters, R. et al. L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer 117, 238–49 (2011).

30. Woo, B. M. H. et al. Hypersensitivity or Development of Antibodies to Asparaginase Does Not Impact Treatment Outcome of Childhood Acute Lymphoblastic Leukemia. 18, 1525–1532 (2000).

31. Shinnick, S. E., Browning, M. L. & Koontz, S. E. Managing hypersensitivity to asparaginase in pedi-

atrics, adolescents, and young adults. J. Pediatr.

Oncol. Nurs. 30, 63–77 (2013).

32. Avramis, V. I. et al. Immunogenicity of Native or Pegylated E . coli and Erwinia Asparaginases Assessed by ELISA and Surface Plasmon Resonance ( SPR-Biacore ) Assays of IgG Antibodies ( Ab ) in Sera from Patients with Acute Lymphoblastic Leukemia ( ALL ). 302, 299–302 (2009).

33. Liu, C. et al. Clinical utility and implications of asparaginase antibodies in acute lymphoblastic leukemia. Leukemia 26, 2303–9 (2012).

34. Zalewska-Szewczyk, B. et al. The anti-asparagines antibodies correlate with L-asparagines activity and may affect clinical outcome of childhood acute lymphoblastic leukemia. Leuk.

Lymphoma 48, 931–6 (2007).

35. Woo, M. H. et al. Anti-asparaginase antibodies following E . coli asparaginase therapy in pediatric acute lymphoblastic leukemia.

1527–1533 (1998).

36. Castells, M. Rapid Desensitization of Hypersensitivity Reactions to Chemotherapy Agents.

Curr. Drug Saf. 1, 243–251 (2006).

37. Castells, M. C. et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J. Allergy Clin.

Immunol. 122, 574–80 (2008).

38. Feldweg, A. M., Lee, C.-W., Matulonis, U. a & Castells, M. Rapid desensitization for hypersensitivity reactions to paclitaxel and docetaxel: a new standard protocol used in 77 successful treatments. Gynecol. Oncol. 96, 824–9 (2005).

39. Siderov, J., Prasad, P., De Boer, R. & Desai, J. Safe administration of etoposide phosphate after hypersensitivity reaction to intravenous etoposide. Br. J. Cancer 86, 12–3 (2002).

40. Zalewska-Szewczyk, B., Gach, A., Wyka, K., Bodalski, J. & Młynarski, W. The cross-reactivity of anti-asparaginase antibodies against different L-asparaginase preparations. Clin. Exp. Med. 9, 113–6 (2009).

41. Rizzari C, Conter V, Stary J, Columbini A,

Moericke A, S. M. Optimizing asparaginase therapy for acute lymphoblastic leukemia. Curr. Opin. Oncol. 25, S1–S9 (2013).

42. Vrooman, L. M. et al. Erwinia Asparaginase After Allergy to E . coli Asparaginase in Children With Acute Lymphoblastic Leukemia. 199–205 (2010). doi:10.1002/pbc 43. Tong, W. H. et al. CLINICAL TRIALS AND OBSERVATIONS A prospective study on drug monitoring of PEGasparaginase and Erwinia asparaginase and asparaginase antibodies in pediatric acute lymphoblastic leukemia. 123, 2026–2034 (2015).

44. Sampson, H. a et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J. Allergy Clin. Immunol. 117, 391–7 (2006).

45. Process, E. E. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 112, IV1–203 (2005).

46. Polovich M, White JM, Kelleher LO, E. Chemotherapy and biotherapy guidelines: Recommendations for practice. Oncol. Nurs. Soc. 2, 83–87 (2005).

47. Banerji, A. et al. Management of hypersensitivity reactions to Carboplatin and Paclitaxel in an outpatient oncology infusion center: a 5-year review. J. allergy Clin. Immunol. Pract. 2, 428–33 (2014).

48. Vogel WH. Infusion reactions: diagnosis, assessment, and management.

Clin J oncol nurs. 14;2. E10-E21. (2010).

49. Common Terminology Criteria for Adverse Events v3.0, DCTD, NCI, NIH, DHHS. Cancer Therapy Evaluation Program. (2006).

AzPA Offers BLS CPR Certification / Renewal

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Arizona Pharmacy Association

FEATURES

Winter 2015 • ArizonA JournAl of PhArmAcy • 23

Academy News American College of Clinical Pharmacy Arizona Chapter Academy News The ACCP Arizona Academy is a teaching and research based organization. The academy seeks a balance in research between writing and asking pharmacists to make discoveries. Through lectures, discussions, and clinical writings, show that pharmacy responds to various modes of inquiry: analytic, hermeneutic, cultural, and historical; thus, the reader is equipped to explore the possibilities of each perspective and emboldened to push beyond their own experience to expand their skills.

Community Pharmacy Academy News Sophia Galloway (academy chair-elect) and I have been hard at work completing our executive board and I am proud to say that all of the positions have been filled! That certainly does not mean you are off the hook, we have plenty of volunteer opportunities and if you are looking to get involved, please contact us.

Just a friendly reminder, our monthly calls are EVERY 3RD THURSDAY at 7am. Future call dates are December 17th, January 21st and February 18th. Any suggestions or recommendations are continually welcome. As always, thank you for being a part of AzPA.

Geriatric Care Academy News The GCA had an exciting year and is closing out 2015 strong! The Fall Conference was successful and one of our GCA members presented on e-cigarettes.

This session is now available on-demand at the AzPA Calendar of Events page.

In October, members participated in an Interprofessional Polypharmacy Clinic at St. Luke’s Home in Tucson Arizona. Be on the lookout for more details about the next Polypharmacy Clinic scheduled for spring 2016.

As a reminder, the GCA holds monthly conference calls on the second Wednesday of every month at 12:30pm. We understand not everyone is able to attend these calls, so we continue to release the GCA Newsletter as a way to reach GCA members (and non-members) who are unable to attend the conference calls.

As we move forward into 2016, I challenge all members to become more involved in the GCA. There are several opportunities to become involved with varying time commitments. If you are interested in becoming more involved, contact me via your AzPA profile messaging.

Jessica DiLeo PharmD Geriatric Care Academy Chair

Valerie Richards, PharmD Community Pharmacy Academy Chair

Happy Holidays!

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

• • • • • • •

Academy Meeting Calendar

ACCP Officer Meeting: 2nd Tues of the month at 12pm 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 Please note that the Health Systems Academy has changed conference call schedules. We will be meeting on the second Wednesday of odd numbered months at 12PM. Our current call schedule for the first half of 2016 is: January 13th, March 9th, May 11th, July 13th.

We are still looking for volunteers for committee work, organizers, topic suggestions, and speakers for upcoming events. If you are interested in participating or have an topic ideas you’d love to hear about, please contact Nicole Murdock or Lisa Tonrey. Your future involvement with the Health Systems Academy is a great way to boost your community visibility & rapport while gaining access to diverse experts within your state. We have opportunities in the following areas: Communications Committee, Continuing Education Committee, Membership Committee, Community Outreach Committee, Legislatve Committee.

The Health-System Academy of the Arizona Pharmacy Association is the Arizona affiliate of the American Society of Health-System Pharmacists (ASHP).

Lisa Tonrey, RPh, FAPhA Health-System Academy Chair hsa@azpharmacy.org

Arizona

Managed Care Academy News The Managed Care Academy has had great ideas for future topics in the upcoming conferences. We will be working on a Meet and Greet event this coming year so stay tuned and will let everyone know when the event is scheduled.

Managed Care hosted a Meet and Greet at the AMCP conference this past October in Orlando, Florida and will hold another one in April, 2016 in San Francisco, CA. Please join us for a great conference that includes up and coming new speciality trends in Managed Care.

Please join us in our monthly morning phone meetings every 3rd Wednesday of the month at 7am. Our meetings have changed from years past so we’ll be looking forward to hearing from you with your thoughts and ideas for future topics, speakers and events.

Just a reminder, don’t forget to sign up for the Tour de Cure Phoenix Susan Halterman, RPh ride in March and help support Team AzPA and the fight against Diabetes.

Managed Care Academy Chair See you there!

Student Pharmacist Academy News This fall quarter was an exciting one for the Student Pharmacist Academies. We held our first general meeting of the school year and welcomed many new first year members.

The Student Pharmacist Academy at Midwestern University COP elected our new Chair-Elect for the Academy, Lacey Simpson! We would like to congratulate her on this position and know that we will see many great things from her. Our big event was Safe Halloween on the MWU campus. At this event, the campus welcomes kids from the community to do some safe trick or treating. Different campus organizations help out by setting up tables where we can reach out to children and teach them about important topics. SPA did a table this year using the Katy’s Kids program to educate the kids on the difference between medication and candy and to explain how pharmacists are medication experts.

The SPA will be reinitiating the Student Conference at the Southwestern Clinical Pharmacy Seminar, February 2016 in Tucson. The conference will offer professional development skills and information.

We would like to thank all of the volunteers who make these events possible, and look forward to a great winter quarter!

Paris Cook, SPA Co-Chair, Midwestern University of College of Pharmacy Glendale Mika Jankowski, SPA Co-Chair University of Arizona College of Pharmacy ACADEMY NEWS

Winter 2015 • ArizonA JournAl of PhArmAcy • 25

Technician Academy News

We’ve had an exciting time in the 2nd quarter of our year. For outreach, AzPA Pharmacy Technicians & Friends teams in Prescott, Tucson, and Phoenix represented the academy and AzPA in support of the American Diabetes Association and the Juvenile Diabetes Research Foundation. We also have our first technician Mentor Connection Program (MCP) participants and are looking forward to growing in future years. For education, we have made presentations at several technician training programs in the state making connections with program directors and students. Together we have taken steps towards setting up a sustainable system to create CE programs tailored to the interests and needs of technicians. For advancement, we are actively researching various trends within the profession including mandatory completion of an accredited training program prior to certification in an effort to determine what positions and roles we should assume going forward. It is our goal to be proactive and position AzPA and our academy as leaders at the forefront of the debate.

Thanks to everyone who has participated in our meetings and those who have worked between calls to get things done. A special thanks to team captains, Allie Joliet, Reg Roy, and Grant Metcalf for building the teams and making each walk for diabetes an enjoyable experience for all involved. Thanks to Laura Lipsy for her patient perseverance in designing the team t-shirts and buttons. Thanks to Reg for his diligence in ensuring that the MCP got off the ground and to Grant for heading up our new Technician Academy CE Subcommittee. Many thanks to program directors Lacey Hoopes of Arizona College – Phoenix, JR Gill of Brookline College – Phoenix, Daniel Sharpe of Carrington College – Mesa, and any others who have welcomed a presentation from AzPA and/or helped with our CE subcommittee since this letter went to print.

We have a lot of work to do in 2016, so please jump aboard as we continue moving forward. Look for more CE events, a presence at the Pharmacy Day at the Capitol, and other exciting opportunities to make an impact in your profession and in the community. Please reach out to me if you’d like to get involved!

Kalani Anderson, C.Ph.T. Contribute to the discussion by email, at our monthly meetings, and through the Facebook Technician Academy Chair group Arizona Pharmacy Technicians.

Mentor Connection Program News The 2015-2016 mentor connection cycle has begun. Mentees and mentors selected received email introductions to officially start the process. Conference calls will be held every 2nd Wednesday of the month at 2pm. The program cycle runs from October - July and is intended to support each individual as well as the profession of pharmacy. Thank you to our volunteer mentors for your time and commitment. Mentees, be sure to reach out to your mentors and take this opportunity to seek as much guidance as possible for your future career. A new call for mentors will begin in August 2016.

Learn more www.azpharmacy.org/mentor

Renew Your Membership Don’t let your membership lapse. To participate in these AzPA academies and committees you must stay as an active member. Lapsed members may miss meeting notifications or other important activities. Plus, just one month’s lapse in your membership could mean you miss out on the next issue of the Arizona Journal of Pharmacy and free continuing education. Renew your membership by logging into your AzPA profile, (select Membership Info on the right hand side), or by calling the office.

Arizona Pharmacy Association

ACADEMY NEWS

www.azpharmacy.org 480-838-3385

CONTINUING EDUCATION From A to Z: Clinical Pearls for the Pharmacist - Part 2.

“Primer on Political Advocacy, Tranexamic Acid in Orthopedic Surgery, Two-Bag System for Fluid Management in Pediatric Diabetic Ketoacidosis, Thiamine for Acute Alcohol Withdrawal, Penicillin Allergies and Cross Reactivity with Cephalosporins/Carbapenems, Integrase Strand Transfer Inhibitors for HIV”

By: Mindy (Throm) Burnworth, PharmD, BCPS, FAzPA, Midwestern University College of Pharmacy-Glendale, Glendale, AZ, Associate Professor, Department of Pharmacy Practice; Cassandra Ehrlich, PharmD, Banner Boswell Medical Center, Sun City, AZ, Clinical Pharmacist; Erica Domer, PharmD, Maricopa Medical Center, Phoenix, AZ, Clinical Pharmacist Specialist-Pediatric; John Radosevich, PharmD, BCPS, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, Critical Care Clinical Pharmacist Specialist; Adeniyi A. Alo, PharmD, M.P.H., BPharm., BCPS, Ph.C, Carlsbad Medical Center, Carlsbad, NM, Staff Pharmacist; James Sanders, PharmD, Ph.D., BCPS, Maricopa Medical Center, Phoenix, AZ, Clinical Pharmacist Specialist-Infectious Diseases Goal: This home-study continuing education activity was developed to educate pharmacists on several “clinical pearls” that are applicable in day-to-day patient care.

pearl” is intended to convey one idea, concept, fact, or other information that a clinician has found useful in day-to-day patient-care, but may not be widely known, understood, published, or taught.1

Objectives: Upon the completion of this activity, the Pharmacist participant will be able to: 1. Define the concept of a “clinical pearl” 2. Evaluate six tools to kindle, fuel, and fortify political advocacyas a pharmacy professional 3. Describe the mechanism of action of tranexamic acid in orthopedic surgery 4. Evaluate current literature to assess the benefits of the twobag system for fluid management in pediatric diabetic ketoacidosis 5. Describe the role thiamine plays in the treatment of patients with acute alcohol withdrawal 6. Recommend an appropriate cephalosporin or carbapenem for patients with non IgE mediated hypersensitivity to penicillins 7. Describe the advantages of utilizing integrase strand transfer inhibitors for the treatment of HIV

Clinical Pearl 1: “Ignite Your Fire Within: A Primer on Political Advocacy” by Mindy (Throm) Burnworth, PharmD, BCPS, FAzPA Sparked by media headlines such as “Need Drug, Take Number” and “Deadly Meningitis Outbreak Grows” it is no wonder that over the last decade several important patient care initiatives have brought pharmacy to the forefront. From these misadventures, the pharmacy profession advocated for changes in legislation to continue to ensure patient safety. For example, from the drug shortages crisis came Title X of the Food and Drug Administration Safety and Innovation Act (FDASIA) which is now public law [P.L. 112-144].1 FDASIA includes wording that advocates for stricter regulations to minimize the effect of drug shortages on patient care. From inappropriate pharmaceutical compounding practices stemmed the Drug Quality and Security Act (DQSA) now signed into law [P.L. 113-154] which helps to ensure safe, sterile preparation of compounded medications.2 These Public Laws add to the pharmacy profession’s track record of successful advocacy initiations. Kindling these success stories, a future headline may read “I Wrote and I Vote! Pharmacists Recognized as Providers!” On March 11, 2014, legislation was introduced into the House (H.R. 4190) to amend title XVIII of the Social Security Act to provide for coverage under the Medicare program of pharmacist services.3 This pearl will ignite your advocacy desire by using a simple stepwise approach to advance pharmacists as providers.

To begin, it is important to understand what advocacy is. A simplistic definition of advocacy is the act or

Background: This continuing education article was written directly from the transcripts of the live continuing education symposium, “From A to Z: Clinical Pearls for Pharmacists,” that was presented at the Arizona Pharmacy Association Annual Convention and Tradeshow on June 28, 2014 at the Wigwam Resort in Litchfield Park, Arizona. This article will serve as the second of a series of written summaries from the live programs. Portions of the information included in this article are represented in the published literature, while the remainder reflects opinions of the presenting faculty, based on their clinical experience.

As defined by Canaday’s Clinical Pearls (2009, Bethesda, MD: American Society of Health System Pharmacists) a “clinical

Winter 2015 • ArizonA JournAl of PhArmAcy • 27

Clinical Pearls process of supporting a cause or proposal.4 For example, on a daily basis pharmacy advocates for the safe and effective use of medications to achieve the best patient outcomes. This comes naturally as we are trained to advocate for our patients.

Take a moment to reflect, when was the last time that you advocated for the profession? Although advocating for one’s profession is important to the longevity of the field, this skill set is seldom taught in the pharmacy curriculum leaving one to learn “hands on.” A simple “hands on” stepwise approach to advocacy will help minimize the learning curve, ignite your fire, and help to secure pharmacist recognition as a healthcare provider.

Remember, I said “hands on” learning. Embrace the era of mobile technology. Get your electronic device out (yes, that means your device that starts with “i” or ends with “Droid”) and let’s take a look at several easy to navigate electronic resources to build your advocacy prowess (Table 1). As you surf around on each of these websites, bookmark or add these universal resource locators (URLs) to your list of favorites and program your representatives contact information right into your phone. By the end of this clinical pearl, you’ll be primed and ready to advance pharmacists as providers!

First, if you are not already a member of a state pharmacy organization, do not delay, join today. Many state pharmacy organizations work hand-in-hand with the State Board of Pharmacy to advance pharmacy initiatives and oppose initiatives that work against pharmacy (Table 1). Did you know that Arizona passed a state level bill (S.B. 1043) that recognizes pharmacists as medical providers on April 22, 2014?6 While this is a step in the right direction, we still need to be recognized on a national level (recall H.R. 4190). This is where joining a national pharmacy organization has its benefits.

For the second resource, identify the national organization that best matches your career interests (Table 1). Using your electronic device join their grassroots advocacy network. For example, if you work in a hospital or health-system, you are probably a member of the American Society of Health-System Pharmacists (ASHP). From ASHP’s homepage, follow the advocacy resources to the grassroots network link. Because your patients need you, take action and ask your member of congress to support H.R. 4190.7 ASHP’s grassroots network may serve as a comprehensive electronic resource that combines the six advocacy resources from Table 1 into a single location for advancing pharmacists as providers.

Third, your legislative representatives are elected (or not elected) by you so you carry significant weight and when they hear personal stories from you, they listen! They want your vote! Now is the time to identify your representative. My personal favorite website is www.votesmart.org (Table 1). Using this e-resource, simply type in your zip code and in a matter of seconds, you will be linked to your elected representative.

Send them an email to ask them to support H.R. 4190 Pharmacists as Providers and be sure to include a personal story about how it affects your practice. Elected representatives pay CONTINUING EDUCATION

Table 1. Pharmacy Advocacy Resources5 Advocacy Resource

Web Portal

Join the State Pharmacy Association and Know

www.naspa.us/statepharmacy.html

the State Board of Pharmacy

www.nabp.net

Join at least one

www.ashp.org

National Pharmacy Association

www.pharmacist.com www.accp.com www.ncpanet.org www.amcp.org

Contact your Representative(s)

www.votesmart.org www.contactingthecongress.org

Contribute to a Political Action Committee

Check the advocacy link on State or

(PAC)

National Association website (see above)

Track proposed Congressional Legislation or get www.senate.gov involved in legislation

www.house.gov www.govtrack.us thomas.loc.gov www.federalregister.gov

Track proposed State Legislation

www.ncsl.org

attention to those stories and when you ask for their action, they listen (remember, it was your vote that got them to their position so you can just as easily vote them out of office).

Fourth, if reaching out to your representatives just does not spark your interest (or makes you uncomfortable), there are many other ways to advocate.

Consider making a small donation (start with $1 and work up to a larger amount) to a Political Action Committee (PAC) and let the PAC do the leg-work and communication for you (Table 1). The funds promote candidates that are pro-pharmacy (specifically those candidates who will further pharmacists as providers).

Finally, reflect on how excited you get when you see the number of “likes” on your Facebook posts grow! Similarly, it may also excite you to determine how many and which legislators have “liked” Pharmacists as Providers (ie. how successful were your advocacy efforts?).

Clinical Pearls You can follow along the progress of H.R. 4190 Pharmacists as Providers via several different portals such as www. senate.gov, www.house.gov, www.govtrack.us, thomas. loc.gov, www.federalregister.gov, or www.ncsl.org (Table 1). Currently, H.R. 4190 has 116 bipartisan co-sponsors.8 Alternatively, trend the progress of the bill on your state or national pharmacy organization’s webpage.

In closing, Table 1 provides a simple stepwise approach to advancing pharmacists as providers. If you were in a public venue using their complimentary Wi-Fi (such as your favorite coffee shop), “match your latte” by making a small $5 contribution to a PAC. Alternatively, while you are waiting in line for that specialty drink (come on, you know you’ll have at least 5 minutes), email your representative and share your personal story about why pharmacists should be recognized as a healthcare provider. That $5 donation or 5-minute correspondence may be the most important action that you do for your profession. Help make H.R. 4190 Pharmacists as Providers [official title, To amend title XVIII of the Social Security Act to provide for coverage under the Medicare program] public law! This bill may make (or break) the future of our profession. Advocate today!

Clinical Pearl 2: “Tranexamic Acid in Orthopedic Surgery”

by Cassandra Ehrlich, PharmD Postoperative anemia and bleeding, necessitating allogeneic blood transfusions, are two major concerns for patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). Although effective, allogeneic blood transfusions do not come without risks and limitations. Limited blood supply and transfusion complications, such as hemolytic reactions, febrile reactions, clotting abnormalities or transmission of infection, have created a need for novel strategies to prevent and manage postoperative blood loss.1 Strategies such as manual compression, autologous blood salvaging procedures and pharmacologic intervention are being used more frequently.2 Tranexamic acid is a pharmacologic agent that is being used more commonly in order to manage and prevent postoperative blood loss.

In order to understand the mechanism of tranexamic acid and its role in orthopedic surgery, it is important to understand the process of hemostasis. When a blood vessel is damaged the body begins the process of hemostasis, or the arrest of bleeding.3 Hemostasis begins with initial vasoconstriction of the injured vessel. Next a platelet plug is formed.

After formation of the platelet plug fibrin forms a more stable, insoluble clot.3 The process ends when the fibrin clot is dissolved by plasmin in a process known as fibrinolysis.3 Decreased fibrinolysis reduces the risk of bleeding that is caused by excess clot lysis, which is useful in surgery, where tissue plasminogen activator (t-PA) is released in response to the tissue damage resulting in a hyper-fibrinolytic state.4 CONTINUING EDUCATION

The agents aminocaproic acid and tranexamic acid are inhibitors of fibrinolysis that have been used clinically to reduce incidences of operative bleeding.5 Tranexamic acid exhibits its antifibrinolytic effect by forming a reversible complex with plasminogen and plasmin.6 Tranexamic acid, a synthetic lysine analog, competitively inhibits the activation of plasminogen to plasmin. Intravenous tranexamic acid is indicated for short-term use, 2-8 days, in patients with hemophilia in order to reduce or prevent hemorrhage in patients who are undergoing tooth extraction.7 The oral formulation is indicated for the treatment of cyclic heavy menstrual bleeding.8 While these are the only approved on-label use for tranexamic acid, it has been used for many off-label purposes. Tranexamic acid has been used to prevent bleeding and reduce the need for blood transfusions in cardiac surgeries, acute upper gastrointestinal bleeding, spinal surgeries, transurethral prostatectomy, cesarean deliveries, and total hip and knee arthroplasties.8,9 Tranexamic acid intravenous solution can be mixed with most diluents, such as dextrose or normal saline.7 The mixture should not be added to blood products or mixed with solutions containing penicillin.7 Once prepared, the solution should be used the same day.7 Doses are usually diluted to 50-250 mL and administered over 5-30 minutes with a maximum rate of 100 mg/minute.9 For orthopedic surgery, dosing strategies have varied widely from study to study and no consensuses on optimal dosing regimens have been reached. Studies have established that intravenous doses of 10 mg/kg are needed in order to reach a therapeutic concentration that will adequately reduce plasminogen.11 Doses of 10 mg/kg will maintain therapeutic concentrations of 10 ng/ml for approximately 3 hours.11 Fibrinolysis begins with surgical trauma and is enhanced by the use of a pneumatic tourniquet, an effect which continues into the post-operative period.11 Because of this prolonged fibrinolytic activity, a second dose of 10 mg/kg dose can be given 3 hours after the first dose, or immediately after the tourniquet is released.9 The optimal dosing regimen for TKA was studied by Maniar et al. who showed that a regimen consisting of a pre-operative dose given 20 minutes before tourniquet application, an intraoperative dose given 15 minutes before tourniquet deflation, and a post-operative dose given 3 hours after the intraoperative dose was the most effective regimen resulting in the least amount of total blood loss.11 For THA 10 mg/kg is given 5-15 minutes before incision and may be followed by subsequent 10 mg/kg doses.10 No maximum doses have been reported in the literature for use in TKA or THA. Doses of up to 100 mg/kg have been safely used in spinal surgery.9 Over 95% of tranexamic acid is excreted unchanged in the urine by glomerular filtration.8 Winter 2015 • ArizonA JournAl of PhArmAcy • 29

Clinical Pearls Reported adverse events are uncommon with hyperglycemia, metabolic acidosis, and hyperosmolar tranexamic acid therapy. The most commonly reported dehydration. One of the mainstays of DKA treatment is effects include nausea, diarrhea, and orthostatic reacfluid management which works to correct electrolyte imtions.6 Based on its mechanism of action, tranexamic acid balances and replace fluid losses. The one-bag system and theoretically increases the risk of thrombosis. However, two-bag system are different methods utilized for fluid there have only been isolated case reports of thrombosis, management in pediatric DKA. With the one-bag system, and the results of randomized clinical trials do not show the patient receives one intravenous (IV) fluid bag which a statistically significant association between tranexamic provides a set concentration of electrolytes (i.e. sodium, use and an increased risk of developing thromboemTable 2. Tranexamic acid dosing and administration pearls bolic conditions.6 Indication Dose Timing Although trials have failed to show an increased risk of developing thromboembolic disease with TKA 10 mg/kg 20 minutes before 15 minutes 3 hours after the use of tranexamic acid, patients with active tourniquet inflation before tourniquet thromboembolic disease, a history of thrombosis or thromboembolism, or an intrinsic risk of thrombotourniquet deflation sis or thromboembolism should not use tranexamic deflation acid.8 Patients with subarachnoid hemorrhage should THA 10 mg/kg 20 minutes before 3-6 hours after not use the injectable formulation, as it may lead to cerebral edema and cerebral infarction.7 Patients incision 1st dose with acquired defective color vision should not use Contraindications: Hypersensitivity to tranexamic acid, active thromboembolic disease, history of tranexamic acid since it interferes with monitorthrombosis or thromboembolism, intrinsic risk of thrombosis (e.g., ing endpoints. Tranexamic acid administration has caused areas of retinal degeneration in cats, dogs, hypercoagulopathy, thrombogenic cardiac rhythm disease), subarachnoid and rats following both oral and intravenous routes hemorrhage, color vision defects when administered at doses between 250-1600 mg/ kg/day.7 As a result, visual abnormalities may occur in courses longer than 7 days. Therefore, ophthalmic exams should be conducted at baseline and at regular intervals to assess for visual acuity, color Table 3. Tranexamic acid dosing in renal dysfunction vision, and visual fields.7 While tranexamic acid is not approved by the Renal Dosing: Food and Drug Administration agency for the use Serum Creatinine 1.36-2.38 mg/dl 2.38-5.66 mg/dl >5.66 mg/dl of preventing total blood loss and decreasing the 10 mg/kg 10 mg/kg daily 10 mg/kg every 48 hours rate of blood transfusions in TKA and THA, there is enough literature to support its use in orthopedic No more than 2 doses or 5 mg/kg every 24 hours surgeries. During orthopedic surgery, damage to blood vessels release t-PA which can result in an increased lytic state, putting the patient at risk for postoperative anemia and bleeding. Tranexamic acid, by potassium, chloride, phosphate) and dextrose. The major inhibiting plasmin, can decrease the risk of bleeding to palimitation with this system is that a new IV fluid bag must tients undergoing orthopedic surgery. Studies have proven be prepared each time the dextrose concentration needs its efficacy in decreasing total blood loss and reducing the adjusted. This can lead to a delay in making IV fluid adjustneed for blood transfusions without increasing the risk of ments, increased hospital costs (due to preparation time developing thromboembolic complications. Tables 1 and 2 and cost of supplies), and increased potential for medicasummarize key pearls to recognize when using tranexamic tion errors.3 acid.

The two-bag system is illustrated in Figure 1 below.

Clinical Pearl 3: “2 Bags 4 DKA: The Two-Bag System for With the two-bag system, the patient receives two IV fluid Fluid Management in Pediatric Diabetic Ketoacidosis” by bags, usually named Bag A and Bag B. Each bag contains Erica Domer, PharmD identical electrolyte content but a different dextrose Diabetic ketoacidosis (DKA) accounts for approxiconcentration (usually Bag A has 0% dextrose and Bag mately 15% of pediatric hospital admissions in the United B has 10% dextrose).3 The two bags are administered States annually and is the leading cause of mortality in simultaneously into the same IV line. The rates of each 1,2 children with type 1 diabetes. DKA is characterized by bag are adjusted according to the patient’s serum glucose CONTINUING EDUCATION

Clinical Pearls metabolic acidosis. Sixteen patients were randomized level in order to provide a customized glucose infusion rate to receive the one-bag system and 17 patients were and minimize the risk of hypoglycemia.2 For example, when randomized to receive the two-bag system. The type of the patient’s serum glucose level is high, the patient should receive a higher proportion of Bag A and a lower propordiluent and potassium salt used in the different IV fluid tion of Bag B. As the patient’s serum glucose level starts to bags was controlled per study protocol. There were decline, the proportion of Bag A administered should be no significant differences between groups in term of decreased and the proportion of Bag B administered should baseline characteristics. During IV fluid therapy, approbe increased to minimize the risk of hypoglycemia. priate labs were documented (i.e. serum glucose, pH, Three studies have been published which compare the electrolytes) in addition to the response time for IV fluid one-bag system to the two-bag system for fluid managechanges and the number of IV bags used. The results ment in pediatric DKA (see Table 1 for results). Grimberg et showed no significant difference between groups in the al. conducted a retrospective case control study including primary outcome, rate of serum glucose correction, or 20 pediatric patients admitted for DKA with a metabolic Figure 1: Sample set up of two-bag system (left); Example of an IV fluid titration table with the two-bag system acidosis and intensive care unit stay.3 Ten patients received (right) Serum Bag A Bag B Dextrose the one-bag system and 10 patients received the two-bag Glucose % of Total % of Total system; the type of diluent and potassium salt used in the Concentration (mg/dL) IV Rate IV Rate different IV bags was not controlled. The groups were matched for age, weight, and duration of IV therapy. The >350 100% 0% 0% patients’ medical charts were retrospectively reviewed to 301-350 75% 25% 2.5% determine the total number of IV bags used per patient, the 251-300 50% 50% 5% cost of IV therapy, and the time delays for IV changes. When compared to the one-bag system, the two-bag system used 201-250 25% 75% 7.5% almost half the number of IV fluid bags which corresponded <250 0% 100% 10% to a significant reduction in the cost of IV fluid therapy. Also, the response time for IV fluid changes was about 30 minutes faster with the two-bag system when compared to the one bag system. All patients in both groups underwent full correction of DKA and there were no documented complications.

A retrospective chart review conducted by So and Grunewalder included 31 pediatric patients with a diagnosis code of DKA on admission.4 Nine patients received the onein the secondary outcomes, rate of serum bicarbonate bag system and 22 patients received the two-bag system; correction and number of IV fluid bags used.

The only secondary outcome to reach significance the type of diluent and potassium salt used in the different was response time, with the time required for IV fluid IV bags was not controlled. The baseline characteristics changes being almost 40 minutes faster with the twowere similar between groups with the exception of baseline bag system when compared to the one-bag system. No serum creatinine (higher in the one-bag system group) and patients in either group had clinical evidence of cerebral initial insulin infusion rate (higher in the two-bag system edema during the study period. Two patients in the onegroup). The patients’ medical charts were reviewed for bag system group did experience hypoglycemia (serum outcomes including rates of serum glucose and bicarbonate glucose <80 mg/dL) during the study period. This obsercorrection and times to pH and ketone correction. When vation suggests that the risk of hypoglycemia is higher compared to the one-bag system, the two-bag system had a with the one-bag system due to the restricted ability to significantly faster rate of serum bicarbonate correction and provide a customized glucose infusion rate; however, a trend towards faster serum glucose correction, although this association has not been studied. this result did not reach statistical significance. The only secThere is currently a lack of strong evidence to ondary outcome that reached significance was time to keascertain the benefits of the two-bag system over the tone correction, with a faster time with the two-bag system one-bag system for fluid management in pediatric when compared to the one-bag system. Interpretation of DKA. Based on the published literature to date, potenthe study end points is limited by the differences between tial benefits of the two-bag system may include: rapid groups in terms of size and baseline characteristics. correction of serum glucose, bicarbonate, and ketones; The only randomized controlled trial to date on this topic decreased response time to make IV fluid changes; and was published by Poirier et al.2 This study included 33 pedidecreased resource utilization (i.e. less IV fluid bags atric patients who presented to the emergency department required), which subsequently results in decreased with signs and symptoms consistent with DKA, including a CONTINUING EDUCATION

Winter 2015 • ArizonA JournAl of PhArmAcy • 31

Clinical Pearls hospital costs. Other hypothetical benefits of the two-bag system, which have yet to be studied, may include: ability to provide a customized glucose infusion rate; decreased risk of hypoglycemia; and reduction in medication errors.

Further studies are needed to establish the benefits of the two-bag system and direct treatment of pediatric DKA in order improve patient outcomes.

Table 1: Summary of results from studies comparing the one-bag system to the two-bag system for fluid management in pediatric DKA One-Bag

Two-Bag

System

System

Number of IV bags used

8.6 ± 1.2

4.8 ± 0.3

0.01

Response time for IV fluid changes (min)

36.7 ± 1.4

7.4 ± 1.1

<0.0001

Cost of IV fluid therapy ($)

1092 ± 147

622 ± 40

0.01

Rate of blood glucose correction (mg/dL/hr)

21.04 ± 16.26

31.04 ± 20.61

NS

Rate of HCO3 correction (mEq/L/hr)

0.606 ± 0.297

0.949 ± 0.553

0.047

Time to pH correction (hr)

9.7 ± 4.3

9.1 ± 7.4

NS

Time to ketone correction (hr)

53.9 ± 34.5

34.2 ± 14.7

0.04

Change in serum glucose (mg/dL/hr)

30.2 ± 19.8

33.1 ± 19.3

NS

Poirier et al.

Change in serum HCO3 (mEq/L/hr)

1.27 ± 0.94

1.19 ± 0.6

NS

(2004)†

Number of IV bags used

3.2 ± 0.42

4.1 ± 0.6

NS

Response time for IV fluid changes (min)

42 ± 30

1 ± 1.6

<0.001

Study

Grimberg et al. (1999)*

So &

Outcomes

p-value

Grunewalder (2009)†

*Data presented as mean ± SEM †Data presented as mean ± SD

Clinical Pearl 4: “EtOH, Carbs, and the Krebs Cycle – Where does B1 fit in?” by John Radosevich, PharmD, BCPS Upon presenting to an acute care facility, alcohol abusers are often started on a “banana bag”, which is a combination of intravenous fluids and various multivitamins, in an attempt prevent or treat encephalopathy associated with a thiamine (vitamin B1) deficiency. Unfortunately, there is substantial variation in clinical practice with respect to the dose, route of administration, and duration of therapy of thiamine for this indication. The goal of this brief clinical pearl is to address the clinical controversies related to the appropriate use of thiamine in the management (prevention and treatment) of Wernicke’s encephalopathy in patients who abuse alcohol.

Thiamine, also known as vitamin B1, is a water soluble vitamin that acts as a cofactor for numerous processes throughout the body, including glucose and lipid metabolism, production of amino acids, and neurotransmitter synthesis.1-3 In the absence of thiamine supplementation or vitamin-rich foods, thiamine stores may be depleted over the course of 2 to 3 weeks, potentially leading to Wernicke’s encephalopathy which has been associated with significant morbidity and mortality.1-4 CONTINUING EDUCATION

Wernicke’s encephalopathy is an acute neuropsychiatric syndrome that is characterized by a triad of symptoms, which include altered mental status, ataxia, and opthalmoplegia. Unfortunately, the “triad” of symptoms is only present in ~20% of patients.1,2 Further complicating the diagnosis of Wernicke’s in clinical practice is the fact that symptoms associated with Wernicke’s are easily attributable to acute alcohol/drug intoxication or withdrawal. Although there are numerous causes of thiamine deficiency, individuals who abuse alcohol are at high risk for developing a thiamine deficiency secondary to excessive alcohol intake and lack of consumption of vitamin rich food. Additionally, individuals who abuse alcohol also have impaired absorption of thiamine in the small bowel due to compromised active transport mechanisms.1,2 The daily requirement of thiamine for the average healthy adult is ~1.5 mg per day.1-4 When given an oral 100 mg dose of thiamine, a healthy adult absorbs ~4.5 mg, which is thought to be the maximum amount of thiamine absorbed from a single oral dose. Given the same oral dose of 100 mg, the malnourished or alcohol abusing patient will absorb between 0.8 mg and 1.5 mg, which is not sufficient to routinely meet the daily requirements for thiamine in a healthy adult.1,2,4 Hence, for the management of an acute deficiency, as is the case in Wernicke’s encephalopathy, it is prudent to administer intravenous thiamine to maximize blood concentrations which will allow for more rapid correction of brain thiamine deficiencies. Multiple intravenous doses should be given daily in order to maximize thiamine concentrations in the brain as thiamine has a half-life of approximately 96 minutes.2 One randomized, controlled study was conducted in high-risk patients being treated for alcohol withdrawal to prevent the development of Wernicke’s encephalopathy.

This study compared varying doses (i.e. 5 mg up to 200 mg) of intramuscular thiamine administered daily for two days. Patients receiving larger doses of thiamine (i.e. 200 mg/day) tended to perform better during a neurological exam, but the results did not indicate a step-wise dose-response, and there was no progression to Wernicke’s in any of the groups.5 Unfortunately, there have not been any randomized, controlled trials to guide the appropriate dose or duration of thiamine therapy for the management of active Wernicke’s encephalopathy. Although there are some case reports of low dose (i.e. 100-250 mg/day) thiamine reversing neurological symptoms associated with Wernicke’s, the combined data indicates larger doses of thiamine (i.e. > 250 mg/day) may be required for reversal of symptoms.1-6 Doses of 1000-1500 mg daily have been safely and successfully utilized in practice in numerous case series.1-4 A 2013 Cochrane review of the available literature indicated insufficient evidence to guide appropriate dose

Clinical Pearls or frequency of thiamine for prevention or treatment of Wernicke’s encephalopathy.6 Despite this, several international organizations have created treatment recommendations for the management of Wernicke’s encephalopathy. The European Federation of Neurological Societies recommends 200 mg of intravenous thiamine three times daily until symptom resolution.7 The Royal College of Physicians recommends more aggressive treatment with 500 mg of intravenous thiamine three times daily for 3 days or until adequate clinical improvement.8 Given the relatively wide therapeutic window for thiamine, and reported mortality of up to 20% in patients with Wernicke’s encephalopathy, it would be reasonable to adopt the aggressive dosing regimens recommended by these organizations despite lack of high quality evidence.

It is rare to have a safe and effective drug to readily reverse a condition of any kind. Given the morbidity and mortality (upwards of 20%) associated with Wernicke’s encephalopathy, it is prudent to aggressively replete full body thiamine stores to reverse the neurological symptoms associated with the syndrome. For patients with active Wernicke’s encephalopathy it is essential to administer high dose thiamine intravenously multiple times daily (i.e. every 6-8 hours) as oral bioavailability is extremely low in malnourished alcohol abusing patients and intravenous thiamine has a half-life of around 1.5 hrs. As for the appropriate dosing regimen for thiamine, clinicians should risk-stratify patients upon presentation and tailor the dosing regimen based upon patient specific factors. Patients with active Wernicke’s encephalopathy should be treated with intravenous thiamine in doses between 500-1500 mg daily. For patients at risk for developing Wernicke’s encephalopathy, high/medium-risk patients would be candidates for oral or intravenous thiamine in doses of up to 300 mg/day, while low risk patients should receive oral or intravenous thiamine in doses of up to 100 mg/day.

Clinical Pearl 5: “Penicillin Allergies and Cross-Reactivity to Cephalosporins and Carbapenems” by Adeniyi A. Alo, PharmD, M.P.H., BPharm., BCPS, Ph.C Immune mediated allergic reactions can be classified according to the Gell and Coombs’ classification system into (1) Type-I/IgE or immediate hypersensitivity, (2) Type-II/IgG or cytotoxic hypersensitivity, (3) Type-III/IgG/ IgM or immune complex reactions, and (4) Type IV or delayed hypersensitivity.1 However, for ease of clinical decision making, the original Gell and Coombs’ classification system can be simplified into two categories namely: IgE mediated allergic hypersensitivity or true drug allergy and non-IgE mediated allergic hypersensitivity/delayed or late onset hypersensitivity.2 IgE mediated allergic hypersensitivity manifests clinically as urticaria, angioedema, bronchospasm, laryngeal edema, erythema, hypotenCONTINUING EDUCATION

sion and/or arrhythmias, anaphylaxis, hyperperistalsis, or pruritic rash.3-4 Non-urticarial rash, drug fever, diarrhea, nausea and/or vomiting, hemolytic anemia, interstitial nephritis, Steven Johnson syndrome, toxic epidermal necrolysis, erythema multiforme minor or erythema multiforme major are some of the clinical manifestations of non-IgE mediated hypersensitivity.3-4 In order to better understand the risk of antibiotic cross-sensitivity, the incidence of allergies to certain antibiotics in the general population is summarized in Table 1.

How can a clinician confirm IgE mediated hypersensitivity?

The methods available are skin prick testing, intradermal testing and patch testing.9-10 If the outcome of the skin prick test is negative, it should be followed with the intradermal test.9 Diagnostic skin testing, however, is of limited value for non-penicillin β-lactam antibiotics because the antigenic determinants produced upon degradation are unknown.9 The clinician should use both the major antigenic determinant (benzylpenicilloyl polylysine, Pre-pen AllerQuest, Farmington Valley Drive, Plainville, CT) and the minor antigenic determinants (unmetabolized penicillin, penicilloate, penilloate, penicillenate, penicillinoic acid, penicillanyl, penicoyl, penilloic acid and other related compounds) of penicillin during skin testing.11 The minor antigenic determinants of penicillin are not commercially available in the United States and can be prepared from freshly diluted aqueous Penicillin G to a concentration of 10,000 units/ml.10,12 Table 1. Incidence of antibiotic allergies in the general population Antibiotic

Incidence

Penicillins

~ 10%

Severity

5

IgE/non-IgE mediated

Cephalosporins

0.02%-0.1%

Carbapenems

<3%7

IgE/non-IgE mediated

1st generation cephalosporins

0.0001%-0.1%8

IgE mediated

6

IgE mediated

A positive skin test was defined as a wheal at least 5 mm in diameter in the Saxon et al study.13 75%-90% of patients may be potentially skin test positive if the major antigenic determinant is utilized. However, use of both the major and minor antigenic determinants will identify 97%-99% of patients that could be potentially penicillin skin test positive.11 A positive penicillin skin test supports the diagnosis of an IgE mediated hypersensitivity (i.e. presence of antigen-specific IgE).9 A negative penicillin skin test has a high negative predictive value which allows the clinician to rule out the possibility of sensitivity to the β-lactam ring and true penicillin allergy.9-10 A negative penicillin skin test does not preclude the tested drug from causing a serious allergic reaction by other non-IgE mediated mechanisms.9 In patch testing, non-irritant concentrations of potential allergens are placed on the patient’s back for 48-72 hours under an aluminum disc and later inspected for local Winter 2015 • ArizonA JournAl of PhArmAcy • 33

Clinical Pearls reaction.5,9 The patch test is useful in conjunction with the intradermal test which is interpreted after 48 hours for detecting delayed hypersensitivity.9 In penicillins, the β-lactam ring is attached to a thiazolidine ring with one side chain. Cephalosporins have the β-lactam ring attached to a dihydrothiazine ring but the dihydrothiazine ring has two side chains. The β-lactam ring in carbapenems is attached to a modified thiazolidine ring that possesses two side chains. However, aztreonam the quintessential monobactam, possesses a β-lactam ring attached to a single side chain.9 See Figure 1.

Figure 1. Structure-Activity Relationship

The Cephalosporium mold was the source of the novel first generation cephalosporins (cephalothin, cephaloridine) before 1980.10 However, early cephalosporin products were contaminated with traces of penicillin.10 The contamination was later traced to the fact that the Cephalosporium mold makes penicillin-like compounds.11 Better purification led to the elimination of contamination of cephalosporins by penicillin in the eighties.10 Approximately 98% of patients with positive histories of penicillin allergies and negative skin test results can tolerate penicillins without any adverse effects.12 80%-90% of patients with self-reported penicillin allergy are not truly allergic as confirmed by skin testing.12 Patients with a history of penicillin allergies are at a 3-fold increased coincidental risk of having an allergic reaction to any other antibiotic compared to patient without penicillin allergies.10 The side chain is usually the antigen rather than the β-lactam ring in allergic reactions to cephalosporins.9 As an example, amoxicillin possesses a similar side chain to the R1 chain of cefadroxil.2 Cephalexin, cefaclor, and ampicillin have the same side chain.2 Cephalexin, cefadroxil, cefaclor, cephradine, cefprozil, ceftriaxone, and cefpodoxime are more likely to cross-react with penicillins.14 Cefazolin, cefuroxime, cefdinir, cefixime and ceftibuten lack the β-lactam side chain and are safer.14 It was historically reported that the cross-sensitivity between penicillins and first generation cephalosporins was between 3%-18%.11,14 The earlier studies over-estimated the level of cross-sensitivity due to contamination of cephalosporins before CONTINUING EDUCATION

1980 with penicillin and some methodological flaws in study design. Some of the study design flaws included very small sample size, retrospective nature of studies, and partial reliance on case reports/series. In terms of cross-sensitivity, first generation cephalosporins are more likely to cross-react than second generation, second generation greater than third generation and third generation greater than fourth generation cephalosporins that are least likely to cross-react.15 Cross-sensitivity with most second and third generation cephalosporins appear to be very low but is not equal to zero.15 The attributable risk is 0.4% for first generation cephalosporins.15 The risk of cross-sensitivity is nearly zero for cefuroxime, cefpodoxime and cefdinir.15 It was historically reported that the cross-sensitivity between penicillins and carbapenems was between 9.2%-25%.16-18 The earlier studies had small sample sizes ranging from 59-266 and were retrospective chart reviews. However, four recent prospective studies have shed light on the true value of this cross-sensitivity and found it to be likely less than or equal to 1%.19-21 No discussion of penicillin allergies and cross-sensitivity to cephalosporins and carbapenems is complete without a mention of aztreonam. The cross-sensitivity of the monobactam, aztreonam with other β-lactam antibiotics involves the side chain and is very rare.9 However, an exception occurs with ceftazidime with which aztreonam shares a common side chain.9 In conclusion, 80%-90% of patients with self-reported penicillin allergies are not truly allergic as confirmed by skin testing. Approximately 98% of patients with positive histories of penicillin allergy and negative skin test results can tolerate penicillins without any adverse effects. The true value of penicillin cross-sensitivity with carbapenems is likely less than or equal to 1%, while the attributable increased risk is 0.4% for first generation cephalosporins.

Clinical Pearl 7: “HIV Treatment: Integrating New Agents into Your Practice” by James Sanders, Pharm.D., Ph.D., BCPS The landscape of human immunodeficiency virus (HIV) treatment continues to change with the integration of novel therapeutic modalities. This clinical pearl will serve to introduce and briefly describe the utility of integrase strand transfer inhibitors (INSTIs or ISTIs), a novel class of antiretroviral agents. Due to the complex life cycle of HIV, several sites of attack exist for treatment of the virus. The INSTIs inhibit HIV through blockade of viral DNA integration into the host genome. As a class, the ISTIs have gained increasing popularity due to improved efficacy and tolerability.1 The three Food and Drug Administration approved INSTIs are raltegravir (RAL, Isentress®), elvite-

Clinical Pearls gravir (EVG/COBI, Stribild®-co-formulated with cobicistat/ emtricitabine/tenofovir), and dolutegravir (DTG, Tivicay®, Triumeq®-co-formulated with abacavir/lamivudine).2-6 The Department of Health and Human Services (DHHS) guidelines recently moved all three INSTIs to recommended initial antiretroviral therapy (ART) regardless of baseline viral load or CD4 cell count.7 The administration of the three available ISTIs may be differentiated based on frequency of administration, ability to crush the tablet, renal and hepatic adjustment and overall pill burden. Of the three available agents, RAL requires twice daily dosing, whereas, DTG and EVG/COBI maintain once daily dosing in treatment naïve patients.2-4 However, DTG requires twice daily dosing in treatment experienced patients and patients receiving interacting concomitant therapy (e.g. rifampin).4,6 For alternative administration, Stribild® may not be crushed.8 In contrast, the other two ISTIs have limited data from case reports and data on file with the drug company supporting crushing of the tablets.2,9-10 Due to the nature of the co-formulation, Stribild® is not recommended for treatment initiation in patients with a creatinine clearance (CrCl) < 70 ml/min and is contraindicated in patients with a CrCl < 50 ml/min. This stems from the need to adjust selectively the emtricitabine/tenofovir component.3,6 RAL and DTG generally do not require renal dose adjustment.2,4,7 However, DTG levels may be lower in patients with a CrCl < 30 ml/min, thus caution should be used in certain patient populations (e.g. treatment experienced patients).4,7 All three agents have limited data in severe hepatic impairment (i.e. Child-Pugh C).2-4,7 Adherence remains a key component of successful treatment of HIV; therefore, pill burden plays an integral part of therapy.7 Currently, two one pill, once a day options exist in the ISTI class: Stribild® (EVG containing) and Triumeq® (DTG containing).3,5 In contrast, RAL requires a daily pill burden of three pills, including twice daily dosing, making it a less attractive option for ensuring patient adherence.2,7 Overall, the ISTIs demonstrate excellent clinical efficacy in the treatment of HIV when compared to other available first line treatment options for treatment naïve patients. In the long term follow up studies, RAL demonstrated superiority to the DHHS recommended regimen of efavirenz/ emtricitabine/tenofovir (Atripla®).11 On the other hand, Stribild® demonstrated only non-inferiority to efavirenz and atazanavir/ritonavir based regimens.12 DTG performed well in all available studies demonstrating superiority to efavirenz and darunavir/ritonavir containing regimens and non-inferiority to RAL in treatment naïve patients.6,13-14 One major distinguishing characteristic of ISTI containing regimens is the rapidity of virologic control. ISTIs induce a rapid decline appreciated at the earliest time points checked (e.g. 4 weeks), whereas, other first line agents take up to 24 weeks or longer to appreciate maximum virologic con-

trol.11-14 The utility and influence of rapid virologic control by the ISTIs remains to be elucidated but may be of utility in the treatment of acute HIV to prevent future sequelae associated with prolonged viremia.

The ISTIs demonstrate a favorable safety profile with nausea, headache and diarrhea cited as the most common adverse events reported in the clinical trials (Table 1).2-4 Of note, all three agents may result in an elevation in creatine kinase, with RAL having the highest reported incidence.2-4 In addition, DTG carries a warning for potential elevation in liver function tests (LFTs) in patients with underlying hepatic disorders warranting close monitoring of LFTs in these patients.4,7 Lastly, DTG and cobicistat may increase the serum creatinine (SCr) through inhibition of renal secretion of creatinine.3-4 The increase in SCr normally is less than 0.4 mg/dL and should plateau after 2-4 weeks, thus higher elevations require further investigation for potential nephrotoxicity of concomitant therapy and/or underlying medical conditions.12-13 Table 1: Common adverse drug reactions associated with ISTIs

In treatment naïve patients, baseline mutations have little effect on the efficacy of ISTIs. The ISTIs demonstrate a lower barrier to resistance relative to other ART regimens. Within the class, DTG demonstrates the highest barrier of resistance with no resistance demonstrated in the treatment naïve studies.13 Once resistance develops, one must remain cognizant of the potential for cross-resistance between RAL and EVG, although DTG may retain activity.11-13 Of the three members, DTG and RAL have the fewest interactions due to the omission of a boosting agent. Table 2 shows a comparison between the three agents for several of the key drug-drug interactions seen with the ISTIs. Due to the ISTI’s mechanism of action, divalent cations, present in antacids and vitamin supplements, interact with all three agents requiring Winter 2015 • ArizonA JournAl of PhArmAcy • 35

Clinical Pearls avoidance or spacing of these agents when used concomitantly with ISTIs.2-4,7 Acid suppression has no clinical effect on these agents; therefore, H2-receptor antagonists and proton pump inhibitors may be use concomitantly.2-4,7 Tuberculosis, a common opportunistic infection in HIV patients, necessitates the use of rifampin and consideration for potential drug-drug interactions with the ISTIs.7 RAL and DTG have approved dose adjustments when used concomitantly, while Stribild® use is not recommended.2-4,7 Lastly, due to the inclusion of the boosting agent (CYP3A4 inhibitor), cobicistat, Stribild® has numerous possible interactions and warrants a close review of potential interactions with concomitant agents.3,7 In conclusion, ISTIs represent a novel class of ART providing safe and efficacious treatment options for HIV. The ability to alter the viral load rapidly may support the use of these agents in acute HIV infections where high levels of viremia are present. These agents have limited adverse reactions and metabolic effects therefore demonstrating enhanced tolerability. Historically drug interactions have limited the utility of other ART regimens; however, within the ISTI class, the drug interactions remain limited for DTG and RAL. Taken together, these advantages support the adoption of the ISTIs as first line ART options.

Conclusion: Sharing of clinical pearls such as “From A to Z” via live educational sessions or written programs is a succinct method to disseminate several ideas, concepts, or facts for quick application in day-to-day patient-care.

Table 2: ISTIs drug-drug interactions

113publ54.pdf. Accessed September 1, 2014.

3. Library of Congress. H.R. 4190 – 113th Congress (2013-2014): To amend title XVIII of the Social Security Act to provide for coverage under the Medicare program of pharmacist services. Available at https://www.congress.gov/ bill/113th-congress/house-bill/4190?q=%7B%22search%22%3A%5B%22H.R.+ 4190%22%5D%7D. Accessed September 1, 2014.

4. Merriam Webster Dictionary. Advocacy – definition. Available at http:// www.merriam-webster.com/dictionary/advocacy. Accessed September 1, 2014.

5. Gohlke AL, Murphy KM, Cannell ME, Ray DB, Burnworth MJ. Igniting the fire within: a primer on political advocacy for pharmacy professionals. Journal of Pharmacy Practice. 2013(26):165-170.

6. Buckley B. We are providers: Arizona passes provider status legislation.

Pharmacy Today. August 01, 2014. Available at http://www.pharmacist. com/we-are-providers-arizona-passes-provider-status-legislation. Accessed September 1, 2014.

7. American Society of Health-System Pharmacists. Grassroots Network.

Available at http://www.ashp.org/menu/Advocacy/GrassrootsNetwork.

Accessed September 1, 2014.

8. Library of Congress. Co-sponsors – H.R. 4190 – 113th Congress (20132014): To amend title XVIII of the Social Security Act to provide for coverage under the Medicare program of pharmacist services. Available at https://www.congress.gov/bill/113th-congress/house-bill/4190/cosponsors?q=%7B%22search%22%3A%5B%224190%22%5D%7D. Accessed September 1, 2014.

Tranexamic Acid in Orthopedic Surgery

1. Maxwell MJ, Wilson MJ. Complications of blood transfusions: continuing education in anesthesia. Crit Care & Pain. Nov 2006;6:225-9.

2. Iperna HJ and Tanzi MG. Use of topical tranexamic acid and aminocaproic acid to prevent bleeding after major surgical procedures. Ann Pharmacother.

Jan 2012;46:97-107.

3. Grossc PL, Murray RK, Rand ML. Hemostasis & Thrombosis. In: Murray RK, Kennelly PJ, Rodwell VM et al. eds. Harper’s Illustrated Biochemistry. 29th ed.

New York, NY: McGraw-Hill; 2011. http://www.accesspharmacy.com/content. aspx?aID=55886653. Accessed September 22, 2013.

4. CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusions in trauma patients with significant haemorrhage (CRASH-2): a randomized, placebo-controlled trial. The Lancet.

2010;DOI:10.1016/S0140-6736(10)60835-5.

5. Zehnder JL. Drugs Used in Disorders of Coagulation. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic & Clinical Pharmacology. 12nd ed. New York, NY: McGraw-Hill; 2012. http://www.accesspharmacy.com/content.aspx?aID=55826748. Accessed September 16, 2013.

6. Dunn CJ and Goa KJ. Tranexamic acid a review of its use in surgery and other indications. Drugs. Jun 1999;57(6):1005-1032.

7. Cyklokapron [package insert]. New York, NY: Pharmacia & Upjohn Co, Division of Pfizer Inc. 2013.

8. Lysteda [package insert]. Atlanta, GA: Ferring Pharmaceuticals Inc; 2011.

9. Lexi-Comp Online, Lexi-Drugs. Hudson, Ohio: Lexi-Comp, Inc.; September 20, 2013.

10. Gandhi R, Evans HMK, Mahomed SR, Mahomed NN. Tranexamic acid and the reduction of blood loss in total knee and hip arthroplasty: a meta-analysis. BMC Research Notes. 2013;6(184).

11. Maniar RN, Orth MS, Orth MCh, et al. Most effective regimen of tranexamic acid in knee arthroplasty: a prospective randomized controlled study in 240 patients. Clin Orthop Relat Res. 2012;470:2605-2612.

View full References list azpharmacy.org/ajpClinicalPrt2Ref References: Introduction to Clinical Pearls

1. Canaday B. ASHP’s Clinical Pearls. Bethesda, MD: American Society of Health-System Pharmacists; 2009.

Primer on Political Advocacy

1. Library of Congress. S. 3187 – 112th Congress (2011-2012): Food and Drug Administration safety and innovation act. Available at https://www.congress.gov/ bill/112th-congress/senate-bill/3187?q=%7B%22search%22%3A%5B%22Title+X+of+the+Food+and+Drug+Administration+Safety+and+Innovation+Act+%28FDASIA%29%22%5D%7D. Accessed September 1, 2014.

2. U.S. Government Printing Office. Public Law 113-54 – Drug Quality and Security Act. Available at http://www.gpo.gov/fdsys/pkg/PLAW-113publ54/pdf/PLAW-

ACPE UAN# 0100-0000-15-087-H04-P This article is accredited for pharmacists only.

To receive CPE credit you must complete the quiz and evaluations on page 37 & 38.

The Arizona Pharmacy Association is accredited by the Accreditation council for Pharmacy Education as a provider of continuing pharmacy education.

CONTINUING EDUCATION QUIZ QUESTIONS

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From A to Z: Clinical Pearls for the Pharmacist - Part 2.“Primer on Political Advocacy, Tranexamic Acid in Orthopedic Surgery, Two-Bag System for Fluid Management in Pediatric Diabetic Ketoacidosis, Thiamine for Acute Alcohol Withdrawal, Penicillin Allergies and Cross Reactivity with Cephalosporins/Carbapenems, Integrase Strand Transfer Inhibitors for HIV” ACPE UAN# 0100-0000-15-087-H04-P 1. A “clinical pearl” is best intended to: a. convey one idea, concept, fact, or other information that a clinician has found useful in day-to-day patient-care, but may not be widely known, understood, published, or taught. b. convey multiple ideas, concepts, facts, or other information that a clinician has found useful in day-to-day patient-care and is widely known, understood, published, or taught.

2. Which of the following resources serve as the most ideal venue to identify an individual’s congressional representative(s) based on zip code? a. www.votesmart.org b. www.nabp.net c. thomas.loc.gov d. www.ncsl.org 3. Which of the following serves as a comprehensive electronic resource combining the six steps of advocacy into a single location for advancing pharmacists as providers? a. www.naspa.us/statepharmacy.html b. www.ashp.org/menu/Advocacy/GrassrootsNetwork c. www.contactingthecongress.org d. www.federalregister.gov 4. Tranexamic acid exerts its antifibrinolytic effect by: a. Inhibiting tissue plasminogen activator b. Inhibiting the release of alpha 2-antiplasmin c. Binding to plasminogen d. Binding to fibrin 5. All of the following are contraindications to tranexamic acid except: a. Active deep venous thrombosis b. Subarachnoid hemorrhage c. Color vision defects d. Recent exposure to aminocaproic acid

6. Potential benefits of the two-bag system for pediatric diabetic ketoacidosis include: a. Rapid correction of serum glucose, bicarbonate, and ketones b. Decreased costs of IV fluid therapy c. Faster response time in making IV fluid changes d. All of the above 7. All of the following are characteristics of the two-bag system for pediatric diabetic ketoacidosis except: a. Bag B contains dextrose and Bag A does not contain dextrose b. Bags A and B have identical electrolyte content c. The IV fluid rates of Bags A and B are always the same d. The IV fluid rates of Bags A and B are adjusted according to the patient’s serum glucose level 8. Which dose of thiamine would be the most appropriate for a patient with severe alcohol withdrawal and nystagmus presenting to the emergency department? a. 100 mg PO b. 100 mg IV c. 500 mg PO d. 500 mg IV 9. What percentage of patients with self-reported penicillin allergies are not truly allergic? a. 50-60% b. 60-70% c. 70-80% d. 80-90% 10. Which of the following is not an HIV integrase strand transfer inhibitor? a. elvitegravir b. dolutegravir c. darunavir d. raltegravir 11. Which of the available integrase strand transfer inhibitors may be used concomitantly (at higher doses) with rifampin? a. elvitegravir b. dolutegravir c. raltegravir d. A and B e. B and C f. All of the above

ACPE UAN# 0100-0000-15-087-H04-P To receive CPE credit you must complete the quiz and evaluations on page 38.

Winter 2015 • ArizonA JournAl of PhArmAcy • 37

CONTINUING EDUCATION ANSWER SHEET:

I.

From A to Z: Clinical Pearls for the Pharmacist - Part 2.

ACPE UAN# 0100-0000-15-087-H04-P Activity accredited date: 10/20/2015 Expiration date: 10/20/2018. This activity is accredited for 1.5 contact hours (0.15 CEUs) 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.

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6. a. b. c. d.

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3. a. b. c. d.

8. a. b. c. d.

4. a. b. c. d.

9. a. b. c. d.

5.

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c. c.

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