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Articles written by students, residents, and new practitioners are welcome. Mentors and preceptors – please consider advising your mentees and students to submit their appropriate written work to NCP for publication.
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For questions, please contact Tina Thornhill, PharmD, FASCP, BCGP, Editor, at tina.h.thornhill@ gmail.com
Official Journal of the North Carolina Association of Pharmacists
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EDITOR-IN-CHIEF
Tina Thornhill
LAYOUT/DESIGN
Rhonda Horner-Davis
EDITORIAL BOARD MEMBERS
Anna Armstrong
Jamie Brown
Lisa Dinkins
Jean Douglas
Brock Harris
Amy Holmes
John Kessler
Angela Livingood
Bill Taylor
BOARD OF DIRECTORS
EXECUTIVE DIRECTOR
Penny Shelton
PRESIDENT
Ouita Gatton
PRESIDENT-ELECT
Bob Granko
PAST PRESIDENT
Matthew Kelm
TREASURER
Ryan Mills
SECRETARY
Beth Caveness
Madison Wilson, Chair, SPF
Anita Yang, Chair, NPF
Katie Trotta, Chair, Community
Jeff Reichard, Chair, Health-System
Dave Phillips, Chair, Chronic Care
Andy Warren, Chair, Ambulatory
Riley Bowers, At-Large
Elizabeth Locklear, At-Large
Macary Weck Marciniak, At-Large
North Carolina Pharmacist (ISSN 0528-1725) is the official journal of the North Carolina Association of Pharmacists. An electronic version is published quarterly. The journal is provided to NCAP members through allocation of annual dues. Opinions expressed in North Carolina Pharmacist are not necessarily official positions or policies of the Association. Publication of an advertisement does not represent an endorsement. Nothing in this publication may be reproduced in any manner, either whole or in part, without specific written permission of the publisher.
As I write my column, it is Labor Day weekend, and in the spirit of this holiday, which pays tribute to the contributions and achievements of American workers, I cannot help but celebrate the accomplishments of the North Carolina Association of Pharmacists. The 2023 year, thus far, has been one teeming with activities designed to build awareness, create value, and generate a voice for the profession. Despite or perhaps due in part to the pandemic, NCAP has been carrying out increasingly more work for and on behalf of North Carolina’s pharmacy professionals. As your Executive Director, for me the work is more than a job; it is a labor of love for both the profession and the relentless pursuit of the Association’s mission and vision
Labor Day is viewed by many as the end of summer, and it is a perfect time to pause, and not only reflect on our accomplishments but also give careful consideration to our direction. The NCAP tagline is “Advancing Pharmacy. Improving Health.” Our tagline, in four words, summarizes our purpose. A purpose that serves as our north star, a purpose that is enduring, and one that always has us reaching for betterment! In essence, NCAP’s purpose, or rather our work in pursuit of purpose, is a journey. To draw from Matthew Kobach’s quote, “Progress isn’t linear, success isn’t linear... life isn’t linear...”, well, the same is true
Penny Shelton, PharmD, FASCP, FNCAP
for NCAP’s journey. Along the way, in the midst of all ‘the doing’, and ‘heads down working hard’, we can lose sight of the best path forward. Time eludes us, and when we look up another year is gone. Life rushes at us, and at work, or even in the running of an Association, we can become swept up in the doing, perhaps even forget how important it is to pause, reset, and reorient ourselves.
Today we have the modern technology of GPS to get us from point A to B, and to keep us from losing our way while traveling. However, for NCAP’s journey, there is no crystal ball to tell us we have set a correct course, and there is no Association GPS to safely guide us to our destination. I would say our navigation checks and balances are more akin to Galileo’s orienteering methods. Furthermore, the speed of information, and the changes happening in healthcare and pharmacy, can take us off course, as well as illuminate new and better paths. All the nebulousness places greater importance on the need for NCAP to periodically stop, look up, and reassess where we are on our journey. As we enter into the Fall of 2023, NCAP will be doing just that. We will be reexamining our operations, partnerships, programming, and resources, and adjusting our strategic plan, with the intent to ensure we are still on a path to success.
One of my favorite songs is Noah (Stand Still) by Noah and Billy Ray Cyrus. The lyrics, “When you don’t know where you’re going, just stand still, soon enough you will...It don’t get easier, just harder, yes, it will, remember, just stand still...67 thousand miles an hour around the sun, and that’s how it feels, just stand still...”, although performed as parent-tochild advice, the message has more universal application. In our work at NCAP, I can particularly relate to the 67 thousand miles an hour line. We have been extraordinarily busy building NCAP value, so much so, that it sometimes feels as though we have hundreds of balls or simultaneously spinning plates in the air. It is time to stand still, take inventory of our labor, and determine whether to continue, discontinue, or adjust actions in our “Advancing Pharmacy. Improving Health.” journey. I look forward to updating you on our progress. Until then give the Cyrus song a listen, and thank you for your labor of love as pharmacy professionals.
As students, the idea of being perfect all the time becomes engrained from the beginning of grade school with the introduction of letter grades tied to performance. From admission to pharmacy school forward, those with self-identified high standards are often the most successful. High achievers get admitted, earn recognition on the dean’s list or within organizations, and may even get preference at rotation sites. In a study that included 72 pharmacy students at the Medical University of South Carolina (MUSC), students rated themselves highly in self-oriented perfectionism (attempts to be perfect in one’s work and to regularly criticize one’s performance) and other-oriented perfectionism (expecting a great deal of others).1 This is concerning, as studies (e.g., Blatt 1995) have shown a “strong association between perfectionism and increased risk for depression, anxiety, obsessive-compulsive symptoms, and suicide.”1,2 This was reflected in the MUSC study group, with pharmacy students showing the highest risk of psychological distress.1
In pharmacy school, having an ‘av-
erage’ GPA with no additional experience may not be enough to get someone to the desired next step in their career. Therefore, being a high achiever becomes the standard, and the bar is constantly raised to match other high performers. Students dedicate themselves to building the best resume or curriculum vitae to look as perfect as possible on paper. Students strive for the highest grades and feel bad about themselves if they do not get A’s.
Unsurprisingly, the profession requires perfection, as anything less puts patients at risk. In school, students train their attention to detail, test their ability to catch mistakes, and identify all problems in patient cases. Students are prepped for the perfection needed to get the job, but what happens when they get the job and find out that wanting to be perfect all the time can be harmful?
Dr. Coble: My baseline perfectionism served me well once I was admitted to pharmacy school with residency in mind. I got excellent grades, interned at a large hospital, participated in clubs and organizations, and completed plenty of research. My professors and preceptors consistently provided positive reinforcement, pushing my self-expectations higher. I was turning myself into the perfect residency candidate, and it worked out for me. I got a PGY1 pharmacy residency, finished my last year of pharmacy school strong, and passed my licensure exams without a problem. I knew I was a perfectionist, and I liked it that way.
Becoming licensed and practicing with individual responsibility was difficult for me. I found myself looking for perfect answers when there was not one, unlike the ideal cases presented in school. The lack of constant positive reinforcement made me doubt the knowledge I had spent years learning. Imposter syndrome was hitting, and it was hitting hard. When my preceptor prompted me to reflect on my perfectionism, I noticed how those tendencies that once served me so well were hurting me. I did not feel in control of my life for the first time and did not know how to handle it. I learned that getting to residency and battling the perfectionism that landed me there is extremely common but does not bode well in the long term. It was clear I would need to adapt my perfectionist tendencies and figure out how to still be successful outside of a student environment.
Dr. Kennedy: In my ten years as a residency preceptor, I have worked with more than sixty pharmacy residents who self-identified as type A overachievers; therefore, this resident was not my first perfectionist. As a “leveling up,” residency is often the first time a learner hears critical feedback about their performance, and they usually take it the hardest. I recognize the general glazed-over look from residents when I am providing praise, waiting for the one thing they are doing wrong because I used to be that resident. I ignored the good, waited for the bad, and planned what I would do to be perfect the next day. I am a “reformed” perfectionist with a similar story described above, but it took years to reach that status. As a resident, I could not accept anything less than perfect in my performance and those of my early learners. It took about 15-20 residents and 3-4 years of precepting to identify an average performance and learn how to coach residents to achieve realistic goals during their short time with me in their career training.
While precepting, I noticed that learners with realistic expectations and growth mindsets did better and seemed to enjoy their residency much more than high achievers with fixed mindsets. Despite this, I was not ready to give up my self-imposed high expectations. After a global pandemic hit and routines were upended, I found my compensatory perfectionism behaviors impossible to maintain. I could plan, something would change, and I would have to create another plan. This happened multiple times, and I began to see the time wasted trying to control each outcome. My self-confidence in problem-solving increased, and I realized I did not have to anticipate every problem. Learners with a growth mindset were also thriving in the pandemic dysfunction. I began to ask myself, could perfectionism be maladaptive?
Sara White references Dr. Tal Ben-Shahar’s categorization of perfectionism into adaptive and maladaptive types in his book “The Pursuit of Perfect.”3-5 While both can lead to problems, adaptive is typically less detrimental, characterized as “excellence seeking,” and associated with optimism, pleasure, and desire to improve. Maladaptive is considered “failure avoiding” and is associated with fear, anxiety, unhappiness, and overall negative mental effects. Surprisingly, research has identified that neither improves performance and eventually negatively impacts general health, self-esteem, productivity, and creativity.3-5 White proposes learning when “good enough” is appropriate in situations that will save time and energy when the margin for error is small.3-5
Pharmacists can only partially rid themselves of the perfectionistic mindset because of patient reli-
ance; however, creating a more sustainable lifestyle is essential. When targeting balance, White suggests making “conscious decisions about how to spend one’s finite time and to be happy with one’s choices rather than striving for perfection.”6 In residency and life, we may only be able to give 80% to an activity based on other things we are balancing. We need to learn to be okay with that because it is still our best at that moment. However, assessing what areas of our work and life can be ‘good’ or ‘very good’ versus situations that require perfection is essential – this may take time and practice and adapting using small steps.6
Encouraging and supporting a growth mindset in ourselves and learners will help to avoid the psychological distress that may come with a fixed mindset. Instead of passing on perfectionistic expectations, approaching precepting with
realistic expectations will save endless stress and instill more encouragement in learners. Professors, mentors, and preceptors can model a growth mindset for all learners, identify high-achievers, and start checking on them early to help them realize that it is okay not to be perfect all the time. The growth mindset can be instilled even in how praise is delivered. Studies have shown that praising hard work and effort will promote a growth mindset versus simply praising intelligence.7 Perfectionism is not sustainable, but practicing taking on new challenges and learning from them, regardless of the outcome, is.
Dr. Coble: Approaching the end of my residency, the journey has come full circle, and I have been able to start crucial conversations with coworkers and other learners. Seeing the realization and relief in others when they identify perfectionism as a stressor in their day-to-day life has only further progressed my learning. In addition to continuing the dialogue, countless resources are available to help educate, motivate, and guide the entire journey (because if we do something, we need to be over-prepared to do it perfectly, right?). Simply looking up “perfectionism” on Google pulls up about 58,800,000 sources, including background, assessments, self-help modules, and books. While there are many strategies to start on the road to becoming a “recovering perfectionist,” I have found a few.
Don’t sweat the small stuff. Giving up creative control is difficult for anyone, but especially a perfectionist. Eventually, we must delegate a project section or autonomy to a learner. Continuously obsessing over details and consistently correcting things because they are not exactly how we would say it will only create a negative working envi-
ronment, internally and externally. Be mindful that unless something is wrong or harmful to a patient, it is likely okay that something is not perfect.
Celebrate the little wins. While outside recognition is typically given once a project or task is completed, it is important to identify the successes along the way. As we get further from the learner role, we must become our own cheerleaders. Set realistic benchmarks and timelines and take the time to feel proud of the work along the way. Approach setbacks open-mindedly, assess the learning opportunities, and apply them to the next attempt instead of backtracking from failure.
Focus on the big picture. Some days may not go exactly as planned; instead of marking it as a bad day, try to widen the lens. Despite failures, applying the situation to the big picture usually reveals something positive.
Letting go of the perfectionistic tendencies is daunting and not something that can be done in one day. It is a long journey with many setbacks, refocuses, and much reflection. The habits were not formed in one day, and perfecting the art of non-perfectionism takes time. While the journey is ongoing, the benefits will be noticeable sooner than expected. Life will become much more enjoyable without the extra pressure and unrealistic expectations placed on ourselves. We often forget to give ourselves grace, forgetting we still practice, learn, and improve daily. “Treat yourself like someone you love.”8 We will not have everything figured out after graduation, residency, or even in the first years of our professional
practice. Therefore, as pharmacists, we should spend every day giving our best at that moment showing up for our patients, and the rest will work itself out.
Authors: Erin Baily Coble, PharmD, at the time of this submission, was a PGY1 Pharmacy Resident at Novant Health New Hanover Regional Medical Center, Wilmington, NC. She is currently a Clinical Pharmacist at Novant Health Forsyth Medical Center, Winston-Salem, NC; bailycoble007@gmail.com. Amanda Kennedy, PharmD, BCPS, Clinical Pharmacist; Novant Health New Hanover Regional Medical Center, Wilmington, NC.
References
1. Henning K, Ey S, Shaw D. Perfectionism, the imposter phenomenon and psychological adjustment in medical, dental, nursing and pharmacy students. Med Educ. 1998;32(5):456-464.
2. Blatt SJ. The destructiveness of perfectionism. Implications for the treatment of depression. Am Psychol. 1995;50(12):1003-1020.
3. White S. Smart Use of Perfectionism. Women in Pharmacy Leadership. 2021
4. MindTools | Home. www.mindtools. com. https://www.mindtools.com/ a4jvsqi/perfectionism
5. Tal Ben-Shahar. The Pursuit of Perfect: How to Stop Chasing Perfection and Start Living a Richer, Happier Life. McGraw-Hill Professional; 2009.
6. White SJ. Perfectionism: A Stumbling Block to Effective Leadership? (Every Pharmacist Must Be a Leader). Hosp Pharm. 2016;51(6):429-430.
7. Mindset Works. The Growth Mindset - What is Growth Mindset - Mindset Works. Mindsetworks.com. Published 2017. https://www.mindsetworks. com/science/
8. Roa A. Treat Yourself Like Someone You Love. https://adamroa.com/products/treat-yourself-like-someone-youlove-3-tools-to-make-self-love-easierbook
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By:
Introduction
Paclitaxel is a cytotoxic chemotherapy agent used commonly in treating breast, ovarian, and lung cancers. Paclitaxel belongs to the taxane class of medications and exerts its effects by inhibiting microtubule function in cells as they replicate.1 In addition to the potential effects of myelosuppression, peripheral neuropathy, hepatotoxicity, and alopecia, paclitaxel can potentially cause life-threatening infusion-related or hypersensitivity reactions.1 Interestingly, this reaction is not caused by paclitaxel itself but rather by the Cremaphor EL solvent in which it is supplied.2 Ninety percent of these reactions occur within the first 10-15 minutes of the patient’s first two infusions. This reaction occurs because of an IgE-mediated release of histamine, which presents with symptoms of flushing, pruritus, urticaria, hypotension, erythematous rash, tachycardia, low back pain, chest pain, and respiratory distress. The severity of these reactions can be assessed using the Common Terminology Criteria for Adverse Events and assigned a grade of 1 through 5, with 5 being the most severe.
Patients with a grade 1 or 2 reaction may require oral intervention and have their paclitaxel infusion lengthened in response to their reaction, but they can proceed with treatment. In general, patients with a grade 3 reaction or higher require intravenous intervention in response to their reaction and should not resume treatment with paclitaxel, resulting in an altered therapy plan.3 Due to this risk, it is recommended that patients receiving paclitaxel are premedicated with diphenhydramine, famotidine, and dexamethasone.1,3
Current Cancer Care Ontario guidelines recommend 20 mg of intravenous dexamethasone as premedication for patients receiving paclitaxel every three weeks and 10 mg for weekly paclitaxel regimens.4 However, recent studies show that a dexamethasone dose of 10 mg is as effective in preventing infusion-related reactions as higher doses of dexamethasone.5 Limiting the dexamethasone dose reduces the potential for adverse effects such as hyperglycemia, insomnia, and immune suppression.
Our health system’s premedication
regimens of dexamethasone for paclitaxel protocols are not standardized, with variability in 10 mg versus 20 mg doses. This study aims to reduce overall steroid exposure by standardizing dexamethasone dosing in paclitaxel order sets in outpatient infusion centers.
This pre-post intervention, IRB-exempt study was conducted across seven oncology clinics within a single health system. Patients were included if they were over 18 years and received a paclitaxel infusion through an established order set. The intervention consisted of updating all paclitaxel treatment plans in the health system to default to a standardized premedication dose of 10 mg intravenous of dexamethasone. Pre- and post-intervention data were gathered on patient demographics, cancer type and stage, chemotherapy regimen, premedication regimen, and adverse reactions experienced. Pre-intervention, retrospective data were collected via chart review from an electronic medical record report
of all patients given paclitaxel at health-system infusion centers. Post-intervention data were collected from a separate report using the same criteria.
The primary outcome measured in this study was the incidence of paclitaxel-related infusion reactions with a standard dexamethasone dose of 10 mg compared to pre-intervention. Additionally, infusion reaction grade was recorded as a secondary outcome.
Patient characteristics were summarized using frequencies, percentages, or means as appropriate, and the chi-square test was used for dichotomous data. Noninferiority was determined using the 95% confidence interval for the difference in the incidence of reaction between the two groups.
Pre-intervention data were collected between July 1st and October 28th, 2021, on 51 patients. The intervention was implemented on July 1st, 2022. Post-intervention data were collected from July 1st to December 1st, 2022, on 97 patients. We did not exclude any patients from our analysis. Overall, baseline characteristics were similar between groups (Table 1).
The average dexamethasone dose per patient was lower in the post-intervention group (12.4 mg vs. 9.8 mg). In the pre-intervention group, 25% of patients received a dexamethasone dose of 20 mg. All
patients in the post-intervention group received a dexamethasone dose of 10 mg or less (Table 2).
Regarding the primary outcome, six patients (11.8%) in the pre-intervention group and six patients (6.2%) in the post-intervention group experienced a hypersensitivity reaction. This resulted in a risk difference of -0.06 (95% CI -0.16 to 0.04, p=0.24) (Figure 1).
In the pre-intervention group, four of the six patients who experienced a reaction received a 10 mg dose of dexamethasone. The remaining two patients who underwent hypersensitivity reactions received a 20 mg dexamethasone dose. All six patients who experienced reactions in the post-intervention group received a 10 mg dexamethasone dose. The six reactions in the pre-intervention group were grade 2, only requiring oral intervention and lengthening of the paclitaxel infusion. Five grade 2 and one grade 3 reactions in the post-intervention group involved bronchospasm and required intravenous intervention. All patients who experienced a hypersensitivity reaction did so with either the first or second dose of paclitaxel. Of patients who underwent infusion reactions, the average paclitaxel dose was similar between the two groups at 121.7 mg/ m2 in the pre-intervention group and 110.0 mg/m2 in the post-intervention group. Of note, all patients who experienced an infusion reaction could continue the infusion (Table 3).
in patients receiving paclitaxel was no different for those who received a 10 mg dose of dexamethasone versus those who received a higher dose. Neither dexamethasone nor paclitaxel dosing correlated with the incidence or grade of infusion reactions, consistent with existing literature.5 Most infusion reactions occurred with administering the patient’s first paclitaxel dose. Nearly all reactions observed were grade 2 reactions, only warranting oral intervention. All patients who experienced infusion reactions could continue the infusion, leaving their overall treatment plan unaffected. As predicted, average steroid exposure per patient was lower in the post-intervention standardized 10 mg dexamethasone dosing group. Although the paclitaxel protocols were normalized to a default dexamethasone dose of 10 mg, some providers did change the order to a lower dose of dexamethasone. This resulted in three patients in the post-intervention group receiving less than 10 mg of dexamethasone with each infusion.
Although this study successfully showed that a dose of dexamethasone 10 mg is non-inferior to 20 mg for preventing hypersensitivity reactions, it has some limitations. First, there was a relatively small patient population despite the study being conducted across several cancer centers. Additionally, we could not track the incidence or severity of chemotherapy-induced nausea and vomiting, which may be a compelling indication to utilize dexamethasone.
In this study, the incidence of experiencing a hypersensitivity reaction
We plan to use this data to inform future studies to decrease further steroid exposure in patients receiving paclitaxel-based chemo-
therapy regimens. Literature has shown promising results for dexamethasone omission in later cycles, as hypersensitivity reactions after the second dose of paclitaxel are rare.6,7,8 Additionally, tapering dexamethasone dosing limits steroid exposure without increasing the risk of hypersensitivity reactions.9 Another option for future studies is the implementation of a decision-tree-based algorithm to assist physicians in selecting steroid doses based on patient-specific factors, such as the risk for steroid-induced side effects.
This study showed that dexamethasone dosing could be safely lowered to 10 mg for premedication in patients receiving paclitaxel.
Authors: Kinsey McClure, PharmD. PGY1 Acute Care Pharmacy Resident, Moses Cone Hospital. kinseymcclure27@gmail.com. Teresa Turner, PharmD. Clinical Informat-
ics Pharmacist, Cone Health Cancer Centers. Andre Harvin, PharmD, MS, BCPS. Executive Director of Pharmacy, Cone Health Oncology. Sarah Mills, PharmD. PGY2 Clinical Pharmacogenomics Resident, Sanford Imagenetics.
1. Paclitaxel [package insert]. Bristol-Myers Squibb Company. 2011.
2. Gelderblom H, Verweij J, Nooter K, Sparreboom A. Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer. 2001 Sep;37(13):1590-8.
3. Weiss RB, Donehower RC, Wiernik PH, et al. Hypersensitivity reactions from taxol. J Clin Oncol. 1990 Jul;8(7):12638.
4. Crespo, A., Forbes, L., Gallo-Hershberg, et al.(2019). Management of cancer medication-related infusion reactions. https://www.cancercareontario.ca/en/guidelines-advice/typesof-cancer/60646. Published August 2019. Accessed June 5th, 2023.
5. Lansinger OM, Biedermann S, He Z, Colevas AD. Do Steroids Matter? A Retrospective Review of Premedica-
tion for Taxane Chemotherapy and Hypersensitivity Reactions. J Clin Oncol. 2021 Nov 10;39(32):3583-3590.
6. Berger MJ, Vargo C, Vincent M, et al. Stopping paclitaxel premedication after two doses in patients not experiencing a previous infusion hypersensitivity reaction. Support Care Cancer. 2015 Jul;23(7):2019-24.
7. Parinyanitikul N, Tanpipattanakul W, Poovorawan N, et al. Incidence of an infusion hypersensitivity reaction after withholding dexamethasone premedication in early breast cancer patients not experiencing two previous cycles of infusion hypersensitivity reaction for weekly paclitaxel chemotherapy. Support Care Cancer. 2018 Jul;26(7):2471-2477.
8. de Castro Baccarin AL, Irene MN, de Iracema Gomes Cubero D, et al. The feasibility of dexamethasone omission in weekly paclitaxel treatment for breast cancer patients. Support Care Cancer. 2019;27(3):927-931.
9. Braverman AS, Rao S, Salvatti ME, Adamson B, McManus M, Pierre S. Tapering and discontinuation of glucocorticoid prophylaxis during prolonged weekly to biweekly paclitaxel administration. Chemotherapy. 2005 May;51(2-3):116-9.
By: Dr. Amanda Day Dr. Lindsey Tincher
Unfractionated heparin (UFH) is an anticoagulant utilized for many conditions, such as acute coronary syndrome and deep vein thrombosis.1,2 Many institutions use aPTT levels for UFH monitoring; however, as anti-factor Xa monitoring has become more cost-effective, increasing evidence has shown decreased time to therapeutic level, increased time in therapeutic range, and decreased adverse events compared to aPTT levels for the monitoring of UFH.3,4 As a result, more institutions are transitioning to anti-factor Xa levels.5 Prompted by integrating two health systems and completing an internal medication use evaluation (MUE), this institution proposed adopting a UFH anti-factor Xa monitoring protocol.
Novant Health New Hanover Regional Medical Center (NHNHRMC) is an 800-bed hospital in Wilmington, North Carolina. It is a regional referral center, teaching hospital, and UNC School of Medicine branch campus. It offers specialty medical and surgical care, including women’s, children’s, orthopedic, rehabilitation, and psychiatric hospitals, as well as a level II trauma center.
NHNHRMC officially became a part of Novant Health on February 1, 2021, and is integrating with Novant Health.6 Integration has prompted a review of many protocols and procedures throughout the hospital, including UFH protocols. Novant Health utilizes anti-factor Xa levels for monitoring UFH, and the integration prompted a comparison of UFH monitoring protocols within the NHNHRMC and Novant Health systems. There was a review of the current aPTT UFH protocols through an MUE, an evaluation of existing literature around UFH monitoring, and a comparison between the current NHNHRMC aPTT protocol and the Novant Health anti-factor Xa monitoring protocol.
An MUE was completed in the fall of 2022 to promote patient-safe heparin practices. At NHNHRMC, UFH protocols utilize nursing-driven titrations to achieve a therapeutic aPTT range of 45 to 68 seconds. Supratherapeutic levels are divided into three timespans: 68.1 to 90 seconds, 90.1 to 133.6 seconds, and more than 133.6 seconds, each requiring a specific nursing action. The MUE results identified protocol
adherence issues with supratherapeutic aPTT levels, mainly when they are greater than 133.6 seconds (41% adherence to protocol). Over half of these cases were associated with incorrect rate adjustments and monitoring.
While comparing the two protocols, several significant differences were noted beyond the change in monitoring parameters. The first is a difference in the weight used to determine dosing for each patient. NHNHRMC utilizes adjusted body weight when BMI exceeds 30 kg/ m2, while Novant Health uses actual body weight in all patients. Secondly, there is no dose cap in the NHNHRMC dosing protocol, while Novant Health uses capped doses. The Novant Health protocol safely ensures adherence to dosing caps using a heparin calculator to facilitate dose cap calculations and minimize dosing errors. Thirdly, while Novant Health’s protocol primarily uses anti-factor Xa levels, some instances, such as recent DOAC use, would necessitate aPTT monitoring instead. Lastly, the therapeutic ranges for aPTT levels differed between the two protocols.
The therapeutic range for aPTT monitoring is not standardized in clinical practice. Therapeutic ranges of aPTT can vary due to the vast number of available reagents used to perform the assay and the variation within their components, such as the amount of activators and phospholipid content.7,8 Keeping current aPTT therapeutic values would require a revision of the Novant Health protocol rather than straightforward adoption. Several logistical barriers arose while considering protocol integration. First, there was consideration of the anti-factor Xa testing and securing resources to perform inhouse testing. Laboratory leadership was able to provide sufficient personnel and equipment to support the necessary number of levels required for heparin monitoring hospital-wide. Additionally, necessary clarification on the procedures around drawing anti-factor Xa levels, including laboratory tubes, result time for a level, and blood draw techniques, were required. As part of the integration, NHNHRMC will change from Epic to Epic Dimensions, which Novant Health utilizes. To promote patient safety, it would be preferred to have the UFH monitoring protocol built before Epic integration, which would require the new order sets and heparin calculator to be built into the existing NHNHRMC Epic. The support and involvement of medical and nursing staff will be integral to a successful UFH protocol integration. Additionally, education and training of pharmacy, medical, and nursing staff personnel are necessary to make this transition as smooth as possible.
Key takeaways from this project include: the potential to improve patient care with heparin anti-factor
Xa monitoring, transitioning from aPTT levels to anti-factor Xa can be met with unforeseen barriers, and transitioning requires long-term planning, staff education, and collaboration from multiple departments.
Authors: Amanda Day, PharmD, Amanda.Day@novanthealth.org ; Lindsey Tincher, PharmD, BCCCP; Novant Health New Hanover Regional Medical Center; Wilmington, NC.
Sean T, White HD, Layland J. Heparin use in acute coronary syndromes and cardiovascular interventions: habit or evidence-based?. European Heart Journal Volume 43, Issue 10, 7 March 2022, Pages 1008–1011, https://doi.org/10.1093/eurheartj/ehab896
McRae SJ, Ginsberg JS. Initial Treatment of Venous Thromboembolism. American Heart Association. 2004;110;I3-9. https://doi. org/10.1161/01.CIR.0000140904.52752.0c
Frugé KS, Lee YR. Comparison of unfractionated heparin protocols using anti-factor Xa monitoring or activated partial thrombin time monitoring. Am J Health
Syst Pharm. 2015;72(17 Suppl 2):S90-S97. doi:10.2146/sp150016
Guervil DJ, Rosenberg AF, Winterstein AG, et al. Activated partial thromboplastin time versus antifactor Xa heparin assay in monitoring unfractionated heparin by continuous intravenous infusion. Ann Pharmacotherapy. 2011;45:861–8.
Vandiver JW, Vondracek TG. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy. 2012;32(6):546-558. doi:10.1002/j.18759114.2011.01049.x
Still JF. Leaders Reflect on One-year Anniversary of Novant, NHRMC Sale Closing. WilmingtonBiz. February 1, 2022. Accessed May 30, 2023. https://www.wilmingtonbiz.com/health_care/2022/02/01/ leaders_reflect_on_one- year_anniversary_of_novant_nhrmc_sale_closing/22817 Kato K, Hatayama Y, Shimohiro H, Ichikawa H, Fukuda T. Differences in the Composition of Activated Partial Thromboplastin Time (APTT) Reagents Affect Clot Waveform Analysis. Yonago Acta Med. 2022;65(3):226-230. Published 2022 Aug 29. doi:10.33160/yam.2022.08.013
Shetty S, Ghosh K, Mohanty D. Comparison of four commercially available activated partial thromboplastin time reagents using a semi-automated coagulometer. Blood Coagul Fibrinolysis. 2003;14(5):493-497. doi:10.1097/00001721-200307000-00011
ZavzpretTM (zavegepant), by Pfizer, was approved by the FDA in March 2023 as an intranasal spray for the abortive treatment of adult patients with acute migraines with or without aura. (1,2) The dose is a single 10mg intranasal spray into one nostril one time a day as needed for treating acute migraine. (1,2). The maximum dose in 24 hours is one spray; there is no safety information regarding the use of zavegepant more than 8 times in 30 days (1,2). Additionally, the use in patients with hepatic or renal impairment has not been studied; thus, zavegepant is not recommended in those with severe hepatic impairment (Child-Pugh Class C) or have a CrCl <30 mL/minute (1,2).
Zavegepant works by antagonizing the CGRP receptor, which blocks the 37-amino acid CGRP neuropeptide from binding. CGRP, a strong vasodilator released from sensory nerves, plays a strong role in the pain pathway. Stimulating meningeal blood vessels may produce pain that can lead to migraines. CGRP re-
ceptors are spread throughout the central and peripheral nervous system, but the ligand itself is unable to permeate the blood-brain barrier. As a result, the action of CGRP is peripheral in nature, and therefore so is the pain associated with migraines. Zavegepant antagonizes these CGRP receptors, thus inhibiting the neuronal signals to abort the migraine.
Following intranasal administration, zavegepant reaches peak plasma concentration after ~ 30 minutes. The absolute bioavailability of the drug is 5%. The protein binding of zavegepant is 90%, and it has a volume of distribution of 1774 L. It is primarily metabolized via CYP3A4, with some activity by CYP2D6 as well. There are no major metabolites present in human plasma. Zavegepant’s half-life is 6.55 hours, and is excreted primarily as inactive metabolites in bile/feces.
Zavegepant received approval for treating acute migraines, with or
without aura, following the results of a phase 3, randomized, double-blind, placebo-controlled trial. The trial randomized 1405 patients in a 1:1 fashion to zavegepant 10mg nasal spray or placebo to treat a migraine of moderate to severe intensity over a 45-day period. Patients in the study had an average age of 40.8 years and were primarily female (83%) and white (83%). In a continuation of the phase 2 clinical trial that established the efficacy of zavegepant, patients were included in the study if their first migraine occurred before age 50 years, had between two to eight migraines of moderate-severe intensity each month, and experienced a migraine or non-migraine headache for less than 15 days each month in the three months before screening. They also had to be able to tell the difference between migraines and other types of headaches.
The co-primary endpoints (evaluated two hours post-dose) of the phase 3 trial were freedom from pain and freedom from the patient’s most bothersome symptom, identi-
fied at the beginning of the trial as either photophobia, phonophobia, or nausea. A nominal, 4-point scale was used to assess freedom from pain, with 0 meaning “no pain” and 4 meaning “severe pain.” The primary endpoint of freedom from the most bothersome symptom was a binary scale of 0, meaning “absent,” or 1 meaning “present.” There were 17 secondary endpoints, including the return to normal functioning ability, sustained pain relief, and no need for rescue medication.
To provide adequate power for the study, each group needed at least 630 patients for 91% power; in the final analysis, there were 623 patients in the zavegepant group and 646 in the placebo group. The superiority of zavegepant to placebo was measured based on an alpha level of 0.05 for the co-primary endpoints and had to be considered superior in both categories to be superior overall.
The phase 3 trial results found zavegepant superior to placebo in the co-primary endpoints. Freedom from pain was experienced by 23% of patients in the treatment group and 15% of patients in the placebo group (95% CI, 4.5-13.1; p < .0001). Freedom from the patient’s most burdensome symptom was experienced by 40% of patients in the treatment group and 31% of the patients in the placebo group (95% CI, 3.4-13.9; p < .0012). For 13 of the 17 secondary endpoints, zavegepant was considered statistically significant over placebo. Adverse events were more common in the treatment group, with the most common being dysgeusia (21%), nasal discomfort (4%), and nausea (3%). However, no serious adverse effects were reported or
caused discontinuation of therapy. This trial, therefore, confirmed the results seen in a previous phase 2 trial, establishing zavegepant’s tolerability and treatment benefits in this patient population.
In a phase 2 randomized, placebo-controlled trial, the efficacy and safety of zavegepant as a nasal spray to treat acute migraines were evaluated. The trial randomized 1673 patients in a 1:1:1:1 manner, with patients receiving either 5 mg, 10 mg, 20 mg, or placebo intranasally. The participants included men and women 18 years of age and older with at least a 1-year history of migraine. This history had to include the onset of migraine occurring before age 50, lasting 4-72 hours if left untreated, no more than eight migraine attacks each month, and being able to tell the difference between migraine and cluster or tension headaches. Participants were primarily female (85.5%) and white (78.3%).
The population was analyzed using intention-to-treat principles, so all patients were analyzed according to the group to which they were originally allocated. The co-primary endpoints were freedom of pain and/or freedom from the symptoms associated with migraines, significant for the co-primary endpoints compared to placebo. Freedom of pain was seen by 22.5% of those in the 10mg group (98.3% CI, 17.5-27.6; p = .0113), 23.1% of patients in the 20mg group (98.3% CI, 18.1-28.2; p = .0055), and 15.5% of patients in the placebo group (98.3% CI, 11.1-19.8).
Patients in the 10 mg, 20 mg, and placebo groups experienced phonophobia, photophobia, or nausea
at a rate of 41% (98.3% CI, 36.047.9; p = .0155), 42.5% (98.3% CI, 36.6-48.4; p = .0094), or 33.7% (98.3% CI, 28.0-39.3), respectively. Data found for the 5mg dose were not statistically significant. The importance of this trial was to assess whether zavegepant was more effective than placebo in treating acute migraines, as well as the doses at which it would work best. As these trials did not compare zavegepant to other common migraine therapies, such as “triptans” or oral CGRP receptor antagonists, further trials may be needed to determine its place in therapy. In addition, due to the lack of patients with renal or hepatic impairment, future trials may include these subsets to assess for safety.
Due to increasing the serum concentrations of zavegepant, the manufacturer recommends avoiding concomitant use with leniolisib, OATP1B1/1B3 inducers, or inhibitors (e.g., gemfibrozil, cyclosporine, rifampicin). Concurrent use with intranasal decongestants should be avoided; however, the package insert states that, if necessary, the intranasal decongestant may be administered one hour after zavegepant use.
The most frequently cited adverse effects were altered taste (18%) and nausea (4%).
Zavegepant should be stored at room temperature (68-77 °F) and not frozen. It may only be used once in 24 hours, with a maximum of 8 monthly doses. If any symptoms of an allergic reaction are seen, such as hives or facial swelling, contact
a healthcare provider immediately.
This medication arrives in individual packages; to receive a complete dose, use all the package contents. Zavegepant should be taken intranasally; first, blow your nose. Remove the device from the package and hold it upright with your thumb on the plunger. Press on one nostril with the other free hand to seal it shut. Insert the nozzle into the opened nostril as high as it is comfortable, and slowly breathe in with your nose as you press the plunger to release the contents.
No available data on use in pregnant women; adverse effects were not reported in reproductive animal studies. CGRP receptor antagonists are not recommended during lactation due to a lack of data.
Keep zavegepant at room temperature (20-25°C), with a temporary temperature of 15-30°C permitted for excursions. Do not freeze.
formulation if they cannot use oral agents.
Author: Kaitlyn Becker, PharmD; Class of 2024 Campbell University College of Pharmacy & Health Sciences. kkbecker0411@email. campbell.edu
References
1. Zavzpret (zavegepant) [prescribing information]. New York City, NY: Pfizer Inc; March 2023.
2. Zavegepant. Lexi-Drugs. Hudson, OH: Lexicomp, 2023. http://online.lexi. com/. Updated May 5, 2023. Accessed May 5, 2023.
3. Ubrogepant. Lexi-Drugs. Hudson, OH: Lexicomp, 2023. http://online.lexi. com/. Updated April 20, 2023. Accessed May 5, 2023.
4. Noor N, Angelette A, Lawson A, et al. A Comprehensive Review of Zavegepant as Abortive Treatment
for Migraine. Health Psychol Res 2022;10(3):35506. Published 2022 Jun 28. doi:10.52965/001c.35506
5. Lipton RB, Croop R, Stock DA, et al. Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: a phase 3, double-blind, randomised, placebo-controlled multicentre trial [published correction appears in Lancet Neurol. 2023 May;22(5):e7]. Lancet Neurol. 2023;22(3):209-217. doi:10.1016/S1474-4422(22)00517-8
6. Croop R, Madonia J, Stock DA, et al. Zavegepant nasal spray for the acute treatment of migraine: A Phase 2/3 double-blind, randomized, placebo-controlled, dose-ranging trial. Headache. 2022;62(9):1153-1163. doi:10.1111/head.14389
7. Zavegepant. Micromedex Solutions Greenwood Village, CO: Truven Health Analytics. http://micromedex.com/. Updated April 6, 2023. Accessed May 5, 2023.
5
Zavegepant is the first CGRP receptor antagonist available as a nasal spray. While the most common treatment for acute migraines is triptans (e.g., sumatriptan), CGRP antagonists provide an alternative for patients with cardiac issues who cannot tolerate triptans or those in whom the class has proven ineffective. One of the most common symptoms of migraines is nausea and vomiting; these patients may be unable to tolerate oral therapies, including some CGRP antagonists (such as ubrogepant and rimegepant). Thus, zavegepant may be a viable option for patients desiring a CGRP antagonist in an intranasal
It is that time of year again; flu shot season is upon us. As busy as this season can be, we know you do not want to worry if you have all the documentation you need in case of an audit. Make it easy on yourself by ensuring you are ready now by following PAAS National®’s best practices to reduce your risk of audit recoupment.
1. Authority to administer as outlined by the state’s licensing board(s)
• A signed order from an authorized prescriber
• A signed protocol that is up to date and includes specific vaccination(s) to be administered or a Collaborative Practice Agreement (CPA)
• When using a protocol or CPA, create a placeholder prescription with all prescription elements
• In states where pharmacists have independent authority to vaccinate, create a placeholder prescription with all pre-
2. Vaccination Information Statement (VIS)
• Required to be given to patient prior to each administration
• Be sure you have the most current VIS forms
3. Screening Checklist
• Not requested by PBMs, however should be retained for your records
4. Vaccination Administration Record (VAR)
• Date of Administration
• Name of vaccine administered and manufacturer
• Lot and Expiration Date of vaccine given
• Site of administration (i.e. right arm)
• Signature or initials and title of person administering
• What VIS form was given
• Date printed on the VIS
• Date the VIS was given to the patient or parent/guardian
VAR and VIS forms, and information regarding what the CDC requires for health care providers to record, can be found on the CDC website1 . PAAS Tips:
• Check dates and vaccine types on your protocols to ensure they are up-to-date
• Have current VIS forms printed for each vaccine you administer
• Have VAR forms printed and educate all staff on how to complete the forms
• All vaccines should be submit-
ted using days’ supply of “1” per NCPDP recommendations
• All vaccines administered via protocol should be submitted with origin code of “5” (pharmacy created) per NCPDP recommendations
• Be sure correct metric quantity is billed
• Keep vaccine documents stored in a system that makes access easy in case of an audit
• When billing for vaccine clinics, DO NOT bill prior to the vaccine being administered
• You may submit claims after the date of service, but the date of administration must be correct on the claim
• PAAS has seen pharmacies flagged for billing claims outside regular pharmacy hours – consider billing for vaccine clinics during regular business hours
PAAS National® is committed to serving community pharmacies and helping keep hard-earned money where it belongs. Contact PAAS today at (608) 873-1342 or info@paasnational.com to see why PAAS Audit Assistance membership might be right for you.
By Trenton Thiede, PharmD, MBA, President at PAAS National®, expert third party audit assistance and FWA/HIPAA compliance.
Copyright © 2023 PAAS National, LLC. Unauthorized use or distribution prohibited. All use subject to terms at https://paasnational.com/ terms-of-use/
References:
https://www.cdc.gov/vaccines/ hcp/admin/document-vaccines. html
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ELIZABETH PALAVECINO
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MICROBIOLOGY UPDATES
MELISSA JOHNSON Presents: ID MYTH BUSTERS
NCAP is excited to present an event that brings together infectious disease pharmacists from all across our state. Don't miss out on catching up with colleagues and earning 5 ACPE accredited live CE hours. Space is limited so register today!
Greensboro Country Club
Friday, October 27 From 8 AM - 3 PM
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