Call for Articles
North Carolina Pharmacist (NCP) is currently accepting articles for publication consideration. We accept a diverse scope of articles, including but not limited to: original research, quality improvement, medication safety, case reports/case series, reviews, clinical pearls, unique business models, technology, and opinions.
NCP is a peer-reviewed publication intended to inform, educate, and motivate pharmacists, from students to seasoned practitioners, and pharmacy technicians in all areas of pharmacy.
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.
Don’t miss this opportunity to share your knowledge and experience with the North Carolina pharmacy community by publishing an article in NCP.
Click on Guidelines for Authors for information on formatting and article types accepted for review.
For questions, please contact Tina Thornhill, PharmD, FASCP, FNCAP, Editor, at tina.h.thornhill@gmail.com
North Carolina Pharmacist is the official journal of the North Carolina Association of Pharmacists
Located at: 1101 Slater Road, Suite 110 Durham, NC 27703
Phone: (984) 439-1646
Fax: (984) 439-1649
www.ncpharmacists.org
Official Journal of the North Carolina Association of Pharmacists
1101 Slater Road, Suite 110
Durham, NC 27703
Phone: (984) 439-1646
Fax: (984) 439-1649
www.ncpharmacists.org
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
Tom D’Andrea
PRESIDENT-ELECT
Leigh Foushee
PAST PRESIDENT
Bob Granko
TREASURER
Ryan Mills
SECRETARY
Macary Marciniak
Cassey Zendarski, Chair, SPF
Micaela Hayes, Chair, NPF
Lisa Dinkins, Chair, Community
Trent Beach, Chair, Health-System
Aparna Krishnamurthy, Chair, Chronic Care
Glenn Herrington, Chair, Ambulatory
Angela Livingood, At-Large
Elizabeth Locklear, At-Large
Leslie Barefoot, 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.
North Carolina Pharmacist
A Few Things Inside
Dear Colleagues,
As President of the North Carolina Association of Pharmacists (NCAP), I’m reaching out today to talk about something essential to our profession’s future: our collective strength. The pharmacy community is powerful, but we can only unlock our full potential if we stand together. That’s why I’m excited to invite you to renew your membership and encourage your colleagues to join this vibrant and growing organization!
Why Membership Matters: Empowering Ourselves and Our Profession
Each day, we face new challenges and opportunities in the world of pharmacy. Whether navigating the complexities of patient care, staying ahead of regulatory changes, or ensuring our voices are heard in health policy decisions, our role in the healthcare system is more important than ever.
As a member of the NCAP, you gain access to a wealth of resources that can help you thrive in your career:
• Professional Development: Stay on the cutting edge of pharmacy practice with exclusive access to continuing education programs, webinars, and conferences that help you enhance your skills and knowledge.
• Networking Opportunities: Connect with fellow pharmacists, phar-
President’s Message: Strengthening Our Profession Together – Why Membership Matters
macy technicians, researchers, and health professionals from across the country. The power of community cannot be overstated. By joining, you become part of a vast network that offers mentorship, collaboration, and support.
• Advocacy and Influence: As a unified organization, we can push for the policies that matter most to us. Your membership helps strengthen our collective voice on important issues such as expanding the role of pharmacists in healthcare delivery, advocating for fair reimbursement rates, and promoting access to essential services like immunizations and screenings.
• Exclusive Resources: From access to clinical guidelines and best practices to industry insights and research tools, being a member ensures you have the latest resources at your fingertips to help you provide the highest standard of care to your patients.
Your Membership is Key to Our Shared Success
Our Association is only as strong as its members. By joining, you’re not just gaining resources – you’re directly impacting the future of pharmacy. The more members we have, the greater our influence. Together, we can shape the future of our profession, advocate for the changes we need, and continue to elevate the role of pharmacists in healthcare.
But our work doesn’t end there. Our
profession is evolving at an unprecedented rate, and it’s essential that we remain adaptable. With your membership, you become part of an organization that is driving innovation, policy reform, and a more inclusive vision for the future of pharmacy.
Join Us in Making a Difference
I urge you to become and remain a member of NCAP today. By doing so, you’re investing in your professional growth and contributing to the collective progress of our entire field. We are stronger when we come together.
Whether you are a new graduate just starting out, a seasoned practitioner, or someone passionate about advancing the field of pharmacy, there’s a place for you in our community. Your voice matters, and we need your perspective, expertise, and enthusiasm to keep moving our profession forward.
Together, we can accomplish great things. Let’s join forces to strengthen the pharmacy profession, support one another, and continue our mission to improve patient care. I look forward to welcoming you as a member and working alongside you in the exciting times ahead.
Sincerely,
Tom D’Andrea NCAP President
ThomasD’Andrea, RPh
The Impact of 340B Programs
By: Allison Beatty, PharmD Candidate
As of March 3, 2025, NCAP had been made aware that the North Carolina Health Care Centers Association (NCHCCA) is planning to run 340B protective legislation. NCAP understands that what NCHCCA is planning aligns with the important legislative needs identified by the NCAP 340B Task Force. At this time, our organizations are in further discussion , and the NCAP Board of Directors will decide whether or not NCAP will support NCHCCA’s legislation or remain neutral. This decision will not be able to be made until their bill is introduced. We are also hopeful that NCHCCA will be working to create a coalition with the shared objective of serving vulnerable popu lations.
Introduction and Background
Author: Allison Beatty , PharmD Candidate, Campbell University College of Pharmacy & Health Sciences. adbeatty1222@email.campbell.edu
References:
The 340B Drug Pricing Program is a federally administered public health program created to serve low-income patients. In recent years, there has been an ongoing conversation about the 340B Program, and the subsidization methods supported by pharmaceutical manufacturers. The 340B Program was created under Section 602 of the Veterans Health Care (VHC) Act of 1992. (1) Congress passed this Act to help entities stretch federal resources and permit more pa-
1. Veterans Health Care Act of 1992, public law 102-585. HRSA. April 2017. Accessed February 2025. https://www.hrsa.gov/oa program-requirements/public-law-102-585#602.
2. 340B eligibility. HRSA. June 2024. Accessed February 2025. https://www.hrsa.gov/opa/eligibility -and-registration.
3. 340B Drug Pricing Program. NCHA. March 11, 2024. Accessed February 2025. https://www.ncha.org/340b -drugdiscount-program/.
tients, who qualify, access to comprehensive services through the 340B Program. Comprehensive services include, but are not limited to free vaccines, medication assistance programs, diabetes education classes, mental health counseling, and community health programs.
4. 340B Health. Detailed Overview. Accessed February 2025. https://www.340bhealth.org/members/340bprogram/overview/.
5. Fact sheet: The 340B Drug Pricing Program: AHA. American Hospital Association. January 28, 2025. Accessed February 2025. https://www.aha.org/fact-sheets/fact-sheet-340b-drug-pricing- program.
covered by Medicaid and Medicare Part B. Through a PPA, the manufacturer agrees to provide front-end discounts on covered outpatient medications purchased by 340B covered entities. The 340B Program was established to serve one of the nation’s most vulnerable patient populations. The qualifications for both 340B covered entities and eligible patients can be found in Table 1.
6. Hospitals and 340B. PhRMA. Accessed February 2025. https://phrma.org/policy -issues/340b.
7. Havlak J. Overcharged: State Employees, Cancer Drugs, and the 340B Drug Pricing Program. North Carolina State Health Plan For Teachers and State Employees. May 8, 2024. Accessed February 2025. https://www.nctreasurer.com/news/press-releases/2024/05/08/state-treasurer-folwell-releases-report-finding-northcarolina-340b-hospitals-overcharged-state.
Covered Entities
What are they?
The 1992 VHC Act requires pharmaceutical manufacturers to enter into a pharmaceutical pricing agreement (PPA) with the United States Health and Human Services Secretary in exchange for having their medications
• Disproportionate share hospitals (DSHs), children’s and cancer hospitals exempt from the Medicare prospective payment system, sole community hospitals, rural referral centers, and critical access hospitals
Must have one of the three following items:
1. owned or operated by the state or local government
2. a public or private non-profit corporation which is formally granted governmental powers by state or local government
3. a private non-profit organization that has a contract with a state or local government to provide care to low-income individuals who do not qualify for Medicaid or Medicare.
340B Patient Eligibility
Pharmaceutical companies provide additional avenues for patients to reduce medication costs, commonly referred
Definition: The patient must receive health care services other than drugs from the 340B covered entity
This includes:
1. The covered entity needs an established relationship with the individual via maintaining records of the individual’s health care
2. They receive health care services from a health care professional who is either employed by the covered entity or provides health care under contractual arrangements so that responsibility for the care provided remains with the covered entity
3. The individual receives a health care service or range of services from the covered entity that is consistent with the service or range of services for which grant funding or FQHC Look-Alike status has been provided to the entity.
Table 1: 340B Covered Entities and Patient Eligibility (2,3)
to as Patient Assistance Programs (PAPs). These programs function as a secondary coordination of benefits, helping lower the copay to the amount that the manufacturer guarantees or covering additional expenses not addressed by the primary insurance.
The Different Perspectives Regarding the Subsidization Debate
The 340B entities, as described in Table 1, often include hospitals, federally qualified health centers, and rural health centers. Entities currently provide medications and services in-house and outsource services, such as establishing contract pharmacies to provide medications to the entity’s 340B eligible patients.
In 2015, the Government Accountability Office reported that program participants can save an estimated 20-50% off medication costs. (4) Hospitals use 340B savings to provide, for example, free care for uninsured patients, free vaccines, services in mental health clinics, medication management, and community health programs. (5)
Since 2019, a growing number of pharmaceutical manufacturers have been implementing restrictions by limiting 340B entities to a single contract pharmacy, limiting the distance between the contract pharmacy and the covered entity, and refusing to ship 340B drugs to contract pharmacies. In addition, the pharmaceutical manufacturers are trying to shift the subsidization method for 340B drugs from upfront discounts to a rebate plan. This rebate model would entail reimbursing hospitals and other 340B entities after providers prove that the patients who receive the drugs are eligible for 340B benefits.
Pharmaceutical manufacturers have been implementing these changes due to concerns that for some covered entities, companies are paying double discounts on medication: the discount
on the front end to the 340B entity, and as a rebate to low-income insurers such as Medicaid. In addition, the companies are concerned that the discounted medications may not always be used for the correct population, and that the Health Resources and Services Administration, which oversees the 340B Program, does not have enough bandwidth to ensure the Program only benefits 340B eligible patients.
The Pharmaceutical Research and Manufacturers of America (PhRMA) has proposed two major changes for the 340B Program. (6) The first is transparency about how healthcare facilities will use the discounts provided by the 340B Program. The second is clearly defining who is a 340B patient and ensuring vulnerable patients benefit from the program. PhRMA has advocated for these changes out of concerns that some 340B entities are mismanaging the program savings and benefiting financially. This was also a concern of the previous NC Treasurer, Dale Folwell, who had an investigative study conducted as part of the Hospital Transparency Project. The study specifically investigated oncology infusion drugs in hospitals across the state. The report found that 340B hospitals had billed cancer patients an average 5.4 times their discounted acquisition costs, while non-340B hospitals showed a 2.9 times markup. (7)
Pharmacists and clinicians working with 340B Programs state that the shift to a rebate model could greatly impair the ability to deliver critical and timely patient care. The change could also increase the costs of administering services within a 340B Program due to some of the requirements that companies choose to impose. The paperwork and wait time to prove that a patient is 340B eligible before providing care could be detrimental to patient access and health outcomes.
Actions Being Taken to Address the Imposed Restrictions
Although there has been much discussion with HRSA and dialogue with Congress to address the divergent concerns of providers versus manufacturers over the 340B Program, there is no federal fix in sight. In recent years, several states have elected to run legislation to expand protections for the 340B Program. Mississippi, Maryland, Arkansas, and Louisiana have passed protection bills within the last two years. Kansas also passed a protection bill that lacked an enforcement clause, and that state’s attorney general has refused to enforce their legislation. Then in West Virginia, a protection bill was approved, but a federal judge issued a temporary block, leading to an appeal still to be heard in federal court. If the appeal is successful, this will likely set up a case for the Supreme Court.
Legislative Efforts in North Carolina
The North Carolina Association of Pharmacists (NCAP) engages with lawmakers to influence policies that impact pharmacists, pharmacies, and patient care. NCAP already advocates for fair reimbursement policies for pharmacies, and we strongly advocate for 340B-covered entities. NCAP pushes back against restrictions and policies that negatively impact pharmacies and patients’ access to care. In December 2024, NCAP formed a 340B Task Force to investigate the landscape of what was happening to 340B Programs nationwide, and to explore opportunities for our Association, including whether or not to run legislation similar to what some other states have done.
The Task Force did a tremendous amount of work in a relatively short time frame. They reviewed other states’ successful legislation and outlined model protective language that would best serve our needs here in North Carolina. The Task Force also discussed the pros and cons of running legislation at this time, as well as delineated suggested strategies, including
who is best suited to lead this type of legislation. The Task Force believed that our state’s environment makes successfully passing 340B protection legislation much more challenging, and that NCAP is perhaps not best suited as the primary organization running any legislation. The Task Force shared that NCAP’s work to date could be used to help form a coalition, one that involved the various 340B entities, and their professional associations, to lead the legislation.
As of March 3, 2025, NCAP had been made aware that the North Carolina Health Care Centers Association (NCHCCA) is planning to run 340B protective legislation. NCAP understands that what NCHCCA is planning aligns with the important legislative needs identified by the NCAP 340B Task Force. At this time, our organizations are in further discussion, and the NCAP Board of Directors will decide whether or not NCAP will support NCHCCA’s legislation or remain neutral. This decision will not be able to be made until their bill is introduced. We are also hopeful that NCHCCA will be working to create a coalition with the shared objective of serving vulnerable populations.
Author: Allison Beatty, PharmD Candidate, Campbell University College of Pharmacy & Health Sciences. adbeatty1222@email.campbell.edu
References:
1. Veterans Health Care Act of 1992, public law 102-585. HRSA. April 2017. Accessed February 2025. https://www.hrsa.gov/ oa program-requirements/public-law-102-585#602.
2. 340B eligibility. HRSA. June 2024. Accessed February 2025. https:// www.hrsa.gov/opa/eligibility-and-registration.
3. 340B Drug Pricing Program. NCHA. March 11, 2024. Accessed February 2025. https://www.ncha. org/340b-drug-discount-program/.
4. 340B Health. Detailed Overview. Accessed February 2025. https:// www.340bhealth.org/members/340b-program/overview/.
5. Fact sheet: The 340B Drug Pricing Program: AHA. American Hospital Association. January 28, 2025. Accessed February 2025. https://www.aha.org/fact-sheets/ fact-sheet-340b-drug-pricingprogram.
6. Hospitals and 340B. PhRMA. Accessed February 2025. https:// phrma.org/policy-issues/340b
7. Havlak J. Overcharged: State Employees, Cancer Drugs, and the 340B Drug Pricing Program. North Carolina State Health Plan For Teachers and State Employees. May 8, 2024. Accessed February 2025. https:// www.nctreasurer.com/news/ press-releases/2024/05/08/ state-treasurer-folwell-releases-report-finding-north-carolina-340b-hospitals-overcharged-state
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As trusted healthcare providers, pharmacists wear many hats, but one of the most vital roles they play is immunizer. From administering vaccines to educating and advocating for patients, pharmacists are on the frontlines of keeping communities safe and healthy. As defined by the North Carolina Board of Pharmacy, an “immunizing pharmacist” is a professional who holds a current CPR certification, has completed an accredited vaccine administration certificate program, and maintains ongoing education to stay competent in vaccine administration. (1) Additionally, they must complete training for the North Carolina Immunization Registry, notify the relevant boards of their status, and administer vaccines according to state regulations. (1) Since May of 2023, immunizing pharmacists in North Carolina (NC) have been legally allowed to administer any Center for Disease Control and Prevention (CDC) and Advisory Committee on Immunization Practices (ACIP) recommended vaccine to adults. Additionally, when a person chooses, or a parent or legal guardian provides written consent for a person under 18 years of age, an immunizing pharmacist may administer an influenza vaccine, a COVID-19 vaccine recommended by ACIP, a COVID-19 vaccine authorized under an emergency use authorization by the United States Food and Drug Administration
Public Health’s Vaccine Experts: Part I—Pharmacy’s Voice, Resources, and Authority
By: Jennifer Plair, PharmD, MSPH
and recommended by ACIP, or a combination of COVID-19 and influenza vaccines recommended by ACIP to a person at least seven years of age. In NC, qualified pharmacy technicians and interns supervised by a pharmacist can also administer any vaccine a pharmacist can give. (1)
During these encounters, pharmacists provide patients with the Vaccine Information Statement, ensuring that everyone is informed about the vaccines they receive. But pharmacists do not stop there—they help patients understand the latest immunization recommendations, explain vaccine approvals, and guide them through the complexities of emergency use authorizations. They are also invaluable resources when it comes to interpreting the CDC’s ever-evolving immunization schedules.
Pharmacists in NC use the North Carolina Immunization Registry (NCIR) to record and track patient vaccinations. (2) The NCIR helps ensure that immunization records are accurate, up-to-date, and accessible to healthcare providers.
Pharmacists must complete training approved by the Division of Public Health’s Immunization Branch to use the NCIR effectively. They input vaccine administration details, such as the type of vaccine, the date it was
given, and patient information, into the system. This allows other healthcare providers to access and update the patient’s immunization history, improving continuity of care and supporting public health efforts to monitor vaccination coverage and prevent disease outbreaks.
With the ACIP-recommended ability to administer additional vaccines, pharmacists now have the opportunity to expand their immunization services, including offering travel vaccines. A follow-up article, scheduled for publication later this year in the NC Pharmacist, will provide further guidance to help pharmacists develop a travel vaccine service.
More than just educators, pharmacists advocate for their patients. They are champions for vaccination, encouraging patients to take action and helping them build the confidence needed to make informed decisions. In a world where vaccine hesitancy can spread like wildfire, pharmacists are there to combat complacency and instill a sense of urgency about the importance of vaccines. (3)
In NC, this mission is further amplified by the North Carolina Immunization Coalition (NCIC), a powerhouse organization uniting healthcare providers, public health officials, and government agencies. (4) Together,
they promote vaccine safety and efficacy, fight vaccine hesitancy, and elevate immunization rates across the state. The NCIC has been actively addressing health disparities in immunization coverage. Notably, they were key in planning and providing input for the inaugural NC human papillomavirus vaccination stakeholders meeting. Additionally, NCIC has been gathering insights on how to leverage community-academic partnerships to promote vaccine equity.
For the past few years, the North Carolina Association of Pharmacists (NCAP) has been a vital partner in the NCIC. With an Executive Fellow serving on the NCIC steering committee, NCAP helps coordinate efforts to inform healthcare professionals and the public about vaccination efforts, while offering a pharmacist’s perspective on the evolving landscape of immunizations. This collaboration allows NCAP to stay plugged into the latest updates and share them with pharmacists across the state.
In addition to participating with NCIC, NCAP provides valuable immunization resources like NCAP’s Immunization Toolkit, including patient questionnaires and consent forms. NCAP ensures its members have the most up-to-date tools and information to stay on top of immunization practices. (5) This toolkit is a lifeline for pharmacists striving to provide the best possible care, informing them on legislation, the NCIR, and more.
An immunizing pharmacist must maintain documentation of three hours of continuing education every two years to ensure competency in disease states, drugs, and vaccine administration. In support of this, NCAP offers a range of immunization resources for pharmacists in the state. These resources include training and certification programs, accredited by the Accreditation Council for Pharmacy Education, to help pharma-
cists become and remain certified in vaccine administration. This includes NCAP’s in-person, live-streamed, and on-demand continuing education on immunization-related topics. These immunization topics include continuing education opportunities to update pharmacists on immunization practices, disease prevention, and vaccine administration. NCAP is working on providing guidance for administering travel vaccines and other specialized immunizations to those looking to expand their services.
NCAP also fosters collaboration among pharmacists, healthcare providers, and public health professionals to improve immunization access and effectiveness across communities. Through partnership, NCAP informs pharmacists about regulatory changes, such as requirements for reporting to the NCIR and other state-specific guidelines. Finally, NCAP advocates for policies that support pharmacist involvement in immunization efforts and helps navigate any legislative or regulatory challenges. These resources ensure NC pharmacists can effectively contribute to public health through immunization services. With NCAP’s resources in hand, in addition to future immunization resources and programming, pharmacists continue to play a critical role in shaping healthier, more informed communities, one vaccine at a time.
Author: Jennifer Plair, PharmD, MSPH, Executive Fellow NCAP. fellow@ncpharmacists.org.
References
1. PHARMACIST, PHARMACY TECHNICIAN, AND PHARMACY INTERN VACCINATION AUTHORITY UNDER AMENDED G.S. § 9085.15B. S.L. 2023-15. 2023, May 19. www.ncleg.gov/EnactedLegislation/ Statutes/PDF/BySection/Chapter_90/ GS_90-85.15B.pdf. Accessed 5 Mar. 2025.
2. North Carolina Department of Health
& Human Services Division of Public Health. North Carolina Immunization Registry. Available at: https://www. dph.ncdhhs.gov/programs/epidemiology/immunization/providers/ncir. Accessed 14 Mar 2025.
3. Shen AK, Tan ASL. Trust, influence, and community: Why pharmacists and pharmacies are central for addressing vaccine hesitancy. J Am Pharm Assoc (2003). 2022 JanFeb;62(1):305-308. doi: 10.1016/j. japh.2021.10.001. Epub 2021 Oct
8. PMID: 34688565; PMCID: PMC8522433.
4. North Carolina Immunization Coalition. Available at: https://letsimmunizenc.org/. Accessed 4 Mar 2025.
5. 5. Viracola C. Immunization Toolkit. North Carolina Association of Pharmacists. www.ncpharmacists. org/immunization-toolkit. Accessed 4 Mar. 2025.
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Abstract
Introduction: Duke University Health System’s institutional guidance recommends utilizing methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) tests for patients receiving empiric anti-MRSA antimicrobial therapy (e.g., vancomycin or linezolid) for pneumonia. The study’s purpose was to investigate the appropriateness of a community hospital’s MRSA PCR test orders, including the percentage of inappropriate antibiotic de-escalation for non-respiratory infections.
Methods: This was a single-center retrospective study at Duke Raleigh Hospital, a campus of Duke University Hospital. One hundred adult patients were randomly selected from a database of all hospitalized patients who had a MRSA nasal PCR test performed at our community hospital from August 2022 through July 2023. The appropriateness of the initial test was determined using the guidance of the existing institution. (1) Providers’ responses to test results were noted (i.e., continuation or discontinuation of antibiotics based on MRSA swab results).
Results: Fifty-seven percent of MRSA nasal PCR tests were clinically appropriate according to existing institution guidance. Forty-three percent of MRSA nasal PCR tests ordered deviat-
Evaluation of Methicillin-Resistant Staphylococcus aureus Nasal Polymerase Chain Reaction Use in a Community Hospital
By: Dr. Drashti Patel, Dr. Cammie McMahan, Dr. David Sugrue, and Dr. Jessica Michal
ed from hospital guidance. Treatment regimens were changed for 37 patients in response to test results, and the average time from test result to anti-MRSA therapy discontinuation was 7.8 hours. MRSA PCR tests were positive in 16% of patients. Cultures returned with MRSA growth in 9% of patients (two blood cultures, seven wound/ abscess cultures), and three patients had nasal screen results discrepant to culture results.
Conclusion: Despite considerable deviation from hospital guidance, responses to results were largely appropriate, indicating good understanding of clinical application of the MRSA nasal screen results but poor diagnostic stewardship.
Keywords: MRSA, PCR test, methicillin-resistant Staphylococcus aureus, pneumonia, stewardship
Introduction
The 2019 Infectious Diseases Society of America (IDSA) guidelines for
community-acquired pneumonia incorporated methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) screening to help reduce unnecessary vancomycin use. (2) In respiratory tract infections, S. aureus has low disease prevalence, and the MRSA nasal PCR has high negative predictive value (approximately 96-99%). (3,4) This makes nasal PCR screening for MRSA useful for de-escalating anti-MRSA therapy. Studies indicate that using nasal screening can reduce the duration of anti-MRSA therapy, leading to cost savings and decreased pharmacy workload. (2,3,5)
The Duke University Health System’s (DUHS) institutional guidance (Table 1) recommends performing MRSA nasal PCR tests for patients receiving empiric anti-MRSA antimicrobial therapy (i.e., vancomycin or linezolid) for pneumonia. At Duke Raleigh, a 204-bed acute care community hospital, a protocol permitting MRSA nasal PCR ordering authority to pharmacists has also been established. The MRSA
Appropriate Clinical Scenarios for MRSA PCR Nasal Screen
• Patients receiving empiric anti -MRSA therapy for pulmonary/respiratory infections and unable to collect respiratory cultures
• Patients who have been on anti-staphylococcal antibiotics for less than 48 hours prior to MRSA nasal swab collection
Inappropriate Clinical Scenarios for MRSA PCR Nasal Screen
• Intra-abdominal, bloodstream, skin and skin structure, and bone/joint infections
• Patients with structural nasal abnormalities, bleeding, or facial fractures
• Negative MRSA PCR nasal screen in the past 14 days
Table 1. DUHS Guidance: When to Order MRSA PCR Nasal Screen
nasal PCR test is a valuable clinical tool with rapid turnaround time (average of 1-2 hours at our hospital campus), allowing clinicians to de-escalate empiric antibiotic regimens, and therefore limit collateral damage and healthcare spending. (3,5)
Based on our institution guidance, we identified a trend of potential test misuse to guide antimicrobial decisions in non-respiratory infections. For example, using a negative result to discontinue anti-MRSA therapy in a patient with diabetic foot infection and possible osteomyelitis, a disease state in which the prevalence of S. aureus is high, would be an example of inappropriate de-escalation per our institution guidance. Avoiding unnecessary nasal screen use represents a potential cost savings opportunity ($247 cost to patients at our hospital), could significantly reduce the workload of laboratory staff, and can prevent inappropriate de-escalation of antibiotic regimens. Data from this laboratory use evaluation (LUE) will help determine if additional education on MRSA nasal PCR tests is needed and estimate the impact on laboratory resources.
Methods
This retrospective LUE was conducted from a randomly selected group of 100 patients at least 18 years of age who had a MRSA nasal PCR test performed at our community hospital between August 2022 and July 2023. The following criteria were used to exclude patients from the study: admission to surgical oncology unit at time of test collection, no clearly documented indication or clinical reason (i.e. signs of infection) for ordering an anti-MRSA agent, and patients in an end-of-life clinical situation.
Appropriate ordering of MRSA nasal PCR was defined as patients with pneumonia (as indicated on the anti-MRSA antimicrobial order) and none of the following: concomitant sepsis (as indicated by provider notes);
severe pulmonary disease including necrotizing infection, cavitary lesions, or empyema; febrile neutropenia; ventilator-associated pneumonia; cystic fibrosis; documented history of MRSA infection in the past year; documented active infection with S. aureus, regardless of availability of susceptibilities; or active infectious disease consult at the time the test was ordered. MRSA nasal swab orders were also considered inappropriate if being used for patients with intra-abdominal, bloodstream, skin and skin structure, or bone/joint infections, or if a negative MRSA swab had resulted in the previous seven days. Regardless of indication for the anti-MRSA therapy, we also investigated and reported whether test results were responded to appropriately (i.e., no change in therapy, drug discontinued, etc.), and the timeliness of these responses. Table 2 outlines the definitions for appropriate and inappropriate provider responses. The type of ordering user (physician, advanced practice provider, pharmacist) and pertinent culture results were also collected.
test use, examine test appropriateness according to ordering user type, determine if results were responded to appropriately, determine timeliness of response to test results, and examine nasal screen result discrepancies with pertinent culture results.
Data Collection and Analysis
Data was collected retrospectively and interpreted via electronic health record review. In the event of repeat MRSA PCR testing, only the first test result during a single admission for a given patient was evaluated. Order appropriateness was determined by one investigator (CM) and independently reviewed by a second investigator (JM) for agreement. Any disagreements were discussed between the reviewers until an agreement was met. Descriptive statistics were used to analyze the data.
Results
Fifty-seven percent of MRSA nasal PCR tests were considered appropriate and aligned with institutional guidelines. Figure 1 shows the PCR
Positive or negative Non-respiratory infection, S. aureus likely pathogen (i.e., skin/skin structure infection, osteomyelitis)
Positive or negative Non-respiratory infection, S. aureus not likely pathogen (i.e., intraabdominal infection with no recent surgery)
Respiratory infection
Continue or discontinue antiMRSA therapy
Continue anti-MRSA therapy Negative Respiratory infection Discontinue anti-MRSA therapy
Objectives
Primary Objective: The primary objective of the study was to determine the percentage of appropriate versus inappropriate use of the MRSA nasal PCR test.
Secondary Objectives: The secondary objectives of the study were to determine the most frequent clinical presentations for MRSA nasal PCR
test indications. Forty-four percent of MRSA nasal PCR tests were ordered for non-respiratory indications, which was the most common reason PCR tests were classified as inappropriate. The most common non-respiratory indication was cellulitis or wound infections (29%).
Test ordering and result response
Table 2. Definitions of appropriate response to MRSA PCR nasal screen results
appropriateness according to ordering user group are outlined in Table 3. Most test results were responded to appropriately (89%) though varied by provider type. The average time from result to anti-MRSA therapy discontinuation was 7.8 hours (range 0 to 38 hours).
has limited utility for bloodstream infections due to the high risk associated with incorrect de-escalation. Intra-abdominal infections also show limited applicability since MRSA is an uncommon pathogen in these cases. (7,8) Nasal screening is questionable for skin and skin structure infections
Table 3. MRSA PCR Nasal Screen Order and Result Response Appropriateness
Number of MRSA PCR Orders, n 100 59 24 17
Appropriate MRSA Order Utilization, n (%) 57 (57) 29 (49) 12 (50) 16 (94)
Appropriate Response to PCR, n (%) 89 (89) 51 (59) 21 (87.5) 17 (100) APP, advanced practice practitioner; RPh, pharmacist
Nasal MRSA PCR tests resulted positive in 16% of patients. Cultures returned with MRSA growth in 8% of patients (two blood cultures, six wound/abscess cultures). Three cases had discrepancies between nasal screen and culture results (Table 4).
MRSA PCR tests resulted positive in 16% of patients. Cultures returned with MRSA growth in 8% of patients (two blood cultures, six wound/abscess cultures). Three cases had discrepancies between nasal screen and culture results (Table 4).
(SSSIs). Some studies have demonstrated negative predictive value of MRSA nasal swabs in SSSIs ranging from 72.8% to 98%, but most have been small retrospective studies with several limitations. (9)
This LUE confirmed suspicion that MRSA nasal PCR tests were unnecessary at our community hospital, primarily in SSSIs. Approximately half of physician and advanced practice practitioner orders for this test were likely inappropriate based on institutional guidelines. Pharmacists’ higher rates of appropriate test ordering (94%) are
Table 4. Patients with discrepant MRSA nasal screen and culture results
Positive MRSA PCR in a patient being treated for cellulitis. Discharged with anti -MRSA outpatient treatment. Wound culture eventually grew MSSA.
Anti-MRSA therapy was discontinued in a patient being treated for cellulitis based on a negative MRSA nasal PCR. Wound culture ultimately grew MRSA, and anti -MRSA therapy was re-initiated.
Negative MRSA nasal PCR, blood culture grew MRSA. Anti- MRSA treatment had not changed after PCR result.
Discussion
The DUHS guidance for MRSA nasal screening is focused on respiratory infections. Using MRSA nasal screening for extrapulmonary infections like bloodstream and intra-abdominal infections is questionable. (6.7) Data suggest that nasal screening has high negative predictive value but poor sensitivity and positive predictive value for these sites. MRSA nasal screening
likely due to having a strict protocol to guide ordering.
While there was a high rate of unnecessary MRSA PCR test ordering, responses to PCR results were largely appropriate (>85%), indicating a good understanding of test result application but a poor understanding of diagnostic stewardship. Utilizing the results of this investigation, the antimicrobial stewardship team developed and deliv-
ered education on proper MRSA PCR use to providers.
This study has several limitations. The retrospective study design, small sample size, and inclusion of patients from a single center limit external validity. There is risk of misclassification bias due to reliance on provider documentation for diagnostic considerations and testing indications. Frequently, the nasal MRSA PCR was ordered before the ordering provider fully knew indications, and the provider acting on the results was not the same provider who ordered the test. It is uncertain if our study’s results could have been different if the same provider both ordered and acted on the test. There is also potential for selection bias that could not be detected retrospectively. This study did not perform a cost analysis; however, optimizing MRSA tests utilization in accordance with guideline-recommended populations may lead to both laboratory and patient cost savings.
Conclusion
Data from this study demonstrated good understanding of clinical application of the MRSA nasal screen results by ordering providers and pharmacists. An opportunity to optimize MRSA nasal screen test ordering with institutional guidance and infection type was identified.
Authors: Dr. Drashti Patel, PharmD, BCPS (corresponding); Cammie McMahan, PharmD; David Sugrue, PharmD, BCCCP; Jessica Michal, PharmD, BCIDP, AAHIVP, Duke Raleigh Hospital, A Campus of Duke University Hospital, Raleigh, NC. drashti.patel@duke.edu
References
1. University Hospital Systems. DUHS Guidance 2022: When to order MRSA nasal swab; DUHS, 2022.
2. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical
Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Idsociety.org. Published 2019. https://www.idsociety.org/practice-guideline/community-acquired-pneumonia-cap-in-adults/
3. Parente DM, Cunha CB, Mylonakis E, Timbrook TT. The clinical utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening to rule out MRSA pneumonia: a diagnostic meta-analysis with antimicrobial stewardship implications. Clin Infect Dis. 2018;67(1):1-7.
4. Dangerfield B, Chung A, Webb B, Seville MT. Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia. Antimicrob Agents Chemother. 2014;58(2):859-864.
5. Meng L, Pourali S, Hitchcock MM, et al. Discontinuation patterns and cost avoidance of a pharmacist-driven Methicillin-Resistant Staphylococcus aureus nasal polymerase chain reaction testing protocol for deescalation of empiric vancomycin for suspected pneumonia.
Open Forum Infect Dis. 2021;8(4):ofab099.
6. Liu C, Holubar M. Should a MRSA nasal swab guide empiric antibiotic treatment? NEJM Evidence. 2022;1(12).
7. Pelham M, Ganter M, Eudy J, Anderson DT. Evaluation of anti-methicillin-resistant Staphylococcus aureus (MRSA) prescribing habits in patients with a positive MRSA nasal swab in the absence of positive cultures. Pharmacy (Basel). 2023 May 3;11(3):81.
8. Bennett SJ, Mullen C, Mistry B, Cucci M. Performance of nasal methicillin‐resistant Staphylococcus aureus screening for intra‐abdominal infections in critically ill adult patients. 2021;41(3):257264.
9. Burgoon R, Weeda E, Mediwala KN, Raux BR. Clinical utility of negative methicillin-resistant Staphylococcus aureus (MRSA) nasal surveillance swabs in skin and skin structure infections. American Journal of Infection Control. 2022;50(8):941-946.
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RapiblykTM, landiolol, was approved by the FDA on November 22, 2024, as a beta-1 selective adrenoreceptor blocker, Class II antiarrhythmic agent. Landiolol is indicated for the shortterm reduction of ventricular rate in adults experiencing supraventricular tachycardia, including atrial fibrillation and atrial flutter. There are no off-label indications currently. (1,2)
Landiolol is contraindicated in patients with severe sinus bradycardia, sick sinus syndrome, or heart block greater than first degree, decompensated heart failure, cardiogenic shock, and pulmonary hypertension. Additionally, the manufacturer states that anyone with a known hypersensitivity or anaphylactic reaction to landiolol or any of its inactive ingredients should not take it. (1)
As a beta-1 selective adrenergic receptor antagonist, it inhibits the positive chronotropic effects of epinephrine and norepinephrine on the heart. At the approved recommended dosage in vitro, landiolol does not demonstrate membrane-stabilizing or intrinsic sympathomimetic activity. (1)
Pharmacokinetics
Absorption: Landiolol reaches steadystate values approximately 15 minutes after infusion begins. Its pharmacokinetics increase proportionally to the dose between the range of 9.3 and 74.6 mcg/kg/min. Peak plasma concentra-
RapiblykTM (landiolol)
By: Katherine Stein, PharmD Candidate 2025
tions (Cmax) are dependent on the dosage of landiolol given as well as the patient’s health status, as outlined in Table 1. (1)
Distribution: Landiolol is < 10% pro-
Landiolol Dosage
proximately 50 to 75% of the administered dose is excreted at 4 hours and 89 to 99% is excreted at 24 hours. (1)
Clinical Efficacy
Landiolol has been studied in cardiac
Healthy Volunteers (mean)
Atrial Fibrillation or Atrial Flutter Patients (range)
9.3 mcg/kg/min 0.2 mcg/mL Not studied
18.6 mcg/kg/min 0.5 mcg/mL Not studied
37.3 mcg/kg/min 1.0 mcg/mL 0.52 to 1.77 mcg/mL
9.3 mcg/kg/min landiolol is equivalent to 10 mcg/kg/min landiolol hydrochloride
tein bound. The volume of distribution at steady state is 0.4 L/kg. (1)
Metabolism: Landiolol is mainly metabolized in the plasma by pseudocholinesterases and carboxylesterases into its active metabolite, M1. The pharmacological activity of M1 is less than 1/40th that of landiolol, and its AUC₀–inf is approximately 12 times higher than that of landiolol. (1)
Elimination: Landiolol has an elimination half-life of 4.5 minutes at steady state. Following a 20-hour continuous landiolol infusion of 37.3 mcg/kg/min, landiolol has a total body clearance of 57 mL/kg/min. (1)
Excretion: Landiolol is excreted through the urine. Following a 60-minute intravenous infusion, ap-
surgery for over 15 years in Japan with a well-documented safety and efficacy ratio. In 2022, it was tested in France with a phase 3 prospective, randomized, controlled, double-blind, parallel-group trial (NCT 03779178). This trial examined landiolol’s dose-dependent hemodynamic and metabolic effects in reducing post-operative atrial fibrillation (POAF) incidence. The trial enrolled 59 patients at the University Hospital Louis Pradel in Lyon, France. Participants were eligible for the study if they were adults and had undergone conventional cardiac surgery with cardiopulmonary bypass. Participants were excluded if they had pre-existing chronic atrial fibrillation, a contraindication to beta-blockers,
Table 1: Peak plasma concentrations (Cmax) of landiolol
circulatory shock, distributive shock, acute respiratory distress syndrome, major post-operative bleeding, or were pregnant. (2,3)
Seventy-two participants were assessed for eligibility. Fifty-nine participants met the criteria and were randomly assigned in a 1:1 ratio to receive either landiolol perfusions or placebo NaCl 0.9% perfusions following cardiac surgery. Landiolol was administered in incremental doses of 0.5, 1.0, 2.0, 5.0, and 10.0 µg/kg/min in 20-minute intervals over 120 minutes. NaCl 0.9% was administered in incremental doses of 0.03, 0.06, 0.12, 0.3, and 0.6 mL/ kg/h in 20-minute intervals over 120 minutes. Baseline characteristics were similar between the groups, with a median age of 66 years old (55-71) and left ventricular ejection fraction of 49% (43-58). (2,3)
The primary endpoint assessed the impact of incremental doses of landiolol on macrocirculatory parameters, including heart rate, blood pressure, stroke volume, and echocardiographic measurements of left and right ventricular performances. Secondary endpoints evaluated the effects of increasing doses of landiolol on metabolic parameters, such as mixed venous oxygen saturation and lactate, and the incidence of POAF. All tests were twotailed, and statistical significance was defined as a p value (p) < 0.05. (2,3)
One patient was excluded due to technical issues, leaving 58 participants for analysis. Of these, two participants were unable to achieve the maximum dose regimen due to a low mean arterial pressure (< 65 mmHg) and/or heart rate (< 60 BPM) and 23 participants required low-dose norepinephrine support. (2,3)
Landiolol significantly decreased heart rate (p < 0.01) in a dose-dependent manner compared to placebo, with greater reductions observed at higher doses. Mean arterial pressure was
slightly decreased in both groups but without a statistical difference (p = 0.05). Stroke volume and pulse-pressure variation did not change in either group during the study. Between post-operative day 0 and post-operative day 5, nine (32%) of the 28 participants in the placebo group experienced POAF compared to five (17%) of 30 participants in the landiolol group but without statistical significance (p = 0.285). (2,3)
While this study found that landiolol does not significantly decrease the incidence of POAF, it did support its favorable safety profile within the specified cardiac surgical setting. It concluded that early post-operative dose regimens of landiolol significantly decrease heart rate without causing remarkable arterial pressure, stroke volume, and ventricular performance changes. (2,3)
In addition, the Journal of Clinical Medicine published a meta-analysis in March 2024 to assess the effects of landiolol administration on heart rate lowering in patients with supraventricular tachyarrhythmia (SVT) and concurrent left ventricular dysfunction. This meta-analysis searched PubMed, Cochrane, Web of Science, and Scopus for observational cohort studies or randomized trials that included the term “landiolol.” (4)
Articles met eligibility criteria if they examined the effects of landiolol treatment on heart rate, blood pressure, adverse events, and follow-up outcomes in adults with SVT and coexisting left ventricular dysfunction who were not septic or in a perioperative period. There were no restrictions on race or ethnicity; however, studies with fewer than ten patients, reviews, editorials, or practice guidelines, as well as studies that assessed the use of landiolol in pediatric patients or that were written in a language other than English, were excluded from the meta-analysis. (4)
The search resulted in 2,304 articles. After removing duplicates and extraneous articles, 37 reports remained and underwent review based on eligibility criteria. Of these, 15 studies were included in the systematic review and 11 in the meta-analysis. Many of the studies took place in Japan or France, and the studies spanned across a tenyear publishing period ranging from 2012 to 2022. Seven of the 11 studies were single-arm trials, two comparing landiolol to digoxin, and two comparing landiolol to diltiazem. The total patient sample size across all 15 studies was 1,674 patients. A summary of each study’s main population characteristics can be found in Table 2.
Baseline characteristics were similar between studies. Nearly 60% of landiolol patients were men in 12 of 15 reported studies. The mean age in the landiolol group was 64.8 + 15 years in 11 of 15 studies. Across all studies, most studies reported three baseline characteristics. Diabetes mellitus affected 26.7% of patients (356/1331), prior coronary artery disease affected 64.4% of patients (1047/1627), and NYHA class III or IV affected 74.5% of patients (1037/1392).
The primary outcome was achieving the target heart rate, which is defined as a reduction in the initial heart rate by at least 20% with a final heart rate of less than 110 beats per minute (BPM). The secondary outcomes were restoration of sinus rhythm and documentation of adverse events or subjective symptoms resulting in landiolol discontinuation. Overall, 75% of the patients treated with landiolol achieved their target heart rate, with a statistically significant mean heart rate reduction of 42 BPM (95% Confidence Interval (CI) 37.40-47.45). In three of the four studies that compared landiolol to an alternative antiarrhythmic agent, landiolol was superior to the other agents in regulating heart rate. Landiolol showed comparable efficacy to diltiazem in the fourth study
but had improved safety as diltiazem significantly lowered blood pressure while landiolol did not. Two studies reported on sinus rhythm, with no statistically significant differences observed between treatment groups. Adverse events or subjective symptoms were reported in 14.7% of the landiolol-treated patients, with the primary adverse event being dose-dependent hypotension. Landiolol was discontinued in 6% of patients.
Overall, this meta-analysis showed that landiolol is efficacious in reducing heart rate among patients with heart failure who are experiencing a sinus ventricular tachycardia with the most common side effect being dose-dependent hypotension. It was not enough to demonstrate the effectiveness and safety of landiolol, but it did demonstrate the potential heart rate reduction benefits of landiolol administration for managing SVT with left ventricular dysfunction.
Drug Interactions
Landiolol may cause myocardial contractility depression and can increase bradycardia or heart block risk. Negative inotropes and chronotropes may increase these effects; therefore, concomitant use with negative inotropes or other medications that slow heart rate or conduction should be avoided. (1)
Beta-adrenergic agonists may counteract the effects of landiolol, while positive inotropes and vasoconstrictors may diminish its effects, ultimately reducing its ability to lower heart rate and blood pressure. (1)
Catecholamine-depleting drugs may have a combined effect with beta-blockers, increasing the risk of adverse events, such as vertigo, syncope, or postural hypotension. Patients who receive landiolol along with a catecholamine depletor (e.g., reserpine, monoamine oxidase inhibitors) should be observed for hypotension or marked
bradycardia, which may exacerbate these adverse events. (1)
Adverse Effects
Hypotension was the most common adverse reaction noted amongst 19 placebo-controlled trials involving 1,761 patients with supraventricular tachycardia or at high risk for supraventricular tachycardia. Infusion-site reactions have been reported with undefined frequency. (1,2)
Pregnancy and Lactation
Currently, there are limited published data on the use of landiolol in pregnant women, making it unclear whether the drug poses a risk of major birth defects, miscarriage, or other adverse outcomes for the mother or fetus. Studies in pregnant rats have demonstrated that landiolol can cross the placenta and reach the fetus, and the use of beta-blockers during pregnancy is associated with known side effects. Additionally, while there is no data on the presence of landiolol in human milk, its effects on breastfed infants, or its impact on milk production, other beta-blockers have been detected in human milk and the milk of lactating rats. (1)
Dosing and Cost
Landiolol is administered as a continuous intravenous infusion. Dose should be titrated as needed for heart rate control, to a maximum of 36 mcg/kg/ min.
Normal cardiac function: Start at 9 mcg/kg/min. Titrate in 10-minute intervals as needed by 9 mcg/kg/min increments.
Impaired cardiac function: Start at 1 mcg/kg/min. Titrate in 15-minute intervals as needed by 1 mcg/kg/min increments.
Landiolol is available as a single-dose vial containing 280 mg landiolol for injection. Current pricing is not available.
Storage
Store unreconstituted product at 20°C to 25°C (68ºF to 77ºF). Excursions are permitted between 15ºC and 30ºC (59ºF and 86ºF). Landiolol can be stored at 25ºC (77ºF) for up to 4 hours after reconstitution with normal saline and 48 hours after reconstitution with Dextrose 5% in Water. (1,2)
Summary/Use in Clinical Practice
The American College of Cardiology (ACC), American Heart Association (AHA), American College of Clinical Pharmacy (ACCP), and Heart Rhythm Society (HRS) Guidelines for the diagnosis and management of atrial fibrillation recommend the use of nondihydropyridine calcium channel blockers (diltiazem and verapamil) and beta blockers as the standard of care for rate control in atrial fibrillation. (5) Digoxin and amiodarone are also mentioned for rate control, with the recommendation to select an appropriate agent based on patient-specific characteristics and response. (5) The current 2023 ACC/AHA/ACCP/HRS guidelines do not mention landiolol as its use for short-term ventricular rate reduction in SVT, including atrial fibrillation and atrial flutter, was not FDA approved until 2024.
Current literature supports the favorable safety profile of landiolol in cardiac surgical settings as well as its ability to effectively reduce heart rate in patients with heart failure, supraventricular tachycardia, and post-operative atrial fibrillation; however, it does not significantly decrease the incidence of POAF and further research is needed to demonstrate the overall effectiveness of landiolol. (1-5)
Author: Katherine Stein, PharmD Candidate 2025, Campbell University College of Pharmacy & Health Sciences. Email: kastein0829@email.campbell.edu
References
1. 1. Landiolol. Package insert. AOP Orphan Pharmaceuticals GmbH; 2024.
2. 2. Landiolol. In: Lexicomp [database online]. Hudson, OH:Lexicomp, Inc. https://www.crlonline. com/lco/action/doc/retrieve/docid/ patch_f/7399009?cesid=66NYRefIHlN&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dlandiolol%26t%3Dname%26acs%3Dfalse%26acq%3Dlandiolol. Accessed January 15, 2025.
3. 3. Ferraris A, Jacquet-Lagrèze M, Cazenave L, et al. Effects of Landiolol on Macrocirculatory Parameters and Left and Right Ventricular Performances Following Cardiac Surgery: A Randomized Controlled Trial. J
Cardiothorac Vasc Anesth. 2022;36(8 Pt B):2864-2869. doi:10.1053/j. jvca.2022.02.016
4. 4. Nasoufidou A, Papazoglou AS, Stachteas P, et al. Intravenous Landiolol for Rate Control in Supraventricular Tachyarrhythmias in Patients with Left Ventricular Dysfunction: A Systematic Review and Meta-Analysis. J Clin Med. 2024;13(6):1683. Published 2024 Mar 14. doi:10.3390/ jcm13061683
5. 5. Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/ HRS Guideline for the Diagnosis and Management of Atrial Fibrilla-
Table 2: Population characteristics of the included studies.
Study ID
Study Type Participants
Nagai et al. 2013 Multicenter RCT 214
Shinohara et al. 2020 Retrospective observational 53
Kiuchi et al. 2017 Retrospective observational 59
Kimura et al. 2016 Prospective observational 64
Yamashita et al. 2019 Prospective observational 1121
Adachi et al. 2014 Prospective observational 52
Shirotani et al. 2022 Prospective casecontrol 60
Iwahashi et al. 2019 Prospective observational 101
Wada et al. 2016 Retrospective observational 39
Matsui et al. 2019 Retrospective observational 67
Oka et al. 2019 Retrospective observational 77
Kobayashi et al. 2012 Prospective observational 20
Kobayashi et al. 2014 Prospective observational 23
Kijima et al. 2017 Prospective observational 33
Sakai et al. 2019 Prospective observational 67
tion. J Am Coll Cardiol. 2023;83(1). doi:https://doi.org/10.1016/j. jacc.2023.08.017
Population
• NYHA class III/IV
• AF/ AFL
• HR > 120 BPM
• LVEF: 25-50%
• AF
• LVEF < 25%
• Acute HF complicated by SVT
• EF < 50%
• HF patients
• SVT
• HR > 110 BPM
• NYHA class III/IV
• LVEF: 25-50%
• AF/ AFL with HR > 120 BPM
• SVT with HR > 100 BPM
• Congestive HF
• LVEF < 40%
• Tachycardia for > 1 h after standard treatment
• ADHF
• AF
• HR > 130 BPM at admission
• NYHA class IV
• AF with LVEF < 40%
• HR > 120 BPM
• Rapid AF, AFL, atrial tachycardia with ventricular response > 120 BPM
• LVEF < 50%
• AF, aflutter, and fast atrial tachyarrhythmia
• ADHF
• NYHA class III/IV
• LVEF < 50%
• HR > 120 BPM
• AF/ AFL/ atrial tachycardia
• ADHF with LVEF < 0.35
• HR > 90 BPM
• Tachycardia for > 4 h after standard treatment
• ADHF
• Rapid AF (HR > 120 BPM)
• NYHA class III/IV and systolic/ diastolic HF
• Acute HF
• AF, aflutter, atrial tachycardia
• LV dysfunction
• ADHF
• AF or atrial tachycardia
Cobenfy™(xanomeline and trospium chloride), is an oral medication approved by the Food and Drug Administration (FDA) for treating adult patients with schizophrenia, targeting both positive and negative symptoms. (1) Xanomeline: Selectively targets M1 and M4 muscarinic receptors in the central nervous system, which helps manage schizophrenia symptoms without affecting dopamine pathways. (1,2)
Trospium Chloride: An anticholinergic agent reduces peripheral muscarinic side effects by blocking receptors outside the central nervous system. (1,2) While the mechanism by which the combination of these drugs improves schizophrenia symptoms is not entirely understood, they work synergistically to modulate the cholinergic system, targeting muscarinic receptors rather than dopamine. (2,3)
Cobenfy™ is available in capsule form in the following strengths: 50 mg/20 mg, 100 mg/20 mg, and 125 mg/30 mg. The recommended initial dosing is xanomeline 50 mg and trospium chloride 20 mg twice daily for ≥2 days, then increasing to xanomeline 100 mg and trospium chloride 20 mg twice daily for ≥5 days, based on the patient’s response and tolerability. (1,2) Since absorption is affected by high or low-fat meals, take at least one hour before or two hours after meals. The maximum dose is xanomeline/ trospium chloride 125 mg/30 mg twice daily.
CobenfyTM (xanomeline and trospium chloride)
By: Minoo Abdollahzadehfard, PharmD Candidate 2025
(1,2)
Xanomeline reaches peak plasma concentration within approximately two hours, while trospium reaches peak concentration in one hour. (1,2) Xanomeline’s half-life is about five hours, and eliminated primarily via urine (78%) and feces (12%), while trospium’s half-life is about 6 hours, with 85%-90% excreted unchanged in urine. (1,2)
Potent CYP2D6 inhibitors, drugs eliminated by active tubular secretion, and oral drugs that are sensitive substrates of CYP3A4 or P-glycoprotein may increase plasma concentrations of xanomeline and trospium chloride, which may increase adverse effects. (1,2) Caution is advised with the use of narrow therapeutic drugs that are substrates of P-glycoprotein. (1,2)
The most common adverse effects of this new medication are nausea (19%), dyspepsia (18%), constipation (17%), vomiting (15%), and hypertension (11%). (1,2)
There is limited data available for xanomeline/trospium chloride’s use during pregnancy or while breastfeeding; therefore, it should be used with caution. (1,2) Xanomeline/trospium chloride is contraindicated in patients with hypersensitivity to either component. It should be used with caution in patients with urinary or gastric retention, untreated narrow-angle glaucoma, or moderate-to-severe hepatic impairment. (1)
The FDA approved xanomeline/trospium chloride for the treatment of schizophrenia based on two randomized, placebo-controlled studies with identical design (EMERGENT 2 and EMERGENT 3). The EMERGENT-2 trial was a 5-week, double blind, randomized, placebo-controlled trial conducted across 22 US inpatient sites to evaluate the effect of xanomeline and trospium chloride. (3) Participants (N = 252) were randomly assigned in a 1:1 ratio to receive either xanomeline/ trospium or placebo. They included patients diagnosed with schizophrenia based on DSM-5 who were 18-65 years old and had acute exacerbation or relapse of psychiatric symptoms requiring hospitalization. Patients were required to have a total PANSS (positive and negative syndrome scale) score between 80 and 120, with a score of four or more on at least two of the following symptoms: delusions, conceptual disorganization, hallucinations, and suspiciousness. Patients with any primary DSM-5 disorder other than schizophrenia in the past year, newly diagnosed schizophrenia, current or a history of clinically significant cardiovascular, hepatic, pulmonary, hematologic, and renal disorders were excluded. They also excluded anyone who had a cumulative total of more than 30 days of psychiatric hospitalization within the 90 days prior to screening. The primary endpoint, PANSS total score change from baseline to week
five, showed significant improvement for the treatment group compared to placebo, with a mean reduction of 21.2 points versus 11.6 points in the placebo group. Secondary endpoints included PANSS Positive Subscale and PANSS Negative Subscale Scores, which assess positive symptoms (e.g., delusions, hallucinations) and negative symptoms (e.g., social withdrawal, lack of motivation). The treatment group showed nearly twice the reduction in symptoms compared to placebo (p <.0001). Common side effects included constipation, nausea, dyspepsia, and dizziness, while rates of weight gain, extrapyramidal symptoms, and somnolence were comparable between the groups. The findings indicated the potential for xanomeline/trospium chloride to be effective and well-tolerated antipsychotic targeting muscarinic receptors, distinct from dopamine-receptor antipsychotics.
The EMERGENT-3 trial was identical to the EMERGENT-2 trial, involving 256 participants, with 125 in the xanomeline/trospium group and 131 in the placebo group. (4) For the primary endpoint, xanomeline/ trospium led to a significantly larger reduction in PANSS total score, showing an 8.4-point greater decrease from baseline to week 5 compared to placebo LS mean difference, −8.4; 95% CI, −12.4 to −4.3; P < .001. The secondary outcomes included the change from baseline to week 5 in the PANSS positive subscale, PANSS negative subscale, PANSS Marder negative factor score, Clinical Global Impression–Severity score, and the percentage of participants showing at least a 30% decrease in PANSS total score. The least-squares mean (SE) change in the PANSS positive subscale score from baseline to week 5 was −7.1 in the xanomeline/trospium group, compared to −3.6 in the placebo group, LS mean difference, −3.5; 95% CI, −4.7 to −2.2; P < .001. The PANSS negative subscale score did not meet statistical significance at week five, however, the LS mean change from baseline in
PANSS negative subscale score and PANSS Marder negative factor score met statistical significance at week four.
This study demonstrated that xanomeline/trospium chloride was associated with clinically and statistically significant improvement in schizophrenia symptoms and although gastrointestinal side effects like nausea and constipation occurred, they were generally mild and temporary, without the common side effects of dopamine-based antipsychotics like weight gain. (4) Summary/Use in Clinical Practice
Schizophrenia is a challenging disorder with high rates of treatment resistance and partial response to existing medications. Xanomeline/trospium chloride offers a new treatment approach by targeting the cholinergic system, potentially providing symptom relief with fewer side effects compared to traditional dopamine-based treatments. (5) The incidence of weight gain, a common side effect of typical and atypical antipsychotics, was no different than placebo in clinical trials. This combination treatment shows promise in improving symptoms of schizophrenia, enhancing cognitive function, and reducing side effects typically associated with antipsychotic drugs.
Author: Minoo Abdollahzadehfard, PharmD Candidate 2025, Campbell University College of Pharmacy & Health Sciences. m_abdollahza0627@ email.campbell.edu
References
1. Cobenfy. Lexi-Drugs. Hudson, OH: Lexicomp, 2023. http://online.lexi.com/. Updated November 8, 2024. Accessed November 5, 2024.
2. Cobenfy (xanomeline and trospium) [prescribing information]. Boston, MA: Karuna Therapeutics Inc; September 2024.
3. Kaul I, Sawchak S, Correll CU, Kakar B, Breier A, Zhu H, Miller A, Paul SM, Brannan SK. Efficacy and safety of the muscarinic receptor agonist KarXT (xanome-
line-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomized, double-blind, placebo-controlled, flexible-dose, phase 3 trial. Lancet. 2024;403(10422):160170. doi:10.1016/S01406736(23)02190-5
4. Kaul I, Sawchak S, Walling DP, et al. Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2024;81(8):749–756. doi:10.1001/jamapsychiatry.2024.0785
5. Kidambi N, Elsayed OH, El-Mallakh RS. Xanomeline-Trospium and Muscarinic Involvement in Schizophrenia. Neuropsychiatr Dis Treat. 2023;19:11451151. Published 2023 May 10. doi:10.2147/NDT.S406371
PRIORITY PHARMACY LEGISLATIVE NEEDS
THE NORTH CAROLINA ASSOCIATION OF PHARMACISTS
Did you know that
Pharmacists do so much more than just dispense medications?
They play an active role in patient care by offering services like flu and COVID testing, prescribing medications such as birth control, administering long-acting injectable treatments, creating custom compounded medications, and even facilitating remote patient monitoring among many other essential healthcare functions!
Pharmacists are highly accessible healthcare providers? Unlike other healthcare professionals, they typically don’t require an appointment, making it easy for patients to consult with them regarding medications, health concerns, and over-the-counter products
Pharmacies have become significant venues for vaccine administration, offering greater accessibility and convenience for patients? In December 2021, pharmacies administered more than two-thirds of COVID-19 vaccines in the United States
REIMBURSEMENT FOR PHARMACISTPROVIDED HEALTH CARE SERVICES (S.B. 335 AND S.B. 357)
The facts:
Pharmacists are legally authorized to prescribe certain medications, including birth control, tobacco cessation products, and HIV prevention treatments
Providing this care involves both assessing patients’ needs and offering education to ensure the most appropriate treatment options
While NC statutes already recognize pharmacists as "healthcare providers" in terms of medical liability, they do not extend this recognition to compensation for the essential services they provide.
Both patients and NC legislators have acknowledged the significant value pharmacists offer in improving access to quality healthcare
Currently, NC Medicaid is the only health plan that has taken steps toward reimbursing pharmacists for some of the healthcare services they provide Pharmacists who work within their licensed scope of practice should be fairly compensated for their contributions
The ask:
We need to amend the insurance code by passing fair legislation to abolish the discriminatory actions used by health plans to prohibit pharmacists from billing for and receiving compensation for the care they provide to patients
Support S.B. 335 Pharmacists/Test and treat/ Influenza (Primary Sponsors Sawrey, Galey, and Burgin)
Support S.B. 357 Pharmacists/357(Primary Sponsors Sawrey, Hise, and Galey)
TREATMENT BY PHARMACISTS (S.B. 335/FLU AND H.B. TBD/OUD)
The facts:
More than 50% of U.S. states have expanded pharmacists' roles to include the ability to test for and provide treatment for conditions such as COVID-19, strep throat, the flu, urinary tract infections (UTIs), and opioid use disorder (OUD)
This expanded role enhances patient access to care, reducing delays in treatment and ultimately lowering both direct and indirect healthcare costs. In NC, pharmacists are currently able to conduct assessments and provide point-of-care tests However, they are not permitted to act on the results by offering treatment
For example, if a pharmacist administers a flu test that returns positive, they can only inform the patient of the diagnosis and advise them to seek a prescription from their physician or an urgent care center, before the prescription can then be filled at the pharmacy.
The 2024-2025 flu season has proven to be one of the most severe NC has faced in years. While opioid overdose deaths in NC have declined in recent years, access to treatment for opioid use disorder remains insufficient to meet the growing demand for services.
Allowing pharmacists to provide treatment for critical public health needs, such as flu and opioid use disorder, would be safe, efficient, and costeffective This is a smart policy change for North Carolina
The ask:
Similar to many other states, NC needs to pass legislation that enables pharmacists to assess, test, and treat specific conditions. By doing so, we would help curb the spread of contagious infections like the flu and more effectively address urgent public health challenges, such as the opioid epidemic
Support S.B. 335 Pharmacists/Test and treat/ Influenza (Primary Sponsors Sawrey, Hise Burgin and Galey)
Support H.B. TBD Name (Primary Sponsors )
PRIORITY PHARMACY LEGISLATIVE NEEDS
THE NORTH CAROLINA ASSOCIATION OF PHARMACISTS
COLLABORATIVE PRACTICE (S.B. 357)
The facts:
All 50 states have some form of Collaborative Practice Authority (CPA), which allows physicians to delegate certain healthcare services to pharmacists, such as ordering lab tests, and initiating, modifying, or discontinuing medications.
NC was a pioneer in enacting CPA for pharmacists in 1998, but our current statute has not been updated since As a result, North Carolina’s CPA has become one of the most outdated and restrictive in the nation.
Under the current law, NC’s CPA does not support population health initiatives and excludes physician assistants (PAs) and nurse practitioners (NPs) from participating in collaborative care with pharmacists. Additionally, it limits collaboration to the physician's office and does not account for opportunities outside of this setting, such as partnerships with community pharmacists or telehealth services
Since 1998, healthcare needs have evolved significantly, and our CPA statute needs modernization to remove barriers that prevent the delivery of high-quality, team-based patient care Updating the CPA will help us meet the growing healthcare demands of all North Carolinians
The ask:
We must pass legislation to update and modernize our current CPA, enabling better collaboration within an interprofessional healthcare team to better serve NC patients
By allowing all healthcare professionals in the state to practice to the full extent of their education and training, we can significantly improve patient care across North Carolina.
Support S.B. 357 Pharmacists/357(Primary Sponsors Sawrey, Hise, and Galey)
PHARMACY BENEFIT MANAGERS REFORM (H.B. 163 AND S.B. 479)
The facts:
Pharmacy Benefit Managers (PBMs) are middlemen between health plans and pharmacies, with three PBMs controlling 80% of the market.
The US is the only country with PBMs and drug prices here are 278% higher than in other developed nations Each year, PBMs grow in influence, contributing to escalating drug costs for patients Between 1987 and 2019, outof-pocket costs for patients soared by 222%
Meanwhile, pharmacies unable to negotiate pricing often receive reimbursement rates that are far below the cost of acquiring medications This financial strain has led to the closure of many independent pharmacies, limiting patient access to essential pharmaceutical services
The practice of "spread pricing" further exacerbates this issue: PBMs charge health plans one price for a medication, reimburse pharmacies at a lower rate, and pocket the difference.
As a result, patients face rising costs and pharmacies are closing, while PBMs continue to generate enormous profits. In 2022 alone, PBMs amassed $495 billion in revenue.
The ask:
We need PBMs to prioritize patient access, ensure fair reimbursement for pharmacies, limit the practice of spread pricing, establish consistent accreditation standards for pharmacies, and promote transparency in medication pricing.
Support H.B. 163 Pharmacy Benefits Manager Provisions (Primary Sponsors Reps Rhyne, Blackwell, Huneycutt, and Lowery).
Support S.B. 479 Script Act (Primary Sponsors Sawrey, Brit, and Galey)
Updated Spring 2025 NC MPJE Study Material Now Available
Getting ready to study for the NC MPJE? NCAP has two study options for you: the NC MPJE Study Guide and the NC MPJE Online Study Course. The updated Spring version is currently available. To learn more and place your order, visit the NCAP NC MPJE webpage. (At the bottom of that page, learn about NCAP’s partner to help you prepare for NAPLEX.)
NCAP’s 2025 Annual Convention
Have you registered for the 2025 NCAP Annual Convention in beautiful Asheville, NC yet? If not, why not? This year’s theme is Prioritizing Public Health: Joining Forces Across Practice Settings for a Healthier North Carolina and our planning committee is busy securing speakers from across NC and neighboring states. The convention has something for everyone in every practice setting and will take place June 23 – 25. To learn more and register to attend, visit our convention website. See you in Asheville!
April Webinar Two Dates to Choose From
The April Sunday Evening Webinar has two dates to choose from, April 6 OR April 27. Join, Dr. Grace Marley, as she presents Test to Know: Fentanyl and Xylazine Test Strips. This session equips pharmacists with the knowledge on how to use fentanyl and xylazine test strips, how to counsel a patient on the use of fentanyl and xylazine test strips, and important ordering logistics regarding each of the test strips. Visit our webinar webpage for more details and to register. The webinar will be ACPE accredited for 1 hour of live CE for pharmacists and pharmacy technicians.
Next Leadership Buzz Book Discussion
The next and final book discussion for this year’s NCAP NPF Leadership Buzz is May 7, 2025. The book selection for discussion is Hidden Potential: The Science of Achieving Greater Things. Leadership Buzz is open to new practitioners in their first 7 years of practice (2018 - 2024), fellows, and recent graduates. To sign up for Leadership Buzz access the registration link from this flyer. To learn more about the program visit the webpage on NCAP’s website.
Save the Date for NCAP’s Residency Conference 2025
NCAP’s 2025 Residency Conference will be Friday, July 18, 2025 in Winston-Salem at the Novant Health Conference Center. This is the premier kickoff event to start your residency year off on the right foot. Mark your calendars and plan to join us with your new residents. Details will be coming soon!
NCAP Executive Director is New NASPA President
The National Alliance of State Pharmacy Associations (NASPA) held their 2025 Spring Meeting. To close out the meeting on Sunday, March 23, NASPA installed the new Board of Directors. Congratulations to NCAP’s Executive Director, Dr. Penny Shelton, who will serve as President this year. Stay updated on NCAP events by visiting the website events calendar at ncpharmacists.org
• Flags (American, Christian, State, College Logo, etc.)
• Clocks (Battery Operated with Logos, etc )
• Crosses with US Flag Motif Made from Recycled Wooden Shipping Pallets See Photos at TarHeel Flags on Facebook/Market Place Contact Jim Knowles, PharmD (Retired) TarHeelFlags@PinevilleDSL.net 704-835-1042 – Please Leave Message
Complete SynMed XF System including Calibrated Containers, Dell OptiPlex 7040 with monitor, Wireless Honeywell bar code scanner, Lexmark laser printer model MA810, Zebra thermal printer model TLP2824 Plus, 4 positioning tray for two sets of blister cards, complete set of calibrated covers for containers, SynMed Image Module, SynMed Assist with includes Touch screen 23" Dell Computer
This unit was bought new when starting up a pharmacy in 2020 It was never used! The unit and all are in pristine condition This would be like buying a new unit for tens of thousands less Total Cost new was over $300,000 For Sale for $190,000 Purchase price does not include shipping charges, any tax and site preparation Contact Tom D’Andrea tdandrea@cstpharmacy.com 919-629-4900
