Pharmacy Practice News - March 2021 by McMahon Group

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UP FRONT

Want more SCCM coverage? Here’s how to access ..............................

OPERATIONS & MGMT

Pharmacy technicians boost CVD outcomes ...

CLINICAL

Hitting a bull’s eye in vancomycin dosing .....

Helping the elderly transition to safer home care ........................

TECHNOLOGY

Mobile health a boon for diabetes, heart disease ................... 17 POLICY

The building blocks of an effective reimbursement strategy .............................

When Disaster Strikes, Hospitals Call in Residents isa Glance Mostafavifar, PharmD, the PGY1 residency program director at The Ohio State University, College of Pharmacy, in Columbus, always held her pharmacy residents in high regard. However, through their work during the COVID-19 pandemic, she realized just how essential their contributions are to helping the pharmacy department provide patient care services. “The commitment our pharmacy residents have shown to providing excellent patient care has never been as evident as it has [been] during the pandemic,” Mostafavifar said. “Plain and simple, we would not have the reach we have without our residents.” The pharmacy residents have been stationed at the COVID-19 vaccination clinic at the Ohio State University Wexner Medical Center (OSUWMC),

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Filgrastim use in oncology saves $500K

Biosimilar Switches Work At Large and Small Centers L

arge health systems as well as small community hospitals can successfully convert to oncology biosimilars and achieve substantial savings, according to presentations at the ASHP 2020 Midyear Clinical Meeting and Exposition. University Hospitals (UH) Health System, in northeastern Ohio, achieved approximately $500,000 in savings annually by switching to the biosimilar filgrastim-sndz (Zarxio, Sandoz). Kalispell Regional Medical Center, a 288-bed hospital in northwestern Montana, had similar success converting to Continued on page 8

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REVIEW ARTICLE

SCCM Survey: Front-Line Pharms Feeling Burnout

Operationalizing NIOSH, USP <800>, and EPA Requirements See page 18.

NEW PRODUCT Ketorolac Tromethamine Injection USP, 60 mg/2 mL (30 mg/mL) in Single-Dose Vials. See page 3.

Volume 48 • Number 3 • March 2021

ith many ICUs reaching or exceeding maximum capacity in spring 2020 due to the COVID-19 pandemic, it may not be a surprise that about 60% of critical care pharmacists reported feeling burned out in a recent national survey. As cases persist in hot spots across the country, there is a need for the profession to highlight coping strategies for the nation’s frazzled front-line caregivers. In the survey, 128 of 221 respondents (58%) reported feelings of burnout such as emotional exhaustion and depersonalization, according to the

No Consensus on Alternative Therapies for Pediatric Sepsis

linicians employ similar tools to treat the approximately 1.2 million cases of childhood sepsis per year, according to pediatric pharmacists: fluid boluses, antibiotics, vasoactive agents such as epinephrine and norepinephrine, and corticosteroids. Despite best efforts, sepsis still leads to significant mortality rates in these vulnerable patients. In the search for added ammunition, some have turned to methylene blue, vitamin C and thiamine in the management of septic shock in children, as well as adults. Panelists at the Society of Critical Care Medicine (SCCM) 2021 Critical Care Congress Virtual Event say the data, while limited, are intriguing. Methylene blue, which originated as a

dye in the textile industry, is “an old chemical with many uses,” said Thomas Moran, PharmD, MS, BCPS, the manager of clinical pharmacy services at the Ann & Robert H. Lurie Children’s Hospital of Chicago. The compound has been used as an antimalarial agent, an antidote in cyanide poisoning and a possible treatment for depression, Moran noted. He explained that it works by blocking chemical pathways that regulate vascular smooth muscle and by decreasing the systemic vascular resistance (vasoplegia) that develops in septic shock. Studies of methylene blue in adults with septic shock have found it increases mean arterial pressure but led to no changes in

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Up Front

Pharmacy Practice News • March 2021

Digital rotoxicity syndrome, marked by seizures, cerebral edema and motor deficits. Access: bit.ly/3pdSsJu.

SCCM on the Web Here’s a sample of our coverage of the Society of Critical Care Medicine (SCCM) 2021 Critical Care Congress Virtual Event. To access full articles, see the URLs below. Quick Identification Necessary For Managing Pediatric Sepsis Timely identification of pediatric sepsis and resuscitation result in improved outcomes, according to interim results from the IPSO FACTO (Improving Pediatric Sepsis Outcomes for All Children Together) study. The goal was addressed by using drivers focusing on: • the timely recognition and treatment of infection, which may lead to sepsis; • recognition of sepsis, diagnosis of sepsis, and where a patient is on the continuum of septic shock; • treatment of sepsis; • de-escalation of inpatient care;

• engagement with patients and their families; and • performance optimization via change strategies. Access: bit.ly/3d1Hyo2 CAR-T Therapy Patients in ICU Likely to Experience Toxicities About one-third of patients who were admitted to ICUs after chimeric antigen receptor (CAR) T-cell therapy for cancer experienced common toxicity syndromes, a study from 11 U.S. medical centers has found. The two most common adverse reactions were cytokine release syndrome, marked by hemodynamic and respiratory failure as well as end-organ damage, and immune effector cell-associated neu-

Bacterial Superinfections In Children Rare but Costly Although cases of bacterial superinfection in hospitalized children are relatively rare, they are likely to result in worse clinical outcomes and the use of more hospital resources (abstract 695). Children with superinfections needed more ICU care, IV antibiotics, radiographs and intubation. The median cost of care was significantly higher for these severely ill patients, at $3,774 versus $2,344 (P<0.001). Access: bit.ly/ 2ZupWsT. Ventilator Synchrony Dosing Helps ARDS Patients Published guidelines for hospitalized patients with moderate to severe acute respiratory distress syndrome recommend the use of neuromuscular blocking agents. However, the guidelines do not make recommendations for a specific dosing scheme. Now, new research suggests that dosing these medications by titrating them to mechanical ventilation goals, also called ventilator synchrony, may allow clinicians to treat patients using less drug and at a lower cost than other types of dosing regimens. Access: bit.ly/ 371dh4M.

EDITORIAL BOARD

NEW PRODUCT Nephron Announces FDA Approval of Ketorolac

ephron Pharmaceuticals Corp. announced FDA approval of its Abbreviated New Drug g Application (ANDA) for Ketorolac Tromethamine Injection USP, 60 mg/2 mL (30 mg/mL)) in Single-Dose Vials. The vials are made of polypropylene plastic with a “luer lock” interface for needle-free dosing and d are manufactured using Blow-Fill-Seal (BFS) technology. Ketorolac Tromethamine becomes one of the first ANDA-approved nonrespiratory generic medications produced by Nephron, according to the company. Nephron secured FDA approval for Sodium Chloride IV Bags earlier this year. Nephron-manufactured Ketorolac Tromethamine is an injectable medication for the short-term treatment (up to 5 days) of moderately severe acute pain. Commonly used after surgeries and other medical procedures, Ketorolac Tromethamine is a nonsteroidal anti-inflammatory drug. Prescribing Information for Ketorolac Tromethamine Injection Vial UPS, 60 mg/2 mL (30 mg/mL) is available at bit. ly/2Y29O0L. Additional product information is available at bit.ly/397N0Dd.

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Volume 48 • Number 3 • March 2021 • pharmacypracticenews.com

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4 Operations & Management

Pharmacy Practice News • March 2021

Cardiovascular Disease

Pharmacy Technicians Help Improve CVD Care

ntegrating pharmacy technicians and clinical decision support into a pharmacist-managed cardiovascular risk reduction service has helped Kaiser Permanente Colorado achieve better patient outcomes and use clinical pharmacists’ time more strategically. The approach represents a significant shift from Kaiser’s previous cardiovascular management model. For nearly 20 years, clinical pharmacists with the

medical practice did the bulk of the support work, primarily in the form of maintaining a registry of all patients with documented cardiovascular disease in its cardiovascular risk reduction service, according to Kari Olson, PharmD, BCPS, a clinical pharmacy specialist in pharmacy outcomes research for Kaiser Permanente’s National Pharmacy. In recent years, she said, the service had grown to the point where

about 15 clinical pharmacy specialists each had a panel of around 1,200 to 1,300 patients, and helped manage lipids, blood pressure, some diabetes markers and medication adherence. Pharmacy technicians were limited to handling incoming calls contacting patients who were overdue for lab draws;

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otherwise, pharmacists handled the bulk of the work. But when the practice incorporated the registry into its electronic medical record (EMR; Epic) in 2019, managers reorganized the service to take advantage of new technology capabilities and to off-load more of the work to pharmacy technicians, Olson said. “What was really nice with the new registry is it had additional functions, so we could have technicians identify patients who were due for labs very quickly and send out bulk mailings to 1,000 to 1,500 patients a month,” said Olson, whose team presented the initiative during the American College of Clinical Pharmacy 2020 virtual annual meeting. “Also, because all information was within the medical record, they could easily see who already had come in for labs, quickly identify patients overdue for labs and streamline workflows across the service.” Pharmacists had done most of the patient outreach, from providing lab results to adjusting medications, Olson added. In the new system, the technicians handle basic outreach to patients and send notices if lab results are within normal limits, as determined by established protocols. The revised system also allows technicians to place orders for patients who are due for lab draws that would go to the pharmacists for a quick sign-off. “[This new practice model] off-loaded a lot of the administrative work to the pharmacy technicians, and patients whose disease was well controlled no longer had to go to the pharmacist for review,” she said. “It allowed the pharmacists to focus on patients at the highest risk [level] who needed intervention.”

Documented Improvements The expanded pharmacy technician program yielded major benefits, according to a study by Olsen and her colleagues. The study included 6,813 patients: 3,130 in the older, pharmacistdriven group and 3,683 in the newer, technician-enhanced group. The mean age was 70.2 years; about 71% were men. After one year of enrollment in each protocol, the proportion of patients who

Operations & Management

Pharmacy Practice News • March 2021

Cardiovascular Disease

71.2% of patients in the technician-enhanced group reached LDL goals versus

58.6% in the pharmacistdriven group. Source: Kari Olson, PharmD

attained cholesterol (low-density lipoprotein [LDL] cholesterol <70 mg/dL, non–high-density lipoprotein [HDL] cholesterol <100 mg/dL) and blood pressure (BP <140/90 mm Hg) target goals was higher in the tech-enhanced group. Specifically, 71.2% of patients in the technician-enhanced group reached LDL goals versus 58.6% in the pharmacistdriven group (P<0.001); 73% of those in the technician-enhanced group attained non-HDL goals versus 60.7% in the pharmacist-driven group (P<0.001); and 88.9% of those in the technician-enhanced group achieved BP goals versus 86% in the pharmacist-driven group (P<0.06). The percentage of encounters handled by pharmacists in the prior system was 84%, compared with 44.7% in the technicianenhanced group (P<0.001). There was some initial hesitancy from pharmacists, who had concerns that good patient outcomes might not be maintained, or that the technicians might miss things, but the study found otherwise, Olson said: “Our results were not from just integrating the technicians; they were the result of the whole program. Using technicians, leveraging our EMR and having the right people do the right work actually improves our outcomes because the pharmacists could focus their efforts on patients who need the care versus those who were already well controlled.” Based on the program’s success, the medical practice intends to expand it to cover patients with diabetes and those with hypertension, Olsen said, adding that the expansion will be done as a subset of the larger cardiovascular risk group.

‘[This new practice model] off-loaded a lot of the administrative work to pharmacy technicians, and … allowed the pharmacists to focus on patients at the highest risk who needed intervention.’ —Kari Olson, PharmD, BCPS that administrative burden using skills well within the scope of technicians.” An article that Di Palo co-authored on the role of pharmacists in hypertension

management (Curr Opin Cardiol 2018;33[4]:382-387) highlighted the benefits of team interventions. Patient management can incorporate changes or

Olson and Di Palo reported no relevant financial disclosures.

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‘A Progressive’ Program Incorporating technicians this way is “a progressive thing to do,” commented Katherine Di Palo, PharmD, the clinical program manager of the hospital readmissions reduction program at Montefiore Medical Center, in New York City. “It’s very smart,” Di Palo told Pharmacy Practice News. Having technicians perform the data mining and outreach as the first touchpoint “is a good way to pull patients into the clinic and allows the clinical pharmacists to make the decisions. It offsets

dose adjustments in medications, scheduling appointments and following up with patients to ensure they picked up medications, she said: “Having another set of eyes on the patient to continue navigation and care coordination can have a positive impact and improve outcomes.” Telehealth offers another avenue for this important work to continue, she noted. —Karen Blum

To learn more about Pfizer’s oncology biosimilars, visit us online at PfizerBiosimilars.com References: 1. IMS Institute for Healthcare Informatics. Delivering on the Potential of Biosimilar Medicines: The Role of Functioning Competitive Markets. Parsippany, NJ: IMS; March 2016. 2. Drugs.com. How many biosimilars have been approved in the United States? https://www.drugs.com/medical-answers/many-biosimilars-approved-united-states-3463281/. Updated December 8, 2019. Accessed April 6, 2020. 3. McGowan S, Jesse M. Biosimilars Pipeline Report. AmerisourceBergen. https:/www.amerisourcebergen.com/-/ media/assets/amerisourcebergen/biosimilars-pipeline-report_0420_v3.pdf?la=en&hash=1071304C7B66ED62628201B8268C0B633 627CB6B. Updated May 1, 2020. Accessed June 4, 2020. 4. Data on file. Pfizer Inc., New York, NY.

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6 Operations & Management

Pharmacy Practice News • March 2021

COVID-19 Pandemic

Calling in the Residents

the pharmacist, pha she explained. “We’ll implementing this change for future be imple disaster situations as well,” Slone said. Despite Despit a frenzy of changes imposed by the pandemic, she said residents ccompleted co mplet their program on time, “with only disruption, and had the on o nly minimal mi cchance hance to interact in even more multidisciplinary team meetings and with tti idiscipl more members than they m o orre leadership le would normally.” wo w ould n

continued from page 1

coordinating staffing, opening and closing the clinic, transferring inventory and vaccinating employees, she said. OSUWMC requires residents to have vaccine training certification from the American Pharmacists Association, or an equivalent vaccine course, along with a current Basic Life Support certificate before they can vaccinate patients, Mostafavifar noted. Outside of the vaccination clinic, throughout the pandemic, university pharmacy residents have been working with specialists to develop and implement several protocols for the care of COVID-19 patients, including those involving prophylaxis and treatment of venous thromboembolism, managing adults with severe COVID-19, and the use of antimicrobials. They interpret new information and communicate their findings to multiple disciplines to obtain consensus, and then revise patient care guidelines as necessary, Mostafavifar said. “We are lucky to have a very large program with about 30 residents, and we’re able to integrate them into all aspects of the department and expose them to real-world situations that prepare them to enter the workforce,” she noted.

King’s Daughters Medical Center During the first wave of COVID-19 cases in March 2020, after some pharmacists at King’s Daughters Medical Center, in Ashland, Ky., were sent home, finding the best way to include residents in patient care was “one of many challenges we were facing on multiple fronts,” Lori-Belle Slone,

PharmD, the pharmacy clinical al manager, residency site director att King’s Daughters, said in a case management agement presentation during the ASHP P 2020 Midyear Clinical Meeting. “A neighboring hospital that had been scheduled to close in September shut ber sh hu utt down early, which meant our patient patient census was unpredictable, and wee n needeeded to adjust staffing to align wi with ith tthis his new census,” Slone said. “As COVID-19 OVID -19 hit, we also had to implementt ssafety afettyy measures to reduce transmission io on rrisk issk k among patients and staff, and wee n needed eeded to continue to meet residency pr program rogram accreditation requirements.” Because pharmacy leaders rss had h ad ad always recognized residents ass ““core core co re members of the pharmacy and p patient ati tieen nt care teams,” one way to keep residents d engaged was to have them participate in the disaster response plan, including daily virtual leadership calls, Slone said. “This experience allowed them to see just how and why certain decisions were made, so they truly felt like part of the leadership team.” In the early stages of the pandemic, residents were critical in assessing the needs of the pharmacy department and helping schedule staff shifts, Slone noted. In addition to taking on administrative tasks, which she believes taught residents some of the skills necessary for managing daily pharmacy operations, pharmacy residents spearheaded the development of drug shortage contingency plans. “For example, one of our residents was assigned to monitor use of sedatives

Brian Heng, PharmD, current PGY1 resident (left), and Steven Hulett, PharmD, MBA, a preceptor-in-training for their program, are part of an effort to enlist residents in the management of patients with COVID-19.

Penn P Pe enn M Medicine

Lindsey Groff, PharmD, a PGY2 infectious diseases pharmacy resident at The Ohio State University, draws up one of the first COVID-19 vaccine doses her team administered in late December 2020.

in COVID-19 patients and our regular critical care population, and to compare the agents with historical, non-COVID usage, and report any trends they find to our pharmacy leadership team during daily COVID calls,” Slone said. Residents also have helped to distribute medications used in the treatment of COVID-19, including remdesivir (Veklury, Gilead Sciences) and monoclonal antibody therapy, and to field questions related to their use, she said. “Residents created educational documents on these medications that include criteria for use, organization-specific restrictions, and dosing and administration.” Furthermore, residents have taken on several other tasks during the pandemic, Slone said. For example, they developed medication handling strategies to help reduce staff exposure and contamination. One of the first steps in that effort was to quarantine medications returned to the pharmacy from COVID-19 units. They also revamped crash-cart processes to improve safety, including minimizing the need for multiple crash carts by assembling COVID-19 emergency bags with essential COVID-19 medications, Slone noted. These bags were placed in automated dispensing cabinets or medication rooms, where they could be quickly removed, she explained. Slone added that residents also developed policies and procedures for an antithrombosis drive-through clinic developed during the pandemic that has helped minimize exposure to SARSCoV-2. One of the policies permits antithrombosis clinic patient visits to be extended to 12-week intervals for wellcontrolled patients, at the discretion of

Att Pen A Penn Presbyterian Medical Center, Philadelphia, PGY1 residents have iin n P hila been helping Kevin Lee, PharmD, an be b een he care clinical pharmacy speaambulatory mbulat cialist, cci ial alist, aand his team continue to provide chronic disease management servvi ide chr id vvices iicces at Penn’s Family Medicine Clinic. we had to move offsite in March ““When When w 2020 due to COVID-19, we temporarily 2 20 020 du rremoved emoved residents from the workflow to ffigure out how to include them in patient care,” Lee recalled during a separate presentation at the ASHP meeting. After customizing a telemedicine workflow for the clinic’s pharmacists, Lee and other pharmacy leaders devised workflow documents specifically for PGY1 residents, training and orienting them to the new processes and ensuring they were familiar with their preceptors’ telemedicine workflows. “It took us six weeks after we went offsite, but we did bring PGY1 residents back into the patient care process by the end of April and early May,” Lee said. Following a period of shadowing their preceptors, residents transitioned to independent patient visits, with preceptors coming in at the end of the visit through Microsoft Teams—a video conferencing platform that Lee and his team used solely for meetings between preceptors and residents. Data suggest the transition to remote patient care at Penn Presbyterian Medical Center was a success, and residents should take part of the credit, Lee said. He and his colleagues found that 63% of the 134 clinical pharmacy patients scheduled for April and May 2020, after the virtual workflow was implemented, attended their telemedicine visits, compared with 51% of 102 patients scheduled for in-person appointments in January and February 2020. “The customized workflow document for residents and the Microsoft Teams [software] helped make the transition to telemedicine seamless and also allowed residents to continue their training,” Lee said. “Overall, our residents have been a great help in providing continuity of care to our patients in the clinic.” —David Wild The sources reported no relevant financial disclosures.

Microbiome-Based Therapy: The Next Frontier in the Management of Clostridioides difﬁcile Infections and Recurrence Download a PDF or request free hard copy reprints

PharmacyPracticeNews.com/MicrobiomeSR A Supplement to

levels. 55,56 Patients infected by also have strains th higher m at produc or ta strains of e all 3 toxin C. dif ficile 57 lity rates than pa s tients wh . In addition In 2017, o carry ot th e es tim to her gastrointes cated by ated na tio as sociate tinal dam the develop d CDI wa na l bu rd age, CDI ment of no stream inf s 235,700 en of he can be co ca se s) wi ections wi socomial case s alt h ca re th m pli an estim th enteric infections pathogen 58 – 77.6 ) pe ated inc ide (95% CI, 221,700 pathogen and blood . It has r 10 0,00 -249,70 0 nc e of 73 s as the m been hypo 0 rity enables po as .3 (9 5% pu sociated ain causati thesized lation. 62 microbial CI, 68.9 CD th Th ve at I e wa th burden of tra circulation 59 e altered s 226,400 cases) wi gut integ. Transloc nslocation from th co ca th m se m an estimate s (95% CI e gut to th ation is th ity due to per 10 0,0 , 20 6,90 0- unitye system e increas disruption 00 populat d62incidence of 70 245,9 00 ic ed of the gu tinal over .4 (95% CI ion. Mos likely unde t barrier fun intestinal permea grow th an , 64.3-76. t estimate restimate bild genera ction. Mor 4) are asso s s of in be CD l changes te ca eo rm I ciated wi us incidence ver, intes s of case e data ar in the bacte th CDI. Tra are s admitted e typically lipopolysa fore do no rial microb nslocation only repo ccharides to the ho t include iota leads to rted spital for (L cell wall, people tre ratio shifte the relea CD into the blo PS ), a component I, an ated as ou se of d toward odstream. 60 of the gram response tpatients. 62 d therea higher ting from prot This induc -negative incidence the Thus, the es produc against LP eins and consum in the co stewardsh health care setting tio ption of ne mmunity S antigen 60 ip progra because setutralization n of host s. Follo 62 can lead m of s. a An lack of an wing trans antibodies othe r fac to sepsis tibiotic to location, in initial CD r th cantly wi at frames ho sp ita ls this casc I (16%), an th recurre the data be ing pe ade nt episode d can inc re porte d 33.1% wi na liz rC ed DI re s: ab ) as th the seco fo in th e Un 27 e signifiove involv ite d States 63 r th eir rate s of CD nd, and 43 .3% with the first there is so I (e sp ec ial es recurrenc . Given .3% with metimes Epidemio e, this finan ly fo r more. 61 a relucta symptom cial cons logy and nce to te s for CDI ideration, Burden of st an pa Recent stu d na tients with a recent rio, empir CDI dies on th infection. 63 ic therap classic States sh e incidenc y is usua the patie In th at ow a de cli lly e nt is nical sceof C. dif started an crea se in ing prop d likely ef recurrenc 63 not accounted fo or tion of overall nu ficile in the United fective bu r e. Unde commun m be rs bu m ated na t r the Hosp epidemiologically tion Prog ity-acquir tio na l bu as having ital-Acquir ram of th ed infectio 62t a growrd en of health ca e Centers a ed ho ns Co sp bo . nd itals’ reim th co m m re –assoc The estifor Medica ition Redu bursemen iated C. un ity-a ss c428,60 0acquired dif ficile is oc iated t is reduce re & Medicaid Se 495,600 CD an 42 rv I are eleva d d if their ices, cases). 62 8,60 0 ca the natio recurrenc ted. 64 Th rates of ho ses (95% Although nal burden e of CDI, e estimate the adjus CI, spitalof health by 36 % hospitaliz d frequen of acquisi ted estim care –ass (95% CI, ations fo tion, and cy of first ate of ociat 24 r CDI rega natio na l in-hospita The rates bu rd en of % -54%), th e ad jus ed CDI decrease rd l les deaths ar s of site d te d estim co unchange e shown very high; of CDI have decr ate of th in Table 1. 62 d over tim 62m m un ity-a cq uired eased re however, e e. The CD I ha s in 2017 fo cently, bu the infec be more overall na re m ain ed t still rem r he alth tions that refractor y tional bu ca re –ass ain (95% CI, pa to re tie an rd nc nt tim oc en e. In 2017 s get se 428,60 0iated CD icrobial th estimate em to , Ma et al 495,600 I was 46 erapy resu mated as Unite d St cases), an 2,100 ca studied th 143.6 (95% ates using se s d the incide e incidenc lting in recurCI, 133.2-1 m a er nc da e cia e ta of 54.0 ) per was estilly ins ured base of 100,000 almost 39 rCDI in the pe op le, between population 62 of wh om m 20 01 and . 45,341 de illion com2012. 65 Du de nc e of ve lop ed ring this CDI inc re CD I period, th ased by e annual 42.7% , fro inciTable 1. m 0.4408 Estimates to 0.6289 of Firs Asso

Microbiome-Based Therapy: The Next Frontier in the Management of Clostridioides difﬁcile Infections and Recurrence Faculty Teena Chopra, MD, MPH Professor, Infectious Disease Wayne State University School of Medicine Detroit, Michigan

Paul Feuerstadt, MD, FACG, AGAF

Kevin Garey, PharmD, MS, FASHP

Assistant Clinical Professor of Medicine/ Attending Physician Yale University School of Medicine/ Gastroenterology Center of Connecticut New Haven, Connecticut

Chair, Department of Pharmacy Practice and Translational Research Professor, Pharmacy Practice University of Houston College of Pharmacy Houston, Texas

he microbiota is a community of microorganisms, such as bacteria, fungi, and viruses, that inhabits a particular location, including the human body.1-4 The human body is home to about 100 trillion bacteria and other microbes comprising up to 36,000 distinct species of bacteria—collectively known as the microbiome.4,5 The gut microbes that inhabit the human body outnumber human cells by several times.6,7 It is recognized that the number of genes in the majority of microbes (microbiome) exceeds the total number of human genes by hundreds-fold.8 Advances in DNA sequencing and bioinformatics made the progress in human microbiome research possible. Driven by the Human Microbiome Project and European MetaHIT program, there are many groups studying the relationships between the microbiome and human health and disease.6,7,9 Gut microbiota have roles in health and disease states across several fields, including gastrointestinal diseases (ie, inflammatory bowel

disease, fatty liver), metabolic diseases (eg, diabetes, obesity), immunologic diseases (ie, allergic conditions), and brain–gut disorders (eg, autism, Parkinson’s disease).2,4,10-12 Change in microbiome, known as dysbiosis, is often caused by dietary factors, stress, and the use of broadspectrum antibiotics, such as cephalosporins or fluoroquinolones.13-15 Such disruption to the gut microbiome leads to an environment suited for the proliferation of Clostridioides difficile (C. difficile). Although antimicrobial therapy is currently the standard of care for the treatment of C. difficile, these agents are somewhat nonspecific. They target C. difficile but also alter the surrounding microbiota milieu, leading to an imbalance of gut microflora and causing recurrence of C. difficile infection (CDI).14,16 Among patients receiving antibiotic treatment for CDI, 20% to 35% experience a recurrence and 40% to 60% of patients have a second recurrence.17-22 Specifically, the risk for a second recurrence increases to 40%,

ciated W

ith CDI in

t Recurre the Unite nce, Hospitalizat ion, and d States: In-Hospi 2017 tal De

Commun ity n (9 5% CI -associated CD ) I, Estimat

ed tota l:

23 5,70 0

cases

Inci de nc e (9 5% CI pe r 10 0,00 0 pe rs )

on s

He al th ca re n (9 5% CI –a ssoc ia te d CD ) I, Estimat

ed tota l:

22 6,40 0

cases

Inci de nc e pe r 10 0,00 0 pe (9 5% CI rson s )

Supported by

CD I, Clo Adapted

stridioides dif ficile inf ection from refere nc e 62.

Estimat ed Recurr en First ce

31,300 (2 6,60 0-36 ,0

00 )

13.3% 9.7 (8.3-11 .2 ) 38,500 (3

12.0 (10.0 -13

.9 )

ions 69,9 00 (6 1,100 -78, 60

Estimat ed In-Hos Deat hs pital 0)

154,100 (14

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47.9 (43.7 -52.0 )

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1.3 (0.7-2.0 )

16,200 (13

)

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00 )

7.1% 5.0 (4.1- 6. 0)

Faculty Teena Chopra, MD, MPH Professor, Infectious Disease Wayne State University School of Medicine Detroit, Michigan

Paul Feuerstadt, MD, FACG, AGAF Assistant Clinical Professor of Medicine/ Attending Physician Yale University School of Medicine/ Gastroenterology Center of Connecticut New Haven, Connecticut

Kevin Garey, PharmD, MS, FASHP Chair, Department of Pharmacy Practice and Translational Research Professor, Pharmacy Practice University of Houston College of Pharmacy Houston, Texas

Supported by

8 Operations & Management

Pharmacy Practice News • March 2021

Oncology

Biosimilar Switches continued from page 1

pegfilgrastim-cbqv (Udenyca, Coherus), netting the medical center close to $400,000 over 11 months.

Comprehensive, Flexible Strategy UH achieved their cost avoidance through a broad strategy for biosimilar implementation throughout the 15-hospital health system. An interdisciplinary group—including providers, nurses, and pharmacists; informatics, precertification, supply chain, and contracting staffs; and others—developed a standard strategy to review and implement biosimilars and monitor the market for new biosimilar entries and payor coverage. Presenting a report on the approach during the ASHP meeting, Indrani Kar, PharmD, the drug policy/formulary specialist at UH, noted that the “strategy identifies a preferred product … supported by therapeutic interchanges through our system formulary processes.”

Practice News. “We strategically chose to only implement biosimilars on newstart patients at go-live. The rest of the patients are switched over when their precertification renews, or there is additional work between pharmacy and provider ahead of time. This continues to be an area for process improvement, as payors start to change their preferred agents,” she added, noting that “this is an opportunity for health systems to engage in advocacy with payors to maintain their implemented strategy.” In addition to switching to filgrastimsndz, in November 2019, UH set pegfilgrastim-cbqv as its preferred pegfilgrastim injectable for adults in both inpatient and outpatient settings. The system also retained the pre-filled pegfilgrastim kit (Neulasta Onpro, Amgen) on the formulary for specific patient needs. Kar said UH employs a “very strategic process” for biosimilar implementation with four main areas: formulary,

‘A key important feature of the successful adoption of biosimilars in these health care systems has been the vital role of pharmacy, from product selection to the mechanics of how to best operationalize biosimilar integration into the health system.’ —Sandra Cuellar, PharmD, BCOP The preferred product is selected after analysis that considers the available evidence as well as contracting and payor coverage. In the electronic medical record (EMR), the orders are listed as generic and default to the preferred agent when dispensed. The verified product label lists the full generic name, including the four-letter suffix. “The pharmacist can dispense the covered product,” Kar said, “after reviewing the prior authorization coverage documented in our homegrown precertification team database.” The strategy provides a process to address insurance denials of the preferred agent and to change the order to the insurance-covered product. To facilitate education on and monitoring of the switches, the biosimilars team provides memos, supporting documents and other materials on the system’s intranet. They also set up a process to account for effects of the new preferred agents on precertification/financial clearance and pharmacy workflow. “Precert is crucial,” Kar told Pharmacy

informatics, implementation and monitoring. The process works well for the most part, Kar noted. “There are challenges with having a device [Onpro] still available,” she said. “Many payors may not support Onpro, so we then need new orders and new appointments for the patient, since the device is treated as a separate product from the biosimilar.” Noting that some of her colleagues at other centers have opted to remove Onpro from their formularies and work with just biosimilar pegfilgrastims, she said “that was not an option UH was willing to explore at this time. There are good reasons to provide Onpro,” she added, such as when patients are unable to come back to get repeat doses of pegfilgrastim-cbqv, provided insurance companies pay for it. When UH started the conversion, most insurance companies would pay for Onpro, but denials are “steadily increasing,” which will necessitate ongoing “monitoring of Onpro usage and further assessment,” Kar said. “Preparation is key in having a

comprehensive strategy with i h iinterdisdi ciplinary input and then supporting that strategy with education and monitoring,” Kar said. She noted that every few years UH will reevaluate based on the literature, contracting, payor landscape, etc. “It’s important to have that monitoring,” she said, “just to ensure that we’re still providing the most appropriate medications for our patients.” Kar said they are still analyzing the annualized cost-savings data for the pegfilgrastim-cbqv switch.

Small Center, Big Savings Faced with rising costs in their outpatient oncology clinic in 2019, pharmacists at Kalispell Regional worked with their oncologists to successfully convert to biosimilar pegfilgrastimcbqv, according to the investigators, led by Hugh Easley, PharmD, the medical center’s director of pharmacy. Misty Klotz, a PharmD candidate who presented the findings at the ASHP meeting, acknowledged that in the beginning, it was a bit of a “bumpy road,” but once a couple of oncologists got “on board, it fell into place.” A few payors require different products and a few patients do not take the biosimilar, but most patients are getting it, and that is increasing over time, she said. “The biggest workflow challenges are around the electronic health record build and insurance authorizations,” Easley said. He recommended that those embarking on such a project should include their informatics team and those involved in the revenue cycle “to ensure a smooth transition.” Kalispell Regional has five oncology pharmacists, three of whom have primary responsibility for rotating through the

clinic and working closely with the clinic’s oncology team with respect to dosing and adverse events, Klotz said. The clinic nursing staff deals with getting coverage, prior authorizations and other logistics related to biosimilars conversions. “I am fortunate to have a strong pharmacy team (board-certified oncology pharmacists) who work in collaboration with the oncologists,” Easley told Pharmacy Practice News. “A few years ago, an oncology stewardship committee was developed as a multidisciplinary team to provide input to the pharmacy and therapeutics [P&T] committee. This [oncology stewardship] committee has evolved naturally over time and is now integral to our P&T committee. With their support, we were able to move and adapt quickly to the biosimilar market, resulting in savings for the organization and the patients.” The costs for pegfilgrastim decreased 27.3%, from $1,413,842 in the preimplementation period (March 2018 to January 2019) to $1,027,704 in the postimplementation period (March 2019 to January 2020), a savings of $386,138. The switch also decreased charges by $632,546 for Kalispell Regional’s patient population, reflecting lowered costs for the patients’ insurance companies. “Hopefully,” he added, this “results in lower monthly premiums (or less of an increase), which could be significant for self-funded plans.”

Success Stories Will Drive Expansion of Biosimilars Commenting on the studies for Pharmacy Practice News, Douglas Hackenyos, PharmD, BCOP, the oncology pharmacy clinical coordinator at UConn Health in Farmington, Conn.,

Operations & Management

Pharmacy Practice News • March 2021

Oncology The costs for pegfilgrastim decreased

27.3% from

$1,413,842 in the pre-implementation period to

$1,027,704 post-implementation Source: Kalispell Regional Medical Center

said id “both b h projects j lend further support to oncology biosimilar conversions through their quantification of actual cost avoidance. Importantly, we can hope such efforts also translate to lower costs for our patients. The more success stories and detailed accounts of implementation and conversion processes we have, the more traction we’ll have for expanding biosimilar use in oncology.” These studies show how “the economic promise biosimilars were anticipated to have on health systems is becoming a reality across both small and large health care systems in the United States,” Sandra Cuellar, PharmD, BCOP, told Pharmacy Practice News. “A key important feature of the successful adoption of biosimilars in these health care systems has been the vital role of pharmacy, from product selection to the mechanics of how to best operationalize biosimilar integration into the health system,” noted Cuellar, the oncology pharmacy team leader and a clinical associate professor at the University of Illinois Chicago College of Pharmacy. “The blueprint for biosimilar adoption will vary with each institution, as payor mix, physician acceptance and IT support are just a few of the hurdles health care systems need to anticipate,” Cuellar said. “Another important feature will be an educational plan for both health care teams as well as patients. Specifically,” she said, “the health care team should have a universal understanding and ability to explain biosimilars to patients.” She also noted that health systems implementing biosimilar programs will likely need to be prepared to stock multiple biosimilar products to account for multiple payors in the market.

‘Preparation is key in having a comprehensive strategy with interdisciplinary input and then supporting that strategy with education and monitoring.’ —Indrani Kar, PharmD Noting that UH and Kalispell Regional “shared positive outcomes with growth factor biosimilars,”

Cuellar pointed out that “biosimilar options are not limited to only supportive care” but also include oncology

therapeutic options. “Biosimilars now exists for our top biologics agents in oncology. Those include rituximab, trastuzumab and bevacizumab. As health care systems continue to recognize the economic value biosimilars [provide] without compromising safety or efficacy, the dream of reducing health care expenditures in oncology can become reality.” —Sarah Tilyou The sources reported no relevant financial disclosures.

10 Clinical

Pharmacy Practice News • March 2021

Infectious Disease

Strategy excels for patients with renal failure

ould a simple table do for vancomycin dosing what checklists did for patient safety? That seems to be the case, based on a new study showing that the pharmacistcreated tables helped more patients at a Michigan hospital achieve targeted trough concentrations than the providers’ past standard practice of dosing based on random vancomycin serum level monitoring. Before implementing a novel vancomycin dosing tool in 2019 at HarperHutzel Hospital, part of Detroit Medical Center, some 37% of 476 patients studied achieved targeted trough level concentrations of 15 to 20 mcg/mL. After using the tool, that percentage increased to 58% among 57 patients receiving scheduled doses. When levels within one standard deviation of the target range were included, this increased to 89%. These results, in hemodynamically unstable critically ill patients with renal failure receiving continuous renal replacement therapy (CRRT), were presented at the American College of Clinical Pharmacy 2020 virtual annual meeting. “There is currently limited research available to guide clinicians on dosing vancomycin in critically ill patients based on CRRT rates,” said Merna Azuz, PharmD, a co-author of the study and pharmacy resident with the hospital. As such, the two-year project was initiated to provide additional dosing recommendations and guide pharmacists. The hospital traditionally gave patients a loading dose of 20 mg/kg of vancomycin, and based subsequent dosing on vancomycin serum monitoring—dosing

that was left to the discretion of the pharmacist. In the first year of the project, from 2018 to 2019, critical care pharmacist Krista Wahby, PharmD, BCCCP, assessed dosing practices at the hospital, noting that 66% of patients who received vancomycin on a schedule achieved targeted trough levels, compared with 37% of patients who were dosed based on monitoring levels. She also analyzed patient records to determine what doses achieved the target range. That information allowed Wahby to establish a vancomycin dosing table using CRRT rates. Specifically, she recommended that: • patients receiving continuous venovenous hemofiltration at an ultrafiltration rate (UFR) of 1,000 to 2,000 mL per hour should be given 15 to 17 mg/kg of vancomycin every 24 hours, starting 12 hours after the loading dose; • patients with a UFR of 2,000 to 3,000 mL per hour should receive 18 to 20 mg/kg of vancomycin every 24 hours, starting eight hours after the loading dose; • patients with a UFR of 3,000 to 4,000 mL per hour should receive 20 to 22 mg/kg of vancomycin every 24 hours, starting six hours after the loading dose; and • patients with a UFR in excess of 4,000 mL per hour should be given 15 mg/kg of vancomycin every 12 hours, starting five hours after the loading dose. During the second year of the project, Azuz validated the table. She educated staff pharmacists at the hospital about vancomycin dosing and pushed use of the dosing tool. “Even though this is a very narrow

trough target, more patients were able to achieve it using the dosing table that we recommended,” Azuz said. The tool also helped reduce the pharmacists’ workload: For every vancomycin level that is drawn, pharmacists must write a chart note. During the study, the amount of notes written by pharmacists per patient per day was halved, from 0.9 to 0.4 (P<0.001). “I’ve spoken with different pharmacists regarding how they like the table, and a lot of them have given me positive feedback,” Azuz said. “It’s meant to be an additional dosing tool, but it should not replace the pharmacists’ clinical judgment, and it is not mandatory for them to use.” The investigators presented the results to the hospital’s antimicrobial stewardship subcommittee and are working on publishing them. The results will be presented to the pharmacy and therapeutics committee and incorporated into the hospital’s protocol, Azuz said.

‘Wait and See’ Not Ideal? The study offers an interesting method to consider when dosing vancomycin in critically ill patients on CRRT, commented Ruben Villanueva, PharmD, a critical care pharmacist at the UNM (University of New Mexico) Hospital, in Albuquerque. “It gives another way to approach it, and suggests that maybe we could be a little more aggressive with scheduling our doses, as opposed to giving a dose and waiting to see what the level is,” he said. Dosing antibiotics in critically ill patients is challenging because their physiology frequently changes, Villanueva said. ICU patients receive large amounts of fluids and vasopressors

Target trough levels achieved, %

Dosing Tool Helps Patients Hit Vancomycin Target 100 80 60 40 20

89%a

37%

Dosing via schedule (with table)

Dosing by levels (without table)

Figure. Vancomycin dosing at Harper-Hutzel Hospital. a

Within 1 SD of the target range. Source: Merna Azuz, PharmD.

that alter their physiology, he explained, and volumes of distribution differ in healthy or noncritically ill patients. Therefore, it may require more drug to “fill the tank,” he said; then, younger patients may have higher renal clearance and may require additional doses more frequently, while older patients with comorbidities may have less renal clearance and require a dosing interval that is more spread out. Although vancomycin has been around for decades, clinicians continue to find the best dosing strategy, he said, adding, “I always appreciate novel methods.” —Karen Blum The sources reported no relevant financial disclosures.

Vancomycin Loading Dose May Not Affect MRSA Outcomes

n a retrospective chart review of 359 patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, of whom 239 received a vancomycin loading dose of at least 20 mg/kg, researchers with ChristianaCare in Newark, Del., found no significant differences in clinical failure whether or not patients received the loading dose. Clinical failure was defined as either day 7 microbiological failure, or a switch to another anti-MRSA antibiotic or inhospital mortality prior to blood culture clearance, according to the research presented at the Society of Critical Care Medicine (SCCM) 2021 Critical Care Congress Virtual Event (abstract 51). Vancomycin guidelines from 2011 recommended a loading dose of 25 to

30 mg/kg in critically ill patients to rapidly achieve serum concentrations of 15 to 20 mcg/mL (Clin Infect Dis 2011;52[3]:e18-e55), according to study co-author Nirali Kalaria, PharmD, a critical care clinical pharmacist at ChristianaCare. However, that recommendation was rated a grade C-III for minimal available evidence. For this reason, Kalaria and her colleagues compared clinical outcomes in their patients with MRSA bacteremia who did and did not receive a vancomycin loading dose, between January 2014 and June 2019. Updated guidelines released in 2020 (after this study was in progress) recommended a loading dose of 20 to 35 mg/kg (Am J Health Syst Pharm 2020;77[11]:835-864), graded B-II, Kalaria noted.

The median initial vancomycin dose in the control group was 16.1 mg/kg, compared with 26 mg/kg in the loading dose group. Baseline characteristics were similar in both groups, except that patients without a loading dose had a significantly higher median baseline serum creatinine (1.94 vs. 0.92; P<0.001). More patients with no loading dose also were on hemodialysis (39 vs. 11; P<0.001), and had a higher median Elixhauser Comorbidity Index score (25 vs. 17; P=0.001). The majority of all patients had vancomycin dosed by the pharmacy. Investigators found no significant difference between groups in the primary outcome of clinical failure, which was about 20% in each cohort. By specific

outcome, percentage of day 7 microbiological failure (14.2% vs. 10.9%; P=0.464), switching to another antibiotic (13.3% vs. 11.3%; P=0.698), and in-hospital mortality (4.2% vs 3.4%; P=0.767) were similar with and without the loading dose, respectively. Significant differences between groups also were not seen in the secondary outcomes of day 4 microbiological failure, in-hospital mortality or nephrotoxicity. More studies are needed to determine the safety and efficacy of a vancomycin loading dose in MRSA bacteremia and the optimal weight-based dosing range, Kalaria said. —Karen Blum Kalaria reported no relevant financial disclosures.

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12 Clinical

Pharmacy Practice News • March 2021

Critical Care

Pediatric Sepsis continued from page 1

mortality rates compared with standard therapy (Korean J Intern Med 2005;20[2]:123-128, and others), Moran said. There have been far fewer studies in children, most in the form of case reports, he said. This includes a recent report of seven young children with vasoplegia (Isr Med Assoc J 2020;22[7]:404-408); six had a favorable hemodynamic response, with an

increase in blood pressure and a reduction in vasopressor and inotropic support needed, but three later died. The largest study of methylene blue in children was conducted in 40 patients who developed vasoplegia. Treatment benefits included higher mean arterial pressure and a reduced need for norepinephrine (Egyptian J Anaes 2016;32[3]:269275), Moran said. However, this was

after cardiopulmonary bypass, not septic shock. The treatment causes some adverse effects, including a blue-green discoloring of the skin or urine, he noted (Pediatrics 2015;136[4]:e1030-e1034). Doses exceeding 2 mg/kg have been associated with issues such as hemolytic anemia, and some studies have documented pulmonary vasoconstriction and cardiac arrhythmias, among other adverse responses (J Anaesthesiol Clin Pharmacol v.26[4];2010PMC3087269). Moreover, because of the ability of methylene blue to absorb light at

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Vitamin C (ascorbic acid) has been tried for sepsis, most recently as part of combination therapy with hydrocortisone and thiamine (also known as HAT therapy).

wavelengths close to those emitted by some oximetry devices, Moran noted, some case reports have highlighted a decrease in oximetry readings. “Overall, evidence for methylene blue in vasoplegia is not strong, and evidence for using it in sepsis is even less so,” he said, adding that the alternative treatment still should be considered as a salvage therapy for vasoplegia that is unresponsive to conventional therapy. As for dosing, methylene blue is most often administered as a 1-mg/kg bolus followed by an infusion or repeat bolus.

The Case for Vitamin C

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Vitamin C (ascorbic acid) also has been tried for sepsis, most recently in combination with hydrocortisone and thiamine—a triple combination known as HAT therapy, noted panelist L. Nelson Sanchez-Pinto, MD, MBI, an assistant professor of pediatrics at Northwestern University, in Chicago. Vitamin C has some pleiotropic effects relevant to sepsis pathobiology, he said, including reducing the damaging effects of reactive oxygen species, such as peroxynitrite, that occur during sepsis. Vitamin C also has been shown to enhance production of catecholamines. Vitamin C, when depleted during sepsis, can be restored through IV administration, he said. In multiple small single-center trials and observational studies, vitamin C appears to be associated with improved outcomes, Sanchez-Pinto said. One study of 47 severely septic adult patients who were treated with HAT therapy found a significant reduction in mortality compared with historical controls (Chest 2017;151[6]:1229-1238). There also has been some evidence for the benefits of vitamin C and HAT therapy in children, he said. A study out of his center (Am J Respir Crit Care Med 2020;201[7]:863-867) demonstrated that the regimen yielded improvements in 30- and 90-day mortality, particularly from preventing early deaths within the first three to four days following admission. Four (9%) of 43 patients treated with HAT therapy died within 30 days compared with 12 (28%) of 333 treated with standard therapies; six (14%) patients treated with HAT therapy died within 90 days compared

Clinical

Pharmacy Practice News • March 2021

with 15 (35%) treated with standard therapies. The average patient had a moderate level of acute respiratory distress syndrome (ARDS). However, two other multicenter trials did not show an association between HAT therapy and outcomes (JAMA 2020;323[5]:423431; JAMA 2020;324[7]:642-650); both studies had a variety of patients with septic shock, not just those with ARDS.

‘Panacea or Snake Oil?’ Questions remain as to whether vitamin C, either alone or administered as part of HAT therapy, is “a panacea or snake oil,” Sanchez-Pinto said. Many vitamin C trials have design flaws, including potentially biased exclusion criteria and time to intervention, he noted. In the studies he discussed, “patients who were very sick and considered to be at imminent death were excluded. Would some of these have benefited from treatment?” The heterogeneity of treatment response suggests there may be a subset of patients who benefit from vitamin C therapy, Sanchez-Pinto said, “so the treatment lands somewhere between a panacea and snake oil,” he said. Phenotyping of sepsis patients may help identify a subset of patients who will benefit more from this treatment, he added. Also, some HAT studies have suggested the earlier the treatment, the better, but two studies delayed therapy by as much as 30 hours. That delay could be problematic, given the pharmacokinetics involved, Sanchez-Pinto noted. “One of the hypothesized mechanisms by which vitamin C works is by counteracting the oxidative burst during the early phase of the inflammatory response in sepsis,” he said. “Thus, the sooner you give it, the more limited the secondary damage from the reactive oxygen species that leads to organ dysfunction. Both the CITRIS-ALI trial [JAMA 2019;322[13]:1261-1270] and ours showed that most of the difference in death occurred very early on in admission.”

‘Overall, evidence for the use of methylene blue in vasoplegia is not strong, and evidence for using it in sepsis is even less so.’ —Thomas Moran, BCPS, MS, PharmD consensus on the benefits, Blowey said. A 2019 cohort study of 15 patients given 1 to 5 mg/kg per day of IV thiamine found no difference in lactate changes from thiamine between cases and controls (Pediatr Crit Care Med 2019;20[9]:e452-e456). Moreover, thiamine did not improve secondary outcomes, including organ

dysfunction severity, pediatric ICU length of stay and hospital mortality. However, Sanchez-Pinto’s 2020 study found IV thiamine at 4 mg/kg per day as part of HAT therapy helped lower mortality. Although the true effect of thiamine administration is unknown, the benefits

Critical Care most likely outweigh the risks in the right patient, Blowey said. “If you’re going to give this or consider it for your patients, protocolize your decision,” she advised. “What cohort will you treat? What regimen will you prescribe? How will you monitor for benefits and risks? And what outcomes will you study to show improvement in patient care?” —Karen Blum The sources reported no relevant financial disclosures.

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The Thinking on Thiamine The jury also is still out on the thiamine component of HAT therapy, said panelist Bridget Blowey, PharmD, BCPPS, a clinical pharmacist with Children’s Hospital of Philadelphia. Current pediatric sepsis guidelines do not recommend its routine use in septic shock; however, thiamine continues to be explored because of its role in many important cellular pathways, she said. Patients in septic shock have relatively high thiamine deficiency; estimates of the deficiency range from 10% to 70% (J Thorac Dis 2020;12[Suppl 1]:S78–S83.doi: 10.21037/jtd.2019.12.82). Thiamine is inexpensive, costing about $5 per 100 mg, and it has a low risk for anaphylaxis from IV administration, yet studies in adults have so far shown no

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14 Clinical

Pharmacy Practice News • March 2021

Geriatrics

Pharmacists are Key Players in Elder Care Transitions P

harmacists can help ensure smooth transitions of care for elderly patients by reviewing medications for appropriateness, maintaining accurate lists and establishing good communication during handoffs, a panel of experts said during the American College of Clinical Pharmacy 2020 virtual annual meeting. The majority of older adults experience multiple chronic health conditions and face an increased risk for greater health care utilization as they age, said Sarah Holmes, PhD, MSW, an assistant

professor at the University of Maryland School of Nursing, in Baltimore. Polypharmacy is a major problem in this population, she said. Nearly half of those aged 65 years and older report taking more than five medications. And studies show that patients discharged from hospitals to skilled nursing facilities, on average, take around 14 medications, she said, citing data from the CDC. “This is alarming, and because older adults are more likely to be taking more medications, they’re also at increased

risk for experiencing drug-related problems and adverse events,” Holmes said. “When patients are moving from one care setting to another, often seeing multiple providers, with different documentation systems, and perhaps using different pharmacies, there are numerous opportunities for errors to occur. And there are concerns around who’s monitoring their medications to prevent these errors.” As many as one in five older adults are readmitted to the hospital within 30 days of discharge, she said, most

commonly for issues such as infections, medication complications or falls. “Most research has focused on the hospital discharge process and immediate postdischarge period, although more work needs to be done to expand our understanding of care transitions to optimize care delivery,” Holmes said. A number of factors contribute to breakdowns in communication or costly errors during transitions of care, she noted. These include unclear or ambiguous roles among providers as

Patients aged

65 years and older discharged from hospital settings to skilled nursing facilities take an average of

14 medications. Source: The CDC.

Delving Into Dementia: When Are Drugs the Culprit? N europsychiatric symptoms—such as depression, psychosis and aggression—are common to all dementias; some 97% of all patients experience at least one, said Lisa Hutchison, PharmD, MPH, BCPS, BCGP, a professor at the University of Arkansas for Medical Sciences College of Pharmacy, in Little Rock. “These can sometimes be more difficult for caregivers than the cognitive symptoms,” she said. Although individual behaviors may vary among the different types of dementia, it’s important to determine the cause, Hutchison said. Acute-onset behaviors could result from an exacerbation of a medical problem or adverse drug event, while persistent behaviors are more likely due to progression of underlying disease. In either case, she said, nonpharmacologic treatment is always the first-line approach. It’s also important to look for and remove any offending medications such as benzodiazepines, which have been linked to impaired cognition (Arch Clin Neuropsychol 2018;33[7]:901-911); evaluate patients for acute or chronic pain; simplify bathing and dressing for patients; and ensure caregivers have good education and support. Hutchison offered the following advice for symptom management: Apathy: Tailor daily activities to patients’ previous interests, and try to keep them involved every day of the week. Overall, medications may not help much. Cholinesterase inhibitors and memantine have had some early positive studies but haven’t been replicated. Methylphenidate and modafinil also had some positive study results, but in small numbers of patients and with high dropout rates due to side effects (Can J Neurol Sci 2017;44[3]:267-275).

Low-dose antipsychotics have mixed results. Depression/mood disorders: Measures such as recreational programs, good lighting and pet therapy may be beneficial (J Am Med Dir Assoc 2012;13[6]:503506.e2). Cognitive-behavioral therapy is less helpful because patients ts lose cognition. Electroconvul Electroconvulsive therapy should ould be avoided because its side effect is amnesia mnesia (N Engl J Med 2007;357[22]:2269-2276). 2269-2276). If symptoms last for at least two weeks, considerr treatment with agents such ch as citalopram, escitalopram, opram, sertraline or mirtazartazapine. Choose agents gents based on sympptoms and drug side effects. Manic-like behavehavior: Investigate precipitating factors. ors. Then, try a mood od stabilizer such as valproic acid, carbamazepine, zepine, lamotrigine or lithium. All pharmacologic ogic choices have many side e effects; consider the risk sk versus the benefit. Psychosis (delusions/hallucielusions/hallucinations): Assess ss how much the patient is disturbed rbed by these symptoms; it may affect caregivers more. re. Rule out

physical or environmental triggers, such as pain or sundowning/confusion that starts in the late afternoon, and then initiate meaningful activities. If there is no improvement after four weeks, consider second-generation antipsychotics, but use low doses, titrate slowly and monitor appr appropriately. After one to three months, consider reducin reducing the dose and discontinuing as the disease may have progressed and the symptoms c changed. Aggression: Mu Music therapy, physical exercise and simplifying routines Am Med Dir Assoc may help (J A 2012;13[6]:5 2012;13[6]:503-506.e2). Pharmacologic opt options include medications for d depression or pain if they are c contributing factors, and cholin cholinesterase inhibitors, memantin memantine and antipsychotics. Sleep d disturbances: Optimize sleep hyg hygiene by establishing routines routines, increasing daytime activ activity, controlling pain and reducing fluids in the ev evening. Preferred medica ications, according to the 2 2019 American Geriatrics Society Beers Criteria, inc include melatonin and ramelt ramelteon, as well as antidepressan pressants such as low-dose doxepin, trazodone, mirtazapine and g gabapentin. Monitor for side e effects including low blood press pressure and risk for falls.

Clinical

Pharmacy Practice News • March 2021

Geriatrics well as patient functional and cognitive impairment. There also can be many medication-related problems during transitions of care, added Nicole Brandt, PharmD, BCGP, BCPP, a professor and the executive director of the Peter Lamy Center on Drug Therapy and Aging at the University of Maryland School of Pharmacy, in Baltimore. There may be many medication changes for older adults during hospital stays, and studies have shown that even within a hospital system, one unit may not always send the right medication list to another unit, Brandt said, let alone provide accurate lists to the

patient and/or their outside provider at discharge. “Too often than not, these changes can lead to rippling effects in terms of medications being continued that shouldn’t be, or medications being abruptly stopped that shouldn’t be,” she said. “If we’re handing off these medications to family members, often they may feel they don’t have all the complete information. … We need to be very mindful, not just of medication reconciliation but the bigger process of medication optimization, during these care transitions so we don’t impact

mortality negatively, we don’t impact function, and we don’t increase the risk of coming back in the hospital.” Pharmacists can play critical roles educating patients and caregivers, and peers, and advocating to improve access to care during transitions, Brandt said. Pharmacist interventions in these settings have been shown to result in a 42% decrease in 30-day readmission rates (Ann Pharmacother 2017;51[10]:866889), a 56% reduction in medication errors (J Patient Saf 2017 Jun 30. doi:10.1097/PTS.000000000000283),

and cost savings that should justify pharmacists as part of teams providing and optimizing care for older adults, she said. For example, a 2018 study found a pharmacist-based transitions of care program yielded an estimated $1.8 million for a managed care plan (Am J Health Syst Pharm 2018;75[1]:613-621). —Karen Blum Holmes reported no relevant financial disclosures. Brandt is a consultant to the Institute for Healthcare Improvement.

Free Opioid REMS CE/CME

Managing Opioid Risk on the Front Lines Wandering: Give patients a safe place to walk, or distract them with seated activities. There is no available drug therapy. Disinhibition: Check for evidence of urinary tract infection or other conditions, then establish toileting and dressing schedules so patients don’t disrobe at other times. Medications such as selective serotonin reuptake inhibitors or progesterone may be helpful but have mainly been shown in case reports (Int Psychogeriatr 2011;23[7]:1182-1188). Two newer drugs to consider for problematic behaviors include dextromethorphan-quinidine (Nuedexta, Avanir) for pseudobulbar affect (uncontrollable laughing or crying) and pimavanserin (Nuplazid, Acadia) for hallucinations and delusions associated with Parkinson’s disease psychosis, although these also should be used with caution, Hutchison said. Dextromethorphan-quinidine appears on the 2019 Beers list as a drug to use with caution because it has limited efficacy in behavioral symptoms of dementia and may increase the risk for falls; it also may interact with other drugs. Pimavanserin carries a boxed warning for increased mortality in elderly patients with dementia-related psychosis.

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FrontlinesCME.com This program is supported by an independent educational grant from the Opioid Analgesic REMS Program Companies. See https://ce.opioidanalgesicrems.com/RpcCEUI/rems/pdf/resources/List_of_RPC_ Companies.pdf for listing of REMS Program Companies. This activity is intended to be fully compliant with the Opioid Analgesic REMS education requirements issued by the US Food and Drug Administration.

—K.B. Hutchison reported no relevant financial disclosures.

Jointly provided by AKH Inc., Advancing Knowledge in Healthcare and Warrior Centric Healthcare Foundation

Distributed by CMEZone.com

16 Clinical

Pharmacy Practice News • March 2021

Critical Care

COVID-19 Burnout continued from page 1

findings of an abstract (No. 41) presented at the Society of Critical Care Medicine (SCCM) 2021 Critical Care Congress Virtual Event. The number of “desirable” activities performed, such as reading literature and documenting interventions, actually correlated with an increased risk for burnout (odds ratio [OR], 1.40; 95% CI, 1.12-1.76). The number of “optimal” activities performed, in contrast, such as creating new services or publishing research, correlated with a decreased risk for burnout (OR, 0.76; 95% CI, 0.60-0.96). Pharmacists who reported burnout performed more activities than those who did not experience burnout, said study co-author Susan Smith, PharmD, BCPS, BCCCP, a clinical assistant professor at the University of Georgia College of Pharmacy, in Athens. Unsurprisingly, Smith said, pharmacists experiencing burnout were more likely to hold additional roles, such as a manager or residency program director, and were more likely to perform added activities such as precepting, research or committee work.

All of the 221 survey urvvey respondents were from academic medical centers and community teaching and nonteaching hospitals. The majority had two or more years of postgraduate training. They performed a median of 11 desirable activities and six optimal activities. An increased census of ICU patients, the number of additional roles performed, and the number of desirable activities performed were determined to be factors independently associated with increased risk for burnout, the authors found. Study limitations include a potential for selection bias and the distribution of the survey in May 2020 during the heart of the COVID-19 pandemic. “It’s possible that the higher-level optimal activities, such as developing a new service or teaching ACLS [advanced cardiac life support], are more satisfying to a critical care pharmacist than the day-to-day desirable activities, such as documenting interventions or reading updated literature,” Smith said. “Future research should delve into activities that are risk factors for burnout among critical

care pharmacists, and [identify] strategies to enhance workplace engagement and minimize burnout.” Smith offered the following tips for managing or avoiding burnout: • Learn to say yes to opportunities and requests that are fulfilling, and say no to ones that may exacerbate burnout. • Choose your friends wisely. You may not have much control over who you work with, but becoming friendly with colleagues can mitigate burnout. • Find a niche that brings you joy and fulfillment, whether mentoring, doing research, teaching, etc. and try to carve out time for it each week. • Celebrate your successes and those of your colleagues.

Doubled Caseload Joanna Stollings, PharmD, FCCP, a clinical pharmacy specialist with the medical intensive care unit (MICU) at Vanderbilt University Medical Center, in Nashville, Tenn., also has seen a large increase in burnout. Stollings cited steadily increasing caseload as a key factor. While she normally covers patients in the 35-bed MICU, the hospital recently was asked to add another 37-bed ICU just for COVID-19 patients, taking her caseload to 72 during surges. “That’s been a lot,” she told Pharmacy Practice News. Part of what keeps her going, she said, is participating in an outpatient clinic twice a month for patients who have been discharged from the ICU. “That’s helped me tremendously, because we all tend to focus on the patients that don’t do so well, but seeing patients that do well is really good for morale,” she said. Stollings also relies on long-distance running, where she takes one step at a time and tries to stay positive. There also are signs of relief in sight. “This past week we went down to 55 patients. It sounds insignificant but that’s a huge morale booster. It’s like, ‘All right, we’re making progress!’” Steven J. Martin, PharmD, BCPS, FCCM, the dean and a professor at the Rudolph H. Raabe College of Pharmacy, Ohio Northern University (ONU), in Ada, said a lot of the stress contributing to burnout comes from pharmacy’s

struggles with a ragged supply chain that already was showing cracks even before the pandemic. “If a manufacturer goes down, or if a facility is disabled, or if a raw ingredient is in short supply—lots of things have played into shortages,” he said. “When there is a shortage of a medication, we work with the patient and the prescriber to identify alternative agents that will be successful.” Hoarding during COVID-19 exacerbated the shortages, and pharmacists have had to spend time searching for new vendors, Martin noted. When the federal government bought up all the rapid COVID-19 antigen tests manufactured in the United States, “we negotiated with a broker who charged us three times the cost of the test.” Testing for COVID-19 has fallen to ONU Healthwise Pharmacy, a community pharmacy owned by ONU, Martin noted. “We had to use our clinicians to obtain the specimens, do the swabs and test them. We have to report the results to the state and report any positive tests to the health department, notify the patient, and help them understand what to do if they test positive. Right now, we’re doing upward of 1,000 tests per week.” Thirteen pharmacy interns do most of that work, supervised by four pharmacists, he said. “Every night, I go home to monitor COVID-19 testing results.” Another stressor has been getting patients access to COVID-19 vaccines. “We’re ramping up,” Martin said, with the initial focus on “signing up the elderly, helping them make appointments and figuring out how to preregister and schedule.” The rocky rollout of the vaccines has created even more stress, Martin said. “Week to week, we don’t know how many vaccines we’re going to get, or which product. We have a –80o C freezer so we can store either of the two vaccines [Pfizer/BioNTech or Moderna], but so far, we haven’t gotten enough vaccines in the county to require storage.” —Karen Blum, David C. Holzman The sources reported no relevant financial disclosures.

Technology

Pharmacy Practice News • March 2021

Mobile Health

Technology improves arrhythmia detection, glycemic control

Remote Monitoring for Diabetes, Heart Disease T

wo studies presented at the American College of Clinical Pharmacy 2020 virtual annual meeting point to the power of mobile technology in helping patients with medication-induced heart problems and with diabetes. The first project demonstrated that community pharmacists can make use of mobile ECG monitors to detect heart conduction abnormalities in their patients and alert prescribing physicians. In a pilot study of 53 patients enrolled at three community pharmacies in Iowa, pharmacists used 30-second ECG measures recorded on a mobile device to study patients’ QTc intervals. All patients were taking medications known to be associated with prolonging the QTc interval, which can cause arrhythmia and result in fainting, seizures or sudden death. Based on QTc interval length calculated from the recordings, pharmacists contacted prescribers about potential drug-induced long QT syndrome in six patients (11% of the study sample). In three cases, prescribers made a medication change. The technology could help “fill a big void” for pharmacists, said lead study author James Hoehns, PharmD, a clinical associate professor at the University of Iowa College of Pharmacy, in Iowa City, and the research director at the Northeast Iowa Medical Education Foundation, in Waterloo. “Pharmacists have been working with these prescriptions, and making judgments about when to try and intervene and get somebody off of a medication, without actually knowing what their QTc interval is at that moment in time, which is really one of the elephants in the room,” Hoehns said. “Now, with this easy technology, we’ve got the ability for a pharmacist in 30 seconds to determine somebody’s QTc interval at the time they are processing this prescription. It’s put a totally new tool in the pocket of the pharmacist to help them with their professional judgment.” More than 100 FDA-approved medications have a known ability to cause druginduced long QT syndrome, he said, including commonly used drugs such as azithromycin, fluconazole, ciprofloxacin and escitalopram. The study was conducted from July 2019 through March 2020. Patients’ mean age was 55.1 years, 38 (72%) were female, and 19 (36%) received newly prescribed medications that could prolong the QTc interval. The ECG measures were recorded on a personal ECG monitor made by KardiaMobile, for which patients place their fingers on a small device that uploads readings to a smartphone.

‘Pharmacists have been working with these prescriptions, and making judgments about when to try and intervene and get somebody off of a medication, without actually knowing what their QTc interval is at that moment in time, which is really one of the elephants in the room.’ —James Hoehns, PharmD The KardiaMobile personal ECG monitor yields readings that can be uploaded to a smartphone and accessed by a caregiver for signs of arrhythmia.

effectiveness of this tool against sites that don’t have it, Hoehns said.

Diabetes Monitoring Researchers found no statistically significant differences between the community pharmacists’ calculations of QTc intervals and those done by family medicine physicians and cardiologists, using five sample recordings. In addition, Hoehns said, study participants responded well to the intervention. In a survey of 19 subjects, all said they agreed or strongly agreed that they were comfortable with the pharmacist obtaining their ECG recordings; that the pharmacist explained the test in a manner that was easy for them to understand; and that after talking with the pharmacist about the test, they felt safer taking a medication that could affect their heart. The next step would be to conduct a randomized clinical trial to better measure the

In the other study, researchers with Teladoc Health Inc. found that Livongo’s remote diabetes monitoring program (RDMP) with cellular-enabled glucose meters, test strips and coach interactions can improve both medication adherence and glycemic control. Investigators noted that during two years of participation, medication adherence (measured as proportion of days covered) increased from 77% to 80% among 870 patients with diabetes enrolled in the program, but decreased from 78% to 69% among 479 matched controls not enrolled. Among RDMP members, each 10-day increase in days covered resulted in a 1-mg/dL decrease in blood glucose per month. “We were pretty astonished to see this real difference at two years of medication adherence,” said Bimal Shah, MD, MBA, the chief medical officer of product and analytics at the company and a

The Livongo remote diabetes monitoring program employs cellular-enabled glucose meters, test strips and coach interactions to help patients with glycemic control.

cardiologist with Duke University School of Medicine, in Durham, N.C. Previous studies showed that people with diabetes who are adherent to medications not only improve clinical outcomes but also save on health care costs over time because they are less likely to have major events such as heart attack, stroke or kidney disease, he said. Patients enrolled in the RDMP program, usually offered through employer, national and regional health plans, are given a two-way cellular glucometer and unlimited testing strips, Shah said. Once a person takes a blood glucose reading, the information is sent to the program’s cloud-based analytics engine and is processed by a computerized algorithm that takes into account the person’s historical readings, medication list and other characteristics. Digital messages are then returned to the patient with tips to help them better manage blood glucose levels. In addition, participants can set up oneon-one coaching appointments at any time with certified diabetes educators, through their glucometer, a web portal or a mobile app, Shah said. If any member registers an unusually high or low glucose reading for their history, one of the company’s diabetes response specialists will call within 90 seconds to walk through American Diabetes Associationrecommended steps to get their blood glucose quickly back to a safe range. The program’s digital and human coaching features use member information to send reminders to take prescribed medications. “We know that only about a third of people with diabetes are adherent to their medications on an ongoing basis,” Shah said. “This is a huge opportunity to promote better glucose control and better diabetes management.” —Karen Blum The University of Iowa College of Pharmacy study was sponsored by the Iowa Pharmacy Association Foundation. Hoehns reported no relevant financial disclosures. Shah reported no relevant financial disclosures other than his stated employment.

18 Policy

Pharmacy Practice News • March 2021

Hazardous Waste Handling

Operationalizing NIOSH, USP <800>, and EPA Requirements CHARLOTTE A. SMITH, RPH

KATHLEEN SKIBINSKI, RPH

MONICA LIVINGSTON

Senior Regulatory Advisor

Manager of Regulatory and Compliance

Senior Implementation Manager

PharmEcology Services, Waste Management National Services, Houston, Texas

he tension between theory and practice has never been greater than in the need to understand and subsequently operationalize the requirements of hazardous drug (HD) and hazardous waste handling.

The purpose of this article is to discuss how these 2 concepts interface in a manner that enables health care managers and front-line professionals to understand and implement these important standards and regulations.

Who’s in Charge Here? For a new practitioner, and perhaps even for some who’ve been at this awhile, it can be very confusing to determine where all these standards and regulations originate. We hope Figure 1 can clarify this for you. Starting from left to right, the hazardous waste regulations were promulgated by the Environmental Protection Agency (EPA) under the Resource Conservation and Recovery Act, passed in 1976 and implemented in 1980. By far the biggest change that affects health care

Occupational Safety and Health Act 1970

RCRA

is Subpart P Hazardous Waste Pharmaceuticals, a new EPA rule that took effect in several states on or about August 19, 2019, and is making its way around the country as each state adopts it. Without getting into too many details here, suffice it to say it’s only the second time in history the EPA has carved out an industry-specific hazardous waste regulation—and one that provides a good deal of relief for health care facilities. You can learn more about the new Subpart P regulations in our last article for Pharmacy Practice News (bit.ly/3oPCwgD). But one thing the regulations did not change is the definition of a hazardous waste, which we’ll briefly review. The second big player is the National Institute for Occupational Safety and Health (NIOSH), which also resides under the federal government

• USP Convention membership • Board of trustees • Council of experts

Public standards and related programs that help ensure the quality, safety, and benefit of medicines and foods

umbrella and whose mission is “to develop new knowledge in the field of occupational safety and health and to transfer that knowledge into practice” (bit.ly/3tvxQA6). It is NIOSH who brings us the periodic updates of HDs and, with the “NIOSH List of Hazardous Drugs in Healthcare Settings, 2020” draft guidance (bit.ly/3cIxno2), has built on previous guidance documents to bring us even more robust recommendations as to the handling of HDs. Finally, we come to USP, which publishes standards around pharmacy practice involving sterile and non-sterile compounding, many of which are covered in its document, USP General Chapter <800> “Hazardous Drugs—Handling in Healthcare Settings” (bit.ly/2YMjzk8). According to USP, the document lays out “standards for safe handling of hazardous drugs to minimize the risk of exposure to healthcare personnel, patients and the environment.”

Understanding NIOSH 2020, USP <800>, And the EPA’s Subpart P Regulations The draft NIOSH 2020 HD list and related documents include components that are very valuable, namely the procedures for developing the list and a greatly expanded discussion of the 4 elements of risk management: hazard identification, exposure assessment, risk assessment, and risk management. USP <800> provides additional requirements and recommendations for all phases of HD handling and management. The EPA’s Subpart P regulations (bit.ly/3cHC69q) provide substantial regulatory relief for the management of hazardous waste pharmaceuticals. So how can your organization best translate these concepts into a workable plan?

Hazard Versus Risk Regulated by DNV Healthcare, TJC, and state boards of pharmacy Federal and state regulations

Figure 1. Relationship among the EPA, RCRA, OSHA, NIOSH, and USP. EPA, Environmental Protection Agency; NIOSH, National Institute for Occupational Safety and Health; OSHA, Occupational Safety and Health Administration; RCRA, Resource Conservation and Recovery Act; TJC, the Joint Commission

Jerald Ovesen, PhD, a pharmacologist with NIOSH, presented a very succinct differentiation between hazard and risk during the ASHP 2020 Midyear Clinical Meeting and Exposition (bit.ly/36JpkU3); he noted that “a hazard is something that has the potential to cause an adverse effect,” and “a risk is the likelihood of a hazard causing harm.” He illustrated these concepts by referring to a shark as a hazard and swimming with sharks as increasing the risk for being attacked. He then noted that drugs listed by NIOSH are the hazards. It is up to the facility

Policy 19

Pharmacy Practice News • March 2021

Hazardous Waste Handling

to evaluate the risks based on the various steps in handling as they apply to the employees involved. The draft NIOSH 2020 list therefore provides organizations with the starting point of the hazard.

Figure 2. NIOSH’s processes for assessing risk of hazardous materials. NIOSH, National Institute for Occupational Safety and Health

Performing an Assessment of Risk In addition to providing the list of HDs, the 2020 NIOSH documents also provide an excellent breakdown of the assessment of risk process, providing pharmacists and their health care colleagues with a road map to accomplish the actual assessment, which then leads to the details of employee protection required in USP <800>. The graphic included in the draft document, “Managing Hazardous Drug Exposures: Information for Healthcare Settings,” which was published in conjunction with the NIOSH 2020 draft list, demystifies this process (Figure 2). Let’s break this down into actionable items. Starting with the hazard side, you will need to create your HD list at the National Drug Code (NDC) level. Be sure to include those drugs that were released after 2015 and are potentially hazardous, because the draft NIOSH 2020 list does not evaluate drugs approved in 2016 and beyond. The NDC level is necessary because the dosage form and packaging are important components of developing your risk assessment. For example, a unit-dosed tablet poses less of a risk to pharmacy staff than counting tablets from a bottle of 100. Your next step is to identify the employees who might be exposed, which typically includes pharmacists, pharmacy technicians, nurses, respiratory therapists, operating room staff, and environmental services personnel. Your organization may have other specialties that need consideration. Moving to the right of Figure 2, you’ll be identifying how exposures occur, which starts at the phase of receiving and moves through storage, preparation, transport, administration, and disposal. This is where you’ll want to combine the NIOSH Table of Control Approaches (bit.ly/3pP72sb) with requirements that are specific to USP <800>. Although not all scenarios are covered, the NIOSH Table of Control Approaches and related guidance provides a good starting point. You must then integrate this evaluation of risk with the specific personal protective equipment

NIOSH hazardous drugs (hazardous to the employee) Genotoxicity Teratogenicity Reproductive toxicity Carcinogenicity Organ toxicity at low doses Similar structures or toxicity profiles

Hazardous drugs that are also hazardous waste Arsenic trioxide Warfarin Cyclophosphamide Mitomycin Melphalan

EPA hazardous waste (hazardous to the environment) P-listed: acutely hazardous U-listed: toxic D-codes: exhibit characteristics of hazardous waste Flammable Toxic Corrosive Reactive

Figure 3. Hazardous drugs versus hazardous waste. EPA, Environmental Protection Agency; NIOSH, National Institute for Occupational Safety and Health

requirements of USP <800>. For example, when compounding sterile and non-sterile HDs in the preparation phase, 2 pairs of ASTM International standard D6978 chemotherapy gloves must be used, remembering that the outer glove must be sterile for sterile compounding. Although gowns, head, hair, and shoe covers are required, the current publication of USP <800> does not specify ASTM standards. Again, both the NIOSH draft document and USP <800> should be used as minimum reference standards. For example, USP <800> requires 2 pairs of ASTM standard D6978 chemotherapy gloves when administering antineoplastic drugs and gowns for injectable NIOSH

table antineoplastics. Very specific requirements are also given for spill cleanup and deactivation and decontamination of the various containment primary engineering controls and other containment devices. From a USP <800> perspective, the minimal elements of your assessment of risk should pair the type of HD, the dosage form, the exposure risk, the packaging, and manipulation with the phases of handling: receipt/storage, preparation, transportation, administration, spill cleanup, and waste disposal. As pharmacists with the most knowledge of drug formulations, your responsibilities also see OPERATIONALIZING, page 20

20 Policy

Pharmacy Practice News • March 2021

Hazardous Waste Handling

OPERATIONALIZING continued from page 19

should extend to assisting nursing with their assessment of risk.

Hazardous Waste Pharmaceuticals And that brings us back to our differentiation between HDs and hazardous waste. Although there are a few drugs that meet both criteria (Figure 3, page 19), the majority are either one or the other.

Let’s review briefly the EPA’s definitions of a hazardous waste that apply to waste pharmaceuticals. The 2 categories we need to consider are P- and U-listed substances. According to the EPA, the P-list identifies acute hazardous wastes from discarded commercial chemical products. The P-listed wastes can be found at Title 40 electronic Code of Federal Regulations (e-CFR) section 261.33 (bit.ly/2YRl5RX). The U-list identifies hazardous wastes from discarded commercial chemical

products. The U-listed wastes can be found at 40 e-CFR section 261.33 (bit.ly/2YRl5RX). If a drug on either of these lists is the sole active ingredient, and unused, it will be a hazardous waste when discarded. The most common P-listed drugs are arsenic trioxide, nicotine, physostigmine salicylate, and warfarin (>0.3%). In addition to the P- and U-lists, we must also consider those formulations that meet the definition of a characteristic hazardous waste: toxicity, ignitability, or corrosivity. For

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example, the m-cresol preservative in insulin and the thimerosal in multidose flu vaccine exceed the concentrations for these 2 D-coded chemicals.

Subpart P Those states that are now operating under Subpart P have excluded over-the-counter nicotine gums, lozenges, and patches, which is one of the major changes in the new EPA rule. Another major change is in the definition of empty for P-listed drugs. Prior to Subpart P, the packaging needed to be disposed as a hazardous waste to capture the residue of the P-listed waste. Containers for most dosage forms— empty warfarin bottles and blister packs, for example—can be disposed as trash under Subpart P. Note that this only applies in those states that have already adopted the regulation. For U-listed drugs, which include several chemotherapy agents, such as cyclophosphamide, daunomycin, and mitomycin C, not as much has changed other than none of these hazardous waste pharmaceuticals will count toward generator status once a state has adopted the new rule. Many states are required to adopt the new rule by July 1, 2021, while some have until July 1, 2022, if they must seek legislative action. A map illustrating some of the states that have already adopted the new rule can be accessed on the EPA’s website (bit.ly/3pAkKhD), but know that this is a moving target and the EPA’s website is not always up to date. So, what is the operational takeaway? When you are messaging for pharmacy personnel and especially for nurses, it is vitally important to ensure that you are clearly differentiating whether the drug is an HD, potentially a risk to the employee, or a hazardous waste and thus potentially a risk to the environment—or possibly both, such as warfarin. It’s important to provide clear and concise messaging in your software systems to help nursing differentiate between an HD and a hazardous waste. To conclude, the confusion between HDs and hazardous waste is pervasive in health care, must be clearly delineated for staff, and supported with educational tools and messaging. Although conducting your assessment of risk must remain a top priority in 2021, also check the status of the EPA’s Subpart P list in your state. The good news is that as USP <800> once again gains traction in the coming months, hopefully your hazardous waste liability will decrease, a rare event in today’s health care ■ environment!

Policy

Pharmacy Practice News • March 2021

Reimbursement

Start with the fundamentals!

Building Blocks for Payment S

everal reimbursement questions and issues posed to me in the past few weeks have a common thread: The pharmacy has been tasked with solving a dilemma, creating a new or improved revenue strategy, or predicting the financial implications of a rule change, only to be stymied as the employees try to move forward. This could be at the very start of the process, not knowing even where to look or how to begin. It could be after arduous work in creating a new strategy, only to have it rejected by any number of internal or external sources. Here are some important reimbursement building blocks and fundamentals that hopefully can make this process less prone to failure.

Status Indicators Medicare has assigned each HCPCS or CPT code a letter signifying both if and how it will reimburse the product or service. The indicator also helps in determining whether policy rules, such as packaging and discounting, apply. Most common to pharmacy are: G: Additional payment for drug/biological pass-through K: Non–pass-through drugs and biologicals, and blood and blood products N: No additional payment, payment included in line items with APCs for incidental service L: Flu/PPV vaccines CMS publishes an Addendum B listing all products and services that are paid for, the corresponding HCPCS or CPT code, and the SI to let you know how the product or drug is classified for payment purposes. The addendum also lists the payment amount. Updates to Addenda A and B are posted quarterly to the OPPS website and offer a snapshot of HCPCS codes and their SIs, APC groups and OPPS payment rates. The updates take effect at the beginning of each quarter and automatically are sent electronically to your revenue cycle team. Besides automatic delivery, you can easily access the updates on the cms.gov website. To get to the pharmacy products, sort the Excel table on the SI column and keep only the SI G, SI K and SI N line items. The Addendum A and Addendum B updates can be accessed at go.cms.gov/2XA4yl6.

Key Areas Affected By Quarterly Updates Here are two key aspects of reimbursement that you need to keep in mind when reviewing the quarterly updates from CMS: 340B reimbursement. Because SI G drugs are immune to 340B

reimbursement cuts and SI N drugs are not paid for separateely, only SI K drugs are affected by any payment policy changes—and —and only when used for fee-for-service rvice traditional Medicare 340B-eligiblee patients in an OPPS setting. Typically, att any given time, there are about 350 to 375 products in this category. Instead of making gross predictions of gain or loss based on all purchases, limit your scope only to the SI K drugs that you actually use. Billing for waste. SI G drugs lose their three-year pass-though status quarterly and can move to SI K or SI N. A move to SI N renders them ineligible for waste billing because the drug is no longer paid for separately, which leads to a waste billing revenue loss. Since this quarterly change is announced in MLN Matters and sent to your revenue cycle team electronically, continuing to bill for waste will result in a rejection of the claim.

Watch Those Injectable Drug Administration Fees Injectable drug administration fees are payable for all injectable drugs, even those that are priced at zero dollars. CMS uses specific definitions and requirements to determine payment of these administration fees. Knowing how to apply these rules affecting zero-priced drugs is a critical skill for your revenue cycle team—particularly when negotiating billing and handling fees for these prolific specialty drugs with payors. These negotiating skills also will be critical when navigating key payor restrictions, such as mandatory white bagging or restricted-distribution supply chain requirements. The goal is to bill for both the drug administration fee and a negotiated handling fee that is not duplicative, even though the drug is zero-priced and won’t be reimbursed (but needs to appear on the claim as such). Here’s another key reimbursement rule to consider: Add-on payments for outpatient drug administration are designed to cover some of the costs of products and supplies required for actual drug administration. It is critically important to understand that the definition of drug administration for the purposes of reimbursement is a bundle in itself, involving both nursing and pharmacy, and includes: • use of local anesthesia; • starting the IV; • access to IV, catheter or port; • routine tubing, syringe and supplies; • preparation of drug; • flushing at completion; and • hydration fluid. The facility that will benefit from submitting these charges is the one that has

a well-oiled mechanism for capturing the data related to drug administration, with the requisite charting being done to substantiate the charges. This is a classic example of the benefits of several departments working together as a team and the need for a global budget for drug purchasing, preparation and administration, rather than maintaining a siloed mentality. It’s also a classic example of a bundled payment that will need to be unbundled and allotted to the respective cost centers involved.

Decoding CPT Codes CPT codes are yet another key part of the reimbursement puzzle that your team needs to solve. Here’s a good place to start: Know that the following two groups of CPT codes cover a wide variety of injectable medication episodes for

“Reimbursement Matters” is a tool for maintaining your health system’s fiscal health. Please email the author at bonniekirschenbaum@ gmail.com with suggestions on reimbursement issues that you would like to see covered.

Bonnie Kirschenbaum, MS, FASHP, FCSHP

both complicated and simple common products. Payment rates between OPPS and PFS differ, but CPT codes and their definitions remain the same. 1. CPT codes 96401-96459 (higher reimbursement levels)

These codes often are referred to as “chemo codes,” which is misleading (more on that below). CMS provides some examples of areas of practice covered by the codes: see BUILDING BLOCKS, page 22

A Reimbursement Lexicon APC, ambulatory payment classification; CMS, Centers for Medicare & Medicaid Services; CPT, Common Procedural Terminology; HCPCS, Healthcare Common Procedure Coding System; MAC, Medicare administrative contractor; OPPS, Outpatient Prospective Payment System; PFS, Physician Fee Schedule; SI, status indicator; TKO, to keep (vein) open

22 Policy

Pharmacy Practice News • March 2021

Reimbursement Matters

BUILDING BLOCKS continued from page 21

• Administration requires advanced practice training and competency for staff. • The medication has special considerations for preparation, dosage or disposal. • There is patient risk and frequent monitoring needed. Examples: frequent changes in infusion rate, prolonged presence of the nurse administering the solution for patient monitoring and infusion adjustments, and frequent conferring with the physician about these issues. 2. Therapeutic, Prophylactic, and Diagnostic Injections and Infusions CPT codes 96360-96379 (lower reimbursement levels) (often referred to as non-chemo); IM and Immunization CPT codes 90461-90474

Here are some touchpoints that CMS uses to determine applicability of these codes: • Stop times on infusions: 16 minutes or more equals infusion. If less than 16 minutes or no stop time (or other substantiating documentation), must be reported as an “iv push” at a lower reimbursement rate • IV push of same substance within 30 minutes is not reported again • Hydration • Incidental when used as a delivery vehicle for drugs • TKO rate • Intracellular concentration of potassium chloride up to 30 mEq/L • Not reported if less than 30 minutes • Not reported if “integral to the procedure”; for example, contrast media given by IV push during CT scan— administration services not reported

Regarding the misleading “chemo” categorization mentioned previously, for more insight, see CMS’s guidance on the use of “chemo” versus “non chemo” administration in the Medicare Claims Processing Manual, Chapter 12, Section 30.5 (go.cms. gov/3qAKpYY). Caveat: Local MACs may have further details or preferences. Here are some relevant highlights from the guidance: “Chemotherapy administration codes apply to parenteral administration of nonradionuclide anti-neoplastic drugs; to anti-neoplastic agents for treatment

of noncancer diagnoses (eg: cyclophosphamide for auto-immune conditions) or to monoclonal antibody agents and other biologic response modifiers. Monoclonal antibodies include: infliximab, rituximab, alemtuzumab, gemtuzumab, and trastuzumab. Hormonal antineoplastics include: leuprolide acetate and goserelin acetate. “The drugs cited are not intended to be a complete list of drugs that may be administered using the chemotherapy administration codes. Local carriers may provide additional guidance as to

which drugs may be considered to be chemotherapy drugs under Medicare.”

Key Takeaways For billing drug administration codes, drug administration billed without a corresponding drug will result in a denial of the administration code. For example, for white bagging or brown bagging, bill the HCPCS code for the drug administered with the correct quantity of billing units and a zero charge as well as the negotiated handling fee if applicable. ■

Indication and Usage HYPERRAB® (rabies immune globulin [human]) is indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies. Limitations of Use Persons who have been previously immunized with rabies vaccine and have a confirmed adequate rabies antibody titer should receive only vaccine. For unvaccinated persons, the combination of HYPERRAB and vaccine is recommended for both bite and nonbite exposures regardless of the time interval between exposure and initiation of postexposure prophylaxis. Beyond 7 days (after the first vaccine dose), HYPERRAB is not indicated since an antibody response to vaccine is presumed to have occurred. Important Safety Information For infiltration and intramuscular use only. Severe hypersensitivity reactions may occur with HYPERRAB. Patients with a history of prior systemic allergic reactions to human immunoglobulin preparations are at a greater risk of developing severe hypersensitivity and anaphylactic reactions. Have epinephrine available for treatment of acute allergic symptoms, should they occur. HYPERRAB is made from human blood and may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The most common adverse reactions in >5% of subjects during clinical trials were injection-site pain, headache, injection-site nodule, abdominal pain, diarrhea, flatulence, nasal congestion, and oropharyngeal pain.

Fundamentals of Drug Reimbursement An online tool kit to build your expertise! Reimbursement is changing at lightning speed, and if you’re not accessing the latest resources on these changes, the financial future of your health system is at stake. Fortunately, Pharmacy Practice News’ Fundamentals of Reimbursement tool kit can help you keep pace and become a financial star for your facility. To access, visit www.pharmacy practicenews.com/ToolKit. Ideas for future modules? Send email to Bonniekirschenbaum@gmail.com.

Do not administer repeated doses of HYPERRAB once vaccine treatment has been initiated as this could prevent the full expression of active immunity expected from the rabies vaccine. Other antibodies in the HYPERRAB preparation may interfere with the response to live vaccines such as measles, mumps, polio, or rubella. Defer immunization with live vaccines for 4 months after HYPERRAB administration. Please see brief summary of Prescribing Information on adjacent page or visit HyperRAB.com for full Prescribing Information.

Policy

Pharmacy Practice News • March 2021

FDA Watch tch

FDA Approves Enhertu to Treat Adenocarcinomas

he FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu, Daiichi Sankyo/AstraZeneca) for adults with locally advanced or metastatic HER2positive gastric or gastroesophageal (GEJ) adenocarcinoma who have received a trastuzumab-based regimen. Efficacy was evaluated in a study of 188 patients with HER2-positive cancer who had progressed on at least two prior chemotherapy regimens (ClinicalTrials.

gov Identifier: NCT03329690). In the trial, patients were given 6.4 mg/kg of fam-trastuzumab deruxtecan-nxki every three weeks or physician’s choice of either irinotecan or paclitaxel monotherapy. The main efficacy outcome measures were overall survival (OS) and objective response rate (ORR). OS was 12.5 months (95% CI, 9.614.3 months) in the fam-trastuzumab deruxtecan-nxki arm compared with 8.4

months in the irinotecan or paclitaxel arm (P=0.0097). Confirmed ORR was 40.5% in the fam-trastuzumab deruxtecan-nxki arm compared with 11.3% (95% CI, 4.7%-21.9%) for those receiving irinotecan or paclitaxel. The most common (≥20%) adverse reactions included anemia, leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, nausea, decreased appetite, increased aspartate aminotransferase,

HyperRAB

-----------DOSAGE FORMS AND STRENGTHS---------300 IU/mL solution for injection supplied in 1 mL, 3 mL and 5 mL single-dose vials.

HIGHLIGHTS OF PRESCRIBING INFORMATION

--------------------CONTRAINDICATIONS--------------------None.

Rabies Immune Globulin (Human) These highlights do not include all the information needed to use HYPERRAB® safely and effectively. See full prescribing information for HYPERRAB. HYPERRAB [rabies immune globulin (human)] solution for infiltration and intramuscular injection Initial U.S. Approval: 1974 ----------------INDICATIONS AND USAGE------------------HYPERRAB is a human rabies immune globulin indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies. Limitations of Use Persons previously immunized with rabies vaccine that have a confirmed adequate rabies antibody titer should receive only vaccine. For unvaccinated persons, the combination of HYPERRAB and vaccine is recommended for both bite and nonbite exposures regardless of the time interval between exposure and initiation of postexposure prophylaxis. Beyond 7 days (after the first vaccine dose), HYPERRAB is not indicated since an antibody response to vaccine is presumed to have occurred. --------------DOSAGE AND ADMINISTRATION------------For infiltration and intramuscular use only. Administer HYPERRAB within 7 days after the first dose of rabies vaccine. Postexposure HYPERRAB • Administer as soon prophylaxis, 20 IU/kg as possible after along with body weight exposure, preferably rabies OR at the time of the first vaccine, after 0.0665 mL/kg rabies vaccine dose. suspected body weight • Infiltrate the full exposure to dose of HYPERRAB Single dose rabies thoroughly in the area around and into the wound(s), if anatomically feasible. • Inject the remainder, if any, intramuscularly.

-------------WARNINGS AND PRECAUTIONS-------------• Severe hypersensitivity reactions, including anaphylaxis, may occur with HYPERRAB. Have epinephrine available immediately to treat any acute severe hypersensitivity reactions. • HYPERRAB is made from human blood; it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. --------------------ADVERSE REACTIONS--------------------The most common adverse reactions in >5% of subjects in clinical trials were injection site pain, headache, injection site nodule, abdominal pain, diarrhea, ﬂatulence, nasal congestion, and oropharyngeal pain. To report SUSPECTED ADVERSE REACTIONS, contact Grifols Therapeutics LLC at 1-800-520-2807 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. --------------------DRUG INTERACTIONS------------------• Repeated dosing after administration of rabies vaccine may suppress the immune response to the vaccine. • Defer live vaccine (measles, mumps, rubella) administration for 4 months.

Grifols Therapeutics LLC Research Triangle Park, NC 27709 USA U.S. License No. 1871

3054805 Revised: 11/2019

fatigue, increased blood alkaline phosphatase, increased alanine aminotransferase, diarrhea, hypokalemia, vomiting, constipation, increased blood bilirubin, pyrexia and alopecia. For additional information, access the prescribing information for fam-trastuzumab deruxtecan-nxki at bit.ly/373r2jg. —PPN Staff

Indicated for all persons suspected of exposure to rabies

THE FIRST AND ONLY HIGH-POTENCY HUMAN RABIES IMMUNE GLOBULIN (HRIG)

HyperRAB® (rabies immune globulin [human]) 300 IU/mL Over 45 years of safe and effective use in over 1 million patients.1-5

45+ YEARS OVER 1 MILLION

OF EXPERIENCE

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RELIABLE SUPPLY

REDEFINING HRIG ADMINISTRATION Please see Important Safety Information and brief summary of Prescribing Information for HyperRAB on adjacent pages, or visit www.HyperRAB.com for full Prescribing Information. HyperRAB® (rabies immune globulin [human]) is indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies. HyperRAB is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent that can cause disease. There is also the possibility that unknown infectious agents may be present in such products.

#1 Prescribed HRIG in the US

References: 1. Cabasso VJ, Loofbourow JC, Roby RE, Anuskiewicz W. Rabies immune globulin of human origin: preparation and dosage determination in non-exposed volunteer subjects. Bull World Health Organ. 1971;45(3):303-315. 2. Aoki FY, Rubin ME, Fast MV. Rabies neutralizing antibody in serum of children compared to adults following post-exposure prophylaxis. Biologicals. 1992;20(4):283-287. 3. Kuwert EK, Werner J, Marcus I, Cabasso VJ. Immunization against rabies with rabies immune globulin, human (RIGH) and a human diploid cell strain (HDCS) rabies vaccine. J Biol Stand. 1978;6(3):211-219. 4. Aoki FY, Rubin ME, Friesen AD, Bowman JM, Saunders JR. Intravenous human rabies immunoglobulin for post-exposure prophylaxis: serum rabies neutralizing antibody concentrations and side-effects. J Biol Stand. 1989;17(1):91-104. 5. Data on ﬁle, Grifols.

October 2020

US-HB3-2000068