Pharmacy Practice News - June 2022 by McMahon Group

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Some ISMP Fixes For NMBA Errors

TECHNOLOGY

Pharmacy students hasten HCV prior authorizations ...................

CLINICAL

PGx improves opioid use in pain management .....................

‘Exciting’ new options for refractory B-cell lymphoma ........................

A call for more guidance on hypotension Rx .............

POLICY

Oncology infusions coming home .................

By Gina Shaw

“Make no mistake: This could happen at your hospital,” warned Mike Cohen, RPh, MS, the president emeritus of the Institute for Safe Medication Practices (ISMP), during a joint ISMP/Just Culture Company webinar on lessons learned in the aftermath of the fatal medication error that led to the felony conviction of RaDonda Vaught, the nurse who made the error. On Dec. 26, 2017, Charlene Murphey, 75, was being transferred from Vanderbilt University Medical Center’s neuro-ICU to a step-down unit after treatment for an intracranial hematoma, and was sent for a PET scan. Ms. Murphey had claustrophobia and requested something to alleviate her anxiety. An anxiolytic was ordered, but neither the radiology nurses nor Ms. Murphey’s regular nurse were available to administer

Continued on page 18

Continued on page 6

How to ‘Lean’ Out Drug Waste In the Hospital By David Wild

REVIEW ARTICLE

Using National Guidelines to Determine

Hyperlipidemia Treatment See page 12

By David Wild

onitoring inventory and waste via Lean management strategies saved Houston Methodist Willowbrook Hospital more than $70,000 in 2021. The hospital used the tool to scrutinize medication flow throughout the hospital, yielding interventions that markedly reduced the amount of wasted medications from automated dispensing cabinets (ADCs), medication carousels and IV drug preparation. “In general, our new approach is about being proactive rather than

Continued on page 20

ISMP cites more system tweaks for avoiding fatal NMBA errors ........ 21

Survey: COVID-19 Patients at Risk for Underfeeding in ICU Seattle—Despite the benefits of providing early enteral nutrition (EN) and parenteral nutrition (PN) to critically ill COVID-19 patients, many physicians remain reluctant to implement this practice, placing ICU patients with COVID-19 at risk for undernourishment, according to a survey highlighted at the American Society for Parenteral and Enteral Nutrition (ASPEN) 2022 Nutrition Science and Practice Conference. Beth Taylor, DCN, a research scientist at Barnes-Jewish Hospital in St. Louis, and her colleagues surveyed 199 physicians and dietitians about their COVID-19 ICU nutrition practices and found that only 9% thought they had met their patients’ energy and protein requirements. This feeding shortfall “was not a result of patients not absorbing nutrients; it was due to the fact that they were not being fed” for a number of reasons, Dr. Taylor noted. For example, 75% of respondents said they were not able to meet their patients’ nutritional needs because the course of their illness was unpredictable and uncertain. Even patients who “seemed to be stable” and were given “some nutrition support suddenly underwent an abrupt and profound deterioration, leading to excessive deficits of energy and protein,” she said. “The impulse in these patients is to turn off enteral Beth Taylor, DCN, a research scientist at Barnesfeeds, but instead we Jewish Hospital in St. Louis, placing a small-bowel tube in a non-COVID-19 ICU patient. should be decreasing the rate of feeding, changing the enteral formulation or starting supplemental PN.” Dr. Taylor said much of the reluctance to use PN is linked to concerns that doing so will worsen outcomes (Table). But as a large randomized controlled trial conducted in the pre–COVID-19 era found, there is no difference in the risk for infection or other complications between early EN and early PN in ICU patients with sepsis (Lancet 2018;391[10116]:133-143).

New payment rules for 2022-2023 ................. 17 OPERATIONS & MGMT

Volume 49 • Number 6 • June 2022

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A journey with ISMP’s Mike Cohen. Visit the Multimedia page at www.pharmacypracticenews.com

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Technology

Pharmacy Practice News • June 2022

Pharmacy Workflow

Software program streamlines process amid COVID-19

Student-Led PA Team Speeds HCV Rx Access By Karen Blum

fter yet another surge in COVID-19 cases, there are powerful lessons to be learned about optimizing pharmacy operations amid an ongoing pandemic. A case in point: As COVID-19 forced many nonessential healthcare personnel to adapt to new hybrid or remote work schedules, the hepatitis C virus (HCV) prior authorization (PA) team at the University of Illinois Hospital and Health Sciences System realized it was time for a much-needed workflow redesign. Adding to the complexity of the job, the medical center also was in the middle of converting to a new electronic health record (EHR) system, noted Michelle T. Martin, PharmD, a clinical pharmacist for the health system and an associate professor at the University of Illinois College of Pharmacy, both in Chicago. The PA team, staffed by pharmacy students, also had some new members. The fifth generation of the PA team (started in June 2014 to facilitate treatment access for liver clinic patients with pharmacy benefits that mandate dispensing by external pharmacies) assumed its role in September 2020, the same month as the EHR conversion. Four PA team members spent 468 hours updating team procedures and completing PAs from September 2020 through May 2021. But it was worth it: Of 50 patients referred for PA management, 71% met all insurance-mandated requirements for PA submission and 100% received PA approval for their hepatitis C medications, Dr. Martin and her team reported at the ASHP 2021 Midyear Clinical Meeting and Exhibition, held virtually. Previous generations of the PA team worked on-site at the medical center, taking turns in a cubicle across from Dr. Martin’s office, where they

could easily knock on the door to get help or ask questions. With COVID-19, she said, no one was coming in. The team also was looking to get away from having to send 20-page faxes or sift through paperwork folders. They turned to the CoverMyMeds software program to streamline the PA process and took advantage of new features in their new EHR (Epic). Now, PA team members complete all shifts remotely. They submit electronic PAs through CoverMyMeds and use a protected health information Box folder—a secure cloud management system—to house necessary PA documents. Only the PA team has access to the folder. To adapt to the EHR conversion, the team proactively approached hospital information technology services and requested support for resources for delivery of PA services. The PA team created and incorporated standardized templates into Epic to streamline communication for fellow team members and clinicians. The team used the Box folder to re-prioritize workflow to ensure timely initial delivery of medications and refill management to maintain continuity of care. The team created four additional electronic folders on the shared drive to facilitate workflow and consistency across shifts, as well as transitions between generations of team members. Contents included procedures, electronic PA submission documents, insurance contact information and HCV clinical resources, as well as a follow-up book in a calendar format to log completed tasks and assign other tasks to future dates. The PA team also introduced new Epic workflow by creating a master patient list and 16 smart text templates, including information regarding insurance and dispensing pharmacies, HCV medications and PA status

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Of 50 patients referred for PA management,

71%

O f

met all insurancemandated requirements for PA submission and 100% received PA approval for their hepatitis C medications.

m m f a P h

PA, prior authorization. Source: Michelle T. Martin, PharmD.

updates. Clear documentation and frequent chart updates allow liver clinicians to quickly identify PA progress. Dr. Martin met with the team periodically to discuss progress and launch procedure updates. “It’s wonderful to have students who are motivated to learn and also to assist our patients in this manner,” Dr. Martin said. “The clinical team benefits [from student involvement] because they can focus on clinical work as opposed to paperwork. And the student team benefits because they see the impact of how important this work is on clinical outcomes.” An added win for the clinic: The students are not paid employees but earn course credit for their efforts. Good communication among team members is essential, Dr. Martin said, as are standardized procedures so everyone knows what steps to take and who to call. When using students, it’s helpful to have people from different years in school, so the matriculating students can help teach the newer ones, she added.

Another Nod to the Value of Students Jacob Langness, PharmD, BCPS, a senior clinical pharmacy specialist with Abbott Northwestern Hospital,

in Minneapolis, hired a dedicated pharmacy technician to do PAs in his previous position working with HCV patients at the University of Colorado, and makes use of a centralized PA team at his current hospital. “I can’t stress the importance of how this allows us to do our job,” he said. “If we didn’t have that, it would just slow patient care so much, because a nurse, clinical pharmacist or physician would have to do this, and when you don’t spend every day doing it, the forms take forever.” HCV medications are not too complicated, Dr. Langness said, and a primary care doctor could very appropriately complete HCV treatment for a patient. The biggest barriers in this clinical area are working through insurance and PAs, he said. Having dedicated PA teams led by students, technicians or other allied health professionals is especially critical during this period, he said, where primary care and other clinicians are being stretched thin. Dr. Langness reported no relevant financial disclosures. Dr. Martin reported that she has served on advisory boards and as a speaker for AbbVie and Gilead; received grant funding from Gilead and Merck; and is a minor shareholder for AbbVie, Gilead and Merck.

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4 Clinical

Pharmacy Practice News • June 2022

Pain Medicine

Evidence Grows for Value of Pharmacogenomics By David Wild

harmacogenomics (PGx) can play an important role in pain management because PGx can increase the likelihood of opioid efficacy and potentially limit the risk for misuse, among other advantages. “Genotyping alone is not a silver bullet for the opioid crisis, but it adds a useful bit of information to help build a comprehensive pain management plan that effectively treats a patient’s pain,” said Mark Dunnenberger, PharmD, the director of pharmacogenomics at NorthShore University HealthSystem Neaman Center for Personalized Medicine, in Evanston, Ill. The CYP2D6 gene is the primary metabolic pathway for pain medications, with polymorphisms accounting for some of the individual variation in response to pain medications (Int J Mol Sci 2019;20[17]:4294). Recent guidelines issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC)—the leading body guiding clinical use of PGx—state that CYP2D6 genetic variations are “clinically relevant” for codeine and tramadol therapy, but only “possibly informative” for hydrocodone therapy, and “not informative” for oxycodone or methadone therapy. Both poor metabolizers and ultrarapid metabolizers of codeine and tramadol should receive alternative pain medications to avoid the likelihood of lower effectiveness or adverse events, the CPIC guidelines recommend (Clin Pharmacol Ther 2021;110[4]:888-896). These guidelines and research can serve pharmacists and clinicians well. In one study of chronic pain patients treated with opioids, physicians changed 50% of those opioid prescriptions in some way after finding out their patients’ CYP2D6 phenotype (J Perspect Med 2021;11[11]:1112). Senior investigator Zvi Loewy, PhD, a professor of pharmaceutical and biomedical sciences and pathology, microbiology and immunology at Touro College of Pharmacy and New York Medical College, both in New York City, and his colleagues retrospectively examined medical records from 107 patients with chronic pain treated with one or more opioids at a single pain management center. They performed PGx testing at an outpatient laboratory and delivered results directly to physicians for their interpretation. All patients were receiving opioids and some were also receiving nonopioid pain medications, including muscle relaxants, anesthetics and GABA analogs. Additionally, patients were taking an average of 1.35 nonpain medications

for other indications. According to Dr. Loewy’s team, PGx testing revealed that 20.2% of patients were intermediate metabolizers of one or more of the opioids they were receiving, 21.6% were poor metabolizers, and 1.4% were ultrarapid metabolizers, depending on the opioid. (An individual can have a different metabolic reaction to each opioid.) The remaining 73.2% of patients were normal metabolizers. Those PGx results prompted physicians to discontinue 33.1% of the opioid prescriptions and to make changes to the dose, route of administration or frequency of another 16.7% of the prescriptions. The other half of the opioid prescriptions remained unchanged, while 70 new prescriptions were added. The effects of these changes on pain control were notable, with the percentage of patients with intense pain falling from 10.5% to 5.6% after treatment adjustments. The redistribution of those patients to lower-grade pain categories led to a slight increase in the number of patients with severe pain (rising from 59% to 61.9%) and moderate pain (increase from 23.8% to 25.7%), while 6.7% of patients had mild pain both before and after PGx testing. Although pharmacists did not play a direct clinical role in Dr. Loewy’s team’s study, “as members of the interprofessional healthcare team involved in pharmacotherapy, pharmacists can play a critical role in the integration of pharmacogenomics, and we should be educating our physicians about the value of pharmacogenomics,” he said.

disorders in the setting of acute pain management following surgery,” Dr. Dunnenberger said. Indeed, some research suggests PGx may have a role in tackling the ongoing opioid epidemic. In one study, 260 patients set to undergo hip or knee arthroplasty were randomized to receive postoperative pain management with or without CYP2D6 guidance (Genet Med 2021;23[4]:621-628) and those authors found patients whose pain medication was guided by CYP2D6 genotyping used significantly lower doses of opioids two weeks after surgery than those whose pain management was not guided by CYP2D6 testing (200 vs. 230 morphine milligram equivalents; P=0.047). Of note, despite using fewer opioids, the two

ways in which a pharmacist can make an impact in the process, particularly when it comes to analgesics and pain management. Pharmacists can help translate the genotype information to clinical phenotype, and they can assess for drug interactions that may impact the clinical phenotype determination.” Dr. Thomas added that there can be variability in phenotype interpretations between labs and tests, and without intervention from a pharmacist or another PGx expert, providers can make inappropriate or unnecessary changes that can negatively affect care. “Pharmacists are also uniquely familiar with relative opioid potency and can convert morphine milligram equivalents and provide recommendations for patients who, based on their phe-

The Case for OpioidBased PGx Testing 20.2% of patients were intermediate metabolizers of one or more of their opioids.

21.6% were poor metabolizers. 1.4% were ultrarapid metabolizers. Based on results, physicians discontinued 33.1% of the opioid prescriptions and adjusted the dose, route of administration or frequency of another 16.7%. Source: J Perspect Med 2021;11(11):1112.

Data Gap in Genotypes Dr. Dunnenberger, who was not involved in the research, said it would have been helpful to know the genotype breakdown of the patient population in Dr. Loewy’s study and the specific opioids that patients received, because “for chronic pain, I would expect most patients to be on something potent, like hydrocodone or oxycodone, but CYP2D6 has less of a clinical effect on these opioids than it does for milder agents like tramadol or codeine.” Additionally, it would have been important to know which other medications patients were receiving because some drugs could also inhibit the CYP2D6 pathway and lead to conversion of the phenotypes identified through PGx, he said. Nevertheless, the results fall in line with other recent studies indicating PGx can help optimize pain management. “I’m very excited for the future of PGx, particularly because of the potential to reduce the risk of opioid misuse

groups achieved similar pain control, the researchers found. These findings are significant because an estimated 6% to 6.5% of opioidnaive patients become persistent opioid users after receiving postoperative opioids, Dr. Dunnenberger noted. “Optimizing pain management through genotype-guided approaches may ultimately provide safer and more effective therapy for pain control while decreasing the risk for opioid misuse,” the authors of a review on the topic noted (J Am Coll Clin Pharm 2022;5[2]:239-250). Pharmacogenomics expert Cameron Thomas, PharmD, a postdoctoral fellow in the Department of Pharmacotherapy and Translational Research, University of Florida Health College of Pharmacy, in Gainesville, said although some institutions give results directly to providers without the involvement of a pharmacist, “there are several

notype, may require an opioid that the prescriber is not intimately familiar with,” he said. Ordering and interpreting results from panel-based PGx tests that include multiple genes also is important for analgesic therapies, Dr. Thomas said, noting “there is a big push to use adjuvant, nonopioid analgesics in pain management,” including nonsteroidal antiinflammatory drugs and other agents that are also subject to PGx.” In general, he said, “having an expert in PGx provide prescribing recommendations, either by directly contacting the provider or indirectly through [electronic health record] alerts or consult notes, can really help patients receive the analgesics most likely to maximize effectiveness while minimizing toxicity.” The sources reported no relevant financial disclosures.

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6 Clinical

Pharmacy Practice News • June 2022

COVID-19 Pandemic

ICU Underfeeding

Table. Survey Responses: Barriers To Providing Adequate Nutrition

continued from page 1

“There are significant misconceptions or personal biases about the risks and benefits associated with use of PN, such as concern about hyperglycemia, which we have learned to manage by not providing excessive calories and practicing early glycemic control,” Dr. Taylor said. “We need to address these beliefs and prejudices and encourage aggressive EN and earlier use of supplemental PN.” She stressed that “a more methodical approach to nutrition support for COVID-19 patients in the ICU” is CO needed, along with “updated ne consensus guidelines on nutrition management to ensure optimal care.” en Given the pressures of G the ongoing pandemic, th Dr. D Taylor acknowledged, this is no easy task. t “Since the very beginning of the COVID-19 pandemic, we have had to roll with the punches and learn as we go as to how to best treat our COVID-19 patients in the ICU,” she said. During those early days, Dr. Taylor and her colleagues realized that COVID-19 patients may require nutritional assistance soon after being admitted to the ICU. “With this virus, the disease process can last a long time, so we need to think about supplemental parenteral nutrition earlier than we normally would in patients who might have a shorter course of illness,” she said. Indeed, recommendations published

in early 2020 (J Parenter Enteral Nutr 2020;44[7]:1174-1184)—and updates issued since then—urge that EN be started within 24 to 36 hours of ICU admission and PN be administered immediately if EN is not tolerated. Those guidelines reflect what is known about the importance of early nutrition in the ICU population, where the strategy can reduce the risk for death by up to 55%, compared with when EN is delayed (Crit Care Med 2018;46[7]:1049-1056).

Barrier

Difficulty in delivering calories enterally (either because of intolerance or, in some cases, because patients receiving high doses of propofol in a lipid emulsion)

Reluctance to perform additional procedures to provide enteral access

Expressed a concern that EN or PN would harm patients

The limited availability of IV access points to devote to PN

Reluctance of respondents to add supplemental PN before seven days if EN was insufficient

Would start exclusive PN if EN was not feasible

EN, enteral nutrition; PN, parenteral nutrition.

Nutrition and Post–Intensive Care Syndrome

Source: ASPEN Survey.

Dr. Taylor said she’d like to see COVID-19 patients in the ICU given better real-world nutritional practices than those reflected in the practice survey (J Parenter Enteral Nutr 2021 Sep 5. https://doi.org/10.1002/ jpen.2263). But other nutrition providers are increasingly looking at the feeding needs of COVID-19 patients after an ICU stay. Todd Rice, MD, MSc, an associate professor of medicine at Vanderbilt University Medical Center, in Nashville, Tenn., told ASPEN attendees that as many as 91% of critically ill COVID-19 patients have post– intensive care syndrome (PICS), which is defined as the presence of physical, cognitive and mental impairments for more than one week after an ICU stay (Crit Care Med 2021;49[9]:1427-1438). “We don’t have good information on nutritional management of COVID-19

Anticipate a Flood of Long-COVID Patients With Unique Nutritional Needs

hanges in smell and taste linked to long COVID can place patients at risk for malnutrition and worsen their outcomes, and clinicians should be ready to help these people, experts urged at the American Society for Parenteral and Enteral Nutrition (ASPEN) 2022 Nutrition Science and Practice Conference. Anosmia (loss of sense of smell), dysgeusia (abnormal sense of taste) and parosmia (smell distortions) “can last for months” and lead to significant impairments in oral intake, said Ryan Hurt, MD, PhD, a professor of medicine and the director of Post COVID Research and Clinical Operations, Department of Medicine, at Mayo Clinic in Rochester, Minn. Dr. Hurt cited a study of 92 patients with long COVID, also known as post–acute sequelae of SARS-CoV-2 infection (PASC). An average of three months after initially testing positive for SARSCoV-2, 48% of these patients were found to be at risk for malnutrition based on reduced nutrient intake, and these patients were more likely to have loss of smell or taste, abdominal pain and diarrhea (Nutrients 2022;14[3]:642). “At the moment, I think we do a very poor job

making sure patients with PASC meet their nutritional needs,” Dr. Hurt said. “In addition to leading to weight loss, abnormal sense of taste and smell can lead to sarcopenia, which is a real risk factor for poor outcomes and something we’ll be seeing more of and having to address from a nutrition perspective.” Data on both the prevalence and impact of malnutrition among patients with long COVID are lacking, but findings presented at the ASPEN meeting revealed the extent of malnutrition in the hospitalized COVID-19 population and the possible impact on disease outcomes (abstract 1114271). Jana Ponce, PhD, RD, an assistant professor of medical sciences in the Division of Medical Nutrition, University of Nebraska Medical Center, in Omaha, and colleagues examined data from 246,272 people hospitalized with COVID-19 across the country and found that almost 13% had preexisting malnutrition and 6% hospital-acquired malnutrition. Those with preadmission malnutrition were 18% more likely to die in the hospital (odds ratio [OR], 1.18; 95% CI, 1.12-1.24; P<0.001) and 11% more likely to experience other nonfatal adverse outcomes,

such as requiring vasopressor use, extracorporeal membrane oxygenation, invasive mechanical ventilation or suffering uffering acute kidney injury (OR, 1.11; 95% CI, I, 1.081.16; P<0.001). “Screening of malnutrition with the implementation of appropriate interventions may improve outcomes in COVID-19 patients [in the hospital setting],” Dr. Ponce and colleagues concluded in their abstract. Although strategies such as enteral and parenteral nutrition can help prevent malnutrition in the severely ill, for those who are not severely ill but are eating less due to changes in smell and taste, treatment options are almost nonexistent, Dr. Hurt said. The only approach that is being tried at the moment is smell retraining, he noted, a treatment involving repeated exposure to different scents— most commonly rose, lemon, cloves and eucalyptus—to stimulate the olfactory system and establish a memory of those smells, he said. “Although there are no data on this intervention, I think it should be offered whenever possible because there’s no harm to doing so and it might help,” Dr. Hurt said.

—D.W.

Dr. Hurt reported no relevant financial disclosures.

Clinical

Pharmacy Practice News • June 2022

COVID-19 Pandemic ‘The impulse in [patients who deteriorate in the ICU] is to turn off enteral feeds, but instead we should be decreasing the rate of feeding, changing the enteral formulation or starting supplemental PN.’ —Beth Taylor, DCN patients with PICS, but borrowing from what we know about other patients with similar inflammation and immunosuppression, there are some possible treatments that might benefit our postCOVID patients,” Dr. Rice said. For example, studies in patients with cancer cachexia and sarcopenia, as well as those with burn-related hypercatabolism—both of which are similar to PICS—hint at the possible benefit of a high-protein diet in COVID-19 patients with PICS (1.5-2 g/kg per day) (Nutr Clin Pract 2017;32[suppl]:121S-127S). In burn victims with persistent catabolism—a feature of PICS—those who received early, aggressive high-protein nutrition support experienced better survival and less bacteremia (Ann Surg 1980;192:505-507), Dr. Rice said.

reduce the inflammatory component of COVID-19 PICS, he said, pointing to a meta-analysis of 49 studies looking at middle-aged and older adults without COVID-19 who had

chronic low-grade inflammation, a feature of post–COVID-19 PICS. That analysis showed marked reductions in levels of inflammatory biomarkers, such as interleukin-6 and

C-reactive protein, with ith probiotic supplementation tation (Ageing Res Rev 2018;46:42-59). “Of all the poten-tial treatments forr PICS, probiotics may ay actually have the bigggest impact on thee inflammatory component,” Dr. Rice said. Drs. Rice and Taylor reported no relevant financial disclosures.

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Leucine and Arginine Although their utility is unproven, supplements of the amino acids leusupp cine aand arginine also may be useful, Dr. Rice said. Leucine can decrease catabolism and c stimulate protein synthesti sis for hypertrophic muscle growth, growt while arginine is critical ca for immune response and wound healing and is part w of o the anabolic process, he explained (Nutr Clin Pract ex 2017;32[suppl]:121S-127S). 20 Because arginine is depleted during periods of severe stress in d sepsis and burn patients, and likely in sepsi PICS patients, “supplementation may PI play a role in recovery from PICS,” Dr. Rice said. Probiotic supplementation is another possible—and also untested—intervention that may help

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8 Clinical

Pharmacy Practice News • June 2022

Infectious Disease

Single-pill combinations, injectables and long-acting regimens expand options

New Paradigms in HIV Therapy to debate just how big an advantage this is. Yes, fewer drugs mean smaller pills, fewer interactions and less toxicity, but most of the other first-line therapies have pretty small pills, few interactions and few side effects already. Cost is another issue. While that’s not necessarily defined by how many drugs are in a regimen, DTG/lamivudine (3TC) did come in at a lower cost than other standard regimens.” A 2016 analysis found that DTG/3TC could save more than $500 million in antiretroviral treatment (ART) costs in the United States over five years (Clin Infect Dis 2016;62[6]:784-791).

Long-Acting Options

By Gina Shaw

ear the end of the first act of Jonathan Larson’s iconic musical “Rent,” which opened on Broadway in New York City in 1996, a beeper goes off loudly. Mimi, an exotic dancer struggling with heroin addiction, tells her date (who unknown to her also has HIV), “AZT break!” Twenty-five years later, living with HIV no longer requires constant reminders to take multiple daily pills with potentially debilitating side effects. These and other advances represent a paradigm shift in HIV management, according to interviews with HIV experts. “The biggest news in HIV management isn’t just how good our therapies are—they are great. But we’ve been there for a long time,” Eric Daar, MD, the chief of the Division of HIV Medicine at Harbor-UCLA Medical Center in Los Angeles, told Pharmacy Practice News. For virtually everyone who starts taking their HIV regimen as prescribed, their viral load will drop to undetectable levels within six months, maintaining their health and preventing transmission of the virus to sexual partners, Dr. Daar noted, citing data from the National Institute of Allergy and Infectious Diseases (bit.ly/3jHIDnV). What is new, he said, is how easy the latest drugs are to take. “Our current regimens are incredibly well tolerated, very safe, with limited drug–drug and drug–food interactions [JAMA 2020;324(16):1651-1669]. They also come in increasingly smaller and smaller single tablets that need to be taken only once a day, and we have several regimens, so those who are unlucky to have some side

effects can usually go on to one of the others with all the same advantages. It just continues to get easier and easier for people to take these medications.” For most people with newly diagnosed HIV, clinicians should start by reviewing the latest information from the Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents (updated June 2021; bit.ly/37TXbKi). The guidelines recommend starting treatment with two nucleoside reverse transcriptase inhibitors administered in combination with a third active antiretroviral (ARV) drug from one of three drug classes: an integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor, or a protease inhibitor with a pharmacokinetic enhancer. (See box for more details.) The latest guidelines removed raltegravir (RAL)-based regimens as initial therapy for most people because RAL has a lower barrier to resistance than bictegravir (BIC) and dolutegravir (DTG), and RAL-based regimens have a higher pill burden than other INSTI-based regimens. In addition, recent study data (Lancet 2021;397[10281]:1276-1292) showed the risk for neural tube defects associated with DTG use during conception is much lower than previously thought, so people of childbearing potential no longer need to choose RAL over DTG. “We’ve known for several years that people whose viral load is already suppressed on a three-drug regimen can switch to two, but now it is possible even in people starting therapy for the first time,” Dr. Daar said. “Now, it’s open

One of the most recent paradigm shifts in HIV therapy is the option for a long-acting regimen. In January 2021, the FDA approved the first long-acting injectable regimen rilpirivine + cabotegravir (Cabenuva, ViiV HealthcareJanssen), which can be given every four or eight weeks. “This simplifies therapy in many ways,” said Roger Bedimo, MD, the chief of the Infectious Diseases Section at the VA North Texas Health Care System. “It addresses issues such as pill fatigue and the daily stigma of oral medications, and because it is administered by a health care provider, it offers ease of documenting adherence.” That’s a pretty “amazing” accomplishment in HIV treatment, according to Dr. Daar. “Patients will go from multiple pills a day, every day, to coming in six days a year and being assured that not only will your disease be suppressed, but you won’t transmit it to your partner.” But there are limitations. Patients must first be virologically suppressed on a stable ARV regimen with no previous treatment failure, so this combination can’t be used as a firstline therapy or in treatment-resistant patients. There also is some inconvenience. “You have to come in to see your health care provider; it can’t be selfadministered,” Dr. Daar said. In addition, “if you skip an injection, you’re at pretty big risk for developing resistance. Both drugs have pretty long half-lives, but one is significantly longer than the other. Skipping a dose translates into using monotherapy, and we know that always selects for resistance.” Other products are currently in the pipeline, including a subcutaneous agent that could be given at home once every six months. “That would be a home run, but we know you can’t do this with one drug, so you need to find another you can give

every six months,” Dr. Daar said. “That’s the challenge: finding drugs that have promise to be long-acting, then figuring out how to pair them.” Today’s ARV regimens are more effective and easier to take than ever, but there is still a small percentage of people living with HIV who are heavily treatmentexperienced and are resistant to multiple classes of drugs (AIDS 2020;34[14]:2051-2059). “The proportion of people with HIV who have two or fewer drug classes available to them has declined significantly since 2000, and represents about 1% of the population today,” Dr. Bedimo said. “This group includes patients who are highly adherent but were started on nonsuppressive regimens that led to selection of highly resistant HIV—fortunately, this is a smaller group—and a somewhat larger group of patients who do not have multidrug resistance, but are nonadherent to therapy due to various challenges and still have viremia.” There is also a pediatric cohort among treatment-resistant patients. A 2019 study of young people who recently transitioned from pediatric to adult HIV care found that 56% of participants had at least one incident of unsuppressed viremia in the year before the transition (Clin Infect Dis 2020;71[1]:133-141). “Some of these new therapies may be able to reduce the treatment-resistant population further,” Dr. Bedimo said. “For the second group—those with nonadherence issues—we can try to simplify the pill burden, reduce frequency of dosing with long-acting injectables, or if vascular or renal tolerability is an issue, try to find agents that mitigate the impact to these organs. As our population ages, they have other non-HIV medications they have to take, so we also need to mitigate potential drug–drug interactions.” For adherent patients who have failed second-line regimens and beyond, the challenges are even greater. “We can use past and current genotypic and phenotypic resistance and ART history in designing a new regimen,” Dr. Bedimo said. “These patients should be on at

Clinical

Pharmacy Practice News • June 2022

Infectious Disease

4 Recommended Starting Regimens 1 2 3 4

BIC/FTC/TAF DTG/ABC/3TC DTG + (FTC or 3TC) + (TAF or TDF) DTG/3TC

3TC, lamivudine; ABC, abacavir; BIC, bictegravir; DTG, dolutegravir; FTC, emtricitabine.

For example, in early August, data on Gilead’s twice-yearly, long-acting injectable lenacapavir, the first HIV capsid inhibitor, were reported at the 11th International AIDS Society Conference on HIV Science in July 2021. The phase 2 Capella study found that lenacapavir in combination with an optimized background regimen produced sustained virologic suppression in 81% of heavily pretreated patients at week 26. In the phase 2 Calibrate study (theprogramme.ias2021.org/ Abstract/Abstract/2211), it also produced

high rates of virologic suppression in treatment-naive patients in combination with emtricitabine/tenofovir alafenamide (F/TAF). However, the FDA issued a complete response letter about lenacapvir on March 1, 2022, because of concerns about the compatibility of the vial with the lenacapavir solution. Gilead said it was working with the agency to solve the inssue, and still plans to seek approval of this investigational long-acting HIV-1 capside inhibitor. “The group of people who need new

options for treatment because of side effects or underlying resistance is not a huge number, but for those who are dealing with it, it’s their life,” Dr. Daar said. “These new options offer huge promise for these people, and it’s rewarding to see that companies have invested in developing treatments for them.” Dr. Bedimo reported that he serves on the advisory committees/boards for Merck, Theratechnologies and ViiV Healthcare. Dr. Daar reported financial relationships with Gilead Sciences, Merck and ViiV Healthcare.

Source: Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents.

least two, and preferably three, fully active agents, but partially active drugs may be used when no other options are available as they can partially suppress progression even if they don’t totally suppress viremia.” He cited several novel agents that either have been recently approved or are currently in the pipeline, as possible options. They include the monoclonal antibody ibalizumab (Trogarzo, TaiMed Biologics), approved in March 2018 for heavily pretreated adults with HIV, administered intravenously every two weeks and used in combination with other ARV drugs; and fostemsavir (Rukobia, ViiV Healthcare), a firstin-class HIV attachment inhibitor approved in July 2020, for people with extensive drug resistance. It’s a twicedaily oral therapy also used in combination with other ARV drugs. “New mechanisms of action and additional long-acting regimens are also coming soon,” Dr. Bedimo noted.

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10 Clinical

Pharmacy Practice News • June 2022

Oncology

Novel Agents Expand Rx for Refractory Lymphoma Boston—Treatment options for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have increased dramatically, with seven new therapies approved between October 2017 and April 2021, and several others in the pipeline.

of initial therapy, the NCCN [National Comprehensive Cancer Network] guidelines have just been updated to recommend CAR T-cell therapy with axicabtagene ciloleucel [Yescarta, Gilead/Kite],” she said. On April 1, 2022, the day after Dr. Chandrasekhara’s presentation, the FDA officially granted approval to

“We’ve seen really exciting changes in the options that are available for these patients,” said Soniya Chandrasekhara, PharmD, a clinical pharmacist in hematology/oncology/bone marrow transplant at Stanford Health Care, in Palo Alto, Calif., during a session at the 2022 annual meeting of the Hematology/ Oncology Pharmacy Association. Patient selection and sequencing of these novel agents are critical for optimizing patient outcomes, she stressed. DLBCL is the most common subtype of non-Hodgkin lymphoma, and although first-line, five-year survival rates range from 60% to 70%, between 20% and 50% of patients will be refractory to the standard first-line therapy of rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), or will relapse after treatment (Blood 2017;130[16]:1800-1808). For many years, based on results of the PARMA trial, these patients typically were treated with salvage combination cytotoxic chemotherapy (usually platinum-based) followed by high-dose myeloablative chemotherapy and autologous stem cell transplantation, which resulted in long-term, disease-free survival in about half of patients (Hemasphere 2019;3[6]:e295). Now, there are more options and factors for clinicians to consider, including three chimeric antigen receptor (CAR) T-cell therapies. “For patients with primary refractory disease or who relapse within 12 months

axicabtagene ciloleucel for this patient population—the first CAR T-cell therapy approved for the initial treatment of R/R DLBCL. The approval, and NCCN’s recommendation, were based mainly on the findings of the ZUMA-7 trial, in which 24-month event-free survival was 41% for axicabtagene ciloleucel compared with 16% for standard of care (P<0.001) (N Engl J Med 2022;386[7]:640-654). Other CAR T-cell therapies for these patients after at least two prior lines of therapy include tisaganleleucel (Kymriah, Novartis), approved in December 2017, and lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb), approved in February 2021. CAR T-cell therapies are typically recommended for patients with adequate organ function without severe cardiac, hepatic or renal dysfunction, or evidence of active central nervous system (CNS) disease, given concerns about toxicity. But Dr. Chandrasekhara pointed out that the TRANSCEND study of lisocabtagene maraleucel included patients with CNS disease and poor organ function with promising results (Lancet 2020;396[10254]:839-852). “Elderly patients with worse performance status have also been treated in the real-world setting,” she said. “Given that we have seen real-world benefits in elderly patients and those with poor performance status, they should not necessarily automatically be excluded from eligibility for CAR T.” In addition to CAR T-cell therapies,

By Gina Shaw

patients with R/R DLBCL who are ineligible for stem cell transplant have four other new treatment options: Polatuzumab vedotin (Polivy, Genentech), a CD79-targeted antibody–drug conjugate, was approved in June 2019 for R/R DLBCL after two or more lines of systemic therapy. Approval was based on the results of a clinical trial that compared it in combination with bendamustine and rituximab versus bendamustine and rituximab alone (J Clin Oncol 2020;38[2]:155-165). “The results were pretty remarkable,” Dr. Chandrasekhara said. “The overall response rate was about 45% versus 17.5%, which translated to a significant benefit in progression-free survival of 7.6 months versus two months, and a longer median overall survival of 12.4 months versus 4.7 months.” Side effects in the polatuzumab vedotin arm included increased rates of neutropenia, anemia and thrombocytopenia, although not in infection risk. However, prophylaxis is still recommended for induction, according to Dr. Chandrasekhara. “There was also a high incidence of peripheral neuropathy, mostly grade 1 or 2, and most patients experienced reversibility.”

Loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics), a CD19 antibody–drug conjugate, was approved for patients with at least two prior lines of systemic therapy. It is administered every three weeks until disease progression or unacceptable toxicity. “In the LOTIS-2 study that led to its approval, the overall response rate was 48.3%, with 24.1% of patients achieving a complete response,” Dr. Chandrasekhara said, noting that all study participants had at least two prior lines of systemic therapy. “Even patients who had double- or triple-hit lymphoma had a 33.3% overall response rate, while those with prior CAR-T had a 53.5% response rate. That tells us this is a therapy option that can be considered even in patients with highrisk characteristics.” The most common adverse events were neutropenia (26%), thrombocytopenia (18%) and gamma-glutamyl transferase (GGT) increase (17%). “The GGT increase did not appear to be associated with an increased risk of liver disease, however,” Dr. Chandrasekhara noted. Follow-up results from the L-MIND study after more than three years of analysis, presented at the most recent American Society of Clinical Oncol-

‘The tricky thing is that none of [these novel agents] have ever been compared to one another, so it is hard to know which patient is the best candidate for which agent and how to sequence them.’ —Victoria Nachar, PharmD Tafasitamab-cxix (Monjuvi, MorphoSys/Incyte) plus lenalidomide (Revlimid, Celgene), an antiCD19 monoclonal antibody and immunomodulator combination, was approved in July 2020, for R/R DLBCL after two or more lines of systemic therapy. Treatment with tafasitamab-cxix is administered weekly for cycles 1 to 3, then every two weeks from cycle 4 to 12 with oral lenalidomide on days 1 to 21 of each cycle followed by tafasitamabcxix monotherapy until disease progression. “This is an interesting regimen,” Dr. Chandrasekhara said. “Until now, we have typically seen a fixed number of cycles, but here we see it extended indefinitely until progression, which is a shift in the way we think about treatment in this setting.” Grade 3 or higher toxicities included high rates of neutropenia (49.4%), as well as thrombocytopenia (17.4%) and febrile neutropenia (12.3%).

ogy meeting, showed there is still a very robust response, with a 57.5% response rate in the study population overall and 67.5% among those who had only one prior therapy. Overall survival was very durable and robust at 33.5 months” (J Clin Oncol 2021;39[15 suppl] :7513-7513). The most common grade 3 or higher toxicities were neutropenia (49.4%), thrombocytopenia (17.3%) and febrile neutropenia (12.3%). Selinexor (Xpovio, Karyopharm Therapeutics), a exportin 1 inhibitor, was approved for R/R patients with at least two prior lines of systemic therapy. The SADAL trial that led to its approval enrolled patients who had received two to five lines of previous therapies and had moderate to poor performance status. The overall response rate was 28% (36/127); 15 (12%) achieved a complete response and 21 (17%) a partial response (Lancet Haematol 2020;7[7]:e511-e522). “The response rate here is not as high

Clinical

Pharmacy Practice News • June 2022

Oncology Cost is also a factor: Some agents are approved in combination with oral drugs and require higher copays for patients, while others are IV only and may involve lower out-of-pocket costs.” Dr. Nachar noted that some of the newer agents could also be used as bridging therapy to get the burden of disease as low as possible before initiating CAR T-cell therapy. “In this case, we would try not to use a drug like tafasitinab, which targets CD19, as we don’t really know if that will impact the outcomes with CAR T. Instead, we might choose

Abnormal large cells from a biopsy of a patient with DLBCL spreading diffusely.

a polatuzumab backbone.” By contrast, if the patient is elderly and either not fit for CAR T-cell therapy or transplant or already has had one, then multiple options are on the table, she said. “Tafasitamab-lenalidomide was studied in elderly patients, but we have found in our practice that it’s a hard regimen for them to tolerate. There is a lot of myelosuppression and fatigue. It also can be more burdensome, with a lot of infusions as well as having to take a pill. Loncastuximab, with lower rates

of neutropenia, may be less burdensome for these patients.” Dr. Nachar also pointed out that traditional chemotherapy still plays a role in the management of R/R DLBCL. “It’s not a sexy new drug, but patients still benefit. We shouldn’t jump ship on the older agents, but instead try to figure out where they fit so we can sequence therapies and patients can live as long as possible, as well as possible.” The sources reported no relevant financial disclosures.

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Source: Lymphoma Action.

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as those we were seeing in the previous agents, but it’s still pretty good compared with the options that were previously available to patients in this setting,” she said. “Of those who responded, 38% had response durations of at least six months and 15% at least 12 months. There is clearly a subset of patients that will do well on selinexor, so it should be considered a viable treatment option.” The most common grade 3 or higher adverse events were thrombocytopenia (46%), neutropenia (24%) and anemia (22%).

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Comparative Data Lacking “All of this is very encouraging,” Victoria Nachar, PharmD, a clinical pharmacist specialist in ambulatory hematology at the University of Michigan, in Ann Arbor, said in an interview with Pharmacy Practice News. “There are many new options for this very hardto-treat patient population, with novel mechanisms of action and good response rates. The tricky thing is that none of them have ever been compared to one another, so it is hard to know which patient is the best candidate for which agent and how to sequence them.” Decision making about patient selection and sequencing involves looking closely at clinical trial data and comparing the patient populations represented in the trials with the patients in your clinic, Dr. Nachar said. “We also consider mechanism of action and target, whether the drug is given alone or in combination, and what we think a patient can tolerate based on toxicity profiles. Some of these agents are approved for first relapse while others require two or more, so in some cases we’re strapped by FDA approvals.

Unit dose oral solids

Strength

UD size

NDC

Folic Acid Tablet

1 mg

100 UD

62584-0897-01

Gabapentin Capsule

300 mg

100 UD

60687-0591-01

Healthylax Powder

17 mg

14 UD

60687-0431-98

Oxycodone Tablet (CII)

5 mg

100 UD

68084-0354-01

Pantoprazole DR Tablet

40 mg

80 UD

68084-0813-09

Liquid unit dose

Cup delivery

Cup strength

UD size (cups/case)

Levetiracetam Solution

5 mL

500 mg / 5 mL

40 UD

NDC 60687-0249-77

Levetiracetam Solution

5 mL

500 mg / 5 mL

50 UD

60687-0249-67

Oxycodone HCI Solution

5 mL

5 mg / 5 mL

40 UD

60687-0406-77

Potassium Cl Oral Solution

15 mL

20 mEq / 15mL

40 UD

60687-0341-64

Potassium Cl Oral Solution

15 mL

20 mEq / 15mL

50 UD

60687-0341-71

Inhalation unit dose

Strength

UD size

NDC

Albuterol Sulfate Inhalation Solution

2.5 mg per 3 mL

30 UD

60687-0395-83

Budesonide Inhalation Suspension

0.5 mg per 2 mL

30 UD

60687-0524-83

Ipratropium Bromide Inhalation Solution

0.5 mg per 2.5 mL

30 UD

60687-0394-83

Ipratropium Bromide & Albuterol Sulfate Inhalation Solution

0.5 mg / 3 mg per 3 mL

30 UD

60687-0405-83

The NDC shown is in the 11-digit format required for the Centers for Medicare & Medicaid Services (CMS) processing, 42 CFR § 447.502 – Deﬁnitions.

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12 Clinical

Pharmacy Practice News • June 2022

Review Article Part 1

Using National Guidelines to Determine

Hyperlipidemia Treatment C. MICHAEL WHITE, PHARMD, FCP, FCCP Distinguished Professor and Chair, Pharmacy Practice University of Connecticut School of Pharmacy Storrs, Connecticut

his is a 2-part series designed to provide front-line pharmacists with the knowledge they need to understand how to use traditional antihyperlipidemic drugs to reduce low-density lipoprotein (LDL) according to national treatment guidelines.

This first installment describes how patients are assessed to determine their risk for an atherosclerotic cardiovascular disease (ASCVD) event; identifies how differing levels of risk drive the intensity and choice of statin therapy; and details key therapeutic mechanisms of action, comparative LDL reductions, and adverse events for statins, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs). Guideline-Directed Medical Therapy Lipid Recommendations

All patients should be encouraged to have a heart-healthy lifestyle: a diet that is low in processed foods, high in fiber, and low in saturated fat and trans-fat, along with ample exercise.1 If drug therapy is indicated to lower LDL, statins are the first-line option whenever possible because of the extent of expected benefit, strength of evidence, tolerability, and price.1 Statin therapy is only available orally, and the drugs and dosages are divided by the intensity of LDL lowering (Table 1). Statins block HMG-CoA reductase, an enzyme in the cholesterol cascade that converts HMG-CoA into mevalonate.2 With less mevalonate, intracellular cholesterol levels fall, and the liver expresses more LDL receptors to recapture the circulating cholesterol for the creation of bile. In primary and secondary prevention, statins have been demonstrated to reduce the risk for subsequent ASCVD events, such as myocardial infarction and stroke, in direct relation to their extent of induced LDL reduction.1,2 Once maximally recommended or maximally tolerable statin dosing is employed, which may include not using any statin therapy for those with contraindications or severe intolerance, 2 other guideline-directed medical therapies can be added to statin regimens to achieve the

target LDL goal.1 Some patients can be treated with a statin plus ezetimibe, a statin plus a PCSK9 mAb, or all 3 therapies.1,2 The molecular target of ezetimibe is Niemann-Pick C1-like 1, which is involved in the intestinal uptake of cholesterol. PCSK9 cross-links LDL receptors to LDL and prevents the intracellular recirculation of the LDL receptor.3 This means more LDL receptors are destroyed and fewer are available to bind and remove circulating LDL.3 PCSK9 mAbs prevent PCSK9 from attaching to LDL receptors, enhancing their concentration on the cell surface.4 Recent clinical trials found that adjunctive treatment with ezetimibe plus statins or PCSK9 mAbs plus statins (with/without ezetimibe) reduce future ASCVD events more than statins alone in people who are at very high risk for ASCVD events (as described in detail below).3,4 Ezetimibe is only available orally, while the PCSK9 mAbs are only available parenterally.3,4

Secondary Prevention Pharmacotherapy High-intensity statin therapy is recommended for all secondary prevention patients, regardless of their plasma LDL levels.1,2 This includes anyone with established ASCVD (history of acute coronary syndromes [unstable angina, myocardial infarction], stable angina, stroke/transient ischemic attack, peripheral artery disease [intermittent claudication or peripheral

arterial occlusive disease], and aortic aneurysm). In secondary prevention, there are only 2 risk categories: high and very high risk. Very high risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple highrisk conditions. In patients who are at very high risk with LDL levels above 70 mg/dL on maximal tolerated statin therapy, it is reasonable to add ezetimibe; if LDL remains elevated, a PCSK9 mAb also should be added. For secondary prevention patients at high risk, therapy is limited to high-intensity statin therapy; or, if this intensity could not be achieved, ezetimibe/PCSK9 mAb therapy can be used to reduce the LDL level by at least 50%.1,2

Primary Prevention Pharmacotherapy The new guidelines advocate a multifaceted approach for risk-stratifying primary prevention patients.1,2 Before starting statins, clinicians should evaluate for key diagnoses, 10-year ASCVD risk, risk enhancers, patient preferences, and risk for adverse effects from statins. These factors should come into play as a holistic determination of the guideline-directed medical therapy for LDL reduction.1,2 High-intensity statin therapy is specifically recommended for adults aged 20 to 75 years with severe hypercholesterolemia (LDL ≥190 mg/dL), regardless of their calculated 10-year risk for ASCVD events.1,2 Many of

these patients are heterozygous (occurs on 1 but not both alleles) or homozygous (occurs on both alleles) for genetic polymorphisms that impede LDL receptor generation or function. If the LDL level remains higher than 100 mg/dL with maximal tolerated statin therapy, ezetimibe can be added; and if the LDL is still above this level, a PCSK9 mAb may be considered.1,2 Moderate-intensity statin therapy is indicated in adults with diabetes, even if they do not have an elevated 10-year risk for ASCVD.1,2 However, it is reasonable to start high-intensity statin treatment if the patient also has an elevated 10-year ASCVD score above 20%, multiple risk-enhancing factors (as specified below), or an elevated intracoronary calcium score (as specified below). Patients with chronic kidney disease or HIV infection also should receive at least moderate-intensity statin therapy with or without ezetimibe and the presence of risk-enhancing factors, and calcium scoring can lead the initiation of high-intensity statin therapy.1,2 For primary prevention patients aged 40 to 75 years without diabetes, chronic kidney disease, or HIV who have LDL levels between 70 and 189 mg/dL, the American Heart Association/American College of Cardiology (AHA/ACC) 10-year risk calculator (www.cvriskcalculator. com) should be used.1,2 This risk calculator considers a patient’s age, sex, race, total cholesterol level, high-density lipoprotein (HDL) level,

Clinical

Pharmacy Practice News • June 2022

Review Article Table 1. Statins and Statin Dosages Are Divided by the Intensity of LDL Lowering High intensity – at least 50% reduction in LDL: • atorvastatin 40 to 80 mg daily • rosuvastatin 20 to 40 mg daily Moderate intensity – 30% to 49% reduction in LDL: • atorvastatin 10 to 20 mg daily • fluvastatin 80 mg daily • lovastatin 40 to 80 mg daily • pitavastatin 1 to 4 mg daily • pravastatin 40 to 80 mg daily • rosuvastatin 5 to 10 mg daily • simvastatin 20 to 40 mg daily Low intensity – less than 30% reduction in LDL: • fluvastatin 20 to 40 mg daily • lovastatin 20 mg daily • pravastatin 10 to 20 mg daily • simvastatin 10 mg daily LDL, low-density lipoprotein.

systolic blood pressure, smoking status, diabetes status, and whether they are receiving treatment for hypertension. Patients’ 10-year ASCVD risk is categorized as: • low risk, less than 5%; • borderline risk, 5% to 7.5%; • intermediate risk, 7.5% to 20%; and • high risk, more than 20%. Although high-intensity statin therapy is indicated in patients at high risk for ASCVD and only lifestyle modifications indicated for lowrisk patients, patients at borderline or intermediate risk require additional data, including assessment of riskenhancing factors and intracellular calcium scores.1,2 • Risk-enhancing factors are those factors that are known to enhance the risk for ASCVD events, but they are not as well described as traditional risk factors in the 10-year ASCVD riskscoring tool.1,2 Risk-enhancing factors are detailed in Table 2. In those cases that are still unclear, the coronary artery calcium measurement can be useful.1,2 If the intracoronary calcium score is 0, statin therapy may be safely withheld unless the patient smokes or has premature cardiovascular disease. If the score is 1 to 99, statin therapy is suggested, whereas therapy is clearly indicated for scores of at least 100.1,2

Major Clinical Trials In Hyperlipidemia Statins are the cornerstone of pharmacotherapy for hyperlipidemia. Early placebo-controlled trials in secondary

prevention (eg, CARE, LIPID, HPS, GREACE trials) found that such populations lived longer and had fewer subsequent ASCVD events after statin therapy was initiated.4 Similarly, placebo-controlled primary prevention studies (eg, WOSCOPS, AFCAPS/ TexCAPS, ASCOT-LLA trials) found fewer ASCVD events after statin therapy was initiated. In those patients at high or very high risk, the use of highintensity statin therapy sufficient to drop LDL below 70 mg/dL provided additional ASCVD event reduction versus low-intensity statin therapy, which reduced LDL to approximately 90 mg/dL in active-controlled trials (eg, PROVE-IT, TNT trials).4 Several trials were conducted in patients with high to very high baseline risk to assess the impact of combination therapy with statin therapy plus ezetimibe or a PCSK9 mAb versus statin therapy alone. Ezetimibe plus moderate-intensity statin therapy was compared against moderate-intensity statin therapy alone in the IMPROVE-IT trial, and combination therapy was associated with additional reductions in ASCVD events. 5 Similarly, the combination of PCSK9 mAbs (alirocumab [Praluent, Regeneron], evolocumab [Repatha, Amgen]) plus statins reduced myocardial infarction, stroke, and coronary revascularization events versus statins alone in pooled assessments of several clinical trials, including ODYSSEY, Olser 1 and 2, and FOURIER.6 Additional LDL lowering, regardless of whether the drug used is a statin alone or statin combined with ezetimibe or a PCSK9 mAb, is strongly linked to fewer major cardiovascular events.3-6 In a meta-analysis of 27 statin trials, the Cholesterol Treatment Trialists (CTT) found a linear relationship of which every 39-mg/dL reduction in LDL yields a 22% reduction in major cardiovascular events over 5 years of therapy.7 Applying data from the IMPROVE-IT, ODYSSEY Long Term, and OSLER 1 and 2 trials to the aforementioned CTT data set does not change the relationship between LDL reduction and major cardiovascular events after 5 years of therapy or the magnitude of that reduction.8

Contemporary Assessments Of Cost-Effectiveness Because statins and ezetimibe are generically available, very inexpensive, and reduce ASCVD events, they are highly cost-effective options for hyperlipidemic patients.4 The 2018 AHA/ACC guidelines comment on the importance of considering the value of treatment in therapy

Table 2. Factors Enhance the Risk for ASCVD Events A family history of premature ASCVD (in men <55 or women <65 years of age) LDL levels between 160 and 180 mg/dL or non-HDL levels (total cholesterol minus HDL cholesterol) between 190 and 219 mg/dL Metabolic syndrome (3 or more): • increased waist circumference by ethnically appropriate cut points • fasting triglyceride level >150 mg/dL • hypertension • elevated glucose • low HDL (<40 mg/dL in men, <50 mg/dL in women) • chronic kidney disease [estimated glomerular filtration rate, 15-59 mL/min/1.73 m2 Chronic inflammatory conditions (psoriasis, rheumatoid arthritis, lupus, and HIV/AIDS) Premature menopause (age <40 years) Elevated high-sensitivity C-reactive protein (≥2.0 mg/L) Preeclampsia High-risk ethnicity or race (South Asian) Another lipid biomarker associated with elevated risk (persistent hypertriglyceridemia [≥175 mg/dL nonfasting], elevated lipoprotein(a) a[≥50 mg/dL or ≥125 nmol/L], elevated apolipoprotein B [≥130 mg/dL]) An ankle-brachial index less than 0.91,2 ASCVD, atherosclerotic cardiovascular disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein.

decisions. At the time, PCSK9 mAbs had an incremental cost-effective ratio of $140,000 to $450,000 per quality-adjusted life-year (QALY), levels above the suggested maximum of $150,000 per QALY. This is reflected in the current guidelines, which suggest adding PCSK9 mAbs only after maximal tolerated doses of statins and ezetimibe have not improved LDL cholesterol (LDL-C) levels significantly in very high-risk patients with ASCVD or those with a family history of premature ASCVD. Since then, the US list prices of PCSK9 mAbs were reduced from $14,000 to $6,000 per year, which dramatically improved their costeffectiveness, including when they are being used adjunctively with statins as well as when high-intensity statins cannot be used alone. Ezetimibe can only reduce LDL levels by approximately 20%, but the PCSK9 mAbs can exceed 50% reductions for monotherapy in patients at high or very high risk, and can be combined with ezetimibe in very high-risk patients not achieving LDL levels below 70 mg/dL.4

Major Adverse Events Of Statins, Ezetimibe, And PCSK9 Inhibitors Although statins are well tolerated, some adverse events should be noted. Myalgia was reported in 1% to 15% of participants in randomized controlled trials, but these studies included a run-in period in which intolerant patients were removed before enrollment. Myalgia was reported in 5% to 20% of patients taking statins in observational

studies. According to the guidelines, patients with statin-associated muscle symptoms should undergo a detailed assessment of symptoms and predisposing factors before determining whether statins are the cause as well as treatment options.1,2 If intolerable adverse effects occur, clinicians should lower the intensity of statin dosing (lower the daily dose or reduce the frequency to every other day), switch to a statin with higher hydrophilicity (atorvastatin, pravastatin, or rosuvastatin), or combine the statin with ezetimibe or ezetimibe plus a PCSK9 mAbs.1,2,9,10 If symptoms persist despite these measures, nonstatin therapies with proven efficacy in randomized controlled trials are recommended.11-13 PCSK9 mAbs have performed well in trials of statin-intolerant patients with or without ezetimibe.2 Recent findings indicate that statins cause dissociation of a binding protein from the sarcoplasmic reticulum (SR) calcium (Ca2+) release channel (ryanodine receptor 1), which then causes ROS-dependent spontaneous SR Ca2+ release events known as Ca2+ sparks.11-13 A SR Ca2+ leak is a myopathic mechanism common to many skeletal muscle diseases, which may be why clinical trials assessing coenzyme Q10 or vitamin D supplementation have been ineffective.14,15 The overall incidence of adverse events reported with ezetimibe was similar to placebo, and the discontinuation rate due to adverse events also was similar for ezetimibe and placebo.3 While ezetimibe monotherapy has a low risk for see HYPERLIPIDEMIA, page 14

14 Clinical

Pharmacy Practice News • June 2022

Review Article

HYPERLIPIDEMIA continued from page 13

elevating liver transaminases, the incidence rates for serum transaminase increases more than 3 times the upper limit of normal were 4.5% versus 2.7%, and for cholecystectomy were 0.6% versus 1.7% for fenofibrate alone and ezetimibe plus fenofibrate, respectively.3 The PCSK9 mAbs are well tolerated, with a discontinuation rate due to adverse events approximating

control therapy. Injection site reactions were the most common adverse events and occurred in 1 of 3 patients.16 The incidence of muscle adverse events or elevated liver transaminases are similar to control therapy.16

Place in Therapy Statins have the most data for clinical benefits in patients with elevated LDL-C and are the backbone of therapeutic regimens for LDL reduction.1,2 However, statins alone

may not reduce LDL sufficiently to ameliorate the negative health consequences of elevated concentrations of circulating LDL, and other patients may not be able to use higher statin doses or any statins at all due to contraindications or adverse events. The use of ezetimibe and the PCSK9 mAbs are proven to further lower ASCVD events when statins alone are insufficient to achieve contemporary aggressive LDL goals, especially in those with heterozygous familial hypercholesterolemia

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and those who had experienced ASCVD events. Other therapeutic modalities such as niacin, bile acid sequestrants, and other natural remedies may reduce LDL but have not been shown to decrease ASCVD events. As such, treatment guidelines make these therapies the adjunctive treatments of choice when statins alone are insufficient. If patients need more than an 18% to 20% reduction in LDL to achieve their optimal goal, ezetimibe cannot be used in monotherapy, while PCSK9 mAbs can reduce LDL by over 50%. PCSK9 inhibitors are very expensive options, but their cost-effectiveness has markedly improved due to reductions in the cost of the drug from the manufacturers.1,2

References 1.

Grundy SM, et al. Circulation. 2019;139[25]:e1082-e1143.

2. Reiter-Brennan C, et al. Clev Clin J Med. 2020;87(4):231-239. 3. Zetia [package insert]. Organon; revised June 2021. Accessed May 5, 2022. www. organon.com/product/usa/pi_circulars/z/ zetia/zetia_ppi.pdf 4. White CM. J Cardiovasc Pharmacol Ther. 2018;23(4):301-308. 5. Cannon CP, et al. N Engl J Med. 2015;372(25):2387-2397. 6. Karatasaskis A, et al. J Am Heart Assoc. 2017;6(12):e006910. 7. Cholesterol Treatment Trialists’ Collaborators. Lancet. 2012;380(9841):581-590. 8. Robinson JG, et al. J Am Coll Cardiol. 2016;68(22):2412-2421. 9. Riaz R, et al. Indian Heart J. 2018;70(4):492-496.

Safe Opioid Prescribing

10. Dale KM, et al. Am J Med. 2007;120(8):706-712. 11. Lotteau S, et al. JACC Basic Transl Sci. 2019;4(4):509-523.

A Patient-Centered Approach to the FDA Blueprint

12. Galtier F, et al. Toxicol Appl Pharmacol. 2012;263(3):281-286.

A 3-Part Series RELEASE DATE: OCTOBER 27, 2021

13. Sirvent P, et al. Toxicol Appl Pharmacol. 2012;259:263-268.

EXPIRATION DATE: DECEMBER 31, 2022

14. Kurnik D, et al. Clin Endocrinol (Oxf). 2012;77(1):36-41. 15. Taylor BA, et al. Atherosclerosis. 2015;238(2):329-335.

This activity is jointly provided by Global Education Group and Applied Clinical Education.

CHAIR

16. Gürgöze MT, et al. Clin Pharmacol Ther. 2019;105(2):496-504.

Charles E. Argoff, MD

FACULTY These activities are supported by an independent educational grant from the Opioid Analgesic REMS Program Companies. Please see https://opioidanalgesicrems.com/Resources/Docs/List_of_RPC_Companies.pdf for a listing of REMS Program Companies. This activity is intended to be fully compliant with the Opioid Analgesic REMS education requirements issued by the U.S. Food and Drug Administration (FDA).

Yvonne M. D’Arcy, CRNP, CNS Marc R. Gerber, MD Courtney M. Kominek, PharmD, BCPS, CPE Bill H. McCarberg, MD, FABM

INDEPENDENT REVIEWER Michael Clark

Distributed by CMEZone.com

Access today at www.cmezone.com/SY212

Part 2: 3 Newly FDA-Approved Options Part 2 of this review, scheduled for the August issue, will foster an understanding of how 3 newly FDA-approved options—bempedoic acid (Nexletol, Esperion), bempedoic acid-ezetimibe (Nexlizet, Esperion), and inclisiran (Leqvio, Novartis)—fit into the treatment armamentarium for patients who are unable to achieve their LDL goals.

Clinical

Pharmacy Practice News • June 2022

Critical Care

No Clear Guidance on Managing ICU Hypotension By David Wild

hen it comes to vasopressor use in patients with septic shock, practice variation is the norm. Although the 2021 Surviving Sepsis Campaign guidelines recommend administering vasopressin, for example, in certain adults with septic shock and refractory hypotension, they are short on specifics. Moreover, “controversy around everything from when to initiate vasopressin in patients with septic shock, how to initially dose it, and how long to continue treatment means it’s difficult to make evidence-based clinical decisions on vasopressin use,” said Cassandra Doyno, PharmD, an assistant clinical professor in critical care and emergency medicine at the University of Connecticut School of Pharmacy, in Storrs. The 2021 Surviving Sepsis Campaign guidelines recommend starting vasopressin when patients have received up to 0.25-0.5 mcg/kg per minute of norepinephrine and continue to have inadequate mean arterial pressure (MAP). However, the recommendation is weak and based on moderate-quality evidence, and “norepinephrine dosing varies in practice as well,” Dr. Doyno explained.

Patterns of vasopressin use in patients with septic shock are as wideranging as the supporting evidence. A meta-analysis found administering catecholamine-sparing agents such as vasopressin as an adjunct to norepinephrine may improve survival by as much as 12% in ICU patients with hypotension, but the analysis did not identify a survival benefit with any specific agent (PLoS One 2015;10[11]:e0142605). The VASST (Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock) trial found no overall difference in 28- or 90-day mortality, length of stay or adverse events when norepinephrine was given with or without adjunct vasopressin. However, a subgroup analysis of those with less severe septic shock found the 28-day mortality rate was 26.5% when vasopressin was used as an adjunct, compared with 35.7% when norepinephrine was administered alone (P=0.05) (N Engl J Med 2008;358[9]:877-887). Other findings have shown that discontinuing vasopressin before norepinephrine can increase the likelihood of hypotension, albeit with no impact on mortality or ICU length of stay (J

Intensive Care Med 2019;34[10]:805-810). Yet another study—the VANISH trial— compared early administration of vasopressin or norepinephrine with or without hydrocortisone in adults with septic shock and found no differences in rate of kidney failure, but wide confidence intervals left open the possibility of a clinical benefit with vasopressin that warranted additional research, the investigators concluded (JAMA 2016;316[5]:509-518). A single-institution study led by Arpita Patel, PharmD, who was a PharmD candidate at the University of British Columbia, in Vancouver, when conducting the research, documented real-world variation in the use of vasopressin as an adjunct to norepinephrine in ICU patients (CJHP 2020;73[3]:209-215). Of the 100 patients in the study, 60 were admitted for sepsis or infection, although smaller numbers were hospitalized following cardiac arrest, or because of acute renal failure, pancreatitis, gastrointestinal bleeding or other conditions. Dr. Patel’s team found vasopressin was initiated a mean of 12 hours after norepinephrine was started, with a wide standard deviation of 21.6 hours, and the mean dose of

Acidemia May Require Tweaks To Septic Shock Therapy By Gina Shaw

atients with septic shock and low arterial pH are at risk for suboptimal responses to vasopressin therapy and require higher catecholamine doses after vasopressin initiation than those with higher arterial pH, according to a new study from the Cleveland Clinic Health System. The impetus for the study was based partly on the fact that more than half of patients with septic shock have a concomitant decrease in blood pH levels and resulting acidemia, which causes a range of hemodynamic complications. Because low blood pH produces a release of internal vasopressin, further contributing to hypotension, vasopressin is sometimes initiated as an adjuvant to catecholamine in patients with septic shock, but no studies to date have evaluated the clinical effectiveness of vasopressin based on arterial pH. To further explore this issue, researchers reviewed the electronic health records for 1,350 patients with septic shock admitted to a medical, surgical or mixed medical/surgical ICU in one of eight hospitals in the Cleveland Clinic Health System between January 2012 and November 2017. All patients were severely ill, with arterial pH levels of 7.28±0.13, Sequential Organ Failure Assessment (SOFA) score of 14.1±3.5, lactate levels of 5.6±4.6 mmol/L and norepinephrine-equivalent catecholamine doses at 32.3±25.4 mcg per minute (Crit Care Explor 2022;4[2]:e0634). Acidemia was present in 85% of patients. When patients were categorized to pH groups (arterial pH ≤7.19, 7.20-7.29, 7.30-7.39 and ≥7.40), those in the lower pH groups were more severely ill. Patients in the lower pH groups also received higher initial vasopressin doses. The researchers found that, as arterial pH decreased, the odds of hemodynamic response to vasopressin also decreased (for each 0.1 unit, arterial pH <7.40; response odds ratio, 0.72; 95% CI, 0.66-0.79; P<0.01). Even after adjusting for lactate and SOFA score, lower arterial pH was independently

associated with lower odds of hemodynamic response to vasopressin. Lower arterial pH at vasopressin initiation also was associated with a subsequent increase in catecholamine dose and less pronounced improvement in the ratio of mean arterial pressure to norepinephrine-equivalent catecholamine dose. Patients in the lower pH groups also had higher 28-day mortality and fewer days alive and free from the ICU, vasoactive medications, and renal replacement therapy. “Similar to other vasopressors, the clinical effectiveness of vasopressin appears to be impaired in the setting of severe academia,” the researchers concluded.

‘We Still Don’t Have Great Data’ “There’s a [common] school of thought ... that the efficacy of vasopressin as a vasopressor is pH-independent,” said Alexander Flannery, PharmD, PhD, BCCCP, BCPS, an assistant professor of pharmacy at the University of Kentucky College of Pharmacy, in Lexington. “This study clearly suggests that, as with catecholamines, pH can impact vasopressin response as well. The challenge is that if you’re escalating your norepinephrine, there are very few other non-catecholamine drugs you can add as an adjunct. It’s either vasopressin or angiotensin II at this point, and we don’t have great data to inform us on which one is better at that juncture.” Dr. Flannery reported a financial relationship with La Jolla Pharmaceutical Co.

norepinephrine at the time of vasopressin initiation was 29.5 mcg per minute (SD, 19.7 mcg per minute). The mean starting dose of vasopressin was 0.04 units per minute (SD, 0.03 units per minute), the mean maintenance dose was 0.037 units per minute (SD, 0.005 units per minute), and vasopressin was continued for a mean of 49.1 hours, again with wide variation (SD, 65.2 hours). There also was disparity in when providers chose to discontinue vasopressin, with the agent stopped prior to norepinephrine in 49 patients. After discontinuation, 60 hypotensive events occurred, and 41 of them took place when vasopressin was discontinued before norepinephrine. However, these episodes were “largely transient in nature and often required no additional vasopressor support,” Dr. Patel’s team noted.

Sparing Norepinephrine The data generally supported the value of vasopressin in reducing the need for more norepinephrine, showing an overall mean reduction of 2.8 mcg per minute (SD, 14.4 mcg per minute) in norepinephrine once vasopressin was initiated. Roughly onethird of patients did not require more norepinephrine to maintain target MAP once vasopressin was discontinued; 13 patients had their norepinephrine dose decreased by a mean of 4.5 mcg per minute (SD, 4.3 mcg per minute) after vasopressin discontinuation; and 14 patients had norepinephrine and vasopressin stopped simultaneously. Eighteen patients required a mean of 4.3 mcg per minute increase in norepinephrine (SD, 2.9 mcg per minute) after vasopressin was discontinued, and 19 patients had treatment—not just norepinephrine and vasopressin—discontinued. Because of the retrospective design of their study and the variability in nursing practices, Dr. Patel’s team could not draw conclusions about the clinical impact of any specific vasopressin treatment regimen. Study design limitations like these mean the merits of a given vasopressin administration approach will continue to be debated for the time being, Dr. Doyno noted. However, she added: “Despite not having a gold standard dosing recommendation due to somewhat weak and conflicting literature, vasopressin continues to have a role within clinical practice in the ICU.” The sources reported no relevant financial disclosures.

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16 Policy

Pharmacy Practice News • June 2022

Oncology

Oncology Infusion Moving From the Hospital to Home By Gina Shaw

Boston—“If your institution, department or program does not have a home infusion setup for your oncology patients, you need to start working on it.” That was the message from Laure DuBois, PharmD, BCOP, pharmacy clinical coordinator at the University of Kansas Medical Center, in Kansas City, discussing the increasing trend toward site-of-care management at the 2022 annual meeting of the Hematology/ Oncology Pharmacy Association. “We first observed this with Aetna wanting to transfer patients on PD-L1 [programmed death ligand-1] inhibitors to home infusion by self-injection or the physician’s office,” Dr. DuBois said. “These policies are increasingly in place for many supportive care medications, as well as some targeted therapies.” Dr. DuBois said their hospital leaders were convinced to start a home infusion program when they were shown that they could keep and treat patients rather than send them to nationwide home infusion companies. “You can start by targeting easier supportive agents, like denosumab [Prolia, Amgen], IVIG [IV immune globulin], antibiotics and leuprolide, and then consider moving to treatments like rituximab [Rituxan, Genentech/Biogen], eculizumab [Soliris, Alexion] and pembrolizumab [Keytruda, Merck].” A crucial step is integrating a new home infusion program into the electronic

health record (EHR), she said. “At first, we had problems. Epic is our EHR and does not have a good platform for home infusion, so we started with a separate electronic ordering system. The doctors then couldn’t tell if the orders they had sent to home infusion were being fulfilled, so I hit the brakes and built home infusion as its own department in our EHR. The doctors are now able to use these order sets, make supportive care plans and treatment plans for home infusion, and then release the prescription to the home infusion pharmacy, after which they can see everything that happens.” Dr. DuBois and her team then created advanced order groups in the EHR. “The physician could then select what medications they were prescribing a patient for home infusion and add them into the plan,” she said. “We also set up takehome prescriptions for an emergency kit to be kept at home, including all possible medications needed for line care and reactions. They were filled and left at the patient’s house during the first infusion.” Dr. DuBois reported no relevant financial disclosures.

5 Steps for Launching a Home Infusion Program Reach out to the patient. The home infusion department should call the patient the day after a home therapy is supposed to be administered. “If the patient says they haven’t yet administered their pegfilgrastim, I’ll sit on the phone with them until they have,” said Laure DuBois, PharmD, BCOP, pharmacy clinical coordinator at UKMC, in Kansas City.

Decouple treatments from physician visits by 24 to 48 hours. This can be helpful in cases where a first home infusion of pembrolizumab is set up for the afternoon following a morning physician visit, but the physician decides to hold therapy after the visit. “Now we allow at least 48 hours from physician visit to infusion to allow for dose changes and held therapy,” Dr. DuBois said.

Be ready for weight-based dosing. “With a drug like trastuzumab [Herceptin, Roche], for example, we are comfortable with the patient doing a weight check at home, and the pharmacist asks them for their recorded weight before filling the prescription,” she said.

Prioritize patient comfort.

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“We have established a warm handoff process from the hospital-based infusion nurse to the home nurse during the hospital visit, where the home nurse meets the patient and explains what the home infusion process will look like,” Dr. DuBois said. “Because safety checks in the hospital setting aren’t always done in the patient’s room, they may not have seen them before. So, when the home nurse calls the hospital pharmacist to do that check, the patient may be concerned that it’s because something is wrong or they aren’t sure what they’re doing. We now make sure to educate the patient that these are the same safety checks we always do.”

Fight for exceptions to site-of-care restrictions. “With some of our new IVIG patients, we have gotten a site-of-care denial for hospital infusion right away,” Dr. DuBois said. “We obviously don’t like to have the first dose in the home due to the possibility of unexpected reactions, so we will fight for a one-time exception to make sure they will tolerate the drug before sending it to the home.”

Policy 17

Pharmacy Practice News • June 2022

Reimbursement Matters

Proposed Payment Rules for FY 2023 M

ultiple sets of payment rules that operate on a fiscal year (FY) beginning Oct. 1, 2022, have been released this spring, affecting both inpatient and outpatient sites of care. Now is the time for your revenue cycle team to review the changes and be prepared to make any needed changes to your billing system to ensure compliance and maximum reimbursement. The complete rules are open for your facilities’ comments until a variety of dates in June, before possible revision and final release. Keep in mind that diagnosisrelated group (DRG) payments remain, and clear, concise and accurate documentation is the driving factor for appropriate International Classification of Diseases, 10th Revision (ICD-10) code assignment and subsequent payment. The Centers for Medicare & Medicaid Services (CMS) has proposed 1,495 changes (new or revised) to ICD-10 codes effective on the October go-live date. How will you incorporate these into your electronic health record documentation? Do you know which ones affect prior authorizations? Is your computerized prescriber order entry file build in need of an overhaul to accommodate these new codes? For more information on the ICD-10 code changes, see CMS’s MLN Matters Number: MM12606 (go.cms.gov/3ypgzgS). Also know that the Outpatient Prospective Payment System (OPPS)/Ambulatory Payment Classification and Physician Fee Schedule rule for outpatient rule sets are on a calendar year beginning Jan. 1 and are expected early summer. Here are some additional key changes to keep an eye on:

IPPS, LTCH FY 2023 Proposed Payment Rules Proposed CMS rules for the FY 2023 Inpatient Prospective Payment System (IPPS) and Long-Term Care Hospital (LTCH) Prospective Payment System (PPS) are critical for your team to heed. These rules cover hospitals, critical access hospitals (CAHs) and longterm care facilities. CMS proposed a $1.6 billion increase to payments, which represents a 3.2% increase. With a focus on holding hospitals accountable for improving health outcomes, particularly for disadvantaged communities and maternal care patients, the increased payments add health equity and maternal health initiatives with a new maternal hospital designation, “birthing friendly hospitals” (October 2023). This designation is designed to help patients choose providers with a proven track record of delivering high-quality maternity care. These facilities must provide maternity services, implement recommended

patient safety practices, enroll in a perinatal quality improvement collaborative initiative, and track their low-risk cesarean deliveries and cases with severe obstetric complications as quality measures. (Note, however, that there haven’t been any changes to the 767 Medicare Severity DRGs in this category.) Several other updates under the IPPS and LTCH banner need to be heeded: COVID-19 Updates

There are several updates to watch for that have been made in response to the ongoing pandemic: 1. Payment adjustments have been issued for domestically sourced supplies such as N95 respirators from domestic manufacturers. These changes might also apply to OPPS payments. 2. Hospitals will be required to continue reporting COVID-19 and flu data until April 30, 2024. 3. Disproportionate share hospitals will lose about $654 million in uncompensated care payments. 4. The hospital readmissions reduction program, which was suppressed during the pandemic, will resume in FY 2024. This program tracks and penalizes hospitals for 30-day readmissions after pneumonia hospitalization. IPPS Quality Reporting Program

This initiative reduces payment to hospitals that fail to meet program requirements. The proposed rule adds 10 new measures, including one that assesses a hospital’s commitment to equity, one on opioid-related adverse events and one that captures screening of social determinants of health. Graduate medical education policies also are addressed, including a proposal to increase flexibility to rural hospitals that participate in a rural track program. In addition, it includes a proposal regarding the treatment of Medicaid Section 1115 demonstration days in the Medicaid fraction that is used in the calculation of Medicare disproportionate share hospital payments. Enhancements to the hospital and CAH conditions of participation for infection prevention and control and antibiotic stewardship programs are in the form of revisions that would require hospitals and CAHs, after the conclusion of the current COVID-19 public health emergency, to continue COVID-19 and seasonal influenza reporting, and would establish new reporting requirements for future declared public health emergencies related to a specific infectious disease or pathogen. Fact sheet: go.cms.gov/3L0Px1I Proposed rule: bit.ly/3MqqTcl

LTCH FY 2023

CMS increased aggregate payments by approximately $25 million relative to FY 2022. This includes an increase for both types of LTCH cases: higheracuity cases that are paid the standard LTCH PPS rate (+$18 million) and the remaining lower-acuity cases (28% 28% of all cases) that are paid a siteeneutral rate (+$8 million). Based on n its expectation for the continued d reduction of COVID-19 hospitalizaations, the agency proposes to return n to using the most recent data available— ble— FY 2021 claims and FY 2020 cost report data—to set payment rates, with certain proposed modifications. Proposed rule: bit.ly/3smltqQ Skilled Nursing Facility Proposed Rule

CMS proposes to reduce skilled nursing facility (SNF) payments by $330 million. It also proposed several changes to ICD-10 code mappings and coding guidelines, and has requested stakeholder feedback on the criteria for coding infection isolation. Feedback is sought on the impact of direct care staffing

“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

requirements and on establishing minimum staffing requirements for longterm care facilities. A new quality measure for the SNF Quality Reporting Program would assess the rate of influenza vaccination coverage among healthcare personnel. Proposed rule: bit.ly/3FrGWnN

More on the Web For more important payment updates, including those affecting hospice payment policies and Medicare Advantage and Part D, see expanded version on www.pharmacypracticenews.com.

18 Operations & Management

Pharmacy Practice News • June 2022

Finance

Leaning Into Drug Waste

10,00O 90,000

continued from page 1

one machine are moved to locations where they might be used prior to expiration. • Set PAR levels according to monthly analyses of usage. The pharmacy also now asks for high-cost unused medications in patient care areas to be returned to the pharmacy at the end of each day for possible redistribution and reuse. When it came to changing their IV room practices, they decided to compound remdesivir and vasopressin in batches only during surges of COVID-19. Importantly, Dr. DePol said, they introduced daily, weekly and monthly standard work and audit activities into the workflow with the aim of continuously improving and informing the interventions they implemented. With these efforts, the team far exceeded its 10% waste reduction goal, seeing a 25% and 35% savings in drug waste in the first and second fiscal quarters of 2021, compared with the same periods in 2020 (Figure), Dr. DePol reported. There was a slight increase in waste in the third quarter of 2021, caused by a COVID-19 surge, during which more higher-cost medications were used, with waste of “even a few of

‘In the IV room, we had been doing lots of batching and, in some cases, lots of that was expiring. That was particularly true for remdesivir and vasopressin, which we were using more of during COVID-19 surges, but not much of during other times.’ —Katie DePol, PharmD, MS “One thing we discovered when we looked at these points in the flow of medication was that par levels were being set based on outdated information,” Dr. DePol said. “Another thing we found was that in the IV room, we had been doing lots of batching and, in some cases, lots of that was expiring. That was particularly true for remdesivir and vasopressin, which we were using more of during COVID-19 surges, but not much of during other times.” Based on their findings, the pharmacy team took the following steps: • Load IV carts every six hours instead of every 12 hours. This strategy reduced the amount of discontinued doses prepared. • Rotate stock between ADCs. This step ensured unused medications in

these drugs” increasing the overall cost by a high percentage. Despite the third-quarter increase, the average monthly cost of drug waste fell from an estimated $29,142 in 2020 to $23,383 in 2021, resulting in an annual $70,000 savings in drug waste in 2021, Dr. DePol said. “Some of the waste is out of our control,” she noted. “For example, [when] physicians order medications, the medication is spiked and hung but is then discontinued, so the dose is never administered. There are also high-cost drugs that we have to carry, but they are rarely used and oftentimes they expire.” Reflecting on the advantages of using Lean methodologies to control waste, Dr. DePol said she appreciates that it was an approach that included

70,000 Savings ($)

reactive, and monitoring and making adjustments according to our monthly needs,” said Katie DePol, PharmD, MS, a pharmacy operations administrative specialist at the hospital. Dr. DePol shared details of her team’s approach at the ASHP 2021 Midyear Clinical Meeting and Exhibition, held virtually. In late 2020, Dr. Depol and her colleagues set out to alleviate the financial and clinical impact of “an unabated rise in drug cost, as well as never-ending drug shortages,” aiming to reduce unnecessary drug waste by 10%. To do so, they employed three Lean management methodologies: 1. Value-Stream mapping, in which the movement of products—in this case, medications—is scrupulously mapped out in graphic form; 2. Standardized work, in which each step in a task—for example, pharmacy IV compounding—is detailed; and 3. Plan Do Check Act (PDCA) cycle, an iterative method for continuous process improvement. The team found a substantial amount of drug waste could be traced to three points in the medication management process: ADCs (Pyxis MedStation, BD), medication carousels (Pyxis Pharmogistics, BD) and IV drug compounding (DoseEdge, Baxter).

84,058.75

83,678.49

82,061.88 77,792.42

80,000 63,542.59

60,000

53,505.70

50,000 40,000 30,000 20,000 10,000 0 Qtr 1

Qtr 2 2020

Qtr 3

2021

Figure. Total waste.

“engaging staff in the auditing process and asking them to generate ideas for improvement. That not only helped create more robust processes, but also left staff feeling more invested and willing to buy into changes to their workflow.” Using the PDCA cycle each month and sharing data on waste with staff has continued to keep them engaged, she added. One takeaway lesson Dr. DePol learned from the project is that “it’s easier to tackle a problem if you’re looking ahead.” Indeed, “being proactive and addressing waste before it happens is much more effective than waiting until after the fact to determine what you could have done differently.”

Targeting OR Operations There are some principles in developing waste reduction strategies that apply across the board, as Dawn Tsang, PharmD, a clinical pharmacist in emergency medicine at Tampa General Hospital, in Florida, told Pharmacy Practice News. Dr. Tsang, who was not involved with Dr. DePol’s presentation, led an initiative to reduce drug waste at her hospital, in the operating room (J Pharm Pract 2020;33[6]:827-831). Although that setting has “a very different model for medication use,” and she did not formally use Lean practices, “collaboration, in

our case with nurse anesthetists, is really important in reducing waste.” Dr. Tsang and her team found OR staff were bringing medications that needed to be refrigerated into the OR in case they needed them, and some of these agents remained at room temperature for too long and had to be discarded. By placing refrigerators in each OR with the most-used medications in that particular room—which Dr. Tsang and her team identified through observation and staff feedback—they reduced the amount of waste by an estimated $45,000 annually. In a separate, unpublished emergency room focused intervention, Dr. Tsang’s team placed “send-back bins” in each of the health system’s ERs, asking nurses to put unused medications in the container throughout the day. Those unused medications were sent back to the pharmacy for redistribution elsewhere in the hospital. According to Dr. Tsang, that initiative highlighted another cornerstone of waste reduction efforts, whether in the OR, emergency department or any other patient care area: “The faster you get a drug back to the pharmacy, the less waste you produce.” The sources reported no relevant financial disclosures.

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Preventing NMBA Errors continued from page 1

the medication. Ms. Vaught, a “help-all” nurse in the neuro-ICU, was summoned to administer the sedative midazolam (commonly referred to by its discontinued brand name, Versed). Ms. Vaught typed the two letters “VE” into the radiology automated dispensing cabinet (ADC), which brought up the paralytic vecuronium. Failing to realize that this was the wrong drug, Ms. Vaught initiated an override and administered the medication without noticing the warning label on the drug’s cap. She then left Ms. Murphey in the radiology holding area and went to the emergency department (ED), where she had been headed with a trainee nurse to conduct a swallowing study before being called in for this task. Ms. Murphey was found unresponsive by a transport technician about 30 minutes later, and died the next day after being withdrawn from life support. Ms. Vaught was immediately forthcoming and transparent about her errors

consider policies on the management of paralytics such as vecuronium. Specific safety measures (box) should be the goal, Mr. Cohen stressed. The “five rights”—right patient, right drug, right dose, right route and right time—is not about blaming individuals, Mr. Cohen said. “A tragedy like this is not all up to one nurse, and yet the jury heard that again and again. The five rights are goals, not procedural guidance. Many errors, including lethal errors, have occurred in situations where the nurse thought they followed the five rights. Without adequate systems in place, we’re going to continue to see this.” “Just culture is the right framework at the end of the day,” Charlene Hope, PharmD, the chief pharmacy quality and medication safety officer at the University of Chicago Medicine, said in an interview with Pharmacy Practice News. “No matter how you look at the scenario and the nurse’s errors, it did not warrant the

‘From a place of personal accountability and commitment to system improvement, RaDonda’s conduct in the aftermath of this event is what the patient safety community has longed for and spent two-and-a-half decades nurturing.’ —Barbara Olson, MS, RN and the sequence of events that resulted in Ms. Murphey’s death, noted Barbara Olson, MS, RN, a senior advisor to the Just Culture Company. “It is important to recognize that RaDonda Vaught told what she knew, as soon as she knew it, to any stakeholder for any purpose, in hopes that understanding actions, her state of mind, her priorities, her omissions and flaws could help her patient or any other,” Ms. Olson said. “From a place of personal accountability and commitment to system improvement, RaDonda’s conduct in the aftermath of this event is what the patient safety community has longed for and spent two-and-a-half decades nurturing.” And the information that Ms. Vaught provided revealed systematic flaws that other hospitals might recognize in their own practices, Mr. Cohen said. “With neuromuscular blockers, many hospitals have been paralyzed by mistakes.” He urged hospitals and health systems to convene a meeting of key medication safety and systems stakeholders, including their pharmacy and therapeutics committees, physicians, nurses and pharmacists. The goal, he noted, should be mutldisciplinary collaboration to

response that occurred, involving a felony prosecution. This could have been handled with a root cause analysis process, with Vanderbilt reporting to CMS [the Centers for Medicare & Medicaid Services], with the organization then doing all the changes that would be required, such as reviewing their ADCs and storage and updating their policies and procedures.” While Dr. Hope praised ISMP’s recommendations, she noted that some might not be feasible in certain institutions. For example, she said, paralytics are sometimes needed in areas where they might not be expected. “In debriefings of codeblue events, we’ve found that they can take place in weird areas, and it’s those places that tend to have worse outcomes. That’s when the minutes really do make a difference,” she said. “Radiology is a perfect example. It’s often tucked away in a not highly accessible area, so to have a pharmacy technician running a paralytic to an area they don’t frequent, when minutes really count, that’s a risk.” Dr. Hope noted that UChicago Medicine requires a two-person check for the administration of paralytics. “That should be a minimum,” she said. “We require an independent double check,

8 Safety Measures From ISMP 1. Retire discontinued brand names. “The brand name Versed was discontinued in 2003, and related errors have happened when ‘Versed’ was typed in on cabinet override,” said Mike Cohen, RPh, MS, the president emeritus of the Institute for Safe Medication Practices. 2. Require five letters to be typed into the ADC when an override is used. “You need more letters than just two,” Mr. Cohen said. “We’re probably selecting for drug errors at a rate that exceeds the handwriting problem we had in the past.” He cited a recent error report received by ISMP in which ceftriaxone (Rocephin, Roche) was confused with rocuronium, another neuromuscular blocker. 3. Eliminate neuromuscular blockers where not routinely needed. Outside the ICU, ED and perioperative settings, provide a sealed box, clear plastic zip bags or a rapid sequence intubation kit. 4. Enable an ADC block load feature where available. This strategy can prevent users from inappropriately stocking the cabinet. 5. Build interactive ADC warnings. One example—“causes respiratory arrest— patient must be intubated to receive this medication!”—requires the user to enter or select the purpose of medication removal (“other” should not be an option), and verify that the patient is or will be manually or mechanically ventilated. 6. Standardize processes. In procedural areas, including radiology, for example, establish a standard process for patients who require sedation that starts with an oral anxiolytic as the medication of choice. 7. Include patient monitoring requirements. This should be done both during and after drug administration, approved by the anesthesia department, to standardize the care of patients who require IV sedation. 8. Take another look at overrides. This should include at least two key steps: taking a global look at all override policies for any needed clarifications, and carefully managing specific override lists.

primarily for IV drip in our ICU.” After the Vanderbilt case, UChicago Medicine also conducted a major overhaul of its override list and established new criteria. To add a product to the override list, it must meet one of four criteria: 1. The product is an antidote. 2. The product is a life-sustaining medication. 3. The time delay equivalent to the average pharmacy processing time may result in additional monitoring or intervention to preclude harm. “An example is dextrose 50%, which is used when a patient has low blood sugar,” Dr. Hope said. “If we order that medication stat but we know we won’t be able to get the drug to the nurse within 30 minutes, that will require additional monitoring and nursing to stay at the bedside.” 4. An initial dose of the product is urgently

needed for comfort measures such as acute pain, nausea or vomiting. “That last criterion is used very judiciously and sparingly,” Dr. Hope said. “One of the things we look at is the risk potential for the drug. For example, IV famotidine for nausea does not carry a high-risk profile in terms of adverse drug reactions, and we don’t want a patient waiting 30 minutes or an hour for a pharmacist to approve it, so that could go on the override list.” Previously, each nursing unit’s Omnicell had its own override list because there wasn’t a formalized process for review, Dr. Hope said. “A nurse manager would email a pharmacy manager, and the drug would go on the list. Now, we have one hospital-wide override list.” The sources reported no relevant financial disclosures.

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More Lessons Learned From RaDonda Vaught Case Myungsun (Sunny) Ro, PharmD, MS, FISMP 2021-2222 ISMP International Medication Safety Management Fellow

Emily B. Holcomb, PharmD, MBA, BCPS 2021-2022 ISMP Safe Medication Management Fellow

edication errors involving potentially fatal neuromuscular blocking agents (NMBAs) can occur, not only during removal from the automated dispensing cabinet (ADC) but also throughout the entire medication-use process across multiple interdisciplinary teams. As the overarching goal of error reporting is to learn from the error and minimize the potential for a future recurrence, there are many safety lessons to take away from the RaDonda Vaught case. Healthcare practitioners, medication and patient safety officers, and administrators can assess their current practices relating to highalert medications such as NMBAs, use

during and after administration as well as an automatic discontinuation of these agents in the electronic health record (EHR) after the patient is extubated. Orders for NMBAs outside of the operating room or procedural areas should be limited to an intubation protocol and include instructions to maintain a specific level of paralysis while the patient is ventilated. In addition, if an NMBA is prescribed for a patient located in a care setting outside of the perioperative areas, for example, on a medical floor where patients are not typically ventilated, build EHR systems with computerized cross-checking of the correct patient and location.

of technology, and staff education to bridge gaps in protocols, initiate conversations with interdisciplinary safety teams, and monitor effectiveness for continuous improvement.

Outline Specific Medications And Strategies for ADC Overrides

Sequester and Safely Store NMBAs Outside of perioperative care settings where they are routinely used, access to NMBAs should be either eliminated entirely or limited to a sealed box or a rapid sequence intubation kit. If allowed by the ADC, block the load feature for NMBAs to prevent users from inappropriately stocking the cabinets without independent double check or approval by the administrator. Lock-lidded pockets also can be used to contain the highalert medication if individual vials must be stored in the ADC.

Standardize NMBA Prescriptions When prescribing NMBAs, eliminate ambiguous instructions, such as “use as needed for agitation,” and standardize order sets to require ventilation support

The override function of the ADC allows for dispensing of medications that may not be correctly prescribed, verified by a pharmacist, or intended for the patient. Institutions are recommended to limit the use of the ADC override function to select only cases and medications that require immediate removal from the ADC and bypass verification by pharmacy. Regardless of an ADC override, every medication dispensed from the ADC should require an associated electronic, print, or telephone order. Additional strategies for an ADC override include a distraction-free environment for staff members to focus on specific tasks. The number of ADC overrides and list of medications most frequently overridden should be monitored and reviewed periodically by administrators and/or (medication) safety offices to verify the appropriateness of use, transcription of orders, and documentation of administration.

ADCs should be profiled as much as possible, meaning medication access should be limited to patient-specific medication profiles that have been reviewed, verified, and deemed appropriate by pharmacy. Profiled ADCs allow practitioners to obtain medications that have been checked by pharmacy and encourage the restriction of ADC overrides to only the emergency situations that have been approved per the institutional protocols.

Promote Safe Search And Selection of Medications In the ADC The Institute for Safe Medication Practices (ISMP) Guidelines for the Safe Use of Automated Dispensing Cabinets recommends the entry of a minimum of the first 5 letters of the medication name. The guidelines support the selection of the correct medication from the list of populated medication names from the search field. However, some practitioners have suggested that the functionality should be applied to only a select number of medications that have high potential for error and harm. When minimum letter entry changes are made to the ADC, it is crucial to communicate effectively and broadly to inform all practitioners with access to ADCs. Some ADCs may allow for the search of medications by both generic and brand names. The simultaneous display of generic and brand names serves as another method to direct the practitioner to select the correct medication among those populated by the ADC search. Institutions are encouraged to check whether this functionality is available by their specific ADC vendor; the practice would lead to a reduction of medication errors.

Display Bold Warnings During Medication Storage and Removal In all areas where NMBAs are stored and dispensed, such as in the pharmacy or inside the ADCs on patient care units, prominent warning labels indicating respiratory paralysis and need for ventilation should be displayed (eg, “WARNING: CAUSES RESPIRATORY ARREST – PATIENT MUST BE VENTILATED”). The labels also should be placed inside the ADC pockets, drawers, and lids where they will be clearly visible upon opening. Affix the auxiliary warning directly on all vials and other containers with the purpose of distinguishing them from other lookalike medication vials and preventing the risk for mix-ups. The warning labels do not have to be limited to physical affixtures. An

electronic and interactive pop-up alert at the ADC that interrupts and requires acknowledgment by the user can be built into the system whenever an NMBA is to be removed from the ADC. (For example, “Patient must be intubated to receive this medication.”) Alternatively, an additional line can be provided to indicate the purpose of the intended medication in another effort to pause the user and confirm the correct patient, identity of the medication, and any other drug-related information needed for appropriate administration.

Other System-Level Strategies For Medication and Patient Safety Implement Barcode Scanning in All Patient Care Areas

The use of technology is a reliable method of detecting medication errors. There are many opportunities for mixups and other types of medication errors to occur, such as human error, look-alike and sound-alike medications, distractions, environmental factors, and more. Technology, more specifically barcoded medication administration (BCMA), limits the human potential for error in the medication-use process and dependably identifies the correct medication each time. ADCs can allow for the use of BCMA at multiple stages of medication use and alert the user whenever a wrong medication is selected. The implementation of BCMA is considered a highly reliable and effective safety strategy that has been named one of the newest ISMP Targeted Medication Safety Best Practices for Hospitals. Avoid Reconstitution of Sterile Compounds Using Flush Syringes

Institutions should purchase or dispense IV push medications in ready-toadminister forms whenever possible, especially when more than 1 medication is prepared in a single syringe or multiple and complex manipulations are needed. In cases when compounding or reconstitution of IV medications are required in patient care areas, flush syringes should never be used for any purpose other than their intended use of flushing the IV lines. Reconstitution of lyophilized powder using flush syringes and any other manipulation with the content of the flush syringe can lead to serious safety risks such as dose alteration, unlabeled or mislabeled syringes, contamination of sterile IV compounds, and deviation from manufacturer recommendations. Furthermore, the flush syringes are not approved by the FDA for reconstitution and administration of IV push medications. see VAUGHT LESSONS, page 22

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VAUGHT LESSONS continued from page 21

Clarify Institutional Protocols Surrounding Sedation Plans And High-Alert Medication Use

A standard process to address a patient’s claustrophobia, the institution’s preferred choice of therapy for sedation, and guidelines for patient monitoring should be established and communicated to practitioners across the relevant care units. In addition, medications commonly used for moderate sedation, such as IV midazolam, should be considered for inclusion in the institution-specific list of high-alert medications and paired with actionable risk-reduction strategies. Increase Awareness, Educate Staff, And Verify Competency

Institutions can only progress forward when they understand and accept the current state of safety practices at their own setting and learn from past errors. Educate staff about the risk for serious errors associated with high-alert medications and inappropriate use of ADCs such as non-protocolized use of the override function. Establish a formal training for practitioners involved in preparing, dispensing, and administering NMBAs, including the need for an adequate airway and respiratory support.1-3 There should be a clear delineation on which practitioners are allowed access to certain unit ADCs, and ongoing competency assessments should be periodically performed for all practitioners handling high-alert medications. Encourage an Open, Fair, Honest Error Reporting Culture

Error reporting in healthcare can identify local system hazards by identifying potential risks, actual errors, causes of errors, and error mitigation strategies. An open, transparent, and honest culture of error reporting values each healthcare member as a meaningful contributor toward patient safety and actively adopts interdisciplinary systemwide safety strategies to continuously learn from past errors. Institutions can only make positive strides toward safety if practitioners and administrators collaborate and reject a culture of punishment in which medication errors are veiled and blamed on the frontline workers. Blaming the individuals, rather than addressing the institution as a system, can have the insidious consequence of instilling fear and defensiveness that diminish the institution’s growth toward improvement. Conduct Timely and Comprehensive Risk Analyses

After a medication error has been identified and shown to cause patient

harm, the interdisciplinary safety committee should decide whether the event warrants a root cause analysis (RCA), a type of retrospective risk identification. The goal of an RCA is to identify the underlying factor(s) that led to the medication error and design strategies that will prevent a future recurrence. A thoroughly conducted RCA is timeand resource-intensive and ideally reserved for cases that have the biggest potential for harm, such as lessons learned, creation of robust safety action plans, and benchmarking of metrics or

goals to be continuously monitored for improvement. Another type of risk analysis, known as the failure mode and effects analysis (FMEA), is conducted proactively in anticipation of a potential safety risk or in response to process changes that may affect several steps in the medication-use process. The goal of an FMEA is to identify points of potential failure and what their consequences would be—before any error actually occurs. A well-conducted RCA or FMEA is timely, comprehensive, and

collaborated by well-rounded interdisciplinary team members who can map the precise steps involved in the medication-use process and detect (potential) errors and failure modes from various perspectives. Set Clear Expectations and Policies Regarding Human Error, At-Risk Behavior, and Reckless Behavior

When describing the reasons and ramifications for a medication error, Just Culture distinguishes between human error, at-risk behavior, and

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Medication Safety reckless behavior and outlines which behavior warrants disciplinary sanction versus acceptance or coaching. Human error includes slips, lapses, or mistakes that are committed unintentionally. At-risk behavior occurs when practitioners “drift” toward overlooking or diminishing the perceived risk for error over time. David Marx argues that at-risk behavior is a natural propensity and part of human nature. Human errors and at-risk behavior do not warrant a disciplinary sanction and should be differentiated from a

reckless behavior, in which the practitioner has consciously recognized the substantial risk harm and still chose to engage in the risky behavior. In Ms. Vaught’s case, the distinction between the terms used to identify the motive behind the fatal error was a particular area of contention, as proponents of Just Culture argued that Ms. Vaught engaged in unintended, not reckless, at-risk behavior. Institutions should carefully outline expectations for staff engaging at-risk versus reckless behaviors to identify which

cases need coaching and competency check versus disciplinary sanctions.

(ISMP). Paralyzed by mistakes – reassess the safety of neuromuscular blockers in your facility. ISMP Medication Safety Alert! Acute Care. 2016;21(12):1-6.

References 1. Institute for Safe Medication Practices (ISMP). Safety enhancements every hospital must consider in wake of another tragic neuromuscular blocker event. ISMP Medication Safety Alert! Acute Care. 2019;24(1):1-6. 2. Institute for Safe Medication Practices (ISMP). Challenges with requiring five characters during ADC drug searches via override. ISMP Medication Safety Alert! Acute Care. 2021;26(21):1-3. 3. Institute for Safe Medication Practices

More on the Web For a more detailed analysis of the fatal medication error that led to RaDonda Vaught’s conviction, and similar errors reported to ISMP over the years, see an expanded version of this review at www.pharmacypracticenews.com.