Pharmacy Practice News - June 2021

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The Best-Read Pharmacist’s News Source

pharmacypracticenews.com

CLINICAL

Reduced tofacitinib dose still safe, effective ............................

New guidelines issued for immune Rx in younger cancer patients .............................

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C 15

POLICY

Drafting a winning outpatient payment team ...................................

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Meeting tougher PPE standards a manageable task .........

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OPERATIONS & MGMT

Despite supply challenges, generics still a cost-saver ...........

Drug Diversion On Radar of the Joint Commission

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onsultants at Joint Commission Resources (JCR) are urging hospitals to double down on efforts to keep controlled substances safe. This is in light of a Joint Commission finding that 10% of hospitals surveyed in 2019 did not meet medication security standards, including those meant to prevent diversion.

Jeannell Mansur, RPh, PharmD, the principal consultant for medication management and safety at JCR and Joint Commission International, in Oakbrook Terrace, Ill., pointed to a range of medication management and storage gaps that leave controlled substances open to diversion in health systems.

Post-anesthesia care units (PACUs) are particularly vulnerable, Dr. Mansur pointed out. She said fentanyl and other narcotics often are administered intermittently to PACU patients in

$32 million in savings

See page 8.

Ensuring Medication Safety With TamperEvident Products See page 12.

EHR Strategy Boosts Generic Drug Utilization

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simple change in an electronic health record (EHR) default setting increased the generic prescription rate at Penn Medicine’s outpatient clinics to almost 99% from 75%, “where it had been stuck for years,” said Mitesh S. Patel, MD, MBA, the director of the the health system’s Nudge Unit.

Over 2.5 years, the nearly 25-percentage-point gain in the generic rate reduced unnecessary spending Continued on page 25

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Program yields sevenfold increase in Rx capture

Meds-to-Beds Launch Survives COVID-19 I

n retrospect, it may not have been the ideal time for the University of Alabama at Birmingham (UAB) Medical West Hospital to launch a new retail pharmacy and meds-to-beds (M2B) program, right on the cusp of the COVID-19 pandemic.

But the joint venture agreement between the 310-bed acute care hospital in Bessemer, Ala., and ShiftRx, the Newberg, Ore.–based ambulatory pharmacy finance and consulting company, was finalized in 2019. By the time the first wave of coronavirus infections hit the United States in late winter and early spring, the M2B program was several months in and the conversion of the former retail pharmacy was complete. At 1,800 square feet, the new pharmacy featured an advanced information technology system that was capable of handling the anticipated surge in discharge prescriptions fueled by M2B patients.

Continued on page 26

REVIEW ARTICLE

Top 10 Errors Related to COVID-19 Vaccination

Volume 48 • Number 6 • June 2021

Continued on page 18

Reaching Out to End Users Helps Stem IT Workarounds

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xperience has shown that every technology introduced in the hospital setting comes with a potential for workarounds, from alert overrides to avoidance of barcode scanning. However, medication safety experts say a robust strategy that incorporates direct observation, staff input about implementation and an empathic approach to understanding caregiver behavior can limit the occurrence of these risky actions.

“If we start with the understanding that humans are fallible, that we are going to make mistakes and that a system will not work for everyone, we can apply that knowledge to create better systems,” said Natasha

Nicol, PharmD, the director of global patient safety affairs for Cardinal Health.

Dr. Nicol said among other reasons for workarounds, staff may be responding to problems with a technology, a lack of confidence in its ability to improve patient safety and the additional time required to use the technology. “A lot of these workarounds happen because the system just doesn’t work for staff, and in many cases, they also have never been explained the safety benefits of the technology.”

Automated dispensing cabinets (ADCs) are particularly vulnerable to overrides or

Late-Breaker: HRSA, manufacturers square off on 340B restrictions.

See page 3.

Continued on page 4

Zero Tolerance for IV Errors

Would you skydive if 1 in every 10 parachutes were improperly packed?

Why are we tolerating errors in 1 out of 10 sterile compounded products?1 A 2020 ISMP survey found alarming gaps in sterile compounding practices across the United States.2 In fact, 74% of survey respondents acknowledged at least 1 sterile compounding error within the past 12 months.

Technology is no longer a “nice to have.” It’s imperative to reaching zero-error sterile compounding.

To learn how technology and automation can help eliminate errors, visit Omnicell.com/IVSolutions.

)O\QQ ( 3HDUVRQ 5( %DUNHU .1 2EVHUYDWLRQDO VWXG\ RI DFFXUDF\ LQ FRPSRXQGLQJ ,9 DGPL[WXUHV DW Ļ YH hospitals. Am J Health-Syst Pharm. 1997;54:904-912.

2. Institute for Safe Medication Practices (ISMP) website. ISMP Survey Provides Insights into Pharmacy Sterile Compounding Systems and Practices. October 22, 2020.

Up Front

Pharmacy Practice News • June 2021

3

Late-Breaker

HRSA, Drugmakers Square Off on 340B Restrictions T he Health Resources and Services Administration (HRSA), which oversees the federal 340B Drug Pricing Program, has directed six drug manufacturers to immediately resume providing 340B discounted pricing to contract pharmacies without restrictions, and warned that they face Civil Monetary Penalties (CMPs) if they do not do so immediately.

In letters sent May 17 to the manufacturers—AstraZeneca, Lilly USA, Novartis, Novo Nordisk, Sanofi and United Therapeutics—HRSA acting Administrator Diana Espinosa, MPP, wrote that each manufacturer “must immediately begin offering its covered outpatient drugs at the 340B ceiling price to covered entities through their contract pharmacy arrangements, regardless of whether they purchase through an inhouse pharmacy.” She also noted that they must comply with 340B statutory obligations and the 340B program’s CMP final rule, and “credit or refund all covered entities for overcharges that have resulted from (the) policy.”

Beginning in the summer of 2020, the six manufacturers had announced that they would no longer extend 340B discount pricing to contract pharmacies, claiming that the program had grown out of control and become a major source of revenue to for-profit pharmacies. Hospitals, Ryan White clinics and other safety net providers considered to be “covered

340B hospitals provide the majority of hospital care for Medicaid patients.

entities” under the 340B program fought back with HRSA and in the courts, arguing that the restrictions have caused them significant financial losses and adversely affected patient care, and that the manufacturers had no authority under the 340B statute to limit contract pharmacies.

Ms. Espinosa agreed, writing, “Section 340B(a)(1) of the Public Health Service (PHS) Act requires that manufacturers ‘shall ... offer each covered entity covered outpatient drugs for purchase at or below the applicable ceiling price if such drug is made available to any other purchaser at any price.’ This requirement is not qualified, restricted, or dependent on how the covered entity chooses to distribute the covered outpatient drugs.”

‘A Step in the Right Direction’ “This is definitely a step in the right direction, and we are pleased that HRSA has taken a stance and is expecting a corrective action plan from the manufacturers,” said Jessica Galens, PharmD, the assistant chief pharmacy officer, business services, at UCSF Medical Center, in San Francisco, who told Pharmacy Practice News earlier this year that the contract pharmacy restrictions had been detrimental to patient care (bit.ly/3eXsTdP).

ASHP praised the HRSA decision.

“HRSA’s aggressive action is necessary to stem manufacturer efforts to illegally undercut the 340B program,” said Tom Kraus, ASHP’s vice president of government relations, in a statement.

“This is exactly what we’ve been hoping HRSA would do,” said Barbara Straub Williams, JD, a principal at Powers Pyles Sutton & Verville, which represents Ryan White Clinics. But she acknowledged the letters are unlikely to produce overnight change. She noted that the manufacturers had until June 1 “to tell HRSA what their plan is to resume selling covered outpatient drugs to 340B covered entities that dispense medications through contract pharmacies. And the CMP process also affords them a right to a hearing and to object to any CMPs.” Manufacturers already have exercised that right. On May 20, Lilly filed a motion challenging HRSA’s decision and seeking an injunction and temporary restraining

order to stop the government from imposing penalties on the company. The motion is related to ongoing litigation based on a December decision by HRSA to finalize the long-awaited 340B Administrative Dispute Resolution (ADR) rule setting up a process for challenging the manufacturer’s restrictions, which was followed quickly by a decision from the Department of Health and Human Services that the restrictions were unlawful. AstraZeneca, Lilly and Sanofi all filed complaints challenging the Advisory Opinion. On March 30, 2021, the U.S. District Court for the Southern District of Indiana granted Lilly’s request for an injunction against the ADR, noting that HHS and HRSA had not reopened a required comment period before issuing the ADR rule.

“The litigation here stretches back to January, and the letter from HRSA earlier this week is an attempt to circumvent this legal process,” Lilly spokesperson Brad Jacklin told Pharmacy Practice News.

“Lilly has consistently and continually followed both the letter and the spirit of the 340B law. We have never stopped providing reduced-price medicine to 340B covered entities, making the HRSA action all the more concerning. Ensuring access to our medicines for all Americans, regardless of income or insurance status, is a top priority of Lilly, and we want to see a 340B program that works for the benefit of those facing affordability concerns.”

AstraZeneca and Sanofi filed similar emergency motions.

Other commercial stakeholders in health care support the HRSA decision. “The announcement by [HRSA] regarding the unilateral actions by

the manufacturers is another positive step among many to right the wrongs,” said Lisa Scholz, PharmD, the head of industry relations for Sentry Data Systems, which markets 340B compliance software. “We support our clients and have been assisting them with determining the financial impact that began in 2020 so that they may take action.”

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—Gina Shaw The sources reported no relevant financial disclosures beyond their stated employment.

Corrections

I

n the article, “Could a Mobile Cleanroom Be a Solution for Your Pharmacy?” (Pharmacy Practice News 2020;48[5]:4,10), a vendor was identified as Cleanroom Design LLC. After the issue was distributed, our source at Cleanroom Design informed us that they are developing mobile cleanrooms as part of a joint venture with another company, and the business name Mobile Cleanrooms LLC should have been used in the article.

The information has been updated in the online edition (bit.ly/3uitLOy).

T

he article, “Coalition Slams White Bagging Push by Payors” (Pharmacy Practice News 2020;48[5]:1,34), included the wrong photo of David Chen, BSPharm, the assistant vice president for pharmacy leadership and planning at ASHP. The correct photo is included here and has been David Chen, added to the online edition BSPharm (bit.ly/3hPMoab).

Source: 340BHealth.org

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4 Technology

Pharmacy Practice News • June 2021

Medication Safety

5 Workaround Triggers

Robust Strategy continued from page 1

workarounds, and often are due to endusers’ perceiving a new ADC process or alert as an unnecessary barrier to accessing medications in a timely manner. In such cases, nurses often will use the ADC’s bypass scanning function or withdraw multiple medications from the same drawer, Dr. Nicol said. Alert fatigue with smart infusion pumps and computerized physician order entry systems also can lead to alert overrides, she added.

When it comes to barcode medication administration (BCMA) systems, a 2008 study conducted at five hospitals in the United States found that nurses overrode BCMA alerts for 4.2% of patients and 10.3% of medications charted (J Am Med Inform Assoc 2008;15[4]:408-423).

“One big problem I’ve seen with BCMA systems that don’t work well—because of problems with the scanners, issues with the wristbands or with connectivity—is nurses placing a barcode somewhere other than the patient’s wrist, like the bed railing, the door, or the patient’s chart,” Dr. Nicol said. “When faced with

these cases, you need to find out why the workaround is happening.”

Prospective and Retrospective Risk Identification Proactively finding out why workarounds might occur is one part of an effective strategy for addressing the problem of medication use errors, acccording to Matt Grissinger, RPh, the director of error reporting programs at the Institute for Safe Medication Practices. One way to identify at-risk behaviors and prevent potential errors is by visiting nursing units and clinical departments, he said.

“It’s so important that pharmacy leaders and supervisors observe and speak with end users to see how they’re employing the technology and to ask if they have concerns with a workflow or a technology,” Mr. Grissinger said.

“Find out whether they feel they have to do workarounds for some reason or if they feel the technology isn’t working as they thought it would. Asking users these questions can help avoid

1. Problems with the technology 2. Inadequate staff education and training 3. Alert fatigue 4. Concern over delays in accessing stat medications 5. No mechanism for problem-solving with end users

errors, rather than waiting for something bad to happen.”

Performing a failure mode and effects analysis (FMEA) ahead of implementation also can help institutions identify where and how a process might fail and

Deadly Errors Drive Focus on Medication Safety

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atasha Nicol, PharmD, the director of global patient safety affairs at Cardinal Health, has come by her passion for medication safety honestly.

In 2001, working as a hospital pharmacist, she and a colleague were filling orders for 450 patients with a six-hour turnaround time. The situation, she said, was “a complete and utter disaster waiting to happen.”

When she received an order for potassium chloride for a 2-year-old patient, Dr. Nicol entered the order, but feeling rushed, she did not review the appropriateness of the dose.

She ended up dispensing an excessive amount of the agent, the patient suffered cardiac arrest and, after two hours of resuscitation attempts, died.

“I haven’t entered another order for a baby and I never will again,” Dr. Nicol said. “I’m even terrified to dose my own kids’ Tylenol, and they now weigh 120 pounds.”

Dr. Nicol found herself involved in another fatal error in 2003, when she was helping to roll out smart infusion pumps across the health system where she was working at the time.

“It was a big-bang rollout and we implemented the [smart pump] system everywhere at the same time,” she recalled.

“We did two weeks of training beforehand, so it was ‘just in time’ training. Still, everybody was able to ‘play’ with the pumps ahead of time and learn how to use them and how to program them. We made sure all the staff competencies were in place, and we did everything we needed to do.”

There was one oversight, however: a nurse who happened to be on vacation during those two weeks. The day the nurse returned to work, she was caring for a patient—who, incidentally, was her best friend’s mother—and because she was absent during training, she didn’t understand how the new pumps worked.

The nurse did what she thought was right in the way she programmed the pump, but ended up administering a large amount of meperidine to the patient in less than 15 minutes.

Tragically, the patient did not survive.

“We didn’t implement the technology correctly. We didn’t make sure we educated every single person. This nurse demonstrated what we consider to be an at-risk behavior, but she believed what she was doing was OK. We need

to try to absolutely prevent errors like these by making sure we implement new technologies with the ‘why’ behind them—and that ‘why’ is to improve safety for both our patients and our staff.”

Dr. Nicol said the first fatal error prompted her to focus on medication safety, and although the second error “was a blow to everyone, myself included, it didn’t diminish my resolve to improve safety; it once again ignited it.”

In the aftermath of the second incident, Dr. Nicol said she took time for “intense self-reflection.” Moreover, she and her colleagues spoke more openly about errors and harm, and about the need “to focus our strategies on understanding and accepting that humans are fallible and our systems needed to be designed with that in mind. We didn’t want anyone else to experience and feel the way that nurse and I did and continue to until this day.”

—D.W. Dr. Nicol reported no relevant financial disclosures other than her stated employment.

to assess the impact of different failures, he said. FMEA works best when it is applied to specific processes, such as prescriber order entry; BCMA nursing administration; use of smart pump libraries; or in evaluating the addition of new technologies, such as ADCs in a specific unit, a new IV compounding technology or interoperability functionality between electronic health records and infusion pumps, Mr. Grissinger noted.

“FMEA should be done in a multidisciplinary group where you can really take a close look at a workflow around the technology and identify risks proactively,” he said. “Look at all the steps in a process and identify what could go wrong or how a step can be worked around. Knowing this will allow you to put strategies in place to prevent such workarounds.”

Reiterating the importance of tackling workarounds in a multidisciplinary fashion, Mr. Grissinger said any work process changes are more likely to be complied with if they are implemented well, which requires involvement from front-line staff.

Fixing Unsafe Behaviors Not a Wise Use of Technology Drug safety expert Daniel Degnan, PharmD, an associate director of Professional Program Laboratories, Purdue University College of Pharmacy, in West Lafayette, Ind., agreed that getting the implementation of a new technology right is critical to reducing workarounds and errors.

“Many workarounds are due to poor understanding of workflow when the technology is implemented or because the technology is being used to ‘fix’ an unsafe behavior or practice, instead of redesigning the process,” Dr. Degnan see ROBUST STRATEGY, page 6

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6 Technology

Pharmacy Practice News • June 2021

Medication Safety

ROBUST STRATEGY continued from page 4

said. “As part of an implementation, we should anticipate what to do when the technology does not work the way the user expected it to.”

Once the technology is implemented, he said, medication safety experts can gain important insights into behaviors through structured observations of staff using the new technology.

“One of my favorite quotes about this comes from Yogi Berra, who said, ‘You

can observe a lot just by watching,’” Dr. Degnan commented.

Although FMEA and observation can help identify and prevent workarounds, analyzing errors when they do occur is critical part of a risk mitigation strategy, Mr. Grissinger said. Reading through device data reports is a good way to do this. “Data reports from a device can help you better understand workarounds, such as which types of alerts and medication classes are being overridden in smart pumps and order entry systems,” he said.

‘Find out whether [end users] feel they have to do workarounds for some reason or if … the technology isn’t working as they thought it would. [Such questions] can help avoid errors, rather than waiting for something bad to happen.’

—Matt Grissinger, RPh

A Just Culture

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Developing the right safety culture— a “just culture”—in an organization can be a cornerstone for safe medication use, Dr. Nicol said. When an error or a near miss occurs, individuals should be rewarded for reporting safety information rather than punished, she said.

“We cannot improve safety without creating a culture in which humans are recognized and accepted as fallible and in which we consider the possibility that the systems we’ve set up may not work well,” Dr. Nicol stressed. “Leaders and front-line staff need to have a sense of shared accountability in making sure systems are designed and used safely.”

Illustrating the importance of a just culture, Dr. Nicol recalled working to improve a client hospital’s medication safety processes. “I met with a nurse manager and asked her how many nurses were using barcode scanning, and she said they had 99% compliance with barcode scanning. I really didn’t believe that number.” Her suspicions proved to be well founded after she spoke with frontline nurses and found out that 37 nurses had been terminated in the previous two years for not using scanning for patients.

“The leadership felt they had dealt swiftly with a patient safety issue and fixed the problem, but it most likely led to underreporting of errors and continuation of a process that was not working for nurses,” Dr. Nicol said, noting that a major reason for noncompliance with BCMA use at the organization was that the wristbands were not scannable if wet, bent or torn.

Despite the challenge of addressing process and device workarounds, she said organizations should include it as a necessary part of ongoing hospital management.

“I like to tell people that safety is a journey, not a destination, and we are never done,” Dr. Nicol said. “As soon as we implement a system change, we introduce another chance for error, another chance for a workaround.”

—David Wild The sources reported no relevant financial disclosures. Portions of this article are based on presentations at the ASHP 2020 Midyear Clinical Meeting.

Clinical

Pharmacy Practice News • June 2021

7

Cardiology

Potassium-Sparing Agents Put a Rise in RAASis

N

ewer agents are reenergizing the treatment of hyperkalemia, a serious condition characterized by elevated serum potassium levels in patients with cardiovascular, renal and metabolic diseases, several experts noted.

This improvement in hyperkalemia management has yielded another key benefit: It has allowed the increased use of drugs for heart failure, such as renin–angiotensin–aldosterone system inhibitors (RAASis), which often have been avoided due to their tendency to raise potassium levels.

The newer agents include patiromer (Veltassa, Relypsa) and sodium zirconium cyclosilicate (Lokelma, AstraZeneca), which the FDA approved in 2015 and 2018, respectively. In clinical trials that led to their approval, both agents were shown to be safe and effective, with minimal adverse events and limited drug– drug interactions (JAMA 2015;314[2]:151161; N Engl J Med 2015;372[3]:211-221; Eur Heart J 2011;32[7]:820-828; JAMA 2014;312[21]:2223-2233; N Engl J Med 2015;372[3]:222-231).

Supporting RAASi Therapy Although RAASi medications are indicated for patients with heart failure and chronic kidney disease (CKD), up to 30% of patients on RAASi therapy develop hyperkalemia (Circulation 2008;118[16]:1609-1611). As a result, RAASi therapy often is modified or discontinued once a patient experiences a hyperkalemic event. In turn, this may lead to a greater threat of heart failure and cardiovascular-related death.

That downturn in RAASi prescribing has been documented in the literature, according to Darren W. Grabe, PharmD, the chair of the Department of Pharmacy Practice and an associate professor of pharmacy at Albany College of Pharmacy and Health Sciences, in New York.

“In a 2017 retrospective study of medical and pharmacy claims, evaluating the impact of hyperkalemia and use of RAASi dosing on costs and care, investigators found that the use of RAASi was below 50% in each of three cohorts: those with heart failure, those with CKD and those with both,” Dr. Grabe said. “Optimal dosing of RAASi in these patients—26.8% of them were receiving RAASi therapy—was associated with lower costs.”

A small study of patiromer in patients with heart failure underscores the drug’s value in supporting RAASi therapy.

Among 17 patients with heart failure who were prescribed patiromer, RAASi use increased 70.6% to 100%. Moreover, “average ejection fraction went from 27.6% pre-patiromer to 31% postpatiromer [J Am Coll Cardiol 2020;75(11

‘I believe we will see more and more patients who were formerly “intolerant” of RAASi inhibitors on therapeutic doses of these drugs.’

—Gates Colbert, MD

suppl 1):1098-1005],” Dr. Grabe said.

The question is now being studied in two larger trials: DIAMOND (ClinicalTrials.gov Identifier: NCT03888066), which is evaluating the use of patiromer to allow for continued use of optimal RAASi therapy in patients with heart failure, and PRIORITIZE HF (ClinicalTrials. gov Identifier: NCT03532009), which is evaluating the risks and benefits of see HYPERKALEMIA, page 17

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8 Clinical

Pharmacy Practice News • June 2021

Review Article

Top 10 Errors Related To COVID-19 Vaccination

Horsham, Pennsylvania

I

mmunization is one of the greatest public health achievements, but its continued success relies on the quality of the process, including how vaccines are stored, prescribed, dispensed, and administered. Many of the

underlying causes of vaccine-related errors are ongoing issues, so health care providers who plan to stock and/or administer COVID-19 vaccines should anticipate the types of errors that can and do happen and take the necessary steps to prepare and mitigate the risk for COVID-19 vaccine–related errors.

A recent analysis of more than 160 COVID-19– related event reports submitted to the Institute for Safe Medication Practices (ISMP) National Vaccine Errors Reporting Program (VERP) from December 14, 2020, through April 17, 2021, underscores that more needs to be done to reduce the risk for vaccination errors because they can lead to inadequate immunity, increased cost, and reduced confidence in the health care delivery system. The brief descriptions of commonly reported COVID-19 vaccine errors herein are meant to help health care providers anticipate risk during what is the largest vaccination effort in US history. Please refer to our recent review of COVID-19–related vaccination errors for additional information.1

1. Shoulder injury related to vaccine administration.

Shoulder injury related to vaccine administration (SIRVA) is inflammation and injury to the shoulder tendons, ligaments, or bursa triggered by the incorrect injection of a vaccine into the shoulder joint instead of the deltoid muscle. SIRVA occurs when health care workers do not correctly identify the deltoid muscle in the upper arm and instead inject the vaccine into and around the shoulder joint. During the COVID-19 vaccination campaign, some health care professionals have volunteered to administer vaccines since their scope of practice allows them to do so. However, they may not have been properly trained to give intramuscular (IM) vaccines into the deltoid.

Symptoms of SIRVA include persistent shoulder pain, weakness, and an inability to move the arm without pain. These symptoms develop within hours to a few days after receiving a vaccine and do not improve with over-the-counter pain medicines. Patients often are diagnosed with inflammatory shoulder injuries (eg, bursitis,

rotator cuff tears, frozen shoulder syndrome, or adhesive capsulitis).

The key to avoiding SIRVA is ensuring health care workers can correctly identify the deltoid muscle and are using the proper technique to give IM vaccines. This means health care workers must demonstrate they can determine the upper and lower borders of a safe IM injection zone. In addition, patients should be told to completely expose their shoulder when receiving an IM vaccine. It is best to have the patient remove their shirt, roll up their sleeve completely, or remove their arm from their sleeve.

2. Not checking/documenting administration in the immunization information system.

The Moderna and Pfizer/BioNTech COVID-19 vaccines require a second dose. Because these different COVID-19 vaccines are not interchangeable, a patient’s second dose must be from the same manufacturer as their first dose. In addition, the Pfizer/BioNTech vaccine doses should be separated by 21 days, whereas the Moderna vaccine doses are administered 28 days apart. The Fact Sheets for COVID-19 vaccines given emergency use authorization by the FDA require providers to accurately document the vaccine that a patient received for their first dose in the state or local Immunization Information System (IIS) or other designated system. Patients also are given a vaccination card that documents the vaccine type and date administered.

To help ensure patients receive the proper vaccine for the second dose, providers should check the vaccine card or IIS before administering the second dose. Repeat doses have been administered to patients at the wrong interval (days before the second dose was due). Some patients have even stated they needed a first dose, yet

when the provider checked the IIS, it documented they had received one already. So, the IIS should be checked even before the first dose.

Confirm that staff members involved in vaccination activities know how to search the vaccine registry, understand the information provided and its level of reliability, and know how to document immunizations in the registry. Current vaccination record cards provided by the government include spaces to document 2 doses of the Moderna and Pfizer/BioNTech vaccines, as well as a reminder to schedule the second dose. This could cause confusion for patients receiving the single-dose Janssen vaccine, but the CDC told us they are not considering updating the vaccination record card for the single-dose vaccine.

3. Wrong diluent.

Using the wrong diluent is another type of error that has been reported. Sterile water for injection has been used instead of 0.9% sodium chloride injection. The Pfizer/BioNTech COVID-19 vaccine requires mixing only with sterile 0.9% sodium chloride (normal saline, preservativefree). Bacteriostatic normal saline or any other diluent should never be used. In one reported case, a pharmacist noticed the error after several patients had already been injected, resulting in a need to call the patients back for a repeat injection. When preparing the Pfizer/BioNTech vaccine, require an independent double check of the dilution process. If it can be done within the time frame for vaccine stability at room temperature, have the pharmacy, or a team of practitioners under the direction of the pharmacy, dispense prefilled, labeled syringes of the vaccine for daily vaccination clinics.

4. Wrong diluent volume.

The Moderna COVID-19 vaccine does not require dilution, but the Pfizer/BioNTech vaccine does, leading to some dilution errors. The multiple-dose vial of the Pfizer/BioNTech vaccine contains a volume of 0.45 mL, supplied as a frozen concentrated suspension that does not contain preservative. Each vial must be thawed and diluted with 1.8 mL of 0.9% sodium chloride

Clinical 9

Pharmacy Practice News • June 2021

Review Article the patient pulling away during vaccination, but more often it is due to vaccine leakage during injection, often because of poor needle attachment to the syringe, premature retraction of a VanishPoint syringe needle, or leakage that we described recently with a Guangdong Haiou Medical Apparatus Company syringe.4 Before administration of any dose, check for a tight fit between the needle hub and the syringe and be familiar with the safety mechanisms of different syringes in use. Be sure to engage them immediately after administration.

9. Age-related events.

injection before doses are administered. If too much diluent is added to the Pfizer/BioNTech vial, doses may be ineffective; if too little diluent is used, doses may invoke stronger adverse effects.

A properly diluted Pfizer/BioNTech vaccine vial holds 2.25 mL and allows for at least 6 doses.

However, in some cases, due to lack of awareness that dilution is needed, there has been a failure to dilute the concentrated suspension at all. Since the IM dose is 0.3 mL and the concentrated liquid is only 0.45 mL, this type of error would be immediately identified upon attempted withdrawal of a second dose because there would not be enough volume remaining. In other cases, syringes filled with 1.8 mL of air have been used accidentally to dilute the vaccine. In some cases, an inadequate volume of diluent was added to the vial (1 mL), also resulting in patients receiving too much of the vaccine. There also have been cases in which too much diluent was added. In one such case, a nurse accidentally added 1.8 mL of diluent to the same vial twice.

5. Errors related to vaccine storage.

After thawing, the Moderna and Pfizer/BioNTech COVID-19 vaccines have been stored near each other in a refrigerator, then subsequently mixed up. To avoid mix-ups, do not store the Pfizer/ BioNTech and Moderna vaccines together in the refrigerator during or after thawing. Store them in separate locations or on separate shelves. In addition, do not place the vaccines close to any other medications. No serious or fatal events have been reported during the period of COVID-19 vaccine administration, but there have been previous reports of vaccines being mixed up in storage, including reports of vaccines being mixed up with insulin2 and neuromuscular blockers.3

6. Mix-ups with other medications during administration.

There have been errors in which an incorrect drug was administered instead of the intended vaccine. In one reported case, 2 patients accidentally were given an EPINEPHrine injection instead of the Moderna COVID-19 vaccine. At the vaccination site, predrawn syringes of epinephrine and

vaccine were in light-protective bags and, thinking both bags held vaccine doses, a nurse took syringes from the bag holding EPINEPHrine and accidentally administered EPINEPHrine to the patients. After the erroneous EPINEPHrine injection, one patient reported feeling tachycardic, but neither patient suffered any lasting or serious effects. COVID-19 vaccination sites should stock only EPINEPHrine autoinjectors rather than predrawn syringes of EPINEPHrine because the EPINEPHrine autoinjectors are visually different from predrawn vaccine syringes and, with training, are very easy to use in an emergency. Doses of EPINEPHrine and vaccine also should be kept in different storage locations but close enough to the vaccinators so they can be retrieved easily and rapidly as needed.

7. Administration of air in empty vaccine syringe.

We have received multiple reports of empty syringes used for diluting the Pfizer/BioNTech vaccine. This has been seen most often during mass vaccination programs, often during preparation of large numbers of syringes for injection of the dose of vaccine. The syringes are removed from their wrapper, all at the same time, and the syringe plunger is pulled back to 0.3 mL (Pfizer/ BioNTech) or 0.5 mL (Moderna or Janssen), depending on which vaccine is to be given. This is the amount of air that will be injected into the vaccine vial at the time of fluid withdrawal. This allows for equilibration of the pressure inside the vial after an equal volume of vaccine is withdrawn. However, the empty syringes often are placed near syringes that are prefilled with vaccine but not labeled. Just as these empty syringes have been used accidentally as diluent (see above), syringes filled with air also have been accidentally injected into patients instead of vaccine. Again, independent double checks and having pharmacy dispense prefilled, labeled syringes can help to prevent such errors.

8. Wrong dose.

Some individuals have received a dose lower than authorized. This is sometimes caused by

One of the most commonly reported COVID-19 vaccine errors is administration of a vaccine to a patient who is younger than the minimum age required in the EUA Fact Sheet, or younger than 18 years for the Moderna and Janssen vaccines or 12 years for the Pfizer/BioNTech vaccine. (On May 10, 2021, the FDA expanded the EUA for the Pfizer/BioNTech COVID-19 vaccine to include adolescents 12 through 15 years of age.) This error has happened most frequently because the vaccine provider did not ask age-related screening questions. In some cases, patients have presented a prescription for the vaccine from their physician.

For example, a 17-year-old at one clinic received the Moderna vaccine instead of the Pfizer/BioNTech vaccine, and a 15-year-old at another clinic inappropriately received the Moderna vaccine.

10. Vaccine competency.

Many errors, such as drawing up incorrect vaccine volume and SIRVA, often are due to competency issues. Be sure that staff screening patients and administering vaccines are educated about the storage, preparation, and administration of the COVID-19 vaccines, as well as the common types of errors that may occur, including those described above. Provide vaccinators with upto-date fact sheets for health care providers for the vaccine(s) being used, and verify their competency related to temperature monitoring, patient assessment before vaccination, age indications for each vaccine, proper dilution of the Pfizer/BioNTech vaccine, withdrawal of the correct dose, identification of the appropriate IM injection site, and proper syringe/needle disposal. In addition, be sure they provide patients with a fact sheet for recipients before vaccination. Finally, make certain they know how to treat anaphylaxis if it occurs.

References 1.

ISMP. Any new process poses a risk for errors: learning from 4 months of coronavirus disease 2019 (COVID-19) vaccinations. April 22, 2021. Accessed May 5, 2021. https://www.ismp.org/resources/any-new-processposes-risk-errors-learning-4-months-coronavirusdisease-2019-covid-19

2. ISMP. Fifty hospital employees given insulin instead of influenza vaccine. May 5, 2016. Accessed May 5, 2021. https://www.ismp.org/resources/fifty-hospital-employeesgiven-insulin-instead-influenza-vaccine 3. Hanson A, Shah N, Cohen MR. Serious errors with twocomponent vaccines risk harm and damage trust. August 25, 2020. Accessed May 5, 2021. https://uppsalareports. org/articles/serious-errors-with-two-component-vaccinesrisk-harm-and-damage-trust/ 4. ISMP. Problems with Guangdong Haiou syringes for COVID-19 vaccinations. ISMP Medication Safety Alert!

April 22, 2021;26(8).

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Pharmacy Practice News • June 2021

Anticoagulation

Tofacitinib Dose Cut Still Yields Positive Outcomes I

n July 2019, the FDA added a boxed warning to the package insert of tofacitinib (Xeljanz, Pfizer), cautioning about the risk for deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients treated with the drug’s 10-mg twice-daily dosage. The agency now requires that clinicians reduce the dosage to 5 mg twice daily as soon as possible to avoid these complications.

However, clinicians and patients with ulcerative colitis (UC) face uncertainty about the risk for relapse after deescalation and whether long-term treatment with tofacitinib increases the risk for DVT and PE. Three studies have found that up to 67% of patients who lose response after deescalation to the 5-mg twice-daily dosage can experience restored clinical and endoscopic remission after reescalation to the 10-mg dose. The results also showed that rates of DVT and PE did not increase over time.

Aline Charabaty, MD, the clinical director of the GI division and Inflammatory Bowel Diseases Center at Johns Hopkins School of Medicine’s Sibley Memorial Hospital, in Washington, D.C., said the findings cement the position of tofacitinib in the treatment armamentarium for UC. “It’s notable that the overall incidence of DVT and PE in patients on tofacitinib reported in this research was similar to the rate we’d expect to see in the general UC population,” said Dr. Charabaty, who was not involved with the studies. All three of the trials examined

data from OCTAVE Open, an ongoing open-label study including participants from three completed trials of induction and maintenance with tofacitinib. In one analysis, Gary Lichtenstein, MD, the director of the Inflammatory Bowel Disease Center at the Hospital of the University of Pennsylvania, in Philadelphia, and his colleagues examined 944 patients receiving 5 or 10 mg of tofacitinib two times daily (DDW Virtual 2020 abstract Tu1857). One subgroup of patients was in remission at the end of a previous 52-week, double-blind maintenance study and initiated open-label treatment at the 5-mg dose. All of the other participants began at the 10-mg dose.

According to Dr. Lichtenstein, the roughly 81% of participants who received the 10-mg twice-daily dosage did so for a median of approximately two years, while the remainder received the 5-mg twice-daily dosage for a median of more than three years.

Using data from all patients, including those who withdrew early or moved to another study, the researchers found that 58.9% and 33.5% of those in the 10- and 5-mg twice-daily groups, respectively, were in remission at 36 months.

Moreover, 64.6% and 37%, respectively, achieved mucosal healing at that time, and 66.9% and 40.2%, respectively,

experienced clinical response.

Four patients experienced PE and one patient experienced DVT, all in the group receiving 10 mg of tofacitinib.

Risk Narrowed to Patients With Other Factors The five cases of DVT and PE were scrutinized in a separate analysis by a team led by William Sandborn, MD, the chief of the Division of Gastroenterology and director of the IBD Center at the University of California, San Diego.

Dr. Sandborn and his colleagues found that all of the cases occurred in patients who had other risk factors for venous thrombosis, including a history of DVT, PE, other cardiovascular illness, a recent history of a long-haul flight, or use of other medications associated with cardiovascular events (DDW Virtual 2020 abstract 684).

When Dr. Sandborn’s team looked at all 1,157 patients with UC enrolled in four randomized, placebo-controlled placebo controlled

studies of tofacitinib, they found two cases each of DVT and PE in the induction and maintenance tofacitinib studies. These cases occurred in patients taking placebo at the time.

Preliminary six-month data from the ongoing randomized, double-blind, parallel-group RIVETING trial presented at the 2020 virtual United European Gastroenterology Week showed that most patients who were in stable remission on 10 mg of tofacitinib twice a day maintained remission after having their dose reduced to 5 mg twice a day (DDW Virtual 2020 abstract OP136).

In the study, eligible patients (n=140) had received tofacitinib 10 mg twice daily for at least two consecutive years and were in stable remission on this dose for at least six months before enrollment. They were randomly assigned in a 1:1 fashion to receive either 5 or 10 mg of tofacitinib two times daily. Efficacy was assessed at month 6, and safety was the study. examined throughout th In total, 777.1% and 90.0% of patients receiving 5 and 10 mg twice a day, respectively, were in remission based respectively modified Mayo score at month 6 on modifie (primary end point) (adjusted differ95% CI, 0.5%-25.0%). ence, 12.9%; 1 When the investigators analyzed Whe subgroups based on baseline sub endoscopic subscore and prior en failure of tumor necrosis facfa tor (TNF) inhibitor treatment, to the differences between the th ggroups ranged from 9.5% to 21.1%. The investigators also 2 found consistent differences fo in the secondary end points of remission and clinical response rem between the dose groups. Among betw patients who received 5 mg two patie daily, those with a baseline times d endoscopic subscore of 0 and those endoscop prior TNF inhibitor failure were without prio more likely to maintain remission than with a subscore of 1 and those patients wit TNF inhibitor failure. with prior T

Adverse E Events Rates of adverse events (AEs) and AEs were similar across dose serious AE There was one PE (in the group groups. The taking 10 mg twice daily). There were no DVT or death. cases of DV noted that UC is a known Dr. Sandborn Sandb risk factor for DVT and PE. He said despite the “low and stable DVT and PE rates” in UC patients receiving either 10 or placebo, “the FDA mg of tofacitinib tofac requires that tha we attempt to deescalate the dose to 5 mg BID, so we need to do it.”

Although deescalation to the 5-mg dose maintains efficacy in many patients, some lose response. However, as findings from another analysis of the

Clinical

Pharmacy Practice News • June 2021

11

Anticoagulation OCTAVE Open data showed, many of these individuals can regain response with reescalation to the 10-mg dose (abstract Tu1855).

Bruce Sands, MD, the chief of gastroenterology at the Icahn School of Medicine at Mount Sinai, in New York City, and his colleagues reported data from 59 patients who underwent deescalation after initial response with tofacitinib 10 mg twice daily, and then reescalation after loss of response with 5 mg two times daily. In an analysis of all patients, including those who withdrew from the study early and were assumed to have been nonresponders to therapy, they found that 40.7% experienced restored response, 39% had mucosal healing again, and 30.5% achieved remission after reescalation to the 10-mg twice-daily dosage.

When the investigators limited their analysis to patients who completed 36 months of the study, they found that 95.2%, 86.4% and 66.7% regained clinical response, mucosal healing and clinical remission, respectively.

thrombosis associated with tofacitinib, although other Janus kinase inhibitors, such as baricitinib (Olumiant, Lilly) and ruxolitinib (Jakafi, Incyte), also have demonstrated increased VTE risk. “This potentially indicates a class-wise medication adverse effect that certainly warrants further study and postmarketing surveillance for thrombotic complications,” Dr. Riello said. In the meantime, he added, “anticoagulation pharmacists should play a critical role in evaluating a patient's candidacy for tofacitinib,” considering factors such as age, body mass index,

use of oral contraceptives or interacting medications, and immobility.”

In addition, Dr. Riello said, it is important to consider alternative agents before initiation of tofacitinib and to use the lowest effective dose of tofacitinib when it is prescribed.

“We’re not yet at the point of providing prophylactic anticoagulation—lowdose, direct-acting oral anticoagulants or low-molecular-weight heparin— to patients taking high-dose tofacitinib who otherwise wouldn’t be prescribed blood thinners,” he said. “But if

subsequent studies continue to demonstrate a significantly increased risk for thrombosis, that may be a risk-versusbenefit conversation that experts in the field have to reach a consensus on.”

—David Wild and Sarah Tilyou Dr. Sandborn reported relationships with AbbVie, Gilead and Pfizer, all of which make Janus kinase inhibitors. Dr. Charabaty reported relationships with AbbVie, Janssen, Pfizer and Takeda. Drs. Lichtenstein and Riello reported a financial relationship with AstraZeneca, Janssen and Portola.

MULTIPLE LAYERS OF

DIFFERENTIATION

A Pharmacist’s Take “The original signal for increased risk of pulmonary embolism and all-cause mortality” was observed in preliminary data from the ongoing A3921133 postmarketing safety trial in rheumatoid arthritis patients with at least one cardiovascular risk factor (NCT02092467), noted Ralph Riello III, PharmD, BCPS, a clinical pharmacy specialist with the cardiac ICU at Yale New Haven Hospital, in Connecticut. This analysis showed that the 10-mg twice-daily dose of tofacitinib “appeared to confer an increased risk of thrombosis and death” compared with anti-TNF drugs and tofacitinib 5 mg two times daily, Dr. Riello told Pharmacy Practice News.

“Interestingly, in phase 2 and 3 trials for UC patients, no such increased risk for VTE was seen,” Dr. Riello said. In addition, although preliminary data from the ongoing long-term extension study

by Lichtenstein et al showed more VTE events among those taking the 10-mg twice-daily dose of tofacitinib patients (n=4) than those taking 5 mg twice a day (n=1), as Dr. Sandborn commented, these patients appeared to have at least some VTE risk at baseline, he added.

“Until the final analysis is reported, it’s difficult to say for certain that the VTE risk is not unique to arthritic patients and may potentially apply to UC as well,” Dr. Riello said. Regardless, he stressed that “it’s important to remember the FDA’s boxed warning does currently apply broadly to both indications for tofacitinib and is likely a dose-dependent phenomenon.”

Dr. Riello said it is “truly puzzling” that no plausible mechanism has been found to explain the increased risk for

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THE SCIENCE BEHIND POSITIVE PATIENT OUTCOMES

Ensuring Medication Safety With Tamper-Evident Products Faculty Paul Stranges, PharmD, BCACP, AE-C Clinical Assistant Professor Department of Pharmacy Practice College of Pharmacy University of Illinois at Chicago Chicago, Illinois

Introduction The Substance Abuse and Mental Health Services Administration and American Nurses Association estimate that 10% of health care workers experience substance abuse, given the access to medications in health care institutions.1-3 One report estimates that, in 2019, 148 million medication doses were diverted by health care employees.4 This report likely underestimates the extent of diversion, given the difficulty to detect it.1,3,5 There are multiple opportunities for diversion within health care facilities: during drug procurement, preparation, administration, and waste disposal.5 “We try as much as possible to prevent diversion at all points and maintain a closed-loop accountability for medications,” said Paul Stranges, PharmD, BCACP, AE-C, a clinical assistant professor at the University of Illinois at Chicago College of Pharmacy. “We’re reliant on documentation and secure storage to maintain chain of custody for medications, but diversion can occur while drugs are in transit, in secure storage, or after dispensing and can be difficult to detect.” The issue of diversion is wide-reaching, affecting patients, practitioners, and institutions.5 In an effort to mitigate drug diversion, initiatives such as tamper-evident packaging have been put forward to enhance the chain of custody of medications. This article describes the effects of diversion on the delivery of patient care and the benefits of using tamper-evident products to mitigate them.

Diversion and Patient Safety Diversion poses a significant threat to patient safety.2 “Diversion is first and foremost a patient safety issue,” Dr Stranges said. “What you worry about with tampering of intravenous (IV) controlled substances (CSs) is that it goes unnoticed for a long time, and it ultimately leads to patient harm.” This can lead to numerous consequences for the patient and health care team. According to Dr Stranges, medications that are diluted or replaced with other solutions after diversion can result in inadequate pain management or anesthesia for patients, which can lead to significant harm.5 Also, there have

12

PHARMACY PRACTICE NEWS • JUNE 2021

been numerous reports of infectious disease transmission through contamination.5 “[Drug diversion] also increases the chance of introducing blood-borne pathogens or waterborne pathogens [into what] we would assume to be a sterile product,” Dr Stranges said. “Unfortunately, you hear about situations where there are outbreaks of hepatitis C or bacterial infections from contaminated drugs after something has been tampered with.”

In addition to substandard care resulting from impaired health care personnel, drug diversion poses a significant risk for practitioners trying to treat their patients and the facilities in which the care is taking place.5 “Drug diversion impacts practitioners who may be unknowingly using drugs that have been tampered with and place the Drug Enforcement Administration holder at regulatory risk,” Dr Stranges said. Any incidences of diversion at a health care facility may lead to detrimental disruptions in the delivery of patient care from audit, resulting in substantial fines and penalties as well as reputational harm.2

Tamper-Evident Packaging and Diversion Diversion prevention requires effective safeguards to ensure the integrity of safe medication practices. The 2013 Drug Supply Chain Security Act (DSCSA) addressed concerns regarding diversion and contamination to the drug supply chain by outlining measures to implement an electronic database by 2023, to track and trace medications and identify those that are counterfeit or diverted.6,7 Among the initiatives that have been implemented to enforce compliance with the act is the use of tamper-evident packaging. Tamper-evident packaging uses barriers or indicators that show evidence of a product being breached.8 “Tamper-evident packaging prevents somebody from accessing medications when they otherwise could have easy access,” Dr Stranges said. “It is a simple way to deter somebody from trying to divert those medications. With tamper-evident packaging, we can have confidence it’s not tampered with or adulterated.”

Different tamper-evident packaging and technology are used at health care facilities to safeguard medications, including tape enclosures, shrink wrap, and tamperevident caps for compounded medications.9 Tamper-evident caps for IV syringes, CADD® cassettes, and IV bags have proven to be beneficial in maintaining aseptic technique and reducing touch contamination, given their ease of use (Figure).10 For medications prepared in oral or enteral syringes, tamper-evident caps can prevent leakage and ensure that patients receive the full, intended dose.10 Tamper-evident packaging increases overall accountability in the chain of custody of the medications. The American Society of Health-System Pharmacists (ASHP)

Figure. Prep-Lock™ Tamper Evident Products by IMI.

guideline on preventing diversion of CSs recommends tamper-evident packaging to ensure integrity and security of medications.2 “There had been times in which we’ve initiated investigations based off of tamper-evident products being found broken,” Dr Stranges said.

Also, USP General Chapter <797> recommends the use of tamper-evident packaging to maintain the quality of compounded sterile products.11 “All packaging should be somewhat tamper-evident,” Dr Stranges said. “Outside of diversion, it provides reassurance the product contains what is labeled and is sterile.” On a wider scope, the FDA outlines various requirements for tamper-evident packaging for certain medications prone to contamination, such as over-the-counter and 503B compounded products.8,12 Although difficult to quantify the true impact of tamper-evident packaging, Dr Stranges acknowledges the importance of using tamper-evident packaging as an effective safeguard. “Use of tamper-evident packaging gives pharmacies, health care work personnel, and patients more confidence,” he said. From the pharmacy’s perspective, “It helps us confirm what we are receiving in our pharmacy from our suppliers and what we are dispensing is what is labeled and is has not been contaminated before use.”

RFID Technology in Drug Security The FDA has recommended tamper-evident packaging as part of a multilayered system for preventing diversion and introduction of counterfeit drugs into the drug supply chain.13 In addition, the FDA indicated that radiofrequency identification (RFID) technology may be a reliable method for reducing diversion and counterfeit products in the drug supply chain.13,14 In health care institutions, RFID is being used to track patients, medical equipment, and medications.15,16

Supported by International Medical Industries, Inc.

Impact on Patient Safety Using RFID technology to trace medications can provide granular information, such as the medication drug, dose, route, and time.16,19 Known as the 5 rights of medication administration—patient, drug, dose, route, and time—these identifiers help to reduce errors and improve patient safety.19 “You can get very detailed with RFID as far as the medication, who is in possession of it, or who is in close proximity to it, and ultimately if it’s making it to the right patient and is the right drug, dose, route, time,” Dr Stranges said. The auto-identification capabilities of RFID can link medications to interaction alerts or relevant institutional protocols, which ultimately reduce adverse events.16 The Centers for Medicare & Medicaid Services also requires medication tracking to improve patient safety.20 The tracking capabilities of RFID can be used to ensure appropriate storage of high-risk medications and quickly identify certain lots of recalled medications, as well as patients affected by recalled lots. Tracking medications during drug delivery, either by hand or in pneumatic tubes, can reduce missing medications that may result in therapy delays.21 Unlike barcode medical administration, which requires conscious thought when manually scanning an individual code, RFID is able to scan multiples codes at once in real time.15,16 “RFID takes all of the benefits of barcodes without having the limitations of needing to use barcode scanners, which have a limited area to scan medications,” Dr Stranges said. “You can use RFID to potentially scan or track movement of medications more efficiently over a larger area, and automatically.”

way that this is being done is through the development of RFID-enabled tamper-evident products to secure and track sterile compounded medications.22 Products, such as tamper-evident RFID caps, can provide interoperability between the track-and-trace requirements of the drug supply chain and hospital chain of custody.22 As part of the growing movement to expand the use of RFID in providing safe drug delivery, DoseID, an industry consortium of companies, including IMI (International Medical Industries, Inc.), was formed to establish standards for the incorporation of RFID-enabled tamper-evident products in managing the drug supply chain more effectively.22,23

Conclusion Although the extent of drug diversion in health care is underestimated, it continues to pose a significant risk on patients, practitioners, and facilities. The use of tamper-evident packaging can provide an effective approach in identifying and mitigating diversion. 6-8 Furthermore, the integration of RFID technology with tamper-evident packaging can improve patient safety, while optimizing the supply chain of custody. “If there were RFID-embedded safety caps, it would turn a 2-step process into 1,” Dr Stranges said. “We’re already adding a safety seal or cap to sterile products, and we may add an RFID tag to the package. If it’s already incorporated, it would be more efficient, and I think a good value.”

References 1.

The Joint Commission. Quick Safety. April 2019:48. Drug diversion and impaired health care workers. April 15, 2019.

Accessed April 2, 2021. https://www.jointcommission. org/-/media/tjc/newsletters/quick_safety_drug_diversion_ final2pdf.pdf

2.

Brummond PW, Chen DF, Chruchill WW, et al. ASHP guidelines on preventing diversion of controlled substances. Am J Health Syst Pharm. 2017;74(5):325-348.

3.

Baldisseri MR. Impaired healthcare professional. Crit Care Med. 2007;35(2 suppl):S106-S116.

4.

$183M lost due to healthcare workforce diverting drugs from patient care in 2019 [news release]. Protenus; September 18, 2020. Accessed April 2, 2021. https://www.protenus.com/ resources/183m-lost-due-to-healthcare-workforce-divertingdrugs-from-patient-care-in-2019

5.

Berge KH, Dillon KR, Sikkink KM, et al. Diversion of drugs within health care facilities, a multiple-victim crime: patterns of diversion, scope, consequences, detection, and prevention. Mayo Clin Proc. 2012;87(7):674-682.

6.

FDA. Drug Supply Chain Security Act (DSCSA). Accessed April 2, 2021. https://www.fda.gov/drugs/drug-supply-chain-integrity/ drug-supply-chain-security-act-dscsa

7.

FDA. Drug Supply Chain Security Act Public-Private Partnership. Accessed April 2, 2021. https://www.fda. gov/drugs/drug-supply-chain-security-act-dscsa/ drug-supply-chain-security-act-public-private-partnership

Diversion Mitigation The use of RFID to track medications provides an effective approach to mitigate drug diversion.18 In fact, the ASHP guideline for preventing drug diversion recommends the use of technology and automation, such as RFID, to track medication chain of custody.2 “We have a very hands-on process for reconciling CSs. RFID is a potential way to automate some of that manual process,” Dr Stranges said. “RFID for movement of CSs is a really great area to move into.”

Integration of RFID Into Tamper-Evident Packaging Steps are being taken to incorporate RFID technology in identifying and mitigating drug diversion. One

8.

FDA. Code of Federal Regulations Title 21, Section 211.132: tamper-evident packaging requirements for

over-the-counter (OTC) human drug products. Revised April 1, 2020. Accessed April 2, 2021. https://www.accessdata.fda. gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=211.132 9.

Zadburke N, Shahi S, Gulecha B, et al. Recent trends and future of pharmaceutical packaging technology. J Pharm Bioallied Sci. 2013;5(2):98-110.

10. International Medical Industries. Prep-Lock™ Tamper Evident Caps. Accessed April 2, 2021. https://imiweb.com/ prep-lock-tamper-evident-caps-2/ 11. USP General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. 2019. https://www.usp.org/sites/ default/files/usp/document/our-work/compounding/ proposed-revisions-gc-797.pdf 12. FDA. Current Good Manufacturing Practice—guidance for human drug compounding outsourcing facilities under Section 503B of the FD&C Act. January 2020. Accessed April 2, 2021. https://www.fda.gov/media/88905/download 13. FDA. Combating counterfeit drugs: a report of the Food and Drug Administration. February 2004. Accessed April 2, 2021. http://old.fda.gov/oc/initiatives/counterfeit/ report02_04.html 14. Taylor D. RFID in the pharmaceutical industry: addressing counterfeits with technology. J Med Syst. 2014;38(11):141.

15. Martinez Perez M, Dafonte C, Gomez A. Traceability in patient healthcare through the integration of RFID technology in an ICU in a hospital. Sensors (Basel). 2018;18(5):1627.

16. Martinez Perez M, Vazquez Gonzalez G, Dafonte C. The development of an RFID solution to facilitate the traceability of patient and pharmaceutical data. Sensors (Basel).

2017;17(10):2247.

17. FDA. DSCSA Pilot Project Program. May 22, 2019. Accessed April 2, 2021. https://www.fda.gov/drugs/drug-supplychain-security-act-dscsa/dscsa-pilot-project-program 18. MacDonald K. RFID and medical management in the hospital: a solution to an ongoing obstacle. Forbes. December 6, 2019. Accessed April 2, 2021. https://www.forbes. com/sites/forbestechcouncil/2019/12/06/rfid-and-medicalmanagement-in-the-hospital-a-solution-to-an-ongoingobstacle/?sh=4ef4cb63b199 19. Engels MJ, Ciarkowski SL. Nursing, pharmacy, and prescriber knowledge and perceptions of high-alert medications in a large, academic medical hospital. Hosp Pharm.

2015;50(4):287-295.

20. Centers for Medicare & Medicaid Services. Stage 2 eligible hospital and critical access hospital meaningful use core measures. Stage 2 tipsheet. August 2012. Accessed April 2, 2021. https://www.cms.gov/regulations-and-guidance/legislation/ehrincentiveprograms/downloads/stage2overview_ tipsheet.pdf 21. Dorn M, Bonkowski JJ. Applications of a real-time location system in pharmacy practice. Am J Health Syst Pharm.

2014;71(24):2109-2110.

22. PPN News Staff. IMI Joins DoseID to further expand RFID interoperability in health care. Pharmacy Practice News.

September 21, 2020. Accessed April 2, 2021. https://www. pharmacypracticenews.com/Industry-News/Article/09-20/ IMI-Joins-DoseID-to-Further-Expand-RFID-Interoperabilityin-Health-Care/59631 23. DoseID. Introducing DoseID. Accessed April 2, 2021. https://doseid.com/ Disclosure: Dr Stranges reported no relevant financial disclosures.

BB216

Successful use of RFID for medication tracking has been reported in high-risk settings, such as intensive care units, and for IV medications.16 “We’re using RFID tags to automate some of our inventory management and get better insight into inventory movement,” Dr Stranges said. “It really helps our efficiency.”

A pilot program organized by the FDA is examining the use of RFID technology to develop a track-and-trace system that will comply with the DSCSA.17,18

PHARMACY PRACTICE NEWS • JUNE 2021

13

14 Clinical

Pharmacy Practice News • June 2021

Oncology

Survey Cites Cholangiocarcinoma Mutation Confusion O

ncologists could use some education about testing for and targeting the major mutations in cholangiocarcinoma, according to survey results presented at the 2021 Gastrointestinal Cancers Symposium.

Targets are emerging to combat this challenging malignancy, and it is imperative that oncologists understand their importance, according to presenter Kinjal Parikh, PharmD, BCOP, the associate director of clinical strategy for Hematology/Oncology at Medscape Oncology, in New York City. “Given the need for a greater understanding of the molecular alterations, varying targets, and the available and emerging therapies, more education is needed,” Dr. Parikh said.

Presenting the results of a CMEcertified clinical practice assessment written by co-investigator Arndt Vogel, MD, of Hannover Medical School, in Germany, Dr. Parikh said oncologists’ responses indicated there are gaps in knowledge, competence and confidence about how to test for mutations and apply targeted therapies in treating patients with advanced disease (abstract 347).

In particular, mutations in isocitrate dehydrogenase isoform 1 (IDH1) and fusions or translocations of the fibroblast growth factor receptor 2 (FGFR2) gene have been identified as drivers in this tumor type. Drugs that target them are becoming available.

The researchers surveyed 104 oncologists to assess knowledge and attitudes; participants gained foundational knowledge and received feedback about their performance compared with that of other test-takers. Most (61%) practiced in the community and most (70%) saw patients with a variety of cancers. About half reported seeing three to five patients per month with cholangiocarcinoma, although about one-fourth saw such patients less than once a month.

Lack of Confidence More than half of the oncologists reported having a lack of confidence in recognizing targets and applying targeted agents.

About 20% did not use next-generation sequencing and biomarkers, while 32% used such testing in patients with progressive disease. Some 35% did not realize that not all panels detect FGFR2 fusions/ translocations, Dr. Parikh reported.

Approximately 30% reported testing for IDH mutations and 60% were familiar with its incidence in cholangiocarcinoma; 56% said they test for FGFR2 mutations.

The oncologists expressed some familiarity with data from the ClarIDHy trial of ivosidenib (Tibsovo, Agios) and the FIGHT trial of the FGFR2 inhibitor pemigatinib (Pemazyre, Incyte). More than 50% recognized that diarrhea and cough are the most common side effects of ivosidenib, and 30% knew the most

common grade ≥3 adverse event with pemigatinib is hypophosphatemia. Thirty percent also knew that three agents are being evaluated for FGFR2 fusions or translocations in the first-line setting.

Slightly more than half (55%) also recognized that HER2 gene alterations occur at a rate of 5% to 8% in patients with cholangiocarcinoma. However, 62% of respondents incorrectly identified drugs targeting the vascular endothelial growth factor as promising novel agents with anti-tumor activity as single agents.

New Opportunities For Collaboration The findings underscore that many oncologists express a lack of confidence in recognizing genomic targets and applying targeted agents, noted Amber Draper, PharmD, BCOP, an oncology clinical pharmacy specialist in gastrointestinal oncology at Emory Winship Cancer Institute, in Atlanta. “Oncology pharmacists have the opportunity to fill this knowledge gap by providing education to providers on both drugs and the required genomic testing.” By “being aware of these and any future targeted therapy drug approvals,” Dr. Draper said, “pharmacists can encourage genomic testing earlier.” Since it can take weeks to get results of these tests, being on top of testing and results can “prevent treatment delays when patients progress through first-line therapies,” she said.

Pharmacists also can help patients navigate the required insurance approval process for pemigatinib and ivosidenib and obtain financial assistance when needed, “ensuring patients receive their medications in a timely fashion,” Dr. Draper told Pharmacy Practice News.

In addition, pharmacists can educate providers and help manage the unique side effects of these targeted therapies, she said.

“Both pemigatinib and ivosidenib represent breakthroughs in a disease with limited treatment options,” Dr. Draper said, noting that “the advent of targeted therapy in cholangiocarcinoma opens up new opportunities for provider and pharmacist collaboration.”

—Caroline Helwick and Sarah Tilyou The study was funded by Incyte Corp. The sources reported no relevant financial disclosures.

Duloxetine May Ameliorate Oxaliplatin-Induced Neuropathy

D

uloxetine significantly improved peripheral neuropathy related to oxaliplatin and was well tolerated, according to data presented at the 2021 Gastrointestinal Cancers Symposium.

“Duloxetine may be considered as an option in ameliorating peripheral neuropathy in these patients,” reported Jeffrey Chi, MD, a fellow with Northwell Health Cancer Institute in Lake Success, N.Y. Duloxetine, a second-generation selective serotonin–norepinephrine reuptake inhibitor, is a common component of chemotherapy regimens for gastrointestinal cancers, but peripheral neuropathy is a dose-limiting toxicity.

Dr. Chi and his co-investigators retrospectively evaluated 53 patients who had received duloxetine for oxaliplatininduced peripheral neuropathy during the treatment of colorectal, pancreatic or gastric cancer (abstract 195). Patients with preexisting neuropathy were excluded.

Patients underwent neurologic evaluation at baseline and then every four weeks during treatment with 30 mg of duloxetine daily, escalating to 60 mg daily if well

Neuropathy improvements after 8 weeks of duloxetine:

19% went from grade 3 to 2

6% went from grade 2 to 1

43% from grade 1 to 0

tolerated. The response rate was 89%, with 11% of patients remaining stable at eight weeks. In addition to improving neuropathy, duloxetine improved depression in 50% of patients and reduced pain scores in 23%, Dr. Chi reported.

After four weeks of duloxetine, neuropathy improved from grade 3 to 2 in 6% of patients, from grade 3 to 1 in 11% and from grade 2 to 1 in 53%. Grade 3 neuropathy remained stable in 26%, and grade 2 was stable in 4%. After eight weeks of treatment, 19% of patients improved from grade 3 to 2, while 6% improved from grade 2 to 1 and 43% from grade 1 to 0.

Many other patients remained stable.

“There were five patients who discontinued duloxetine due to grade 3 drowsiness, insomnia, dry mouth and headache, but, overall, duloxetine was well tolerated, with the majority of side effects grade 1 or 2,” Dr. Chi said. However, he urged caution regarding potential drug interactions with duloxetine.

Commenting on the study, Kelly Fritz, PharmD, BCOP, a clinical oncology pharmacist at Huntsman Cancer

Institute, in Salt Lake City, said it shows that duloxetine is “a promising therapeutic option for patients experiencing oxaliplatin-induced peripheral neuropathy.” Early intervention with standard doses of duloxetine “may allow patients to continue to receive oxaliplatin without dose reduction, especially in those deriving clinical benefit,” Dr. Fritz said.

Duloxetine’s added benefit of decreasing depressive symptoms and pain scores makes “the potential addition even more formidable,” she said.

Noting that the authors underscored the potential for drug interactions with duloxetine, Dr. Fritz said, “having an oncology pharmacist review home and supportive care medications prior to the addition of duloxetine is highly beneficial, and could help de-prescribe unnecessary or duplicative therapies to prevent these interactions.”

—Caroline Helwick and Sarah Tilyou The sources reported no relevant financial disclosures.

Clinical

Pharmacy Practice News • June 2021

15

Oncology

A New Direction for Immunotherapy in Children, AYAs T

he response rates of cancer immunotherapies are notable, but they come with unique, severe toxicities that can result in rapid deterioration in patients. To foster optimal management of pediatric and adolescent and young adult (AYA) patients taking these therapies, an international panel of pediatric cancer experts published comprehensive consensus guidance, covering diagnosis, grading and management of immunotherapy-related toxicities.

The guidance discusses adverse events (AEs) such as cytokine release syndrome (CRS), immune effector cellassociated neurotoxicity syndrome and infusion reactions seen in patients taking immune checkpoint inhibitors (ICIs), bispecific T-cell engagers, immune effector cells and other therapies (Nat Rev Clin Oncol 2021 Feb 19. doi:10.1038/s41571-021-00474-4).

Overall, younger patients may do better with immunotherapy than adults, in part because they have fewer or no comorbidities, according to senior panel author Kris Mahadeo, MD, MPH, the section chief and medical director of pediatric stem cell therapy at The University of Texas MD Anderson Cancer Center, in Houston. “At the same time,” Dr. Mahadeo told Pharmacy Practice News, “because a lot of these new therapies are first tried in adults, we have to remain vigilant to recognize these toxicities in children, because they may present differently.”

Need for Younger Patients In Clinical Trials Chief among the group’s 14 consensus recommendations is the need to include pediatric and AYA cancer patients in well-designed clinical trials as soon as possible. “That’s the only way that we’re going to continue to advance the field and make therapies available for children as quickly as we can,” Dr. Mahadeo said.

Another important aspect is using ageappropriate criteria to assess AEs so they can be managed promptly, said Estela Mireles, PharmD, a co-author of the consensus statement and a clinical pharmacy specialist in pediatrics at MD Anderson.

This incorporates the use of age-related vital signs, estimation of body surface area, renal and endocrine function, and stool output, Dr. Mireles said.

Whenever possible, baseline comprehensive organ assessments should be performed to facilitate monitoring of outcomes and toxicities, the panel stated. Also, interdisciplinary and front-line staff should demonstrate and maintain competency in prompt recognition and management of complications caused by immunotherapy in children and AYAs, using clinical algorithms for rapid

Clinicians can use the acronym LEGS to remember, in reverse order, the timing of adverse event symptoms.

L Liver abnormalities E Endocrine abnormalities G Gastrointestinal issues S Skin problems

‘Some AEs may not be as [obvious], such as endocrine or liver issues, so that’s where we would play more of a role in tracking those, monitoring and giving recommendations on what to do with dosing.’

—Giselle Carrero, PharmD escalation of care when indicated. The guidelines also make some suggestions for treatment-specific monitoring, such as serial monitoring of corticotropin, thyrotropin, luteinizing hormone and follicle-stimulating hormone in children receiving ICIs and monitoring for graftversus-host disease in patients receiving allogeneic immune effector cells.

“We know that immune effector cell therapies have been shown to be effective in relapsed/refractory cancers, such as acute lymphocytic leukemia, and have been shown to [result in] durable remissions, so we feel they are pretty effective, but there’s still so much to learn from all of the different agents that are evolving and becoming available,” Dr. Mireles said. Noting that immune effects can start as soon as the first dose of ICIs, she stressed that it’s important to monitor patients early.

The guidance also features tables listing common toxicities and management

strategies, as well as a flowchart for how to work up a patient presenting with symptoms of CRS. Of particular concern is screening, diagnosis and management of potential late effects of immunotherapy, starting as early as one month after therapy initiation, Dr. Mahadeo said.

“Curing cancer is important, but it’s not just about that. It’s about really extending the life of a child to be able to experience anything they were going to otherwise achieve.”

Some AEs Are Not Obvious Giselle Carrero, PharmD, a hematology/oncology clinical pharmacy specialist at Children’s National Hospital, in Washington, D.C., told Pharmacy Practice News that she was glad to see the statement emphasize prompt recognition of AEs. Some AEs “are very easy to see,” Dr. Carrero said.

“You can monitor blood pressure or see a rash,” for example. However,

she added, “some AEs may not be as [obvious], such as endocrine or liver issues, so that’s where we would play more of a role in tracking those, monitoring and giving recommendations on what to do with dosing.”

In monitoring for AEs, Dr. Carrero and her colleagues use the acronym LEGS to remember, in reverse order, the way symptoms appear. Skin side effects are seen first, she said, followed by gastrointestinal issues such as diarrhea, then endocrine abnormalities and, finally, liver problems. Her institution has built treatment regimens into its computerized order sets, so pharmacists, nurses and physicians are in sync when it comes to AE management.

—Karen Blum The guidance was written by a multidisciplinary group of members of the Pediatric Acute Lung Injury and Sepsis Investigators Network Hematopoietic Cell Transplantation-Cancer Immunotherapy Subgroup, the Paediatric Diseases Working Party of the European Society of Blood and Marrow Transplantation, the Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium, and the MD Anderson Cancer Center CAR T Cell TherapyAssociated Toxicity Program. Dr. Mahadeo reported financial relationships with Atara Biotherapeutics and Jazz Pharmaceuticals.

Drs. Mireles and Carrero reported no relevant financial disclosures.

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16 Clinical

Pharmacy Practice News • June 2021

Oncology

Speedier Busulfan Washout A Plus in HCT Conditioning?

T

he washout period between the last dose of metronidazole and the first dose of the alkylating agent busulfan can be reduced from seven to three days, according to research from The University of Texas MD Anderson Cancer Center, in Houston.

Busulfan, frequently used as part of conditioning for hematopoietic cell transplantation (HCT), has a well-established drug–drug interaction with metronidazole, which suppresses busulfan clearance and boosts treatment-related toxicity, the investigators noted.

Before this study, the washout period between metronidazole and busulfan at MD Anderson was seven days, or 168 hours. But patients don’t always have a full week to wait before starting their transplant conditioning, said Jitesh Kawedia, PharmD, a clinical pharmacy specialist MD Anderson. “In those situations, the question is: ‘How long should we wait?’”

To answer that question, Dr. Kawedia and his colleagues retrospectively observed every HCT recipient at MD Anderson who received busulfan less than 168 hours after the last dose of metronidazole between March 2016 and July 2019. They found nine such instances.

All nine adult patients (eight men and one woman) received metronidazole and busulfan within a 168-hour period. The patients received the first busulfan dose between eight and 161 hours from the last metronidazole dose.

Patients starting busulfan at MD Anderson receive a test dose to determine a patient’s individual drug clearance and dose, according to Dr. Kawedia, who noted that the clearance of busulfan increases an average of 10% between the test and initial therapeutic dose. If a patient was given busulfan shortly after the last dose of metronidazole, the antibiotic initially would suppress busulfan clearance, he said, and follow-up pharmacokinetic results would show increased clearance of busulfan as the system recovered.

As a result, the researchers hypothesized that any increased busulfan clearance between the test and initial therapeutic dose above 15% for the study patients would indicate the influence of metronidazole. One patient, who received busulfan eight hours after metronidazole, experienced a 24% increase in busulfan clearance. Meanwhile, a patient who

received busulfan within 52 hours had a 16.5% increase, and the patient who received busulfan within 66 hours had a 2.5% increase.

Follow-up pharmacokinetics showed the recovery of busulfan clearance as expected, Dr. Kawedia said. When the patient receiving busulfan eight hours after metronidazole was tested at 56 hours, the results showed a 3.9% increase in busulfan clearance; when the patient who received busulfan 66 hours after metronidazole was tested at 90 hours, the results showed a 0.2% increase in busulfan clearance. All nine patients showed no difference in treatment-related toxicity.

Four patients died from either post-HCT relapse, respiratory failure or infection.

Because busulfan is given every 24 hours and busulfan clearance fell below the expected 10% to 15% range at 66 hours, the researchers concluded that busulfan could be administered safely in the next 24-hour treatment window, or 72 hours after the last dose of metronidazole.

Based on these results, MD Anderson will change its washout period protocol for metronidazole and busulfan from seven to three days, Dr. Kawedia said.

“Previously, there was an undue burden that we had to wait seven days before we can give busulfan. Now we don’t have to do that anymore,” he added. “So, it saves us those four extra days.”

Small Sample Size The small sample size limits the conclusions that can be drawn from these results, commented Jai Patel, PharmD, the chair of cancer pharmacology and pharmacogenomics ain the Division of Hematology/Oncology at Atrium Health Levine Cancer Institute, in Charlotte, N.C. There is large patient variability in busulfan clearance time, which would be difficult to account for in such a small study, he said. “It provides at least some piece of data, but I’m not sure that I would necessarily change an entire clinical protocol or anything like that based off of this because it’s such a small sample size.”

—Jillian Mock The sources reported no relevant financial disclosures. They presented their study (abstract CT104) at the 2020 Virtual Hematology/Oncology Pharmacy Association annual meeting.

Clinical

Pharmacy Practice News • June 2021

17

Cardiology Up to

30%

HYPERKALEMIA

of patients

continued from page 7

sodium zirconium cyclosilicate for the same purpose. (The latter study has been terminated early due to the COVID-19 pandemic.) “We will have to see what these studies find, but I think these agents provide an opportunity to optimize RAASi therapy for patients with CKD and heart failure,” Dr. Grabe said.

That shift to patiromer or sodium zirconium cyclosilicate remains more of an “aspirational goal” than a reality, said nephrologist Gates Colbert, MD, an assistant professor of medicine at Texas A&M College of Medicine in Dallas. “It’s being discussed a lot, but we’re not seeing universal use of these oral potassium binders in clinical practice yet,” commented Dr. Colbert, who co-authored an upcoming article in Mayo Clinic Proceedings on the clinical management of hyperkalemia. “There is a reluctance to add an additional medication to an already complex medication regimen. In addition, both of these medications are constituted as drinkable liquids, and some patients don’t like to drink medicine, which is something to overcome.”

But two new guideline revisions over the past year may improve the adoption of oral potassium binders for this patient population. In June 2020, the Journal of the American College of Cardiology’s “State of the Art Review” on abnormalities of potassium in heart failure (75[22]:2836-2850) recommended the consideration of potassium binders for management of hyperkalemia.

In September 2020, the updated KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease pointed out that RAASi medications aren’t the only ones that may be optimized via the use of oral potassium binders. “Hyperkalemia associated with the use of an ACEi [angiotensin-converting enzyme inhibitor] or ARB [angiotensin II receptor blocker] can often be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping ACEi or ARB immediately,” the guidelines stated. The guideline cited the use of oral potassium binders as one of those measures (Kidney Int 2020;98[4S]:S1-S115).

Maximum RAASi Dose Now Possible Despite the aforementioned limitations of the drugs, Dr. Colbert said he has been successful in adding potassium binders to his therapeutic armamentarium, with about 25% to 30% of his patients given the drugs to allow them to take the maximum dose of RAASis, with few side effects. “If you can get on that maximum RAASi dose, the data show increased cardiovascular benefits, better

process takes time to show effect, but we have to start somewhere if we are going to see these benefits down the road. In the future, I believe we will see more and more patients who were formerly ‘intolerant’ of RAASi inhibitors on therapeutic doses of these drugs.”

—Gina Shaw

on RAASi therapy develop hyperkalemia.

RAASi, renin– angiotensin–aldosterone system inhibitor Source: Circulation 2008;118(16):1609-1611.

blood pressure control and lower risk for stroke and lower mortality,” he said.

“Patients with chronic kidney disease will

have decreased proteinuria and reduced decline in glomerular filtration rate over time. Now, this is not immediate, and the

Dr. Grabe reported no relevant financial disclosures. Dr. Colbert reported financial relationships with AstraZeneca and Relypsa. Portions of this article are based on presentations at the resentation at the American College of Clinical Pharmacy 2020 Virtual meeting.

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18 Operations & Management

Pharmacy Practice News • June 2021

Ambulatory Pharmacy

Meds-to-Beds continued from page 1

Not surprisingly, the first year of operation has been extremely challenging, said Keith Pennington, PharmD, UAB Medical West’s president and CEO. After an initial spike in prescription volume, he said, the numbers tapered off as COVID-19 cases reduced hospital visits and elective surgeries.

“We’re just starting to get back to where we anticipated we would be with the program,” Dr. Pennington told Pharmacy Practice News. The target, according to Lisa Riding, the chief strategy and customer officer at ShiftRx, was approximately 300 prescriptions per day at full capacity.

To underwrite the operation, ShiftRx provided the investment capital to acquire the independent pharmacy in the medical building next to the hospital and build and equip a new larger pharmacy designed to handle the higher prescription volume. The pharmacy’s modular design will enable it to be relocated to Medical West’s new 200-bed replacement facility when it opens in about three years.

Before the M2B program, the retail pharmacy was capturing about 10% of discharge prescriptions, according to Ms. Riding. Now the percentage is “basically in the high 70s,” she said. Pharmacy technicians at the retail pharmacy deliver discharge medications to patients at the bedside. Clinical pharmacists from the hospital are available to counsel patients, Dr. Pennington said.

The pharmacy is open from 7 a.m. to 7 p.m. on weekdays and four hours on Saturday. “We expect to see hours increase as the effects of COVID-19 start to lift and patient populations and demand increase,” Ms. Riding said.

Nick Campolongo, RPh, MBA, ShiftRx’s president of pharmacy services, said since patients were going home with medications, “adherence can probably be assumed.” Regarding whether adherence has resulted in fewer readmissions, “no, we don’t have hard evidence,” he said. Ms. Riding added: “But we’re evaluating that.”

Multiple Benefits Having a retail or specialty pharmacy on the campus can bring many benefits, said Denise Scarpelli, PharmD, the executive director of ambulatory pharmacy and business development at the University of Chicago Medicine. “Prescription revenue is generated from filling those prescriptions,” Dr. Scarpelli noted. “But a long-term benefit for a health system is really the patient’s medication adherence.” There are better outcomes and reduced complications because treatment is not delayed, she said.

“Patient satisfaction increases,” she added. “Most health systems survey patients, and one finding is that patients like having a pharmacy on-site, where all their medication needs are met, and all their medical records are together and shared with a physician.”

However, the benefit depends on the model, Dr. Scarpelli noted. Some health systems have an outside pharmacy, like a Walgreens or CVS, on-site. If it’s their own pharmacy, obviously they gain access to patients from a pharmacy perspective.

UChicago Medicine has three retail pharmacies: a traditional model, another providing specialty medications, and a third located in the emergency department (ED) at the health system’s Level 1 adult trauma center on the South Side of Chicago. Before the pharmacy opened, the ED had been seeing many patients who really did not need to be admitted but kept coming back, often just to get a prescription filled, Dr. Scarpelli noted.

“We’ve been open for about a year, and we’ve actually seen an average 20% to 30% decrease in admissions by having the pharmacy there.”

In addition, UChicago Medicine offers an M2B program. “We feel that one way to really decrease readmissions is making sure patients have their drug in hand and understand how to take it,” Dr. Scarpelli said. “We try to eliminate any barriers these patients experience in getting their medications once they enter the community.

“Some smaller hospitals may not have the service lines to open a specialty pharmacy,” she added. “But they do have the potential for a M2B program if they have a retail pharmacy on-site. A M2B program is enough to sustain a retail pharmacy on most hospital campuses.”

Retail Agreements A Growing Trend?

It’s difficult to determine how many hospitals and health systems operate their own retail pharmacies or have retail pharmacy agreements with chains, independents, wholesalers or other outside organizations. But there still is room for growth, especially for smaller and midsize hospitals that could bolster revenues and improve medication adherence by integrating an M2B program into retail pharmacy operations.

That’s why it is so important for health systems to learn from the experiences of existing M2B programs—particularly those that have navigated the practice challenges of COVID-19. One such program is University Hospital, located in San Antonio. The Level 1 trauma, academic

How UAB Medical West Did It: An M2B Time Line October 2019: In a joint venture agreement, UAB Medical West and ShiftRx acquire an independent pharmacy serving the hospital.

December 2019: Partners begin remodeling to accommodate expanded services and complete the work in March 2020.

Daily operations and dispensing activities continue during construction phase.

January 2020: The meds-to-beds (M2B) program is launched.

February 2020: A new pharmacy information technology system is implemented to support the expanded program.

March 2020: As COVID-19 cases begin to appear, the M2B program is expanded to include emergency department patients.

May 2020: Upgraded medication storage and inventory equipment is installed.

medical center serves 22 counties in the South Texas region and is licensed for approximately 700 beds, comprising three free-standing, high-rise towers. In 2018, University Hospital initiated an M2B program that increased the monthly prescriptions dispensed from the discharge pharmacy from 3,000 to more than 15,000 per month, according to Jennifer Hillman, MBA, PharmD, the director of pharmacy in the University Hospital’s Department of Pharmacotherapy and Pharmacy Services. Since the COVID-19 pandemic began, Dr. Hillman said, several modifications have been made to allow staff to continue to serve patients in the M2B program.

Prior to COVID-19, prescription submission to the M2B program at University Hospital was accomplished primarily through printed paper prescriptions, she noted. Paper prescriptions were picked up several times per day on the hospital floors by the M2B technicians and hand delivered to the discharge pharmacy. With the onset of COVID-19, the health system encouraged providers to use the electronic prescription submission functionality.

As a result, electronic prescription rates increased to 90%, according to Dr. Hillman. Electronic prescriptions have reduced staff exposure to potential infection via time spent on the floors and touch contamination.

More COVID-19 Precautions To Ensure Safety University Hospital employed several other measures to ensure patient and provider safety, Dr. Hillman noted. For example, the discharge pharmacy lobby was originally designed with densely packed seating. The pandemic necessitated removal of more than half the chairs to create at least six feet of distance between each patient. Social distancing floor demarcations were installed in the lobby and the exterior hallway leading to the lobby, directing patients to physically distance themselves in a safe manner. Handsanitizing stations were mounted in the pharmacy lobby, and clear plexiglass barriers were installed in prescription drop-off and pickup areas.

University Hospital pharmacy staff monitor the pharmacy lobby and proactively intervene if the lobby becomes noticeably full, Dr. Hillman said. Staff members triage patients in line. If prescriptions are not urgent, staff ask the patient if they would accept prescriptions for mail or same-day courier. This flexible strategy has been effective in reducing the number of patients congregating in a small space.

—Bruce Buckley The sources reported no relevant financial disclosures.

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20 Policy

Pharmacy Practice News • June 2021

Reimbursement Matters

Drafting an Outpatient Payment Action Team “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

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s sites of care rapidly expand outside of the inpatient environment, so do opportunities for pharmacists to bill for multiple services they can offer in these care settings. This type of care applies to patients covered by government plans such as Medicare and Medicaid, as well as to those with commercial insurance and to Medicare Advantage patients covered by plans paid for by Medicare but administered or provided by commercial insurers in a public– private partnership. Has possible revenue escaped without you even knowing it?

While your C-suite is developing your facility’s COVID-19 recovery and stimulus strategy and leveraging analytics to identify suboptimized service line performance and opportunities for rapid improvement, you can step up with new or enhanced offerings. Be part of the team to advance initiatives after determining the best options for revenue optimization. Cost containment alone is not enough; there must be additional sources of revenue.

Opportunities for billing for pharmacist services are listed in Table 1.

What’s going to make your patient feel safe and connected? Does providing these services diminish the high costs of poor clinical communication?

Remember that payments are possible only when the payor has agreed to pay and the patient wants the service. Commercial payors: which ones? You'll be targeting this group. The first hurdle is ensuring you automatically get payor info on every outpatient. Prepare your “ask” document and keep it to no longer than one page. Include a brief background of why you’re asking, what it covers and how much you’re asking for. Work with the finance/revenue cycle team to determine how and when pharmacist services will be billed. It’s not an “auto add-on charge”; it’s a patient-specific add-on charge for a specific payor when a specific service is provided. No “robo-billing” is involved here. Determine who in your facility or system negotiates agreements with commercial payors and work with that person or group to hone your “ask sheet.” They’ll be presenting the ask to the payor, not you. You’re the only

Table 1. 13 Billing Opportunities for Pharmacist Services

Table 2. Overview of CPT Basics Service

Applicable CPT Codes

Annual wellness visit (AWV)

G0438, G0439

Anticoagulation management

93792-93793

Behavioral health integration

99484

Chronic care management (CCM) and complex chronic care management

99490, G2058, 99487, 99489

Continuous glucose monitoring (CGM)

95249, 95250, 95251

Diabetes self-management training (DSMT)

G0108, G0109

E/M established patient

99211, 99212-99215

E/M new patient

99202-99205

7. Medication therapy management in specialty areas

General care management (CCM, PCM for FQHC [Federally Qualified Health Center] only)

G20511

8. Population health

Medicare diabetes prevention program

G9873-G9879, G9880G9885, G9890, G9891

9. Remote Physiologic Monitoring (RPM) services

Medication therapy management services

99605, 99606, 99607

10. Rural health services

Principal care management (PCM)

G2065

11. Telehealth

Remote physiologic monitoring

99453, 99457, 99458

12. Transitions of care

Transitional care management (TCM)

99495, 99496

13. Vaccine administration

Vaccination

Multiple

1. Annual wellness visits 2. Anticoagulant monitoring 3. Chronic care management 4. Diabetes education 5. Medicare Diabetes Prevention Program 6. Medication therapy management CPC+ program for comprehensive medication management

one who knows what the ask is for, so it’s critically important to convey that in clear terms and ensure complete understanding.

Avoid being turned down or led astray or derailed because payors don’t understand what you want. Adapt and adjust; it’s about pharmacy’s piece fitting into the integral puzzle of patient care. Don’t wait, be proactive, develop a strategy and champion it. Remember that effective deals carefully weave together strategic, financial and legal considerations to deliver business value.

Pharmacists’ Scope of Practice Because Medicare is such a dominant payor in most health systems’ payor mix, it’s important to take a deeper look at how the Centers for Medicare & Medicaid Services (CMS) views pharmacist services. From a Medicare perspective,

the 2021 Physician Fee Schedule (PFS) rules reiterated the clarification that CMS provided in its May 1 COVID-19 IFC (85 FR 27550-27629) rule (bit.ly/ 3d3HMuq) that pharmacists fall within the regulatory definition of auxiliary personnel under “incident to” regulations. As such, pharmacists may provide services incident to the services, and under the appropriate level of supervision, of the billing physician or nonphysician practitioners (NPPs), if payment for the services is not made under the Medicare Part D benefit.

This includes providing services incident to services of the billing physician or NPP and in accordance with the pharmacist’s state scope of practice and applicable state law. Collaborative practice agreements are required in most cases. An excellent review, “Physician Fee Schedule Proposed Rule:

Understanding 4 Key Topics Listening Session,” is available on the CMS website (go.cms.gov/39WqIUZ).

Current Procedural Terminology (CPT) codes are another critical piece of the puzzle when seeking reimbursement for pharmacist services. The American Medical Association manages the CPT code set that is the language of medicine, and as such, the codes are the basis for reimbursement, an enabler of research and a method to reduce administrative burden. They provide education with modules on office evaluation and management (E/M) codes, as well as an overview of CPT basics (Table 2). Evaluation and Management (E/M) 2021 CPT code revisions released last fall included: • 329 changes with 206 new codes, 54 deletions and 69 revisions; • CPT codes and guidelines for office

Policy

Pharmacy Practice News • June 2021

21

Reimbursement Matters and other outpatient E/M services, the first major revision in more than 25 years. Some changes include eliminating history and physician exam as elements for code selection, permitting code level selection based on medical decision making and adding more detail to CPT code descriptors to promote payor consistency; • additional CPT codes related to the COVID-9 pandemic; an additional eight codes to improve documentation for continuous cardiac monitoring and detection, replacing four deleted codes; and • new and revised CPT codes to enhance screening and care of patients with diabetes (this is especially of interest to pharmacy).

Under these E/M coding and payment changes, some providers, such as primary care physicians, saw substantial reimbursement bumps, while others, such as radiologists, saw decreases in payment. The CMS rationale for this discrepancy: Prioritizing investment in preventive care and chronic disease management reflect the challenges of providing care to Medicare patients, particularly those with chronic conditions.

Pharmacists are valuable additions to these teams. Clarifying the times when prolonged office and outpatient E/M and management visits can be reported with a revaluing (increasing payment) applied to a wide range of clinical services, including: • maternity services; • therapy evaluation; • end-stage renal disease monthly capitation payment services; • transitional care management services; • cognitive impairment assessment and care planning; • initial preventive physical examination and initial and subsequent annual wellness visits; and • emergency department visits and psychiatric diagnostic evaluations and psychotherapy services.

To learn more about how to use the CPT code set to bill outpatient and office procedures, visit the AMA website at bit.ly/3s3seuC.

Remote Services Given the growth of telepharmacy and other methods of providing remote clinical services, it’s important to understand the following key concepts.

Remote Physiologic Monitoring (RPM) is a set of remote services related to monitoring of physiologic parameters (e.g., weight, blood pressure, pulse

oximetry, respiratory flow rate) that CMS first approved in Physician Fee Schedule (PFS) 2019 and 2020; 2021 PFS clarifies and expands on that approval.

CPT codes 99453, 99454, 99091, 99457 and 99458 E/M services: can be ordered and billed only by physicians or NPPs eligible to bill Medicare for E/M services. Important note: Pharmacists aren’t eligible to bill Medicare and, therefore, may not bill for RPM services.

CPT codes 99453-99454. These codes may be provided by clinical staff

or auxiliary personnel under the general supervision of the billing physician or NPP; CPT codes 99457-99458 may be provided by clinical staff under the general supervision of the physician or NPP. Note: Pharmacists may perform RPM services under general physician or NPP supervision.

CPT code 99091: may only be used by physicians or other qualified health care professionals authorized to independently bill Medicare for services. RPM services may be provided to patients with chronic and acute conditions. ■

Free CME/CE now available!

1.0 AMA PRA Category 1 Credit™ 1.0 contact hour (0.10 CEU) of the ACPE 1.0 contact hour of the AANP (which includes 0.10 hour of pharmacology)

Buprenorphine In Chronic Pain Management: A New Look at a Familiar Agent RELEASE DATE: AUGUST 5, 2020 EXPIRATION DATE: SEPTEMBER 30, 2021

Coming Soon Reimbursement Matters topics for future issues:

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

Faculty

• Avoiding revenue loss

Joseph V. Pergolizzi Jr, MD

• The 2022 FY and CY payment years: what CMS is proposing

Senior Partner Naples Anesthesia and Pain Associates, Inc. Naples, Florida

• New coding changes that your revenue cycle team can’t afford to miss of• Impact of site-ofcare changes

This activity is supported by an educational grant from BioDelivery Sciences International, Inc. Distributed by Anesthesiology News, Pain Medicine News, and CMEZone.com

Yvonne D’Arcy, MS, APRN, CNS, FAANP Pain Management & Palliative Care Nurse Practitioner Point Verde Beach, Florida

Access today at cmezone.com/CU206

22 Policy

Pharmacy Practice News • June 2021

Worker Safety

Meeting Tougher PPE Standards a Manageable Task C

omplying with new, more stringent requirements for personal protective equipment (PPE) under USP Chapter <800> can be done without unduly affecting the speed of batch syringe preparation, opening the door for safer workplace practices, according to a new study by Duke University Hospital researchers.

USP <800> became official on Dec. 1, 2019, but because of pending appeals on several other standards, including general chapters <795> (Pharmaceutical Compounding—Nonsterile Preparations) and <797> (Pharmaceutical Compounding—Sterile Preparations), it is considered to be only “informational and not compendially applicable” until the appeals process is completed for the other chapters.

Nevertheless, some institutions— including Duke—moved ahead with workflow changes that already had been in progress. “This chapter has been a long time coming and we’d done a great deal of planning to prepare, so we decided not to delay putting those plans in place,” said Matt Kelm, PharmD, MHA, the associate chief pharmacy officer for inpatient pharmacy services and ambulatory care services at the hospital, whose team presented the study at the ASHP 2020 Midyear Clinical Meeting & Exhibition.

This early adoption gave Duke’s pharmacy an opportunity to measure the effect of the workflow changes, including new PPE standards. Compounded nonsterile hazardous oral syringe preparation has traditionally involved relatively minimal PPE: gown and gloves for the technician preparing the syringe in the negative pressure room, and

‘The addition of more stringent PPE and protective settings did not significantly impact technician or pharmacist time when preparing daily batches of hazardous syringes.’

—Matt Kelm, PharmD, MHA

gloves for the pharmacist reviewing the syringe. Now USP <800> calls for the pharmacy technician to wear a gown and two pairs of chemotherapy gloves, as well as head, hair and shoe covers when preparing hazardous medications.

The Duke investigators conducted a pre- and post-modification observational study, comparing the average time in seconds it took technicians to compound oral hazardous syringe batches and pharmacists to verify the syringe batches, during two time periods: from Sept. 15 to Oct. 31 (before USP <800> implementation) and Jan. 15 to Feb. 29 (a few weeks after implementation).

Technicians recorded the time they started the daily batch and when they finished, while pharmacists recorded their start and finish times for checking each daily batch. (The same three technicians prepared the batches during the two time periods.)

“We were able to detect a small time increase per dose with the new PPE and workflow,” Dr. Kelm said. Specifically, the average batch size (number of syringes) prepared by a technician in a shift fell from 60 to 52, with the average number of seconds it took to prepare each syringe increasing from 136.4 to

151.7—an increase of 15.3 seconds. Similarly, the average batch size verified by a pharmacist in a shift decreased from 57 to 40, with the average number of seconds it took to verify each syringe increasing from 12.4 to 15.6—an increase of 3.32 seconds. This difference, however, was not statistically significant (P=0.16).

“The addition of more stringent PPE and protective settings did not significantly impact technician or pharmacist time when preparing daily batches of hazardous syringes,” Dr. Kelm said.

“There was a trend towards longer preparation and verification time, but adding it all up, we found that the increased time was neither statistically significant, nor probably clinically significant.”

He noted that in a batch process that takes several hours, the time required for garbing and ungarbing is a small part of the overall workflow. He also pointed out that there was significant variation in the time it took for pharmacists to verify syringes, probably due to the fact that pharmacists are frequently interrupted for other requests during the verification process.

Dr. Kelm said the most efficient approach is clearly to do all syringe preparation and checking in a single garbing,

3 PPE Lessons Learned at Duke 1. Heed new USP rules requiring technicians to wear extra layers of PPE when preparing hazardous medications.

2. Take an ergonomic approach to donning and doffing of PPE to boost efficiency.

3. Measure PPE workflow changes; expect small but manageable increases in garbing time.

but other demands on the pharmacist and/or technician’s time may not always permit it. “We have also found that taking an ergonomic approach to donning and doffing of PPE, such as having a seating option so someone can safely don shoe covers, assists with efficiency.”

The additional PPE requirements are likely to have a more significant impact in the sterile products environment, Dr. Kelm said, but a study of that effect has not been conducted.

Kudos for Sharing Success It’s reasonable to expect that putting new PPE requirements in place will add a little time to the compounding process, said Fred Massoomi, PharmD, the senior director, hospital and health-system pharmacy services for Visante. “It won’t be too much, but it could add up if you’re a site that compounds a great deal of products. We’ve come a long way since 2004, where we only used gloves for compounding and they weren’t even required to be sterile. One thing most folks who remember the prior changes that were made to PPE is that we didn’t do a good job of educating the nurses and the physicians about what to expect.

Sharing studies like this can help them understand that adding new PPE will involve a little more time. The last thing we want is for the pharmacists and techs to be pushed to hurry up. We want them to garb appropriately so that it protects them and their patients as they are in the process of compounding and verifying.”

—Gina Shaw The sources reported no relevant financial disclosures.

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24 Operations & Management

Pharmacy Practice News • June 2021

Finance

Amid Supply Challenges, Generics Still a Cost-Saver T

he dramatic growth in generic drugs has been a huge economic success story in the United States, generating savings of nearly $2.2 trillion from 2010 to 2019, according to the Association for Accessible Medications (AAM 2020 Generic Drug & Biosimilar Access & Savings Report; bit.ly/3tGmTdD).

But the dynamics that fueled this commercial success—the crowded field of generic drug competitors and the resulting “race to be bottom” in commoditylevel prices—has led to drug shortages, caused at least in part by market con-

and have generic versions on the market (67%) (bit.ly/3tDvEFm). Drugs in shortage also were typically sold at low prices, meaning slim profit margins for even the most efficient producers. According to the report, the median pre-shortage price for a shortage drug was $8.73, and for injectables, it was $11.05.

Erin R. Fox, PharmD, the senior director of drug information and support services at the University of Utah Health, in Salt Lake City, cited the high percentage of injectables in short supply—the very drugs that hospitals rely on for their

to increase market capacity to ensure a stable supply. “A new factory with added capacity could add resilience to the market,” Dr. Fox said. “Right now, we have a limited amount of capacity. It's like moving pieces of the pie around, but the pie isn’t any larger.”

Help for Health Systems In 2018, Civica Rx expanded the pie for its health-system members by establishing generic supply relationships with contract manufacturers.

This year, the nonprofit organization

Civica Rx has begun construction on a 120,000-square-foot manufacturing plant that will use advanced technology to produce essential generic medications.

solidation and a consequent drop in manufacturing capacity, according to an FDA task force report on the root causes of the shortages (bit.ly/3tDvEFm).

Certain types of medications are most vulnerable to these market forces, according to the FDA task force.

The agency’s investigators conducted a study comparing 163 drugs in shortage from 2013 to 2017 and similar medicines with adequate supplies. Drugs in short supply, they found, were more likely to be sterile injectables (63% of sample)

patients—as a particular concern. “Injectables are hard to manufacture. You need specialized factories and machinery, and in general we don’t have many factories able to do that. Building a brand-new factory from scratch is going to take at least three years,” Dr. Fox said. “Even if a company were willing to go through all of the FDA hurdles and regulatory requirements, there is usually not enough time to make a difference in a shortage.”

One solution would be to incentivize manufacturers and other stakeholders

5 Civica Rx Generic Manufacturer Partnerships

A

dozen generic manufacturers have signed long-term supply agreements with Civica Rx in the past year and a half, and more are expected in the coming months.

So far, five have been made public: Exela Pharma Sciences, Hikma Pharmaceuticals, Sandoz, Thermo Fisher Scientific and Xellia Pharmaceuticals.

Here are more details on the partnerships: 1. Last year, Hikma began shipping heparin and seven additional injectables, including dexamethasone, ondansetron, morphine sulfate and metoprolol.

2. Last November, Sandoz initiated shipments of pantoprazole for injection 40 mg, the first of at least six Sandoz generic injectables that Civica Rx will supply to members under its own label.

3. Exela is supplying several dosage strengths of sodium bicarbonate injection, an essential emergency therapy that has been consistently in shortage.

4. Thermo Fisher Scientific signed a seven-year agreement last January, to develop Civica Rx–owned abbreviated New Drug Applications for certain essential medications.

5. In a partnership announced in 2019, Xellia Pharmaceuticals agreed to supply essential anti-infectives, including vancomycin and daptomycin, to member hospitals.

—B.B.

launched the second phase in its strategic plan. In partnership with Phlow Corporation, of Richmond, Va., and the U.S. Biological Advanced Research and Development Authority (BARDA), Civica Rx began construction of a new state-of-the-art sterile injectable manufacturing facility in Petersburg, Va. The 120,000-square-foot plant, scheduled to open within three years, will use advanced technology to produce essential medications from beginning to end, starting with raw materials for active pharmaceutical ingredients (APIs) and completing the cycle with finished sterile injectable dosage forms.

“We’ll be able to produce 90 million vials and 50 million prefilled syringes a year,” Martin VanTrieste, BPharm, Civica Rx’s president and CEO, told Pharmacy Practice News.

Mr. VanTrieste said discussions with Eric Edwards, MD, the CEO of Phlow, and BARDA started two years ago. The question they looked at “was how we could work together to take this large, very complex and fragile supply chain, with many suppliers around the globe, and really shorten it and make it really robust,” he said.

What emerged was the concept of one large, technologically advanced manufacturing site with end-to-end production capability and direct distribution to hospitals. “They liked the idea,” Mr. VanTrieste said.

The COVID-19 pandemic and acute shortage of critical medicines added urgency to the project, and in January, the agreement was announced. Phlow signed a $354 million deal with BARDA as the primary contractor overseeing the operation. Civica Rx will produce the finished dosages in vials and syringes for its member hospitals and the U.S. Strategic National Stockpile.

Civica Rx already has more than 50 sterile injectable medications available through contract manufacturers for its members’ more than 1,400 hospitals

The Value of Generic Drugs $313 billion U.S. generic drug savings in 2019

4 billion Generic prescriptions filled

90 % of prescriptions filled generically

20 % of drug spending for generic drugs

$6.97 Average generic copay

Nearly $2.2 trillion Generic drug savings, 2010-2019 Source: Association for Accessible Medicines 2020 Generic Drug & Biosimilar Access & Savings Report.

(sidebar). By 2023, the number could exceed 100 as more generic drug companies come on board and as Civica Rx gains FDA Abbreviated New Drug Application approvals to make generic injectables in the new facility.

—Bruce Buckley Dr. Fox reported an unpaid position on Civica Rx’s advisory board. Mr. VanTrieste, the unpaid CEO of Civica Rx, reported no relevant financial disclosures.

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Finance

Leveraging the EHR continued from page 1

by $32 million, Dr. Patel and his colleagues reported. The change? Placing a dispense-as-written checkbox on the EHR prescribing screen—an option long imprinted on paper prescriptions to boost generic rates. “Because it was a digital platform, initially we didn’t realize we had to put that checkbox in place,” said Nishaminy Kasbekar, PharmD, the chief pharmacy officer at Penn Presbyterian Medical Center, in Philadelphia.

Generic Rates Soar ‘Virtually Overnight’ After the opt-out default was added to the EHR, clinicians’ generic prescribing rates soared “virtually overnight,” Dr. Patel told Pharmacy Practice News.

The Nudge Unit investigators looked at monthly prescribing rates for the 75 most frequently ordered oral medications in therapeutic categories, including acid reflux, anxiety and/or insomnia, bacterial infection, depression, diabetes, hyperlipidemia, hypertension and/or heart failure, hyperthyroidism, and pain. In the medication study sample, 98.4% of 2.6 million prescriptions were generic, compared with 75.4% of 720,318 prescriptions in a six-month pre-intervention period (P<0.001).

One outlier to the nearly 99% generic rate was hypothyroidism, a condition that can be extremely challenging to control in some patients. The team found that generic levothyroxine was prescribed 80% of the time. But that still represented a major improvement: Before the opt-out default was installed, only 50% of hypothyroid patients were prescribed the generic, noted Dr. Patel,

who is also the founder of Catalyst Health, a behavioral change and technology firm.

Dr. Patel said clinicians strongly supported the change, which was accomplished in a team effort involving pharmacy and clinical leadership as well as information technology. “[The clinicians] kept saying they wanted to prescribe more generics,” he said. “‘The medications are just the same,’ they told us, ‘but more affordable for our patients.’”

But the volume of patients and the complexities of drug regimens often made brands easier to prescribe, he noted.

“When a patient came in with 10 medicines, for example, a clinician might just type in Lipitor [atorvastatin, Pfizer] or Coreg [carvedilol, GSK] or another brand-name prescription. Without the DAW [dispense-as-written] box,” brandname drugs essentially became the default medication, he explained. “It was too much extra work to prescribe the generic. A lot of clinicians said [the EHR change] made their work easier.”

Although Dr. Patel and his team published the results of their generic drug utilization initiative in a 2019 paper (J Gen Intern Med 2019;34[3]:349-350), he said the 99% utilization “is holding true today.”

Changing the Default The Penn Medicine study reinforced the concept that “most providers follow the EHR defaults, and that control of the defaults is one of the most powerful tools available to help enhance medication stewardship efforts,” Eric Tichy, PharmD, MBA, the vice

What’s in a Nudge?

T

he Penn Medicine Nudge Unit (nudgeunit.upenn.edu) describes itself as “the world’s first behavioral design team embedded within a health system.

Our mission is to leverage insights from behavioral economics and psychology to design and test approaches to steer medical decision-making toward higher value and improved patient outcomes.”

In addition to its electronic health record–based generic prescribing project, the Penn Medicine Nudge Unit behavioral design team has published dozens of research papers, including several related to medication utilization: • Effect of Passive Choice and Active Choice Interventions in the Electronic Health Record to Cardiologists on Statin Prescribing: A Cluster Randomized Clinical Trial (JAMA Cardiol 2021;6[1]:40-48) • Association Between Electronic Medical Record Implementation of Default Opioid Prescription Quantities and Prescribing Behavior in Two Emergency Departments (J Gen Intern Med 2018;33[4]:409-411)

‘Control ‘C Con ontr t ol ol of of [EHR] [EHR [E EHR HR] defaults defa de efaul faults fa ults ul ts is is one one off the on the he most mo osst powerful powe po w rf we rful ull tools too oolls ls available ava ail ilab lab abl ble le to to help he elp enhance enhan nhance nh ance an e medication m me dication di n stewardship stte eward ewa rdsh ship efforts.’ sh eff ffo orts s’ —Eric Tichy, PharmD, MBA chair of supply chain management for Mayo Clinic in Rochester, Minn., told Pharmacy Practice News. “It does not surprise me to see these Penn Medicine results sustained over a long period of time. I view this as evidence to support a best practice for managing medication ordering systems.”

Dr. Tichy added that his own experience underscores the value of changing defaults to affect medication utilization—in his case, with intravenous

immune globulin dosing. “We defaulted our ordering system to ideal body weight dosing, which has been shown to yield more consistent results, and greater than 95% of the dosing is now done by ideal body weight as a result.”

—Bruce Buckley Dr. Patel reported financial relationships with HealthMine Inc., Holistic Industries and Life.io. Drs. Kasbekar and Tichy reported no relevant financial disclosures.

26 Operations & Management

Pharmacy Practice News • June 2021

Compliance

TJC and Drug Diversion continued from page 1

small doses, which results in nurses reusing the same vial repeatedly for a given patient. Such repeated access poses a diversion danger, she noted during the ASHP 2020 Midyear Clinical Meeting and Exhibition. To lower the risk, “it is important to keep these vials locked up between doses,” Dr. Mansur said, adding that anesthesia carts located in rooms should be under surveillance at all times when the room is not in use and unlocked.

Dr. Mansur said surveyors also have found cases of controlled substances being stored in refrigerators that can be accessed “by anyone with a key to that refrigerator. Surveyors have also seen instances where controlled substances are transferred between the pharmacy and automated dispensing cabinets [ADCs] without adequate security controls.”

Kim Dove, PharmD, a controlled substance management expert at Omnicell, echoed the need to keep a careful eye on ADCs. Although the advent of ADCs has improved the safety of controlled substance storage on the nursing unit, Dr. Dove noted, there are still vulnerabilities in the transport from pharmacy to the patient floor.

“All medications, whether controlled or non-controlled, are delivered by a pharmacy technician who is responsible for restocking the meds in the ADCs, and these techs often use an open cart for delivery, which creates a potential diversion opportunity,” she explained. “We always joked that if someone wanted to get the narcotics, they just had to watch for the person with the cartful of paper bags!” said Dr. Dove, who was not involved with the ASHP presentation.

Expired Controlled Substances Another potential point of vulnerability in the medication management process that Dr. Mansur cited is the storage of expired controlled substances in the pharmacy. She said pharmacies should keep expired medications under lock and key until the drugs leave the premises or are destroyed, and also need to develop processes to mitigate the risk for diversion from this stock. For example, Dr. Mansur said, pharmacies can schedule regular counts of expired drugs and investigate any missing inventory, and they can place cameras in the controlled substances area to help review any activities that may have occurred there, in case of possible diversion.

“You need to control these expired medications to the same extent as you would other controlled substances,” Dr. Mansur said. She added that weaknesses in the storage and transfer of controlled substances not only leave the drugs open to diversion, these potential failure points

also mean “there is likely no documented chain of custody.”

Dr. Mansur said knowing who has access to a controlled substance at each point in the medication management process—beginning from the receipt of medications in the pharmacy, to the delivery of these drugs to hospital units, their return to the pharmacy and their disposal—is critical to preventing diversion. “A strong

Diversion Red Flags in Health Care Workers • Abnormal behaviors • Altered physical appearance • Poor job performance.

Source: The Joint Commission

Indication and Usage HYPERRAB® (rabies immune globulin [human]) is indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies.

Limitations of Use

Diversion Red

Persons who have been previously immunized with rabies vaccine and have a confirmed Flags Health adequate rabiesin antibody titer should receive only vaccine.

Care Workers

For unvaccinated persons, the combination of HYPERRAB and vaccine is recommended for both bite and nonbite exposures regardless of the time interval between exposure and • Abnormal behaviors initiation of postexposure prophylaxis.

• Altered physical appearance

Beyond 7 days (after the first vaccine dose), HYPERRAB is not indicated since an • Poor job performance. antibody response to vaccine is presumed to have occurred.

Important Information Source: Safety The Joint Commission For infiltration and intramuscular use only.

Severe hypersensitivity reactions may occur with HYPERRAB. Patients with a history of prior systemic allergic reactions to human immunoglobulin preparations are at a greater risk of developing severe hypersensitivity and anaphylactic reactions. Have epinephrine available for treatment of acute allergic symptoms, should they occur.

HYPERRAB is made from human blood and may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

The most common adverse reactions in >5% of subjects during clinical trials were injection-site pain, headache, injection-site nodule, abdominal pain, diarrhea, flatulence, nasal congestion, and oropharyngeal pain.

Do not administer repeated doses of HYPERRAB once vaccine treatment has been initiated as this could prevent the full expression of active immunity expected from the rabies vaccine.

Other antibodies in the HYPERRAB preparation may interfere with the response to live vaccines such as measles, mumps, polio, or rubella. Defer immunization with live vaccines for 4 months after HYPERRAB administration.

Please see brief summary of Prescribing Information on adjacent page or visit HyperRAB.com for full Prescribing Information.

Operations & Management

Pharmacy Practice News • June 2021

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Compliance chain of custody is a hallmark of a tight medication management system,” Dr. Mansur stressed. To that end, she urged organizations to audit points along the movement of controlled substances to make sure there are no gaps in the chain of custody.

Review Discrepancies As institutions prepare for their next Joint Commission survey, Dr. Mansur said they should be ready for surveyors to review their policies for managing controlled substances discrepancies. “Take

a look at who is allowed to resolve discrepancies when they occur and whether there are red flags that should be addressed,” she said. “For example, if one or more individuals has a large number of discrepancies,” that type of outlier behavior needs to be examined.

Dr. Mansur said creating policies for discrepancy investigation is key, but perhaps more important is ensuring compliance with these policies. If a policy directs resolutions to take place within a specified amount of time, make sure that time line is being met, she said.

®

Dr. Mansur added that when surveyors find a lax approach to compliance with controlled substances management and storage policies, they may suspect compliance issues with other organizational requirements, and they may review other aspects of controlled substances oversight or management.

Dr. Dove said the best way to achieve compliance with policies for controlled substances management is through the creation of “multidisciplinary diversion committees that review reports, refine processes, handle diversion issues and

HyperRAB

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

HIGHLIGHTS OF PRESCRIBING INFORMATION

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

Rabies Immune Globulin (Human) These highlights do not include all the information needed to use HYPERRAB® safely and effectively.

See full prescribing information for HYPERRAB. HYPERRAB [rabies immune globulin (human)] solution for infiltration and intramuscular injection Initial U.S. Approval: 1974 ----------------INDICATIONS AND USAGE------------------HYPERRAB is a human rabies immune globulin indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies.

Limitations of Use Persons previously immunized with rabies vaccine that have a confirmed adequate rabies antibody titer should receive only vaccine.

For unvaccinated persons, the combination of HYPERRAB and vaccine is recommended for both bite and nonbite exposures regardless of the time interval between exposure and initiation of postexposure prophylaxis.

Beyond 7 days (after the first vaccine dose), HYPERRAB is not indicated since an antibody response to vaccine is presumed to have occurred.

--------------DOSAGE AND ADMINISTRATION------------For infiltration and intramuscular use only.

Administer HYPERRAB within 7 days after the first dose of rabies vaccine.

Postexposure HYPERRAB • Administer as soon as possible after 20 IU/kg prophylaxis, exposure, preferably body weight along with at the time of the first OR rabies vaccine, after 0.0665 mL/kg rabies vaccine dose. body weight • Infiltrate the full suspected exposure to dose of HYPERRAB Single dose rabies thoroughly in the area around and into the wound(s), if anatomically feasible.

• Inject the remainder, if any, intramuscularly.

-------------WARNINGS AND PRECAUTIONS-------------• Severe hypersensitivity reactions, including anaphylaxis, may occur with HYPERRAB. Have epinephrine available immediately to treat any acute severe hypersensitivity reactions.

• HYPERRAB is made from human blood; it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

--------------------ADVERSE REACTIONS--------------------The most common adverse reactions in >5% of subjects in clinical trials were injection site pain, headache, injection site nodule, abdominal pain, diarrhea, flatulence, nasal congestion, and oropharyngeal pain.

To report SUSPECTED ADVERSE REACTIONS, contact Grifols Therapeutics LLC at 1-800-520-2807 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

--------------------DRUG INTERACTIONS------------------• Repeated dosing after administration of rabies vaccine may suppress the immune response to the vaccine.

• Defer live vaccine (measles, mumps, rubella) administration for 4 months.

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

3054805 Revised: 11/2019

educate staff. Awareness and accountability are everyone’s responsibility.”

When trying to raise awareness of diversion at your health system, she added, it may help to remind colleagues about the high stakes involved. “Diversion not only hurts the diverter, but can jeopardize the safety of patients, colleagues and the organization.”

—David Wild The sources reported no relevant financial disclosures other than their stated employment.

Indicated for all persons suspected of exposure to rabies

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

HyperRAB® (rabies immune globulin [human]) 300 IU/mL Over O ver 4 45 5y years ears o off safe safe and and effective eff ffe ective use use iin n 1-5 over 1 million patients.

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REDEFINING HRIG ADMINISTRATION Please see Important Safety Information and brief summary of Prescribing Information for HyperRAB on adjacent pages, or visit www.HyperRAB.com for full Prescribing Information.

HyperRAB® (rabies immune globulin [human]) is indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies.

HyperRAB is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent that can cause disease. There is also the possibility that unknown infectious agents may be present in such products.

#1 Prescribed HRIG in the US

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

For more information, visit www.HyperRAB.com © 2021 Grifols

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