Pharmacy Practice News - November 2021

The Best-Read Pharmacist’s News Source

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Longer storage times now permitted if testing performed

CLINICAL

IDWeek: Should you wash your hands after tying your shoes?..

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Pandemic spurs nutrition gap in ICUs ..... 6 HOPA: When to stop ABx for febrile neutropenia ........................

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POLICY

2022 outpatient payments: What’s on the table? ...................

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Going above and beyond USP Chapters <795>, <797> .................

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USP Releases Newly Proposed <797> Revisions

Volume 48 • Number 11 • November 2021

$80 million recovered at just one health system

Replacing Lost Revenue During the Pandemic

A

fter almost two years of anticipation, USP has issued its new proposed revisions to Chapter <797>, “Pharmaceutical Compounding— Sterile Preparations.” What does this mean for sterile compounding in your pharmacy?

For most hospitals, which already had prepared to comply with the original <797> revisions, the temptation is to answer, probably “not much.” But complacency is not advisable, experts warned. They stressed that the release still provides an important opportunity to check compliance with key provisions, and to become familiar with an important and much-awaited decision on beyond-use dating (BUD).

After the original publication

W

ith normal revenues severely constricted by the influx of critical COVID-19 patients, health systems and hospitals tals across the country have had to find other ways to replace vanished income streams.

“One of the biggest challenges with COVID-19 has been the continunuing downward pressure on the financials,” said James Jorgenson, MS, RPh, the CEO of Visante, a pharmacy consulting firm. “Operating margins for the average hospital right now are somewhere in the 1% to 3% range.”

Continued on page 24

OPERATIONS & MGMT

ASHP leadership conference: managed care survival skills .......

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SPECIALTY PHARMACY

How to become an outcomes powerhouse ...................

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Little things can cause big problems in patient care ...............

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TECHNOLOGY

TJC, ISMP tips for smart pump safety .....

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Strategies for optimizing IV-WMS ....

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Continued on page 34

A call for major reform

One expert: 21% rate ‘boggles my mind’

340Bs Push Back On Abuses Cited In COA Report

IV-WMS: Slow Adoption Remains A Threat to Compounding Safety

T

he Community Oncology Alliance (COA) has accused some safety net hospitals of gaming a federal drug discount program to boost profits.

The group says disproportionate share hospitals (DSH) participating in the 340B Drug Pricing Program charge nearly four times their acquisition costs for expensive oncology drugs, and pocket the margins.

Since 1992, the 340B program has required drug manufacturers to Continued on page 26

A

lthough the COVID-19 pandemic continues to strain budgets and resources, U.S. hospital pharmacies have made progress in adopting IV workflow management systems (IV-WMS), which pharmacy leaders say is critical to improving the safety and efficiency of IV drug compounding.

Still, progress is slow. With a minority of hospitals using IV-WMS, advocates are questioning why the technology remains so underused despite years of guideline recommendations and robust evidence of its benefits.

“Why aren’t IV workflow systems in every hospital in the country?” asked Christopher R. Fortier, PharmD, the chief pharmacy manager

Management of

Idiopathic Pulmonary Fibrosis See page 14.

at Massachusetts General Hospital (MGH), in Boston, during Illuminate 2021, Omnicell’s digital medication management conference.

“Adoption is really low. It boggles my mind.

This technology has been around for 10 or more years, so why [the delay]?”

Several factors may contribute to the low rate of adoption, but Dr. Fortier’s theory is that hospitals were incentivized to focus on implementing electronic health record (EHR) systems when IV-WMS first hit the market. “I think IV workflow got put on the back burner,” he said. But he and many of his colleagues hope that change is on the horizon.

Continued on page 40

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Clinical

Pharmacy Practice News • November 2021

3

Infectious Disease IDWeek: managing amid a pandemic

Stewardship, C. difficile and Hand Hygiene In these highlights from our coverage of IDWeek 2021, held virtually, we present the latest findings about the effects of the COVID-19 pandemic on antibiotic stewardship and hand hygiene, including whether we should be washing our hands after tying our shoes.

Antibiotic Stewardship Efforts Persist Despite Pandemic After an initial spike in antibiotic prescribing at Veterans Affairs’ medical centers during the COVID-19 pandemic, antibiotic use returned to prepan-

demic levels, according to a study’s lead researcher, Matt Goetz, MD, the chief of infectious diseases at the VA Greater Los Angeles Healthcare System (poster 170).

“In our previously published work, we demonstrated that antibiotic use in the

Important Safety Information ALBUTEIN® 25% (albumin [human] U.S.P.) is indicated for: hypovolemia, cardiopulmonary bypass procedures, acute nephrosis, hypoalbuminemia, ovarian hyperstimulation syndrome, neonatal hyperbilirubinemia, adult respiratory distress syndrome (ARDS), and prevention of central volume depletion after paracentesis due to cirrhotic ascites.

ALBUTEIN® 5% (albumin [human] U.S.P.) is indicated for: hypovolemia, cardiopulmonary bypass procedures, hypoalbuminemia, and plasma exchange.

ALBUTEIN 5% and 25% are contraindicated in patients with a history of hypersensitivity to albumin preparations or to any of the excipients, and in patients with severe anemia or cardiac failure with normal or increased intravascular volume.

Allergic or anaphylactic reactions require immediate discontinuation of the infusion and implementation of appropriate medical treatment.

Hypervolemia may occur if the dosage and rate of infusion are not adjusted to the patient’s volume status. At the first clinical signs of fluid overload, the infusion must be slowed or stopped immediately. Use albumin with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk to the patient.

The colloid-osmotic effect of human albumin 25% is approximately five times that of blood plasma. Therefore, when concentrated albumin is administered, care must be taken to assure adequate hydration of the patient. Patients should be monitored carefully to guard against circulatory overload and hyperhydration. Patients with marked dehydration require administration of additional fluids.

Concentrated (20% - 25%) human albumin solutions are relatively low in electrolytes compared to 4% - 5% human albumin solutions. Regularly monitor the electrolyte status of the patient and take appropriate steps to restore or maintain the electrolyte balance when albumin is administered.

Regular monitoring of coagulation and hematology parameters is necessary if comparatively large volumes are to be replaced. Care must be taken to ensure adequate substitution of other blood constituents (coagulation factors, electrolytes, platelets and erythrocytes).

Regularly monitor hemodynamic parameters during administration of ALBUTEIN® 5% and 25% (albumin [human] U.S.P.).

ALBUTEIN 5% and 25% must not be diluted with sterile water for injection as this may cause hemolysis in recipients.

Albumin is a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) is also considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for ALBUTEIN 5% or 25%.

The most serious adverse reactions with use of albumin are anaphylactic shock, heart failure and pulmonary edema. The most common adverse reactions are anaphylactoid type reactions. Adverse reactions to ALBUTEIN normally resolve when the infusion rate is slowed or the infusion is stopped. In case of severe reactions, the infusion should be stopped and appropriate treatment initiated.

Please see accompanying full Prescribing Information for ALBUTEIN 5% and 25%.

© 2021 Grifols All rights reserved September 2021 US-AFB25-2100023

VA increased by 11% in the first five months of 2020, largely reversing declines in VA antimicrobial utilization that had occurred since 2015,” Dr. Goetz said. “We wanted to see whether these changes persisted throughout the COVID-19 pandemic.” see IDWeek, page 4

4 Clinical

Pharmacy Practice News • November 2021

Infectious Disease

IDWEEK continued from page 3

Dr. Goetz and his team analyzed data on antimicrobial use in acute inpatient care units at 108 level 1 VA facilities and two other VA facilities between January 2020 and February 2021. They included COVID-19 and non–COVID-19 patients.

A level 1 unit cares for the most complex, high-risk patients.

Monthly total acute care antibiotic use increased from a low of 533 days of treatment per 1,000 patient care days in

January 2020, to 583 days of treatment per 1,000 days of care in April 2020.

After that initial rise, antibiotic use declined to 495 days of treatment per 1,000 days of care in September 2020, and remained at prepandemic levels subsequently, with fewer than 500 days of treatment per 1,000 days of care in February 2021.

“This decrease [occurred] despite rises in COVID-19 care, which accounted for 24% of all patient care in January 2021,” Dr. Goetz noted.

When the investigators analyzed

ALBUTEIN

FlexBag 5% (albumin [human] U.S.P.) 5% solution These highlights do not include all the information needed to use ALBUTEIN FlexBag 5% safely and effectively. See full prescribing information for ALBUTEIN FlexBag 5%.

ALBUTEIN FlexBag 5% (albumin [human] U.S.P.) 5% solution Initial U.S. Approval: 1978 ------------------------------------------INDICATIONS AND USAGE -----------------------------------------ALBUTEIN 5% is an albumin solution indicated for: • Hypovolemia.

• Cardiopulmonary bypass procedures.

• Hypoalbuminemia.

• Plasma exchange.

--------------------------------------DOSAGE AND ADMINISTRATION-------------------------------------For Intravenous Use Only Dosage and infusion rate should be adjusted to the patient’s individual requirements.

Indication

Dose

Hypovolemia

Adults: Initial dose of 20 g (including renal dialysis).

For acute liver failure: initial dose of 12 to 25 g.

Cardiopulmonary bypass procedures

Adults: Initial dose of 25 g.

Hypoalbuminemia

Adults: 50 to 75 g For pre- and post-operative hypoproteinemia: 50 to 75 g.

For burn therapy after the first 24 h: initial dose of 25 g and dose adjustment to maintain plasma protein concentration of 2.5 g per 100 mL. Third space protein loss due to infection: initial dose of 50 to 100 g.

Plasma exchange

The dose required depends on the volume of plasma removed during the procedure.

ALBUTEIN

FlexBag 25% (albumin [human] U.S.P.) 25% solution These highlights do not include all the information needed to use ALBUTEIN FlexBag 25% safely and effectively. See full prescribing information for ALBUTEIN FlexBag 25%.

ALBUTEIN FlexBag 25% (albumin [human] U.S.P.) 25% solution Initial U.S. Approval: 1978 ------------------------------------------INDICATIONS AND USAGE -----------------------------------------ALBUTEIN 25% is an albumin solution indicated for: • Hypovolemia.

• Cardiopulmonary bypass procedures.

• Acute nephrosis.

• Hypoalbuminemia.

• Ovarian hyperstimulation syndrome.

• Neonatal hyperbilirubinemia.

• Adult respiratory distress syndrome (ARDS).

• Prevention of central volume depletion after paracentesis due to cirrhotic ascites.

--------------------------------------DOSAGE AND ADMINISTRATION-------------------------------------For Intravenous Use Only Dosage and infusion rate should be adjusted to the patient’s individual requirements.

Indication

Dose

Hypovolemia

Adults: Initial dose of 25 g (including renal dialysis).

For acute liver failure: initial dose of 12 to 25 g.

Cardiopulmonary bypass procedures

Adults: Initial dose of 25 g.

Acute nephrosis

Adults: 25 g together with diuretic once a day for 7 - 10 days.

Hypoalbuminemia

Adults: 50 to 75 g For pre- and post-operative hypoproteinemia: 50 to 75 g.

For burn therapy after the first 24 h: initial dose of 25 g and dose adjustment to maintain plasma protein concentration of 2.5 g per 100 mL. Third space protein loss due to infection: initial dose of 50 to 100 g.

Ovarian hyperstimulation syndrome

Adults: 50 g to 100 g over 4 hours and repeated at 4-12 hour intervals as necessary.

antibiotic use patterns according to COVID-19 and non–COVID-19 patients, they found antibiotic use decreased from a high of 550 days of treatment per 1,000 days of care during the early phase of the pandemic for non–COVID-19 patients to 509 days of treatment per 1,000 days of care between November 2020 and February 2021 for this group. Similarly, antibiotic use among COVID-19 patients dropped from a peak of 590 days of treatment per 1,000 days of care in the early phase of the pandemic to

Do not dilute with sterile water for injection as this may cause hemolysis in recipients.

------------------------------------DOSAGE FORMS AND STRENGTHS -----------------------------------ALBUTEIN 5% is a solution containing 50 g per L of total protein of which at least 95% is human albumin.

---------------------------------------------CONTRAINDICATIONS--------------------------------------------• Hypersensitivity to albumin preparations or to any of the excipients.

• Severe anemia or cardiac failure with normal or increased intravascular volume.

--------------------------------------WARNINGS AND PRECAUTIONS-------------------------------------• Suspicion of allergic or anaphylactic reactions requires immediate discontinuation of the injection and implementation of appropriate medical treatment.

• Hypervolemia may occur if the dosage and rate of infusion are not adjusted to the patient’s volume status. Use with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk to the patient.

• Monitor electrolytes, coagulation and hematology parameters, and hemodynamic status when albumin is given.

• Do not dilute with sterile water for injection.

• This product is made from human plasma and may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease agent.

528 days of treatment per 1,000 days of care between November 2020 and February 2021.

“These data support the continued effectiveness of antimicrobial stewardship programs in the VA,” Dr. Goetz concluded.

Did COVID-19 Permanently Change Hand Hygiene Practices?

The COVID-19 pandemic increased attention to hand hygiene, but did it really have a lasting effect? Not likely, according to a behavior study (poster 422).

“Hand hygiene is an important infection prevention and control practice to limit the transmission of infection, including COVID-19, in a health care setting,” said Victoria Williams, MPH, an infection prevention and control epidemiologist at Sunnybrook Health Sciences Centre, in Toronto.

-------------------------------------------- ADVERSE REACTIONS -------------------------------------------The most common adverse reactions are anaphylactoid type reactions.

To report SUSPECTED ADVERSE REACTIONS, contact Grifols Biologicals LLC at 1-888-GRIFOLS (1-888-474-3657) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

------------------------------------- USE IN SPECIFIC POPULATIONS ------------------------------------• Pregnancy: No human or animal data. Use only if clearly needed.

Revised: 07/2021

Manufactured by: Grifols Biologicals LLC 5555 Valley Boulevard Los Angeles, CA 90032, U.S.A. U.S. License No. 1694

3061038

Indication

Dose

Neonatal hyperbilirubinemia

1 g per kilogram body weight prior to or during exchange transfusion.

Adult respiratory distress syndrome (ARDS)

Adults: 25 g over 30 minutes and repeated at 8 hours for 3 days, if necessary.

Prevention of central volume depletion after Adults: 8 g for every 1000 mL of ascitic fluid removed. paracentesis due to cirrhotic ascites Do not dilute with sterile water for injection as this may cause hemolysis in recipients.

------------------------------------DOSAGE FORMS AND STRENGTHS -----------------------------------ALBUTEIN 25% is a solution containing 250 g per L of total protein of which at least 95% is human albumin.

---------------------------------------------CONTRAINDICATIONS--------------------------------------------• Hypersensitivity to albumin preparations or to any of the excipients.

• Severe anemia or cardiac failure with normal or increased intravascular volume.

--------------------------------------WARNINGS AND PRECAUTIONS-------------------------------------• Suspicion of allergic or anaphylactic reactions requires immediate discontinuation of the injection and implementation of appropriate medical treatment.

• Hypervolemia may occur if the dosage and rate of infusion are not adjusted to the patient’s volume status. Use with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk to the patient.

• When concentrated albumin is administered, care must be taken to assure adequate hydration of the patient.

• Monitor electrolytes, coagulation and hematology parameters, and hemodynamic status when albumin is administered.

• Do not dilute with sterile water for injection.

• This product is made from human plasma and may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease agent.

-------------------------------------------- ADVERSE REACTIONS -------------------------------------------The most common adverse reactions are anaphylactoid type reactions.

To report SUSPECTED ADVERSE REACTIONS, contact Grifols Biologicals LLC at 1-888-GRIFOLS (1-888-474-3657) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

------------------------------------- USE IN SPECIFIC POPULATIONS ------------------------------------• Pregnancy: No human or animal data. Use only if clearly needed.

Manufactured by: Grifols Biologicals LLC 5555 Valley Boulevard Los Angeles, CA 90032, U.S.A. U.S. License No. 1694

Revised: 05/2019

3055225

To evaluate long-term hand hygiene performance through subsequent waves of the pandemic, Ms. Williams and her colleagues studied the practice at 56 inpatient, acute care units located in six university and seven community acute care hospitals in Ontario.

An electronic monitoring system tracked the use of alcohol hand rub and soap sink dispensers located in and outside of patient rooms. Data were collected from Nov. 1, 2019, through May 31, 2021, and divided into a prepandemic baseline period and three subsequent COVID-19 waves: 1. wave 1 (March 1 through June 30, 2020); 2. wave 2 (Oct. 1, 2020, through Feb. 28, 2021); and 3. wave 3 (March 1 through May 31, 2021).

During the baseline period of Nov. 1 through Dec. 20, 2020, median adherence to hand hygiene was 43% and peak adherence reached 49%.

Hand hygiene performance rose before the arrival of the first COVID-19 wave in Ontario, likely as news began to spread about the pandemic. During wave 1, adherence increased sharply, reaching a median of 64% and peak of 79%.

However, the improvement was not sustained. Hand hygiene adherence returned to baseline following wave 1

Clinical

Pharmacy Practice News • November 2021

5

Infectious Disease of the pandemic, and did not measurably increase over the course of wave 2 (median, 49%; peak, 53%) or wave 3 (median, 47%; peak, 52%).

“The increase in hand hygiene adherence seen during wave 1 of the COVID-19 pandemic indicates high levels of adherence are possible in response to events,” Ms. Williams said. “But quality improvement initiatives are required to sustain the change in practice.

“In this specific instance,” Ms. Williams continued, “the improvement was likely associated with fear and desire for self-preservation in the context of a novel pathogen. Once the perceived risk of COVID-19 had decreased, hand hygiene decreased as well, despite subsequent community waves of infection.”

Are Shoes a Vector For C. difficile Infections?

Strongly consider washing your hands the next time you tie your shoelaces. According to an international study of nearly 12,000 environmental isolates, up to 45% of samples from shoe soles contain Clostridioides difficile spores. The pathogen also was found on surfaces and floors in houses,

parks and public bui buildings u ldings (oral abstract 18).

Considering thatt one-third of C. diffficile infections (CDIs) DIs) originate in the comommunity, researcherss are urging at-risk individuals dividuals to implement measures to minimize exposure to the pathogen. “[I would advise] patients at high risk of [CDI] to clean their house with a sporicidal and, if you’re going out into the community, for the first month after hospitalization, wear a mask,” said senior investigator Kevin Garey, PharmD, a professor of pharmacy practice and the chair of the Department of Pharmacy Practice

and Transl ati o n al Research at the University of Houston College of Pharmacy.

Lead researcher Jinhee Jo, PharmD, a postdoctoral infectious disease fellow in Dr. Garey’s laboratory, and her colleagues c ol l e cte d 11,986 environmental samples in the United States and nine other ccountries in Europe, Asia, aand Central and South America between 2014 and A 2017. The samples came from 201 outdoor environments, private outdo shoe soles, public rresidences, re sid buildings and acute care setbuild tings. Positive samples underwent confirmatory polymerase chain reaction (PCR) testing for toxin genes and fluorescent PCR ribotyping.

According to Dr. Jo, 27% of the samples tested positive for toxigenic C. difficile, with similar rates in the United States and other countries. Samples from shoe soles had the highest positivity rate, at 45%, and the ribotypes

EDITORIAL BOARD ADMINISTRATION Robert Adamson, PharmD, Livingston, NJ

—David Wild and Ethan Covey

2021 Silver Award Winner

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How-to Feature

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James A. Jorgenson, MS, RPh, St. Paul, MN

Volume 48 • Number 11 • November 2021 • pharmacypracticenews.com

Indu Lew, PharmD, Livingston, NJ

were similar for shoe soles and surrounding environmental samples. Other non–health care locations with high positivity rates were private residences (26.2%), outdoor environments (24.1%) and public buildings (17.2%). A subanalysis of samples from Texas showed that 24% of isolates from health care facilities included C. difficile spores.

Dr. Jo noted that it is possible shoe soles could serve as a vector for C. difficile transmission—and possibly other pathogens that cause what usually are considered health care–associated infections—but more studies are needed to confirm that suspicion.

In the interim, she said community infection control measures may help reduce transmission. Interventions might include disinfecting floors in public buildings and other areas with high foot traffic, such as universities and grocery stores, she said.

Dr. Garey added that although there is no evidence that removing shoes indoors reduces the likelihood of CDI, it makes intuitive sense to do so as a way of reducing risk for C. difficile transmission.

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6 Clinical

Pharmacy Practice News • November 2021

Nutrition

COVID-19 Puts Pressure on ICU Nutrition Support M

ost critically ill COVID-19 patients are not having their nutrition needs fully met, according to a new survey. Fortunately, this management gap can be filled by enlisting the aid of non-nutrition support clinicians and other staffing strategies, according to several experts who spoke during a webinar convened during the American Society for Parenteral and Enteral Nutrition (ASPEN) Malnutrition Awareness Week, held Oct. 4-8, 2021.

Only 9% of the nearly 200 respondents, who included dietitians and physicians, reported that COVID-19 patients met their full nutritional support needs in the ICU, and 63% reported that these patients typically received less than 60% of their energy/protein goals (JPEN J Parenter Enteral Nutr 2021 Sep 5. doi:10.1002/jpen.2263).

“We’ve had multiple patients who are having difficulty tolerating enteral nutrition [EN] for a variety of reasons,” said Sarah Cogle, PharmD, BCNSP, an associate clinical professor at Auburn University Harrison School of Pharmacy, in Alabama. “Many have severe acute respiratory distress syndrome, and are on different therapies like proning and

population should be lower than in n typical ICU patients (JPEN J Parenterr Enteral Nutr 2020;44:1174-1184).

Patients of particular concern aree those with septic shock and/or requir-ing high-pressure respiratory support, t, she noted. “It’s currently suggested thatt after a week or so, if you’re not at targett with enteral nutrition, to consider sup-plemental PN. Some studies have start-ed PN a little sooner for patients who o were not receiving target feeds around d day 3” (Clin Nutr 2019;38[5]:2408-2416). ).

But in the survey, 24% of clinicianss said they would use PN in COVID-19 9 patients only if there were noticeable malnutrition, weight loss or the presence of severe disease. Moreover, 17% said they would not use supplemental PN under any circumstances in patients already receiving EN. The biggest concerns conveyed by non-nutrition support clinicians, Dr. Cogle said, is that they believe moving to PN will produce worse outcomes, including higher mortality rates and increased rates of infection. “Recent trials have not shown that,” she said.

“We haven’t seen major improvements in mortality outcomes, but outcomes

‘With past practices, sometimes we were literally overfeeding people, which led to much higher rates of infection. Make sure that your non-nutrition support colleagues are aware that today we do a much better job at writing and managing these orders and achieving glycemic control.’

—Sarah Cogle, PharmD continuous or intermittent neuromuscular blockade. Many have issues with hypotension and aren’t getting good perfusion. In some, all these things are going on at once. We’re still trying to feed enterally, but we’re seeing a lot more intolerance of feeding via the enteral route among these patients.”

Reaching Outside the Specialty The decision on when to begin parenteral nutrition (PN) in a patient who had been enterally fed can be a challenging one, particularly in the context of COVID-19. For nutrition support clinicians, it’s one that requires close collaboration with clinical colleagues outside the specialty.

“We don’t have a lot of specific, clear evidence as to when we should switch,” Dr. Cogle said. She noted that supplemental COVID-19 guidelines issued by ASPEN and the Society of Critical Care Medicine in 2020 recommend that the threshold for switching to PN in this

have not been worse either. While supplemental PN may not be for everyone, there are certain patients who are perhaps at more nutritional risk who may be appropriate.”

Earlier trials, such as the 2011 EPaNIC study, found increased infections and longer ICU length of stay with early PN initiation (N Engl J Med 2011;365[6]:506-517), Dr. Cogle noted, but several more recent trials have found no differences in mortality, functional outcomes or infectious complications (N Engl J Med 2014;371[18]:1673-1684; Lancet 2018;391:133-143; Crit Care 2017;21[1]:142).

“These studies found that patients who got supplemental PN received more calories and protein, but they didn’t necessarily see a difference in outcomes,” Dr. Cogle said. “But many of these trials didn’t focus on functional outcomes. A 2021 review of the literature hypothesized that EN plus PN may be associated with a trend toward lower mortality in patients at higher nutrition

‘If you look only at height, weight and body mass index [to detect malnutrition], you’re not necessarily considering how sick the patient is now, or other preexisting factors that may be putting the patient at risk for malnutrition.’

—Carol McGinnis, DNP risk, and the authors recommended that a focus on functional outcomes may be appropriate in future trials” (JPEN J Parenter Enteral Nutr 2021 Apr 26. doi:10.1002/jpen.2125).

Most prescribers are big believers in EN, Dr. Cogle said. “I am, too, but a lot of the concern with PN stems from older data with higher infection and complication rates and worse outcomes. We need to be an educational resource for our teams, providing education about the shift, listening to the concerns of non-nutrition support clinicians and providing information about factors that have led to better outcomes, such as the fact that we do a much better job managing PN now, and central line care is much better.”

Another reason for recent improvements in outcomes is elimination of hyperalimentation. “With past practices, sometimes we were literally overfeeding people, which led to much higher rates of infection,” Dr. Cogle said. “Make sure that your non-nutrition support colleagues are aware that today we do a much better job at writing and managing these orders and achieving glycemic control. We can adjust the formula every day to be sure we are not overfeeding.”

An Individualized Approach Deciding when to move from EN to PN, whether in a complex COVID-19 patient or any patient, should be individualized, Dr. Cogle said. “You may first want to focus on optimizing EN if at all possible, particularly with patients who are on so many other continuous drips.”

She recommended using validated

nutrition risk assessment scores recommended by ASPEN, such as the NUTRIC score, for critically ill patients.

“Don’t rely on weight alone to detect malnutrition,” agreed Carol McGinnis, DNP, APRN-CNS, CNSC, a clinical nurse specialist in nutrition support at Sanford USD Medical Center, in Sioux Falls, S.D. “If you look only at height, weight and body mass index, you’re not necessarily considering how sick the patient is now, or other preexisting factors that may be putting the patient at risk for malnutrition.”

Don’t just look at what has been ordered in terms of a patient’s nutrition; also pay attention to what they have actually received over a several-day period, according to Dr. Cogle. “There may be interruptions in feeding; for example, if a patient vomits and [feeding is withheld] for the rest of the day, the feeding was ordered but not received,” Dr. Cogle said. “Or if a patient goes to surgery and that surgery is postponed, their feeds may be held longer. Work with your non-nutrition support colleagues, such as nurses, to keep track of what the patient is actually getting.”

“The best nutritional outcomes, including patient safety, depend on the synergy of a high-functioning team where contribution of each member is valued and solicited,” Dr. McGinnis said.

—Gina Shaw Dr. Cogle reported that she is a speaker and study investigator for Fresenius Kabi.

Dr. McGinnis reported no relevant financial disclosures.

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8 Clinical

Pharmacy Practice News • November 2021

Oncology

Debate at HOPA Meeting:

When Is It Safe to Stop ABx for Febrile Neutropenia?

I

t may be safe to discontinue or deescalate antibiotics in some cancer patients who develop febrile neutropenia (FN) before the condition resolves, but guidelines and studies aren’t yet fully conclusive, a panel of speakers said during the Hematology/Oncology Pharmacy Association’s 2021 virtual annual conference.

Marked by fever and absolute neutrophil count (ANC) of less than 500 cells/mm3, the incidence of FN varies between 10% and 50% in solid tumors and is reportedly greater than 80% in hematological malignancies (Clin Infect Dis 2004;39:S32–S37. doi: 10.1086/383050). Risk factors include myelosuppressive chemotherapy regimens, older age and advanced disease, said Devon Greer, PharmD, BCOP, a clinical pharmacy specialist at Barnes-Jewish Hospital, in St. Louis. (For an online FN risk calculator in cancer, visit bit.ly/ 3CezeLn.) Although some patients are given granulocyte colony-stimulating factor or fluoroquinolones as prophylaxis, the complication still can occur, she said. If so, patients generally are given broad-spectrum IV or oral antibiotics until ANC recovers. Whether to stop

documented infection, or died. However, the study was small, with 17 patients in the group for whom antibiotics were halted, she noted.

“For the first time, this showed us we really should be continuing treatment until count recovery,” Dr. Signorelli said. “The trial showed that discontinuing antibiotics can have devastating outcomes, and the benefit of continuing really outweighed the risk of increasing multidrug-resistant organisms.”

A more recent study, from 2014 (Clin Microbiol Infect 2014;20[7]:O453-5), also supports continuing antibiotics in FN. In this study of 38 patients with 59 episodes of neutropenia, only seven patients met the criteria to discontinue antibiotics. The average number of days of antibiotics saved was four; however, three patients had recurrent fever, of which two had gram-negative bacterial infections and one had septic shock. The trial was stopped early because 66% of patients with fever recurrence developed bacteremia, leading the authors to conclude that high-risk neutropenic patients are not appropriate candidates for antibiotic discontinuation, Dr. Signorelli said.

‘Just because we deescalate does not mean you cannot reintroduce antibiotics and still have favorable outcomes.’

—Jared Matya, PharmD, BCOP antibiotics sooner has been a topic of interest, Dr. Greer said.

Guidelines from the Infectious Diseases Society of America and the National Comprehensive Cancer Center recommend continuing antibiotics until ANC reaches at least 500 cells/mm3, said Jessie Signorelli, PharmD, BCOP, an attending clinical pharmacist at Massachusetts General Hospital, in Boston.

Both organizations suggest considering deescalation to prophylactic antibiotics if patients are afebrile and hemodynamically stable. However, neither group provides any clinical criteria to guide decision making, she noted.

Some studies used for these guidelines date back decades, Dr. Signorelli noted. A 1966 study (Ann Intern Med 1966;64[2]:328-340) of patients with leukemia found that once ANC dropped below 500 cells/mm3, the rate of infection increased. A study (Am J Med 1979;67[2]:194-200) of pediatric patients with fever and neutropenia showed that when antibiotics were discontinued, some patients had recurrent fevers or

Better Stewardship On the flip side, arguments can be made for better antibiotic stewardship for patients with FN. Society guidelines now contain “hedging language” noting that clinicians can consider deescalation or prophylactic antibiotics in the right patient population, said Jared Matya, PharmD, BCOP, a focused population pharmacist at Nebraska Medicine, in Omaha. Still to be determined is which patients are most appropriate for this option, he cautioned.

There are more effective antibiotics available today than when the 1979 study was conducted, Dr. Matya said, and diagnostic and imaging tests also have come a long way. “Just because we deescalate does not mean you cannot reintroduce antibiotics and still have favorable outcomes,” he said, adding that although fevers are important, they can be caused by factors other than infection, he noted.

The ANTIBIOSTOP study (Infect Dis 2018;50[7]:539-549) of early discontinuation of antibiotics in 238 neutropenia patients either after 48 hours of being

Too Early Can Be Risky When antibiotics were stopped after 4 days: • 3 patients had recurrent fever (one had gram-negative bacterial infection and one had septic shock).

• 66% of patients with recurrent fever developed bacteremia.

Source: Clin Microbiol Infect 2014;20(7):O453-5.

afebrile or after five days even if febrile provides some support for discontinuing antibiotics, Dr. Matya said. The study had a fairly high percentage of patients receiving induction chemotherapy for leukemia, who may be at higher risk for FN, he said, and also included some patients undergoing allogeneic stem cell transplant. The overall duration of antibiotic use was five to seven days— shorter than waiting for patients to defervesce—and patients continued to have fever at the same rate regardless of when antibiotics were discontinued, he said, indicating antibiotics can be safely discontinued after 48 hours.

The How Long trial (Lancet Haematol 2017;4[12]:e573-e583) randomized 157 FN patients to continue antibiotics until ANC rose above 500 cells/mm3 or discontinue them after 72 hours if patients were afebrile, had normal vital signs and no evidence of infection. The number of antibiotic-free days was higher in the discontinued group, but other outcomes such as all-cause mortality and recurrent fever did not differ by much. There also was an increase in secondary infections such as candidiasis in the continued therapy group.

Drug Resistance Another Issue Antibiotic resistance is a documented problem in both the general population and patients with cancer, Dr. Matya said.

Prior antibiotic therapy is a risk factor for infection with multidrug-resistant organisms, rendering patients more likely to require ICU admission or mechanical ventilation and leading to worse outcomes such as increased medical costs and mortality (Int J Antimicrob Agents 2012;40[2]:123-126). An antibiotic use duration of more than seven days confers the greatest risk, he said.

A recurrent theme in some studies is that patients continuing on empiric therapy often receive two to three weeks of antibiotics, which is a longer course than is given for known infections, Dr. Matya said. “It’s another potential argument for using good stewardship.”

Continuing antibiotics until neutrophil counts recover is the safest option

and an approach supported by treatment guidelines, Dr. Signorelli said.

However, the strategy has limitations.

“We are seeing an increase in the development of multidrug-resistant organisms in people with cancer,” she said, and continuing IV antibiotics requires patients to stay in the hospital, increasing length of stay and decreasing quality of life. Conversely, deescalating antibiotics is not yet fully endorsed by national guidelines and could increase resistance to fluoroquinolones.

Another uncertainty is how long broad-spectrum antibiotics should be used before deescalation, Dr. Signorelli said. Some studies suggest five to seven days, while others recommend doing so after 48 to 72 hours. Also, what clinical criteria should be used?

Should clinicians deescalate to fluoroquinolones or discontinue antibiotics altogether? Furthermore, should patients remain in the hospital for monitoring versus being discharged home? If patients are discharged, how soon should follow-up occur?

Criteria for deescalation derived from studies (Ann Hematol 2020;99[8]: 1917-1924, and others) indicate patients should be afebrile and hemodynamically stable for at least 72 hours, have no signs or symptoms of infection or documented microbiological or clinical infection, and have not taken antibiotics prior to becoming febrile, Dr. Signorelli said.

The studies also suggest that to ensure success, patients should remain hospitalized for 48 hours of surveillance following antibiotic discontinuation if ANC is 500 cells/mm3 or lower. They should not be discharged if they reside more than 30 minutes from the nearest hospital and should have a caregiver who can drive them to the hospital if necessary. If fever recurs, patients should stay on broad-spectrum antibiotics until the neutrophil count rises to at least 500 cells/mm3, Dr. Signorelli said.

—Karen Blum The speakers reported no relevant financial disclosures.

UNANIMOUSLY RECOMMENDED BY THE ACIP1

PROTECTING YOUR ADULT PATIENTS FROM HEPATITIS B

IS AS EASY AS

HEPLISAV-B IS THE ONLY 2-DOSE, 1-MONTH HEPATITIS B VACCINE FOR ADULTS2,3 INDICATION HEPLISAV-B is indicated for prevention of infection caused by all known subtypes of hepatitis B virus in adults 18 years of age and older.

IMPORTANT SAFETY INFORMATION Do not administer HEPLISAV-B to individuals with a history of severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of HEPLISAV-B, including yeast.

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of HEPLISAV-B. Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to HEPLISAV-B. Hepatitis B has a long incubation period. HEPLISAV-B may not prevent hepatitis B infection in individuals who have an unrecognized hepatitis B infection at the time of vaccine administration.

The most common patient-reported adverse reactions reported within 7 days of vaccination were injection site pain (23%-39%), fatigue (11%-17%), and headache (8%-17%).

Please see Brief Summary of full Prescribing Information on the preceding pages.

heplisavb.com

2 DOSES. 1 MONTH. DONE.2

Abbreviation: ACIP, Advisory Committee on Immunization Practices.

REFERENCES: 1. Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for use of a hepatitis B vaccine with a novel adjuvant.MMWR Morb Mortal Wkly Rep. 2018;67(15):455-458. 2. HEPLISAV-B [package insert]. Emeryville, CA: Dynavax Technologies Corporation; 2020. 3. Freedman M, Kroger A, Hunter P, Ault KA. Recommended Adult Immunization Schedule, United States, 2020. Ann Intern Med. 2020;172(5):337-347.

© 2021 Dynavax Technologies Corporation.

All rights reserved. September 2021 US-21-00-00225

BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION

Table 1 Study 1: Percent of Subjects Who Reported Local or Systemic Reactions Within 7 Days of Vaccination

HEPLISAV-B [Hepatitis B Vaccine (Recombinant), Adjuvanted] Solution for Intramuscular Injection 1 INDICATIONS AND USAGE HEPLISAV-B is indicated for prevention of infection caused by all known subtypes of hepatitis B virus. HEPLISAV-B is approved for use in adults 18 years of age and older.

2 DOSAGE AND ADMINISTRATION For intramuscular administration.

2.1 Dose and Regimen Administer two doses (0.5 mL each) of HEPLISAV-B one month apart.

2.2 Administration HEPLISAV-B is a clear to slightly opalescent, colorless to slightly yellow solution.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered.

Administer HEPLISAV-B by intramuscular injection in the deltoid region using a sterile needle and syringe.

3 DOSAGE FORMS AND STRENGTHS syringes. [see How Supplied/Storage and Handling (16.1)].

4 CONTRAINDICATIONS Do not administer HEPLISAV-B to individuals with a history of severe allergic reaction (e.g. anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of HEPLISAV-B, including yeast [see Description (11)].

5 WARNINGS AND PRECAUTIONS 5.1 Managing Allergic Reactions Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of HEPLISAV-B. 5.2 Immunocompromised Individuals Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to HEPLISAV-B. 5.3 Limitations of Vaccine Effectiveness Hepatitis B has a long incubation period. HEPLISAV-B may not prevent hepatitis B infection in individuals who have an unrecognized hepatitis B infection at the time of vaccine administration.

6 ADVERSE REACTIONS 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the A total of 9597 individuals 18 through 70 years of age received at least 1 dose of HEPLISAV-B in 5 clinical trials conducted in the United States, Canada, and Germany. Data from 3 of these trials are provided below.

Study 1 in Subjects 18 through 55 Years of Age Study 1 was a randomized, observer-blind, active-controlled, multicenter study in Canada and Germany in which 1810 subjects received at least 1 dose of HEPLISAV-B and 605 subjects received at least 1 dose of Engerix-B® [Hepatitis B Vaccine (Recombinant)].

Enrolled subjects had no history of hepatitis B vaccination or infection. HEPLISAV-B was given as a 2-dose regimen at 0 and 1 month followed by saline placebo at 6 months.

Engerix-B was given at 0, 1, and 6 months. In the total study population, the mean age was 40 years; 46% of the subjects were men; 93% were white, 2% black, 3% Asian and 3% Hispanic; 26% were obese, 10% had hypertension, 8% had dyslipidemia, and 2% had diabetes mellitus. These demographic and baseline characteristics were similar in both vaccine groups.

Solicited Local and Systemic Adverse Reactions Subjects were monitored for local and systemic adverse reactions using diary cards for a 7-day period starting on the day of vaccination. The percentages of subjects who reported local and systemic reactions are shown in Table 1.

Table 1 Study 1: Percent of Subjects Who Reported Local or Systemic Reactions Within 7 Days of Vaccination

Reaction Local Injection Site Pain

Engerix-B %

Post-Dose*

Post-Dose*

1

2

1

2

3

Headache

16.9

12.8

19.2

12.3

9.5

Malaise

9.2

7.6

8.9

6.5

6.4

N=1784

N=1764

N=596

N=590

N=561

1.1

1.5

1.8

1.7

1.8

Reaction

Fever‡

Note: only subjects having data are included. Clinical trial number: NCT00435812 *HEPLISAV-B was given as a 2-dose regimen at 0 and 1 month followed by saline placebo at 6 months. Engerix-B was given at 0, 1, and 6 months † Redness and swelling ≥ 2.5 cm. ‡ Oral temperature ≥ 100.4°F (38.0°C).

Unsolicited Adverse Events: Unsolicited adverse events within 28 days following any injection, including placebo, were reported by 42.0% of HEPLISAV-B recipients and 41.3% of Engerix-B recipients.

Serious Adverse Events (SAEs) vaccine. The percentage of subjects reporting serious adverse events was 1.5% in the HEPLISAV-B group and 2.1% in the Engerix-B group. No acute myocardial infarctions were reported. No deaths were reported.

Potentially Immune-mediated Adverse Events dose of vaccine were reported in 0.2% (n = 4) of HEPLISAV-B recipients and 0.7% (n = 4) of Engerix-B recipients. The following events were reported in the HEPLISAV-B group in one subject each: granulomatosis with polyangiitis, lichen planus, Guillain-Barré syndrome, and Grave’s disease. The following events were reported in the Engerix-B group in one subject each: Bell’s palsy, Raynaud’s phenomenon, and Grave’s disease. One additional Engerix-B recipient with a history of mixed connective tissue disease had p-ANCA-positive vasculitis.

Study 2 in Subjects 40 through 70 Years of Age Study 2 was a randomized, observer-blind, active-controlled, multicenter study in Canada and the United States in which 1968 subjects received at least 1 dose of HEPLISAV-B and 481 subjects received at least 1 dose of Engerix-B. HEPLISAV-B was given as a 2-dose regimen at 0 and 1 month followed by saline placebo at 6 months. Enrolled subjects had no history of hepatitis B vaccination or infection. Engerix-B was given at 0, 1, and 6 months. In the total population, the mean age was 54 years; 48% of subjects were men; 82% were white, 15% black, 1% Asian and 6% Hispanic; 44% were obese, 30% had hypertension, 30% had dyslipidemia, and 8% had diabetes mellitus. These demographic and baseline characteristics were similar in both vaccine groups.

Solicited Local and Systemic Adverse Reactions Subjects were monitored for local and systemic adverse reactions using diary cards for a 7-day period starting on the day of vaccination. The percentages of subjects who experienced local and systemic reactions are shown in Table 2.

Table 2 Study 2: Percent of Subjects Who Reported Local or Systemic Reactions Within 7 Days of Vaccination HEPLISAV-B %

Engerix-B %

Post-Dose*

Post-Dose*

1

2

1

2

3

N=1952

N=1905

N=477

N=464

N=448

Injection Site Pain

23.7

22.8

18.4

15.9

13.8

Injection Site Redness†

0.9

0.7

0.6

0.2

0.2

Injection Site Swelling†

0.9

0.6

0.6

0.6

0.2

10.8

12.8

12.1

9.4

Reaction Local

Systemic

HEPLISAV-B %

Engerix-B %

Fatigue

12.6

Post-Dose*

Post-Dose*

Headache

11.8

8.1

11.9

9.5

8.5

7.7

7.0

8.6

7.1

5.1

8.5

6.4

9.6

8.0

4.5

N=1923

N=1887

N=472

N=459

N=438

1

2

1

2

3

Malaise

N=1810

N=1798

N=605

N=603

N=598

Myalgia

38.5

34.8

33.6

24.7

20.2

Injection Site Redness†

4.1

2.9

0.5

1.0

0.7

Injection Site Swelling†

2.3

1.5

0.7

0.5

0.5

17.4

13.8

16.7

11.9

10.0

Systemic Fatigue

HEPLISAV-B %

Fever‡ 0.6 0.6 0.6 0.9 0.7 Note: only subjects having data are included. Clinical Trial Number: NCT01005407 *HEPLISAV-B was given as a 2-dose regimen at 0 and 1 month followed by saline placebo at 6 months. Engerix-B was given at 0, 1, and 6 months † Redness and swelling ≥2.5 cm. ‡ Oral temperature ≥ 100.4°F (38.0°C).

Unsolicited Adverse Events Unsolicited adverse events within 28 days following any injection, including placebo, were reported by 35.4% of HEPLISAV-B recipients and 36.2% of Engerix-B recipients.

Serious Adverse Events vaccine. The percentage of subjects reporting serious adverse events was 3.9% in the HEPLISAV-B group and 4.8% in the Engerix-B group. Acute myocardial infarction occurred in 0.1% (n=2) of HEPLISAV-B recipients and 0.2% (n=1) of Engerix-B recipients.

Autoimmune Adverse Events Subjects were monitored for the occurrence of new-onset potentially immune-mediated to whether they were autoimmune by an external group of experts blinded to treatment assignment. As determined by the adjudicators, new-onset autoimmune adverse events were reported in 0.2% (n=3) of HEPLISAV-B recipients: two subjects with hypothyroidism and one subject with vitiligo. None of these events was considered related to vaccination by the expert group. No new-onset autoimmune adverse events were reported in the Engerix-B group. Although not referred to the external group of experts, one HEPLISAV-B recipient was determined to have Tolosa-Hunt syndrome which is presumed to have an immune-mediated etiology. This event was not considered related to vaccination.

Deaths One subject (0.05%) died of a pulmonary embolism in the HEPLISAV-B group and 1 subject (0.2%) died of heart failure in the Engerix-B group. Neither death was considered related to vaccination.

Study 3 in Subjects 18 through 70 Years of Age Study 3 was a randomized, observer-blind, active-controlled, multicenter study in the United States in which 5587 subjects received at least 1 dose of HEPLISAV-B and 2781 subjects received at least 1 dose of Engerix-B. Enrolled subjects had no history of hepatitis B vaccination or infection. HEPLISAV-B was given as a 2-dose regimen at 0 and 1 month followed by saline placebo at 6 months. Engerix-B was given at 0, 1, and 6 months. In the total study population, the mean age was 50 years; 51% were men; 71% were white, 26% black, 1% Asian, and 9% Hispanic; 48% were obese, 36% had hypertension, 32% had dyslipidemia, and 14% had type 2 diabetes mellitus. These demographic and baseline characteristics were similar in both vaccine groups.

Unsolicited Medically-Attended Adverse Events Subjects were monitored for unsolicited medically-attended adverse events, those for medically-attended adverse events were reported in 46.0% of HEPLISAV-B recipients and 46.2% of Engerix-B recipients. Herpes zoster was reported in 0.7% of HEPLISAV-B recipients and 0.3% of Engerix-B recipients. Unsolicited medically-attended adverse events within 28 days following any injection, including placebo, were reported by 20.1% of both HEPLISAV-B and Engerix-B recipients.

Serious Adverse Events of vaccine. The percentage of subjects who reported serious adverse events was 6.2% in the HEPLISAV-B group and 5.3% in the Engerix-B group. Acute myocardial infarction (AMI) was reported in 0.25% (n=14) of HEPLISAV B recipients and 0.04% (n=1) of Engerix-B recipients. An analysis of serious adverse events likely representing myocardial infarction (MI) was conducted using the standard Medical Dictionary for Regulatory subjects (0.3%) and 3 Engerix-B subjects (0.1%) with events included in the SMQ for MI (these events include the 15 reports of AMI). Additional evidence, including information on temporal relationship and baseline risk factors, does not support a causal relationship HEPLISAV-B recipients, three occurred within 14 days, nine occurred within 53-180 days, and seven occurred more than 180 days following any dose of HEPLISAV-B. Among the 203 days following any dose. All 19 HEPLISAV-B recipients and 3 Engerix-B recipients reported one or more baseline risk factors for cardiovascular disease.

Autoimmune Adverse Events Subjects were monitored for the occurrence of new-onset potentially immune-mediated to whether they were autoimmune by an external group of experts who were blinded to treatment assignment. As determined by the adjudicators, new-onset autoimmune adverse events were reported in 0.1% (n=4) of HEPLISAV-B recipients [one each of: alopecia areata, polymyalgia rheumatica, ulcerative colitis, and autoimmune thyroiditis (with concurrent diagnosis of papillary thyroid carcinoma)]. None of these events was considered to be related to vaccination by the external experts. No new-onset autoimmune adverse events were reported in the Engerix-B group.

Deaths During the study death was reported in 25 subjects (0.4%) in the HEPLISAV-B group and 7 subjects (0.3%) in the Engerix-B group. No death was considered related to vaccination.

7 DRUG INTERACTIONS 7.1 Use with Immune Globulin There are no data to assess the concomitant use of HEPLISAV-B with immune globulin.

When concomitant administration of HEPLISAV-B and immune globulin is required, they should be given with different syringes at different injection sites.

7.2 Interference with Laboratory Tests Hepatitis B surface antigen (HBsAg) derived from hepatitis B vaccines has been transiently detected in blood samples following vaccination. Serum HBsAg detection may not have diagnostic value within 28 days after receipt of HEPLISAV-B.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to HEPLISAV-B during pregnancy. Women who receive HEPLISAV-B during pregnancy are encouraged to contact 1-844-443-7734.

Risk Summary All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In clinically recognized pregnancies in the US general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20%.

There are no clinical studies of HEPLISAV-B in pregnant women. Available human data on risks in pregnancy.

In a developmental toxicity study, 0.3 mL of a vaccine formulation containing 2.5 mcg HBsAg and 3000 mcg cytosine phosphoguanine (CpG) 1018 adjuvant was administered to female rats prior to mating and during gestation. These animal studies revealed no evidence of harm to the fetus due to this vaccine formulation [see Data].

Data Animal data Developmental toxicity studies were conducted in female rats. Animals were administered 0.3 mL of a vaccine formulation containing 2.5 mcg HBsAg and 3000 mcg CpG 1018 adjuvant twice prior to mating, and on gestation days 6 and 18 (a single human dose of HEPLISAV-B contains 20 mcg HBsAg and 3000 mcg CpG 1018 adjuvant). No adverse effects on pre-natal and post-natal development up to the time of weaning were observed.

There were no vaccine-related fetal malformations or variations observed.

8.2 Lactation Risk Summary It is not known whether HEPLISAV-B is excreted in human milk. Data are not available to assess the effects of HEPLISAV-B on the breastfed infant or on milk production/excretion. with the mother’s clinical need for HEPLISAV-B and any potential adverse effects on the breastfed child from HEPLISAV-B or from the underlying maternal condition. For preventive vaccines, the underlying condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use Safety and effectiveness of HEPLISAV-B have not been established in individuals less than 18 years of age.

8.5 Geriatric Use Clinical trials included 909 adults 65 through 70 years of age who received HEPLISAV-B. Among subjects who received HEPLISAV-B, a seroprotective level of antibody to HBsAg was achieved in 90% of those 65 through 70 years of age compared to 96% of those aged 18 through 64 years of age.

Safety and effectiveness of HEPLISAV-B in adults older than 70 years of age were 8.6 Adults on Hemodialysis Safety and effectiveness of HEPLISAV-B have not been established in adults on hemodialysis.

17. PATIENT COUNSELING INFORMATION • vaccination, as well as the importance of completing the immunization series.

• cause hepatitis B infection.

• Advise vaccine recipient to report any adverse events to their healthcare provider or to the Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 and www.vaers.hhs.gov.

• Provide the Vaccine Information Statements, which are available free of charge at the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines).

Manufactured by: Dynavax Technologies Corporation Emeryville, CA 94608 USA © 2020, Dynavax Technologies Corporation. All rights reserved.

US-20-00-00172

12 Clinical

Pharmacy Practice News • November 2021

Oncology

HAI a Promising Option for Liver Cancer Patients F

irst developed more than 50 years ago, hepatic arterial infusion (HAI), which delivers high doses of chemotherapy directly to the liver through an external pump, has been optimized over the past two decades to be a viable treatment for people with cancer who have liver metastases.

The liver is a frequent metastatic site for gastrointestinal cancers, with its rich blood supply and humoral growth factors, said Cindy L. O’Bryant, PharmD, BCOP, a professor of clinical pharmacy at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, in Aurora.

For example, she said, 15% to 20% of patients with colon cancer have liver metastasis at diagnosis and 50% will develop liver metastasis during the course of their disease (Clin Transl Oncol 2020;22[5]:647-662).

In a presentation at the Hematology/ Oncology Pharmacy Association’s 2021 virtual annual meeting, Dr. O’Bryant discussed the role of HAI in the treatment of liver metastases, noting that HAI in combination with systemic chemotherapy, or even alone, can increase resectability and response rates as well as survival (JAMA Surg 2019;154[8]:768-776).

A study presented at the 2021 Gastrointestinal Cancers Symposium (abstract 96) adds support for the use of HAI. Of 32 patients treated with this therapy at the University of Miami, most along with chemotherapy, 13 (41%) were rendered disease-free in the liver. In the remaining 19 patients (59%), hepatic progressionfree survival was 7.3 months. The team, led by senior investigator Jashodeep Datta, MD, a surgical oncologist at the University of Miami Sylvester Comprehensive Cancer Center and the coleader of the University of Miami’s HAI program, concluded, that “implementation of a HAI program for multimodality liver-directed management of unresectable [colorectal liver metastases] is

liver can result in biliary toxicity, so it’s important to monitor liver function tests, Dr. O’Bryant said. Treatments include adding dexamethasone to the heparinized saline infusion, using ursodiol to help with biliary flow, holding further FUDR chemotherapy until lab results stabilize or discontinuing HAI therapy.

Patient Selection and Education

feasible and is associated with meaningful clinical outcomes unlikely to be achieved with systemic therapy alone in heavily pretreated patients.”

How HAI Works For HAI, a titanium pump about the size of a hockey puck is surgically implanted into a subcutaneous pocket in a patient’s abdomen, with a catheter inserted via the gastroduodenal artery to perfuse the hepatic artery, Dr. O’Bryant said. Two types of HAI pumps are available, she said, one that has two chambers, a drug chamber and a charging chamber with a propellant and bellows, and another that uses programmable software and is battery-powered. The two-chambered pump delivers 1.2 mL per day and the programmable pump delivers 0.3 to 1 mL per day, she said.

The most commonly used medication delivered via HAI in the United States is floxuridine (FUDR), a prodrug of 5-fluorouracil, Dr. O’Bryant said. It generally is given with dexamethasone to prevent biliary inflammation, as well as heparin and normal saline. It may be given as monotherapy or in combination with systemic chemotherapy, which, Dr. O’Bryant said, can affect dosing, which is weight-based and adjusted according to liver function test results. Using the HAI pump, 14-day infusions of FUDR are alternated with 14-day infusions of heparinized saline until a patient has disease

progression, complications or is able to go to surgery, she noted.

The HAI pump can be used within two weeks of pump placement, Dr. O’Bryant said. However, she added, if the patient is getting adjuvant treatment, it’s important to wait four to six weeks after surgery to ensure the liver heals.

Potential Complications Despite its benefits, HAI has some potential complications to consider, Dr. O’Bryant said. Infections can develop in the pump pocket. These should be treated with antibiotics or the pump may have to be removed, she said. Another complication is fluid or blood filling the pump pockets, causing seromas or hematomas.

Such fluid would need to be aspirated, she said. The pump also can flip or move out of position; radiographs can determine whether an intervention is necessary to adjust placement. In addition, several factors can influence patency and flow, including temperature and pressure changes; the device should be monitored to assess patency. Other potential complications include misperfusion of the liver due to hepatic arterial anomalies, which can cause pain or ulcers.

Nuclear medicine scans can be done to assess catheter placement. In addition, delivery of chemotherapy directly to the

“The critical aspect of applying HAI in the metastatic setting is to really select the patients in whom we believe a regional approach to treating the liver metastasis is going to be of benefit,” Dr. Datta told Pharmacy Practice News.

Ideally, clinicians should select patients who are healthy and able to tolerate the rigors of HAI, are appropriate clinically (have liver-dominant or liver-confined disease), have favorable tumor biology for the treatment (Ann Surg 2020 Nov 17. doi:10.1097/SLA.0000000000004613), and show good responses to systemic chemotherapy that could be augmented

by HAI, he said.

Education is another factor that can drive successful HAI therapy, according to Dr. O’Bryant. Patients should be taught to report any signs and symptoms of biliary toxicity, such as jaundice or itching, take acid-reducing medication daily, and keep all clinic appointments to allow for appropriate monitoring, she said. Because elevated body temperature can increase the pump flow rate, patients also should report fevers, and avoid hot tubs, saunas and electric blankets. Large changes in pressure also can affect pump rate, so patients should not scuba dive. In addition, she said, patients taking HAI should avoid strenuous exercise, heavy lifting and rough physical activities.

—Karen Blum The sources reported no relevant financial disclosures.

FDA Approves Verzenio for Early Breast Cancer

T

he FDA approved abemaciclib (Verzenio, Lilly) with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of adults who have hormone receptor (HR)positive, HER2-negative, node-positive, early breast cancer at high risk for recurrence and a Ki-67 score of 20% or higher, as determined by an FDA-approved test.

The agency also approved the Ki-67 IHC MIB-1 pharmDx (Dako Omnis, Agilent) assay as a companion diagnostic for selecting patients for this indication.

“We are encouraged by the marked

reduction in the risk of recurrence even beyond the two-year treatment period in these patients, and I’m grateful to be able to offer this as a treatment option to my patients,” said Sara Tolaney, MD, a medical oncologist at Dana-Farber Cancer Institute, in Boston, who was an investigator on the monarchE study on which the approval was based.

The monarchE trial included adults with HR-positive, HER2-negative, nodepositive, resected, early breast cancer with clinical and pathologic features consistent with a high risk for disease

recurrence (ClinicalTrials.gov Identifier: NCT03155997). Patients were randomly assigned to receive either two years of abemaciclib (150 mg twice daily) plus standard endocrine therapy or endocrine therapy alone. Patients in both treatment arms continued to receive adjuvant endocrine therapy for up to five to 10 years.

The major efficacy outcome measure was invasive disease-free survival (IDFS).

Among patients with a high risk for recurrence and Ki-67 score of 20% or higher (N=2,003), the trial demonstrated a significant improvement

in IDFS (hazard ratio, 0.626; 95% CI, 0.488-0.803; P=0.0042). The IDFS at 36 months was 86.1% (95% CI, 82.8%-88.8%) for patients receiving abemaciclib plus tamoxifen or an aromatase inhibitor and 79.0% (95% CI, 75.3%-82.3%) for those given just tamoxifen or an aromatase inhibitor. Overall survival data were not mature at the time of the IDFS analysis.

—Pharmacy Practice News Staff Based on press releases from the FDA and Lilly.

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14 Clinical

Pharmacy Practice News • November 2021

Review Article

Management of

Idiopathic Pulmonary Fibrosis MELANIE RADI, PHARMD, CSP Manager, Clinical Programs AllianceRx Walgreens Prime Gibsonia, Pennsylvania

I

diopathic pulmonary fibrosis (IPF) is a progressive, debilitating, and often fatal interstitial lung disease characterized by scarring of the lungs with unknown

etiology.1 This scarring causes the alveolar walls to

become stiff and thick, preventing inflation, which reduces lung capacity and makes the exchange of oxygen and carbon dioxide more difficult. The decreased lung capacity and oxygen exchange increases breathlessness and decreases mobility and independence.2

Epidemiology Although the precise cause of IPF is unknown, there is evidence that risk factors including age and environmental exposures play a role. The disease tends to affect adults in their sixth or seventh decade of life.3 In addition, there is a strong correlation between smoking and IPF, as well as evidence of a detrimental effect of smoking on survival.4 Environmental exposures to certain types of manufacturing-related dust and genetic factors also are contributors.5

Prognosis and Disease Course Common symptoms of IPF include dry cough, shortness of breath, fatigue, chest pain, and unintentional weight loss.2 Because these symptoms are nonspecific and are associated with other diseases, such as asthma, chronic obstructive pulmonary disease, emphysema, and heart disease, the diagnosis of IPF often is delayed.1 Thus, significant declines in lung function can occur by the time a patient is correctly diagnosed. It is imperative to start patients on FDA-approved therapies as soon as possible to preserve lung function, reduce the risk for acute exacerbations, and improve outcomes.1 The prognosis of patients with IPF is poor; median survival duration is less than 4 years.1 The clinical course of IPF can vary by patient, with some

patients experiencing a slowly progressive course and others rapidly progressing. At diagnosis, there are no distinguishing clinical characteristics to indicate the clinical course a patient is likely to experience. Acute exacerbations with clinically significant worsening of lung function and/or dyspnea can occur at any time during the course of the disease and are associated with a high risk for mortality.1

Treatment Historically, the only treatment options available to patients with IPF were focused on symptom relief and not slowing the disease course.

In 2014, the FDA approved 2 oral antifibrotic therapies for IPF: nintedanib (Ofev, Boehringer Ingelheim) and pirfenidone (Esbriet, Genentech) (Table).3 Current guidelines from respiratory societies recommend

antifibrotic agents as first-line therapy for patients with IPF.6 In addition, patients can benefit from a holistic approach to care that includes pulmonary rehabilitation, education and support, vaccinations, and supplemental oxygen.2,7 Although there is no cure for IPF, medications combined with lifestyle changes can help to slow the decline see IPF, page 16

Table. Antifibrotic Agents Approved to Treat Idiopathic Pulmonary Fibrosis Medication

Dose

Common AEs

Warnings/Precautions

Counseling Notes

Nintedanib (Ofev, Boehringer Ingelheim)

Recommended dose: 150 mg twice daily every 12 h with food

• Diarrhea

• Hepatic impairment

• Nausea

• Elevated liver enzymes

• Stomach pain

• GI disorders

• If AEs occur, consider a temporary dose reduction to 100 mg twice daily

Pirfenidone (Esbriet, Genentech)

Mild hepatic impairment (Child-Pugh A): 100 mg twice daily every 12 h with food

• Decreased appetite • Embryo-fetal toxicity • Headache • Weight loss

• Arterial thromboembolic events

• High blood pressure

• Bleeding events

• Titration dose:

• Nausea

• Elevated liver enzymes

• Days 1-7: 267 mg 3 times daily (801 mg/d)

• Rash • Abdominal pain

• Photosensitivity reaction or rash

• Days 8-14: 534 mg 3 times daily (1,602 mg/d)

• Upper RTI

• GI disorders

• Days 15 and beyond: 801 mg 3 times daily (2,403 mg/d)

• Fatigue

• Diarrhea

AEs, adverse events; GI, gastrointestinal; RTI, respiratory tract infection Based on references 8 and 9.

• Pregnancy category D

• GI perforation • Patients who miss ≥14 d should restart with 2-wk titration regimen • Take with food • Pregnancy category C

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The First and Only Antiemetic Approved for Rescue Treatment of PONV Despite Prophylaxis • Barhemsys® is a selective dopamine-2 and dopamine-3 receptor antagonist, TKKJWNSL F UMFWRFHTQTLNHFQ TUYNTS \NYM IJRTSXYWFYJI XFKJY^ FSI JK‫ܪ‬HFH^ at the doses approved for PONV management1 • Barhemsys 10 mg was more effective than placebo at treating PONV in patients who failed prophylaxis: 42% vs 29% achieved the primary endpoint of complete response; P=0.0031,2,* • In patients who failed prophylaxis, 70% (160/230) of patients met the criteria for complete response at 2 hours after receiving a 10 mg dose of Barhemsys compared with 49% (116/235) of placebo-treated patients (secondary endpoint)2,* • The most common adverse reaction reported for Barhemsys 10 mg (N=418) and at a higher rate than placebo (N=416) was infusion site pain (6% vs 4%)1,†

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Indications

Packaging and vial shown are not actual size.

Barhemsys is a selective dopamine-2 (D2) and dopamine-3 (D3) receptor eceptor antagonist indica indicated ated iinn aadults dults for: • prevention of postoperative nausea and vomiting (PONV), eitherr alone or in combination with an antiemetic of a different class hylaxis with an agent of a different class or have not received prophylaxis • treatment of PONV in patients who have received antiemetic prophylaxis

Select Important Safety Information Contraindication: 'FWMJRX^X NX್HTSYWFNSINHFYJI್NS UFYNJSYX \NYM PST\S M^UJWXJSXNYN[NY^ YT FRNXZQUWNIJ ್ PST\S M^UJWXJSXNYN[NY^ YT FRNXZQUWNIJ ್ QT Prolongation: Barhemsys causes dose- and concentration-dependent prolongation of the QT interval. The recommended dosage is ್RL್TW ್RL FX F XNSLQJ NSYWF[JSTZX .; ITXJ NSKZXJI T[JW YT RNSZYJX &[TNI 'FWMJRX^X NS UFYNJSYX \NYM HTSLJSNYFQ QTSL 69 X^SIWTRJ FSI NS UFYNJSYX YFPNSL IWTUJWNITQ *QJHYWTHFWINTLWFR *(, RTSNYTWNSL NX WJHTRRJSIJI NS UFYNJSYX \NYM UWJ J]NXYNSL FWWM^YMRNFX HFWINFH HTSIZHYNTS INXTWIJWX JQJHYWTQ^YJ FGSTWRFQNYNJX J L M^UTPFQJRNF TW M^UTRFLSJXJRNF HTSLJXYN[J MJFWY KFNQZWJ FSI NS UFYNJSYX YFPNSL TYMJW RJINHNSFQ UWTIZHYX J L TSIFSXJYWTS ್TW \NYM TYMJW RJINHFQ HTSINYNTSX್PST\S YT UWTQTSL YMJ 69 NSYJW[FQ Please see Brief Summary of Prescribing Information for Barhemsys on next page.

Barhemsys was evaluated as rescue treatment of PONV in a randomized, double-blind, multicenter trial in adult patients who had undergone elective FRGZQFYTW^ TW NSUFYNJSY XZWLJW^ ZSIJW LJSJWFQ NSMFQFYNTSFQ FSJXYMJXNF FSI KFNQJI UWNTW FSYNJRJYNH UWTUM^QF]NX 9MJ UWNRFW^ JK‫ܪ‬HFH^ JSIUTNSY \FX HTRUQJYJ WJXUTSXJ IJ‫ܪ‬SJI FX FGXJSHJ TK FS^ JUNXTIJ TK JRJXNX [TRNYNSL TW WJYHMNSL TW ZXJ TK WJXHZJ RJINHFYNTS \NYMNS YMJ ‫ܪ‬WXY MTZWX FKYJW YWJFYRJSY J]HQZINSL JRJXNX NS YMJ ‫ܪ‬WXY RNSZYJX † 7JUTWYJI NS Մ TK FIZQY UFYNJSYX YWJFYJI \NYM 'FWMJRX^X RL FSI FY F MNLMJW WFYJ YMFS UQFHJGT KWTR YMJ 543; YWJFYRJSY FSI WJXHZJ YWJFYRJSY YWNFQX PONV=postoperative nausea and vomiting.

1. 'FWMJRX^X @UFHPFLJ NSXJWYB .SINFSFUTQNX .3 &HFHNF 5MFWRF .SH 2. -FGNG &8 JY FQ Anesthesiology. 2019;130:203-212. *

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16 Clinical

Pharmacy Practice News • November 2021

Review Article

IPF continued from page 14

in lung function, decrease respiratory symptoms, and reduce acute exacerbations.1

Antifibrotic Agents NINTEDANIB Nintedanib is a tyrosine kinase inhibitor that targets multiple growth receptors involved in the pathogenesis of fibrotic tissue remodeling in interstitial lung disease. The

recommended dose is 150 mg orally twice daily with food.8 A dose reduction to 100 mg orally twice daily should be considered for patients with mild hepatic impairment or for the management of adverse events (AEs).8 The most common AEs are diarrhea, nausea, and vomiting. The nintedanib labeling includes warnings and precautions related to hepatic impairment, elevated liver enzymes, gastrointestinal disorders, embryofetal toxicity, arterial thromboembolic events, and bleeding events.8

Brief Summary of Prescribing Information for Barhemsys (amisulpride) injection ®

See package insert prior to prescribing Barhemsys Indications: Barhemsys is a selective dopamine-2 (D2) and dopamine-3 (D3) receptor antagonist indicated in adults for: • prevention of postoperative nausea and vomiting (PONV), either alone or in combination with an antiemetic of a different class • treatment of PONV in patients who have received antiemetic prophylaxis with an agent of a different class or have not received prophylaxis Dosage & Administration: The recommended adult dosage of Barhemsys: • Prevention of PONV, either alone or in combination with another antiemetic: 5 mg as a single intravenous dose infused over 1 to 2 minutes at the time of induction of anesthesia.

• Treatment of PONV: 10 mg as a single intravenous dose infused over 1 to 2 minutes in the event of nausea and/or vomiting after a surgical procedure.

Protect from light. Barhemsys is subject to photodegradation. Administer Barhemsys within 12 hours of removal of the vial from the protective carton.

See full prescribing information for preparation and administration instructions.

Dosage Forms and Strength: Injection: 5 mg/2 mL (2.5 mg/mL) or 10 mg/ 4 mL (2.5 mg/mL) as a clear, colorless sterile solution in a single-dose vial.

Contraindication: Barhemsys is contraindicated in patients with known hypersensitivity to amisulpride.

QT Prolongation: Barhemsys causes dose- and concentration-dependent prolongation of the QT interval. The recommended dosage is 5 mg or 10 mg as a single intravenous (IV) dose infused over 1 to 2 minutes. Avoid Barhemsys in patients with congenital long QT syndrome and in patients taking droperidol.

Electrocardiogram (ECG) monitoring is recommended in patients with pre-existing arrhythmias/cardiac conduction disorders, electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, and in patients taking other medicinal products (e.g., ondansetron) or with other medical conditions known to prolong the QT interval.

Adverse Reactions: Common adverse reactions reported in ≥ 2% of adult patients who received Barhemsys 5 mg (N=748) and at a higher rate than placebo (N=741) in clinical trials for the prevention of PONV were: chills (4% vs. 3%), hypokalemia (4% vs. 2%), procedural hypotension (3% vs. 2%), and abdominal distention (2% vs. 1%). Serum prolactin concentrations were measured in one prophylaxis study where 5% (9/176) of Barhemsys-treated patients had increased blood prolactin reported as an adverse reaction compared with 1% (1/166) of placebo-treated patients. The most common adverse reaction, reported in ≥ 2% of adult patients who received Barhemsys 10 mg (N=418) and at a higher rate than placebo (N=416), in clinical trials for the treatment of PONV was infusion site pain (6% vs. 4%).

Drug Interactions: Barhemsys causes dose- and concentration-dependent QT prolongation. To avoid potential additive effects, avoid use of Barhemsys in patients taking droperidol. ECG monitoring is recommended in patients taking other drugs known to prolong the QT interval (e.g., ondansetron).

Reciprocal antagonism of effects occurs between dopamine agonists (e.g., levodopa) and Barhemsys. Avoid using levodopa with Barhemsys.

Postmarketing Experience: The following adverse reactions have been identified during postapproval chronic oral use of amisulpride outside of the United States (Barhemsys is not approved for oral dosing or chronic use).

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Blood and Lymphatic System Disorders: agranulocytosis; Cardiac Disorders: bradycardia, torsades de pointes, ventricular tachycardia, prolonged QT by electrocardiogram; General Disorders: neuroleptic malignant syndrome; Immune System Disorders: angioedema, hypersensitivity, urticaria; Hepatic Disorders: increased hepatic enzymes; Nervous System Disorders: agitation, anxiety, dystonia, extrapyramidal disorder, seizure; Psychiatric Disorders: confusional state, insomnia, somnolence; Vascular Disorders: hypotension.

Use in Specific Populations: Pregnancy—Risk Summary: Available data with amisulpride use in pregnant women are insufficient to establish a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. The estimated background risk of major birth defects and

In clinical trials, nintedanib resulted in statistically significant reductions in the annual rate of lung function decline, as measured by forced vital capacity (FVC), preserving lung function, and reduced the risk for acute exacerbations in the first year of therapy.8 PIRFENIDONE Pirfenidone is an antifibrotic medication that is thought to have multiple effects. It has been shown to regulate important profibrotic and

miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Lactation—Risk Summary: Based on case reports in published literature, amisulpride is present in human milk at concentrations that are 11- to 20-fold higher than human plasma in patients taking multiple oral doses of amisulpride (200 to 400 mg/day). The estimated infant daily dose ranged from 5% to 11% of the maternal dose. There are ways to minimize drug exposure to a breastfed infant (see Clinical Considerations). There are no reports of adverse effects on the breastfed child and no information on the effects of amisulpride on milk production. The pharmacological action of amisulpride, a dopamine-2 (D2) receptor antagonist, may result in an increase in serum prolactin levels, which may lead to a reversible increase in maternal milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Barhemsys and any potential adverse effects on the breastfed child from Barhemsys or from the underlying maternal condition. Clinical Considerations: A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 48 hours after Barhemsys administration to minimize drug exposure to a breastfed infant. Females and Males of Reproductive Potential— Infertility: In animal fertility studies, administration of repeated doses of amisulpride over a 10-day period to female rats resulted in infertility that was reversible. Pediatric Use—Safety and effectiveness in pediatric patients have not been established. Geriatric Use—No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Renal Impairment—Avoid Barhemsys in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2). The pharmacokinetics of amisulpride in patients with severe renal impairment have not been adequately studied in clinical trials. Amisulpride is known to be substantially excreted by the kidneys, and patients with severe renal impairment may have increased systemic exposure and an increased risk of adverse reactions.

No dosage adjustment is necessary in patients with mild to moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m2).

Overdosage: Doses of oral amisulpride (Barhemsys is not approved for oral dosing) above 1200 mg/day have been associated with adverse reactions related to dopamine-2 (D2) antagonism, in particular: cardiovascular adverse reactions (e.g., prolongation of the QT interval, torsades de pointes, bradycardia and hypotension), and neuropsychiatric adverse reactions (e.g., sedation, coma, seizures, and dystonic and extrapyramidal reactions). There is no specific antidote for amisulpride overdose. Management includes cardiac monitoring and treatment of severe extrapyramidal symptoms. Since amisulpride is weakly dialyzed, hemodialysis should not be used to eliminate the drug.

How Supplied/Storage and Handling: Barhemsys (amisulpride) injection is supplied as follows: • NDC 71390-125-20: Package of 10 cartons. Each carton (NDC 71390-12521) contains one single-dose vial of amisulpride injection, 5 mg in 2 mL (2.5 mg/mL).

• NDC 71390-125-50: Package of 10 cartons. Each carton (NDC 71390-12551) contains one single-dose vial of amisulpride injection, 10 mg in 4 mL (2.5 mg/mL).

Store vials at 20°C to 25°C (68°F to 77°F) Patient Counseling Information: QT Prolongation—Instruct patients to contact their healthcare provider immediately if they perceive a change in their heart rate, if they feel lightheaded, or if they have a syncopal episode. Drug Interactions—Advise patients to report to their healthcare provider if they are taking drugs which prolong the QT interval. Lactation—Women may consider reducing infant exposure through pumping and discarding breastmilk for 48 hours after Barhemsys administration.

BAR HCP BS 08/2021 Barhemsys® is a registered trademark of Acacia Pharma Limited. © 2021 Acacia Pharma Inc. All rights reserved. PP-BAR-2141 09/2021 Acacia Pharma Limited and Acacia Pharma Inc. are wholly owned subsidiaries of Acacia Pharma Group Plc.

pro-inflammatory cytokine cascades in vitro and to reduce fibroblast proliferation and collagen synthesis in animal models.9 The recommended maintenance dose of pirfenidone is 801 mg 3 times daily taken with food, but patients will titrate to the full dosage over a 14-day period.9 The most common AEs are nausea, rash, and abdominal pain. The labeling for pirfenidone includes warnings and precautions about elevated liver enzymes, photosensitivity, rash, and gastrointestinal disorders.9

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Clinical

Pharmacy Practice News • November 2021

17

Review Article In clinical trials, pirfenidone was shown to significantly reduce the risk for lung function decline as measured by FVC and to preserve lung function.9

Role of the Specialty Pharmacist At AllianceRx Walgreens Prime, due to the complex nature of IPF, specialty pharmacists play a critical role educating, counseling and monitoring patients. Educating patients about the disease and the importance of receiving all recommended vaccinations is essential.1 Specialty pharmacists can provide counseling and support related to healthy lifestyle changes, such as smoking cessation, improved nutrition, and increased exercise.1,5 Because the diagnosis of IPF often is delayed due to misdiagnosis, patients likely will have had declining lung function for quite some time. Thus, it is crucial for pharmacists to educate patients about the importance of starting antifibrotic therapy as soon as possible to preserve lung function, slow disease progression, and improve outcomes.1 In addition, specialty pharmacists can educate

Do you receive your

patients and monitor for AEs associated with antifibrotic therapies. Both medications approved for IPF have warnings and precautions associated with their use. Pharmacists can counsel patients about signs and symptoms to be aware of and when to seek medical attention. Pharmacists also can help ensure patients keep their appointments for laboratory monitoring. By supporting IPF patients in these ways, specialty pharmacists can help optimize outcomes for this population.

References 1.

Maher TM, Strek ME. Antifibrotic therapy for idiopathic pulmonary fibrosis: time to treat. Respir Res. 2019;20(1):205.

2. Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. N Engl J Med. 2018;378(19):1811-1823.

3. Hayton C, Chaudhuri N. Current treatments in the management of idiopathic pulmonary fibrosis: pirfenidone and nintedanib. Clin Med Insights: Therapeutics. June 30, 2017. doi:10.1177/1179559X17719126 4. Oh CK, Murray LA, Molfino NA. Smoking and idiopathic pulmonary fibrosis. Pulm Med. 2012;2012:808260.

5. Taskar VS, Coultas DB. Is idiopathic pulmonary fibrosis an environmental disease?

Proc Am Thorac Soc. 2006;3(4):293-298.

6. Raghu G, Rochwerg B, Zhang Y, et al.

An official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis: an update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015;192(2):e3-19.

7. Swigris JJ, Brown KK, Make BJ, et al. Pulmonary rehabilitation in idiopathic pulmonary fibrosis: a call for continued investigation. Respir Med. 2008;102(12):1675-1680.

8. Ofev (nintedanib) [package insert].

Boehringer Ingelheim Pharmaceuticals, Inc; 2020.

9. Esbriet (pirfenidone) [package insert].

Genentech USA, Inc.; 2016.

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10258394

4858015

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10258893

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5703582

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10258214

5726450

2329555

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18 Clinical

Pharmacy Practice News • November 2021

Hepatology

The Benefits of a 2-Dose Hepatitis B Vaccine A

dministration of the two-dose adjuvanted hepatitis B virus vaccine (Heplisav-B, Dynavax Technologies) may be cost-effective in many of the adults recommended for HBV vaccination by the CDC and may result in cost savings in some high-risk groups (Vaccine 2021;39[33]:4733-4741).

However, uptake of the two-dose vaccine may not be as high as it could be, according to Catherine Freeland, MPH, the public health program director of the Hepatitis B Foundation.

“I don’t think it has gotten a lot of attention, although it is fairly new,” said Ms. Freeland, who admits her involvement in the hepatitis B arena may bias her opinion. “There could be a lot more awareness among the adult general practitioner community and a lot more outreach done to increase uptake.”

HBV Trends, Vaccinations In 2018, 3,322 cases of acute HBV were reported to the CDC, but with adjustment for under-ascertainment and underreporting, the estimated number is about 21,600. Between 850,000 to 2.4 million people in the United States are chronically infected with HBV (Hepatology 2021 Mar 3. doi:10.1002/hep.31782).

The CDC currently recommends HBV vaccination in all people from

ages 0 to 18 years, all adults in risk groups for HBV infection, and any adults who want to be protected against HBV (MMWR Morb Mortal Wkly Rep 2018;67[1]:1-31). Unfortunately, recent numbers from the CDC estimated that as of 2018, a little less than one-third of U.S. adults had received a series of HBV vaccine (MMWR Morb Mortal Wkly Rep 2021 May 14).

Two HBV vaccines are approved by the FDA. GlaxoSmithKline’s threedose HBV vaccine Engerix-B was originally approved as a serum vaccine in 1989 and later as a recombinant vaccine. Dynavax Technologies’ two-dose Heplisav-B for adult vaccination was approved in late 2017.

“The standard of care for many years was a three-dose adjuvant vaccine,” said Randall Hyer, MD, PhD, the senior vice president of global medical affairs at Moderna, and a former employee of Dynavax Technologies. “We know that if you get vaccinated, you want the antibody titer to exceed 10 million IU/mL. The problem with the three-dose adjuvant vaccine was not everybody got to 10, and you had to get three doses.”

The three-dose vaccine is given at baseline, one month and six months. A 2011 study using data from the National Health Interview Survey found that

about half of high-risk individuals and 40% of those without risk factors got one or more doses, but only 42% and 34%, respectively, completed the three-dose series (Vaccine 2011;29[40]:7049-7057).

“The third dose is really a challenge, and that leaves people not fully immunized,” Ms. Freeland said. “In the public health space it is hard to get people to follow up, so a two-dose vaccine makes it less of a burden on the individual.”

The two-dose vaccine combines hepatitis B surface antigen (HBsAg) with a proprietary toll-like receptor 9 agonist adjuvant CpG 1018; it is given over the course of one month. When the Advisory Committee on Immunization Practices Hepatitis Vaccines Work Group conducted a systematic review of evidence, it found seroprotective antibody levels to HBsAg were achieved in 90% to 100% of patients given the two-dose vaccine compared with 70.5% to 90.2% of patients given the three-dose vaccine (MMWR Morb Mortal Wkly Rep 2018;67[15]:455-458).

More recently, final data from a study at Kaiser Permanente Southern California showed that of more than 10,000 adults who initiated the HBV vaccine series, 62.7% completed the two-dose vaccine at 360 days compared with 34.9% who completed the three-dose vaccine (JAMA

First 72 hours critical for preventing infection

Neonatal HBV/IG Injections About 90% Effective

W

ithout postexposure immunoprophylaxis, roughly 40% of infants born to hepatitis B virus (HBV)infected mothers in the United States will develop chronic HBV infection, according to the e CDC. Fortunately, since the implementation mentation of universal childhood HBV vaccination in the early 1990s, “we have made tremenemendous inroads in decreasing new w cases of neonatal HBV, on the order of about 90%,” said Ravi Jhaveri, MD, FIDSA, a professor of pediatrics cs at Northwestern University Feinberg School of Medicine, in Chicago.

Ideally, the infants should receive both the hepatitis B vaccine and hepatitis B immune globulin (HBIG) within the first 12 hours after birth, according to Dr. Jhaveri. “The combination of these two injections will prevent about 90% of neonatal HBV cases,” he said. “HBIG basically serves to neutralize the virus that might be passed from mother to child, whereas the vaccine stimulates the infant’s own immunity so the infant is protected on an ongoing basis.”

There is a window of 72 hours where the two injections can be administered, “but the sooner, the better,” Dr. Jhaveri said.

Over the past decade, additional measures have decreased the rates of HBV breakthrough cases in mothers and infants. “We know that pregnant women have higher levels of hepatitis B infection and that the DNA levels in their bloodstream are very high: above the 200,000-IU/mL threshold,” he said. “If we start treating these mothers during pregnancy with an antiviral medicine in the 28-week range, we can reduce the amount of virus, and we can then

prevent the transmission to babies. Mothers might also continue taking the medicine a bit after they deliver.”

Current therapy for b both mother and infant is well tolerated without any repor reported adverse events. “The babies do w well and obviously they grow and tthrive,” Dr. Jhaveri said.

John W. Ward, MD, a professor of p public health at Emory University, in At Atlanta, and the director of the Coalition for Global Hepatitis Elimination, said an infant infected with HBV at birth has a 90 90% chance of developing a chronic infec infection, along with a 25% risk for premature de death from hepatitis B–related liver disease, inc including liver cancer. “For many, this is a shortening of several de decades of their life expectancy,” he said.

More than 90% of pre pregnant women in the United States are screened for HBV infection, according to Dr. Ward. “We know that the virus is transmitted to the infant typically during birth, not earlier in the development process,” he said. “So, by giving a vaccine to the infant immediately after birth, the vaccine can interrupt transmission.”

For mothers who test positive for HBV infection during pregnancy and have a high viral load, “there is an increased chance that the infection will overwhelm the vaccine protection because there are simply too many viruses to contend with,” Dr. Ward said. “Hence, to assure protection of these infants, there is value in giving the expectant mother hepatitis B therapy to lower her viral load and increase the protection of her infant provided by the vaccine.”

—Bob Kronemyer Dr. Jhaveri is a consultant to Dynavax Technologies. Dr. Ward reported no relevant financial disclosures.

Network Open 2020;3[11]:e2027577).

Cost Also a Key Determinant A cost–utility analysis assessing the two-dose vaccine found that it led to cost savings compared with the threedose vaccine in adults with diabetes, obesity, chronic kidney disease, HIV, and in older adults and people who inject drugs (Vaccine 2020;38[51]:8206-8215).

Anecdotally, however, Ms. Freeland said she has heard both pros and cons to the pricing of the two-dose vaccine.

Another key consideration is perceived challenges related to the two-dose vaccine’s availability. “There is definitely a lack of awareness about hepatitis B in general, and even less awareness that this new vaccine even exists,” Ms. Freeland said. “Viral hepatitis just does not get a ton of attention and remains a not discussed issue in the community.”

Dr. Hyer also admitted that uptake of the two-dose vaccine, which has been on the market for more than three years, is not what people expected. He said this may partly be due to incentivizing use of the three-dose vaccine over the two-dose vaccine by packaging it with other types of vaccines at a lower price point.

“One thing we can say right now is that the word vaccine is front and center; it is on the front page almost every day,” Dr. Hyer said. “It generates [awareness] in the scientific community that vaccines work and work well. How that will translate into the public health setting for other diseases is a bigger question.”

—Leah Lawrence Ms. Freeland reported no relevant financial disclosures. Dr. Hyer is a former employee of Dynavax Technologies.

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20 Clinical

Pharmacy Practice News • November 2021

Pediatric

Should We Premedicate Kawasaki Disease Pts Before IVIG?

P

remedicating pediatric patients with Kawasaki disease (KD) using hydration and agents such as acetaminophen, antihistamines, histamine 2 receptor antagonists or corticosteroids to prevent infusion-related reactions associated with intravenous immune globulin (IVIG) may not necessarily be helpful, according to a recent study by pharmacists from Jersey Shore University Medical Center, in Neptune, N.J.

Authors of the study (Pediatr Allergy Immunol 2021;32[4]:750-755) reviewed records for 66 pediatric patients with KD who were given 81 IVIG administrations between January 2014 and June 30, 2019. This included 42 boys and 24 girls, aged 4 months to 15 years.

Sixty-four patients (97%) were premedicated before infusion. However, 17 in 66 patients (26%) experienced IVIGrelated adverse events, most commonly

chills, vomiting and spiking fever.

Despite appropriate medication management, five patients (7.6%) developed coronary abnormalities.

There were strong patterns in premedication, said lead study author Elaine Liu, PharmD, a PGY-2 infectious diseases pharmacy resident at Hartford Hospital, in Connecticut. She was a pharmacy student at the Ernest Mario School of Pharmacy at Rutgers, the State University

of New Jersey, at the time of the study, and continued her PGY-1 training at the N.J. medical center. The most common premedication regimen seen in the study was a combination of acetaminophen and diphenhydramine, which accounted for 65% of regimens used and was given prior to 63% of IVIG infusions. Other commonly used regimens were diphenhydramine alone, and a triple combination of acetaminophen, diphenhydramine

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An Assessment of Exposed Syringe Inner Walls as a Route of Exposure from Hazardous Drugs Stephen F. Eckel, PharmD, MHA, University of North Carolina Eshelman School of Pharmacy

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and famotidine. Of the 25 documented adverse events, 16 were immediate, occurring within six hours of starting IVIG, and nine were delayed, occurring after six hours. Overall, she said, patients demonstrated appropriate clinical outcomes, with an average fever duration of eight days and average hospital stay of about four days, similar to national data.

Although premedication was not shown to adversely affect patient outcomes, Dr. Liu said, “we didn’t really observe much of a benefit when looking at a reduction in adverse events, at least compared with historically reported incidences of adverse event profiles with IVIG” of about 20%.

More Studies Needed Due to a lack of formal guidelines or recommendations on premedication regimens prior to IVIG therapy, more studies are needed, said senior study author Anita Siu, PharmD, BCPS, the neonatal and pediatric pharmacy clinician at K. Hovnanian Children’s Hospital at Jersey Shore, in Neptune, N.J., and a clinical professor of pharmacy practice and administration at the pharmacy school at Rutgers. Published studies on the use of premedication agents have been conflicting, she said. Ultimately, the efficacy of premedication continues to pose a clinical question, Dr. Siu said.

Secondary consequences of premedication, such as unnecessary drug exposure, IVIG treatment delays and increased costs, are issues to be considered in the face of what could be a

Clinical

Pharmacy Practice News • November 2021

questionably beneficial yet widely used practice, she said. “We really hope that larger randomized controlled trials will come out of this.”

Dr. Liu added, “Ours was a singlecenter study, and there are many other patient demographics and a lot of other institutions [using IVIG for KD]. We would love to see more data arise to get a bigger picture of overall practice and really discern if there is a benefit in this strategy.”

In the pediatric population, Drs. Liu and Siu said, adverse events from IVIG occur

Pediatric

‘Ours was a single-center study, and there are many other patient demographics and a lot of other institutions [using IVIG for Kawasaki disease]. We would love to see more data arise to get a bigger picture of overall practice and really discern if there is a benefit in this strategy.’

—Elaine Liu, PharmD less inclined to use them himself to see how well patients tolerate IVIG, and only add them if adverse reactions can’t be controlled by slowing the infusion rate.

21

“There’s nothing particularly wrong with using premedication,” he stressed.

“But keep in mind, you still could have breakthrough [reactions] with any

premedication regimens. The strategy that will reduce reactions more than anything will be the rate of infusion.”

A clinical trial underway at Shanghai Children’s Medical Center, in China, is evaluating lower doses of IVIG in this population, such as 1 g/kg once or twice, compared with the standard dose to see if that would impact reactions, he said.

—Karen Blum The authors reported no relevant financial disclosures.

26% of patients experienced IVIG-related adverse events, most commonly chills, vomiting and spiking fever.

7.6% developed coronary abnormalities.

Discover the S.M.O.F. difference

Source: Pediatr Allergy Immunol 2021;32(4):750-755.

in an estimated 1% to 40% of patients (Eur Ann Allergy Clin Immunol 2017; 49[1]:11-14). Other than premedication, common mitigation strategies include slowing the infusion rate, switching from IV to subcutaneous immune globulin, changing to another immune globulin product or discontinuing infusion.

Higher Doses = Higher Risk Normal dosing of IVIG for KD, 2 g/ kg as a single dose, is higher than given for other conditions (500 mg/kg to 1 g/kg), and about 20% of patients will need a second dose, commented Jerry Siegel, PharmD, FASHP, a clinical associate professor at The Ohio State University College of Pharmacy, in Columbus, and the vice president of business development and managing partner of Safe Medication Management, in East Greenwich, R.I. It’s also given in a short period, he said. Therefore, adverse reactions aren’t unexpected.

“Anytime we use a high dose like that, you can expect higher side effects,” Dr. Siegel said. Most common side effects can be minimized by adjusting each patient’s individual maximum infusion rate, he said.

Rapid infusion of IVIG, an antibody, can bring about reactions such as histamine release or activation of complement, which contribute to fever, chills, etc. Slowing the infusion rate can give the body more time to adjust to the substance and determine whether or not to attack it, Dr. Siegel said. Premedication practices do vary, he said, though he is

SMOFlipid is the FIRST and ONLY lipid injectable emulsion (ILE) with 4 oil sources.

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SMOFlipid is indicated in adults as a source of calories and essential fatty acids for parenteral nutrition (PN) when oral or enteral nutrition is not possible, insufficient, or contraindicated. Limitations of Use: The omega-6: omega-3 fatty acid ratio and Medium Chain Triglycerides in SMOFlipid have not been shown to improve clinical outcomes compared to other intravenous lipid emulsions. Contraindications: Known hypersensitivity to fish, egg, soybean, or peanut protein, or to any of the active ingredients or excipients. Severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides >1,000 mg/dL.

WARNING: DEATH IN PRETERM INFANTS • Deaths in preterm infants after infusion of intravenous lipid emulsions have been reported in the medical literature.

• Autopsy findings included intravascular fat accumulation in the lungs.

• Preterm infants and low-birth-weight infants have poor clearance of intravenous lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion.

Please see Brief Summary of Prescribing Information including Boxed Warning for SMOFlipid on the next page.

22 Policy

Pharmacy Practice News • November 2021

Reimbursement Matters Knowing the rules empowers future decision making

Outpatient Payments in 2022: What’s on the Table T he payment calendar year (CY) for the outpatient setting is almost upon us. It begins Jan. 1, 2022, and encompasses all that we do in the outpatient and ambulatory surgery arenas, as well as setting payments covered by the physician fee schedule. These rules from the Centers for Medicare & Medicaid Services (CMS) reflect the agency’s payment

philosophies, and they also take into consideration other programs or mandates that have been set, sometimes by external agencies. Although it might seem arduous to read through the explanations substantiating the decisions that CMS has reached, this background information can guide you through the decisions that your facility will be making going forward.

SMOFLIPID (lipid injectable emulsion), for intravenous use BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR HEALTHCARE PROVIDERS This brief summary does not include all the information needed to use SMOFlipid safely and effectively. Please see full prescribing information, including Boxed Warning for SMOFlipid (lipid injectable emulsion), for intravenous use at www.FreseniusKabiNutrition.com.

WARNING: DEATH IN PRETERM INFANTS • Deaths in preterm infants after infusion of intravenous lipid emulsions have been reported in the medical literature.

• Autopsy findings included intravascular fat accumulation in the lungs.

• Preterm infants and low-birth-weight infants have poor clearance of intravenous lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion.

INDICATIONS AND USAGE SMOFlipid is indicated in adults as a source of calories and essential fatty acids for parenteral nutrition (PN) when oral or enteral nutrition is not possible, insufficient, or contraindicated.

Limitations of Use The omega-6: omega-3 fatty acid ratio and Medium Chain Triglycerides in SMOFlipid have not been shown to improve clinical outcomes compared to other intravenous lipid emulsions.

DOSAGE AND ADMINISTRATION The recommended daily dosage in adults is 1 to 2 grams/kg per day and should not exceed 2.5 grams/kg per day. SMOFlipid 1000 mL is supplied as a Pharmacy Bulk Package for admixing only and is not for direct infusion. Prior to administration, transfer to a separate PN container.

CONTRAINDICATIONS Known hypersensitivity to fish, egg, soybean, or peanut protein, or to any of the active ingredients or excipients.

Severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides > 1,000 mg/dL. WARNINGS AND PRECAUTIONS • Death in Preterm Infants: (see BLACK BOX WARNING) • Hypersensitivity Reactions: SMOFlipid contains soybean oil, fish oil, and egg phospholipids, which may cause hypersensitivity reactions. Cross reactions have been observed between soybean and peanut oil. Signs or symptoms of a hypersensitivity reaction may include: tachypnea, dyspnea, hypoxia, bronchospasm, tachycardia, hypotension, cyanosis, vomiting, nausea, headache, sweating, dizziness, altered mentation, flushing, rash, urticaria, erythema, pyrexia, or chills. If a hypersensitivity reaction occurs, stop infusion of SMOFlipid immediately and undertake appropriate treatment and supportive measures.

• Risk of Catheter-Related Infections: Lipid emulsions, such as SMOFlipid, can support microbial growth and is an independent risk factor for the development of catheter-related bloodstream infections. The risk of infection is increased in patients with malnutrition-associated immunosuppression, long-term use and poor maintenance of intravenous catheters, or immunosuppressive effects of other concomitant conditions or drugs.

• Fat Overload Syndrome: This is a rare condition that has been reported with intravenous lipid emulsions. A reduced or limited ability to metabolize lipids accompanied by prolonged plasma clearance may result in a syndrome characterized by a sudden deterioration in the patient’s condition including fever, anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia, fatty liver infiltration (hepatomegaly), deteriorating liver function, and central nervous system manifestations (e.g., coma).

• Refeeding Syndrome: Reintroducing calories and protein to severely undernourished patients with PN may result in the refeeding syndrome, characterized by the intracellular shift of potassium, phosphorus, and magnesium as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop.

Common themes for 2022 include an emphasis on health equity and patient access, with the goal of creating a health care system that results in better accessibility, quality, affordability, empowerment and innovation. The approach of CMS to outpatient reimbursement also touches on multiple facets of health care, from requirements for price transparency to

• Aluminum Toxicity: SMOFlipid contains no more than 25 mcg/L of aluminum.

During prolonged PN administration in patients with renal impairment, the aluminum levels in the patient may reach toxic levels. Preterm infants are at greater risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Patients with renal impairment, including preterm infants, who receive parenteral intakes of aluminum at greater than 4 to 5 mcg/kg/day can accumulate aluminum to levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration of PN products.

• Risk of Parenteral Nutrition-Associated Liver Disease (PNALD): PNALD has been reported in patients who receive PN for extended periods of time, especially preterm infants, and can present as cholestasis or steatohepatitis. The exact etiology is unknown and is likely multifactorial. Intravenously administered phytosterols (plant sterols) contained in plant-derived lipid formulations have been associated with development of PNALD, although a causal relationship has not been established. If SMOFlipid-treated patients develop liver test abnormalities, consider discontinuation or dose reduction.

• Hypertriglyceridemia: Impaired lipid metabolism with hypertriglyceridemia may occur in conditions such as inherited lipid disorders, obesity, diabetes mellitus, and metabolic syndrome.

• Monitoring/Laboratory Tests: Routinely monitor serum triglycerides, fluid and electrolyte status, blood glucose, liver and kidney function, blood count including platelets, and coagulation parameters throughout treatment.

Monitoring patients for signs and symptoms of essential fatty acid deficiency (EFAD) is recommended.

• Interference with Laboratory Tests: Content of vitamin K may counteract anticoagulant activity. The lipids contained in this emulsion may interfere with some laboratory blood tests (e.g., hemoglobin, lactate dehydrogenase [LDH], bilirubin, and oxygen saturation) if blood is sampled before lipids have cleared from the bloodstream.

ADVERSE REACTIONS Most common adverse drug reactions >1% of patients who received SMOFlipid from clinical trials were nausea, vomiting, hyperglycemia, flatulence, pyrexia, abdominal pain, increased blood triglycerides, hypertension, sepsis, dyspepsia, urinary tract infection, anemia and device-related infection.

Less common adverse reactions in ) 1% of patients who received SMOFlipid were dyspnea, leukocytosis, diarrhea, pneumonia, cholestasis, dysgeusia, increased blood alkaline phosphatase, increased gamma-glutamyltransferase, increased C-reactive protein, tachycardia, liver function test abnormalities, headache, pruritis, dizziness, rash and thrombophlebitis.

The following adverse reactions have been identified during post-approval use of SMOFlipid in countries where it is registered. Infections and Infestations: infection.

Respiratory, Thoracic and Mediastinal Disorders: dyspnea.

To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC, at 1-800-551-7176, option 5, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS Coumarin and Coumarin Derivatives, Including Warfarin: Anticoagulant activity may be counteracted; monitor laboratory parameters.

USE IN SPECIFIC POPULATIONS • Pregnancy and Lactation: There are no available data on risks associated with SMOFlipid when used in pregnant or lactating women.

• Pediatric Use: The safety and effectiveness of SMOFlipid have not been established in pediatric patients.

• Hepatic Impairment: Parenteral nutrition should be used with caution in patients with hepatic impairment. Hepatobiliary disorders are known to develop in some patients without preexisting liver disease who receive PN, including cholestasis, hepatic steatosis, fibrosis and cirrhosis (PN associated liver disease), possibly leading to hepatic failure.

OVERDOSE In the event of an overdose, fat overload syndrome may occur. Stop the SMOFlipid infusion until triglyceride levels have normalized. The effects are usually reversible by stopping the lipid infusion. If medically appropriate, further intervention may be indicated. Lipids are not dialyzable from serum.

REFERENCE: 1. Deckelbaum RJ, et al. Biochemistry (Mosc). 1990;29(5):1136-1142.

Fresenius Kabi USA, LLC Three Corporate Drive, Lake Zurich, IL 60047 Phone: 1.888.386.1300 www.fresenius-kabi.com/us

©2021, Fresenius Kabi USA, LLC. | All rights reserved. | 1252-SMF-05-12/20

“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

increased reimbursement rates for ambulatory surgery centers (ASCs) and a variety of efforts toward patient safety.

A Practical Example A prevailing theme for the past few years, and again in CY 2022, is to continue to give beneficiaries more affordable choices on where to obtain care and potentially reduce out-of-pocket expenses. Although there had been pushback from hospitals and a reluctance to embrace site-of-care changes for a variety of reasons, the need to provide care in nonhospital settings during the pandemic showed that change indeed was possible.

Beginning in 2020 and continuing forward, there has been a move to shrink the inpatient-only list with some procedures now eligible for Medicare payment both in inpatient and outpatient settings as well as at ASCs. This change began with total hip arthroplasty, six spinal procedure and five anesthesia codes, grew rapidly in 2021, and has been retracted to a much smaller list for CY 2022.

Addressing the Opioid Crisis At the same time, the march to reduce opioid use continues with the wellrecognized fact that the point of origin often is the surgical and/or dental setting. As a pharmacist, you are part of the team working diligently to mitigate this risk for opioid misuse and abuse.

The Department of Health and Human Services continues to support scienceand community-based efforts to combat the opioid crisis with a five-point strategy: 1) better prevention, treatment and recovery services; 2) better data; 3) better pain management; 4) better availability of overdose-reversing drugs; and 5) better research (bit.ly/3C6AAYr).

Beginning several years ago, CMS did its part by instituting a packaging policy for nonopioid pain management treatments that affected both hospital outpatient departments and ASCs. In the ASC setting, CMS continued to pay separately at average sales price ASP+6% for the cost of nonopioid pain management drugs that function as surgical supplies in the performance of

Policy

Pharmacy Practice News • November 2021

ASP+6% Scenario for Drug XYZ 100 mga • • • • • • a

Reimbursement Matters

J1745 billing unit is 10 mg paid at $85.811 per billing unit Bill 10 billing units for a 100-mg dose Total reimbursement is $858.11 ($85.811 x 10) CMS pays you 80%: $686.49 ($858.11 x 0.8) Patient copay of 20%: $171.62 Sequestration deducts 2% from the CMS amount to pay: $672.76

Example based on using the quarterly ASP tables, which publish the ASP+6% rate that applies to non-340B facilities.

surgical procedures. This payment was outside the surgical bundle payment and required the facility to bill for it separately. How did you ensure your revenue cycle department understood the nuances of the rule and actually made provisions for a separate payable line item to be included on the claim?

At the same time, hospital outpatient departments would continue to package payment for nonopioid pain management drugs that function as surgical supplies in the performance of surgical procedures with no separate reimbursement for any drug-related line items.

The CY 2022 packaging policy for nonopioid pain management treatments continues to pay separately at ASP+6% for nonopioid pain management drugs functioning as surgical supplies in the performance of surgical procedures only when performed at an ASC. Currently, there are two eligible products defined

by CMS: Exparel (HCPCS [Healthcare Common Procedure Coding System] Code C9290, Injection, bupivacaine liposome, 1 mg) and Omidria (HCPCS Code J1097, phenylephrine 10.16 mg/ml and ketorolac 2.88 mg/ml ophthalmic irrigation solution, 1 ml).

Sequestration Squabbles Sequestration comes from the Latin word “sequestrare,” which means something that is locked away for safekeeping. When the ancient Romans couldn’t agree on who owned a piece of property, they gave it to a third party called the sequester, who held it until the two sides resolved their differences. In the present, sequestration applies to budget limits that Congress created in the Budget Control Act of 2011. At that time, there was a consensus to use sequester threats to force legislators to reach deficit limit agreements. Sadly, threats didn’t work, implementing the sequester to cut spending from 2013 to 2021. Subsequently, expiration dates continue to be extended into the future as each budget deficit looms larger (now into the 2030s).

How do past and present political squabbles affect your department? The sequestration payment cut implemented in 2013 reduced reimbursement by 2% for all government payments including those for health care. Remember this 2% reduction applies only to the 80% that Medicare reimburses and not the 20% patient copays.

The COVID-19 pandemic paused the sequestration of minus 2%, and

this has been renewed several times.

However, the proposed infrastructure bill discussions maintain an expiration date of Dec. 31, 2021, with no further extensions of the pause. (See

23

box for how should this information be used when calculating impacts on the budget.)

Remember that sequestration applies to the 80% facility payment only, and

applies whether or not your facility is part of the 340B program.

Update: Moderna and Janssen (J&J) Booster Shots Effective Oct. 20, 2021, FDA amended the emergency use authorizations for the Moderna and Janssen (Johnson & Johnson) COVID-19 vaccines to allow for use of a single booster dose for certain populations. For more information on the most current list of billing codes, payment allowances and effective dates, visit go.cms.gov/3C9lzF5.

■

Evidence Matters.

Super-fast phenotypic MIC results and the evidence to back them up.

Get the data: axdx.com/evidence © 2021 Accelerate Diagnostics, Inc. All Rights Reserved. “ACCELERATE DIAGNOSTICS,” “ACCELERATE PHENO,” “ACCELERATE PHENOTEST” and diamond shaped logos and marks are registered trademarks of Accelerate Diagnostics, Inc.

24 Policy

Pharmacy Practice News • November 2021

Sterile Compounding

USP <797> Release continued from page 1

of the revision on June 1, 2019, USP received appeals on several aspects of the chapter, primarily related to BUD. In November 2019, the organization announced that the planned Dec. 1, 2019, implementation date for the Chapter <797> would be delayed indefinitely while it considered the various appeals filed by stakeholders. Some 22 months later, the revisions spurred by those appeals are finally in effect.

Assuming your institution was preparing for implementation of the revised Chapter <797> as it stood in November 2019, you can continue with those same preparations, albeit with some special considerations for 503A compounders.

their shelves and want a longer BUD than 14 days,” said Seth DePasquale, RPh, BCSCP, the senior director of hospital and health system services for Visante.

“Those are the compounders who will primarily be affected by this revision.”

2 Key Categories The 2019 proposed revision of <797> had two categories of CSPs. Category 1 CSPs, assigned a BUD of 12 hours or less at controlled room temperature, or 24 hours or less refrigerated, may be prepared in an unclassified segregated compounding area. Category 2 CSPs, assigned a BUD of greater than 12 hours at controlled room temperature or great-

sterile-to-sterile compounds and are not pursuing BUDs beyond even what’s listed in the current standards, there isn’t much difference between this and the original proposal,” said Patricia Kienle, RPh, MPA, BCSCP, the director of accreditation and medication safety at Cardinal Health. “That’s probably 98% of hospital-based sterile compounders.

You can’t make something with extended BUDs one or two days a month and only follow the requirements on those days; you have to do all of it, all the time.

The chapter is much more specific on what needs to be done and why it needs to be done.”

Category 2 compounders also have some additional changes to their BUDs, but the biggest changes in this category don’t apply to most hospital-based facilities, said Kristina Bryowsky, PharmD, the

‘Historically, we’ve had to identify the genus of all detected microorganisms and then act on it if it’s highly pathogenic; now we only have to identify it if it’s above actionable levels. [That] … gives compounders more flexibility in remaining open while we do remediation.’

—Kristina Bryowsky, PharmD

BUD Extended With Adequate Testing The primary changes relate to BUD. In the currently official <797>, which was last revised in 2008, longer storage times are permitted if sterility testing is performed. “The BUD can be assigned based on professional experience and careful interpretation and application of stability and sterility considerations,” noted an informational document published alongside the latest proposed revisions (bit.ly/3FbQGSB). The 2019 proposed revisions limited BUDs based on concerns regarding stability, sterility, environmental monitoring and personnel monitoring—prompting the appeals that led to the implementation delay and the latest revision.

“The people who complained about the BUDs are the independent compounders, large and small, that are doing batch compounding and have CSPs [compounded sterile preparations] on

er than 24 hours refrigerated, are given specific BUDs dictated by the method of sterilization, whether or not a sterility test is performed and passed, and the storage temperature of the preparation.

The new <797> also established a Category 3, which allows for longer BUDs than those established for Category 2 CSPs, up to a maximum of 180 days, with requirements that a compounding site must meet at all times to be permitted to employ these extended BUDs. The requirements include the use of stability-indicating analytical methods validated based on USP’s Chapter <1225> “Validation of Compendial Procedures”; heightened standards for personnel competency and garbing; increased environmental monitoring in all classified areas where Category 3 CSPs are compounded; and increased frequency of sporicidal disinfection.

“For the people who are only making

pharmacy director at SSM Health, which operates more than two dozen hospitals and health centers in Wisconsin, Illinois, Oklahoma and Missouri, and became the first hospital-based system to register as a 503B in 2014. “Most hospitals and health systems still only get 10 days in the refrigerator and 45 days in the freezer. To get the 45 days at room temperature, 60 days refrigerated and 90 days in the freezer, you have to do terminal sterilization and pass sterility testing, which most institutions don’t do.”

One set of modifications that does apply to compounding pharmacies at hospitals and health systems is a change in just how specific one has to be in identifying microorganisms recovered during surface and/or air sampling. For airborne sampling, if colony-forming units (CFUs) exceed 1 in an ISO Class 5 room, 10 in an ISO Class 7 room and 100 in an ISO Class 8 room, identification of the microorganism to the genus level must be attempted. For surface sampling, genus-level identification must be sought if CFUs are 3 or more in ISO Class 5, greater than 5 in ISO Class 7, or greater than 50 in ISO Class 8 rooms.

“This is different from evaluating the gloved fingertip/thumb samples.

In those situations, you are looking to answer the question, is there growth or not?” Ms. Kienle explained. “Those issues were already incorporated in the 2019 revision, but the new revision offered the chance to reword the section to make it clearer.”

Check With Your State Board of Pharmacy Dr. Bryowsky noted that some state boards of pharmacy may have different requirements and that it’s important for each institution to check before making any changes. “I do like how [USP has] changed the details around what does and does not need to be identified,” she said. “Historically, we’ve had to identify the genus of all detected microorganisms and then act on it if it’s highly pathogenic; now we only have to identify it if it’s above actionable levels. That’s a good element that gives compounders more flexibility in remaining open while we do remediation.”

—Gina Shaw Ms. Kienle reported that she serves on the USP Compounding Expert Committee but did not speak in that capacity in her interview. The other sources reported no relevant financial disclosures.

Stronger Basis for USP Changes “I’m glad that USP had the appeal and were put to the task to come up with scientific reasoning behind what they’re saying,” Mr. DePasquale said. “I’m confident that the changes in the chapter are there for very good reason, and they’ve come up with revisions that make a lot of sense and aren’t just doing things for the purpose of checking boxes.”

Compounding Resources All of the details of the new Chapter <797>, and revisions to <795> for nonsterile compounding, can be found online at bit.ly/3mxprJN. In addition to the fully revised chapters, USP has provided documents detailing the scientific rationale for the proposed revisions.

Policy

Pharmacy Practice News • November 2021

25

Sterile Compounding

Above and Beyond USP Chapters <795> and <797> Aim for CGMP-like environmental monitoring standards in your 503A compounding pharmacy

I

f your hospital or health system has a compounding pharmacy, it’s almost certainly classified as a 503A facility, permitted to do small-batch compounding, primarily for individual prescriptions, and is governed by your state board of pharmacy and USP General Chapters <797> and <795>. Your environmental monitoring and other practices are not required to meet the much more rigorous Current Good Manufacturing Practice (CGMP) regulations demanded of largebatch 503B outsourcing compounding facilities. So, why would CGMP be relevant to environmental monitoring in your 503A facility?

“There are many reasons why you should design an environmental monitoring program for your 503A that exceeds USP <797>,” said Tenille Davis, PharmD, BCSCP, the pharmacist-in-charge at Civic Center Pharmacy, in Scottsdale, Ariz., during a session on “quality built in” at the 2021 Compounding Pharmacies Grand Salon, held virtually. “First, it improves patient safety; but also, it comes closer to what the FDA is looking for during inspections. Some observations on 483s issued by the FDA are beyond <797> requirements. Knowing what the FDA would like to see can help you build a more robust pro-

months, it will take years and years to see trends. The more testing you can do, the more data points you have to trend your results and mitigate any sort of problems.”

Taking as much of your sampling and testing in-house as possible can help you conduct more testing without the added expense and delays of using an outside certification company. “Many 503As are outsourcing their testing to outside companies, which makes it difficult to react in a timely manner if you have an actionable exceeded level,” Ms. Roth said. “Sometimes the certifier can’t come in for another two weeks to resample, which means that depending on what the excursion was, that may mean you’re now operating at a reduced beyond-use date.

It puts a lot of strain on your organization to not have control over the sampling.”

Once you’ve invested in your own air sampler, all you have to pay for on a regular basis are the sampling media, Dr. Davis said. “Those are really inexpensive, and it allows you to have more control of the process and get more data points.”

You can also improve your sampling procedures with guidance from supplemental resources, such as the Controlled Environmental Testing Association’s (CETA) Application Guide CAG-009, “Viable Environmental Monitoring for Sterile Compounding Facilities” (bit.

‘If you’re only doing surface sampling every six months, it will take years and years to see trends. The more testing you can do, the more data points you have to trend your results and mitigate any sort of problems.’

—Tenille Davis, PharmD, BCSCP actually looking for? It shouldn’t just be whether or not action limits for viable microorganism colony-forming units are exceeded. “If there are increasing numbers of colonies over time, even if action levels aren’t exceeded, that should be a red flag,” Dr. Davis said.

“Are you seeing continued growth in the same area? That tells you it’s a hot spot you need to monitor and develop

‘Has your organization implemented a really good hand hygiene and garbing program? Does everybody comply?

Does everybody know how to use the primary engineering controls? Do you have good material handling procedures?

All those things will … reduce the chance that your compounded preparations were contaminated.’

—Abby Roth gram and give you more control of your space, which improves patient safety.”

One way to do that is by increasing the frequency of your surface and air sampling. The proposed revised USP Chapter <797>—released to much fanfare on Sept.

1 (see page 1)—requires only two sampling points per year for 503A compounders.

(By comparison, 503Bs must sample at least once per shift.) “The chapter tells us that we have to trend data, but you can’t trend data with two air-sampling points a year,” said Abby Roth, the senior director of business operations for Critical Point LLC, who moderated the session. “If you are doing sterile-to-sterile compounding, we suggest that you do both air and surface sampling at least monthly.”

“Twice a year is not enough to trend anything,” Dr. Davis agreed. “If you’re only doing surface sampling every six

ly/3uNvddM); USP’s Chapter <1116>, “Microbiological Control and Monitoring of Aseptic Processing Environments” (bit.ly/3oGGkEn); and the FDA’s Aseptic Processing Guideline (bit.ly/3BlpSNt).

“USP <797> tells you what to do, while documents like these can help you with how to do it,” Ms. Roth said. “CAG-009 will provide information to fill in the gaps. For example, the chapter doesn’t talk about how to ship samples to a lab or get into specifics about control plates, or things an org might run into if they’re outsourcing the analysis of their samples to a lab. While <1116> focuses on the limitations of environmental monitoring, what it’s meant to do and things like what you should look for in air samplers.”

Once you have more environmental monitoring data and can actually look for trends, what information are you

an action plan for what to do if those kinds of trends continue.”

What do you do if action levels are exceeded? “You need an out-ofspecification plan: How do you investigate your results; what do you do to remediate them; and how often do you retest?” Dr. Davis asked. “A lot of pharmacies are just checking boxes. They don’t want growth in the buffer room, so they clean the location three times with bleach and then retest. Maybe it doesn’t grow anything, but that doesn’t solve any underlying problems.”

Instead, Ms. Roth recommended repeating sampling for five days to determine whether the result is a trend or a one-off, while assessing other factors such as air pressure differentials and personnel involved. “If you have the same finding five days in a row, you

have a clear problem you need to think about fixing,” she said. “Use data to figure out how to mitigate contributing factors so they don’t keep happening.

Do you need to retrain people in handwashing and garbing, for example? Do you need to change up your cleaning products or increase fingertip testing?”

Ms. Roth cautioned that environmental monitoring has its limits. “It’s a snapshot in time. What’s here now might not be here 15 minutes from now or five days from now,” she said. “And it’s a tool, not a box check for chapter compliance.

You can’t use environmental monitoring as a sterility test for your compounded sterile preparations. Just because you recover organisms in your buffer room, anteroom or even your ISO [International Organization for Standardization] 5 primary engineering control, that doesn’t mean that everything produced during that time is contaminated. The way you build quality into your operations is what gets to be important. Has your organization implemented a really good hand hygiene and garbing program? Does everybody comply? Does everybody know how to use the primary engineering controls? Do you have good material handling procedures? All those things will mitigate the risk that even if we do recover something in that space with environmental testing, it will reduce the chance that your compounded preparations were contaminated.”

—Gina Shaw Dr. Davis reported that she is on the board of directors for the Alliance for Pharmacy Compounding. Ms. Roth reported no relevant financial disclosures.

26 Policy

Pharmacy Practice News • November 2021

Finance

Pushback on COA Report

The following advertorial is provided by Medi-Dose. It is designed to support the adjacent advertisement.

continued from page 1

provide significant discounts on outpatient drugs for qualifying institutions that serve high numbers of low-income and uninsured patients. DSH, which account for most 340B participating institutions, are supposed to receive a minimum 23.1% discount off the average sales price (ASP), but actual discounts are estimated to be upward of 34.7% on average.

The COA is calling for reform of the 340B program. The group says 340B pricing practices are driving up premiums for commercially insured individuals, and it questions why drug discounts aren’t being passed on to the patients served by safety net hospitals.

“Non-profit 340B hospitals charge both commercial payors and uninsured patients extraordinarily high prices and use an aggressive form of price discrimination between payors,” industry analyst and lead study author Aharon Gal, PhD, of the consultancy firm Moto Bioadvisors, said in a COA press release announcing the report (bit.ly/3Ec8SKo).

However, 340B advocates harshly criticized the report. 340B Health, an association of 340B hospitals and health systems, stated in a blog on its website that “the report is highly flawed and presents an inaccurate picture of the role 340B plays in America’s health care safety net.”

Besides challenging the methods and conclusions of the study, 340BHealth said the authors misunderstood that the 340B program is designed to support a broad range of services for low-income patients using hospital savings from the lower drug prices (bit.ly/3Gl4vOV).

COA Seeks a More Informed Debate The Centers for Medicare & Medicaid Services (CMS) enacted new transparency regulations this year, requiring all hospitals to report the actual drug prices they negotiate with each payor (go.cms.gov/3ntSRsE). COA saw access to these data as an opportunity to enable a more informed debate about the 340B program, which it has long criticized for causing competitive disadvantages for private practices. With this goal in mind, the organization commissioned the study to evaluate a sample of 340B hospitals for compliance with the new CMS regulations, and their contract prices for oncology drugs as reported in their own price transparency data.

As of this April, 876 of the 1,087 acute care 340B hospitals in the sample had a publicly accessible price transparency file on their website, most of which only reported the list prices (charge master data) required before this year. CMS has reported low compliance with the new transparency

Q & A

regulations across all hospital systems, and plans to increase what are now considered relatively minor penalties of $300 per day for facilities not meeting the new transparency standards (bit.ly/ 3bbMW5A). Of hospitals that did attempt to comply, 123 published individual drug prices negotiated with each payor. From these, the researchers analyzed more than 52,000 individual prices negotiated with mostly commercial payors (85%) for a roster of 59 oncology drugs, which accounted for the highest Medicare Part B drug costs in 2019.

The report’s key findings are that 340B hospitals: • charge a median of 3.8 times their acquisition costs for oncology drugs, ranging from markups of 240% (brentuximab vedotin; Adcetris, Seagen) to 1,100% (epoetin alfa; Epogen, Amgen); • fail to reduce drug prices for uninsured or cash-paying patients, or when acquisition costs decline; • price drugs inconsistently between and within hospitals; and • prefer innovator biologics over lower-cost biosimilars.

340B Health noted that the report draws conclusions about 340B hospitals’ behavior with a very small sample of DSH (123 of more than 1,000) and without comparing it with non-340B hospitals.

The group also criticized the report for overstating the value of the 340B discount. Rather than the difference between the acquisition and reimbursement costs, the discount’s real value is in the spread between the acquisition cost and what providers would have paid without the program, the group noted in its blog post.

Drug Pricing at Odds With 340B Mission?

A major contentious issue is COA’s allegation that the practice of charging similar prices whether patients are insured or paying out of pocket conflicts with the mission of 340B hospitals to provide affordable care to the uninsured population. “To the extent 340B institutions fulfill their mission of providing lower cost care, we are not seeing it reflected in their drug prices,” the authors wrote.

COA argued that these pricing practices show 340B drug discount savings are not being directly passed on to patients.

The problem with this argument, 340B advocates say, is the 340B program was designed to allow participating hospitals to use the savings from drug discounts to fund community programs and services. “Lawmakers created the 340B program to allow savings from lower drug costs to support a broad range of services for patients with low see 340B PUSHBACK, page 28

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28 Policy

Pharmacy Practice News • November 2021

Finance

340B PUSHBACK continued from page 26

incomes,” 340B Health wrote in its blog post. “In other words, 340B is working as intended. … [The] report fails to consider the many ways 340B hospitals are using the savings to provide uncompensated and unreimbursed care as well as vital services that cost more to deliver than the reimbursements they bring in, including trauma and burn care, HIV care, and inpatient mental health care.”

Preserving the Safety Net Peggy Tighe, JD, and Barbara Williams, JD, health care attorneys with Powers Law, who represent 340B-covered entities, argued that Ryan White Clinics are a strong example of a safety net facility that depends on 340B drug discount savings to fund comprehensive clinical care and social services for low-income patients— in this case, half of all people living with HIV/AIDS in the United States.

According to a white paper released in October 2020, Ryan White Clinics detailed exactly where their 340B discount dollars go to benefit the patients they serve, which included funding for free or low-cost primary HIV/AIDs medical care; health insurance coverage counseling and copay assistance; and support services, such as medical transportation, respite care for caregivers, nonmedical case management, and housing and food assistance (bit.ly/3B8gonP).

“Without the 340B program, there’s really no way that Ryan White Clinics can do all that they do for the communities they serve,” Ms. Tighe said. “The reason is pretty simple: Not only did they get discounts on outpatient prescription drugs because they’re eligible to participate in the 340B program, they were able to invest the savings and additional insurance revenue in comprehensive care services. So those monies enable the Ryan White Clinics to do a lot more than just get discounted drugs.”

Ms. Williams noted that the language Congress used when it wrote the legislation that enacted the 340B program entrusted non-profit safety net providers to reinvest drug discount savings in the services needed by their particular communities. “Congress didn’t say you have to directly pass along the drug discount to the patient,” she said. “Most 340B-covered entities have financial assistance programs, so if a patient needs the discount, they can get it. But if a patient is privately insured, and they’re an eligible patient of that 340B-covered entity, then the savings goes back to that covered entity and is used to provide other community services.”

Pricing Discrimination Another key observation made in the COA report about pricing discrimination

is that 340B hospitals charge private insurers much higher rates than the reimbursement they receive from Medicare for the same drug. As an example, the report outlines how 340B hospitals would make 15 times as much profit from a commercially insured patient versus a Medicare patient prescribed the multiple myeloma drug

Figure.

Part of the problem with the 340B Drug Pricing Program is a lack of pricing transparency from participating entities, despite new federal regulations requiring such transparency, according to a report from the Community Oncology Alliance. In this figure, the COA claims that only 123 of the 1,087 acute care 340B hospitals included in its analysis published individual negotiated payor price data for drugs.

Source: Community Oncology Alliance

on Rapid

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Byfavo® VIQMQE^SPEQ -RXIRXMSREPP] HIWMKRIH EW E VETMH SRWIX VETMH SǻWIX sedative that may be used across many procedures and adult patient types.

Rapid Onset

Š QMRYXIW XS SRWIX SJ WIHEXMZI IǻIGXW 3.0–3.5 minutes to peak sedation after initial 5 mg dose

Indication: Byfavo is a benzodiazepine indicated for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.

Important Safety Information WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS • Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer Byfavo.

• Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation.

• Byfavo has been associated with hypoxia, bradycardia, and hypotension.

Continuously monitor vital signs during sedation and through the recovery period.

• Resuscitative drugs, and age- and size-appropriate equipment for bag/ valve/mask assisted ventilation must be immediately available during administration of Byfavo.

• Concomitant use of benzodiazepines with opioid analgesics may result in profound sedation, respiratory depression, coma, and death.

The sedative effect of intravenous Byfavo can be accentuated by concomitantly administered CNS depressant medications, including other benzodiazepines and propofol. Continuously monitor patients for respiratory depression and depth of sedation.

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11.0-14.0 minutes to fully alert after last dose

Contraindication: Byfavo is contraindicated in patients with a history of severe hypersensitivity reaction to dextran 40 or products containing dextran 40.

Personnel and Equipment for Monitoring and Resuscitation: See Boxed Warning. Consider the potential for worsened cardiorespiratory depression prior to using Byfavo concomitantly with other drugs that have the same potential (eg, opioid analgesics or other sedative-hypnotics). Administer supplemental oxygen to sedated patients through the recovery period. A EHQ]RGLD]HSLQH UHYHUVDO DJHQW ŴXPD]HQLO VKRXOG EH LPPHGLDWHO\ DYDLODEOH during administration of Byfavo.

Risks From Concomitant Use With Opioid Analgesics and Other SedativeHypnotics: See Boxed Warning.

Hypersensitivity Reactions: Byfavo contains dextran 40, which can cause hypersensitivity reactions, including rash, urticaria, pruritus, and anaphylaxis.

Byfavo is contraindicated in patients with a history of severe hypersensitivity reaction to dextran 40 or products containing dextran 40.

Neonatal Sedation: Use of benzodiazepines during the later stages of pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) in the neonate. Observe newborns for signs of sedation and manage accordingly.

Pediatric Neurotoxicity: Published animal studies demonstrate that anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term FRJQLWLYH GHƓFLWV ZKHQ XVHG IRU ORQJHU WKDQ KRXUV 7KH FOLQLFDO VLJQLƓFDQFH of this is not clear. However, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through WKH ƓUVW VHYHUDO PRQWKV RI OLIH EXW PD\ H[WHQG RXW WR DSSUR[LPDWHO\ \HDUV RI

Policy

Pharmacy Practice News • November 2021

29

Finance daratumumab (Darzalex, Janssen Oncology) ($213,696 vs. $14,259). COA suggested that the much higher value of commercial patients could motivate 340B hospitals to acquire younger, healthier, commercially insured patients instead of the underserved populations for which they are tasked with caring. But 340B Health says there is no evidence for this claim, and that findings from the Medicare Payment Advisory Commission and other studies show 340B hospitals are more likely to serve low-income, racially diverse and disabled patients.

“When these types of reports find their way into the public dialogue over the 340B program, they obscure the tremendous good the program does for the health care safety net and the patients it serves. Policymakers who understand the benefits and intent of the program will recognize the holes in these arguments,” 340B Health said.

Ms. Tighe said she suspects that calls for greater transparency by 340B hospitals from COA and other groups is really an attempt to gain access to information that can be used to reduce the size of

the drug discount program—an ongoing effort among many stakeholders.

As Pharmacy Practice News previously reported (bit.ly/3EivTeW), 340B hospitals are in litigation with drug manufacturers who have refused to provide drug discounts through 340B contract pharmacies.

“What we’ve said for a long time is transparency is a buzzword,” Ms. Tighe noted. “What’s really happening here is, increased transparency and reporting is really intended to diminish savings, and also consequently would diminish that

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age in humans. Anesthetic and sedation drugs are a necessary part of the care of children needing surgery, other procedures, or tests that cannot be delayed, DQG QR VSHFLƓF PHGLFDWLRQV KDYH EHHQ VKRZQ WR EH VDIHU WKDQ DQ\ RWKHU Decisions regarding the timing of any elective procedures requiring anesthesia VKRXOG WDNH LQWR FRQVLGHUDWLRQ WKH EHQHƓWV RI WKH SURFHGXUH ZHLJKHG DJDLQVW the potential risks.

Adverse Reactions: 7KH PRVW FRPPRQ DGYHUVH UHDFWLRQV UHSRUWHG LQ ! of patients (N=630) receiving Byfavo 5-30 mg (total dose) and undergoing colonoscopy (two studies) or bronchoscopy (one study) were: hypotension, hypertension, diastolic hypertension, systolic hypertension, hypoxia, and diastolic hypotension.

8VH LQ 6SHFLƓF 3RSXODWLRQV Pregnancyŋ7KHUH DUH QR GDWD RQ WKH VSHFLƓF effects of Byfavo on pregnancy. Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates. Monitor neonates exposed to benzodiazepines during pregnancy and labor for signs of sedation and respiratory depression. Lactation—Monitor infants exposed to Byfavo through breast milk for sedation, respiratory depression, and feeding problems.

A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 5 hours after Byfavo administration. Pediatric Use—Safety and effectiveness in pediatric patients have not been established. Byfavo should not be used in patients less than \HDUV RI DJH Geriatric Use—No overall differences in safety or effectiveness were observed between these subjects and younger subjects. However, there is a potential for greater sensitivity (eg, faster onset, oversedation, confusion) in some older individuals. Administer supplemental doses of Byfavo slowly to achieve the level of sedation required and monitor all patients closely for cardiorespiratory complications. Hepatic Impairment—In patients with

One sedative. Many patients.™

severe hepatic impairment, the dose of Byfavo should be carefully titrated to effect. Depending on the overall status of the patient, lower frequency of supplemental doses may be needed to achieve the level of sedation required for the procedure. All patients should be monitored for sedation-related cardiorespiratory complications.

Abuse and Dependence: Byfavo is a federally controlled substance (CIV) because it contains remimazolam which has the potential for abuse and physical dependence. %<) +&3 ,6,

Please see the Brief Summary of Prescribing Information for Byfavo on next page.

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freedom of local communities making these determinations about how these savings are used. I don’t think anybody should question why there is a hesitancy in the hospital community to hand over more information when the information they give away is used against them.”

—Adam Leitenberger Ms. Tighe and Ms. Williams reported that they represent a range of 340B institutions.

For more 340B coverage, see page 30.

30 Policy

Pharmacy Practice News • November 2021

Finance Access to affordable medications a key focus

340B Program, PAPs Help Ensure Specialty Rx Success A ctively managing participation in the federal 340B Drug Pricing Program and other financial assistance and medication access efforts can help maximize savings and ensure the overall success of specialty pharmacy services, a panel of experts said during the 2021 ASHP Conference for Pharmacy Leaders, held virtually.

For example, when the FDA approved the pediatric cystic fibrosis medication elexacaftor-tezacaftor-ivacaftor (Trikafta, Vertex) in June, the specialty pharmacy team at Atrium Health Wake Forest Baptist, in Winston-Salem, N.C., worked with eligible patients and their families to ensure they were completing necessary lab tests and education

counseling during clinic visits leading up to the approval so patients would be ready, said Regina Schomberg, PharmD, BCPS, the system director of pharmacy, retail and specialty pharmacy services.

With the help of a medication access specialist, they were able to obtain prior authorization for 19 patients within one week of the FDA approval, and all

&VMIJ 7YQQEV] SJ 4VIWGVMFMRK -RJSVQEXMSR for Byfavo© VIQMQE^SPEQ JSV -RNIGXMSR 7II TEGOEKI MRWIVX TVMSV XS YWMRK &]JEZS ;%62-2+ 4)67322)0 %2( )59-41)28 *36 132-836-2+ %2( 6)797'-8%8-32 %2( 6-7/7 *631 '32'31-8%28 97) ;-8, 34-3-( %2%0+)7-'7 %2( 38,)6 7)(%8-:) ,=4238-'7 4IVWSRRIP ERH )UYMTQIRX JSV 1SRMXSVMRK ERH 6IWYWGMXEXMSR • Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer Byfavo.

• Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation.

• Byfavo has been associated with hypoxia, bradycardia, and hypotension. Continuously monitor vital signs during sedation and during the recovery period.

• Resuscitative drugs, and age- and size-appropriate equipment for bag-valve-mask–assisted ventilation must be immediately available during administration of Byfavo.

6MWOW *VSQ 'SRGSQMXERX 9WI ;MXL 3TMSMH %REPKIWMGW ERH 3XLIV 7IHEXMZI ,]TRSXMGW Concomitant use of benzodiazepines, including Byfavo, and opioid analgesics may result in profound sedation, respiratory depression, coma, and death. The sedative IǻIGX SJ MRXVEZIRSYW &]JEZS GER FI EGGIRXYEXIH F] GSRGSQMXERXP] EHQMRMWXIVIH '27 HITVIWWERX QIHMGEXMSRW including other benzodiazepines and propofol.

Continuously monitor patients for respiratory depression and depth of sedation.

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patients were able to have their prescriptions sent either to the hospital’s internal specialty pharmacy or another specialty pharmacy within the first week. They also were able to use 340B savings to support pharmacy staff to continue providing personalized care to this vulnerable population.

Solid organ transplant patients

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Policy

Pharmacy Practice News • November 2021

Finance

340B disproportionate share hospitals provide

60% of all unreimbursed and uncompensated care in the U.S., yet make up only

38% of all acute care hospitals.

Source: 340BHealth.

also can benefit from ongoing specialty pharmacy care and 340B funding. “Financial assistance continues to

31

be the largest barrier these patients experience,” Dr. Schomberg said. “You can imagine the severity of being

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overwhelmed with the desire to continue with their newly transplanted organ, and the need for finance assistance with medication payment.”

During a patient outreach call, one of her pharmacy technicians discovered that a patient had lost their job two months prior, was at risk for losing insurance coverage, and had been paying out of pocket for the medication.

The patient shared that he or she went without medication because there was not enough money to pay for the new script. The pharmacy technician found

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a patient assistance program (PAP) and contacted the manufacturer for approval within a few days.

Year to date, Dr. Schomberg and her colleagues’s work on PAPs has garnered millions of dollars of medication savings.

They also use a computerized system that allows searching for PAP, foundation or grant funding, and they keep track of the paperwork to assist patients. Their efforts to maximize 340B savings also have paid off. But Dr. Schomberg stressed that the program doesn’t just benefit patients; at her institution, 340B savings also are invested in staff, including two designated medication-access specialists fully devoted to PAPs.

UC Davis Approach The UC Davis Health System in California also established specialty services to help solid organ transplant patients with medication access needs, said David Mitchell, PharmD, MBA, the health system’s pharmacist manager of specialty pharmacy operations. Dr. Mitchell’s team used 340B savings to hire and train staff to perform tasks such as billing Medicare B for immunosuppressants, supporting the prior authorization process and obtaining financial assistance when needed. They also established a meds-to-beds delivery system to provide prescriptions to patients before discharge. Technicians call patients every month to ensure they continue on therapy.

But those 340B savings don’t magically appear, Dr. Mitchell stressed. His specialty pharmacy has clinical pharmacists embedded in clinics who make sure that orders for specialty medications sent to the internal specialty pharmacy are eligible for 340B savings. They also are responsible for ensuring that orders patients choose to have filled at external pharmacies—or that payors mandate be sent to a specialty pharmacy—still remain in the health system’s contract pharmacy network.

Clinical pharmacists also guarantee that orders are eligible for 340B savings by ensuring patients are seen within a specified time frame. It not only makes for great patient care, Dr. Mitchell said, but guarantees that patient orders are issued from a qualified encounter.

He said pharmacy staff perform additional activities to optimize 340B savings, such as checking 340B accumulations before placing orders to maximize orders through the 340B account and minimize orders from the wholesale acquisition cost account. The 340B team also reviews orders that are not automatically qualified and manually qualifies them if initially rejected, if they meet certain criteria.

—Karen Blum The sources reported no relevant financial disclosures.

32 Policy

Pharmacy Practice News • November 2021

FDA Watch FDA Grants Cyltezo Biosimilar ‘Interchangeable’ Status

T

he FDA expanded the designation of adalimumab-adbm (Cyltezo, Boehringer Ingelheim) to include interchangeable status—marking the second such approval to date.

The drug, which was initially approved in 2017, is now biosimilar to and interchangeable with adalimumab (Humira, AbbVie). Cyltezo is one of six biosimilar agents scheduled to reach the market by

2023, according to the Center for Biosimilars (bit. ly/2Z5TyAj).

“The interchangeable designation will allow pharmacists to substitute Cyltezo for the originator product without consulting with the prescribing physicians,” the group said. “This is expected to open doors to wider patient access, although all states have now enacted conditions that govern the interchangeable designation.”

Cyltezo is approved for the following indications in adults:

• moderately to severely active Crohn’s disease; • moderately to severely active ulcerative colitis; • moderately to severely active rheumatoid arthritis; • active psoriatic arthritis; • active ankylosing spondylitis; and • moderate to severe chronic plaque psoriasis.

The drug also is indicated for moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older, and children ages 6 years

and older who have Crohn’s disease.

Cyltezo comes as a citrate-free, singledose, pre-filled glass syringe (40 mg/0.8 mL, 20 mg/0.4 mL) and is administered subcutaneously. The most common adverse events associated with use of the drug are upper respiratory and sinus infections, injection site reactions, headache and rash, according to the FDA. Malignancies also have been reported, among other severe reactions outlined in the drug’s boxed warning.

FDA Expands Indication for Flucelvax Quadrivalent

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he FDA expanded the indication for a cell-based quadrivalent influenza vaccination (QIVc; Flucelvax Quadrivalent, Seqirus) for children as young as 6 months old.

The expanded age indication is supported by a phase 3 clinical study demonstrating that QIVc was as safe and immunogenic as a standard quadrivalent seasonal influenza vaccine (QIV) in children 6 months to 3 years of age during the U.S. 2019-2020 influenza season, according to data presented at the Pediatric Academic Society virtual annual meeting on May 1, 2021.

Safety profiles also were comparable between QIVc and QIV. The most common adverse events (AEs) were similar between vaccinated groups, and included tenderness, erythema at the injection site, irritability and sleepiness. The rate of serious AEs was less than 1% for each vaccine group.

Cell-based influenza vaccines are designed to produce an exact match to World Health Organization–selected influenza virus strains by avoiding eggadapted changes, and therefore may have the potential for greater effectiveness, according to the CDC. Children younger than 5 years old, particularly those younger than 24 months, are at increased risk for developing serious influenza-related complications, including pneumonia, brain dysfunction, and in rare cases, even death. According to the CDC, almost 50,000 hospitalizations occurred in children during the 2019-2020 U.S. influenza season, and there were more than 486 influenzarelated deaths in this age group.

The CDC recommends everyone 6 months of age and older without contraindications receive an influenza vaccine annually.

Jakafi Approved To Treat Chronic GVHD In Adults and Children

T

he FDA approved ruxolitinib (Jakafi, Incyte) for chronic graftversus-host disease (GVHD) after fail-

Policy

Pharmacy Practice News • November 2021

33

FDA Watch

ure of one or two lines of systemic therapy in adults and children ages 12 years and older.

“Nearly half of the people who develop chronic GVHD do not respond adequately to steroids—the current standard of care—making this life-threatening condition particularly challenging to treat,” noted Robert Zeiser, MD, the principal investigator of the REACH3 trial, on which the approval was based.

Dr. Zeiser called the approval “a significant advancement in the treatment of appropriate patients with chronic GVHD—for both the patients who face a poor prognosis and the health care providers who struggle to effectively treat them.”

The phase 3 REACH3 study compared ruxolitinib with best available therapy for treatment of steroid-refractory chronic GVHD after allogeneic stem cell transplantation. In the trial, investigators randomly assigned 329 patients to receive either ruxolitinib 10 mg twice daily or best available therapy. The major efficacy outcome used to support approval was overall response rate through week 24. Full results from the trial were published in The New England Journal of Medicine (2021;385[3]:228-238).

The overall response rate was 70% (95% CI, 63%-77%) for the ruxolitinib arm and 57% (95% CI, 49%-65%) for the best available therapy arm.

The most common hematologic adverse events (incidence >35%) were anemia and thrombocytopenia. The most common nonhematologic adverse events (incidence ≥20%) were infections (pathogen not specified) and viral infection.

For more information, see the complete prescribing information for ruxolitinib (bit.ly/3pm4Yuo).

Brukinsa Granted Accelerated Approval For R/R MZL Treatment

using the 2014 Lugano criteria.

In the MAGNOLIA trial, investigators evaluated 66 patients with relapsed or refractory MZL who received at least one anti-CD20–based regimen, including 26 with extranodal subtype, 26 with nodal subtype, 12 with splenic subtype and four with unknown subtype. The ORR was 56% (95% CI, 43%-68%) with a complete response (CR) rate of 20% based on assessment using CT and 67% (95% CI, 54%-78%) with a CR rate of 26% based on assessment-prioritizing PET/CT. The DOR was not reached at the median

follow-up time of 8.3 months; 85% of responders still were in remission at 12 months (95% CI, 67%-93%). Responses were observed in all MZL subtypes.

In the BGB-3111-AU-003 trial, 20 patients were evaluated, including nine with extranodal subtype, five with nodal subtype and six with splenic subtype.

The ORR was 80% (95% CI, 56%-94%), with a CR rate of 20%, based on assessment using CT. The median DOR was not reached at the median follow-up time of 31.4 months; 72% of responders still were in remission at 12 months

(95% CI, 40%-88%).

The prescribing information (bit. ly/3E2BBS2) includes warnings and precautions for hemorrhage, infections, cytopenias, second primary malignancies and cardiac arrythmias.

The most common adverse reactions, including laboratory abnormalities (incidence, ≥30%), in the pooled safety population of 847 patients were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash and musculoskeletal pain.

■

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EASY TO DIFFERENTIATE: Unique label design with prominent, easy-to-read drug name and strengths to support accurate medication selection

READY TO USE: Premix bags provide efficiency and convenience and help reduce the risks of contamination and compounding errors

EASY TO READ: Drug name and strengths are printed on multiple sides of the carton and overwrap to help the product stand out on the shelf

T

he FDA granted accelerated approval to zanubrutinib (Brukinsa, BeiGene) for adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20–based regimen.

The approval is based on the pivotal phase 2 MAGNOLIA (BGB-3111-214) trial (ClinicalTrials.gov Identifier: NCT03846427) and the phase 1/2 BGB-3111-AU-003 trial (NCT02343120).

In both trials, zanubrutinib was administered orally at 160 mg twice daily or 320 mg once daily. The efficacy measures were overall response rate (ORR) and duration of response (DOR), as assessed by an independent review committee

Every SAGENT® product features PreventIV Measures® Packaging and Labeling, which is designed to enhance patient safety and may help reduce the risk of medication errors.

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Sagent Pharmaceuticals, Inc. Schaumburg, Illinois 60195 www.SagentPharma.com The SAGENT logo, SAGENT, SAGENT Pharmaceuticals and PreventIV Measures are registered trademarks of Sagent Pharmaceuticals, Inc. ©2021 Sagent Pharmaceuticals, Inc. 2856

34 Operations & Management

Pharmacy Practice News • November 2021

COVID-19 Pandemic

Profits and the Pandemic continued from page 1

At Wellforce, a multiple-hospital network that includes Tufts Medical Center, in Massachusetts, adding pharmacists on the care team “not only [helps] with the bottom line, but ultimately, it will lower the total cost of care because we are going to be able to keep patients’ treatment within our system,” said chief pharmacy officer Keith B. Thomasset, PharmD, MBA.

In practical terms, “hospitals have had to get a lot more creative and innovative in finding programs and resources to replace lost revenue and margin,” Mr. Jorgenson said. “For the profession of pharmacy, that has been tremendous because for a lot of organizations, pharmacy has really been an undervalued, underutilized resource with a lot more to contribute. We have never been busier supporting the accelerated growth of high-performance pharmacy services and the associated contributions.”

Health-system pharmacy often has risen to meet challenges. One example is the University of California, San Francisco (UCSF). “With so much lost revenue early on in the pandemic, we had to think outside of the box to be more efficient and effective,” said Desi Kotis, PharmD, the chief pharmacy executive at UCSF. Thanks to that approach, UCSF’s financial statement for the fiscal year ended June 30 showed more than $80 million in medication management savings and increased pharmacy revenues.

Improvements ranged from relatively modest to very large. A focus on IV dose rounding, for instance, saved approximately $500,000; a specialty pharmacy push yielded an additional $31 million; and a focus on leveraging UCSF’s 340B purchasing program and managing drug wholesale acquisition cost together added $40 million more (box).

Savings Start at Home Other health systems and hospitals are taking different paths to revenue building and saving costs. Norton Healthcare, a five-hospital, 1,800-bed health system covering Louisville, Ky., and southern Indiana, is weighing the financial benefit of launching a home infusion therapy program, according to Paul Allen, PharmD, the vice president for pharmacy services.

With more payors pushing home infusion because it is less expensive to deliver those services at home versus

a hospital, such a program “would be another revenue generator for us,” Dr. Allen said. “It would also enhance our ability to take care of patients across the continuum of care, including when they go home from the hospital.”

Steve Rough, MS, RPh, a senior vice president at Visante, also sees a big financial upside for hospitals in the home infusion market. “Setting up home infusion therapy programs and separate home infusion suites can provide hospitals with additional venues for infusing drugs outside of the traditional hospital-based site of care,” he said.

Mr. Rough also is bullish on the growth potential for specialty and retail pharmacy programs, by “moving the needle on the capture rate for high-cost, highmargin drugs that patients need to get the best outcomes.”

Dr. Allen is on board with expanding both pharmacy areas. Norton already has “pretty robust specialty pharmacy and retail pharmacy programs,” he said, with revenues that provide “a significant net margin stream for the organization.” Specialty pharmacy alone, he noted, generates year-over-year growth of at least 10%, owing in large part to the health system’s

ability to gain access “to more limiteddistribution products than in the past.”

Norton is looking to capitalize on those gains by improving the specialty pharmacy capture rate for patients coming out of its specialty clinics or discharged from its hospitals. Another goal is to build its medsto-beds program, “so we ensure patients have their discharge medications before they leave the hospital, and then we can capture additional pharmacy revenue.”

At Wellforce, a multiple-hospital health system including Tufts Medical Center, in Massachusetts, Keith B. Thomasset, PharmD, MBA, the chief pharmacy officer, said the aim is frictionless and total care and “to optimize the volume that we fill internally by having our pharmacists spend more time in our clinics, helping our providers. Not only is that going to help with the bottom line,” Dr. Thomasset said, “but ultimately, it will lower the total cost of care because we are going to be able to keep patients’ treatment within our system.”

Supply Chain Savings Wellforce also has worked to leverage its size to optimize supply chain purchasing agreements. This year alone, he said, that effort saved the health system nearly $2.5 million. Wellforce’s 340B program also has helped. Specifically, he said with COVID-19 shifting a lot of care to the home, “we have tried to capitalize on our 340B potential” by targeting contract pharmacy agreements to a handful of high-use home infusion companies.

Partway through this year, he noted, that approach has yielded nearly $150,000 in additional revenue.

Dr. Thomasset cited two additional drug initiatives that added more than a half-million dollars in savings. First, he said, by insourcing, rather than outsourcing, a specific sedative medication, Wellforce saved roughly $400,000 over the past year. Another $200,000, he added, was saved by switching from cephalosporin to an alternative antibiotic.

For other health systems, rising patient

An $80 Million Windfall

I

n May 2020, when Desi Kotis, PharmD, the chief pharmacy executive at University of California, San Francisco (UCSF), moved from Northwestern Medicine to join the UCSF executive team, she said one of the first things she was asked was, “What can we do to decrease expenses by being more efficient and effective?”

More than a year later, the health system’s financial picture has been brightened by more than $80 million in pharmacy revenue enhancements and savings.

These are some of the year’s highlights: • drug use management of biosimilars: $7.7 million—$1.7 million above $6 million targeted; • dose rounding of injectable drugs, with a special focus on UCSF’s two pediatric hospitals: $500,000; • converting IV medications (including IV acetaminophen) to oral administration: $3.4 million; • partnering with the revenue cycle department to reverse authorization denials, especially for biosimilars: $1 million; and • improving billing practices, including use of the Medicare JW modifier to maximize payments for unused and discarded drugs and biologics in singleuse vials: $6 million.

—B.B.

The Right Structure Is Key

H

ow can pharmacy help to improve hospitals’ financial performance?

“You need the right pharmacy structure,” said Steve Rough, MS, RPh, a senior vice president at Visante. “You also need to empower your pharmacy leadership team to go after the opportunities in the face of limited resources and competing priorities.

“When you do that, it frees up additional margin for your organization to invest in the overall pharmacy enterprise in terms of patient care services,” he added. “That can give the organization the financial capacity, for example, to elevate pharmacy technicians’ salaries and positions to where they ought to be. You establish a model in which the best pharmacy practitioners want to work and want to practice, and where they are empowered to make a difference in optimizing patient quality outcomes and doing everything pharmacists are trained to do.”

—B.B.

acuity levels driven largely by the pandemic have left little time for developing revenue-building pharmacy programs.

That has been the case for the threehospital Baptist Health system in the Montgomery, Ala., area.

“I don’t know if we’ve done anything particularly innovative in reaction to the pandemic,” said Eric Morgan, PharmD, the CEO at Prattville Baptist Hospital, in Alabama, the smallest member of the group. “But we’re kind of the offensive line on the team,” he said, referring to pharmacy. “We keep our heads down doing what we do.” This means remaining “nimble” in the face of rising demand, reacting to FDA emergency use authorization guidelines and moving quickly to get new therapies approved by the system’s pharmacy and therapeutics committee and monitoring their use. It also has meant, he said, “proactively ordering stock of critical care drips and medications that have gone in and out of supply over the pandemic.”

Dr. Morgan said he didn’t know if any of the measures saved money. “Our pharmaceutical buyers are buying more than they ever have.” They’ve been judicious, he added, “but our pharmaceutical expenses are well above pre-pandemic levels.”

—Bruce Buckley The sources reported no relevant financial disclosures.

Operations & Management

Pharmacy Practice News • November 2021

35

Managed Care Pharmacy leaders:

Stay Nimble in Rapidly Changing Market

M

anaged care market dynamics are changing quickly, so pharmacy leaders need to be nimble and work with their managed care teams to maintain a competitive strategy, speakers said at the 2021 ASHP Conference for Pharmacy Leaders, held virtually.

Mega-mergers have affected the market, with payors such as UnitedHealth Group joining forces with or acquiring pharmacy benefit managers and pharmacies, said Paul Spencer, MBA, the vice president of managed care and revenue cycle for Froedtert Health, in Milwaukee. “I don’t see this trend abating,” Mr. Spencer said, noting these compa-

nies are likely to continue establishing more vertical arrangements to round out their continuum of care. Some of them are even referring to themselves as providers, he said.

It’s important to remember that when negotiating with these companies, with their deep pockets and broad reach, “they have a scale we do not.” These forces have pitted providers against payors to see who is going to emerge as the patient’s trusted advisor, and it’s not clear how it will play out, Mr. Spencer noted. There is more blurring of traditional provider– payor relationships.

He cited telehealth and artificial intelligence as other trends to watch, with the technologies spurring more interactions between patients and companies delivering or directing care. Providers have an advantage in being the legacy trusted advisor, but payors have an advantage in that they can direct where they will pay for care.

The landscape is changing fast, with the entry of private equity money to try to fix the problem of lowering costs of drugs through mail-order companies, said Philip Brummond, PharmD, FASHP, the chief pharmacy officer at Froedtert Health. Another trend is payors continuing the push to outpatient or home care as a major cost-saver.

To compete in these vertically integrated spaces, pharmacy leaders need to leverage their integrated delivery models, with access to electronic health records and patient data, Dr. Brummond said.

How to use these data, how to determine what kind of therapy is needed for which patients, and how to get outcomes that pharmaceutical manufacturers and others expect are areas that are “incredibly

important to spend time on,” he said.

Highlight metrics such as the Net Promoter Score and patient testimonials, be wise in what you do versus what you outsource, and work to restore transparency by driving lower costs.

There’s no time better than now to start developing a strategic vision and plan, with an eye toward making pharmacy

a central component, Dr. Brummond stressed. He added these tips: • Get buy-in from executive leaders.

Help them understand the value of pharmacy as it relates to managing costs and improving quality outcomes.

• Align the pharmacy team around your strategy.

• Evaluate where your team’s time is

spent, and what actions and outcomes are being achieved.

• Make sure the pharmacy executive has influence at the executive table.

“It’s easier said than done,” he said. “But more and more people are [assuming] roles that have that influence, and health systems are seeing the value that pharmacy is bringing to the overall enterprise.”

—Karen Blum The sources reported no relevant financial disclosures.

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Key steps for becoming an ‘outcomes powerhouse’

Health Systems Prove Value in Specialty Care

C

ompared with other types of specialty pharmacies, those based in health systems have superior access to patients and providers, as well as information in medical records, speakers said during a session at the virtual 2021 ASHP Specialty Pharmacy Conference.

These factors can be leveraged to demonstrate value to various stakeholders.

“Metrics commonly used to measure specialty pharmacy services today focus mostly on operational requirements,” said Amber Skrtic, PharmD, CSP, AAHIVP, a clinical pharmacist with Trellis Rx at Parkview Health, in Fort Wayne, Ind. “While we perform better on these metrics, they don’t show the full impact of our integrated services. Proving our value

lies in showing how our higher level of integration allows us to provide differentiated services [and improve] clinical and qualitative outcomes.”

Determining what metrics to measure is not always straightforward, especially in disease states that don’t have clinical markers, Dr. Skrtic said. She recommended looking to clinical trials,

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evidence-based guidelines, peer organizations and stakeholder colleagues for guidance. One metric all stakeholders agree on is better outcomes, she noted. Once you determine outcomes to measure, then decide what activities are needed to achieve them. A health-system specialty pharmacy should consider three critical strategies to become an “outcomes powerhouse,” Dr. Skrtic said: 1. Develop disease-specific protocols. These should account for the full patient journey, she emphasized.

It’s also important to consider patient onboarding to ensure they can afford therapy and start in a timely manner, how to proactively manage refills, and how to determine what clinical activity is needed to ensure therapy is appropriate and patients receive support to remain adherent.

2. Leverage electronic health records (EHRs). EHRs can be a critical technology for deploying these protocols and workflows, Dr. Skrtic said. Ideally, the programming/protocol should trigger interventions automatically based on data captured by the EHR or the specialty pharmacy team. The programming/protocol also should collect data in a consistent, reportable fashion.

3. Embed pharmacists and liaisons on-site. The pharmacists should work closely with providers to see patients in person whenever possible, Dr. Skrtic said. The pharmacists also need access to the EHR to see pertinent information and document updates.

In one project, Dr. Skrtic and her colleagues at Parkview Health—a 10-hospital health system in Indiana and Ohio that launched integrated specialty pharmacy services in 2019 with Trellis Rx—evaluated their impact on lost work productivity among patients experiencing migraines.

These patients were covered under Parkview’s employee health plan and prescribed calcitonin gene–related peptide specialty medications for migraine. Pharmacists routinely conducted patient-reported outcome measure assessments and performed interventions, if necessary, based on the results.

Over an eight-month period, pharmacists performed 29 interventions, such as dose or therapy changes, adherence counseling and adverse event management for 38 patients. The number of migraine days per month decreased by 55%, and lost productivity per month, including workdays missed and productivity lost during migraine attacks, decreased by 60%.

4 Steps to Demonstrating Value When using metrics and measures to demonstrate value, consider four points, said Ann McNamara, PharmD, the director of clinical development at Fairview

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Mining Claims Data Can Make Your Case

T

here is an urgency for hospital and health-system specialty pharmacies to leverage and optimize their patient care models, a panel of experts said at the 2021 ASHP Specialty Pharmacy Conference, held virtually.

Such an approach is key to ensuring the sustainability and growth necessary to continue to care for patients and evolve in an increasingly competitive health care market, they noted.

Health-system specialty pharmacies do well helping patients with access to medications and education, making sure they are taking medications as directed and that they don’t have side effects, and are seeing improved outcomes in quality of life and health care costs, said Erin Hendrick, PharmD, BCPS, the senior vice president of Health System Strategy for Shields Health Solutions, in Atlanta. Now they need to show that investing in this area “really will pay off for the health system,” she said. Claims data are great to use to prove your point.

It’s key to have pharmacists embedded in physician practices and, if allowed by states, to have collaborative practice agreements, said Angela Ward, BSPharm, MSB, the senior vice president of specialty services for AmerisourceBergen, in Carrollton, Texas. “That lets the pharmacist really have that supercritical face time with

Specialty Pharmacy, in Minneapolis: 1. Look to the Quadruple Aim for value. Consider metrics to prove how you lower costs, improve outcomes and the patient–provider experience, or that pursue health equity. For costs, describe how you decrease hospitalizations and emergency department (ED) visits, or how you encourage the use of less costly options, such as generics and biosimilars, when appropriate. For clinical outcomes, show cures in hepatitis C therapy completions or how you monitor disease activity, and how you document interventions when patients don’t meet treatment goals. “Activity metrics such as assessments and interventions are important, and help demonstrate your pharmacy takes an active role in meeting treatment goals,” Dr. McNamara said.

2. Partner with key stakeholders.

Look for opportunities with your clinics, pharmaceutical manufacturers or payors for areas where you have mutual goals.

“Pharmacies that are part of a health system have great opportunity to collaborate with clinics to define and report metrics that can be used to demonstrate value,” she said, such as working with a hemophilia treatment center to showcase ED or medical resource utilization, or adherence to prophylactic regimens.

There also are opportunities to find projects with drug manufacturers that don’t involve promoting their products. Go beyond adherence to show value.

3. Combine metrics with other information to tell a more holistic story. Use metrics along with descriptions of your process, interventions and cases. “Often, cases tell the reality of the situations, the complexity of specialty patients, and how assessments and interventions over time result in supporting

the patient,” she said. A recent study (Am J Health Syst Pharm 2021;78[11]:962-971) showed that patient and provider satisfaction was significantly higher using inhouse versus external specialty pharmacists.

There are opportunities to showcase specialty pharmacy skills more broadly and creatively, said Denali Cahoon, PharmD, the chief operating officer for Trellis Rx, in Atlanta. She mentioned seeing hospitals use this model to support patients during transitions of care or for those with common chronic conditions, such as diabetes.

Marketing efforts can signify to pharmaceutical manufacturers and payors that there are benefits to working with hospital specialty pharmacies, in areas such as lowered product abandonment, said Thomas Renshaw, RPh, MBA, MCSD, the senior director of business solutions at Acentrus Specialty, in Lewisville, Texas. “But first we need several things to get truly meaningful outcomes data,” he said: • having access to robust, clean data; • having the clinical expertise to ask the right questions from that data; and • having some type of program to alert providers at the point of care to make those insights actionable. This can change care prospectively, not retrospectively.

patients in meeting treatment goals,” Dr. McNamara said. Describe your strategic approach, services and metrics for each disease state.

4. Know your audience. It also is important to provide metrics that are most relevant to your audience, she noted.

For many payors, health equity and costeffective use of anti-inflammatory medications are top of mind. To gain access to limited distribution drugs, think about what’s important to manufacturers, such as time to fill, patient adherence and experience. For internal audiences, demonstrate that you are efficiently providing services that affect the Quadruple Aim. As an example, Dr. McNamara discussed a program in which the pharmacy worked with a hospital health coach and chaplain to provide extra help to patients whose needs went beyond the usual expertise of the pharmacy. This included adjusting to living with new diagnoses, the loss of loved ones or mental health issues. With COVID-19, many patients were isolated, gained weight or lost jobs. Together, the pharmacy, therapy management team, chaplain and health coach wrote a program description, process and services, and agreed on metrics to measure.

The health coach and chaplain intervened when necessary, referring patients to health care and other resources, therapists, physicians, palliative care, psychologists and social workers, among others.

One patient with multiple sclerosis who had lost two loved ones and was caring for four young children was connected to county services for housing, child care resources during a hospitalization and financial assistance to purchase an air conditioner, and was able to seek grief counseling. “Cases really demonstrate how powerful the interventions are and

Pharmacies tend to be insular and work on their own, Dr. Hendrick noted. Take advantage of the fact that health-system specialty pharmacies “have long tentacles,” she said: Being aligned with finance, network contracting, information technology and other teams provides great opportunities to leverage skills and resources across departments.

Even smaller hospitals are getting into the specialty pharmacy space, Ms. Ward added. “If we can work together, we’d be a force to be reckoned with.”

—K.B.

the work that you do,” Dr. McNamara said.

In patient surveys, 100% of respondents agreed that they were satisfied with the program, with the majority (85%-97%) stating their physical and

mental health were positively affected.

—Karen Blum The speakers reported no relevant financial disclosures.

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A challenge for health-system specialty pharmacies

Little Things Can Cause Big Issues in Patient Care T

he patient—a woman with a neuroendocrine tumor—had waited at Baystate Medical Center’s infusion center for three hours. The lanreotide (Somatuline Depot, Ipsen) injection for her tumor treatment had not arrived from the out-of-state third-party pharmacy mandated by her insurance. No one at the hospital could trace it. The drug was reordered and the patient’s treatment had to be rescheduled. Although she received her treatment, the delay could have compromised her care.

In another case, IV immune globulin was scheduled for delivery at a specific address at the Baystate campus so it could be signed for and then walked over to the integrated specialty pharmacy, but it did not arrive. It was later discovered that the third-party drug supplier had used the wrong address.

(Baystate is a large system in western Massachusetts and has multiple addresses.) Eventually, the drug was found and delivered, but the amount of time and effort expended because of a clerical error was enormous and caused significant distress to the patient.

Although much attention has been given to treatment delays caused by prior authorization hurdles, sometimes patient care in specialty pharmacy is interrupted by simple clerical errors such as those in the cases above. While treatment in both cases was ultimately rescheduled as soon as possible and shipping addresses and contact information were updated, the problems could have been avoided, said Gary Kerr, PharmD,

the chief pharmacy officer at Baystate Health, who noted that the health system tries to gain access and control of the shipping process so it can provide the drug directly whenever possible.

“The things that derailed treatment in these two cases were all little things. It’s basically logistics—packing, shipping and delivery issues—especially when the drug is mandated by a payor or PBM [pharmacy benefit manager] to be sourced from a supplier in another state or region. Once we have the drug in our possession, the process typically runs very smoothly.”

On a more systemic level, Dr. Kerr added, “it’s about providing more patient access and choice. We have found it makes a dramatic positive impact on the entire therapy delivery process, and more importantly, on patient care.”

Beware of ‘Handoff Gaps’ Like many health systems, Baystate Health has a state-of-the-art integrated specialty pharmacy and is not immune to the industrywide challenges posed by drug delivery channels mandated by payors and/or PBMs. When a drug is sourced from out of state, out of region or even simply outside of preferred channels, there is a higher risk that these “handoff gaps” will occur, said Dr. Kerr, who noted that Baystate tries to work with insurance companies to reduce restrictions that limit where prescriptions can be filled.

“Our pharmacy is literally 100 yards from our cancer center, and 25% of the patient panel in our integrated

specialty pharmacyy is from the cancer center,” he said. “How does it make sense that we are forced to purchase a drug from a supplier plier in Houston or Miami when I could uld walk outside my door, throw a rock and hit the cancer center? When hen we supply the drug ourselves, s, if a physician writes an order at 3 p.m. Eastern time on Monday, we could start therapy on Tuesday or, worst case, on Wednesday.”

When it’s allowed d to work as intended, the integrated specialty pharmacy model at Baystate has reduced fragmentation in care and improved d patient outcomes across a number of metrics. According to internal data, time to start therapy erapy in one study was cut in half lf (now averaging 2.2 days); prior authorization rization turnaround time was reduced to o less than a day; and clinical metrics across oss a number of disease states improved. d.

“Our multiple sclerosis lerosis relapse rates are world-class, with th more than 87% of patients reporting zero flares,” Dr. Kerr added. “For our patients ents on HIV therapy, 91% have achieved d suppression, while 97.2% of our hepatitis titis C patients have achieved sustained viral response. In oncology, 5.3% of our patients on service have had ED [emergency department]

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visits or hospitalizations related to their cancer diagnosis—significantly below the national benchmark.”

To bring attention to the quality of care delivered by health-system specialty pharmacies, Baystate and a number of other health systems launched the Health System Owned Specialty Pharmacy Alliance (HOSP) in October 2020.

This nationwide organization of leading health systems is specifically focused on the interests of health-system that own specialty pharmacies. They advocate for an integrated model, set best practices, work on technology solutions and bring attention to key operational and clinical challenges faced by members.

In addition to Baystate Health, some of the other health systems involved in HOSP leadership include Minnesotabased Fairview Health, New York’s Northwell Health, the University of Massachusetts Memorial Medical Center and WVU Medicine in West Virginia.

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are shipped from an outside pharmacy to the patient’s site of care. “Clear bagging” has typically been the term used when a health system’s own specialty pharmacy delivers medication for administration to a patient, but HOSP has coined a new phrase: “gold bagging.” This, HOSP says, exemplifies the “gold-medal” service provided when a prescription is filled inhouse by their own specialty pharmacy staff, packaged and delivered to the final place of administration usually on the same campus as the hospital, office or infusion clinic.

“These locally managed logistics are largely foolproof when a healthsystem–owned specialty pharmacy is involved,” Dr. Kerr said. “Everything is done and managed within the healthsystem campus as opposed to trying to manage drug delivery remotely from many miles away that may not match a patient’s real-time needs. In the unlikely event of a lost order or last-minute dosage changes, the on-campus pharmacy is able to ensure a new dispense can happen in real time so that the patient appointment is not rescheduled and the treatment regimen remains intact. The ultimate aim is for the right drug, in the

right dose, at the right time, [to be] provided to the right patient within their existing continuum of care.”

Another Player The HOSP Alliance isn’t the only effort to band health-system specialty pharmacy stakeholders together. Another group, Excelera, seeks strength in numbers via its own network of providers.

Tim Affeldt, PharmD, the vice president for Specialty/Infusion Pharmacy Operations at Fairview Health Services, is member of both HOSP and Excelera.

Asked to compare the two organizations in a December 2020 interview with Specialty Pharmacy Continuum (bit.ly/3F1tYwd), Dr. Affeldt said although they share a common focus on providing integrated specialty pharmacy care, their operating models are different. “Excelera is a for-profit company that helps health systems start, operate and optimize specialty pharmacies,” he explained. HOSP, in contrast, is a nonprofit trade association that “is not going to help anyone start a pharmacy; they’re not going to help their

membership run their operations.”

Dr. Affeldt stressed, however, that HOSP offers significant benefits to its participants. “HOSP members can focus on our unique issues and commitment to patients and their care team. This is why Fairview has been very interested in HOSP from the beginning.”

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

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40 Technology

Pharmacy Practice News • November 2021

Medication Safety

IV-WMS Adoption continued from page 1

The most recent national practice survey by ASHP found about 21% of U.S. hospitals used IV-WMS, a 1% increase from the previous year (Am J Health Syst Pharm 2021;78[12]:1074-1093). For comparison, the rate was 13% in 2017.

“Fortunately, we’ve had a little bit of a push, but there’s still a long way to go,” Dr. Fortier said.

Many hospitals have at least adopted key components of IV-WMS, such as barcode scanning (33.8%), image verification (25.3%) and gravimetrics (5%), and small numbers reported the use of robotics (3.4%), said Amey C. Hugg, BSPharm,

ASHP’s director of member relations for the Section of Pharmacy Informatics and Technology. (For one hospital’s experience with robotics, see page 46.)

“When all technologies are considered … 52.7% of hospitals do not use any technologies for compounding sterile preparations, which is decreased from 2017, when 64% of hospitals did not use any technology for sterile product compounding activities.”

Delay Despite Society Support The slow rollout has occurred despite societies of pharmacy recommending the

use of IV-WMS for more than a decade.

That’s an unfortunate delay, Dr. Hugg noted. “[IV-WMS], technology and automation are proven to improve patient safety by reducing potential for human error associated with manual processes,” she said. “Use of such technologies is strongly advocated by ASHP [bit.ly/3j68Wn3] and the Institute for Safe Medication Practices [ISMP; bit.ly/3nrdkhN].”

The risks for human errors in manual preparation of IV medications are well established. A 2020 ISMP survey showed 74% of pharmacy staff were aware of at least one compounding error during the previous 12 months, most of which were incorrect doses (58%) (bit.ly/3jhGC17).

The benefits of IV-WMS in reducing

‘ workflow management systems, technology and ‘IV automation a are proven to improve patient safety by reducing potential for human error associated with manual processes. Use of such technologies is strongly advocated by ASHP and the Institute for Safe Medication Practices.’

—Amey C. Hugg, BSPharm

these errors also are well established, said Dr. Fortier, noting a half-dozen studies published in the American Journal of Health-System Pharmacy over the 2010s that all demonstrated “a major amount of error detection” using IV-WMS, as well as staff satisfaction.

IV-WMS Versus Barcoding A team at MGH demonstrated the benefits of implementing an IV-WMS in a recent study, according to Blake Barlow, PharmD, MBA, MS, a former resident at the hospital and now the clinical pharmacy manager for adult medicine and cardiology at WVU Medicine, in Morgantown, W.Va. Unlike studies that compare IV-WMS with manual processes such as the syringe pull-back method, Dr. Barlow and his colleagues compared an IV-WMS (Omnicell IXV) with its existing barcode system (Epic Dispense Prep/Check) after implementation across the institution’s entire nonhazardous formulary (five sterile compounding suites, two off-site infusion pharmacies, 350,000 IV doses dispensed annually, 21 technicians and nine pharmacists).

Using failure modes and effects analysis, Dr. Barlow and his colleagues found the IV-WMS significantly reduced the

10 Tips for Implementing an IV-WMS

B

lake Barlow, PharmD, MBA, MS, the clinical pharmacy manager for adult medicine and cardiology at WVU Medicine, in Morgantown, W. Va., and Andrew C. Lodolo, PharmD, BCPS, BCCCP, the pharmacy manager for inpatient services at Eskenazi Health, in Indianapolis, shared key lessons they learned when implementing an IV-WMS at their institutions: Involve staff early. Dr. Barlow recommended that pharmacists and technicians be integrated into the process as early as possible so they know what the device is, how it works and why it’s important for patient safety. “We saw that if you’re not integrating early, you might see some failures down the line due to [lack of] staff buy-in.”

Train support staff. “Utilize training and education resources to prepare pharmacist and technician subject-matter experts for ongoing staff support in addition to the management team,” Dr. Barlow said.

Maintain existing systems as a backup. It’s important to maintain operation of your existing compounding workflow during early implementation as a safety backup. Dr. Barlow noted that a staff member “might get confused about how to proceed, or if there’s a tech error up front, you need a safety system to fall back onto so a patient can get the right medicine as quickly as possible.”

Share progress. “We utilized an implementation daily go-live project dashboard that we found very successful to really promote our progress with the group, cheer them on, show them our success … so that everybody was kept in the loop on a daily basis as far as how well we were going with the process,” Dr. Barlow said.

Decrease batch time intervals. Dr. Barlow said his institution plans to reduce batch times so staff can focus on a smaller volume of orders. “With a

brand-new device, we found that the staff were getting a little overwhelmed when a lot of batch orders were printing out at once. Even though those orders might not be due for four to five hours, just the sheer volume that was sitting next to them maybe made them feel a little stressed and try to rush the process.”

Identify key stakeholders up front.

Dr. Lodolo emphasized the importance of aligning key stakeholders at the beginning of the product selection process.

“We identified key stakeholders that would be needed to weigh in on this decision of implementing an IV workflow solution that included: 1) senior leadership that would provide the financial backing for this initiative, 2) pharmacists, both front-line and those that would maintain the system, and 3) IT [information technology] team members, as we knew we wanted an integrated system, and our EHR specialist,” he said. “At go-live, we knew it would be important to identify other key stakeholders like subject-matter experts and super users.”

Release medications in phases. Dr. Lodolo said he “was really hopeful for a big bang go-live … for all compounded sterile products. Unfortunately, that wasn’t an option. Therefore, we introduced biweekly phased releases of two to four medications into production. This allowed for staff buy-in because they were still able to use the systems that they were comfortable with.”

Create and maintain a test environment. A test environment is something Dr. Lodolo recommended for any health system planning to implement an IV-WMS. “This allows us to develop protocols in a safe space and complete robust testing before we implement that into the production environment.”

Use protocol selection. Dr. Lodolo recommended using gravimetric verification whenever possible, especially for products with patient-specific dosing, such as high-alert medications or partial vials.

For whole vials, “we might implement volumetric workflows because we know you’re going to typically use the whole vial, so there’s no reason to slow down the process if you don’t have to.”

Develop a synced cadence. Dr. Lodolo’s institution developed a synced cadence as “a tryout approach with our operations team, our EHR analytics team and our IV-WMS consulting team.

This has allowed for robust evaluation of ordering capabilities within EHR to make sure all orders transition to IV-WMS appropriately. It also allows us the opportunity to troubleshoot protocols before they go into the production environment.”

—A.L.

Technology

Pharmacy Practice News • November 2021

41

Medication Safety potential for errors, particularly in the technicians’ compounding workflow, with a 53% reduction (P=0.02). The IV-WMS also reduced the risk for severe errors in the technicians’ workflow by 81% (P<0.001). “Not only did it provide a much safer environment for our patients,” Dr. Barlow told attendees at Illuminate 2021, “the staff as a whole—both pharmacists and technicians—actually preferred the use of the device, perceiving it to be both safer and more accurate.”

However, total turnaround time increased by about five minutes (24.6 vs. 29.6 minutes), with a longer compounding process (15.4 vs. 22.2 minutes) and slightly shorter verification (9.2 vs. 7.4 minutes).

Slower Turnaround Times A Trade-off for Safety Concern about longer turnaround times is understandable, but slower turnaround is a trade-off for improved safety, according to Dr. Fortier. “It primarily will slow down the technician,” he said. “But that’s the give-and-take of having a much safer situation. On the flip side, it will improve the efficiency of the pharmacist verification because … it can be done remotely [and there will be] better information for that pharmacist to verify those medications.”

Beyond turnaround, the cost of implementation is perhaps the most commonly cited barrier to adoption of an IV-WMS. But as previously reported, research has shown the potential cost savings of this technology can offset the up-front investment. One study of

is not incentivized,” she said.

The recently released update to USP Chapter <797> guidelines for compounding sterile preparations (page 1) does not include requirements for an IV-WMS (bit.ly/3lL6949).

Navigating Vendor Selection Another challenge can be selection of a vendor when adopting an IV-WMS. To help evaluate product features, Dr. Fortier recommended THRIV Coalition’s technology checklist for five standard capabilities an IV-WMS should have (www.thrivcoalition.org/technologychecklist/). The criteria are: • interfaced software that guides staff step-by-step through the compounding process; • barcode scanning; • volume verification using images, gravimetrics or volumetrics; • auto-labeling; and • auto-documentation.

All these and other barriers to adoption disproportionately affect smaller institutions, which explains why their adoption rates are lower, Ms. Michalek noted.

“Smaller hospitals definitely have unique challenges, especially with financial and human resources,” she said.

Ms. Michalek encouraged pharmacy leaders to remain dedicated to improving safety through IV-WMS adoption despite these obstacles. “If you are struggling with gaining support, stay committed,” she said. “If you’ve gotten support for acquisition of ster-

—Christina Michalek, BSPharm, RPh

A New Standard of Practice Christina Michalek, BSPharm, RPh, a medication safety specialist and an administrative coordinator for the Medication Safety Officers Society at ISMP, noted that the up-front investment barrier could be mitigated if an IV-WMS were to become a required standard of practice. “It’s not required, and unlike other technologies like CPOE [computerized provider order entry] and BCMA [barcode medication administration], it

53% reduction in potential errors by compounding technicians and reduced the risk for severe errors in the technicians’ workflow by

81%.

Source: Blake Barlow, PharmD, MBA, MS

‘Stay Committed’

‘[IV-WMS is] not required, and unlike other technologies like [computerized provider order entry] and [barcode medication administration], it is not incentivized.’

IV-WMS implementation at Cincinnati Children’s Hospital showed the system significantly reduced medication waste (P<0.001) and projected more than $500,000 in annual savings (Int J Med Inform 2018;115:73-79).

IV-WMS yielded a

ile compounding technology and are beginning implementation, leverage resources from your peers, vendors, national organizations and ISMP’s forthcoming guidelines. We hope the upcoming guidelines will drive more discussions related to the need for technology in sterile compounding as well as draw attention to the best practices for their use.”

—Adam Leitenberger The sources reported no relevant financial disclosures other than their stated employment.

ISMP, TJC push for more use of dose error reduction software in IV-WMS. See page 42.

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42 Technology

Pharmacy Practice News • November 2021

Medication Safety

Dose error reduction software an underused feature

ISMP, TJC Urge Safer Smart Pump Practices A lthough “smart” programmable IV pumps have become commonplace across hospitals and health systems, simply having the technology in place does not necessarily mean the brains of the device—namely, dose error reduction software (DERS)—are being used.

“There is room for improvement in monitoring of DERS use and in addressing the causes of non-utilization,” said Robert Campbell, PharmD, the clinical director of the Standards Interpretation Group and director of Medication Management, the Joint Commission, in Oakbrook Terrace, Ill.

To help organizations increase use of DERS by staff, the Joint Commission recently issued a Sentinel Event Alert (bit.ly/3G2g1ic) providing a slew of recommendations for organizations to consider for reducing the likelihood of users programming an infusion in basic mode or bypassing safety features (sidebar). In 2020, the Institute for Safe Medication Practices (ISMP) published its own guidelines nudging institutions to make greater use of built-in DERS for nearly every type of infusion in all settings (bit.ly/3lW4c5e).

Leading hospitals around the country have demonstrated that measures such

The Joint Commission’s Recommendations For Optimizing DERS Safety • Create a multidisciplinary project team or department to assume responsibility for smart infusion pump interoperability, including dose error reduction software (DERS), the oversight of drug library revisions or additions, infusion protocols, smart infusion pump maintenance, and related issues.

• Define a process to create, test, regularly engage with, and maintain a drug library, including standardizing parameters, creating subsets and limiting availability of custom concentrations.

• Train and assess competency of all clinical staff who use smart pumps.

• Make the optimal use of DERS expected practice.

• Monitor alerts, overrides, equipment or software recalls and adverse event and close-call reports.

• If your organization has the capability, connect your smart pump fleet to your electronic health record system to enable autoprogramming.

• Identify and address human and environmental factors that contribute to programming errors. These can include understaffing, workflow distractions and low lighting or glare.

• Keep the smart pump fleet safe from security threats and during downtime.

Source: The Jont Commission (bit.ly/3G2g1ic)

as those laid out by the two patient safety organizations are effective.

Stacy Carson, PharmD, a medication safety officer and co-chair of the smart pump oversight committee at AdventHealth, in Altamonte Springs, Fla., helps manage a fleet of smart pumps (Plum 360, ICU Medical and Medfusion 4000 and CADD-Solis, Smiths Medical) at eight AdventHealth facilities in the Orlando area. One initiative that she and her colleagues rolled out in 2018 led to a 23% increase in DERS compliance.

Dr. Carson said effort included partnering with the pump vendor to perform walkrounds, improving general staff knowledge of the library, relaunching the smart pump oversight committee and updating the library with improvements.

“One simple improvement we made at the time that had a big effect on library compliance was moving the ‘no drug selected’ option in each library profile entry from the top of the list of options down to its alphabetical location,” Dr. Carson said. “Although there are times when it’s necessary to manually program an infusion outside of the drug library, changing the location of this option made it easier to do what’s right and harder to do what’s wrong.”

After implementing the initiative, the organization saw DERS compliance increase from 70.2% to 94.1% over a twomonth period, Dr. Carson said.

At Vanderbilt University Medical Center, in Nashville, Tenn., where Terry Bosen, PharmD, is the medication safety program director, smart pump

optimization efforts are part of everyday practice. For example, nurse leaders check infusion pumps during rounds, Dr. Bosen said. “If they see that an infusion has been programmed in basic mode, they switch it to the library entry.”

To further optimize their smart pump usage, she and her colleagues periodically analyze the trove of data on alerts, alarms, overrides and other potentially valuable metrics generated by smart pumps—a strategy that the Joint Commission recommends to enhance pump safety.

“Based on our alert data evaluation, we decide whether to change dose and infusion alert limits to reduce nuisance alerts and decrease programming alert fatigue,” Dr. Bosen said.

Until recently, she and her colleagues also were part of the REMEDI network, a collaborative of health care organizations that shared their experiences employing smart infusion pumps. “Being able to see other institutions’ drug entry builds was particularly helpful for those entries that are more complicated to create, and comparing drug entry limits helped us evaluate our standards of practice.

“We’re all doing the same quality improvement work and are very busy, which makes collaborating so important and effective,” Dr. Bosen added, lamenting that REMEDI is being shuttered as of November 2021.

Team Looks ‘at Big Picture’ Emily Grant, RN, a patient safety coordinator at UCHealth University of Colorado Hospital (UCH), in Aurora, said her organization has made smart pump optimization a priority by building a multidisciplinary group to oversee its use of these devices—another recommendation outlined in the Joint Commission’s Sentinel Event Alert. The team includes representatives of departments ranging from pharmacy to nursing, clinical engineering and informatics, information technology, and electronic health record (EHR) analytics, among others.

“This team sees the big picture while also identifying subtle gaps that, when aligned, could allow an error to reach the patient,” Ms. Grant said.

As the Joint Commission recommends, the team regularly reviews the smart pump drug library (they use Alaris pumps), including new formulary additions, top alerting drugs and guardrail alerts. This process is an opportunity to ensure all library entries are current, they support clinical practice for a diverse patient population, and that parameter limits are appropriate and do not lead to alert fatigue, Ms. Grant said.

Automatic DERS Compliance Unlike most organizations across the country (ASHP sidebar), UCH has integrated smart pumps with its EHR (Epic). The move “was a game changer,

Technology

Pharmacy Practice News • November 2021

2020 ASHP National Survey Of Pharmacy Practice in Hospital Settings providing the obvious benefit of automatic DERS compliance and allowing us to truly reap the rewards of autoprogramming by protecting patients from the majority of wrong dose, weight, duration, rate and concentration errors,” Ms. Grant said.

Since linking their smart pumps to their EHR in 2015, Ms. Grant and her colleagues shifted from looking at DERS compliance to focusing on compliance with EHR–pump autoprogramming.

Reducing the chance that an end user will have to manually program after an infusion is autoprogrammed has required paying close attention to how orders are built in the EHR, Ms. Grant said.

For example, she noted, EHR “builds” should accommodate workflow considerations such as overfill in a bag and any additional volume added in the priming process. “If you don’t take that into account, users will have to manually adjust the volume to be infused after it is sent to the pump.”

Ms. Grant said she and her team encourage use of interoperability by explaining the patient safety benefits of the practice. They also have made it a point of ensuring a reliable wireless network is in place wherever smart pumps are being used with interoperability functionality

• 262 hospitals surveyed in 2020.

• 87.9% reported using smart infusion pumps, up from 32.2% in 2005.

• Use of smart infusion pumps varied by hospital size, with 79.6% of hospitals with 50 or fewer beds using the technology, compared with 100% of hospitals with 600 or more beds.

• 13.4% said they had a smart pump–EHR interface that autoprograms pumps with information from the EHR, up from 8.9% in 2017.

• 14.9% of respondents said they have an EHR–pump interface allowing smart pumps to autopopulate infusion data to the EHR. • The remaining 85.1% of hospitals require nurses to manually document infusion data in the EHR. Source: Am J Health Syst Pharm 2021;78(12):1074-1093.

because users “lose faith in the system and start seeking workarounds” when connectivity is spotty, she said.

“One of our newer hospitals opened up some shelled space during the pandemic and had dismal integration compliance,” Ms. Grant added. “After reviewing the data, we quickly saw that a weak wireless network was the culprit.”

Leveraging Nurses Nurses have played a central role in smart pump quality improvement initiatives at UCH, Ms. Grant noted, explaining that they can shed light on whether smart pump alerts are triggered because a drug library entry does not support clinical practice or whether “there is an

Don’t Miss Our Next Issue!

Be sure to keep an eye out for these topics from the latest pharmacy conferences, along with enterprize reporting on hot practice trends: ❖ Ig FAQs: What does the future of immune globulin therapy look like? ❖ New paradigms in HIV therapy: single-pill combinations, injectables and long-acting regimens expand options ❖ The Year in Review for 2021 drug approvals ❖ New data confirm savings, effectiveness of rituximab biosimilar across all indications ❖ Telepharmacy and other operational tweaks that are here to stay even after COVID-19 wanes ❖ Strategies for boosting biosimilars across the entire health care continuum

opportunity to reeducate staff on recommended workflow.”

Nurses also are encouraged to report pump issues and errors using a convenient streamlined incident report process initiated directly in the EHR. “We have incentives for reporting, such as a point-based recognition program with redeemable awards, and we celebrate those whose reports result in fixes and safety initiatives,” Ms. Grant added.

The combination of nurse reporting and leadership-driven change has led to impressive integration compliance. “At one of our main hospitals, compliance increased from 92% in 2019 to 92.5% in 2020, and thus far in 2021, it is averaging 92.7%,” she noted, saying “even small

43

Medication Safety increases in compliance during a pandemic are laudable.”

ISMP’s Take Michelle Mandrack, MSN, RN, the director of consulting services at ISMP, emphasized that although integrating smart pumps and EHRs is “the new horizon” for smart pumps “and eliminates a big chunk of opportunities for programming errors, getting that EHR integration in place is a lengthy and costly interdisciplinary effort, and not necessarily within everyone’s reach at the moment.” She added that the ISMP and Joint Commission smart pump practice recommendations are a good place to start making full use of the safety features offered by the infusion devices. “We’ve had smart pumps for 20-plus years, and many institutions are not maximizing what this technology can do for us on its own.”

—David Wild Dr. Carson reported financial relationships with ICU Medical and Smiths Medical. The remaining sources reported no relevant financial disclosures.

For more IV automation, see pages 44-46.

44 Technology

Pharmacy Practice News • November 2021

Medication Safety

Optimizing IV Workflow Mgmt at Your Institution A fter you have gotten buy-in from the departmental and/or institutional leadership at your hospital to invest in an IV workflow management system (IV-WMS) for your sterile compounding, all your worries about compounding errors are over, right?

Not so fast.

Leading medication safety experts, such as the Institute for Safe Medication Practices (ISMP), advocate for the

widespread adoption of IV-WMS in compounding to detect and intercept the errors that humans—even when they are highly trained, experienced and vigilant—can unwittingly commit and fail to catch. Even though research and real-world experience have shown that IV-WMS can significantly reduce these errors, it’s up to the people who put this technology in place to use it most effectively.

“Automation, even a tool as advanced as IV-WMS, doesn’t remove the potential or substitute for human work,” said Charlene Hope, PharmD, the chief pharmacy quality and medication safety officer at the University of Chicago Medicine. “Rather, it creates new human work and changes the kinds of errors that people can make. There may be data overload, workload bottlenecks and new demands on your attention.

Free CE/CME now available!

You can maximize the benefits of your IV-WMS by addressing workarounds and errors.”

The University of Chicago began rolling out IV-WMS in July 2018, beginning with its off-site freestanding chemotherapy clinics and then adding inpatient chemotherapy services a month later.

“This phased-in approach involves fewer staff in the initial phase, so you can put in the workflow, train them and observe glitches with the system in a limited formulary,” Dr. Hope said.

“You’re taking a complex, high-demand area and introducing software that’s going to impose constraints, which then start to reveal a lot of challenges.”

For example, if you have an IV formulary that has limited standardization, now is the time when you may realize that you can no longer accommodate

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Technology

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45

Medication Safety

four different standard concentrations and should move to two, Dr. Hope noted. “Once everything is loaded into the software, there needs to be testing and validation because this becomes the source of truth,” she said.

By early February 2019, IV-WMS had been rolled out for all IV preparation at the University of Chicago. Soon Dr. Hope and her team observed that there were several challenges to making the most of the new system, including adding new products, expectations around turnaround time, STAT dosing and bypasses.

“We had a medication event that was a good catch by one of our nurses,” Dr. Hope said. “She was about to give an intrathecal injection and realized that the wrong drug had been made. Investigating what happened, I reviewed the IV-WMS images and saw that the product had been bypassed.”

It turned out that IV room practices on the use of bypass were inconsistent: Technicians might decide when to bypass a product on their own. There was a verbal understanding that a technician should get a pharmacist’s approval before bypassing, but no standard protocol was in place. Subsequently, the institution developed policies and procedures outlining when drugs can be bypassed in the IV-WMS and when they cannot be, and indicating that pharmacists must always approve any bypass.

Turnaround Times a Sore Point Changes in turnaround times can be frustrating when an institution has just adopted IV-WMS. “What might have previously been a three-minute process may now double in time, so you need to educate your nursing and medical staff as to why this may happen and that it is safer for their patients,” Dr. Hope said.

“We have also established a threshold at which [when] the number of IVs in our verification queue reaches an overwhelming level, the pharmacist is to send out an all-bulletin page to the rest of the department to say that we’re backed up so other pharmacists can jump in and help to check product, to remove that pressure of engaging a workaround to get through the queue.”

Turnaround times also should be less of an issue with newer IV-WMS, said Derek Gillespie, BSPharm, MBA, an advocate for patient safety in pharmacy. “I had an early version of Baxter’s DoseEdge, and they readily admitted it took longer to process, on the order

of 20 to 30 seconds, which can add up if you start multiplying. If you’re in a small hospital with 50 to 100 admixtures a day, that’s not a big issue; but at a huge hospital, that’s a significant amount of time to add to your day.”

More recent versions of the systems from vendors such as BD Cato, Omnicell and DoseEdge have streamlined their operations. “The newer integrated machines don’t ask the user to take the photo, weigh the product or read the barcode using a foot pedal or a touch screen; they do those steps automatically,” Mr. Gillespie said. “You follow the instructions on how to admix a product and the machine will do the rest.”

‘Super Users’ and Continuing Vigilance An effective strategy the University of Chicago group employed to support IV-WMS use was the designation of a “super user” for each shift. “Managers may be working during the day, but what if you encounter issues on the overnight shift?” Dr. Hope asked.

“You need to ensure that you have trained staff who are competent at problem solving and critical thinking who can help other team members on every shift. For example, new drugs and new concentrations: About 90% of your compounds will be standardized in the system, but sometimes patients have a special need and you may need to work outside the confines of the system. Often it’s those special orders where there is a high risk of error, and having a super user on the team to help out is a great safety strategy.”

Another recent caught mistake at the University of Chicago illustrates this point. An overnight pharmacist noticed that the vial the technician used for a preparation for a pediatric patient was the wrong concentration, which would have produced a 10-fold dosing error.

“We found out that the new strength was not yet built into the program,” Dr. Hope said. “So although you have the IV workflow system, and yes, it builds in that level of checking, you can’t be complacent, either. You know that gut feeling when you think something doesn’t look quite right? Stop and check again.”

Strategies such as super users and stricter bypass policies and procedures had their intended effect. During the first week of full IV-WMS implementation at the University of Chicago, Dr. Hope reported, there were 3,920 bypasses out of a total of approximately 8,500 doses. By the fifth week, bypasses were down to 476, with approximately the same doses compounded. Meanwhile, between 3,000 and 4,000 incorrect doses were caught and canceled by the IV-WMS each week.

‘What might have previously been a three-minute process may now double in time [using IV-WMS], so you need to educate your nursing and medical staff as to why this may happen and that it is safer for their patients.’

—Charlene Hope, PharmD “I have not spoken to a single person that has done the work of adopting IV-WMS who would consider going back,” Mr. Gillespie said. “Once you get those reports and you see what the system is intercepting—and it’s a larger volume than you would have imagined, with greater seriousness than you would have imagined—how could you go back?”

He noted that there are many errors intercepted by IV-WMS that occur repeatedly over extended periods of time without change. “At one hospital I worked with, we had a certain number of insulin mis-dispenses that were caught,” he said. “I reported this back to the staff, but the numbers stayed pretty much the same. That’s a measure of the human condition. If I were to go

into an IV room and had to check one thing occasionally, I’m probably not going to make an error on that because it’s not what I do every day. When I’m asked to check something in those circumstances, I’m going to make sure it’s completely accurate. But if I’m signing 1,000 labels a day, No. 954 might get by me—not because people don’t care, don’t want to do a good job, don’t want to protect the public, but because we’re human beings and our brains are created in ways that teach us to take shortcuts we don’t even understand.”

—Gina Shaw Mr. Gillespie reported serving as a consultant to Omnicell for Central Rx Solution Design. The remaining sources reported no relevant financial disclosures.

46 Technology

Pharmacy Practice News • November 2021

Medication Safety

Allegheny Makes a Case for IV Robotics O

utsourcing sterile IV medications can put a big dent in a hospital’s drug budget.

Allegheny General Hospital, in Pittsburgh, for example, had been paying 503B outsourcing facilities about $2.6 million per year for compounded IV products, according to Arpit Mehta, PharmD, MPH, MHA, the director of pharmacy. But that was before the hospital’s first compounding robot recently went fully live.

Now with the arrival of a second Omnicell IV robot, which will double the hospital’s automated nonhazardous dose output to around 100,000 bags and syringes per year, Dr. Mehta expects the outsourcing bill to drop to $500,000,

employee safety, it eliminates touch contamination and it makes our process much more efficient.”

Dr. Mehta said he didn’t have baseline safety or error data because the robotically compounded drugs were all previously acquired from a 503B facility. But according to Dennis Wright, MBA, Omnicell’s senior director of central pharmacy product marketing, the literature makes a strong case for the risks inherent in manual compounding.

He pointed to one widely cited study showing a 9% error rate for manually prepared admixtures (Am J Health Syst Pharm 1997;54[8]:904-912).

Mr. Wright said Omnicell’s “whole goal is to remove humans from those areas

saving more than $2 million. (Chemotherapy and other hazardous drugs are compounded manually for specific patients, he said.)

It’s not just cost reduction that has elevated the robots’ value, Dr. Mehta said.

“From a patient safety perspective and error prevention in general, it has been fantastic. Leveraging the IV robotic technology has truly allowed us to have full visibility of the compounded medications we’re using in our critical care units and operating rooms [ORs]. And it gives us the flexibility to make the quantity we need on time, without running into any shortages or quality assurance issues.”

Compounded IV bags include vasopressin, norepinephrine, phenylephrine, fentanyl and hydromorphone, he said, and neostigmine, ephedrine and ketamine are among the syringe-containing medications compounded for the OR. “From a patient safety perspective, [using compounding robots] is leaps and bounds ahead of where we were before,” he said. “And from the viewpoint of

where they can introduce risk, either by making mistakes or introducing potential contamination, and apply robotics, which [provides] automated safety checks and a standardized compounding workflow in a completely isolated ISO Class 5 environment.”

Striking a Balance Between Manual and Robotics At Allegheny General Hospital, about 30% of the 360,000 IV doses administered each year are compounded by the robot, Dr. Mehta noted. Most of the balance still needs to be compounded manually, he said, because Allegheny’s Omnicell robots are not equipped to handle individual dose variations.

Small quantities are still outsourced “from strategic partners whom we have visited and know the quality of their products meets the standards,” he added. But even for manually compounded medications, Dr. Mehta said the pharmacy is bolstering preparation accuracy and safety by converting to the

Omnicell IVX Workflow system, which integrates barcode scanning, gravimetric or volumetric verification, multispectral imaging, photo documentation and label printing into the compounding process.

Robotics also enhance Allegheny’s ability to meet the documentation standard of USP General Chapter <797>. “That process is now 100% automated,” he said, “so we don’t have to have a person manually tracking any information. If there’s a recall or other concern, we can pull data pretty much all the way to the individually compounded bag or syringe level and assess it for any concerns.”

For Allegheny General Hospital, the conversion to robotics and IV automation paralleled the opening of new stateof-the-art pharmacy on the third floor of its landmark “skyscraper” building in Pittsburgh. The move doubled the size of the old pharmacy on the floor below and allowed the installation of a new larger and better- equipped cleanroom facility that adheres to USP <797> safe compounding standards.

In its automation startup, Allegheny has relied on what amounts to a partnership with Omnicell. Mr. Wright explained that the company had “changed the traditional model of just selling an IV robot and having the customer figure out how to optimize it to where we now bundle it into a complete service offering” that provides “the technology, tools and resident expert operators who are colocated with the technology.”

After-installation services include a formulary tool kit that provides a beyond-use dating (BUD) library. The tool “allows our health system and hospital partners to extend beyond-use dating,” Mr. Wright said.

Allegheny fully uses that extended BUD opportunity, Dr. Mehta said. “We follow the normal routine of quarantining the product and sending a sample out to a third-party lab for testing because we want that extended BUD for these products. Once the results come back, the product is released from quarantine and it becomes generally available. The majority of medications that we compound in the robot are stored in our automated dispensing cabinets on the nursing units as well as in our anesthesia carts in the OR.” Although robots can seem prohibitively expensive, Dr. Mehta said he expects a net savings of $1.6 million per year once they are both fully operational. That includes, he said, the cost of the medications, the technology, the third-party testing and even the salary of a pharmacist dedicated to managing the program.

“It’s not necessarily about the finances,” he said. “There is a safety component and the drug shortage component, and we have control of our inventory.

But at the end of the day we do need to justify the investment. And this is a huge financial saving and a benefit to the organization.”

Uptake Still Slow Despite technological advances, hospital adoption of robotic IV compounders has remained relatively limited. According to a recent Institute for Safe Medication Practices survey, only about 8% of hospital pharmacies use a robot to prepare sterile medications (bit.ly/3qN37fF).

That rate may be expected to increase, however, as the technology continues to progress and vendor competition makes the return on investment more attractive to hospital executives.

“Robotic compounding systems are improving all the time,” said Jerry Fahrni, PharmD, a health information technology expert. “They offer improved safety for both employees and patients by removing human hands from many of the steps in the compounding process. This is especially true for hazardous drugs compounding.

“Although these robots don’t completely automate the entire CSP [compounded sterile product] process,” he added, “they have automated safety features such as object recognition, barcode scanning, image capture of critical steps and plus/minus scales.”

Those scales refer to a measurement of accuracy obtained via gravimetrics, a technology that is one of the main advantages of IV robotics, Dr. Fahrni noted.

Gravimetrics can be used to precisely weigh the ingredients of a prepared drug dose. The final product is considered acceptable by the robot if it falls between plus or minus 5% of the expected weight (J Oncol Pract 2012;8[6]:344-349).

“I’ve always liked the idea of using robots for CSP production,” added Dr. Fahrni, a member of the Pharmacy Technology Report advisory board. “But in my opinion they were never quite ready for prime time. Five years ago, I don’t think I would have had much good to say. But times changes and things get better. Overall, one could argue that there is a potentially positive return on investment for compounding robots in specialized situations. They’re not for everyone, but for those situations where they fit, I think they hold value.”

—Bruce Buckley Dr. Fahrni reported that he sits on the Omnicell IV Automation Innovation Group.

Dr. Mehta reported no relevant financial disclosures.

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