Pharmacy Practice News (September 2020) by McMahon Group

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OPERATIONS & MGMT

ASHP drug forecast takes COVID-19 into account ........................4 COVID-19 pushes more at-home cancer care ..... 6 Pharmacists shine in primary care clinics ........

HEM/ONC IN FOCUS

Pharmacogenomics testing, breast cancer breakthrough, growth of oral chemotherapy, and more ............................

CLINICAL

Wormwood for COVID-19? Not so fast! .....................

CMS Eyes Deeper 340B Rate Cuts; Hospitals Cry Foul

ospitals that serve large numbers of patients who are uninsured or covered by Medicaid and Medicare took another big hit on Aug. 4, when the Centers for Medicare & Medicaid Services (CMS) unveiled a new round of cuts to the federal 340B drug program as part of its 2021 Medicare Hospital Outpatient Prospective Payment System (OPPS) and Ambulatory Surgical Center Payment System Proposed Rule (CMS-1736-P). The additional 6.2% cut to Medicare Part B reimbursement for 340B drugs came just a few days after the Court of Appeals for the District of Columbia Circuit upheld the 2018 OPPS final rule that cut reimbursement for 340B drugs by nearly 30%. The proposed rule ends up with a 340B reimbursement rate of average sales price (ASP) minus 34.7%, with 6% added overhead

What Have We Learned? How Do We Move Forward? O

n Jan. 19, a patient who had recently returned from Wuhan, China, walked into an urgent care clinic in Washington state with a cough. The rest is history (N Engl J Med 2020;382[10]:929-936). The patient was the first one in the United States to be diagnosed with SARS-CoV-2, the virus that causes COVID-19. He was admitted to Providence Regional Medical Center, one of 51 facilities that make up Providence St. Joseph Health, located throughout several western states, Texas and Alaska. Quickly, it became obvious that this was no ordinary infection. “As a system, we suddenly found ourselves as one of the locations in the national spotlight,” with the outbreak affecting every aspect of the hospital, including the pharmacy, said Jennifer Fulmer Groves, RPh, MPH, the system’s vice president of pharmacy operations. Continued on page 22

25 HEM/ONC IN FOCUS

REVIEW ARTICLE

Biosimilars in Oncology Managing Product Selection: Part 1 of 3 See insert after page 14.

COVID-19:

Continued on page 21

TECHNOLOGY

Website shines light on COVID-19–related diversion ...........................

Volume 47 • Number 9 • September 2020

Dose Rounding A Hedge Against High Cancer Cost

s the volume of costly new biologic oncology drugs expands, health systems increasingly are turning to automated dose rounding protocols to reduce the use of single-use vials and trim millions from their overly burdened drug budgets. The University of California, San Francisco (UCSF), for example, last year saved roughly $2.5 million in drug costs based on average wholesale price (AWP) by rounding doses of 21 oncology medications, Continued on page 18

Communication Is Key During Pandemic

well-executed communication approach has been key to coping with the first wave of the COVID-19 pandemic, experts said during a recent webinar hosted by the Institute for Safe Medication Practices (ISMP) and ECRI, an organization that focuses on health care safety, quality and cost-effectiveness. Paul Milligan, PharmD, a system medication safety pharmacist at BJC HealthCare, in St. Louis, said the health system had to cope with a flood of demand for hydroxychloroquine (HCQ) for COVID-19 prophylaxis. To ensure appropriate prescribing and preserve stock for those who needed it— including patients with rheumatoid arthritis,

Special Focus:

COVID-19 Pandemic More coverage on pages 4, 6, 8, 10, 25, 26.

systemic lupus erythematosus and malaria—BJC HealthCare formed a COVID-19 Treatment Guidance Task Force to develop COVID-19 policies and therapy guidelines, including parameters for use of HCQ. The system’s antimicrobial stewardship pharmacist facilitated the task force, which also included infectious disease and intensive care providers and pharmacist specialists, Dr. Milligan said. “As the risk-to-benefit evidence [for HCQ] became stronger, we identified current prescribers of the drug and communicated directly with them [about] the risks of QT prolongation, particularly when [HCQ is] used with azithromycin.” Continued on page 24

Take the guesswork out of USP <800> compliance.

Up Front

Pharmacy Practice News • September 2020

Multimedia

Making Residency Research More Meaningful O

ne of ASHP’s objectives for PGY-2 pharmacy residents is that they produce an original research paper suitable for publication. However, there is no ASHP requirement to actually publish the paper or present the research at a meeting. In fact, most residents don’t, according to Jenny Bingham, PharmD, a clinical instructor and the residency program director at the University of Arizona College of Pharmacy, in Tucson, and the director of ambulatory care residency programs and research at Tabula Rasa HealthCare (TRHC). “We see that about two-thirds of residents upon graduating from their residency program are not able to publish their research within a full calendar year,” said Dr. Bingham, who also serves as the president of the TRHC Research Strategy Committee. There are a lot of challenges for residents, but dedicated time and better guidance through the research process, including the institutional review board application, data acquisition and analysis, were among the most pressing, Dr. Bingham explained during a video interview with Pharmacy Practice News. The University of Arizona and SinfoníaRx collaborated to make the residency research experience more

Jenny Bingham, PharmD, discusses a pathway for creating meaningful research for residents.

meaningful for ambulatory care residents. The goal: perform publicationworthy research and get it published or presented. “We collaborated with a universitybased research team in response to some of the resident feedback that we received toward the infancy of our program,” she explained. In the first year of the program, “the residents felt that maybe they didn’t have as much guidance, and the

preceptors did not feel they had specific expertise to lead their project.” The following year, additional research mentorship was integrated into the program structure and received positive feedback. In addition to assigning a preceptor, the program now pairs a resident with a graduate research student who serves as a mentor to guide them in research methodology. In the article (Pharmacy 2020

EDITORIAL BOARD

Jul 31. [Epub ahead of print]. https:// doi.org/10.3390/pharmacy8030134), Dr. Bingham shares the lessons learned from eight years in this program. The article describes a month-by-month approach for each activity that the preceptor, graduate student mentor and university-based research team complete with residents to make them more successful. The program also carves out time for residents to perform and disseminate their research. “One way that we addressed the initial residents’ concerns about not having guidance was pairing them one-onone with the graduate research student, making sure that we built a time line into their weekly schedule, set expectations up front, and provided live peer review sessions, including their research preceptors and the [university] research team,” Dr. Bingham said. As a result of the 13 residents who have undergone the program in eight years, three were published, one was just accepted for publication, and all 13 presented their research at either a regional or national conference. For more details on the program, check out the video interview with Dr. Bingham at bit.ly/32mtmio-PPN. —Marie Rosenthal

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Volume 47 • Number 9 • September 2020 • pharmacypracticenews.com

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AMBULATORY CARE Meghan D. Swarthout, PharmD, MBA, BCPS, Sallston, MD

NUCLEAR PHARMACY Jeffrey Norenberg, PharmD, Albuquerque, NM

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4 Operations & Management

Pharmacy Practice News • September 2020

Finance

ASHP Eyes Rx Trends Amid Pandemic T he 13-member expert team working on the 2020 edition of ASHP’s 20th annual drug expenditures forecast was facing a formidable challenge. In the midst of researching and analyzing the myriad factors that go into producing a national drug spending model, a rare “black swan” event in the form of COVID-19 was threatening to throw projections into disarray. Erin Fox, PharmD, the senior director

of Drug Information and Support Services at University of Utah Health, in Salt Lake City, described the uncertainty facing not only the ASHP team but also health systems and hospitals nationally that were trying to factor their own epidemiology and drug use data into reasonably accurate cost estimates. “You need to prepare for a surge in patients, but you don’t know how many are coming,” Dr. Fox told Pharmacy Practice News. “And

it’s not knowing what you’re going to be treating. Will there be fewer transplants and cancer infusions? Will there be as many elective surgeries? Because of all of that uncertainty, it’s really difficult.” The ASHP team rose to the challenge. “We recognized early on that this [report] would be impactful,” said Eric M. Tichy, PharmD, the vice chair of supply chain management at Mayo Clinic in Rochester, Minn., and the leader of the team that

O UR TEST, Y O U R C U R E . . .

produced the 2020 forecast orecast (Am J Health Syst Pharm 2020;77[15]:1213-1230).. Dr. Tichy said although ough the report alreadyy had been written and submitubmitted to AJHP before the he full force of the COVID-19 9 pandemic became evident, nt, “we had time to make revisions visions before the final publication, so we definitely took the potential impact of COVID-19 into account.” The team considered whether the accelerated pace of branded and generic drug approvals seen in in the past few years would slow this year, given that many agency staff members might be working at home out of fear of infection. “Initially, we thought FDA might delay some approvals. That’s what we expected,” said Matthew H. Rim, PharmD,

Forecast Data Sample • 2019 prescription drug spending rose 5.4% to $507.9 billion • 2020 projected overall drug expenditure growth rate: 4.0% to 6.0% • Projected clinic and hospital drug spending growth rates: 9.0% to 11.0% and 2.0% to 4.0%, respectively Source: IQVIA data and projected growth estimates from Am J Health Syst Pharm 2020;77(15):1213-1230.

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the associate director of specialty pharmacy services at the University of Illinois at Chicago and a co-author of the report. But a review of FDA approvals in July showed that the approval process was right on schedule, Dr. Rim said. “So, COVID-19 really didn’t change our predictions on new medications.” The forecasting team, which included pharmacy leaders from across the United States and Canada as well as IQVIA representatives, began work on the 2020 report in late January after receiving 2019 prescription drug spending figures from IQVIA. Some categories of medications, such as specialty drugs and biosimilars, drew special attention for their potential to move drug cost estimates up or down. “Most of the new, really expensive drugs are those that can be administered in the clinic setting,” Dr. Tichy said, “and specialty drugs are a big part of that.” Indeed, specialty drugs growth in the clinic sector, including physicians’ offices, increased by 13.9% in 2019 to $71.7 billion, or 29.4% of all specialty drug spending. Dr. Rim said, “It’s really hard to project your drug budget properly [without considering specialty drugs] because they’re such high-dollar medications.” He noted that they now account for at least 80% of medications in the pipeline. The ASHP report had singled out five specialty oral

Operations & Management

Pharmacy Practice News • September 2020

Finance

Table. Ta T ab blle. Biosimilars in Waiting Brand Br B ran a d Ve Version

Biosimilar

Humira Hu H um u mir iira ra a (adalimumab, (a ((ad ad a da ali li limu um m AbbVie) Ab A bb b bVie Vie i )

• Adalimumab-afzb (Abrilada, Pfizer) • Adalimumab-bwwd (Hadlima, Samsung Bioepis) • Adalimumab-fkjp (Hulio, Mylan/Kyowa Kirin Biologics) • Adalimumab-adbm (Cyzelto, Boehringer Ingelheim) • Adalimumab-atto (Amjevita, Amgen)

Enbrel En E nb n brel rell ((etanercept, ett Amgen) Am Amg A mge mg gen en) n)

• Etanercept-szzs (Erelzi, Sandoz) • Etanercept-ykro (Eticovo, Samsung Bioepis)

cancer drugs expected to receive approval at the time of writing. All five have cleared that hurdle: tucatinib (Tuksya, Seattle Genetics), for HER2-positive metastatic breast cancer; selpercatinib (Retevmo, Lilly), for advanced RET-positive non-small cell lung cancer (NSCLC) and thyroid cancer; capmatinib (Tabrecta, Novartis), for MET-positive metastatic NSCLC; pemigatinib (Pemazyre, Incyte), for FGFR2-positive cholangiocarcinoma; and ripretinib (Qinlock, Deciphera), for advanced gastrointestinal stromal tumor.

lot on remdesivir, which was a novel drug that came on board quickly to treat an acute problem. But it’s frustrating when

you’re spending a lot of money on something that should be a fraction of the cost.” What does it take to get a handle on rising costs? “It takes a nimble approach,” said John S. Clark, PharmD, the associate chief pharmacy officer at Michigan Medicine, in Ann Arbor, and one of the report’s authors. In such cases, he said, “nurses, medical team and pharmacy can work together to evaluate the pipeline and produce readiness in their organization for generic and biosimilar implementation once they’re available.” Dr. Fox said pharmacists “are one of the

best resources health systems have to try to keep costs down. You’ve got pharmacists working with physicians every day to try to help them prescribe the most cost-effective medications. If you eliminate those positions [through COVIDimposed furloughs], you won’t have that anymore. It’s not something you can just program into AI [artificial intelligence].” —Bruce Buckley The sources reported no relevant financial relationships.

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6 Operations & Management

Pharmacy Practice News • September 2020

Ambulatory Care

COVID Jump-Starts Cancer Care at Home A

s the COVID-19 pandemic spread across the country and hospitals reduced in-person visits to a bare minimum, health systems—such as Partners Healthcare, M Health Fairview and Northwestern—worked to ensure that patients in their cancer centers had access to therapy in their own homes whenever possible. To ensure optimal outcomes, care teams switched some patients to oral oncology medications instead of infused therapy and expanded home infusion services—efforts that continue during the ongoing pandemic. Health systems with integrated specialty pharmacies have a particular advantage in managing these patients because they already have robust, comprehensive internal resources and infrastructure to build home-based care programs. Even when the pandemic ends, some of these health systems anticipate that patients will prefer home-based care and ask to continue it.

The Move to Telehealth As with many other clinical service lines, cancer centers have reported a marked shift from in-person clinic visits to telehealth wherever possible, particularly given the immunocompromised status of many patients. “At least 75% of our visits are now being done via telephone or video as a substitute for a clinic visit, to decrease exposure for both the patient and the clinic staff,” said Sarah Slater, PharmD, a pharmacist in hematology/oncology at Northwestern Medicine, in Chicago. Telehealth primarily is employed for patients on maintenance therapy but also can be used for patients starting new therapies. For example, someone who is beginning treatment on a new oral anticancer agent can receive all of their counseling about taking the drug, what to expect, and potential side effects over the phone, with handouts and calendars sent to them by email, to reduce the number of people with whom that patient must come into contact. The move to phone counseling has gone well overall, although some aspects have proven challenging, Dr. Slater said. “You don’t have those nonverbal cues as to whether or not the patient actually understands the information you’re giving them. Many of these regimens are only given on certain days, and the easiest way to teach the cycles is to have the patient in front of you with a calendar,” she noted. “Teaching injections is also best done in person, but we sometimes have not had that luxury. We talk them through it on the phone and supplement that with a very good YouTube video, which we ask patients to watch at least twice before doing the injection on themselves for the first time.”

Even patients who are new to Northwestern have, in some cases, been managed largely via telehealth. “We are a referral center, so we often see patients who are diagnosed at an outside hospital and then referred to our center for follow-up care management after biopsy and surgery. We can sometimes manage their care with minimal further in-person visits,” Dr. Slater said. “Lab work, chemotherapy and radiation therapy are the only things that really need to be done in person. Appointments are spaced out so that there are fewer people in clinic at a given time, and furniture has been removed to keep infusion stations at least 6 feet apart. And any of our clinic staff who are not in direct patient care roles have been working from home to decrease the number of people in the infusion center.” Northwestern still has two specialty pharmacists on-site and approximately four technicians filling prescriptions, and a pickup window remains open. But other than the pharmacists and techs who actually fill prescriptions, the rest of the specialty pharmacy staff also are working remotely, including the call center, benefits investigation team and financial assistance specialists.

Excelera at Home Excelera, a national network of health systems that includes Northwestern, has seen similar trends at most of its member systems’ cancer programs, said Amy Swanson, the senior director of member relations. “The pandemic forced the issue on telehealth by removing the in-clinic care option for a lot of patients. Because they weren’t able to start therapies in clinic, patients were being counseled via telehealth for the first time as they moved from IV therapy to oral medications.” Darcy Malard Johnson, PharmD, an oncology pharmacy program manager at M Health Fairview in Minnesota, reported a similar trend at her institution, which also is an Excelera member. “We started to do some planning for the pandemic in February. We had a command center working on our strategies for the cancer clinics and the infusion centers, where we see both oncology and nononcology patients. As a pharmacy team, we looked at the treatments we provide to identify opportunities to provide care in a different way: subcutaneous injections that patients could self-administer at home; switching from one infused product to another dosed at longer intervals so the patient doesn’t have to come in as often; switching to oral therapy so the patient doesn’t have to come in at all for some amount of time; and leveraging home infusion capabilities.” M Health Fairview has its own home infusion pharmacy and already had

‘I imagine in-clinic infusions will never go back to the volume that we had in the past, and many things will continue to be moved to oral therapies, home infusion and televisits, especially for patients who live far away.’ —Amanda Manoogian, PharmD been working to move patients from infusion centers to home infusion even before the pandemic. This was done for improved patient convenience and to free up infusion chairs for patients with more acute needs, Dr. Malard Johnson noted. “We had our first patient receive Velcade [bortezomib, Millennium/ Takeda] in the home just as the pandemic was starting,” she said. “We’ve also had a number of patients transition to home infusion for fluids and other supportive therapies.”

Multiple Myeloma a Model Multiple myeloma has been managed similarly. “Many of our patients who were getting Velcade as a subcutaneous injection or IV in an infusion center have been switched to a newer oral agent, Ninlaro [ixazomib, Millennium/Takeda],” Dr. Slater said. “We’ve switched at least 20 patients since the start of the pandemic.” At Partners Healthcare in Boston, oncologists and specialty pharmacists also have switched a number of patients with lung cancer from IV etoposide to its oral counterpart. These patients typically receive chemotherapy infusions of carboplatin and etoposide on day 1 of a therapy cycle, followed by IV etoposide infusions on days 2 and 3. Infusions on the second and third days now usually are replaced by the oral therapy. “That treatment approach has been a huge relief for these patients and the clinic,” said Amanda Manoogian, PharmD, the specialty pharmacy manager of oncology clinical services at Partners Healthcare. “Many 5-fluorouracil infusion patients have been switched from in-clinic disconnect on day 3 of their cycle to home disconnect. A home health care nurse comes to the patient’s home for the disconnect and to administer a growth factor subcutaneous injection. Small changes like this help us decrease exposure for these

patients, who are already immunocompromised,” she said. Switching to oral anticancer therapy is not appropriate for every patient, Dr. Slater noted. “Patients who have low health literacy, are confused or don’t have a lot of caregiver support may not be good candidates for an oral therapy that requires them to keep track of cycles and take a different number of pills at different times of the day, on different days of the week,” she said. “But in patients for whom it is appropriate, it’s empowering to have that option and feel more in control of their health care during this time.” Dr. Manoogian predicted that many of the COVID-19–related changes to out-ofclinic options will become permanent. “Partners is still recommending to stay as is for at least the foreseeable future. I imagine in-clinic infusions will never go back to the volume that we had in the past, and many things will continue to be moved to oral therapies, home infusion and televisits, especially for patients who live far away.” M Health Fairview recently has resumed necessary in-person visits. “As primary care visits open up and patients get mammograms or other screenings, we have been getting more referrals to our oncologists,” Dr. Malard Johnson said. “But for the patients getting home therapies, the plan is to leave them in that setting as long as they are tolerating the treatment and their disease state is either stable or improving.” Ms. Swanson said many of the systems in the Excelera Network have the same perspective. “No one is in a rush to bring patients back into the clinic if it’s not absolutely necessary.” —Gina Shaw The sources reported no relevant financial relationships.

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An FDA-approved ɢơǌ˪ ȍǌɭŔɽʋǫȟ ŹǫȶɽǫȟǫȍŔɭࡳ2 áơǌ˪ ȍǌɭŔɽʋǫȟ࢛ƃŹɩʽ ࢏č7F¥ĵ- ॽ࢐ ǫɽ ¥ŔʋǫȶȥŔȍ -ȶȟɢɭơǠơȥɽǫʽơ -Ŕȥƃơɭ ¥ơʋˁȶɭȇॽ ࢏¥--¥ॽ࢐ ɭơƃȶȟȟơȥƎơƎ3

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ࡥ ɽ ȶǉ ʠȥơ ࠁ߿ࠁ߿࡬ ʋǠơ ɢơǌ˪ ȍǌɭŔɽʋǫȟ ɢɭơ˪ ȍȍơƎ ɽˊɭǫȥǌơ ࢏ábò࢐ ȟŔɭȇơʋɢȍŔƃơ ǫȥƃȍʠƎơɽ ŁzFĴþF¥Ł¶ॽ ࢏ɢơǌ˪ ȍǌɭŔɽʋǫȟ࢛Źȟơ˖࢐࡬ bʠȍɢǠǫȍŔॽ ࢏ɢơǌ˪ ȍǌɭŔɽʋǫȟ࢛ǿȟƎŹ࢐࡬ ŔȥƎ ¥ơʠȍŔɽʋŔॽ ࢏ɢơǌ˪ ȍǌɭŔɽʋǫȟ࢐ࡳ References: 1. zæĪz zȥƃࡳ ¡ȶȥʋǠȍˊ ¥ŔʋǫȶȥŔȍ òŔȍơɽ áơɭɽɢơƃʋǫʽơ 7ŔʋŔࡳ ࠁ߿ࠁ߿ࡳ 2. č7F¥ĵ- ॽ ࢏ɢơǌ˪ ȍǌɭŔɽʋǫȟ࢛ƃŹɩʽ࢐ ɢŔƃȇŔǌơ ǫȥɽơɭʋࡳ èơƎˁȶȶƎ -ǫʋˊ࡬ - ࡫ -ȶǠơɭʠɽ %ǫȶòƃǫơȥƃơɽ࡬ zȥƃࡳࡸ ࠁ߿ࠀࠈࡳ 3. èơǉơɭơȥƃơƎ ˁǫʋǠ ɢơɭȟǫɽɽǫȶȥ ǉɭȶȟ ʋǠơ ¥--¥ -ȍǫȥǫƃŔȍ áɭŔƃʋǫƃơ eʠǫƎơȍǫȥơɽ ǫȥ ¶ȥƃȶȍȶǌˊ ࢏¥--¥ eʠǫƎơȍǫȥơɽॽ࢐ ǉȶɭ qơȟŔʋȶɢȶǫơʋǫƃ eɭȶˁʋǠ bŔƃʋȶɭɽ Īࡳࠁࡳࠁ߿ࠁ߿ࡳ ॼ ¥ŔʋǫȶȥŔȍ -ȶȟɢɭơǠơȥɽǫʽơ -Ŕȥƃơɭ ¥ơʋˁȶɭȇ࡬ zȥƃࡳ ࠁ߿ࠁ߿ࡳ ȍȍ ɭǫǌǠʋɽ ɭơɽơɭʽơƎࡳ ƃƃơɽɽơƎ ɢɭǫȍ ࠁࠁ࡬ ࠁ߿ࠁ߿ࡳ þȶ ʽǫơˁ ʋǠơ ȟȶɽʋ ɭơƃơȥʋ ŔȥƎ ƃȶȟɢȍơʋơ ʽơɭɽǫȶȥ ȶǉ ʋǠơ ǌʠǫƎơȍǫȥơɽ࡬ ǌȶ ȶȥȍǫȥơ ʋȶ ¥--¥ࡳȶɭǌࡳ ¥--¥ ȟŔȇơɽ ȥȶ ˁŔɭɭŔȥʋǫơɽ ȶǉ Ŕȥˊ ȇǫȥƎ ˁǠŔʋɽȶơʽơɭ ɭơǌŔɭƎǫȥǌ ʋǠơǫɭ ƃȶȥʋơȥʋ࡬ ʠɽơ ȶɭ ŔɢɢȍǫƃŔʋǫȶȥ ŔȥƎ ƎǫɽƃȍŔǫȟɽ Ŕȥˊ ɭơɽɢȶȥɽǫŹǫȍǫʋˊ ǉȶɭ ʋǠơǫɭ ŔɢɢȍǫƃŔʋǫȶȥ ȶɭ ʠɽơ ǫȥ Ŕȥˊ ˁŔˊࡳ

č7F¥ĵ- ǫɽ Ŕ ɭơǌǫɽʋơɭơƎ ʋɭŔƎơȟŔɭȇ ȶǉ -ȶǠơɭʠɽ %ǫȶòƃǫơȥƃơɽ࡬ zȥƃࡳ ŁzFĴþF¥Ł¶ ǫɽ Ŕ ɭơǌǫɽʋơɭơƎ ʋɭŔƎơȟŔɭȇ ȶǉ ¥ȶʽŔɭʋǫɽ eࡳ bʠȍɢǠǫȍŔ ǫɽ Ŕ ɭơǌǫɽʋơɭơƎ ʋɭŔƎơȟŔɭȇ ȶǉ ¡ˊȍŔȥ zȥɽʋǫʋʠʋǫȶȥŔȍ zȥƃࡳ ¥ơʠȍŔɽʋŔ ǫɽ Ŕ ɭơǌǫɽʋơɭơƎ ʋɭŔƎơȟŔɭȇ ȶǉ ȟǌơȥ zȥƃࡳ ॼ ࠁ߿ࠁ߿ -ȶǠơɭʠɽ %ǫȶòƃǫơȥƃơɽ࡬ zȥƃࡳ ȍȍ ɭǫǌǠʋɽ ɭơɽơɭʽơƎࡳ ߿ࠆࠁ߿࢛č7ĵ࢛áࠃࠂࠂʽࠁ

8 Operations & Management

Pharmacy Practice News • September 2020

Ambulatory Care

Extending care during a pandemic

The Pharmacist Will See You Now I

n 1995, Geisinger tried an experiment. At the main hospital in Danville, Pa., it started its first pharmacist-run anticoagulation clinic. While the clinic was initially met with resistance from a small group of physicians, others expressed their support and created a solid patient referral base. The experiment was a success, and over the next 25 years, Geisinger began adding pharmacists to other services, including primary care offices. Today, it has 58 primary care clinical pharmacists embedded in 51 sites across the system, as well as 20 pharmacists practicing in specialty medicine sites. According to Gerard Greskovic, BS Pharm, the system director of ambulatory pharmacy programs, these embedded pharmacists perform more than 30,000 patient encounters each month, managing patient care for more than 20 medical conditions or disease states. But it’s not just about volume. “At Geisinger, we’ve shown that having clinical pharmacists embedded in our medical practices results in improved clinical outcomes, higher scores on quality metrics, increases in prescription capture within system-owned pharmacies, reductions in emergency department and hospital utilization, high patient satisfaction, and improvement in physician appointment access.” An increasing number of physician practices have opened their doors to pharmacists, according to Mary Ann Kliethermes, PharmD, the director of medication safety and quality at ASHP. “I believe every college of pharmacy likely has faculty practicing in this manner at various clinics, physician groups or health systems.” The practice model may get an additional boost as the number of patients with chronic diseases grows, predicted

Michael Korczynski, PharmD, the manager of clinical services, pharmacy–ambulatory care, at Allegheny Health Network (AHN), in Pittsburgh, which also has embedded pharmacists. Clinicians can focus on diagnosis and treatment, and refer medication management questions to the pharmacist, he noted. “If you have a pharmacist in place, it makes all those other team members more efficient. You reach your quality and clinical goals much quicker.”

How It Works In 2004, Dr. Korczynski was the only AHN pharmacist embedded into a primary care practice. In 2016, as the organization decided to embrace the concept of team-based care, it added more pharmacists to more primary care practices, as well as chronic care practices and a clinic that manages patients with autoimmune disorders. Today, there are 13 embedded pharmacists at AHN. “Since 2016, the expansion has been pretty significant,” he told Pharmacy Practice News. “And we’re planning on continuing it.” Under Pennsylvania policy, physicians can place a referral to the pharmacist if they have a collaborative practice agreement in place. This enables the pharmacist to make adjustments to patients’ drug regimens, order lab tests or issue referrals, Dr. Korczynski noted. When a doctor prescribes a new medication—say, for blood pressure or diabetes—the doctor refers the patient to the pharmacist, who monitors the patient’s clinical markers and checks their medications. At Geisinger, the embedded clinical pharmacists also have collaborative practice agreements with their physician partners that allow for a significant expansion outside the traditional pharmacist scope of practice, Mr. Greskovic noted.

During either office visits, televideo visits or telephone calls, pharmacists titrate and monitor chronic disease medication regimens based on patient tolerability and treatment response, order and assess lab work, and conduct point-of-care tests such as measuring hemoglobin A1c levels. Clinical pharmacists typically have longer appointment slots than physicians, he said, which gives them more time with patients, educating and designing the most appropriate and cost-effective medication regimens. “The pharmacists also are able to take the chronic disease management off the physicians to open up their schedule to take on more complex and/or acute patient appointments,” Mr. Greskovic said. Embedded pharmacists help “offset the physician’s patient load,” Melanie R. Smith, PharmD, the director of the ASHP section of ambulatory care practitioners, told Pharmacy Practice News. The model has particular utility during a pandemic, when patients may have limited connection to their doctor’s office, Dr. Korczynski noted. A pharmacist saves nurses and doctors a check-in by calling the patient, educating them about maintaining their health, scheduling lab tests, processing refills, and reinforcing COVID-19–related precautions. “It’s just another team member who is closing quality gaps,” he said.

So What’s the Catch? One reason most primary care clinics don’t have embedded pharmacists likely stems from reimbursement challenges. State and federal laws recognize medication dispensing services by pharmacists, but not services typically provided when integrated in physician offices, such as optimizing the therapy plan to maximize effectiveness of the medications for that

YouTube Pharmacists Teach During COVID-19

or years, when saying goodbye to patients who had received their first prescription for a complicated medicine, Michael Korczynski, PharmD, the manager of clinical services, pharmacy–ambulatory care, at Allegheny Health Network (AHN), in Pittsburgh, sometimes included a link to a YouTube video in their after-visit summary. In the videos, created by Fairview Physician Associates, an embedded Fairview pharmacist demonstrates how to use epinephrine, insulin and asthma medications, among others. The video is something patients can watch over and over, he said, to refresh their memories from the in-person instruction. “There’s so many advantages to doing something like this.” Dr. Korczynski said he has since been trying to create AHN’s own patient education videos. Amid the pandemic, this type of remote instruction has become even more

v valuable, he said. So far, he’s been talking with AHN p pharmacists about which questions they receive m most frequently, and the most common mediications with which patients need help. AHN h has 30 ambulatory pharmacists, he said. “If I can get each pharmacist to make one video, we’ll have a great library.” To access the videos, visit www.youtube. com/user/FPANetwork/videos. This is a great idea, Melanie R. Smith, PharmD, the director of the ASHP section of ambulatory care practitioners, told Pharmacy Practice News. Instructional videos by pharmacists help patients and remind them that pharmacists do much more than fill prescriptions, she said. “It will allow both patients and other providers to see pharmacists as the medication expert and a valued member of the health care team.” —A.M.

A pharmacist embedded in a Geisinger primary care clinic meets with a patient pre–COVID-19.

patient and minimizing or preventing any untoward effects a patient may experience, Dr. Kliethermes noted. “Consequently, to cover the cost of pharmacists’ services, pharmacists and their organizations must use work-around methods through existing regulations and policy. They do not always fit well.” In one such work-around, AHN, as a health system, has collaborative practice agreements between providers and pharmacists, under which they bill insurers as an “incident to” a doctor’s visit. However, primarily due to lack of provider recognition by insurance providers and the Centers for Medicare & Medicaid Services, pharmacists can bill only at a level 1 visit, “which is significantly less than what they do,” Dr. Korczynski noted. Another option, Dr. Kliethermes noted, is to cofund embedded pharmacists with the college of pharmacy, in which the practice pays a portion of a pharmacist’s salary equivalent to the work they are providing for the practice. “Pharmacists are employees of either the college they are funded through or the clinic they are working in,” Dr. Smith explained. At AHN, embedded pharmacists are employees of the clinic where they work, said Dr. Korczynski; as a result, they are not a “consultant or tourist,” he said, and can access patients’ electronic health records.

Making the Case To Administrators Funding challenges can make embedding pharmacists a hard sell to administrators, but there is evidence that they can improve clinical outcomes. AHN internal data show, for example, that when patients with diabetes are monitored by pharmacists embedded in primary care or chronic care specialty services or a pharmacist-run medication therapy management clinic, hemoglobin A1c levels above 9% can fall an average of 2 to 3 percentage points within three months.

Operations & Management

Pharmacy Practice News • September 2020

Ambulatory Care With Pharmacists On Board in PCP Clinics: Hemoglobin A1c levels above 9% fell an average of 2 to 3 percentage points within three months. Patients with multiple sclerosis and atrial fibrillation (taking warfarin) had 28% and 18% fewer visits to the ED per year, respectively. Patients with hypertension experienced an average decrease in systolic pressure of 20.1 mm Hg; diastolic pressure fell by 8.8 mm Hg.

Geisinger has documented similar benefits after placing its pharmacists in primary care settings. For example, patients with multiple sclerosis and atrial fibrillation (taking warfarin) who were monitored by Geisinger pharmacists had 28% and 18% fewer visits to the emergency department per year, respectively, relative to Geisinger patients who weren’t managed by pharmacists (Am J Health Syst Pharm 2017;74[18]:1422-1435). In addition, the program offsets a portion of its cost through billable CPT codes, such as “incident to” (99211), placement of a continuous glucose monitor (95249), or anticoagulation management (93793). Geisinger also has negotiated with insulin pump manufacturers to reimburse pharmacists for initiation and ongoing management of new patients on insulin pumps, Mr. Greskovic noted. He added that Geisinger administrators clearly see the value of embedded pharmacists, based on the financial support it gives to the practice model.

outcomes in HIV (J Manag Care Spec Pharm 2020;26[2]:95-102), and increased rates of flu vaccines and cancer screening (J Am Pharm Assoc 2019;59[4S]:S85-S90). These clinical improvements, as noted, can translate to major cost savings: • In the first five years Blue Cross Blue Shield embedded pharmacists into primary care practices, it contained or avoided nearly $37 million in costs, according to a report on the savings posted to the payor’s website (bit.ly/3gGk7iS).

• Patients with cardiovascular disease comanaged by clinical pharmacy specialists and registered nurses at Kaiser Permanente Colorado generated $21,900 per year less in health care expenditures than cardiac patients who didn’t enroll in the program (Pharmacotherapy 2010;30[11]:1127-1135). • A July 2020 report from the GTMRx Institute concluded that team-based medication management services have a financial return on investment that averages between 3:1 and 5:1 (bit.ly/30L7Unm).

—Alison McCook The sources reported no relevant financial relationships.

Visit our new website! www.freseniuskabinutrition.com

As an alternative ILE with four oil sources, SMOFlipid aligns with the most current SCCM/ASPEN guidance for COVID-19 patients requiring ICU care, which recommends limiting the use of pure soybean oil ILEs.1

o bean Oil oy (͘-6)

Provides essential fatty acids

Medium-chain triglycerides are a source of rapidly available energy 2

More Evidence Other researchers have documented this practice model’s success: • Patients who attended a pharmacist-managed hypertension clinic embedded in a primary care clinic experienced significant improvements in systolic and diastolic readings (average decrease in systolic pressure, 20.1 mm Hg; P<0.0001); diastolic pressure fell by 8.8 mm Hg (P<0.0001) (J Pharm Pract 2020 May 26. [Epub ahead of print]. doi: 10.1177/0897190020926841). • Having at least one visit with a pharmacist embedded in a primary care clinic significantly reduced hemoglobin A1c (–0.4%; P=0.01) among Black patients with type 2 diabetes (J Gen Intern Med 2020 Mar 6. [Epub ahead of print]. doi: 10.1007/s11606-02005750-0). • Other research has linked embedded pharmacists to improved patient

In-the-trenches reactions from clinicians also have been strong, Dr. Korczynski noted. “I get unsolicited feedback to the point of ‘I can’t believe we weren’t doing this before.’ It’s overwhelmingly positive,” he said. “I really feel like we are scratching the surface of how effective pharmacists can be in these clinical settings.”

͘-3) Source of EPA and DHA3

(͘ Supply of monounsa fatty acids

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.

>(9505.! +,(;/ 05 79,;,94 05-(5;: +LH[OZ PU WYL[LYT PUMHU[Z HM[LY PUM\ZPVU VM PU[YH]LUV\Z SPWPK LT\SZPVUZ OH]L ILLU YLWVY[LK PU [OL TLKPJHS SP[LYH[\YL (\[VWZ` Ä UKPUNZ PUJS\KLK PU[YH]HZJ\SHY MH[ HJJ\T\SH[PVU PU [OL S\UNZ 7YL[LYT PUMHU[Z HUK SV^ IPY[O ^LPNO[ PUMHU[Z OH]L WVVY JSLHYHUJL VM PU[YH]LUV\Z SPWPK LT\SZPVU HUK PUJYLHZLK MYLL MH[[` HJPK WSHZTH SL]LSZ MVSSV^PUN SPWPK LT\SZPVU PUM\ZPVU

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

10 Operations & Management

Pharmacy Practice News • September 2020

Generics

Civica Rx Takes a Seat at Drug Supply Chain Table

ivica Rx has earned a key role in a new federally funded public–private partnership to maintain adequate supplies of essential medications during pandemics and other future public health emergencies. The collaboration was announced soon after the company relieved critical shortages of generic sterile injectables for more than 1,200 member hospitals during the COVID-19 pandemic’s crushing first wave.

At the Department of Health and Human Services (HHS), teams are involving Civica Rx in their build of “a 100% U.S.-owned and operated, endto-end domestic drug manufacturing infrastructure to secure essential sterile injectable drugs and prevent future shortages of these vital medicines,” Martin VanTrieste, RPh, the president and CEO of the nonprofit company, told Pharmacy Practice News.

SMOFLIPID (lipid injectable emulsion), for intravenous use BRIEF SUMMARY OF PRESCRIBING INFORMATION 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.smoflipid.com. >(9505.! +,(;/ 05 79,;,94 05-(5;: +LH[OZ PU WYL[LYT PUMHU[Z HM[LY PUM\ZPVU VM PU[YH]LUV\Z SPWPK LT\SZPVUZ OH]L ILLU YLWVY[LK PU [OL TLKPJHS SP[LYH[\YL (\[VWZ` ÄUKPUNZ PUJS\KLK PU[YH]HZJ\SHY MH[ HJJ\T\SH[PVU PU [OL S\UNZ 7YL[LYT PUMHU[Z HUK SV^ IPY[O ^LPNO[ PUMHU[Z OH]L WVVY JSLHYHUJL VM PU[YH]LUV\Z SPWPK LT\SZPVU HUK PUJYLHZLK MYLL MH[[` HJPK WSHZTH SL]LSZ MVSSV^PUN SPWPK LT\SZPVU PUM\ZPVU

Already, Civica Rx has provided 1.6 million doses of critical medicines to the Strategic National Stockpile for the COVID-19 response. The neuromuscular blocking agents, pain relievers and sedatives for intubation, broad-spectrum antibiotics for secondary infections, and other drugs to treat comorbidities were supplied in partnership with the Phlow Corporation, in Richmond, Va. The Biomedical Advanced Research

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.

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.

• 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.

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.

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.

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

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.

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. • 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

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

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. 9,-,9,5*,:! Martindale R, Patel JJ, Taylor B, Warren M, McClave SA. Nutrition therapy in the patient with COVID-19 disease requiring ICU care. Joint Recommendations om SCCM and ASPEN. Published online at https://www.sccm.org/COVID19RapidResources/Resources/NutritionTherapy-in-the-Patient-with-COVID-19-Dis. Updated April 1, 2020. Accessed June 17, 2020. Deckelbaum RJ, Hamilton JA, Moser A, et al. Medium-chain versus long-chain triacylglycerol emulsion hydrolysis by lipoprotein lipase and hepatic lipase: implications for the mechanisms of lipase action. Biochemistry (Mosc). 1990;29(5):1136-1142. Kalish BT, Fallon EM, Puder M. A tutorial on fatty acid biology. JPEN J Parenter Enteral Nutr. 2012;36:380-8. 388.

90% The percentage of surveyed U.S. hospitals that say they’ve had to find alternative therapies due to drug shortages and price increases. Source: American Hospital Association.

and Development Authority of HHS’s Office of Assistant Secretary for Preparedness and Response awarded Phlow a four-year, $354 million contract as lead partner (contract value could rise up to $812 million) to expand U.S. generic drug manufacturing, and create stockpiles of active pharmaceutical ingredients, chemical precursor ingredients and essential generic sterile injectable medications prone to shortage. Civica Rx’s role will be to make the finished dosage forms of essential medications, including vials and syringes, using

The Next Target: Expanding Generic Meds at Lower Cost

t has been five months since Civica Rx announced it would form a subsidiary to create more affordable choices of generic drugs, an effort funded with $55 million from the Blue Cross Blue Shield Association and 18 of its member companies. Calling it still “premature to share or confirm” drug categories it will target, Martin VanTrieste, RPh, Civica Rx president and CEO, said the company is “setting up” its subsidiary’s leadership, as well as drugs it will prioritize with the Blue Cross Blue Shield drug selection advisory committee, “certainly considering current challenges like COVID-19.” The first products from this joint venture, due out in 2022, will be seven to 10 generic drugs that treat a wide range of health conditions, have high savings

Operations & Management

Pharmacy Practice News • September 2020

Generics

OK to Stockpile During COVID-19?

he practice of stockpiling medications to optimize patient care isn’t a sure bet, even in a pandemic. “Just about every hospital did that in the first wave of COVID-19, and that was one factor driving shortages” of key critical care medications such as sedatives, neuromuscular blocking agents and antibiotics where and when they were needed most, said Erin Fox, PharmD, the senior director of Drug Information and Support Services at University of Utah Health, in Salt Lake City. “On the other hand, if you don’t do it, your ICU patient population could potentially grow four to 10 times overnight. You have to be prepared for that,” Dr. Fox added. “You may guess right buying a three-month supply that turns out to be a two-week supply in this situation, or you could guess wrong and risk having expiring medications on hand.” Most hospitals don’t keep excess pharmaceutical inventories because of issues with space, convenience and cash flow, she noted. Utah Health didn’t see a huge spike in COVID-19 patients in March or April, but now that the state is opening up, it has the most COVID-19 patients ever, she said. “We rose to 5,000 patients identified statewide from 3,000 over a single weekend [heading into June]. People here were worried we stocked up too much, but now they feel glad we have medications on hand.”

—A.H.

its established network of manufacturing partners. Civica Rx also will build its own finished dosage-form manufacturing facility on the same site as Phlow’s other partners, Virginia Commonwealth University’s Medicines for All Institute and AMPAC Fine Chemicals.

potential, and help the venture enhance competition for certain generic drugs, he noted. The subsidiary will acquire and develop Abbreviated New Drug Applications for selected generics, which Civica Rx and its manufacturing partners will produce. In a related development, in early July, Sandoz Inc. announced it had entered into a long-term agreement with Civica Rx to manufacture and supply critical injectable generic medicines “to help reduce supply shortages and ensure acute care settings can deliver optimal patient care.” Under the five-year agreement, Sandoz said it will supply six injectable medicines widely used at Civica’s U.S. member hospitals. Types of medications include antibiotics, acid reducers, blood thinners, antihypertensives “and medicines required in the operating room,” Sandoz noted in a press release. The company added that initial supplies are expected to begin shipping to Civica Rx later this year. —A.H.

A 300% Surge in Demand At Member Hospitals The pandemic that exposed America’s medication supply vulnerabilities was Civica Rx’s toughest challenge in only its second full year of operation. “Generics are treated like commodities, so there’s no real inventory in the pipeline. It was a big body blow to the supply chain when demand surged 300% during COVID-19 for some of the medications we deliver to members,” Mr. VanTrieste said. Yet “we were able to serve all of their day-to-day needs” because Civica Rx maintains a sixmonth inventory stockpile, has redundant suppliers and safety stock, had daily contact with hospital members in hot spot cities and manufacturer partners, and closely tracked FDA and ASHP drug shortage lists and IQVIA sales data and patterns, he noted. Mr. VanTrieste said attuned “members can be the first ones to identify demand surges and also possible shortages, through something as simple as two orders in a row that weren’t full. By trying to connect the dots with them, we have a higher probability of understanding what’s going to happen.” Such a proactive approach is key, he noted, because “once a house is on fire, you can’t buy fire insurance. And you can’t develop robust supplies in a pandemic.

Every day at Civica, we measure risk and manage our business model around the potential risk we see. We are preparing for ongoing COVID-19 waves.”

A Better Way: Allocate to Need Mr. VanTrieste considered it “very surprising that manufacturers that weren’t yet partners with us called to say they had, for instance, plenty of vecuronium bromide despite drug shortages being recorded. They’d ask, ‘Can you make sure it gets to your member hospitals that need it?’ and I said yes.” Rather than “spread peanut butter across bread, where everybody gets something,” Mr. VanTrieste urged development of “a real allocation system between pharmaceutical companies and health care providers to allocate to hospitals facing the most significant need. When hospitals are ‘underwater’ financially from patients they’re seeing, while others have no COVID-19 patients, peanut butter isn’t the best approach. We distributed appropriately because we’re so close to members.”

Past Use Not a Good Indicator Erin Fox, PharmD, a drug shortage expert and the senior director of Drug Information and Support Services at University of Utah Health, in Salt Lake City, agreed that a tailored, real-time

approach often is the best solution for mitigating drug shortages. “Restricting hospital access based on past use makes zero sense,” she stressed. “The system set up that way means the system is broken.” Dr. Fox, an unpaid volunteer on Civica Rx’s advisory committee, also pointed to contracting as a potential weak point in drug shortages management. “At last year’s FDA drug shortage meeting, we asked manufacturers what it would take for them to make a sustained supply. They want guaranteed volume and longer term contracts. These two things are missing from the current drug system except for the Civica Rx model.” That model is on point based on the included medications, Dr. Fox noted. “Some of the drugs Civica Rx has been supplying have been absolutely needed for COVID-19,” she stressed, “especially fentanyl and midazolam.” The company “provides members with psychological safety because they know they can access product,” Dr. Fox said, and leaves more essential medications available in the nation’s supply chain for others. —Al Heller The sources reported no relevant financial relationships other than their stated employment.

12 Operations & Management

Pharmacy Practice News • September 2020

Collaborative Care

In PCP clinics:

Pharmacists Deliver Diabetes Best Practices

linical pharmacists in the ambulatory care setting can greatly improve physicians’ prescribing, according to research presented at the American College of Clinical Pharmacy’s 2020 Virtual Symposium (abstract 187). “Providers in an ambulatory clinic seem to learn from pharmacist evidence-based prescribing and then incorporate that new knowledge and

practice into their own patient care,” said Benjamin Smith, PharmD, the director of Population Health Pharmacy Services at the Duke Population Health Management Office, Duke Health, in Durham, N.C. Dr. Smith came to this conclusion after studying changes in the prescribing of sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1

(GLP-1) agonists for patients with type 2 diabetes mellitus after a clinical pharmacist was embedded in a Duke Health primary care clinic. According to the American Diabetes Association, SGLT2 inhibitors and GLP-1 agonists should be considered for patients with atherosclerotic cardiovascular disease, heart failure or chronic kidney disease (Diabetes Care 2020;43[suppl 1]:S98-S110).

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The clinical pharmacist, Patrick Gregory, PharmD, began working at the clinic one half-day per week beginning August 2017, specifically focusing on patients with diabetes and hypertension. Dr. Gregory can prescribe medications under a collaborative practice agreement. To determine the effect that Dr. Gregory’s presence had on physician prescribing of SGLT2 inhibitors and GLP-1 agonists, Dr. Smith and his colleagues compared prescribing data before Dr. Gregory’s arrival, between May and July 2017, and then two years after, between May and July 2019. The investigators also compared the prescribing of these medications during the same periods at two similar Duke primary care clinics that did not include a clinical pharmacist. They did not include in their analysis any prescriptions that Dr. Gregory himself wrote for patients. The data included 2,794 patients and revealed that baseline prescribing rates were similar among the three clinics, but while there was a roughly 10% increase in the prescribing of SGLT2 inhibitors and GLP-1 agonists between 2017 and 2019 at the primary care clinic where Dr. Gregory was placed, there were increases of only 3.5% and 5.35% at the two control clinics. “Anecdotally, we thought prescriber utilization of these drugs would likely be higher in the intervention clinic, but it was surprising to see the level of increase compared to the control clinics,” Dr. Smith noted.

Operations & Management

Pharmacy Practice News • September 2020

Collaborative Care important gap in pharmacy research and metrics tracking. “We can track the direct benefits and outcomes from patients that pharmacists have encounters with, but it is more difficult to demonstrate the clinical impact beyond these specific patients,” he said. “Our analysis supports one possible strategy for doing so.”

‘As payment models shift more to value-based incentives for primary care clinics, it has become more common for pharmacist time ... [to help] achieve these measures, which should also translate to better patient outcomes and satisfaction.’ —Toni Fera, PharmD Prior to Dr. Gregory’s arrival, many clinic providers likely did not have much clinical experience prescribing SGLT2 inhibitors and GLP-1 agonists. Dr. Gregory did not conduct educational interventions for providers to encourage them to prescribe these agents, but instead communicated best practice by modeling good prescribing. “It’s likely that providers in our intervention clinic were able to see the positive results that the use of these medication classes by the pharmacist had in their patients, and they then incorporated the prescribing of these agents into their own patient encounters,” Dr. Smith said. Emphasizing that Dr. Gregory was only at the primary care clinic a half-day per week, Dr. Smith said the results show that “even minimal embedded pharmacist time at an ambulatory care clinic may have intangible benefits for patient care.” He said his team is studying how prescribing changes are affecting outcomes in the study population.

Novel Design Measures Indirect Benefits Dr. Fera applauded the researchers for conducting a well-designed study, including “a large patient and provider

population, adequate time line for evaluation, and a control group—all attributes that increase the strength of the results.” Dr. Smith said the study addresses an

The sources reported no relevant financial relationships.

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14 Focus on Hematology/Oncology

Pharmacy Practice News • September 2020

PGx Testing IDs Drug Metabolism Issues in Patients P

harmacogenomics testing for cancer patients can help identify genetic anomalies affecting drug metabolism and alert pharmacists about the need to evaluate therapy options for pain and supportive care, Mayo Clinic researchers reported.

associate program director for outpatient pharmacy education at Mayo Clinic in Arizona. Genetic variants can affect supportive care medications used in oncology and contribute to differences in risk for adverse drug effects and/or reduced efficacy, she said.

In a pharmacogenomics study that assessed factors including patients’ genotypes and drug–drug–gene interactions, the majority of the 200 patients tested were found to metabolize in a way that could affect their processing of certain pain medications, antidepressants and antiemetics. Based on the results, which were presented at the American Society of Clinical Oncology’s 2020 virtual annual meeting, pharmacists were able to make recommendations for alternative medications for 97 patients (abstract e24114). “Our results were not surprising, knowing that about 95% of us typically have at least one enzyme that will have some clinical relevance,” said lead study author Adrijana Kekic, PharmD, a pharmacogenomics pharmacist and an

Between June and December 2019, 200 patients with solid tumors were enrolled in a pharmacogenomics prospective study at Mayo Clinic in Arizona, and 196 were genotyped using a multigene panel. The panel assessed 27 genes, including CYP2C9, CYP2C19, CYP2D6, CYP3A4 and COMT, which encode for drugmetabolizing enzymes; HTR2A and OPRM1, which encode for drug receptors; and SLC6A4 and other transporter genes. All the genes they studied are associated with response to pain medications, antidepressants and antiemetics. Patients also were assessed for drug– drug–gene interactions. The patients had a range of cancers, including prostate (19.9%), colorectal (17.9%), melanoma (14.8%) and others (47.4%). The median age of the patients was 65 years; 59.2% were men. All the patients were found to have

at least one actionable polymorphism related to the three types of medications, with the most significant findings related to the CYP2C19 and CYP2D6 genes. Of the 196 patients, 132 (67.3%) were found to have an “other than normal” CYP2D6 metabolizer phenotype

effects, such as respiratory depression. “Our recommendations were made after assessing not only patients’ genetic results but also really taking into consideration the overall patient picture; in other words, how is the presence of other medications potentially changing patients’ phenotypes?” Dr. Kekic said. This includes a review of which medications preNearly one-fourth scribed are active of all medications, drugs versus prodrugs, she said. including A prior study by Dr. Kekic and her antidepressants, colleagues performsome antiemetics and ing pharmacogepain medications, nomics testing on 50 patients with active are metabolized malignancies found 33 (66%) did through the that not normally procytochrome cess genes, including CYP2D6 and P450 2D6 CYP2C19, necespathway ‘so this sitating either drug avoidance because was a significant of toxicity risks or finding, not just substantial dose adjustments to be statistically but efficacious (J Clin clinically.’ Oncol 2019;37[31 suppl]:126-126). The study results —Adrijana Kekic, PharmD appear consistent with other published work indicating that 90% to 95% of cancer patients, if tested (57.1%) were found with a pharmacogenomics panel, will and 112 (57. to have an “o “other than nor- have at least one variant that could CYP2C19 metabolizer help guide drug prescribing, commal” CYP2C1 phenotype. Based on these find- mented J. Kevin Hicks, PharmD, PhD, ings, pharmacists recommended a personalized medicine specialist medications for 37 at Moffitt Cancer Center, in Tampa, alternatives to pain med patients, alternatives to ondansetron Fla. “This study was able to show the for nine patients, and alternatives to potential value of pharmacogenomic antidepressants for 51 patients. testing in a cancer population, but Nearly one-fourth of all medica- implementation studies can be crititions, including antidepressants, some cized for lacking a control arm and antiemetics and pain medications, outcomes data,” he said. are metabolized through the cyto“Even though you know there were chrome P450 2D6 (CYP2D6) path- recommended drug changes, it’s less way, Dr. Kekic said, “so this was a clear from the abstract if those changes significant finding, not just statisti- were accepted and how that impacted cally but clinically.” Enzymes encoded clinical care,” Dr. Hicks added. “In pharby the CYP2C19 gene are responsible macogenomics, I do think we’re going to for metabolism of many medications, have to have more outcomes-type studincluding some antidepressants, proton ies … to understand how these changes pump inhibitors and clopidogrel, she are affecting patient care.” said. Patients who have abnormalities —Karen Blum in enzymes encoded by these genes will not process medications as expectDr. Kekic reported no relevant ed, Dr. Kekic said, and they could have financial relationships. Dr. Hicks reported a financial relationship with OneOme. less pain relief or concerning side

Focus on Hematology/Oncology 15

Pharmacy Practice News • September 2020

Large Study Sheds Light on Pneumonitis in NSCLC A

history of pneumonitis increases es the risk that patients with advanced ed non-small cell lung cancer (NSCLC) receiving chemotherapy or immune checkpoint inhibitors (ICIs) will develop treatment-associated pneumonitis (TAP), according to a study of real-world and clinical trial data preesented at the American Association for or Cancer Research (AACR) 2020 virtual ual annual meeting. The study investigators also found d a higher incidence of TAP among patients receiving ICIs with or without chemotherapy compared with those receiving chemotherapy alone. “Immune checkpoint inhibitorss are becoming a more important part art of cancer treatment, with seven drugs gs approved in 18 cancer types,” said presenting investigator Qi Liu, PhD, MSTAT, a senior science advisor in the FDA’s Office of Clinical Pharmacology. “Noninfectious pneumonitis is a potentially life-threatening adverse event of special interest for [ICIs],” Dr. Liu said, noting that previous research has shown that “1% to 7% of the patients suffer from any-grade pneumonitis after receiving an ICI.” The study presented at AACR was a collaborative effort by researchers from the FDA, the San Francisco–based medical data company Syapse, and Advocate Aurora Health, in Milwaukee (abstract 86). The clinical trial data came from eight randomized trials comparing ICI with and without chemotherapy with chemotherapy alone in patients with advanced NSCLC. Cases of pneumonitis were identified using the terms acute interstitial pneumonitis, interstitial lung disease, pneumonitis and pneumonitis chemical, Dr. Liu said. The real-world data analysis included a cohort of patients with a diagnosis of stage III or IV NSCLC confirmed by Advocate Aurora Health chart review. Pneumonitis cases with infectious etiology were excluded. The investigators obtained treatment information, including medication type and treatment date, from the Syapse database and confirmed the information via chart review. In the clinical trial cohort, among

Table. Incidence of Treatment-Associated Pneumonitis Clinical Trials

Real-World Data

ICI With/Without Chemotherapy (n=3,723)

Chemotherapy (n=2,768)

ICI With/Without Chemotherapy (n=615)

Chemotherapy (n=647)

Yes

5/30 16.7%

2/18 11.1%

3/21 14.3%

1/12 8.3%

164/3,693 4.4%

27/2,750 1.0%

17/594 2.9%

14/635 2.2%

History of Pneumonitis

ICI, immune checkpoint inhibitor

patients with no history of pneumonitis, those treated with ICIs with or without chemotherapy had a TAP incidence of 4.4%, and those treated with chemotherapy alone had an incidence of 1%. Among patients in that cohort with a history of pneumonitis, those treated with ICIs with or without chemotherapy had a TAP incidence of 16.7%, and those treated with chemotherapy had an incidence of 11.1%. Similar trends were noted in the real-world data (Table). “We observed a consistent numerical increase in TAP incidence with a past medical history of pneumonitis,” Dr. Liu reported. “This trend was observed in ICI- and chemotherapy-treated groups, and in both the clinical trials and realworld data sample. Most patients with a past medical history of pneumonitis

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or TAP in the real-world data sample received prior radiation therapy.” Dr. Liu pointed out some limitations of the study. “First, the sample size is small for the patient subgroups with a past history of pneumonitis. The numbers of TAP in the real-world data cohorts are also relatively small,” he said. “In addition, the patient follow-up duration was variable. Lastly, the realworld data from this study was taken from one health care system, making it unclear whether this trend would be seen in other practice settings.” Asked to comment on the study, Samantha Spencer, PharmD, a clinical assistant professor and the assistant director of the Drug Information Group at the University of Illinois at Chicago, said, “The study is helpful, as it tries to

characterize the real-world incidence of treatment-associated pneumonitis and helps [us] better understand the risk– benefit ratio for using immunotherapies or traditional chemotherapies in advanced NSCLC.” She said the most surprising result was the magnitude that a history of pneumonitis appeared to have on the development of TAP. “I think the bottom line is that the risk for treatment-associated pneumonitis is increased significantly in patients with a prior history, and in these patients, there should be a more careful discussion of the risk–benefit ratios of using immune checkpoint inhibitors,” Dr. Spencer said. “The risk itself cannot be eliminated by avoiding immune checkpoint inhibitors, because those who received chemotherapy also had a fairly elevated incidence as well,” she added. Noting that some of the risk for pneumonitis “might be mitigated by using chemotherapy [alone],” she said “the risk of pneumonitis is just one piece of the decision, as chemotherapies are associated with their own toxicities.” Andrew Li, PharmD, a clinical oncology pharmacist at St. Luke’s Mountain States Tumor Institute, in Boise, Idaho, said the rates of pneumonitis with ICIs were to be expected, but he called the high rates of pneumonitis in the chemotherapy-alone arm in patients with a history of pneumonitis “striking.” —Kate O’Rourke Drs. Liu and Spencer reported no relevant financial relationships.

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16 Focus on Hematology/Oncology

Pharmacy Practice News • September 2020

A push to practice ‘at the top of their license’

As Oral Chemo Agents Surge, Pharmacists Respond T

he growing array of oral chemotherapy agents has created an urgent demand for more clinical oncology pharmacists to practice “at the top of their license,” said Eve Segal, PharmD, the lead clinical pharmacist for hematology/oncology at the University of Washington’s Seattle Cancer Care Alliance (SCCA). At SCCA and elsewhere, that message is being heeded. Pharmacists have established themselves as active participants in cancer treatment programs, providing quality assurance and safety initiatives ranging from clinical verification of chemotherapy orders to patient adherence monitoring to drug interaction checks. But perhaps the most important role for pharmacists is in education. That’s because cancer patients leaving clinics with oral medication prescriptions “are

‘We want to make sure we have the most up-todate medication list in our system, so we can run an interaction check and make sure there are no interactions between oral chemotherapy and the patient’s entire medication list.’ —Laura Haynes, RPh in conjunction with an oncologist’s clinical session, or one-on-one with the pharmacist soon afterward. “If we don’t [try] to catch them then,” Dr. Darling added, “we’ll ask them to come back to the clinic” for an education session or conduct one at home by telephone. After the initial meeting, pharmacists continue to follow up by telephone “to readdress key points and answer any questions that come up.” The frequency of follow-up calls depends on the

IV chemotherapy, for example, might need a much longer visit than a patient on a single targeted oral chemotherapy agent, she said, adding that patients with a language barrier or learning disabilities “will require more time and attention.”

An Interdisciplinary Approach At smaller oncology clinics such as SCCC, pharmacists also have taken on an active role in patient cancer care. SCCC, which maintains an oncology clinic in

Documenting the Value of Oncology Pharmacists

and the patient’s entire medication list,” said Laura Haynes, RPh, SCCC’s co-team leader for oncology pharmacy. Interspersed with pharmacists’ interventions are routine calls by a nurse navigator on day 1 to ensure everything is all set, and then follow-up calls by a nurse around days 8 and 22. The COVID-19 pandemic has had a definite effect on oncology pharmacists’ intervention practices. Dr. Darling described the changes as “speed bumps. … We’re having to do significantly more education over the phone,” she said. But that can present some barriers to patients’ understanding. “You can’t write things down for them, or give them a patient calendar,” she said, “which we like to do in person.” However, the situation is starting to return to normal. “The whole pharmacy team has returned to the clinic,” she said, “and most physicians are back doing in-person visits.”

handful of studies have shown the value of oncology pharmacists’ patient encounters. The oral chemotherapy pharmacy team at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, in Indianapolis, for example, undertook a small pilot study involving the center’s gastrointestinal patient population. “We wanted to make sure we weren’t adding to their already challenging day by increasing the time they needed to be here talking about their treatment,” Julianne O. Darling, PharmD, a clinical pharmacy specialist in outpatient oncology at the center, said. The study included 18 patients. “We found that 98% [of the 18 patients in the study] strongly agreed the visits were beneficial, and we were able to shorten the time to treatment initiation for those folks who saw us in person” (Pharmacy [Basel] 2020;20;8[1]:46. doi: 10.3390/pharmacy8010046). At Southcoast Centers for Cancer Care, in Massachusetts, clinical oncology pharmacists conducted a study to determine patients’ perception of the value of their interventions, including a day 15 brown-bag medication evaluation clinic for every patient receiving oral chemotherapy medications. Of the 174 patients who saw pharmacists between October 2016 and June 2019, 55 returned surveys. The researchers assessed patient response with an abbreviated, previously validated, Patient Satisfaction with Pharmacist Services

basically on their own,” said Patrick Skeffington, PharmD, the co-team lead for oncology pharmacy at Southcoast Centers for Cancer Care (SCCC) in Fairhaven, Mass. “It’s not like a patient sitting in a chair in an infusion clinic where we can make sure they receive the right dose and it’s given on time.” At the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, in Indianapolis, clinical oncology pharmacists provide “quite a few touchpoints for education,” said Julianne O. Darling, PharmD, a clinical pharmacy specialist in outpatient oncology at the center. The initial encounter with a pharmacist, she explained, often takes place

Questionnaire (PSPSQ 2.0) that employed a Likert scale format (1 = strongly agree; 4 = strongly disagree). Average scores hovered around 1 (strongly agree) for each question. Anecdotally, the “overall care provided by the pharmacist was super,” wrote a study co-author, which was presented during the American College of Clinical Pharmacy’s 2020 Virtual Poster Symposium (poster 169; https://bit.ly/31brLMX).

patient and treatment regimen. Those with complicated medication histories who have had trouble with adherence receive calls within the first week or two, Dr. Darling said. Others may be called every three weeks. “We essentially touch base every cycle.” The length and depth of pharmacists’ education sessions are determined not only by the complexity of the patient’s drug regimens but also by pharmacists’ assessment of how well the patient, or caregiver, understands what needs to be done at home. “It really depends on the patient,” Dr. Segal said. “Some of the regimens are quite complex with lots side effects.” A patient getting high-dose

—B.B.

Fairhaven and a second clinic in Fall River, Mass., uses an interdisciplinary approach to ensure patient adherence throughout patients’ treatment cycles. Pharmacists conduct preliminary drug– drug interaction checks based on new chemotherapy orders and drugs in the patient’s electronic health record. At day 15 or thereabouts, patients are asked to return to the clinic for a quasi– brown-bag review of all medications, including herbals and nutraceuticals. “We want to make sure we have the most up-to-date medication list in our system, so we can run an interaction check and make sure there are no interactions between oral chemotherapy

Telemedicine Added to the Mix Oncology pharmacists at SCCA are not only using phone calls but also telemedicine in their virtual patient education visits. SCCA uses a HIPAAcompliant Zoom app supplied by the University of Washington to conduct virtual education visits. Mary Chi, PharmD, the clinical operations manager for oncology pharmacy at SCCA and a clinical associate professor at the University of Washington, in Seattle, emphasized that pharmacists also are available on-site for patient visits. “There are many reasons why we would do it in person,” she said. “It might be a patient with a disability or language barrier. Sometimes it’s a patient preference. A lot of patients are still uncomfortable with telehealth. I’ll hear a pharmacist saying, ‘On the left! Click on the little microphone so we can hear you!’” —Bruce Buckley Dr. Darling reported financial relationships with AstraZeneca and Incyte.

Focus on Hematology/Oncology 17

Pharmacy Practice News • September 2020

New TKI May Be a Game Changer for Metastatic Breast Ca

dvances in therapy have improved overall survival for patients with HER2-positive metastatic breast cancer, but for those with brain metastases—as much as 50% of that population—the outlook has remained grim. “We don’t generally see drugs that have a survival advantage in this setting,” said Rita Nanda, MD, an associate professor of medicine and the director of breast oncology at the University of Chicago. A new oral oncology drug may change that picture. In April, the FDA approved the novel tyrosine kinase inhibitor (TKI) tucatinib (Tukysa, Seattle Genetics), in combination with trastuzumab and capecitabine, for adults with unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, who received one or more prior anti–HER2-based regimens in the metastatic setting. “To have a regimen that’s not only very well tolerated but also effective in controlling brain disease is an improvement over current therapies,” Dr. Nanda told Pharmacy Practice News. “To be able to avoid or delay whole brain radiation, which is generally associated with more side effects, is important and helps to preserve quality of life,” she added. The FDA based its approval on the multicenter HER2CLIMB trial, in which 612 patients with HER2-positive metastatic disease were randomly assigned to receive either tucatinib or placebo, plus trastuzumab and capecitabine. Twothirds of patients (n=410) were assigned to the tucatinib arm. All patients had previously been treated with trastuzumab, pertuzumab and T-DM1 (N Engl J Med 2020;382[7]:597-609). The results, Dr. Nanda said, were “quite impressive.” Patients receiving the tucatinib combination had a 46% lower risk for disease progression or death than those in the placebo arm (hazard ratio, 0.54; 95% CI, 0.42-0.71; P<0.00001). Furthermore, overall survival among patients receiving tucatinib was 21.9 months (95% CI, 18.3-31.0 months) versus 17.4 months (95% CI, 13.6-19.9 months) in the placebo arm. Just as striking, she said, was the outcome in patients with brain metastases who received tucatinib. Median progression-free survival in that group was 7.6 months (95% CI, 6.2-9.5 months) versus 5.4 months in the control arm (95% CI, 4.1-5.7 months). Dr. Nanda said it was “pretty exciting to see a benefit in patients who generally have a less favorable outcome.”

‘Practice-Changing’ Results The HER2CLIMB trial and subsequent tucatinib approval are having

‘This drug will touch a majority of metastatic HER2-positive breast cancer patients at some point in their [disease course].’ —Victoria Nachar, PharmD an impact on breast cancer treatment strategies. At Michigan Medicine in Ann Arbor, for example, Victoria

Nachar, PharmD, a clinical pharmacist specialist in the Rogel Cancer Center breast cancer clinic, said the trial had

been practice changing. “We already have patients started on tucatinib, capecitabine and trastuzumab,” she said. Before this trial, Dr. Nachar noted, “there weren’t a lot of good options after the two standard lines of therapy— usually trastuzumab and pertuzumab and then trastuzumab emtansine.” But with tucatinib, she said, “we saw a significant benefit in terms of efficacy” for see NEW TKI, page 20

18 Focus on Hematology/Oncology

Pharmacy Practice News • September 2020

Dose-Rounding Savings continued from page 1

including bevacizumab, daratumumab (Darzalex, Janssen) and rituximab. At Michigan Medicine in Ann Arbor, automatic rounding of 24 oncology drug doses from July 2018 to June 2019 decreased wholesale acquisition costs by $3.6 million, with an average per-dose saving of $1,432. And at Mayo Clinic, nearly $5 million was saved in the first half of 2019

alone by rounding doses of 15 biologic oncology medications. Additional savings of nearly $2.3 million were generated by dose rounding some three dozen oncolytic agents. Between biologics and oncolytics, a total of 9,814 vials were saved systemwide. Those are just three of the health systems that have integrated dose-rounding protocols into their electronic health

record systems to reduce drug waste and costs and improve workflow efficiency. Such initiatives are supported by studies and guidelines that testify to the safety and efficacy of the practice. In 2018, the Hematology/Oncology Pharmacy Association (HOPA) published a guideline for the safe dose rounding of biologic and cytotoxic anticancer agents (J Oncol Pract 2018;14[3]:e130-e136). The investigators reported that rounding physician-ordered doses up or down to within 10% of the nearest vial size was “acceptable for routine clinical care” and

would not “reduce the safety or effectiveness of therapy.” Although 10% has become the norm, some health systems, including UCSF, have adopted 5% as their dose-rounding standard. Hansen Ho, PharmD, an associate clinical professor at USCF School of Pharmacy and an oncology clinical pharmacist at UCSF Medical Center, said when the dose-rounding project first got underway in 2016, the decision was made to take a more conservative approach. But that may change: Dr. Ho said in the light of the

NUZYRA® (omadacycline) injection for intravenous use NUZYRA® (omadacycline) tablets, for oral use BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION For complete details, please see Full Prescribing Information.

INDICATIONS AND USAGE Community-Acquired Bacterial Pneumonia (CABP) NUZYRA is indicated for the treatment of adult patients with communityacquired bacterial pneumonia (CABP) caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus inﬂuenzae, Haemophilus parainﬂuenzae, Klebsiella pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. Acute Bacterial Skin and Skin Structure Infections (ABSSSI) NUZYRA is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by the following susceptible microorganisms: Staphylococcus aureus (methicillinsusceptible and -resistant isolates), Staphylococcus lugdunensis, Streptococcus pyogenes, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Enterococcus faecalis, Enterobacter cloacae, and Klebsiella pneumoniae. USAGE: To reduce the development of drug-resistant bacteria and maintain the effectiveness of NUZYRA and other antibacterial drugs, NUZYRA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

CONTRAINDICATIONS: NUZYRA is contraindicated in patients with known hypersensitivity to omadacycline or tetracycline-class antibacterial drugs, or to any of the excipients. WARNINGS AND PRECAUTIONS Mortality Imbalance in Patients with Community-Acquired Bacterial Pneumonia-Mortality imbalance was observed in the CABP clinical trial with eight deaths (2%) occurring in patients treated with NUZYRA compared to four deaths (1%) in patients treated with moxifloxacin. The cause of the mortality imbalance has not been established. All deaths, in both treatment arms, occurred in patients >65 years of age; most patients had multiple comorbidities. The causes of death varied and included worsening and/or complications of infection and underlying conditions. Closely monitor clinical response to therapy in CABP patients, particularly in those at higher risk for mortality. Tooth Discoloration and Enamel Hypoplasia-The use of NUZYRA during tooth development (last half of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during longterm use of the tetracycline-class drugs, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported with tetracycline-class drugs. Advise the patient of the potential risk to the fetus if NUZYRA is used during the second or third trimester of pregnancy. Inhibition of Bone Growth-The use of NUZYRA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. Advise the patient of the potential risk to the fetus if NUZYRA is used during the second or third trimester of pregnancy. Hypersensitivity Reactions-Hypersensitivity reactions have been reported with NUZYRA. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with other tetracycline-class antibacterial drugs. NUZYRA is structurally similar to other tetracycline-class antibacterial drugs and is contraindicated in patients with known hypersensitivity to tetracycline-class antibacterial drugs. Discontinue NUZYRA if an allergic reaction occurs. Clostridium difficile-Associated Diarrhea-Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use.

Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. Tetracycline-Class Effects-NUZYRA is structurally similar to tetracyclineclass of antibacterial drugs and may have similar adverse reactions. Adverse reactions including photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests), have been reported for other tetracycline-class antibacterial drugs, and may occur with NUZYRA. Discontinue NUZYRA if any of these adverse reactions are suspected. Development of Drug-Resistant Bacteria: Prescribing NUZYRA in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

ADVERSE REACTIONS: The following clinically signiﬁcant adverse reactions are described in greater detail in the Warnings and Precautions section of the labeling: • Mortality Imbalance in Patients with CommunityAcquired Bacterial Pneumonia

• Inhibition of Bone Growth

• Tooth Development and Enamel Hypoplasia

• Tetracycline-Class Effects

• Hypersensitivity Reactions

Clinical Trials Experience-Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Overview of the Safety Evaluation of NUZYRA: NUZYRA was evaluated in three Phase 3 clinical trials (Trial 1, Trial 2 and Trial 3). These trials included a single Phase 3 trial in CABP patients (Trial 1) and two Phase 3 trials in ABSSSI patients (Trial 2 and Trial 3). Across all Phase 3 trials, a total of 1073 patients were treated with NUZYRA (382 patients in Trial 1 and 691 in Trials 2 and 3) of which 368 patients were treated with only oral NUZYRA. Imbalance in Mortality: In Trial 1, eight deaths (2%) occurred in 382 patients treated with NUZYRA as compared to four deaths (1%) in 388 patients treated with moxifloxacin. All deaths, in both treatment arms, occurred in patients >65 years of age. The causes of death varied and included worsening and/or complications of infection and underlying conditions. The cause of the mortality imbalance has not been established [see Warnings and Precautions (5.1)]. Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation: In Trial 1, a total of 23/382 (6.0%) patients treated with NUZYRA and 26/388 (6.7%) patients treated with moxifloxacin experienced serious adverse reactions. Discontinuation of treatment due to any adverse reactions occurred in 21/382 (5.5%) patients treated with NUZYRA and 27/388 (7.0%) patients treated with moxifloxacin. Most Common Adverse Reactions: Table 4 lists the most common adverse reactions occurring in ≥2% of patients receiving NUZYRA in Trial 1. Table 4: Adverse Reactions Occurring in ≥2% of Patients Receiving NUZYRA in Trial 1 NUZYRA (N = 382)

Moxiﬂoxacin (N = 388)

Alanine aminotransferase increased

3.7

4.6

Hypertension

3.4

2.8

Gamma-glutamyl transferase increased

2.6

2.1

Insomnia

2.6

2.1

Vomiting

2.6

1.5

Constipation

2.4

1.5

Nausea

2.4

5.4

Aspartate aminotransferase increased

2.1

3.6

Headache

2.1

1.3

Adverse Reaction

Focus on Hematology/Oncology 19

Pharmacy Practice News • September 2020

At Mayo Clinic, nearly HOPA guidelines, UCSF was weighing an increase to 10%. In addition to cost savings and waste reduction, automated dose rounding also can enhance workflow efficiency. “It doesn’t require any extra work for pharmacists or physicians,” Dr. Ho noted. And it increases transparency. “When doses are rounded automatically,” he said, “they’re displayed on the screen. Physicians can see the rounding dose and change it, if necessary, to more precisely measure their intended dose.” There are other benefits. For one, cost

$5 million was saved in the first half of 2019 alone by rounding doses of 15 biologic oncology medications. savings are automatic and multiply over time as the number of patients increases and drug indications expand. “The nice thing about rounding is that once it’s implemented, the potential cost savings are ongoing,” said Edward Yoo, PharmD,

an APeX pharmacy applications analyst at UCSF Health. Dr. Yoo cited rituximab as an example. Last year, UCSF saved about 600 100-mg vials through dose rounding. “At AWP, that added up to savings of about $563,000,” he said. Another

NUZYRA® (omadacycline) injection for intravenous use NUZYRA® (omadacycline) tablets, for oral use Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation: In the pooled ABSSSI trials, serious adverse reactions occurred in 16/691 (2.3%) of patients treated with NUZYRA and 13/689 (1.9%) of patients treated with comparator. Discontinuation of treatment due to adverse events occurred in 12 (1.7%) NUZYRA treated patients, and 10 (1.5%) comparator treated patients. There was 1 death (0.1%) reported in NUZYRA treated patients and 3 deaths (0.4%) reported in linezolid patients in ABSSSI trials. Most Common Adverse Reactions: Table 5 includes the most common adverse reactions occurring in ≥2% of patients receiving NUZYRA in Trials 2 and 3. Table 5: Adverse Reactions Occurring in ≥2% of Patients Receiving NUZYRA in Pooled Trials 2 and 3 Adverse Reaction

NUZYRA (N = 691)

Linezolid (N = 689)

Nausea*

21.9

8.7

Vomiting

11.4

3.9

Infusion site reactions**

5.2

3.6

Alanine aminotransferase increased

4.1

3.6

Aspartate aminotransferase increased

3.6

3.5

Headache

3.3

3.0

Diarrhea

3.2

2.9

*In Trial 2, which included IV to oral dosing of NUZYRA, 40 (12%) patients experienced nausea and 17 (5%) patients experienced vomiting in NUZYRA treatment group as compared to 32 (10%) patients experienced nausea and 16 (5%) patients experienced vomiting in the comparator group. One patient (0.3%) in the NUZYRA group discontinued treatment due to nausea and vomiting. *In Trial 3, which included the oral loading dose of NUZYRA, 111 (30%) patients experienced nausea and 62 (17%) patients experienced vomiting in NUZYRA treatment group as compared to 28 (8%) patients experienced nausea and 11 (3%) patients experienced vomiting in the linezolid group. One patient (0.3%) in the NUZYRA group discontinued treatment due to nausea and vomiting. **Infusion site extravasation, pain, erythema, swelling, inﬂammation, irritation, peripheral swelling and skin induration. Selected Adverse Reactions Occurring in Less Than 2% of Patients Receiving NUZYRA in Trials 1, 2 and 3: The following selected adverse reactions were reported in NUZYRA-treated patients at a rate of less than 2% in Trials 1, 2 and 3. Cardiovascular System Disorders: tachycardia, atrial ﬁbrillation; Blood and Lymphatic System Disorders: anemia, thrombocytosis; Ear and Labyrinth Disorders: vertigo; Gastrointestinal Disorders: abdominal pain, dyspepsia; General Disorders and Administration Site Conditions: fatigue; Immune System Disorders: hypersensitivity; Infections and Infestations: oral candidiasis, vulvovaginal mycotic infection; Investigations: creatinine phosphokinase increased, bilirubin increased, lipase increased, alkaline phosphatase increased; Nervous System Disorders: dysgeusia, lethargy; Respiratory, Thoracic, and Mediastinal disorders: oropharyngeal pain; Skin and Subcutaneous Tissue Disorders: pruritus, erythema, hyperhidrosis, urticaria.

DRUG INTERACTIONS

during mating and early pregnancy resulted in embryo loss at 20 mg/kg/day; systemic exposure based on AUC was approximately equal to the clinical exposure level. Results of studies in rats with omadacycline have shown tooth discoloration. The estimated background risk of major birth defects 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 15-20%. Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity also has been noted in animals treated early in pregnancy. Lactation: Risk Summary—There is no information on the presence of omadacycline in human milk, the effects on the breastfed infant or the effects on milk production. Tetracyclines are excreted in human milk; however, the extent of absorption of tetracyclines, including omadacycline, by the breastfed infant is not known. Because there are other antibacterial drug options available to treat CABP and ABSSSI in lactating women and because of the potential for serious adverse reactions, including tooth discoloration and inhibition of bone growth, advise patients that breastfeeding is not recommended during treatment with NUZYRA and for 4 days (based on half-life) after the last dose. Females and Males of Reproductive Potential Contraception Females: NUZYRA may produce embryonic or fetal harm. Advise patients to use an acceptable form of contraception while taking NUZYRA. Infertility Males: In rat studies, injury to the testis and reduced sperm counts and motility occurred in male rats after treatment with omadacycline.

Approaching 99% Accuracy

Females: In rat studies, omadacycline affected fertility parameters in female rats, resulting in reduced ovulation and increased embryonic loss at intended human exposures.

Over time, the rounding process has continued to improve. “When we went live in March 2018,” Dr. Shah said, “we had about 80% to 85% of dose rounding correct. By the end of the year, we were around 95% accurate on what we were trying to achieve.” He added: “Some drugs are hard to dose-round because of their concentration and dosing requirements. So we’ll never get to 100%, but today we’re close to 99%.” Katie Eschenburg, PharmD, a clinical pharmacist at Michigan Health’s Rogel Cancer Center Infusion Pharmacy, in Ann Arbor, said dose rounding offers multiple benefits. In addition “to the obvious savings from drug waste, in many cases, we have been able to reduce the number of vials needing to be reconstituted.” This is the result, she noted, “of both automatic rounding to within 10% of the nearest vial size and purposely applying logic to limit the number of vials used per dose when possible. This saves a bit of compounding time and also helps to reduce stress on our technicians’ hands.” —Bruce Buckley

Pediatric Use-Safety and effectiveness of NUZYRA in pediatric patients below the age of 18 years have not been established. Due to the adverse effects of the tetracycline-class of drugs, including NUZYRA on tooth development and bone growth, use of NUZYRA in pediatric patients less than 8 years of age is not recommended. Geriatric Use-Of the total number of patients who received NUZYRA in the Phase 3 clinical trials (n=1073), 200 patients were ≥65 years of age, including 92 patients who were ≥75 years of age. In Trial 1, numerically lower clinical success rates at early clinical response (ECR) timepoint for NUZYRA-treated and moxifloxacin-treated patients (75.5% and 78.7%, respectively) were observed in CABP patients ≥65 years of age as compared to patients <65 years of age (85.2% and 86.3%, respectively). Additionally, all deaths in the CABP trial occurred in patients >65 years of age. No significant difference in NUZYRA exposure was observed between healthy elderly subjects and younger subjects following a single 100 mg IV dose of NUZYRA. Hepatic Impairment-No dose adjustment of NUZYRA is warranted in patients with mild, moderate, or severe hepatic insufficiency (Child-Pugh classes A, B, or C). Renal Impairment-No dose adjustment of NUZYRA is warranted in patients with mild, moderate, or severe renal impairment, including patients with end stage renal disease who are receiving hemodialysis.

Anticoagulant Drugs-Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while also taking NUZYRA. Antacids and Iron Preparations-Absorption of oral tetracyclines, including NUZYRA, is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron containing preparations.

OVERDOSAGE No speciﬁc information is available on the treatment

USE IN SPECIFIC POPULATIONS

Distributed by: Paratek Pharmaceuticals, Inc. Boston, MA, USA

Pregnancy: Risk Summary—NUZYRA, like other tetracycline-class antibacterial drugs, may cause discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimester of pregnancy. The limited available data of NUZYRA use in pregnant women is insufﬁcient to inform drug associated risk of major birth defects and miscarriages. Animal studies indicate that administration of omadacycline during the period of organogenesis resulted in fetal loss and/or congenital malformations in pregnant rats and rabbits at 7 times and 3 times the mean AUC exposure, respectively, of the clinical intravenous dose of 100 mg and the oral dose of 300 mg. Reductions in fetal weight occurred in rats at all administered doses (see Data). In a fertility study, administration to rats

$331,000 was saved on 416 unopened 100-mg vials of bevacizumab, he noted. At Mayo Clinic, the dose-rounding protocol went live in March 2018, enabled by the systemwide implementation of a new electronic health record system. Vishal S. Shah, PharmD, a hematology/oncology informatics pharmacist at Mayo Clinic in Arizona, said it took about three months of technical development to get the project underway after approvals from three interdisciplinary committees. Candidates for the rounding protocol were drawn from a list of injectable oncology drugs in Mayo Clinic’s electronic medical record, Dr. Shah noted. They were reviewed and analyzed by hematology/oncology pharmacists representing infusion centers, the inpatient setting and research. “We included all drugs used in the treatment of cancer, regardless of cost,” he said. “There were no other criteria.” Two separate rounding rules were applied to the protocol. Rule No. 1, he explained, was round to the nearest vial size if within 10% of the prescribed dose. “That’s where most cost savings come from.” Rule No. 2 kicks in, Dr. Shah explained, when the ordered dose falls outside of the 10% limit. Then the dose may be converted into a convenient volumetric measure for a 1- or 2-mL syringe within 10% of the ordered dose. Dr. Shah said the second rule had made it easier for pharmacy technicians to measure doses and reduced compounding time, but “we haven’t looked at the financial impact from that.”

of overdosage with NUZYRA. Following a 100 mg single dose intravenous administration of omadacycline, 8.9% of dose is recovered in the dialysate. To report SUSPECTED ADVERSE REACTIONS, contact Paratek Pharmaceuticals, Inc. at 1-833-727-2835 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

PARATEK® and the hexagon logo are registered trademarks of Paratek Pharmaceuticals, Inc. NUZYRA® and its design logo are registered trademarks of Paratek Pharmaceuticals, Inc. For patent information: www.paratekpharma.com/products/patent. © 2019 Paratek Pharmaceuticals, Inc. All rights reserved.

US-NUA-0166 07/19

The sources reported no relevant financial relationships.

20 Focus on Hematology/Oncology

NEW TKI continued from page 17

patients with brain metastases—47% of study participants, 19% of whom had treated brain metastases and 28% who had progressive or untreated brain disease. “This drug will touch a majority of metastatic HER2-positive breast cancer patients at some point in their [disease course],” Dr. Nachar said. She also noted that tucatinib was “well tolerated compared with other smallmolecule tyrosine kinase inhibitors for

Pharmacy Practice News • September 2020

HER2-positive breast cancer. Roughly only about 6% of patients discontinued therapy due to a side effect, which is quite impressive when you compare across the spectrum of available agents.” Dr. Nachar cited neratinib and lapatinib as examples of other TKIs indicated for metastatic HER2-positive breast cancer that have higher discontinuation rates. “Discontinuation due to any adverse event,” she noted, “occurred in 10.9% of patients treated with neratinib plus capecitabine and 14.5% of patients treated with lapatinib plus capecitabine [doi:

10.1200/JCO.2019.37.15_suppl.1002].” Dr. Nachar stressed to oncology pharmacists the importance of developing a side effect management plan to “help patients stay on tucatinib combination therapy for as long as possible and derive the greatest benefit.” She said the majority of tucatinib’s common side effects, such as diarrhea, nausea, vomiting and peripheral neuropathy were mild. “Diarrhea generally occurred within the first 12 days of treatment and resolved within eight days.” As for management strategies, “for most

Patients receiving a tucatinib combination had a

46% lower risk for disease progression or death than those in a placebo arm. Source: N Engl J Med 2020;382(7):597-609.

patients, diarrhea can be treated with standard antidiarrheals,” she said. “Patients should have as-needed antiemetics for nausea or vomiting on hand at home with [information] on when to take them and how often. As always, the importance of oral hydration should be stressed.” In addition, she said patients should be educated about common side effects, as well as “how to self-manage at home, if appropriate, and when to notify the oncology team.”

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Deepak Singh, PharmD, the director of clinical value and outcomes at Seattle Genetics, who joined Dr. Nanda in a recent company-sponsored webinar presented by AMCP, said tucatinib was the first drug “to be powered to look at a patient population with brain metastases” and “to demonstrate an overall survival advantage.” He added: “Historically, this patient population has been excluded from trials done in this setting. The only patients with brain metastases that have been included in clinical trials have been [those] with stable brain metastases.” He noted that a “significant percentage” of the nearly half of patients with brain metastases in the HER2CLIMB trial had undiagnosed, untreated or progressive brain disease. Dr. Singh said as a result of this trial, tucatinib has been “recognized with a category 1 level of evidence” in the National Comprehensive Cancer Network’s updated Clinical Practice Guidelines in Oncology, and is included in the network’s Drug and Biologics Compendium for Central Nervous System Disorders. —Bruce Buckley Dr. Nachar reported no relevant financial relationships. Dr. Singh reported employment by Seattle Genetics. Dr. Nanda reported financial and/or research relationships with Aduro, AstraZeneca, Athenex, Celgene, Clovis, Corcept Therapeutics, Daiichi Sankyo Inc., G1 Therapeutics, Genentech/Roche, Immunomedics, MacroGenics, Merck, OBI Pharm Inc., Odonate Therapeutics, Pfizer and Seattle Genetics.

Policy

Pharmacy Practice News • September 2020

Finance

340B Cuts continued from page 1

and handling costs, for a net proposed rate of ASP minus 28.7%. ASHP noted that it “is deeply disappointed in the court’s decision, which will allow CMS to continue its draconian cuts to reimbursement for 340B drugs. Given the challenges many hospitals are already facing due to COVID-19, cuts to the 340B program are even more likely to result in cuts to vital patient services.” “It is incredibly shortsighted to—at the height of a pandemic—cut a program that allows hospitals to expand their patient care services,” said Tom Kraus, the vice president of government relations at ASHP. “CMS should immediately and fully restore funding for 340B hospitals to avoid doing more harm to vulnerable patients who rely on these entities.” Maureen Testoni, the president and CEO of 340B Health, which represents hospitals that participate in the 340B program, also underscored the importance of preserving 340B funding during the pandemic. “340B hospitals treat a significant share of patients with low incomes enrolled in Medicaid and Medicare, including many who are living with chronic conditions such as diabetes,” Ms. Testoni said. Since 2018, these hospitals have been underpaid and forced to make tough decisions on what services to cut to maintain the core of their care for patients in need. 340B disproportionate share hospitals (DSHs) provide 75% of Medicaid hospital care to patients, services that are reimbursed at rates lower than what it costs to deliver them. “It should go without saying that during a global pandemic, it is foolhardy for the administration to stubbornly push and worsen a Medicare payment policy that hurts safety net hospitals and their patients,” she stressed. “The ASP minus 22.5% cuts are bad enough. But adding another 6.2% just takes a bad situation and makes it worse,” agreed Jim Jorgenson, RPh, MS, FASHP, the CEO of Visante, which works closely with many 340B hospitals. “With the majority of hospitals sustaining significant financial losses in the second quarter due to the COVID-19 pandemic and really struggling to stay financially viable, hitting the hospitals that cover the most vulnerable patients with further reimbursement cuts at this time does not seem like the best idea.” Mr. Jorgenson noted that the cuts will result in hospitals being “upside down” on some drugs, with the drug cost exceeding the reimbursement at the proposed cut levels. The American Hospital Association also criticized the proposed rule in a public statement from Executive Vice President Tom Nickels. “These cuts

decimate the intent of the 340B program and only exacerbate the strain placed on hospitals serving vulnerable communities,” Mr. Nickels said. “These cuts also conflict with Congress’ clear intent and defer to the government’s inaccurate interpretation of the law. For more than 25 years, the 340B program has helped hospitals stretch scarce federal resources to reach more patients and provide comprehensive services to vulnerable communities. Today’s proposal will result in the continued loss of resources for 340B hospitals at the worst possible time.”

Did COVID-19 Drive Program Cuts? The new cuts are based on a hospital acquisition cost survey conducted by the Department of Health and Human Services in April 2020 amid the COVID-19 pandemic. Covered entities were given three weeks to respond to the survey, with either detailed information on their 340B acquisition costs or certification that they purchase 340B drugs at the ceiling price. Only 7% of hospitals provided a detailed response, 55% chose to certify the ceiling price, and 38% did not respond. 340B Health criticized the survey at the time of distribution in a letter to CMS. “Hospitals are left to choose between an option requiring significant staff resources at a time when those resources are stretched or a quick option with ambiguous language that hospitals are concerned could result in unintended representations about their drug acquisition costs,” they wrote. CMS has claimed that the 340B rate cuts ultimately benefit patients, with savings passed on in reduced out-of-pocket costs. In a 2018 press release when the earlier cuts were finalized, the agency stated, “Beneficiaries are saving an estimated $320 million on out-of-pocket payments for these drugs in 2018 alone.” But Mr. Jorgenson questioned that assertion. “Once patients hit their outof-pocket max, there is no additional savings passed on to them, and for a large portion of these patients, the hospitals waive their copays anyway. I think any impact on patient out-of-pocket costs as a result of these cuts will be minimal at best.” Ethan Davidoff, the CEO of Atlas Health, which provides artificial intelligence technology to connect patients with financial assistance programs, anticipates that the need for these programs will become even greater as a result of the cuts. “This probably couldn’t have come at a worse time,” he told Pharmacy Practice News. “Consider just one drug, Keytruda [pembrolizumab, Merck], as an example. After these cuts, 340B hospitals and health systems will be in the red [by more than] $1,000 for every standard dose. They are there to help patients and serve the community, but how do they

break even, stay solvent, and keep the doors open? The need for philanthropic programs will become even more acute for these hospitals and their patients as a result of these cuts.”

340B Critics Also Concerned Even critics of the 340B program warn that the timing of the cuts is illadvised. Sayeh Nikpay, PhD, an associate professor in the Division of Health Policy and Management at the University of Minnesota School of Public Health, has written extensively about the 340B program, recently co-authoring an April 2020 study finding that although hospitals newly participating in the program may increase their charity care, those increases appear to be fully offset by reductions in other community benefit programs (Health Serv Res 2020;55[2]:157-169). “340B has at its core a safety net mission, but was written in such a way that it opens the door to abuse,” Dr. Nikpay said. “We have run down the publicly available data sources as far as they can take you, but we don’t have a good way of distinguishing between 340B providers acting in the spirit of what Congress intended and those who are not. A number of studies looking at a wide

variety of hospitals, however, do suggest that in many cases these revenues are not used to increase safety-net care.” Although she favors reform in the 340B program, Dr. Nikpay argued that the scope and timing of the cuts could be risky. “Reform must start with transparency,” she said. “This [savings] tool is not a scalpel, it’s a battering ram. Even though the amount of money lost to each individual hospital may not be huge, because it’s such a blunt instrument and hospitals are so different in terms of their financial stability and the impact of COVID-19, applying these cuts right now could be catastrophic for some facilities.” Dr. Nikpay recommended delaying the cuts and combining them with a more fine-tuned approach to reform, starting with mandating more transparency from hospitals on the information they already collect about their 340B participation. —Gina Shaw The sources reported no relevant financial relationships.

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22 Clinical

COVID-19 Pandemic

Lessons Learned continued from page 1

An immediate pressing issue was shortages that began to arise, Ms. Groves recalled. For instance, hand sanitizer was difficult to obtain, not only for this multiregional health system but across the nation. To meet the needs of the 120,000 caregivers serving millions of patients, each acute care hospital would have had to store 55-gallon drums of alcohol—which was “not feasible,” Ms. Groves said during an ASHP webinar titled “COVID-19 pharmacy response across a multi-region health-system: lessons learned and the future of pharmacy.” Providence needed to start making its own product. Pharmacists worked with the home infusion pharmacy team to develop compounding recipes. Together, they made the sanitizer, kept it in a central location, and distributed it throughout the vast health network.

Remaining Nimble Communication, creativity, splitting up responsibility and being nimble: These were some of the key elements of Providence St. Joseph Health’s response to this unprecedented crisis. Now they’re taking what they’ve learned during the first stage of the pandemic and using it to prepare for the future, including making plans for business recovery and an additional resurgence of COVID-19 patients—while keeping the entire health system financially solvent. Their approach is a great example of how to weather a health crisis such as the pandemic, noted David Chen, BS Pharm, MBA, the assistant vice president for pharmacy leadership and planning at ASHP. “The Providence St. Joseph’s team has implemented a comprehensive action plan that leverages lessons learned during their months of managing COVID preparation and its impact on organizational operations,” Mr. Chen told Pharmacy Practice News. For “almost all health systems, the pandemic has resulted in significant revenue losses that need to be systematically addressed,” he said, noting that systems also need to stay “in a constant state of readiness for future COVID patient demands.”

Success, Step-by-Step

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In the early days of COVID-19, communication was key because Providence St. Joseph Health has hospitals and clinics in seven states. Although each region would have specific needs, pharmacy leadership knew there needed to be a coordinated approach. The system pharmacy team, including regional pharmacy leaders, began daily huddles on COVID-19 and established a virtual command center, from which members issued regular and

rapid communications across the pharmacy enterprise. Under this system, any changes—such as switching the entire network from nebulizers to metereddose inhalers to reduce exposures to aerosols—could happen efficiently, safely and effectively. To prevent shortages at any facility—known as a ministry—system pharmacists created a list of the top 150 drugs ordered by providers, updated daily by wholesalers and referenced by pharmacy buyers to make sure they had enough of these essential products. A shortages group developed clinical algorithms to point clinicians to alternative products when their first choice was unavailable. Seeing system pharmacy step up— and the positive response from regional pharmacy teams—was inspiring and validated the intent of the structure, Ms. Groves noted. The system pharmacy positions were created less than one year ago, much to the concern of some regional providers, she said. “There was healthy skepticism of the value the roles would bring.” But without a system team, any changes to workflow would have to be vetted in detail by each region. In contrast, with the system’s approach, “once a good idea surfaced, it was quickly vetted by the pharmacy governance council and socialized, and then each region could act on it.” That strategy is resonating with member hospitals. Indeed, “regional pharmacy members say they cannot imagine how much more difficult navigating COVID would have been without the system pharmacy team,” Ms. Groves said. Such positive feedback makes the hard work worthwhile, she stressed. “Although the COVID pharmacy response involved long, arduous days, there were many bright spots that resulted from all of this transformative work.”

Regional Level Actions Regional pharmacy teams at Providence St. Joseph Health also did their part. In the northwest corner of Oregon, the health system operates three acute care ministries, including a large teaching institution with more than 500 beds (Providence St. Vincent Medical Center); a community hospital with 50 beds (Providence Newberg Hospital); and a critical access point hospital with 25 beds (Providence Seaside Hospital). Each facility serves very different needs, according to Saly Daoud, PharmD, MBA, the westside director of pharmacy, Oregon region. Located on the west side of Portland, Providence St. Vincent treated many of the city’s

Clinical

Pharmacy Practice News • September 2020

COVID-19 Pandemic COVID-19 patients while maintaining quality care in other inpatient services, such as oncology and pediatrics. “We really needed to tweak our response to each ministry according to the needs and the specific patients we’re serving in those areas,” Dr. Daoud said during the webinar. In addition to inpatient pharmacy, Providence Seaside also serves outpatient retail, primary care and infusion clinics. The outpatient services offered testing for COVID-19 and implemented drive-thru international normalized ratio (INR) testing for its anticoagulation clinic (see sidebar). The pharmacotherapy clinic ramped up telehealth services to engage patients in virtual visits, and has even noticed a slight increase in compliance versus in-person visits, Dr. Daoud noted, although she cautioned they won’t have final numbers until the end of the year. Telehealth is “definitely becoming the future, as more and more patients are looking for options beyond coming to the hospital.” Regional pharmacists in Oregon also realized they needed timely, quick communication. “Changes were happening on the hour, not even just every day,” Dr. Daoud recalled. They held team huddles twice a day, with a standing agenda item about how many COVID-19 patients were in each ministry and any issues with the supply chain. Minutes of each meeting were emailed to the pharmacy team, who also had access to a website that posted regular updates. “That way, all different forms of communication would go out to the front lines, and everyone is aware of the happenings,” Dr. Daoud said.

Saving the System One of the painful truths of the pandemic is its financial cost, due in part to increased procurement of related medications and supplies. “Our No. 1

The Features of a Networked Practice Model

goal is always to continue to provide safe, quality care, but we also had a financial responsibility that we had to pay attention to and we had to address,” Dr. Daoud noted. In Oregon, staffing had no choice but to switch from a fixed to variable workforce. That meant making some tough decisions, with providers’ input, Dr. Daoud said. “We really didn’t want that process to come from a top-down approach,” she said during the ASHP webinar. Pharmacy leaders gathered different groups of caregivers, including physicians, clinical pharmacists and pharmacy technicians, to brainstorm solutions. Pharmacists and technicians helped develop a flexed-plan playbook, which included six tiers of staffing based on patient census data and, when available, workload statistics and revenue indicators, added Long D. Trinh, PharmD, the interim regional executive director of pharmacy/regional director of pharmacy operations and compliance for the Oregon region at

Coagulation Testing in Cars P

rovidence St. Joseph Health isn’t the only health system to begin offering drive-thru INR testing in the wake of the COVID-19 pandemic. “Ambulatory care pharmacists, including those in anticoagulation clinics, have had to adapt to the pandemic safety guidelines and address patient concerns about attending non-urgent care visits,” said Toni Fera, PharmD, a senior consultant based in Pittsburgh. “A drive-thru INR clinic is a creative solution that minimizes contact time for the providers and patients, but still provides the necessary testing for monitoring therapy.” Health systems need to consider state regulations as well as billing and revenue, and implement procedures to ensure the safety of patients and providers, according to Dr. Fera. Not every patient taking blood thinners may need drive-thru INR testing; some patients may be able to switch to a non–vitamin K oral anticoagulant, extend the time between tests if stable, or conduct self-testing, she noted. Regardless, pharmacists can play a key role in monitoring anticoagulation during the pandemic. At

Providence St. Joseph Health, which includes eight acute care hospitals. Tactics included—but were not limited to—shortening shifts and managers pitching in on the front lines, he noted. There are other ways to be mindful of expenses besides workforce planning, Dr. Trinh noted. Before the pandemic, his pharmacy team had several capital projects set to go live in the summer, such as new carousel hardware and inventory management software, as well as renovation of the inpatient pharmacies. These plans were paused temporarily but will resume soon, he said, adding, “I’m sure we all envisioned a different future for 2020.” Despite the upheavals brought on by the pandemic, Dr. Trinh stressed that the Providence team has continued to favorably manage medication and supply expenses by optimizing formulary utilization and purchasing. Throughout that process, he noted, administrators

remained mindful that they had a responsibility to keep patients and providers safe during a health crisis. “As leaders, we have the opportunity now to make some of the most important decisions of our career—keeping patients and caregivers safe, while also ensuring we are good financial stewards.” For ASHP’s Mr. Chen, “nimble” has to be one key word in any health-system’s approach to COVID-19 preparedness. “There also must be fluidity and flexibility in reimagining how patient care services are provided,” he said. “The reality of optimizing resources while leveraging the willingness of patients and providers—as well as continued necessity—to use technology will create opportunities that must both be seized as well as adapted to.” —Alison McCook The sources reported no relevant financial relationships.

drive-thru clinics, pharmacists can conduct the tests and follow up with patients in person or via telephone, if a physician’s input is necessary, Dr. Fera said. In Oregon, pharmacists review patient records to assess INR Drive-thru INR clinics are one way innovative health systems are helping trends or any adverse to deliver patient care despite the limitations posed by COVID-19. events and use those data to tailor recommendations to optimize indiface-to-face appointments post-COVID.” vidual patients’ therapy, noted Saly Daoud, PharmD, Anticoagulation monitoring is not something many MBA, Providence St. Joseph Health’s westside direcpatients can put off until the pandemic subsides, tor of pharmacy, Oregon region. Furthermore, their so drive-thru testing likely will continue and expand help extends beyond the clinic, she noted. “One of the throughout the health system, Dr. Daoud added. main pharmacist roles is to provide patient education “This will be one of the main areas that we will need to ensure compliance, including education on at-home to expand and look at as a system.” INR testing if the patient is not comfortable doing —A.M.

24 Clinical

Pharmacy Practice News • September 2020

COVID-19 Pandemic

Communication continued from page 1

The organization ultimately limited use of HCQ to COVID-19 patients enrolled in clinical trials and those with an approved indication, as per FDA guidance (bit.ly/30Rzf7G). Theyy built electronic health record alerts to prevent providers from prescribing outside of these parameters, and pharmacists double-checked orders to ensure adherence, Dr. Milligan explained. “Until recently, we also held dailyy pharmacy leadership huddles, attended by everyone from outpatient pharmacists to supply chain managers from our 15 hospitals,” he said. During the huddles, they updated each other on changes in therapy and guidance documents. Pharmacy and nursingg leaders vetted these documents and passed them on to the organization’s incident command center, which distributed them. “Having broad stakeholder involvement and approval from respected leadership led to a high-level acceptance by staff and providers.” Webinar participant Steven Meisel, PharmD, the director of medication safety at Fairview Health Services, a system of 11 hospitals across Minnesota, said his organization relied on a “very well-organized central command center” that is responsible for making emergency preparedness policies and decisions for the organization, “while bypassing what might otherwise be ‘red tape.’” He added that another key player—the system vice president of pharmacy—liaises with command staff and uses their input to direct pharmacy leaders. A separate group of clinical leaders creates treatment guidelines and protocols, which are available online to health-system employees, he added. Dr. Meisel said this leadership structure was effective when demand for HCQ surged early in the pandemic and when they received their first shipment of remdesivir.

Work-Arounds Although communication has been effective overall during the pandemic, Andrew Martin, MSN, RN, a patient safety analyst at ECRI, said poor communication during the pandemic response has been a theme in reports that his organization has received. “When health care workers feel they are missing important information, they’re going to fill in the blanks by doing work-arounds,” Mr. Martin said. For example, ECRI found that in the absence of clear information from leadership as to the supply of critical personal protective equipment, staff at

some hospitals decreased the number of times they enter patients’ rooms by moving infusion pumps into the hallway (sidebar) or using fewer staff to reposition patients. Although work-arounds like these may be necessary, “leadership

should be making the difficult decisions and deploying resources the best they can, and not just leave it in the Mr. hands of individual employees,” employ Martin said. Christina Michalek, RPh, a medication safety specialist at IS ISMP, who co-moderated the webinar, said communication during the first firs wave of the pandemic was “pretty ggood,” but highlighting there have been reports hi room for improvement. For example, in some cases, she noted, organizacommunicating new tions lagged in communica guidelines to their employe employees (bit.ly/ 31PULdW). —David Wild —D The sources sourc reported no releva relevant financial re relationships.

Is There a Danger Zone for Smart Pumps?

ven when smart pumps are available, COVID-19 has necessitated workflow changes to ensure safety. Specifically, some hospitals are stationing the pumps outside the rooms of critically ill patients with COVID-19. Doing so can reduce the number of times health care workers enter patients’ rooms, preserving personal protective equipment and cutting the risk for SARS-CoV-2 exposure. However, as experts from ECRI and ISMP said during a recent webinar, with new workflows come new concerns. ECRI has tested the five most common smart infusion pump brands using up to 20 feet of microbore extension, which many organizations have opted to use because of the smaller priming volume, noted Erin Sparnon, MEng, a senior engineering manager at ECRI. Ms. Sparnon said the pumps performed as they typically do at the bedside for flow rates ranging from roughly 5 to 300 mL per hour—rates that are sufficient for most infusions, she noted. “However, at both ends of the spectrum is where we get problems, specifically with alarms.” At flow rates below 5 mL per hour and with long tubing sets, she explained, pumps were slow to detect occlusions close to the patient, thus delaying alarms. On the other hand, with flow rates above 300 mL per hour, fluid pushed through the low-volume and small-diameter microbore tubing can lead to higher downstream resistance and more frequent occlusion alarms. “At either end of the spectrum, there’s the risk of the patient not getting the medication they need,” Ms. Sparnon said, noting that it is impractical for busy nurses to attend to frequent alarms. A challenge that comes with using microbore extension sets is that when small-volume infusions are administered, much of the drug can remain in the tubing and needs to be flushed when the infusion is complete, according to ISMP’s Michelle Mandrack, MSN, RN. “It’s really important to know the total volume of the bag to make sure you get all the drug to the patient access site,” she stressed. Using extension sets also can affect infusions that require titration, she said, noting that “if titrations are done more proximal to the pump in the hallway and there is a long extension of tubing, there can be delays in the effect of the

Photo courtesy of Lehigh Valley Health Network, Allentown, Pa.

titration. So you might consider placing these types of infusions closer to the patient.”

A Limit on Double Checks Perhaps one of the most important consequences of placing infusion pumps in the hallway is the potential to compromise the safety of the medication administration process, Ms. Mandrack said. “The independent double-check process for high-alert medications has definitely been impacted by this practice,” she noted. “The separation of infusion pumps from the patient at their bedside has frequently limited these double checks to verifying the medication, concentration and dose, and pump setting but not the patient’s barcode bracelet.” A number of hospitals are labeling the pump itself with the patient’s name and date of birth as well as scanning a “proxy bracelet,” a duplicate patient-barcoded bracelet that two nurses have verified is an exact match to the bracelet the patient is wearing, Ms. Mandrack noted. However, she cautioned that “this proxy situation carries its own risks, particularly when you’re using mobile infusion poles and the bracelet may be accidentally left on the pole after it’s been transferred for use for another patient.” —D.W.

Clinical

Pharmacy Practice News • September 2020

COVID-19 Pandemic

Not Yet Sweet on Wormwood for COVID-19

hardy and prolific plant known as sweet wormwood, or Artemisia annua, contains a potent ingredient that could become a new medicinal weapon in the battle to stem the COVID-19 pandemic. Or it could be just one more promising treatment that showed strong antiviral activity in the laboratory but failed in human trials against an implacable foe. That question is what investigators at the University of Kentucky (UKY) are determined to answer. They are about to launch two new clinical trial arms to test whether an extract from the dried leaves of Artemisia brewed in tea or coffee, or the tablet form of the antimalarial drug artesunate—also derived from sweet wormwood—are effective in newly diagnosed COVID-19 patients with cancer or other comorbid conditions that put them at high risk for severe disease. The two trial arms will be integrated into the larger COVID-19 research program begun in early May by the UKY’s Markey Cancer Center, College of Medicine and College of Pharmacy, according to Jill Kolesar, PharmD, coleader of Markey’s Drug Development Program. A time line for the two trials is hard to predict: “It all depends on how much COVID-19 infection we have in Kentucky,” Dr. Kolesar said. If Artemisia leaves or artesunate proves effective, ramping up production would not be difficult, she noted. The plant has long been available as an over-the-counter folk remedy for fever, inflammation and malaria. The injectable and oral formulations of artesunate, although not approved in the United States, have been used worldwide for years to treat malaria. Dr. Kolesar said an extract from the sweet wormwood plant is also under investigation for cancer. “It’s in the regulatory approval process.” C. Michael White, PharmD, the department head and a professor at the University of Connecticut School of Pharmacy, in Storrs, said he applauded “all researchers looking for new candidate treatments against SARS-CoV-2. We desperately need drugs that can prevent COVID-19 infection or make the illness less severe.” Dr. White noted the availability of only two therapies—dexamethasone, “which modestly reduces mortality in the sickest patients, and remdesivir, which modestly speeds recovery in the moderately ill. We have nothing for COVID-19 prophylaxis and nothing to stop newly infected patients from needing hospitalization.” He added: “As our group found in our Annals of Internal Medicine review [doi.org/10.7326/

M20-2496] and in results of trials stopped prematurely, other antimalarial drugs [hydroxychloroquine and chloroquine] with in vitro efficacy against SARS-CoV-2 have had lackluster effects in prevention and provide no benefits in treating COVID-19.” Dr. White pointed out that the in vitro environment “has many substantial differences from the human environment. The three-dimensional structure of

human tissues, the impact of blood flow, confounders from other endogenous and ingested exogenous substances in the body, and cell lines that have key dissimilarities from actual human tissues can all explain why in vitro results may not ultimately drive human effects,” he noted, citing a paper he co-authored in The Journal of Clinical Pharmacology (doi.org/10.1002/jcph.1569). “So it warrants human study,” Dr.

White said, “but we should be cautious about promoting its benefits.” —Bruce Buckley

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26 Technology

Pharmacy Practice News • September 2020

COVID-19 Pandemic

Is Diversion an Overlooked Concern During COVID-19? A

rrests for thefts of personal protective equipment (PPE), ventilators, hydroxychloroquine and opioids from health care facilities are beginning to surface in the United States. According to some security experts, the diversions may be an unrecognized offshoot of the unprecedented scramble to cope with the COVID-19 pandemic that continues to spike in hot spots across the nation. Consider these reports as a case in point: • The U.S. Attorney for the Southern District of Indiana charged a cleaning crew member at the Central Indiana Cancer Center, in Indianapolis, and accomplice, with the theft of 30 carpujects of morphine from a restricted medication storage area as well as PPE, including seven boxes of isolation masks, 50 tubs of disposable wipes, 10 containers of soap, 20 bottles of hand sanitizer, eight bottles of hand deodorizer, and six tubs of bleach wipes. • A pharmacy technician was charged with the theft of more than 700 hydroxychloroquine tablets and azithromycin from Harbor-UCLA Medical Center in West Carson, Calif. • A respiratory therapist from the Veterans Affairs Medical Center in Seattle was arraigned on Aug. 6 for theft of government property of one portable Philips ventilator, one bronchoscope and one WatchPAT sleep apnea detection device, each valued at more than $1,000.

• A hospital warehouse manager was arrested for the theft of 100 N95 masks from the Del Sol Medical Center warehouse in El Paso, Texas. These are among the “dozens” of COVID-19–related diversion leads that chairman Tom Knight said he’ll post to his nonprofit HealthcareDiversion.org website in the next few months, after independently verifying them with public information from law enforcement sources, criminal proceedings, media reports, or physician, nurse and pharmacist state licensing boards. (See sidebar on his verification process.) Hospitals spending more energy on COVID-19 instead of diversion are more vulnerable, said Charlie Cichon, the executive director of the National Association of Drug Diversion Investigators (NADDI), which trains law enforcement, state licensing board members and hospital staff each year. “Has diversion stopped? Absolutely not. Until a hospital sets up a team diversion program involving pharmacy, nursing, physicians, human resources and a team investigator, they’ll unfortunately find there’s more going on.” At Upstate University Hospital, in Syracuse, N.Y., the COVID-19 peak reached 50 patients, according to Derek Empey, RPh, MSHI, a clinical informatics pharmacist for controlled substance compliance and analytics. The 800-bed two-campus health system tracks opioids, COVID-19 medications and PPE,

and “treats them all as controlled substances at this time. We review electronic documentation and fluctuations in patients’ pain scores [an indication of possible painkiller diversion], and speak with nurses about what they’ve seen,” added Mr. Empey, who also serves as Upstate’s drug diversion program manager. Despite limiting access to COVID-19 patient rooms to minimize spread and conserve masks and gowns— which means fewer checks and less drug waste witnessing—Mr. Empey said he is aware of “an uptick in pain scores” at his institution. But he stressed that the uptick could be due “to increased acuity in our COVID-19 patients,” rather than the theft of controlled substances, so more investigation is needed. “We’re also investigating a couple of peculiar events with fentanyl PCAs [patient-controlled analgesics],” he said.

HealthcareDiversion.org Database In reviewing the HealthcareDiversion.org database of incidents, coupled with quarterly exchanges with his multidisciplinary advisory board and cooperative entities—such as the

‘Has diversion stopped [during COVID-19]? Absolutely not. Until a hospital sets up a team diversion program involving pharmacy, nursing, physicians, human resources and a team investigator, they’ll unfortunately find there’s more going on.’ —Charlie Cichon

How Posts Land on HealthcareDiversion.org

he HealthcareDiversion.org website allows anonymous entries of diversion incidents. Yet, unlike on social media, none appear as posts until the team or its 18-member board of advisers independently verify entries through public records. These include state medical, pharmacy and nursing licensure board proceedings, as well as criminal indictments or prosecutions published by the Department of Justice, state or local authorities, and media reports, explained chairman Tom Knight. More than 90% of the website’s posts come from his team’s and volunteer multidisciplinary board’s own research and networking efforts for leads, which they then verify before posting. Less than 10% come from individual submissions. Mr. Knight said he discards one-third to one-half of them because he is unable to verify entries. All sources combined feed him reports from major metropolitan areas and all 50 states. The site launched with 300 posts on May 1, 2019, and now has 459 posts. Mr. Knight said he’s in preliminary talks with state boards, law enforcement authorities and organizations such as the National Association of Drug Diversion

Investigators (NADDI) and International Health Facility Diversion Association, so leads will flow in and lessen his need for an initial search. The vast majority of publicly verified posts name a health care facility where an incident occurred. In more than one year of operation, no facility has pushed back, sought a correction, sued, or threatened to sue him for any reason related to this website, Mr. Knight noted. In early August 2020, the website redacted the name of an individual from a drug diversion post after confirming that “all court documentation had been expunged,” he said. Posts typically include a link to the source or sources used to verify the incident. “The information on this website is a win-win for law enforcement, health care facilities and the public,” said Charlie Cichon, NADDI’s executive director. “We know perpetrators keep hopping from hospital to hospital, and even move across state lines. If a post doesn’t name an individual, the website still maps incident locations and makes patterns visible to help us prevent more diversion.” —A.H.

International Health Facility Diversion Association (www.ihfda.org) and NADDI (www.naddi. org)—Mr. Knight has observed a diversion trend that he believes is critical for hospitals to heed: “If health care workers who divert in a large hospital think they may get caught, they’ll switch to where there’s less surveillance—even transfer within the same health system to a nursing home, small ambulatory center, home health care or hospice division,” he said. “We see they either quit or were fired, then a year or two later were caught again taking the patient’s medications.” Mr. Empey urged alertness to “even minor blips on your diversion radar for proper vetting and follow-up” because COVID-19 lowers a hospital’s daily census by 30% to 40% in some cases [due to lack of elective surgeries].” By default, he added, “this will lower total removals of controlled substances and potentially mask diversion patterns that would otherwise be more apparent via reporting and analytics.”

Counterfeiting Remains A Concern Diversion isn’t the only illegal activity health systems need to heed during the turmoil and disrupted workflow of COVID-19. Counterfeiting is another area of concern, Mr. Cichon noted. He explained that states and hospitals pursuing PPE and COVID-19 treatments in short supply face risks for inadvertently buying counterfeit products. “There’s a lot of federal and state money out there that scammers want. It doesn’t surprise me at all that criminals would move into the theft of pharmaceuticals and PPE, where jail time is less if they’re caught,” said Mr. Cichon, who used to run counterfeit drug investigations in the Americas for Eli Lilly and Co. As of June 1, the Department of Homeland Security announced its Customs and Border Protection division had seized approximately 750,000 counterfeit face masks in 86 incidents, 107,300 FDA-prohibited COVID-19 test kits in 301 incidents, and 11,000 FDAprohibited chloroquine tablets in 91 incidents. —Al Heller The sources reported no relevant financial relationships.

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