Pharmacy Practice News (October 2020) by McMahon Group

See ADVER RTISERS IND DEX polybagged with h this issue e

The Best-Read Pharmacist’s News Source

pharmacypracticenews.com

The power—and peril—of protein in the ICU ..........................

An urban medical center tackles the opioid crisis .....................

OPERATIONS & MGMT

Ambulatory pharmacists provide value during COVID-19 ......................... 26

POLICY

Talking turkey about reimbursement .............

Amid COVID-19, challenge of DIY 503B continues ............

TECHNOLOGY

CSTDs: Tips for product selection and review ......................

SPECIALTY PHARMACY

A $500K windfall from biosimilars ...........

REVIEW ARTICLE

Biosimilars in Oncology The Role of Pharmacists In Education: Part 3 of 3 See page 18.

Overworked staff, lax medication handling among risk factors seen

CLINICAL

Outpatient antibiotic stewardship spreads its wings ...........................

Volume 47 • Number 11 • November 2020

‘Pandemic Nursing’ Is a Lethal Problem; ISMP Cites ‘Blame and Shame’ Culture A

dd “pandemic nursing” to the list of COVID-19 threats to medication safety. The practice pressure has led to at least one lethal drug error in a hospital scrambling to cope with a surge in cases, according to a new report from the Institute for Safe Medication Practices (ISMP). The ISMP’s Medication Safety Alert included details about a nurse working at a hospital where the death occurred. “The nurse works in a busy ICU treating about 20 COVID-19 patients daily, most of whom have multiple high-alert medication infusions (e.g., fentaNYL, propofol, norepinephrine, cisatracurium) administered via smart infusion pumps located inside their rooms,” the newsletter reported.

Accreditors Ease Off Rules Amid COVID-19

eading accreditation bodies for specialty pharmacy have modified their procedures and requirements for initial accreditation and ongoing reporting in response to the COVID-19 pandemic, according to presentations at the National Association of Specialty Pharmacy 2020 Annual Meeting & Expo. “Something we’ve become fond of saying is ‘normal processes are for normal times,’” said Jon Pritchett, PharmD, a program director at the Accreditation Commission for Health Care (ACHC). “At the end Continued on page 42

The care provider described an under-resourced environment, high patient-to-nurse ratios, and stashes of medication infusions left in patients’ drawers and closets—an aggregation of risk factors that led to wrong-concentration and titration errors, including Continued on page 6

Automated Dose Rounding Yields $3.6 Million in Savings I ntegrating an automatic dose-rounding policy into an electronic health record (EHR) system can lead to millions in cost savings on oncology infusions, according to an abstract presented at the Hematology/ Oncology Pharmacy Association (HOPA) 2020 virtual conference. Researchers at Michigan Medicine developed a system that automatically rounded doses that were within 10% of the nearest vial size when physicians placed electronic orders for infusions of monoclonal antibodies and cytotoxic agents. Over one year, the system led to approximately $3.6 million in savings on two dozen high-cost oncology medications. Now, the system has become

Special Focus:

COVID-19 Pandemic More coverage on pages 4, 12, 14, 26, 34, 38, 40.

routine at Michigan Medicine, according to the study authors. “Like all organizations that treat cancer patients, we continue to see the cost of cancer drugs increase over time,” said Shannon Hough, PharmD, BCOP, the pharmacy manager of oncology clinical programs at Michigan Medicine, in Ann Arbor, and a co-author on the study. The average FDA-approved therapy is significantly more expensive now than it was 10 years ago, she said. “So, anytime we have the opportunity to modulate some of those costs, both for us and for our patients, we’d like to work on those things.” Continued on page 39

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Up Front

Pharmacy Practice News • November 2020

Letters

Clarification on Dilution of Rabies Treatment A

supplement to Pharmacy Practice News, a Special Report, titled “Rabies Post-Exposure Prophylaxis: A PatientCentric Approach to Care,” contained information that needs to be clarified. Page 4 of the supplement includes the following text: “The 300-IU/mL HyperRab® can be diluted as needed, if a larger volume is required to appropriately infiltrate multiple wounds. If dilution is required, using dextrose 5% in water (D5W) is recommended by the manufacturer (HyperRab [prescribing information] Grifols Therapeutics LLC; 2018). The 2 lower potency 150IU/mL HRIG products—KEDRABTM (rabies immune globulin [human]) (KEDRION Biopharma) [and] rabies immune globulin (human) USP, heat treated, Imogam® rabies-HT (Sanofi Pasteur)—also can be diluted with D5W if needed” (Vaccine 2018;36[37]:5500-5505; KEDRAB [prescribing information]. Kedrion Biopharma Inc.; 2017; Imogam [prescribing information]. Sanofi Pasteur; 2014). Following further review, it was determined that the package inserts for Imogam and KEDRAB contain no instructions for further dilution. Responding to a request for

clarification, Sanofi medical information noted that dilution is not discussed in the Imogam package insert and is not recommended. “Sanofi does not recommend the use of Imogam RabiesHT in a manner that is inconsistent with the approved product labeling”; however, the company points out that the World Health Organization recommendations state that “rabies immunoglobulins can be diluted if necessary, with physiological buffered saline to ensure

the infiltration of large and multiple wounds” ( Sa n o f i Me d i c a l Information, personal communication). Also responding to a request for information, a clinical support representative from Kedrion noted that section 3 of the KEDRAB full prescribing information states that “KEDRAB is supplied in singleuse vials containing 2 mL or 10 mL of ready-to-use solution with a nominal potency of 150 IU/mL.” The representative wrote that “Kedrion Biopharma does not recommend dilution of the KEDRAB ready-to-use solution, as there have been no studies done to determine how KEDRAB would interact with D5W. We also do not know if KEDRAB would remain efficacious if diluted with D5W, and since the consequences of rabies can be dire without adequate treatment, we suggest that all such dilution cases be treated as adverse events” (Lorena Rodriguez, RN, personal communication).

EDITORIAL BOARD

In a revised version of the supplement, now available for download on pharmacypracticenews.com, the text has been updated to read: “Dilution is not recommended for the 2 lower potency 150-IU/mL HRIG products— KEDRAB™ (rabies immune globulin [human]) (Kedrion Biopharma) and rabies immune globulin (human) USP, heat treated, Imogam® rabies–HT (Sanofi Pasteur).” Portions of this clarification were written with the help of Jerry Siegel, PharmD, vice president of business development and managing partner, Safe Medication Management, in East Greenwich, RI. Siegel also is a clinical associate professor in The Ohio State University College of Pharmacy, in Columbus, Ohio.

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4 Clinical

Pharmacy Practice News • November 2020

COVID-19 Pandemic

Countering COVID-19’s Thromboinflammation E

ven before Yale New Haven Hospital, in Connecticut, started receiving an influx of COVID-19 patients this spring, staff there heard from colleagues in New York City about some unexpected complications from the causative virus. Chief among them was multisystem inflammatory syndrome (MIS). The syndrome, characterized by fever, systemic inflammation and organ dysfunction (Ann Intern Med 2020 Jul 29. doi: 10.7326/L20-0882), also can lead to vascular damage. “Going from hearing about MIS in young adults to seeing it was jaw-dropping,” said Ralph Riello III, PharmD, BCPS, a clinical pharmacy specialist with the cardiac ICU at the hospital. “We had some 27- and 28-year-old patients with no past medical history, and certainly no cardiac history, coming in with COVID-19 and clots in both ventricles in their heart or pulmonary embolism in their lungs,” Riello said, noting that at age 31, he had never managed patients younger than himself in the cardiac ICU. “These patients were otherwise healthy. The only thing that changed about their medical history was they had, unfortunately, contracted COVID-19.”

Multiple Organ Involvement Reviewing some case reports on MIS prompted Paul Dobesh, PharmD, to write an article for the journal Pharmacotherapy (in press) on the coagulopathy and thrombotic potential associated with COVID-19. It’s becoming clear that some patients have an inflammatory response to COVID-19 that affects multiple organs, said Dobesh, a professor of pharmacy practice and science at the University of Nebraska Medical Center, in Omaha. “Most people think of COVID-19 as a pulmonary infectious process, but it is just as much a thrombotic process,” he said. “A lot of people die from pulmonary embolism when you actually dig deep into their cause of death, as opposed to pure respiratory failure.” Sometimes that’s hard to separate, Dobesh added, because someone who has a big pulmonary embolism also will have respiratory failure. Because the significant inflammatory response coincides with thromboses, some clinicians are using the terms immunothrombosis or thromboinflammation. “They are clearly tied together in these patients,” he said. Treating affected patients has been a challenge, Riello and Dobesh said. Studies have reported mixed results using full-dose therapeutic anticoagulation (J Thromb Haemost 2020;18[5]:10941099; J Am Coll Cardiol 2020;76[1]:122124). Some critically ill patients have high rates of venous thrombotic disease despite receiving standard doses of

venous thromboembolism (VTE) prophylaxis, Dobesh said. Complicating matters is the fact that nearly everything reported so far are observations, so it’s unclear whether patients who do poorly on a particular therapy also have comorbidities or are sicker than others. “We don’t know if there is a difference in the regimen they received or in the patients getting the regimen, which makes it all very difficult to interpret and determine how to step forward with providing the best care,” Dobesh said. A recently published, small, randomized controlled trial provides some support for therapeutic dosing (see “Small Trial Looks at Anticoag Dosing for COVID-19 Patients,” page 12), but larger controlled trials are needed. Until results from such trials are available, the American Society of Hematology (ASH) is recommending a conservative approach. On Oct. 8, ASH released draft guidelines recommending use of “prophylactic-intensity over intermediate-intensity or therapeuticintensity anticoagulation” for patients with acute or critical illness related to COVID-19 “who do not have suspected or confirmed VTE” (bit.ly/3nv40Zk). However, these draft recommendations are “conditional” and “based on very low certainty in the evidence about effects.” The guidelines will undergo public and internal ASH review over the next two months.

Stratifying Patient Risk: Biomarkers and Lab Tests Riello and his colleagues, understanding the risks for not just VTE but also for arterial thromboses including myocardial infarction and stroke, developed anticoagulation protocols specifically for COVID-19 patients. Instead of using a standard approach for all patients, the team chose to use biomarkers and lab test

results to help stratiffy patients based on risk as much as possible, Riello said. They rely heavily on the D-dimer blood test, which measures small protein fragments produced by dissolved blood clots. “It’s indicative of any coagulation activation going on,” Riello said. “It’s kind of like the calm before the storm, so if that’s elevated, you have a really good idea of the risk of thrombosis for that patient.” The team developed an algorithm that uses these test results. Anyone who had COVID-19 with normal lab results receives standard prophylaxis with lowdose heparin or enoxaparin. Patients with COVID-19 and elevated lab findings are given intermediate-dose prophylaxis, and those with a high clinical suspicion of an active thrombus receive full-dose prophylaxis. They repeat the lab tests before patients are discharged to determine who needs to stay on anticoagulation therapy for an extra month or so at home. They also meet with patients to explain their continued risk and need to remain on therapy, and they use telehealth visits to check on patients within a week after discharge. Because of the unprecedented nature of the pandemic, the team decided to make their protocol publicly available, including their approach to anticoagulation and justifications for updates (bit.ly/3npo9jo). At his center, Dobesh recommends standard-dose prophylaxis, such as 40 mg of enoxaparin daily for all hospitalized patients with COVID-19; however, critically ill patients in the ICU would get an intermediate dose of 40 mg twice daily, or 0.5 mg/kg. Extended prophylaxis to reduce the incidence of VTE has been studied in clinical trials, he said, including the APEX trial with betrixaban (Bevyxxa,

Portola) (N Engl J Med 2016;375:534-544) and the MARINER trial with rivaroxaban (Xarelto, Janssen) (N Engl J Med 2018;379:1118-1127). Although those studies were conducted before the COVID-19 pandemic, Dobesh said, “if you look at the inclusion criteria, most COVID patients would have been in these trials,” so clinicians should consider extended prophylaxis for appropriate patients. He also cautioned about the use of low-molecularweight heparin in outpatients because it is associated with more bleeding.

Skin Rashes May Be a Marker As clinicians wrestle with determining the best strategies to prevent thromboembolism in COVID-19 patients, a recent report found some skin rashes to be a possible sign of coagulopathies (JAMA Dermatol 2020. doi: 10.1001/jamadermatol.2020.2800). If that can be validated as a precursor for blood clotting events, that finding, along with D-dimer and C-reactive protein measures of inflammation, could provide a well-rounded approach to identifying high-risk patients. Skin rashes also may be a sign to switch patients from preventive treatment to at least intermediate dosing before a complication occurs, Riello said. “It’s remarkable how much we’re learning about this disease as time goes on,” he said. “If there is [a significant increase in COVID-19 cases] this fall before a vaccine is FDA approved and widely available, I’m hoping we can take all this information we learned and really apply it for emergency preparedness.” —Karen Blum Dobesh reported a financial relationship with Janssen and Portola. Riello reported a financial relationship with AstraZeneca, Janssen and Portola.

New data support therapeutic doses of enoxaparin in COVID-19 patients: See page 12

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6 Clinical

Pharmacy Practice News • November 2020

Medication Safety

Pandemic Nursing continued from page 1

at least one that resulted in a patient’s death. Overall, the nurse described a blame-and-shame culture in the face of these errors that runs counter to the c “just culture” approach to ap

medication errors that has been championed in health care over the past decade. “This is the most troubling part of the report,” said Steven Meisel, PharmD, the director of patient safety at Fairview Health Services, based in Minnesota. “The nurse felt like he wasn’t

being heard and that there were issues with escalation of concerns. That’s not a problem specific to COVID, although COVID may have been the precipitant. It’s a culture-of-safety problem.” Clinicians at other institutions have told ISMP that COVID-19 has strained their safety culture, too, said Judy Smetzer, BSN, RN, an ISMP vice president and the co-author of the newsletter that reported on this problem of “pan-

7 Tips: Avoiding Rx Errors During COVID-19 Standardize to a single concentration of IV high-alert medication infusions whenever possible. Standardize the dose-rate (mcg/kg per hour vs. mg per hour) for certain IV infusions, ensure only these standard dose-rates are available as a choice in smart pump drug libraries, and require the use of standardized order sets. For common infusions, use premixed, commercially available solutions that are visually distinct, whenever possible.

6 Tips:

Affix bold auxiliary labels to critical care infusions when dispensing a nonstandard concentration or a neuromuscular blocking agent (e.g., “Warning: Paralyzing Agent,” “Patient Must Be Ventilated”).

Steering Clear of Remdesivir Trouble

he investigational drug remdesivir (Veklury, Gilead), which was approved by the FDA on Oct. 22, had been used through an emergency authorization (EAU) since May. Since that EAU was issued, the FDA has received several reports of medication errors with the antiviral, involving wrong formulation, wrong preparation and incorrect storage. The Institute for Safe Medication Practices cautions hospitals and providers to follow several steps to avoid these types of errors:

Label all IV lines between the smart pump and source container, and close to the access point of the patient’s body; trace the line prior to hanging a new source container or programming a pump.

Refer to the remdesivir prescribing information (bit.ly/3mcNT19) and EUA Fact Sheet (bit.ly/3koxLcd) for details about remdesivir use. Use standardized order sets to guide the selection of the appropriate formulation and to ensure it is specified in each order. For pediatric patients weighing 3.5 kg to less than 40 kg, only use remdesivir for injection (lyophilized powder). Remdesivir injection (concentrated solution) is only for use in adults and pediatric patients who weigh 40 kg or more. Provide clear, step-by-step instructions for reconstitution and dilution of remdesivir. Ensure proper storage of each formulation before and after dilution. Unopened remdesivir for injection (lyophilized powder) vials can be stored at room temperature, whereas remdesivir injection (concentrated solution) vials should be stored at refrigerated temperature but must be brought to room temperature (up to 12 hours) before dilution. Once prepared, diluted remdesivir solutions can be stored up to four hours at room temperature or up to 24 hours refrigerated. Consider putting an alert in computerized order entry systems, as well as a possible hard stop requiring entry of the patient’s actual weight, for orders of remdesivir injection (concentrated solution). Warning labels in storage areas alerting staff that this formulation is “ONLY for patients weighing 40 kg or more” also are advised. Update order forms and electronic systems to include both the proprietary (Veklury) and generic (remdesivir) names.

Establish a process for conducting independent double checks before administering certain critical infusions.

demic nursing”—but she said there were fewer reports than expected. “We have not heard a lot through our standard reporting mechanisms about pandemic-related errors, but some people we have heard from said that in many cases they just didn’t have time to report, even internally, because they were so overwhelmed,” she said. “If you look at pictures of the hallways with all the smart pumps outside, you can see how an error could happen. You could switch the pumps accidentally or think you’re titrating one drug when you’re actually titrating another. A number of places have abandoned independent double checks that they used to use, and might not be catching some of these things in a rushed and hectic environment.” Pharmacists can be instrumental in streamlining the error reporting process and participating in daily safety huddles, Smetzer said. “They often have great ideas on how to impact safety in nursing practice. When they hear about some

Conduct daily safety huddles with physicians, pharmacists and nurses. ISMP, Institute for Safe Medication Practices

of these issues, they often say, ‘I can fix that. I can put a sticker on. I can put an auxiliary label on. We can send it out differently.’ Involving the pharmacist in these huddles can be eye-opening.”

A Boost From Reviewing The Workflow The ISMP report also profiled a health system that has taken steps to address COVID-19 practice pressures. At the beginning of the pandemic, the University of Maryland Medical Center, in Baltimore, established a process to review relevant workflow changes and patient safety events per the hospital’s Medication Safety Council. The interdisciplinary committee focuses its see PANDEMIC NURSING, page 8

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8 Clinical

Pharmacy Practice News • November 2020

Medication Safety

PANDEMIC NURSING continued from page 6

efforts on identifying risk mitigation strategies to minimize potential medication errors. “It was very stressful, especially at the beginning, when we knew so little. Our top priority was to protect our patients and our staff and minimize potential risks for exposure,” said Glorimar Rivera, PharmD, a medication safety clinical pharmacy specialist who served as the pharmacist

in charge of the state’s Baltimore Convention Center Field Hospital. As recommended in the ISMP newsletter (see box, page 6), the University of Maryland facility standardized to a single concentration for highalert medications whenever possible. “Standardizing the hospital formulary to include one concentration of certain medications, especially those that are high-alert, is one of the risk mitigation strategies that can be implemented to prevent medication errors associated with the administration of

the wrong concentration of a medication,” Rivera said.

Keeping Smart Pumps Inside the Room However, neither Fairview nor the University of Maryland has adopted the practice used in some institutions of placing IV pumps outside the rooms of COVID-19 patients to limit staff exposure to infected patients. “We considered but never accepted that approach, because we thought the downside was too great and potentially created

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more problems than it solves,” Meisel said. “Beyond potential medication errors, you have issues with negative airflow when you drill holes in the rooms; there are tripping hazards; and the additional extension tubing puts more pressure on the supply chain.” (For a health system that has succeeded in developing a safe method for placing pumps outside patient rooms, see bit.ly/3os0K1s-PPN.) A measure that the University of Maryland facility did adopt to reduce staff exposure to COVID-19 patients was to temporarily eliminate the requirement for two nurses to dually sign the administration of medications that are not high alert. “For noncritical medications, we decided to remove the requirement of nurses to have witnesses when documenting the administration of certain medications to minimize the risks of exposure to the virus, and ensure the safety of our staff and our patients,” Rivera said.

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Pharmacists can play a key role in identifying ways that independent double checks can still happen when needed, while reducing unnecessary exposure to the virus, ISMP’s Smetzer said. “We recently talked with a pharmacist who was working with their nursing partners to develop the optimal process for setting up barcode scanning so that it could be conducted inside of isolation rooms. They ended up putting duplicate ID bands outside the room and inside the room, so that there could be an independent double check without that other person entering the room.” Health systems also can take steps to ensure their prescribers are heeding any safety alerts about medications that have received an emergency use authorization from the FDA, such as remdesivir (Veklury, Gilead), which until its approval on Oct. 22 was only available through an EUA (see sidebar, page 6). “We haven’t seen errors with the use of remdesivir in our institution so far,” Rivera noted. “This medication is restricted, and we established a process to allow only one clinician—a pharmacist specialized in infectious diseases—to order remdesivir for patients who meet the criteria to receive this medication. That minimizes errors in the ordering phase.” Baltimore Convention Center Field Hospital also has established a process to monitor the inventory of remdesivir “and all doses that are compounded in the pharmacy,” Rivera said. “The technology we use during the compounding phase of the medication allows us to ensure that it is prepared correctly.” —Gina Shaw The sources reported no relevant financial relationships.

n n, s

h ea

Clinical

Pharmacy Practice News • November 2020

Cardiology

More Heartache for Patients With Infections

n 2012, the FDA issued a warning for azithromycin, linking the antibiotic to cardiac events. However, a new study found that it might not be azithromycin itself, but how it is combined with other medications that could affect the electrical functioning of the heart and increase cardiac events. “We found that when taken together with drugs that affect the electrical impulses of the heart, the combination is linked with a 40% increase in cardiac events, including fainting, heart palpitations and even cardiac arrest,” said Haridarshan Patel, PharmD, a researcher in the Department of Pharmacy Systems, Outcomes and Policy at the University of Illinois at Chicago College of Pharmacy. The QT-prolonging drugs include antihypertensives; antipsychotics; some antidepressants and fluoroquinolones; antimalarial drugs, such as hydroxychloroquine and chloroquine; opioid medications; and muscle relaxants (JAMA Netw Open 2020;3[9]:e2016864). “Because QT-prolonging drugs are used so commonly, our findings suggest that doctors prescribing azithromycin should be sure that patients are not also taking QT-prolonging medications,” Patel said. In a previous study, Patel and his colleagues found that one in five people prescribed azithromycin also were taking a QT-prolonging drug.

4-Million Patient Database Previous studies looking at azithromycin and cardiac events examined populations that tend to be older and have more health issues, including Medicaid patients and veterans. But in this study, the researchers used the Truven Health Analytics MarketScan database, which contains medical data on millions of patients in the United States with a mean age of 36 years. The risk for cardiac events with azithromycin was evaluated against amoxicillin, another antibiotic that has never been linked to cardiac events and does not affect the QT interval. The team looked at data from more than 4 million patients enrolled in private health insurance plans who were hospitalized or visited an emergency department for a cardiac event between 2009 and 2015 and who started taking either amoxicillin or azithromycin within five days of their hospital visit. There were approximately 2 million episodes in each group. Cardiac events included ventricular arrhythmias, fainting, palpitations, cardiac arrest and death. “Drugs often prolong QT interval but may not necessarily result in cardiac events and self-resolve over time,” Patel said. “We looked at events that led to emergency department visits or hospitalizations in this study.”

Among patients taking azithromycin and a QT-prolonging medication, the risk for cardiac events was

40% higher compared with amoxicillin alonea a

95% CI, 1.04-1.87

Source: JAMA Netw Open 2020;3[9]:e2016864.

Patel and his colleagues found that the likelihood of cardiac events with azithromycin compared with amoxicillin was not significantly higher at five days (odds ratio [OR], 1.08; 95% CI, 0.98-1.20) and 10 days (OR, 1.05; 95% CI, 0.97-1.15), and these events actually were quite low or rare in both groups, with the most common cardiac events including fainting and palpitations. However, among patients taking both a QT-prolonging medication and azithromycin together, the risk for cardiac see HEARTACHE, page 17

BUILT TO WEATHER POSTSURGICAL PAIN Non-opioid EXPAREL, powered by DepoFoam® technology, delivers precise pain control to help enhance recovery through the critical ﬁrst few days after surgery.1,2

Go to www.EXPAREL.com to learn why surgeons and anesthesiologists have trusted EXPAREL more than 7 million times.3 Indication

Warnings and Precautions for Bupivacaine-Containing Products

EXPAREL is indicated for single-dose inﬁltration in adults to produce postsurgical local analgesia and as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia. Safety and efﬁcacy have not been established in other nerve blocks.

Central Nervous System (CNS) Reactions: There have been reports of adverse neurologic reactions with the use of local anesthetics. These include persistent anesthesia and paresthesia. CNS reactions are characterized by excitation and/or depression. Cardiovascular System Reactions: Toxic blood concentrations depress cardiac conductivity and excitability which may lead to dysrhythmias, sometimes leading to death. Allergic Reactions: Allergic-type reactions (eg, anaphylaxis and angioedema) are rare and may occur as a result of hypersensitivity to the local anesthetic or to other formulation ingredients. Chondrolysis: There have been reports of chondrolysis (mostly in the shoulder joint) following intra-articular infusion of local anesthetics, which is an unapproved use. Methemoglobinemia: Cases of methemoglobinemia have been reported with local anesthetic use.

Important Safety Information EXPAREL is contraindicated in obstetrical paracervical block anesthesia. Adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via inﬁltration were nausea, constipation, and vomiting; adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via interscalene brachial plexus nerve block were nausea, pyrexia, and constipation. If EXPAREL and other non-bupivacaine local anesthetics, including lidocaine, are administered at the same site, there may be an immediate release of bupivacaine from EXPAREL. Therefore, EXPAREL may be administered to the same site 20 minutes after injecting lidocaine. EXPAREL is not recommended to be used in the following patient population: patients <18 years old and/or pregnant patients. Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease. Warnings and Precautions Speciﬁc to EXPAREL Avoid additional use of local anesthetics within 96 hours following administration of EXPAREL. EXPAREL is not recommended for the following types or routes of administration: epidural, intrathecal, regional nerve blocks other than interscalene brachial plexus nerve block, or intravascular or intra-articular use. The potential sensory and/or motor loss with EXPAREL is temporary and varies in degree and duration depending on the site of injection and dosage administered and may last for up to 5 days, as seen in clinical trials.

For more information, please visit www.EXPAREL.com or call 1-855-793-9727. Please refer to brief summary of Prescribing Information on adjacent page. References: 1. Lambert WJ, Los K. DepoFoam® multivesicular liposomes for the sustained release of macromolecules. In: Rathbone MJ, Hadgraft J, Roberts MS, Lane ME, eds. Modiﬁed-Release Drug Delivery Technology. Vol 2. 2nd ed. New York, NY: Informa Healthcare USA, Inc; 2008:207-214. 2. Gorﬁne SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2011;54(12):1552-1559. 3. Data on File. 6306. Parsippany, NJ: Pacira BioSciences, Inc.; July 2020.

10 Clinical

Pharmacy Practice News • November 2020

Nutrition

The Power—and Peril—of Protein in the ICU

elivering adequate protein to patients in the ICU is critical. But just how much protein to deliver, to which patients—and when—remains unclear, according to a presentation at the ASPEN20 Virtual Conference. “Emerging data suggest that protein requirements in critical illness are probably more important than energy or kilocalorie requirements,” said presenter Todd Rice, MD, an associate professor

Brief Summary (For full prescribing information refer to package insert) INDICATIONS AND USAGE EXPAREL is indicated for single-dose infiltration in adults to produce postsurgical local analgesia and as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia. Limitation of Use: Safety and efficacy has not been established in other nerve blocks. CONTRAINDICATIONS EXPAREL is contraindicated in obstetrical paracervical block anesthesia. While EXPAREL has not been tested with this technique, the use of bupivacaine HCl with this technique has resulted in fetal bradycardia and death. WARNINGS AND PRECAUTIONS Warnings and Precautions Specific for EXPAREL As there is a potential risk of severe life-threatening adverse effects associated with the administration of bupivacaine, EXPAREL should be administered in a setting where trained personnel and equipment are available to promptly treat patients who show evidence of neurological or cardiac toxicity. Caution should be taken to avoid accidental intravascular injection of EXPAREL. Convulsions and cardiac arrest have occurred following accidental intravascular injection of bupivacaine and other amide-containing products. Avoid additional use of local anesthetics within 96 hours following administration of EXPAREL. EXPAREL has not been evaluated for the following uses and, therefore, is not recommended for these types of analgesia or routes of administration. • epidural • intrathecal • regional nerve blocks other than interscalene brachial plexus nerve block • intravascular or intra-articular use EXPAREL has not been evaluated for use in the following patient population and, therefore, it is not recommended for administration to these groups. • patients younger than 18 years old • pregnant patients The potential sensory and/or motor loss with EXPAREL is temporary and varies in degree and duration depending on the site of injection and dosage administered and may last for up to 5 days as seen in clinical trials. ADVERSE REACTIONS Clinical Trial Experience Adverse Reactions Reported in Local Infiltration Clinical Studies The safety of EXPAREL was evaluated in 10 randomized, double-blind, local administration into the surgical site clinical studies involving 823 patients undergoing various surgical procedures. Patients were administered a dose ranging from 66 to 532 mg of EXPAREL. In these studies, the most common adverse reactions (incidence greater than or equal to 10%) following EXPAREL administration were nausea, constipation, and vomiting. The common adverse reactions (incidence greater than or equal to 2% to less than 10%) following EXPAREL administration were pyrexia, dizziness, edema peripheral, anemia, hypotension, pruritus, tachycardia, headache, insomnia, anemia postoperative, muscle spasms, hemorrhagic anemia, back pain, somnolence, and procedural pain. Adverse Reactions Reported in Nerve Block Clinical Studies The safety of EXPAREL was evaluated in four randomized, double-blind, placebocontrolled nerve block clinical studies involving 469 patients undergoing various surgical procedures. Patients were administered a dose of either 133 or 266 mg of EXPAREL. In these studies, the most common adverse reactions (incidence greater than or equal to 10%) following EXPAREL administration were nausea, pyrexia, and constipation. The common adverse reactions (incidence greater than or equal to 2% to less than 10%) following EXPAREL administration as a nerve block were muscle twitching, dysgeusia, urinary retention, fatigue, headache, confusional state, hypotension, hypertension, hypoesthesia oral, pruritus generalized, hyperhidrosis, tachycardia, sinus tachycardia, anxiety, fall, body temperature increased, edema peripheral, sensory loss, hepatic enzyme increased, hiccups, hypoxia, post-procedural hematoma. Postmarketing Experience These adverse reactions are consistent with those observed in clinical studies and most commonly involve the following system organ classes (SOCs): Injury, Poisoning, and Procedural Complications (e.g., drug-drug interaction, procedural pain), Nervous System Disorders (e.g., palsy, seizure), General Disorders And Administration Site Conditions (e.g., lack of efficacy, pain), Skin and Subcutaneous Tissue Disorders (e.g., erythema, rash), and Cardiac Disorders (e.g., bradycardia, cardiac arrest). DRUG INTERACTIONS The toxic effects of local anesthetics are additive and their co-administration should be used with caution including monitoring for neurologic and cardiovascular effects related to local anesthetic systemic toxicity. Avoid additional use of local anesthetics within 96 hours following administration of EXPAREL. Patients who are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics: Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic cyclophosphamide, flutamide, hydroxyurea, ifosfamide, agents rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine Bupivacaine Bupivacaine HCl administered together with EXPAREL may impact the pharmacokinetic and/or physicochemical properties of EXPAREL, and this effect is concentration dependent. Therefore, bupivacaine HCl and EXPAREL may be administered simultaneously in the same syringe, and bupivacaine HCl may be injected immediately before EXPAREL as long as the ratio of the milligram dose of bupivacaine HCl solution to EXPAREL does not exceed 1:2. Non-bupivacaine Local Anesthetics EXPAREL should not be admixed with local anesthetics other than bupivacaine. Nonbupivacaine based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more. There are no data to support administration of other local anesthetics prior to administration of EXPAREL.

of medicine in the Division of Allergy, Pulmonary and Critical Care Medicine at Vanderbilt University School of Medicine, in Nashville, Tenn. Both European and U.S. guidelines suggest giving patients sufficient, high doses of protein—between 1.2 and 2 g/kg of body weight per day. Yet both guidelines grade the quality of evidence to support this practice as low. For a healthy person, about 0.8 g/kg of body weight of protein

Other than bupivacaine as noted above, EXPAREL should not be admixed with other drugs prior to administration. Water and Hypotonic Agents Do not dilute EXPAREL with water or other hypotonic agents, as it will result in disruption of the liposomal particles USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary There are no studies conducted with EXPAREL in pregnant women. In animal reproduction studies, embryo-fetal deaths were observed with subcutaneous administration of bupivacaine to rabbits during organogenesis at a dose equivalent to 1.6 times the maximum recommended human dose (MRHD) of 266 mg. Subcutaneous administration of bupivacaine to rats from implantation through weaning produced decreased pup survival at a dose equivalent to 1.5 times the MRHD [see Data]. Based on animal data, advise pregnant women of the potential risks to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. Clinical Considerations Labor or Delivery Bupivacaine is contraindicated for obstetrical paracervical block anesthesia. While EXPAREL has not been studied with this technique, the use of bupivacaine for obstetrical paracervical block anesthesia has resulted in fetal bradycardia and death. Bupivacaine can rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity. The incidence and degree of toxicity depend upon the procedure performed, the type, and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus, and neonate involve alterations of the central nervous system, peripheral vascular tone, and cardiac function. Data Animal Data Bupivacaine hydrochloride was administered subcutaneously to rats and rabbits during the period of organogenesis (implantation to closure of the hard plate). Rat doses were 4.4, 13.3, and 40 mg/kg/day (equivalent to 0.2, 0.5 and 1.5 times the MRHD, respectively, based on the BSA comparisons and a 60 kg human weight) and rabbit doses were 1.3, 5.8, and 22.2 mg/kg/day (equivalent to 0.1, 0.4 and 1.6 times the MRHD, respectively, based on the BSA comparisons and a 60 kg human weight). No embryo-fetal effects were observed in rats at the doses tested with the high dose causing increased maternal lethality. An increase in embryo-fetal deaths was observed in rabbits at the high dose in the absence of maternal toxicity. Decreased pup survival was noted at 1.5 times the MRHD in a rat pre- and post-natal development study when pregnant animals were administered subcutaneous doses of 4.4, 13.3, and 40 mg/kg/day buprenorphine hydrochloride (equivalent to 0.2, 0.5 and 1.5 times the MRHD, respectively, based on the BSA comparisons and a 60 kg human weight) from implantation through weaning (during pregnancy and lactation). Lactation Risk Summary Limited published literature reports that bupivacaine and its metabolite, pipecoloxylidide, are present in human milk at low levels. There is no available information on effects of the drug in the breastfed infant or effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EXPAREL and any potential adverse effects on the breastfed infant from EXPAREL or from the underlying maternal condition. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Of the total number of patients in the EXPAREL local infiltration clinical studies (N=823), 171 patients were greater than or equal to 65 years of age and 47 patients were greater than or equal to 75 years of age. Of the total number of patients in the EXPAREL nerve block clinical studies (N=531), 241 patients were greater than or equal to 65 years of age and 60 patients were greater than or equal to 75 years of age. No overall differences in safety or effectiveness were observed between these patients and younger patients. Clinical experience with EXPAREL has not identified differences in efficacy or safety between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Hepatic Impairment Amide-type local anesthetics, such as bupivacaine, are metabolized by the liver. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations, and potentially local anesthetic systemic toxicity. Therefore, consider increased monitoring for local anesthetic systemic toxicity in subjects with moderate to severe hepatic disease. Renal Impairment Bupivacaine is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. This should be considered when performing dose selection of EXPAREL. OVERDOSAGE Clinical Presentation Acute emergencies from local anesthetics are generally related to high plasma concentrations encountered during therapeutic use of local anesthetics or to unintended intravascular injection of local anesthetic solution. Signs and symptoms of overdose include CNS symptoms (perioral paresthesia, dizziness, dysarthria, confusion, mental obtundation, sensory and visual disturbances and eventually convulsions) and cardiovascular effects (that range from hypertension and tachycardia to myocardial depression, hypotension, bradycardia and asystole). Plasma levels of bupivacaine associated with toxicity can vary. Although concentrations of 2,500 to 4,000 ng/mL have been reported to elicit early subjective CNS symptoms of bupivacaine toxicity, symptoms of toxicity have been reported at levels as low as 800 ng/mL. Management of Local Anesthetic Overdose At the first sign of change, oxygen should be administered. The first step in the management of convulsions, as well as underventilation or apnea, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously. Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously. The clinician should be familiar, prior to the use of anesthetics, with these anticonvulsant drugs. Supportive treatment of

per day is generally enough to support the proper growth, mobility and synthesis of enzymes that power the biochemical reactions in the body. For an acutely ill patient in the hospital, however, protein requirements often increase. Rice explained that protein and other macronutrients are critical for healing wounds, fighting infections and maintaining muscle and lean body mass. If critically ill patients receive

circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine to enhance myocardial contractile force). If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted. Endotracheal intubation, employing drugs and techniques familiar to the clinician, maybe indicated, after initial administration of oxygen by mask, if difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated. DOSAGE AND ADMINISTRATION Important Dosage and Administration Information • EXPAREL is intended for single-dose administration only. • Different formulations of bupivacaine are not bioequivalent even if the milligram strength is the same. Therefore, it is not possible to convert dosing from any other formulations of bupivacaine to EXPAREL. • DO NOT dilute EXPAREL with water for injection or other hypotonic agents, as it will result in disruption of the liposomal particles. • Use suspensions of EXPAREL diluted with preservative-free normal (0.9%) saline for injection or lactated Ringer’s solution within 4 hours of preparation in a syringe. • Do not administer EXPAREL if it is suspected that the vial has been frozen or exposed to high temperature (greater than 40°C or 104°F) for an extended period. • Inspect EXPAREL visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer EXPAREL if the product is discolored. Recommended Dosing in Adults Local Analgesia via Infiltration The recommended dose of EXPAREL for local infiltration in adults is up to a maximum dose of 266mg (20 mL), and is based on the following factors: • Size of the surgical site • Volume required to cover the area • Individual patient factors that may impact the safety of an amide local anesthetic As general guidance in selecting the proper dosing, two examples of infiltration dosing are provided: • In patients undergoing bunionectomy, a total of 106 mg (8 mL) of EXPAREL was administered with 7 mL infiltrated into the tissues surrounding the osteotomy, and 1 mL infiltrated into the subcutaneous tissue. • In patients undergoing hemorrhoidectomy, a total of 266 mg (20 mL) of EXPAREL was diluted with 10 mL of saline, for a total of 30 mL, divided into six 5 mL aliquots, injected by visualizing the anal sphincter as a clock face and slowly infiltrating one aliquot to each of the even numbers to produce a field block. Regional Analgesia via Interscalene Brachial Plexus Nerve Block The recommended dose of EXPAREL for interscalene brachial plexus nerve block in adults is 133 mg (10 mL), and is based upon one study of patients undergoing either total shoulder arthroplasty or rotator cuff repair. Compatibility Considerations Admixing EXPAREL with drugs other than bupivacaine HCl prior to administration is not recommended. • Non-bupivacaine based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more. • Bupivacaine HCl administered together with EXPAREL may impact the pharmacokinetic and/or physicochemical properties of EXPAREL, and this effect is concentration dependent. Therefore, bupivacaine HCl and EXPAREL may be administered simultaneously in the same syringe, and bupivacaine HCl may be injected immediately before EXPAREL as long as the ratio of the milligram dose of bupivacaine HCl solution to EXPAREL does not exceed 1:2. The toxic effects of these drugs are additive and their administration should be used with caution including monitoring for neurologic and cardiovascular effects related to local anesthetic systemic toxicity. • When a topical antiseptic such as povidone iodine (e.g., Betadine®) is applied, the site should be allowed to dry before EXPAREL is administered into the surgical site. EXPAREL should not be allowed to come into contact with antiseptics such as povidone iodine in solution. Studies conducted with EXPAREL demonstrated that the most common implantable materials (polypropylene, PTFE, silicone, stainless steel, and titanium) are not affected by the presence of EXPAREL any more than they are by saline. None of the materials studied had an adverse effect on EXPAREL. Non-Interchangeability with Other Formulations of Bupivacaine Different formulations of bupivacaine are not bioequivalent even if the milligram dosage is the same. Therefore, it is not possible to convert dosing from any other formulations of bupivacaine to EXPAREL and vice versa. Liposomal encapsulation or incorporation in a lipid complex can substantially affect a drug’s functional properties relative to those of the unencapsulated or nonlipid-associated drug. In addition, different liposomal or lipid-complexed products with a common active ingredient may vary from one another in the chemical composition and physical form of the lipid component. Such differences may affect functional properties of these drug products. Do not substitute. CLINICAL PHARMACOLOGY Pharmacokinetics Administration of EXPAREL results in significant systemic plasma levels of bupivacaine which can persist for 96 hours after local infiltration and 120 hours after interscalene brachial plexus nerve block. In general, peripheral nerve blocks have shown systemic plasma levels of bupivacaine for extended duration when compared to local infiltration. Systemic plasma levels of bupivacaine following administration of EXPAREL are not correlated with local efficacy. PATIENT COUNSELING Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to seek immediate medical attention if they or someone in their care experience the following signs or symptoms: pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue.

Pacira Pharmaceuticals, Inc. San Diego, CA 92121 USA Patent Numbers: 6,132,766 5,891,467 5,766,627 8,182,835 Trademark of Pacira Pharmaceuticals, Inc. For additional information call 1-855-RX-EXPAREL (1-855-793-9727) Rx only November 2018

inadequate protein for a significant period, they may have greater difficulty in recovering from illness and may face major functional declines during and after hospitalization. Recent observational studies have found reduced mortality for ICU patients with the delivery of between 1.2 and 1.5 g/kg of body weight per day (J Parenter Enteral Nutr 2012;36[1]:6068; Crit Care 2014;18[6]:701); better outcomes for ventilated ICU patients who receive more than 90% of target protein (Crit Care 2016;20[1]:386); and a decrease of 6.6% in the odds of death for every 10% increase in protein delivered to an ICU patient (Crit Care Med 2017;45[2]:156-163). Another study found a gain of 1% in survival for each additional gram per kilogram of body weight per day of protein delivered (Crit Care 2016;20[1]:367). But the protein-to-outcomes relationship is not necessarily linear, nor black and white. Observational trials can mislead due to confounding issues. For example, patients in a study who are not as sick may be better able to tolerate greater quantities of calories and protein compared with sicker patients. “Maybe it’s not the protein or calories but the fact that they are less sick,” Rice said. Randomized controlled trials remove many of the biases. Yet the results of these trials on protein delivery in the ICU have so far been “all over the map,” he said. “They have shown things like higher protein improving creatinine clearance. But we have not been able to show that protein delivery in randomized trials improves mortality.” In fact, one study found that delivering full protein actually might be detrimental, reducing the chance of an ICU patient being discharged alive (odds ratio [OR], 0.92 on day 3; P<0.05). However, the study found that this risk resolved after day 7 (Am J Respir Crit Care Med 2013;187[3]:247-255). “All of the trials have some deficiencies and some flaws, and that may be part of the reason that we don’t see a huge signal here,” Rice said.

A Patient-Driven Approach A closer look at the randomized data begins to uncover somewhat stronger signals. The evidence suggests that the amount of protein that proves beneficial may vary between patients as well as over the course of a patient’s illness. “There are different protein requirements for different populations and in different settings,” Rice said. The odds of survival for a septic patient, for example, may be increased with a moderate amount of protein, not with the highest level, according to one study

Clinical

Pharmacy Practice News • November 2020

Nutrition

There was a

decrease of

6.6% 10%

in the odds of death for every

increase in protein delivered to an ICU patient Source: Crit Care Med 2017;45[2]:156-163.

(Clin Nutr 2019;38[2]:883-890). Another study found that during the acute phase of illness—usually the first few days—it may be best not to deliver high amounts of protein. Instead, protein delivery should be ramped up to goal during the stabilization phase, which is usually between days 4 and 7. Then, during the recovery and rehab phases, protein delivery up to 1.5 or 2 g/kg of body weight per day may improve outcomes (Clin Nutr 2019;38[1]:48-79). Rice cautioned that it is unlikely the duration of these phases would be the same for all patients or occur on similar days of their illness. In some patients, the acute phase may last just two days or could extend to six days, he explained, adding, “We need to better investigate markers that indicate a patient has transitioned from the acute to the subacute or chronic or rehabilitation phase.” Moreover, “to reach protein requirements, we often have to use protein supplements,” Rice said. “Two grams is a lot of protein. You don’t get that with the administration of normal daily volumes of standard formulas.”

complication that could add to an already challenging issue. Critical illness and disease put the human body into a highly catabolic state, resulting in a significant breakdown of protein and rapid losses of muscle and organ mass. “So just providing more protein may not overcome all this protein degradation [or proteolysis],” Rice explained. “Maybe we need to add something with this protein, such as resistant exercise to help the body use it.” As for current tips, “it’s pretty clear that the old practice of restricting

protein in patients with renal or hepatic failure needs to be stopped. And we should increase protein for patients with burns or other trauma, as well as those on continuous renal replacement therapy or extracorporeal membrane oxygenation (ECMO),” he said, noting the potential relevance for COVID-19 patients on ECMO (J Parenter Enteral Nutr 2016;40[2]:159-211).

The Pharmacist’s Role Jacob Hall, PharmD, BCNSP, a clinical pharmacy specialist at The University of

Texas MD Anderson Cancer Center, in Houston, who was not involved in the session, emphasized the role pharmacists can play in providing protein as a “lowrisk to high-benefit ratio intervention. “As clinical pharmacists in the ICU,” Hall said, “we should evaluate protein doses in our patients [and ensure] the correct dose to optimize outcomes, similar to how we work to optimize medication dosing.” —Lynne Peeples Rice is a consultant to Baxter and Nestlé. Hall reported no relevant financial relationships.

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New Formulas Hold Promise However, new formulas in development, such as a very high intact-protein formula (VHPF) for enteral feeding used in one clinical trial, promise to deliver more protein without higher amounts of calories that could put a patient at risk for overfeeding. In the study, the investigators compared a VHPF (8 g protein/100 kcal; 32% of energy) tube feed (1.25 kcal/mL) with standard enteral feeding (Crit Care 2018;22[1]:156). Protein intake at day 5 was significantly higher in the VHPF group (1.49 g/kg adjusted body weight [ABW] per day; 95% CI, 1.21-1.78 g/kg) than in the standard enteral feeding group (0.76 g/kg ABW per day; 95% CI, 0.49-1.03 g/kg), with a difference of 0.73 g/kg ABW per day (P<0.001). “We need to rigorously study these formulas to understand their effects on critically ill patients,” Rice said. Rice pointed to one potential

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12 Clinical

November 2020

COVID-19 Pandemic

Small Trial Looks at Anticoag Dosing for COVID-19 Patients

n patients with severe COVID-19, therapeutic doses of enoxaparin improved gas exchange and decreased the need for mechanical ventilation compared with standard thromboprophylaxis in the phase 2 HESACOVID trial, the first prospective, randomized controlled trial in this setting. In the trial, Lemos et al randomly assigned patients with COVID-19 who required mechanical ventilation to receive enoxaparin (n=10) or standard anticoagulant thromboprophylaxis (n=10) (Thromb Res 2020 Sep 20. [Epub ahead of print]). The enoxaparin group received subcutaneous enoxaparin dosed according to age and adjusted daily by creatinine clearance (maximum dose, 140 mg twice daily). The standard thromboprophylaxis group received physician’s choice of subcutaneous unfractionated heparin (5,000 IU three times daily for patients <120 kg; 7,500 IU three times daily for patients >120 kg) or enoxaparin (40 mg once daily for patients <120 kg; 40 mg twice daily for patients >120 kg). The investigators evaluated gas exchange using the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, and seven and 14 days after randomization, as well as the time to successful weaning from mechanical ventilation and the number of ventilator-free days. The investigators found a significant increase in the PaO2/FiO2 ratio over time in the therapeutic group, from 163 (95% CI, 133-193) at baseline, to 209 (95% CI, 171-247) after seven days and 261 (95% CI, 230-293) after 14 days (P=0.0004). They did not observe an improvement in the prophylactic group, which had a gas exchange ratio of 184 (95% CI, 146-222) at baseline, 168 (95% CI, 142-195) after seven days, and 195 (95% CI, 128-262) after 14 days (P=0.487). Patients in the therapeutic group also were more likely to be weaned from mechanical ventilation (hazard ratio, 4.0; 95% CI, 1.035-15.053; P=0.031) and had more ventilator-free days compared with the prophylactic group (15 days; interquartile range [IQR], 6-16 days vs. 0 days; IQR, 0–11 days; P=0.028). Commenting on the study, Ralph J. Riello III, PharmD, a clinical pharmacy

specialist in the cardiac ICU at Yale New Haven Hospital, in Connecticut, said it provided “an eagerly anticipated first peek at a pivotal clinical question that all front-line health care providers managing COVID-19 patients are facing: Is a higher intensity of prophylactic anticoagulation warranted to combat the significantly elevated risk of venous and arterial thrombotic events in coronavirus patients?” Although the generalizability of the results is “limited by the study’s singlecenter, open-label design and small sample size,” Riello said he is “encouraged by the positive findings with respect to better pulmonary gas exchange and, especially, improved duration of mechanical ventilation and more successful extubation attempts,” both of which he considered to be “more clinically relevant outcomes than PaO2/FiO2 ratio.” He also pointed to the trend toward fewer ICU days as an important finding, although noting that “this difference narrowly missed statistical significance (P=0.067).” A “disappointing omission of the study,” Riello said, was the lack of inclusion of D-dimer to stratify the risk for thrombosis and “provide more justification for therapeutic intensity anticoagulation.” He explained that D-dimer “is a wellvalidated laboratory biomarker that we employ across Yale New Haven Health System to better understand an individual coronavirus patient’s thrombosis risk and provide adequately dosed anticoagulation treatment. D-dimer has already been shown to correlate well with disease severity and even reliably predicts mortality in hospitalized COVID-19 patients” (Lancet 2020; 395[10229]:1054-1062). (See “Countering COVID-19’s Thromboinflammation,” page 4). Although HESACOVID was not powered to find differences in outcomes such as thrombosis, bleeding or mortality, Riello said it is “important to note that there were no concerning signals to suggest that therapeutic intensity anticoagulation confers any harm and at least an inkling that there may be a clinical benefit for respiratory function. This is especially important, as empirically anticoagulating patients at full therapeutic doses of enoxaparin without the presence of a confirmed acute blood clot may give clinicians pause for concern due to increased bleeding risk.” —Sarah Tilyou Riello reported a financial relationship with AstraZeneca, Janssen and Portola.

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14 Clinical

Pharmacy Practice News • November 2020

Practice Pearl

Adapting a Meds-to-Beds Program to COVID-19 By Jennifer Hillman, MBA, PharmD Director of Pharmacy Department of Pharmacotherapy and Pharmacy Services University Hospital San Antonio, Texas

Introduction University Hospital, located in San Antonio, Texas, is a Level 1 trauma, academic medical center that serves 22 counties in the South Texas region. The hospital is licensed for approximately 700 beds and is comprised of 3 free-standing, high-rise towers. In 2018, the hospital initiated a meds-to-beds program that has proved extremely successful, increasing the monthly prescriptions dispensed from the discharge pharmacy from 3,000 to more than 15,000 per month. Since the COVID-19 pandemic began, several modifications have been made to allow staff to continue to serve patients in the program. This article shares these innovations with other health-system pharmacies to ensure patient access to discharge medications despite the ongoing COVID-19 pandemic.

Strategic Location The meds-to-beds program was started using the discharge pharmacy located on the first floor in the south end of the hospital. This location is significantly far from the main 10-story Sky tower on the north side of the hospital, where more than 50% of hospitalized patients are admitted. At its farthest point, it can take up to 12 minutes for staff to travel from the pharmacy to the top floor of the Sky tower. To reduce the travel time between the discharge pharmacy and the patient bedside, the pharmacy opened a second meds-to-beds location in the main Sky

tower. This new meds-to-beds, closeddoor pharmacy is strategically positioned on and between the highest-volume discharging floors. The close proximity of the pharmacy to patients enables the meds-to-beds technician to use either the elevators or stairs, thereby reducing travel between deliveries and increasing efficiency. The second location, focused exclusively on meds-to-beds patients, reduced phone calls and eliminated front counter distractions. Because the meds-to-beds operation is a closed-door pharmacy, there is no risk for infection transmission from patient contact. The pharmacy department split the staff to keep a team of members who were unexposed to patients in the meds-to-beds operation. In the event of an outbreak of COVID-19 among the

discharge pharmacy staff, a team of segregated pharmacy staff is available to keep the operation functioning.

Patient Consent Meds-to-beds programs require patients to voluntarily fill prescriptions using the hospital pharmacy. Pharmacy staff explain the basic components of the program to patients in their hospital rooms. If the patient is interested, technicians obtain the patient’s consenting signature. Since the pandemic began, admitted patients who were designated as COVID-19-positive or under investigation for possible COVID-19 are asked to participate in the meds-to-beds program using a revised method. Technicians still approach the patient room; however, instead of entering, the technicians stop

LEFT TO RIGHT: A meds-to-beds technician “in action,” delivers medication to a patient. The discharge pharmacy at University Hospital, in San Antonio, shows the pharmacy lobby with social distancing demarcation in yellow. A pharmacist works at University Hospital’s new Sky tower location, which features a closed-door pharmacy meds-to-beds model.

at the observation window. They call the patient’s hospital room telephone from their cleanable mobile phone. The observation window allows the patient to see the meds-to-beds pharmacy technician while maintaining a safe barrier. Technicians sign the consent form on behalf of the patient and note “verbal approval obtained COVID.” Using this adapted method, the department has been able to maintain enrollment rates. A secondary benefit of this modified approach is the conservation of personal protective equipment, which at times has been a limited resource.

Prescription Transmissions Prior to COVID-19, prescription submission to the meds-to-beds program was see MEDS-TO-BEDS, page 16

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16 Clinical

Pharmacy Practice News • November 2020

Practice Pearl

MEDS-TO-BEDS continued from page 14

accomplished primarily through printed paper prescriptions. Paper prescriptions were picked up several times per day on the hospital floors by the meds-to-beds technicians and hand delivered to the discharge pharmacy. With the onset of COVID-19, the health system encouraged providers to use the electronic prescription submission functionality. As a result, electronic prescription rates increased to the current rate of 90%. Electronic

prescriptions have reduced staff exposure to potential infection via time spent on the floors and touch contamination. The pharmacy department has requested that discharge prescription transmission occur as early as possible, including up to a day before anticipated discharge. The purpose of the request is to expedite prescription processing, with the goal of preventing patients from remaining on the hospital floor to wait for their medications or relocating to the hospital transitional unit, pharmacy lobby or hospital lobby to

wait. If providers are not certain about a particular medication for discharge but are sure about others, the pharmacy will fill 100% of the confirmed prescriptions and hold processing those that are being reconciled until final discharge. Filled prescriptions awaiting delivery are kept in the meds-to-beds pharmacy until the discharge is confirmed.

Pharmacy Lobby Modifications The discharge pharmacy lobby was originally designed with densely packed seating. The pandemic necessitated

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removal of over half the chairs to create at least 6 feet of distance between each patient. Social distancing floor demarcations were installed in the lobby and the exterior hallway leading to the lobby, directing patients to physically distance themselves in a safe manner. Hand-sanitizing stations were mounted in the pharmacy lobby, and clear plexiglass barriers were installed in prescription dropoff and pick-up areas. Pharmacy staff monitor the pharmacy lobby and proactively intervene if the lobby becomes noticeably full. Staff members triage patients in line. If prescriptions are not urgent, staff ask the patient if they would accept prescriptions for mail or same-day courier. This strategy has been effective in reducing the number of patients congregating in a small space.

Alternate Delivery Methods The emergency department (ED) is serviced by the meds-to-beds program. This area is known to have a higher percentage of suspected and confirmed COVID-19 patients. To minimize the risk for exposure to the virus, the medsto-beds program has elected to use the pneumatic tube system to deliver medications to the ED instead of hand delivering to the bedside. A single tube station within the ED is designated for discharge medications. The nurse providing care to the patient retrieves the medicines from the designated pneumatic tube system and dispenses them to the patient.

Payment Transactions Patients retrieving prescriptions at the discharge pharmacy pay at the front counter. To reduce the transaction time at the pharmacy window and touch contamination, patients are allowed to request a prescription bill be sent to their residence.

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The majority of discharge prescriptions are not written with refills. For prescriptions that do have refills, the discharge pharmacy team coordinates them ahead of time, contacting the patients by telephone and arranging for mail or home delivery. This change has averted patients from traveling to the hospital to request and/or pick up refills.

Conclusion COVID-19 has dramatically changed the way outpatient care is delivered. New practices aimed at reducing exposure for both patients and staff continue to evolve. The alternate pathways developed by University Hospital’s meds-to-beds program have proven successful, as shown by maintaining the number of discharge prescriptions dispensed to patients’ preand post-COVID-19 environments. Hillman reported no relevant financial relationships.

Clinical

Pharmacy Practice News • November 2020

Cardiology

HEARTACHE continued from page 9

events was 40% higher compared with that in the amoxicillin group (95% CI, 1.04-1.87). “Because both QT-prolonging drugs and azithromycin are so commonly prescribed, the risk for cardiac events due to the combination, while still rare, is serious,” Patel said, adding this risk should be considered carefully among patients who are taking QT-prolonging medications.

highest decile of risk for cardiovascular disease had an estimated 245 additional cardiovascular deaths per 1 million antibiotic courses. Post-myocardial infarction or heart failure patients have higher baseline QTc intervals (420-460 mseconds) than the average patient, so even smaller changes in the QTc interval with azithromycin would push patients closer to risk levels for torsades de pointes,” he said. White added that a study of patients with hypertrophic cardiomyopathy (JACC Heart Fail 2013;1[2]:149-155) found

a 1.2-fold increased likelihood of experiencing a ventricular arrhythmia for every 10-msecond increase in QTc interval (OR, 1.2; 95% CI, 1.03-1.39; P=0.02). In another study, Patel et al looked at two models that could be used to predict which patients might be at risk for increased cardiac effects from azithromycin (PLoS One [Epub Oct 15, 2020]. doi.org/10.1371/journal.pone.0240379). From that, they developed a score for the Assessment of Cardiac Risk with Azithromycin (ACRA) (bit.ly/ ACRA_2020). The ACRA score may

help identify patients who are at higher risk for cardiac events after treatment with azithromycin. “The take-home message,” White stressed, “is that QTc interval prolongation is an important phenomenon, but [it’s] even more dangerous in those on multiple QTc interval–prolonging drugs or those with prolonged baseline QTc intervals.” —Marie Rosenthal The sources reported no relevant financial relationships.

Accelerating Risk For Torsades de Pointes The Patel et al study in JAMA Network Open “shows that the concurrent use of azithromycin along with other QTc interval–prolonging drugs, such as hydroxychloroquine or fluoroquinolones, markedly increases the risk of torsades de pointes over [that seen with] azithromycin alone,” said C. Michael White, PharmD, FCCP, the department head and a distinguished professor of pharmacy practice in the Department of Pharmacy Practice, University of Connecticut School of Pharmacy, in Storrs. “Since the QTc interval–prolonging effects of azithromycin are very modest (<10 mseconds), average patients have a baseline QTc interval of 400 mseconds, and the risk of torsades de pointes does not accelerate until the QTc interval is greater than 500 mseconds or increased by 30 to 60 mseconds from baseline, this is not surprising but still very important,” said White, a Pharmacy Practice News editorial advisory board member. “It validates, in an incredibly large data set with strong controlling for confounders, the suspicion that concurrent dual use of modest QTc interval prolongation drugs is more dangerous than either agent alone.” Despite the FDA warning in 2012, subsequent studies provided mixed results. A similarly sized study from 2012 found azithromycin use was associated with an increased risk for cardiovascular death (hazard ratio [HR], 2.49; 95% CI, 1.38-4.50; P=0.002) and death from any cause (HR, 2.02; 95% CI, 1.24-3.30; P=0.005) versus amoxicillin (N Engl J Med 2012;366[20]:1881-1890). “How can we reconcile the smaller increase in risk from azithromycin from the [Patel et al] study versus the one in the New England Journal?” White asked. “First, the NEJM study did not separate their results based on whether or not people were receiving other QTc interval–prolonging drugs concurrently. We now know how potent a risk factor dual QTc prolonging–effects can be, given the JAMA Network Open results,” said White, who was not involved in either study. “Second, in the NEJM study, patients in the

18 Clinical

Pharmacy Practice News • November 2020

Review Article

Practical Considerations for Implementation of Biosimilars in Oncology

DOUGLAS HACKENYOS, PHARMD, BCOP Oncology Pharmacy Clinical Coordinator Department of Pharmacy UConn Health Farmington, Connecticut

The Role of Pharmacists In Education: Part 3 of 3

he continued development and approval of biosimilar agents bring both opportunities and challenges to health care. Biosimilars stand to provide price competition and cost savings sorely needed

in cancer care. Unfortunately, significant knowledge gaps have been identified that add to the challenge of implementing biosimilar use. This article is the last in a 3-part series focusing on practical management and uptake in oncology practice of biosimilars—biologics that are highly similar to and have no clinically meaningful differences from an approved reference product with respect to safety, purity, and potency.1 The first 2 installments discussed biosimilar product selection and information technology integration, respectively, and this final article highlights the role of pharmacists in educating providers and patient about biosimilars.

Becoming Informed as a Pharmacist The rapid introduction of multiple biosimilar agents has challenged all clinicians, including

pharmacists, to stay informed. In a 2019 survey conducted by the International Society of Oncology Pharmacy Practitioners, respondents identified 3 key areas that required more training: biosimilar comparative efficacy to innovator products (74%), practical guidance for managing biosimilar conversions (74%), and biosimilar medication safety, including immunogenicity (74%).2 Pharmacists must have a fundamental understanding of biosimilars to be in a position to implement them and educate providers and patients about their use. Numerous review articles, including publications geared specifically toward oncology pharmacists, discuss biosimilars.3,4 Pharmacists also can stay abreast of the most recent biosimilar approvals through

Table. Key Patient Counseling Points for Biosimilar Agents What are biosimilars?

• These biologic agents are highly similar to a reference product and are safe and effective. • Biosimilars are tested and compared with reference products before FDA approval. • These agents are not generic versions. As biologics, they are large, complicated molecules made by living cells that can’t be copied exactly.

Why use biosimilars?

• These agents provide more treatment options. • They enhance competition and increase cost savings in health care. • Biosimilars improve access to care. • Insurance coverage may require use of biosimilars.

Is it safe to switch to a biosimilar?

• There are no meaningful differences in effectiveness or side effects of biosimilars compared with reference products. • The function, purity, potency, and immunogenicity of biosimilars are similar to those of reference products. • Biosimilars use the same dosage and administration as reference products and are produced in FDA-licensed facilities. • Safety tracking continues after the biosimilar has been approved and reaches the market.

resources such as FDA Alerts and weekly FDA briefings from the Hematology/Oncology Pharmacy Association (HOPA).5,6

Educating Clinicians About Biosimilars Several studies have identified areas for improvement in oncology clinicians’ understanding of biosimilars, and pharmacists may play a key role closing these knowledge gaps.7,8 Position statements and resources from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), HOPA, and Oncology Nursing Society (ONS) can be very helpful in supporting pharmacist-led education of clinicians and, ultimately, increasing acceptance of biosimilars.9-12 Educational efforts and identification of a physician to champion biosimilar use can be critical for successful biosimilar implementation. In addition to clinician education, support staff should be informed about new considerations related to the addition of biosimilars. Pharmacists can facilitate the education of staff involved in patient access and prior authorization by explaining care plan changes, emphasizing changes in preferred products, and providing clinical rationales for biosimilar prior authorizations. Pharmacy technicians also should be educated to minimize the risk for look-alike, sound-alike errors in compounding and dispensing.

Educating Patients About Biosimilars Patient education remains a vital component of cancer treatment using antineoplastic biosimilars. The education of patients newly taking biosimilars is comparable to that of patients initiating treatment with a biologic. Given the growing potential for changing payor and institutional formularies based on cost savings, it may be appropriate to introduce the patient to the term biosimilar and explain key concepts of biosimilar switching, safety, immunogenicity, and production (Table). The massive amount of information that patients must process at the start of a new regimen necessitates succinct, patient-friendly written information. Biosimilar manufacturers often provide helpful explanations and easily interpreted figures, and these aids can help if branded patient educational materials are permitted at your institution. In addition, the FDA has a host of nonbranded materials with infographics that quickly explain key concepts related to see BIOSIMILARS, page 20

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20 Clinical

Pharmacy Practice News • November 2020

Review Article

BIOSIMILARS continued from page 18

biosimilars in patient-friendly terms.13 Education at the time of conversion from an antineoplastic reference product to a biosimilar is an important, sensitive step to maintain a respectful patient-provider relationship during implementation. Conversions may be driven by institutional cost-savings opportunities or insurance formulary preferences; in either case, it is important to be open about

the general motivation for increasing biosimilar use. In the outpatient setting, education must be coordinated in advance of order conversion, prior authorization, and eventual treatment with the biosimilar. An example conversion time line may include patient education about the biosimilar in person or via telephone at the time of their treatment with a reference product, prior authorization between treatments, order conversion, and follow-up at the first biosimilar infusion.

Whether patients need to re-consent when converted to an antineoplastic biosimilar is a frequently asked question. Pharmacists can review institution-specific consenting policies and consult in-house legal counsel (if available) to help determine the most appropriate course of action. Either way, it may be appropriate to update consent forms or policies to contain broader wording (eg, “treatment with: X drug and similar products”) to allow for future conversions.

Conclusion Successfully incorporating biosimilars into oncology practice requires education and understanding by all people involved in the medication use process. Adequate patient counseling and support when newly initiating therapy or converting to a biosimilar are critical. Pharmacists are uniquely positioned to provide clinician and patient education and will play a significant role in increasing adoption of biosimilars for cancer treatment.

References 1.

I N T R O DUC ING ™ F UN G I T E L L STAT ™ FU NG

FDA. Biosimilar product information: FDA-approved biosimilar products. bit.ly/2G3Pnes-PPN. Accessed September 28, 2020.

2. Chan A, Patel H, Siderov J, et al. Assessing biosimilar education needs among oncology pharmacy practitioners worldwide: an ISOPP membership survey. J Oncol Pharm Pract. 2020;26(3 suppl):11-21. 3. Cuellar S, McBride A, Medina P. Pharmacist perspectives and considerations for implementation of therapeutic oncology biosimilars in practice. Am J Health Syst Pharm. 2019;76(21):1725-1738. 4. Foreman E, Chan A, Biosimilars Task Force. Biosimilar implementation in clinical practice: an ISOPP collection for oncology pharmacists. J Oncol Pharm Pract. 2020;26(3 suppl 2). 5. FDA. Get email updates. https://fda.gov/ about-fda/contact-fda/get-email-updates. Accessed September 28, 2020. 6. Hematology/Oncology Pharmacy Association. Drug updates. https:// www.hoparx.org/table/resources/ drug-updates-from-the-fda/. Accessed September 28, 2020. 7. Cook JW, McGrath MK, Dixon MD, et al. Academic oncology clinicians’ understanding of biosimilars and information needed before prescribing. Ther Adv Med Oncol. 2019;11:1758835918818335. doi: 10.1177/1758835918818335

A Single Sample Format (1J3)-`-D-Glucan Detection Assay For Rapid Invasive Fungal Infection (IFI) Screening. Fungitell STAT™ is the first and only single sample format FDA-cleared and CE marked rapid in vitro diagnostic screening test for IFI (including Candida, Aspergillus and Pneumocystis) that detects (1J3)- ` - D -Glucan in serum.

8. Williamson C, Berger L, Sullivan TP, et al. Addressing oncologists’ gaps in the use of biosimilar products. Am J Manag Care. 2019;25(6 Spec No.):SP188-SP191. 9. Zelenetz AD, Ahmed I, Braud EL, et al. NCCN Biosimilars White Paper: regulatory, scientific, and patient safety perspectives. J Natl Compr Canc Netw. 2011;9(4 suppl: S1-S22. 10. Lyman GH, Balaban E, Diaz M, et al. American Society of Clinical Oncology statement: biosimilars in oncology. J Clin Oncol. 2018;36(12):1260-1265. 11. Hematology/Oncology Pharmacy Association. Biosimilars issue brief: an important new category of medications for cancer patients. http://www.hoparx. org/images/hopa/advocacy/IssueBriefs/HOPA_Biosimilars_Issue_Brief. pdf. Revised December 2015. Accessed September 28, 2020. 12. Vizgirda V, Jacobs I. Biosimilars: considerations for oncology nurses. Clin J Oncol Nurs. 2017;21(2):E54-E60. 13. FDA. Patient materials: biosimilar basics for patients. https://www.fda.gov/drugs/ biosimilars/patient-materials. Updated March 23, 2020. Accessed September 28, 2020.

w w w. f u n g i t e l l . c o m • 8 8 8 . 3 9 5 . 2 2 2 1 MKT#20-043

Hackenyos reported no relevant financial relationships.

Clinical

Pharmacy Practice News • November 2020

Pain Management

How One Urban Med Center Tackled the Opioid Crisis I

n 2016, Kevin Horbowicz, PharmD, BCPS, was tired. Every day, he came to work at Boston Medical Center (BMC), the large urban hospital in the historic South End neighborhood, which has been hit hard by the opioid crisis. As the associate director of inpatient clinical pharmacy services, Horbowicz saw the signs of suffering all around—crime, homelessness and addiction. He and other stakeholders believed they could do better to confront this crisis. So they decided to tackle the problem in the only way they could: by changing the way BMC doctors prescribe opioids and treat addiction. It was a comco plex process, which included expanding nding the presence of pharmacists on surgery floors, and overhauling the electronic health record (EHR) to modify default prescription settings. But it was all worth it, said Horbowicz; in fiscal year (FY) 2018, BMC providers dispensed 74,000 fewer opioid pills than the year before. “I’m very proud of the collaborative multidisciplinary work that we did,” Horbowicz said.

A Local Issue Massachusetts is one of the top 10 states with the highest rates of opioid-related overdose deaths. To help combat the crisis, in 2017, BMC received a $25 million grant from Eilene and John Grayken. Executive leadership and other stakeholders—from surgery, nursing, emergency medicine, information technology and, of course, pharmacy—were all committed to making a difference in prescribing habits. The first place they tackled was inpatient utilization. They started by expanding the presence of pharmacists on acute care surgery floors, so pharmacists could suggest opioid alternatives, such as acetaminophen, ketorolac and other nonopioid pain medications, for appropriate patients. The strategy “gave pharmacists a seat at the table to help them contribute to those daily decisions that were made by the surgical team,” Horbowicz said. Indeed, this change alone reduced the use of opioids among acute care surgery inpatients by 12%, according to data that Horbowicz presented at the ASHP 2019 Midyear Clinical Meeting, in Las Vegas. In the emergency department, the pharmacy team worked with nurses and doctors to administer buprenorphine-naloxone (Suboxone, Indivior) or methadone earlier, connect more patients to treatment, and increase access to intranasal naloxone (Narcan, Adapt Pharma). And for patients who want to seek treatment for opioid use disorder, the emergency department now hands out free two-day buprenorphine-naloxone kits, a “bridge

agreed that many of BMC’s opioid-related interventions are possible elsewhere, and said many health systems are taking similar approaches. “The way BMC has done it with a multipronged [strategy] is the right way,” McLellan told Pharmacy Practice News. “It’s not just one solution that solves the problem.”

BMC Successes: Reduced the use of opioids among acute care surgery inpatients by 12% Dispensed nearly 74,000 fewer opioid pills in FY 2018 than in FY 2017 Reduced inpatient use of opioids among surgical patients by 41% Source: Kevin Horbowicz, PharmD, BCPS

therapy,” until they can th aattend their appointment with providers, he said. Perhaps the most effective change was e modifying the EHR to alter pain scale range orders and the 55 postoperative order sets used by more than two dozen surgical specialties at BMC. “Those two IT changes were the most important,” Horbowicz said, adding that in the past, surgical patients who reported pain scores of 1 to 3 (out of 10) were given 5 mg of oxycodone every four hours as needed— which was “just too much.” So stakeholders agreed on a new set of standard doses for pain scales, in which patients do not receive an opioid unless their pain is at 4 or higher. If patients had additional pain,

prescribers had the option to prescribe more opioids as needed. As noted, BMC dispensed nearly 74,000 fewer opioid pills in FY 2018 than in FY 2017; between 2016 and 2019, the inpatient use of opioids among surgical patients fell by 41%. Horbowicz acknowledged that smaller facilities may not have the same resources as BMC, given the size of the grant that fueled many of his team’s opioidreduction initiatives. Still, “many of these changes—such as changing order panels to omit opioids for mild pain—are possible anywhere,” he said. “It just requires some persistence, focus and courage.” Christine McLellan, PharmD, MHA, the pharmacy clinical coordinator at Emerson Hospital, in Concord, Mass.,

Move Away From Opioids For instance, she said, many other organizations have moved away from giving opioids to patients with only mild pain. “Some of this can be done without a grant, but you definitely need the support of administration, and you need physician champions to support those efforts,” she said. Seeing the success of a large center such as BMC helps make the case that well-designed and executed opioid management strategies will be worth it, added McLellan, who moderated the session at the ASHP Midyear Clinical Meeting. “It helps other hospitals recognize they can do this, too.” To McLellan, giving pharmacists an integral role is the most crucial step at any facility to reducing opioid use. Pharmacists can help with everything, she said: revising order sets, being on the surgical floor to recommend nonopioid therapies, and suggesting intranasal naloxone for high-risk patients at discharge. “The pharmacist is primed for opportunities like this to be able to combat the opioid crisis,” she said. “I think the pharmacist is the key to a lot of it.” —Alison McCook The sources reported no relevant financial relationships.

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22 Clinical

Pharmacy Practice News • November 2020

Practice Pearl

Thinking Outside the Ideal Body Weight The Pharmacist’s Role in Management of Bariatric Surgery Patients Madeline Lutz, PharmD Clinical Pharmacist

Elizabeth Powell, PharmD, BCACP Clinical Pharmacist AdventHealth Celebration Celebration, Florida

ariatric surgery brings many different changes to a patient, from the physical altering of the gastrointestinal tract to the psychological changes that come after a life-altering surgery. As we know, patients who undergo bariatric surgery can experience rapid weight loss. With this weight loss comes inevitable changes to medications used to control disease states. Pharmacists can play an integral role in a patient’s bariatric surgery journey by providing patient-specific consultations and making recommendations to adjust medication therapy both before and after surgery.

Table. Criteria to Identify Risk Factors For Readmissiona BMI >50 kg/m2 Chronic obstructive pulmonary disease Complication or extended surgery Length of hospital stay >4 d Deep vein thrombosis Medicare and Medicaid insurance Metabolic syndrome Surgical site infection Urinary tract infection Other risk factors identified during the initial surgical consultation Based on references 2 and 3. a

After bariatric surgery; based on the Decreasing Readmission through Opportunities Provided Initiative.

At our pharmacist-run ambulatory care clinic within a large medical group, pharmacists work closely with a bariatric surgeon’s office to provide optimal care to patients who are undergoing bariatric surgery and have complex medical conditions managed by numerous medications. A small retrospective, single-center study done at our practice site in 2015 to 2016 assessed 30-day all-cause readmissions. Of the 113 patients included, 63 patients met with a pharmacist for a 2-week postoperative follow up. Of these, 4 patients (6.3%) who met with a pharmacist were readmitted within 30 days compared with 5 patients (10%) in the

Figure. Workflow for bariatric postoperative visits. control group (P=0.48). (The estimated national average 30-day readmission rate after bariatric surgery is 5%.1) Although our institution saw a smaller percentage of patients readmitted within 30 days if a pharmacist was involved at a 2-week postoperative appointment, the results were not statistically significant. Since the conclusion of this study, our clinic services have expanded to include optional preoperative disease state optimization, a preoperative visit, and additional postoperative follow-up visits as detailed below. Patients typically are referred to our service by the bariatric surgeons’ offices during initial surgical consultations. These patients may benefit from medication management services based on certain criteria set forth by bariatric providers. Suggested criteria include patients taking 5 or more maintenance medications, high-risk medications (eg, anticoagulants), or diabetes medications, as well as patients on dialysis and patients who may be at high risk for readmission as described in the DROP (Decreasing Readmission through Opportunities Provided) initiative (Table).2,3 The criteria are not set in stone, and it is up to the provider’s discretion to refer patients to this service. After referral, patients are seen in our clinic before surgery. The focus of the visit includes a medication reconciliation and recommendations (eg, smoking cessation) to optimize management of diseases such as diabetes and hypertension before surgery. A preoperative visit typically is scheduled 2 to 4 weeks before surgery to review medications, provide medication holding instructions before surgery, and provide counseling on medications typically prescribed immediately after surgery. This visit usually coincides with the patient’s preoperative clearance and lab review visit with the bariatric surgeon.

After the visit, the pharmacist documents an up-to-date and accurate medication history and consultation note in the inpatient and outpatient electronic health records. This update is completed before admission to the hospital for surgery. After surgery, patients are scheduled for appointments at 2 and 6 weeks, 3 and 6 months, and 1 year to coincide with their follow-up visits at the bariatric surgeon’s office. Again, at each visit, a medication reconciliation occurs; this is especially important because medication therapy is very dynamic during this time. The workflow for postoperative visits is shown in the Figure. During these visits, we assess the patient’s entire medication regimen and make recommendations to the bariatric surgeon or prescribing doctor to adjust medications. We assess perioperative medications for appropriate use and duration of therapy, considering most recent lab results and giving special attention to medications that have a narrow therapeutic index, vitamin levels, and kidney and liver function. Adherence to a bariatric vitamin regimen is crucial for these patients to prevent malnutrition and/or vitamin deficiency. As pharmacists, we can help these patients identify specific formulations of vitamins and/or supplements that will best fit their needs. We review blood glucose and blood pressure logs to make recommendations for diabetic and hypertension-controlling medications. We also counsel on ways to avoid dumping syndrome, bloating, and constipation; the importance of diet and exercise; avoidance of alcohol; appropriate contraception (if applicable); and any other issues specific to the patient’s needs. At all of these visits, the patient’s medications are screened for potentially inappropriate ones used after bariatric surgery. These agents may include

extended-release formulations and medications with high risk for gastrointestinal irritation. Bariatric surgery is a lifelong journey and patients are offered optional follow-up after the 1-year postoperative visit. We assess patient-specific needs for additional follow-up appointments, scheduling them routinely or on an asneeded basis, whichever is most appropriate for each patient. Our services are billed at each visit by charging a facility fee. Each patient has a unique journey while undergoing bariatric surgery. Pharmacists are formally trained medication experts who serve as an integral part of a patient’s interdisciplinary team. We aim to bridge the gap between different providers by performing medication reconciliation and providing recommendations to providers to help patients achieve optimal medication management of their disease states during their bariatric surgery journeys.

References 1. Abraham CR, Werter CR, Ata A, et al. Predictors of hospital readmission after bariatric surgery. J Am Coll Surg. 2015;221(1):220-227. 2. Morton J. The first metabolic and bariatric surgery accreditation and quality improvement program quality initiative: decreasing readmissions through opportunities provided. Surg Obes Relat Dis. 2014;10(3):377-378. 3. Morton J, Brethauer S, Fraker T, et al. Decreasing readmissions through opportunities provided (DROP): The First National Quality Improvement Collaborative from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP). Surg Obes Relat Dis. 2016;12(7 suppl ): S1-S2. https://www.soard.org/article/ S1550-7289(16)30209-X/fulltext.

The authors would like to acknowledge the following pharmacists: Stephanie Cox, PharmD, and Julia Nickerson-Troy, PharmD, MS, BCACP.

Clinical

Pharmacy Practice News • November 2020

COVID-19 Pandemic

Remdesivir for COVID-19: Where Does It Stand? P

reliminary positive findings led remdesivir to become a staple in the armamentarium to treat hospitalized patients with COVID-19, but the latest data from two wo large studies by the National Institutes nstitutes of Health and the World Health Organization (WHO) indicate cate the drug provides no mortality ity benefit. Despite this finding, on Oct. 22,, the FDA approved remdesivir (Veklury, Gilead) as the firstt treatment indicated for COVID-19 9 (bit.ly/2TyC6h7). The NIH COVID-19 treatment ment guidelines also continue to recommend mmend the drug for patients with severe COVID-19 (bit.ly/2G00tkL), while stating that health care providers should prioritize its use in “hospitalized patients with COVID-19 who require supplemental oxygen but who do not require oxygen delivery through a highflow device, noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation” (bit.ly/3dWapsc). The antiviral portion of the guidelines indicated that the section on remdesivir “would be updated soon.” At press time, the update was still pending. A WHO panel is working on its own guidelines on remdesivir, looking at “the totality of the evidence,” said Janet Diaz, MD, the head of the clinical unit in the WHO’s emergency programm, at a press conference on Oct. 23. She said they expect the guidelines to be published in three to four weeks. Underscoring the importance of these guidelines, Michael Ryan, MD, the executive director of the emergency programme, said it is the role of the regulatory process to guide “what can go on the shelf,” but it is the guidelines that help clinicians determine how “to use what’s on the shelf.”

SOLIDARITY Trial Disappoints Evaluated as part of the WHO-sponsored SOLIDARITY trial, remdesivir did not improve the outcomes of mortality, initiation of ventilation and duration of hospitalization, according to findings released in a preprint in MedRxiv on Oct. 15 (bit.ly/3mq4Cy5). The ongoing multinational, open-label, randomized SOLIDARITY trial conducted at 405 hospitals in 30 countries was designed to evaluate four antiviral agents—remdesivir, hydroxychloroquine, lopinavir/ ritonavir (Kaletra, AbbVie), and interferon-β1a in adults hospitalized with COVID-19. After results from the United Kingdom’s Recovery trial, released in June, showed that hydroxychloroquine and lopinavir/ritonavir did not increase survival (www.recoverytrial.net/results),

Interpretation of the SOLIDARITY findings should reflect

the confidence interval (0.79-1.05), which ‘absolutely excludes the suggestion that

remdesivir can prevent a substantial fraction of all deaths.’ Source: WHO Solidarity Trial Consortium (bit.ly/3mq4Cy5).

SOLIDARITY the SOL halted those investigators hal study arms. The interferon arm was halted on Oct. 16. The results reported in the preprint show none of the study drugs, including remdesivir, “had any definite effect on mortality, either overall … or in any subgroup defined by age or ventilation at entry (or other entry characteristics, or geographic region, or corticosteroid use).” More specifically, the investigators found that the rate ratio (RR) for death with remdesivir (200 mg on day 0, and 100 mg on days 1 through 9 or until death or discharge) was 0.95 (95% CI, 0.81-1.11; P=0.50; 301/2,743 vs. 303/2,708).

No Mortality Benefit in NIH Trial Final results from the remdesivir versus placebo stage of the NIH’s Adaptive COVID-19 Treatment Trial-1 (ACTT1), published Oct. 8 (bit.ly/2J20zti), also showed no mortality benefit for remdesivir, but the drug reduced hospital length of stay and helped reduce the risk for death in some patients with COVID-19 who were receiving oxygen. Median recovery time was 10 days (95% CI, 9-11 days) in remdesivir-treated patients versus 15 days (95% CI, 13-18 days) in the placebo group (RR for recovery, 1.29; 95% CI, 1.12-1.49; P<0.001 by log rank test). Mortality varied considerably between groups according to baseline severity, with the greatest benefit seen among patients with a baseline ordinal score of 5 (hospitalized and requiring any supplemental oxygen, but not high-flow oxygen or noninvasive or invasive ventilation) (hazard ratio [HR], 0.30; 95% CI, 0.14-0.64). Considering the ACTT-1 mortality findings along with those from their own trial as well as two smaller studies, the SOLIDARITY investigators underscored that their trial provides “more than three-quarters” of the evidence related to remdesivir. Using the combined results of the four trials— SOLIDARITY (604 deaths among

approximately 5,000 patients), ACTT1 (136 deaths among approximately 1,062 patients) and 41 deaths in two smaller trials—they calculated the remdesivir RR for death to be 0.91 (95% CI, 0.79-1.05). However, they stressed that interpretation of these findings “should chiefly reflect not the P-value (P=0.21) or point estimate (RR=0.91) but the confidence interval (0.79-1.05), which ... absolutely excludes the suggestion that remdesivir can prevent a substantial fraction of all deaths. The confidence interval is comfortably compatible with prevention of a small fraction of all deaths, but is also comfortably compatible with prevention of no deaths.” Commenting on the study, Jeffrey R. Aeschlimann, PharmD, an associate professor at the University of Connecticut School of Pharmacy, in Storrs, and adjunct associate professor at UConn School of Medicine’s Division of Infectious Diseases, in Farmington, said the “SOLIDARITY results align with the ACTT-1 trial results,” which indicate that “remdesivir therapy does not appear to significantly reduce overall mortality from COVID-19 infection in patients who are sick enough to warrant inpatient hospital care.”

Benefit for Other Outcomes Despite the lack of mortality benefit, Aeschlimann said there is “a strong argument for granting FDA approval to a drug that can shorten the duration of symptoms and/or allow patients to get discharged from inpatient hospital care quicker—especially if that disease is causing a pandemic that is stressing health care systems worldwide.” In a FAQ sheet about remdesivir on its website, the FDA noted: “While both the SOLIDARITY trial and the ACTT-1 trial contribute to our understanding of interventions to help treat COVID-19, the two clinical trials had different ... designs and primary goals. The design of ACTT-1 (i.e., randomized, placebocontrolled, double-blinded) was better suited to rigorously assess a time to

recovery end point compared to a trial with an open-label design, such as the SOLIDARITY trial. Based on the findings of the ACTT-1 trial, benefit to patients for [remdesivir] was demonstrated, including a shorter time to recovery and better odds of clinical improvement. The SOLIDARITY results do not refute these findings of benefit to patients” (www. fda.gov/media/137574/download). In addition to being a different type of trial from ACTT-1 with a different focus and primary end point, SOLIDARITY did not include “enough detailed data collection about day-to-day symptom severity” to allow comparisons with ACTT-1 trial results on those measures, Aeschlimann told Pharmacy Practice News. “Also, the data on hospital length of stay should be interpreted with caution,” he said, “because the trial design did not really permit a scientifically rigorous assessment of impact of therapy on duration of hospitalization.” Although he recognized the need for the FDA to consider outcomes other than mortality in its approval process, Aeschlimann said he was “disappointed that the FDA approval language wasn’t more specific in its guidance for why [remdesivir] should be used, and which types of COVID-19-infected patients it seems to benefit most—patients who have not progressed to needing invasive mechanical ventilation.” The bottom line, Aeschlimann said, is the “SOLIDARITY trial results reinforce the current scientific opinions of most clinician researchers about the drug: It is an anti-COVID-19 therapy that can provide some modest overall therapeutic benefits when started in the right patients. It is not a drug that will help us to significantly lower the risks of death in patients with severe COVID-19 infections.” —Sarah Tilyou Aeschlimann reported no relevant financial relationships.

n Jr., SHP

24 Operations & Management

Pharmacy Practice News • November 2020

Leadership in Action

Mind and Body: The Untapped Health Resource ‘The key to a healthy life is having a healthy mind.’ —Richard Davidson

e hear so much concern about burnout in health care workers. Many professional societies are focusing on this important practice issue, including sessions at several

recent ASHP meetings. We are all aware that stress is not good for our health, but being a pharmacy leader is particularly challenging. How are you responding to these pressures?

It’s important to remember that although you cannot control the majority of the circumstances that cause stress in your life or work, you can control how you respond to those stressors. The stakes are high for success: A recent study found that a pessimistic outlook proved to be deadlier than congestive heart failure or smoking 50 or more packs

of cigarettes every year (Circulation 2000;102[15]:1773-1779). Wow! Let’s dig deeper to understand the interconnection between the mind and body.

Our Perceptions Affect Our Health

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A positive person views a problem as an opportunity for a solution that advances the situation. Pharmacists face this decision constantly throughout the day: Are you positive or negative in your thinking? These mindsets affect our health, not just our leadership. As medical professionals, we are well aware of the placebo effect. If patients feel positive about a treatment because they think they’re getting the active drug, they do better—regardless of whether they actually are in the active treatment group. What more evidence of positive thinking do you need? Well, consider this: researchers have found that people with a family history of heart disease who had a positive outlook were one-third less likely to have a heart attack or other cardiovascular event within five to 25 years than those with a more negative outlook (bit.ly/2RhMFDL). Of course, the converse also is true: A study of 5,888 Americans over the age of 65 years at Johns Hopkins University found that a poor image of one’s health roughly doubled the risk for

“Leadership in Action” is authored by Ernest R. Anderson Jr., MS, RPh, FASHP, FMSHP, of Brockton, Mass. Mr. Anderson welcomes your input on leadership issues, at ernestanderson1130 @gmail.com.

Ernest R. Anderson Jr., MS, RPh, FASHP, FMSHP

death within five years, regardless of other health risk factors (Circulation 2000;102[15]:1773-1779). Kindness also has been tied to clinical outcomes. In a 2014 study, the authors explored various psychosocial risk factors in cardiovascular disease. They found that anxiety, depression, chronic stress, isolation and low sense of purpose all increased people’s risk for experiencing heart failure (Circulation: Heart Failure 2014;7:385-387). Conversely, the same study showed that higher rates of optimism, compassion and kindness reduced stress, strengthened our immune systems, and helped reduce anger, anxiety and depression. Patients who exhibited those positive attitudes and qualities were at a lower risk for heart failure. But here’s the challenge: Acts of kindness begin in our minds; there needs to be an intention to be kind before acts of kindness manifest. Fortunately, the payoff is worth it: Being kind benefits our interpersonal relationships—and, as noted in these clinical studies—benefits our health as well.

Neuroscience Holds the Key Neuroscience partly explains how this mind–body connection plays out. Studies have shown that negative thoughts and stress increase our heart rate, respiratory rate and cortisol levels (the fight-or-flight hormone) and decrease immunity. Conversely, positive thoughts lower heart rate and respiratory rate and release endorphins, enkephalins, serotonin and dopamine (the feel-good hormones). This in turn reduces pain, increases our mood and sense of calm, and allows us to look at challenges realistically. Therefore, how we view life’s hardships and challenges matters. Do we view these as opportunities to grow or do we stress out? I’ve often asked in these columns, given two equally qualified people, would you hire the pessimist or optimist? This should stimulate your mind to develop questions to go after this answer during the interview. You may have heard it said that we become our thoughts. This is true, partly because repetitive thoughts build dendrites and neurons in the brain, which help facilitate the formation of

Operations & Management

Pharmacy Practice News • November 2020

Leadership in Action short-term memory, and when repeated enough, then become part of our longterm memory. Our view of the world and what we say and do come out of these cerebral processes. This is why it is so important to take in positive thoughts and stimuli and not negative, toxic thoughts. You become what you think about. So, it may be time to think more about your thinking! Perhaps you should put a reminder in your daily schedules to check your thinking periodically. My recommendation: If you feel out of control or are thinking negatively, take a break; take some deep, long belly breaths and slow down your mind. Being an adrenaline junkie is not a healthy state. Instead, think kind thoughts and put others first.

Effect on Health Care If all this positive thinking is physiologically good for you, perhaps we should teach it to our patients, because they need to do more than eat right, exercise and reduce stress; they need a healthy mindset as well. The idea is to teach our patients, and ourselves, to reframe circumstances in our lives before they, or we, let our emotions get the best of us⎯sometimes referred to as “an amygdala hijack” ⎯and we act out of control without thinking, in essense enslaved by the baser impulses that reside in our prefrontal cortex. We need to teach people to ask questions to determine the “why” behind a situation, and ask whether it is true and the degree to which we may think it is a crisis. Then we can reframe, de-escalate and decide our next steps. Remember, we are in control of our response to our circumstances.

and replace them with positive ones. For example, the two universal issues that all people face are fear and selfdoubt. If you ruminate on these two negative “loops” in your mind, they will become part of your thinking and memory. However, if you challenge the veracity of that fear and self-doubt and overcome it with more positive affirmations of your self-worth, you will become the victor. Eleanor Roosevelt said: “You gain strength, courage and confidence by every experience in which you really stop

to look fear in the face. You are able to say to yourself, ‘I have lived through this horror. I can take the next thing that comes along.’ You must do the thing you think you cannot do.” Even she realized the power of the mind, without benefit of modern-day brain scan technology.

So, What Do We Do? We are largely a set of memorized, learned behaviors, reactions, skills, beliefs, perceptions and attitudes in our short- and long-term memory learned by about 35 years of age. So,

what if we are operating out of the wrong paradigm for some items and need to change? Are we hopeless? No, we can train ourselves to think differently. Positive attitudes and habits can be cultivated and learned, giving us another way to think, which will improve our relationships and our health. It is widely accepted that it takes 21 days to develop a habit, and it takes three cycles to make it automatic. So, fear not: You can change your thinking paradigm, with resilience and new thinking being the invaluable results. ■

Read Specialty Pharmacy Continuum Anywhere, Anytime!

Choosing What We Will Think Yes, we will become our thoughts unless we examine negative thoughts

Next Column: Lion’sLead: The Magic Bullet For Pharmacy Leaders Most pharmacy leaders have taken a myriad of leadership tests, but are they really assessing leadership? No, most tests assess personality, not leadership. LionsLead is a true leadership test, measuring learned behavior that influences outcomes, not personality profiles of a person’s tendencies. Don’t miss it!

www.specialtypharmacycontinuum.com

26 Operations & Management

Pharmacy Practice News • November 2020

COVID-19 Pandemic

Ambulatory Pharmacists Provide Value During Pandemic

they contribute now will have benefits beyond this crisis, experts believe.

rom swab and serologyy testing to monitoringg patients’ oxygen saturation level, ambulatoryy pharmacists have ample opportunities to demonstrate their value beyond medication dispensing and counseling during the COVID-19 pandemic. The extent to which

HHS Recognizes Profession’s Value As Tom Kraus, JD, the vice president of government affairs at ASHP, noted, pharmacists have already been called upon to help in important ways, such as expanding COVID-19 testing availability. He pointed to authorization by the Department of Health and Human Services (HHS) for pharmacists to order and provide serology testing (bit.ly/3lo3FFX). “We’ve also seen a number of governors do the same thing through executive orders,” Kraus said, noting these state-level emergency orders temporarily waive enforcement of some limits in scope of practice laws. Although expanded testing is a critical step in mitigating the spread of COVID-19, initiatives by pharmacists could include administration of a vaccine and antiviral medications, should they be found, he said. “If an effective antiviral emerges, pharmacists would be in a good position to initiate therapy if it can be provided in an ambulatory setting, since they are already testing,” Kraus said. “That would be particularly true if the antiviral’s administration was time-sensitive, like oseltamivir [Tamiflu, Roche], which needs to be given within 48 hours of influenza infection to be effective.”

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Yale New Haven Leverages Telehealth Elsewhere, ambulatory pharmacists are taking on other innovative roles during the pandemic. At Yale New Haven Health (YNHH) in Connecticut, for example, recent growth in telehealth has opened up opportunities for outpatient and ambulatory care pharmacists to help reduce the burden on their provider and nurse colleagues, said LeeAnn Miller, MS, PharmD, the vice president and chief pharmacy officer at YNHH. “Our pharmacists have been able to provide virtual care for patients in the community—primarily those with chronic hypertension as well as patients on anticoagulation therapy— and help reduce the patient load for the health system’s physicians and nurses,” Miller said. Pharmacists here also have helped manage shortages of hydroxychloroquine, which has been touted as a potential COVID-19 treatment, she said. When prescribing of hydroxychloroquine ramped up, YNHH pharmacists “quickly put together guidance for zebra.com | temptimecorp.com

see AMBULATORY, page 28

Q&A

Pharmacy Practice News • November 2020

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on stainless steel surfaces. Contact your Contec Healthcare sales representative to learn more.

Is it OK to use sterile lint-free gauze? According to the USP <797> Sterile Preparations guide,1 “sterile 70% IPA wetted gauze pads or other particle-generating material shall not be used to disinfect the sterile entry points of packages and devices.” Suggested operating procedures should state that nonessential objects that shed particles shall not be brought into the buffer area, including pencils, cardboard cartons, paper towels and cotton items (e.g., gauze pads). 1. 2012 USP–NF General Chapter <797> Pharmaceutical Compounding — Sterile Preparations.

28 Operations & Management

Pharmacy Practice News • November 2020

COVID-19 Pandemic

AMBULATORY continued from page 26

ambulatory care providers, both within our health system and in the community, explaining that there is no evidence that hydroxychloroquine is effective for COVID-19 prophylaxis,” Miller said. Instead, they identified the most effective treatments for COVID-19, noting that these efforts minimized inappropriate prescribing of hydroxychloroquine and ensured the medication is available for patients who need it, such as those with rheumatoid arthritis. Such an approach with hydroxychloroquine is supported by recent data. In a randomized trial testing the drug as postexposure prophylaxis for COVID-19, the incidence of a new illness compatible with COVID-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]) (N Engl J Med 2020;383:517-525).

Pulse Oximetry Option An innovative role that Miller’s team is trying to carve out for YNHH ambulatory pharmacists is the capability to dispense pulse oximetry devices

to nonhospitalized COVID-19–positive patients, she said. “We’ve seen COVID-19 patients with low oxygen saturation who are still speaking, where they’d typically be gasping for air or clearly struggling to breathe with that level of oxygenation. Because of this unusual presentation, some very sick patients are waiting too long to go to the hospital.”

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Distributing pulse oximeters in the community could help identify emergency cases based on their oxygen saturation levels, Miller said, and her team is collaborating with physicians to determine how they can help provide the device to patients who are prescribed one by a physician.

Lack of Reimbursement Impedes Access Like Kraus, Miller believes COVID-19 testing and vaccination are a natural fit for ambulatory and community pharmacists, as well as pharmacy technicians. However, a lack of direct mechanisms for reimbursement hinders widespread rollout of testing and possible vaccination by pharmacists, she said. “Adequate reimbursement would make it easier to justify the added resources required to support these services.” Pharmacists at YNHH have collaborative practice agreements in place, providing them a channel through which to offer financially sustainable direct patient care for chronic conditions as well as potentially COVID-19 services. However, many pharmacists across the country would rely on Medicare Part B reimbursement for testing and vaccination, ASHP’s Kraus said. At the moment, he noted, reimbursement through Medicare Part B is only available through “complex administrative mechanisms,” such as incidentto billing. Although the HHS guidance authorizes that pharmacists can order and administer tests, it does not address the question of reimbursement, according to Kraus. “If we’re not able to get Medicare to reimburse pharmacists in a straightforward manner, at least with regard to testing during the emergency, that’s going to be a potential barrier to access,” Kraus said. ASHP has urged federal lawmakers

to create some type of Medicare reimbursement mechanism for COVID-19– related services that pharmacists are authorized to provide, but he said Congress has yet to act on these recommendations. Meanwhile, reimbursement by commercial insurers and Medicaid depends on state rules, most notably laws affecting scope of practice, and these differ by state, Kraus said. “We’ve put out a series of recommendations to state lawmakers laying out both the scope-of-practice authorities and payment avenues that need to be in place in order to ensure access to care by pharmacists.”

A Channel in Medicare Part B Daniel Nam, RPh, Esq, an associate principal in pharmacy policy at Avalere Health, a health policy consulting and analytics firm in Washington, D.C., is optimistic that pharmacists will see a direct Medicare Part B reimbursement mechanism for testing and vaccination for COVID-19, particularly given the “tremendous value pharmacists provided in rolling out vaccinations during the H1N1 pandemic. “We also have the mass immunizer roster billing process, through which pharmacists can administer influenza and pneumococcal vaccines under Medicare Part B,” Nam added. The mass immunizer roster billing process is a payment mechanism for providers and nonproviders of population-level vaccinations as defined by the Centers for Medicare & Medicaid Services. Although COVID-19 vaccinations are not yet included under the mass immunizer program, Nam said, “it could be expanded to cover those vaccinations.”

A Boost for Provider Status Demonstrating pharmacists’ value during “tough situations like the COVID-19 pandemic” could boost the

Operations & Management

Pharmacy Practice News • November 2020

COVID-19 Pandemic case for provider status, Nam believes. However, “to really move the conversation forward, pharmacists need to continue to quantify the outcomes and provide evidence that their interventions are indeed having an impact,” he said. “I also think that although it’s typically been an all-or-nothing process in terms of getting provider status legislation, there is a parallel approach in which pharmacists can inch toward provider status by incrementally taking on broad Medicare reimbursement for additional services, which are

Statement of Ownership

‘If we’re not able to get Medicare to reimburse pharmacists in a straightforward manner, at least with regard to testing during the pandemic], that’s going to be a potential barrier to access.’ —Tom Kraus, JD already temporarily available to them to provide during the pandemic, like point-of-care testing.” Kraus agreed with that assessment,

saying that novel ways to “more fully utilize the skills of pharmacists will certainly inform future provider status discussions.

“One could imagine that some of the authorities [that] pharmacists are given during the pandemic could be left in place afterward if there’s a recognition that they provide a lot of value in their services to their communities,” Kraus said. “I think we’ll see a push long after the pandemic to access those points of care, which would feed into the provider status argument.” —David Wild The sources reported no relevant financial relationships.

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30 Clinical

Pharmacy Practice News • November 2020

Infectious Disease

Part 1 of a 2-part series

ABx Stewardship Spreads Its Wings A

ntimicrobial stewardship programs are on the rise. What started as an effort to improve antibiotic prescribing and reduce antibiotic resistance in inpatient settings has been gradually expanding to ambulatory care, emergency departments (EDs), and even some settings outside of traditional health systems. “We’ve seen, in the last 10 years, tremendous growth in antimicrobial stewardship programs,” said Anna Legreid Dopp, PharmD, the senior director of clinical guidelines and quality improvement at ASHP. In a 2018 ASHP survey, about 45% of responding hospitals said they had antimicrobial stewardship programs, she noted. That number today is over 90%. In addition, the survey suggests there are opportunities for antimicrobial stewardship practices to extend beyond hospitals, into ambulatory settings. This includes 90% of responding larger hospitals with more than 600 beds, and 30% of smaller hospitals. “We know that close to 30% of antibiotics used in outpatient settings are prescribed unnecessarily, so there’s definitely a huge need for it,” Dopp said. Stewardship is being evaluated in many areas, said Susan Davis, PharmD, the president-elect of the Society of Infectious Diseases Pharmacists and a professor of pharmacy practice at Wayne State University, in Detroit. Pharmacists are recognizing that although the broad-spectrum antibiotics might be used in hospitalized patients, the bulk of antibiotics are used outside of the hospital. “That means inpatient stewardship experts are having to learn practice models they haven’t previously been involved in, so partnering with pharmacists in community and ambulatory care settings is really essential,” Davis said. One ongoing project at her health system involves working with primary care and urgent care clinics to offer symptom relief gift bags to patients

218 The number of interventions clinical pharmacists made on daily rounds to optimize antimicrobials.

26 The number of recommendations made to optimize anticoagulation.

20 Patients educated at discharge about their high-risk medications.

100% Of interdisciplinary clinicians strongly agreed that a pharmacist should continue on the ABx stewardship care team.

presenting with common respiratory illnesses—such as sinusitis, bronchitis or sore throat—who don’t need antibiotics. Borrowing an idea posted on Choosing Wisely by Mayo Regional Hospital in Maine, the Detroit pharmacists developed a symptom relief guide for patients, naming over-the-counter products to address their symptoms. They also put together bags containing items such as saline nasal spray, tissues, lip balm and sugar-free cough drops, as well as a card referring them to an outpatient pharmacy within the health system, where pharmacists help patients choose products that may provide relief. “It’s really hard to send someone home and say, ‘Sorry, we can’t do anything for you,’” she said. “That’s the last thing a clinician wants to do.” Davis and her colleagues tracked results during the first year of the program and got “some great uptake,” especially in downtown hospitals. Some 500 gift bags were distributed in five walk-in clinics in 2018, with half of pharmacy vouchers redeemed for over-the-counter products. From there, the team received a grant from the Michigan Pharmacists Foundation to provide 650 bags in nine clinics in 2019. “It’s something that our pharmacists feel excited to do,” she said.

At Duke, EDs a New Focus Outpatient, urgent care and EDs are another area of growth for antimicrobial stewardship programs. Rebekah Wrenn, PharmD, an infectious diseases clinical pharmacist at Duke University Hospital, in Durham, N.C., and her colleagues have been tackling antibiotic prescribing for urinary tract infections (UTIs) in the ED. About 13.7 million antibiotic prescriptions are written by emergency physicians nationally, and about half of outpatient antibiotic prescriptions are expected to be inappropriate, said Wrenn, citing 2017 CDC data (bit.ly/ 30DNbBG) Her team is focusing on socalled “treat-and-release” patients who present to the ED but are not admitted. “Patients are seen briefly, and clinicians don’t have a lot of data when making antibiotic decisions,” she said. “We felt clinicians really needed tools to help treat patients appropriately that fit into the workflow of the ED, which is quite different than inpatient treatment.” In a pilot project at three hospitals in the Duke University Health System (DUHS), Wrenn and her colleagues created a UTI antibiogram based on outcomes from treat-and-release patients at the institutions, as well as current treatment guidelines. They also conducted in-person education sessions

At Duke University Hospital, in Durham, N.C., the antimicrobial stewardship and evaluation team (aset) created pocket cards (left) on appropriate antibiotic prescribing and placed the cards at workstations. The cards are part of Duke CustomID, a decision support tool intended to provide clinicians with institution-specific, accessible, easily customizable information about the diagnosis and treatment of infectious diseases.

for resident physicians on appropriate prescribing and made recordings of those sessions available for attending providers. A pocket card on appropriate antibiotic prescribing was placed at workstations and added to a centralized tool, Duke CustomID. The team has provided feedback on how the ED providers are doing with guidelines concordance on a monthly basis; that is being expanded to look at individual provider performance. A poster about the work, presented at IDWeek (No. 45), showed that these interventions improved DUHS’s guidelines concordance in the first six months of the project, from 31% to 39% at one hospital, from 48% to 49% at a second hospital, and from 48% to 60% at the third hospital. Further studies will tease out how to continue these improvements. The goal is not to get to 100% guidelines concordance, Wrenn noted. For example, there will be cases in which patients have prior cultures indicating they need a different antibiotic or have adverse reactions to the guidelines-recommended treatment. Wrenn’s team also is sampling some cases in which providers didn’t follow the guidance and doing a deep chart review to identify why.

PeaceHealth Southwest Keeps Stewardship in the Family UTIs also were the focus of a pharmacist-led ambulatory antimicrobial stewardship program in a family medicine clinic at PeaceHealth Southwest Medical Center, in Vancouver, Wash. There, a combination of in-person education for clinicians, a guidelines-based antibiotic treatment summary made available in the electronic health record (EHR), and treatment defaults in the electronic order sets nearly doubled guidelines-based treatment adherence for uncomplicated cystitis and pyelonephritis (J Clin Pharm Ther 2020 Jul 24. [Epub ahead of print]. doi: 10.1111/jcpt.13210). In 2018, before

the intervention, 37% of patients were given the proper antibiotics at the appropriate dose and duration; that increased to 71.6% after the intervention (P<0.001). Although it can be helpful to have stewardship teams in the background making changes to the EHR, the work gains traction in the live education and training of residents and clinicians, noted study co-author and clinical pharmacist Luke Vander Weide, PharmD. Clinics that have resident physicians who turn over annually can benefit from periodic reeducation about proper antibiotic selection, added study co-author and clinical pharmacist Julia McCormick, PharmD.

Johns Hopkins Bayview Reaches Into Underserved Departments Pharmacists also can make a difference extending stewardship to previously untapped areas of the hospital. Johns Hopkins Bayview Medical Center, in Baltimore, did not have a clinical pharmacist dedicated to general and orthopedic surgery. Because pharmacy staff received a lot of clinical questions from this area, they wanted to see what would happen if a pharmacist was assigned to the units, said Farrah Tavakoli, PharmD, formerly with the medical center and now a formulary management pharmacist with the University of Maryland Medical System. In just a two-week period, the clinical pharmacist attended daily multidisciplinary rounds and made 218 interventions, including 38 recommendations to optimize antimicrobials, 26 recommendations to optimize anticoagulation, and provided education for 20 patients who were discharged on high-risk medications (J Pharm Pract 2020 Jul 21. doi. org/10.1177/0897190020938196). In an anonymous survey of multidisciplinary staff on these floors, 100% of respondents strongly agreed that a clinical pharmacist should be part of the team.

Clinical

Pharmacy Practice News • November 2020

Infectious Disease said. Through these arrangements, a centralized stewardship team can track data on antibiotic use and resistance and review any challenging cases with a local physician or pharmacist, who can then talk to patients in person. She said Allegheny Health Network in western Pennsylvania and New York has such a system, and demonstrated that telehealth stewardship reduced the use of broad-spectrum antibiotics by 24% in a six-month period (Clin Infect Dis 2020;71[3]:539-545). During COVID-19, ID pharmacists have helped with stewardship efforts

The hospital is in the process of working toward a full-time clinical pharmacist dedicated to that area, but meanwhile has central antimicrobial stewardship clinical pharmacist support to consult on and review key decisions, said study co-author Stacy Dalpoas, PharmD, the assistant director for decentralized and clinical pharmacy services for the hospital.

in managing patients facing the novel infection, Dopp and Wrenn said. Moving forward, there could be a role for antimicrobial stewardship in specialty clinics that see other conditions in which these drugs are frequently used, such as gastroenterology, oncology, urology, obstetrics and otolaryngology, Dopp said. Outpatient parenteral antimicrobial therapy, in which patients are discharged home or referred to an outpatient clinic with an IV antibiotic, also is an area for needed stewardship principles, she

Telehealth for Smaller Hospitals Some smaller and rural hospitals that don’t have their own stewardship teams are getting centralized telehealth help from pharmacists at a larger center, Davis

—Karen Blum The sources reported no relevant financial relationships.

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Beyond the Hospital Walls Some antimicrobial stewardship efforts are moving outside of hospitals. Wrenn’s group at Duke, for example, is providing basic stewardship education this fall to dentists with the UNC School of Dentistry. “Dentists prescribe 10% of all antibiotics in the U.S. [J Am Dent Assoc 2017;148(12):878-886] and often don’t have the support of an ID pharmacist there to help guide them in agent selection, duration and antibiotic allergies,” Wrenn said. Long-term care facilities also have unique challenges for antimicrobial stewardship, said Kerry LaPlante, PharmD, with the VA Providence Healthcare System, in Rhode Island, and a professor of pharmacy at the University of Rhode Island, in Kingston. “What we typically see in long-term care is an older adult population with more vulnerability, increased UTIs, and more pneumonias and respiratory tract infections,” LaPlante said. “It’s much more challenging to discern if they have an active infection or not.” Wanting to do no harm, physicians tend to give residents antibiotics, she said. “But it’s important that if there is a status change, that the providers and nurses in long-term care facilities evaluate the whole patient to determine if there is an environmental change, social changes, new medications or dehydration contributing to that status change. We really need to do a better job ruling out all other causes and not just think it’s a UTI and give an antibiotic.”

said. Dialysis clinics and substance use disorder programs present still more opportunities to expand, Davis said. “Pharmacists can take a real prominent role in antimicrobial stewardship programs,” Dopp said. “They’ve demonstrated it in hospital settings and in emergency departments, so they should be considered as partners as some of these new locations are being considered.”

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32 Policy

Pharmacy Practice News • November 2020

Reimbursement Matters

Planning for 2021 reimbursement:

A Holiday of Opportunities and Responsibilities A

s we’re entering the holiday season, let’s pause for a moment to see that we’re on track for all those important changes that will affect pharmacy reimbursement in 2021, in addition to the ones in the proposed 2021 Outpatient Prospective Payment System rules published previously (bit.ly/3jr7DwS). Not all are in “pharmacy-specific” rule sets or decisions, which makes bursting out of that silo and exploring other opportunities or recognizing implications of payment changes ever more important.

(FY 2021 IPPS Final Rule; bit.ly/ 3nuTem2). NTAPs provide separate payment outside of the diagnosis-related group (DRG) payment for new technology for a defined period of time when the products are used in the inpatient setting. This policy is applied in a similar manner to pass-through drugs, which provide separate payment in an outpatient setting. The Table summarizes those medications losing NTAP status and those with continuing status through fiscal year (FY) 2021.

There also are important new payment changes under NTAPs addressing chimeric antigen receptor (CAR) T-cell therapy products and certain antimicrobials: CAR T-Cell Therapy

Payments for CAR T-cell therapy fall under CMS’s Medicare Severity (MS)DRG 018 for CAR T-cell treatment stays, with differential reimbursement based on whether the product was provided as part of a clinical trial. MS-DRG 018 includes several important additional

Hospital Price Transparency (Effective Jan. 1, 2021) Use this to your competitive advantage! Each U.S. hospipital is required ed to provide clear, ar, accessible pricricing information mation online about the he items and services they hey provide in two ways: 1) a comprehensive machine-readable ine-readable file with all items and services, and 2) a display lay of shoppable services in a consumer-friendlyy format. What role has your pharmacy played layed in showcasing the drug component of the shoppable services chosen by your facility? Still fuzzy on what’s required? Do you need more information to quickly move to being compliant? Check out these resources from the Centers for Medicare & Medicaid Services (CMS): • Hospital Price Transparency FAQs: go.cms.gov/30sFH4d • 8 Steps to a Machine-Readable File of All Items & Services: go.cms. gov/30sO14c • Quick Reference Checklists: go.cms. gov/33niOkz • 10 Steps to Making Public Standard Charges for Shoppable Services – This document contains a wealth of information, including how to make a consumer-friendly display to aid pricing transparency: go.cms. gov/2EYxb5I • For an overview of the pricing transparency requirements, check out the final rule in the Federal Register at bit.ly/33plnD2.

NTAPs for FY 2021 The new technology add-on payment (NTAP) program is a payment system designed by Congress to encourage the uptake of new and costly medical technologies in the hospital setting under the Hospital Inpatient Prospective Payment System (IPPS) in Medicare Part A.

Table. Table T bl F FY Y 20 2021 21 N NTAPs TA AP Max NTAP FY 2021

Product (NEW)

ICD-10-PCS Code

IMFINZI® (durvalumab) and TECENTRIQ® (atezolizumab)

XW03336 or XW04336 (IMFINZI) & XW033D6 or XW034D6 (TECENTRIQ)

$6,875.90

Soliris (eculizumab)®

XW033C6 or XW043C6

$21,199.75

NUZYRA (omadacycline) for Injection

XW033B6 or XW043B6

$1,552.50

RECARBRIO™ (imipenem, cilastatin, and relebactam)

XW033U5 or XW043U5

$3,532.78

XENLETA™ (lefamulin)

XW03366 or XW04366 or XW0DX66

$1,275.75

ZERBAXA® (ceftolozane and tazobactam)

XW03396 or XW04396

$1,836.98

Andexxa™ (coagulation factor Xa (recombinant), inactivated-zhzo)

XW03372 or XW04372

$18,281.25

AZEDRA® (iobenguane Iodine-131) Solution

XW033S5 and XW043S5

$98,150.00

CABLIVI® (caplacizumab-yhdp)

XW013W5, XW033W5, and XW043W5

$33,215.00

ELZONRIS™ (tagraxofusp-erzs)

XW033Q5 and XW043Q5

$125,448.05

Balversa™ (erdafitinib)

XW0DXL5

$3,563.23

SPRAVATO™ (esketamine)

XW097M5

$1,014.79

XOSPATA® (gilteritinib)

XW0DXV5

$7,312.50

JAKAFI™ (ruxolitinib)

XW0DXT5

$4,096.21

Source: Federal Register (the NTAP section of the IPPS final rule): bit.ly/30JttnY

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

Bonnie Kirschenbaum, MS, FASHP, FCSHP

features and reimbursement codes to keep in mind: • Payment rate of $239,928.79, assuming a wage index adjustment of <1, not including adjustments • Relative weight for the CAR T-cell MS-DRG (37.290) is the highest under the IPPS • Maps the following ICD-10-PCS (Procedure Coding System) codes to the new MS-DRG (both used to report administration of tisagenlecleucel [Kymriah, Novartis] and axicabtagene [Yescarta, Kite Pharma]): -XW033C3: introduction of engineered autologous chimeric antigen receptor t-cell immunotherapy into central vein, percutaneous approach, new technology group 3 -XW043C3: introduction of engineered autologous chimeric antigen receptor t-cell immunotherapy into central vein, percutaneous approach, new technology group 3) • New ICD-10-PCS codes for brexucabtagene autoleucel (Tecartus, Kite Pharma) and lisocabtagene maraleucel (liso-cel, Bristol-Myers Squibb) to MS-DRG 018. (Note that lisocabtagene maraleucel is an investigational CAR T-cell therapy in development for the treatment of adult patients with relapsed or refractory large B-cell lymphoma; it has not yet been approved by the FDA.) There are two additional CAR T-cell therapy reimbursement wrinkles to consider: 1. Cost-to-charge ratios (CCRs). “There is nothing that precludes hospitals from setting their drug charges consistent with their CCRs,” CMS noted in the NTAP section of the IPPS final rule (bit.ly/30JttnY). CMS added that tumor-infiltrating lymphocyte therapy and engineered T-cell receptor therapy are on the horizon; the agency thus plans to engage stakeholders to ensure prompt patient access. 2. Discontinued coverage. It’s critical to note that NTAPs for tisagenlecleucel and axicabtagene have been discontinued for FY 2021 due to time limits. The cost criterion threshold for the new MS-DRG

Policy

Pharmacy Practice News • November 2020

Reimbursement Matters 018 is set at $1,237,393. Unfortunately, NTAP applications for brexucabtagene autoleucel and liso-cel didn’t meet the July 1 deadline for FDA approval and aren’t eligible for the FY 2021 NTAP. Antibiotic Therapy

CMS established an alternative NTAP policy for certain antimicrobial products: FY 2020: Products with the FDA’s qualified infectious disease product (QIDP) designation are considered new and not substantially similar to an existing technology for purposes of NTAP. As such, they don’t need to meet the “substantial clinical improvement” criterion but only the cost criterion. FY 2022: CMS expands the alternative NTAP pathway for QIDPs to include products approved through the FDA’s limited population pathway for antibacterial and antifungal drugs (LPAD pathway). There aren’t any products approved under the LPAD pathway to date. FY 2022 and subsequent years: If an antimicrobial product is approved through the FDA’s LPAD pathway, it will be considered new and not substantially similar to an existing technology for purposes of an NTAP, and does not need to meet the “substantial clinical improvement” criterion but only the cost criterion. For QIDPs that do not receive FDA approval by July 1, and products that do not receive approval through the FDA’s LPAD pathway by July 1 but otherwise meet the applicable addon payment criteria, CMS will provide conditional NTAP approval to enable certain antimicrobial products to receive an NTAP sooner, effective for discharges the quarter after the date of FDA approval.

Recurring Denials And Incomplete Claims! Do whatever you need to do to stop this. Why continue to waste time and resources appealing denied claims over and over again. Get to the root cause of the problem, and change your problematic standard operating procedures to which an analysis of patterns of denials point. Is it prior authorizations? Other payor requirements? Billing unit conversion errors? Healthcare Common Procedural Coding System (HCPCS) errors/miscoding? Poor/ incomplete documentation? Outdated charge description masters? Inappropriate scrubbing or hard stops? Missing national drug codes? Unidentified/incorrect payor info? Randomly pick 10 denied outpatient charges and follow each step along the way, from the computerized prescriber order entry order to actual payment or denial to find the missteps. You cannot afford to be complicit in this recurring problematic cycle—especially

at a time when your facility is in desperate need of revenue.

Reporting Bevacizumab For Ophthalmologic Use Local coverage article A53121 Information Regarding Uses, Including OffLabel Uses, of Anti-Vascular Endothelial Growth Factor (anti-VEGF), for The Treatment of Ophthalmological Diseases on 2.13.2020 has been revised to clarify billing instructions. Physicians providing bevacizumab for ophthalmologic use should report HCPCS code J7999

(compounded drug, not otherwise classified). Each 1.25-mg dose administered is considered one unit. The total dosage administered should be noted in the “remarks” section of the claim.

A Shout-out to APhA! Recognizing that many pharmacists and technicians need more background on reimbursement, the American Pharmacists Association (APhA) began a helpful series, “Learn the Lingo.” The latest is “Learn the Lingo—Bundled Payment Models,” which APhA members

may access at bit.ly/2GHS2dVZ.

New Patient Assistance Resource MLN Connects, the official CMS news from the Medicare Learning Network, announced a new section dedicated to information in assisting you in working with your patients. The inaugural piece is “Making Insulin More Affordable for Medicare Patients Beginning January 1,” which can be accessed on CMS’s Fact Sheet: Part D Senior Savings Model at go.cms.gov/2SC3afb. ■

34 Policy

Pharmacy Practice News • November 2020

Sterile Compounding

Amid COVID-19, the Challenge of DIY 503B Continues

n retrospect, Vanderbilt University Medical Center hit “pause” on creating its own in-house 503B compounding facility at just the right time. As 2019 drew to a close, the medical center’s Department of Pharmaceutical Services determined that, before moving forward, it would take the time to put key products through the enhanced stability testing required for meeting the extended beyond-use dating (BUD)

‘In these critical [pandemic] situations, I cannot underscore enough the importance of having these [outsourcing] relationships, and even multiple relationships for redundancy.’ —Deidra Dickerson, PharmD

standards that are part of the FDA’s current good manufacturing practice requirements for 503B compounding outsourcing facilities. “We wanted to send all of our products through that level of testing just as a measure of preparedness for the future,” Deidra Dickerson, PharmD, the manager of sterile and nonsterile compounding at the Nashville, Tenn., institution, told Pharmacy Practice News. “So at the end

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

Policy

Pharmacy Practice News • November 2020

Sterile Compounding ‘[It] costs, by conservative estimates, $5 [million] to $15 million and three years to open your [503B] doors. It’s not a quick fix, not just <797> on steroids.’ —Eric Kastango, MBA, BSPharm of 2019, we made the decision to start using a 503B outsourcing facility while pulling back from our own internal program, planning to ramp back up later

once the results started trickling in.” After meeting with several outsourcing facilities, Vanderbilt settled on QuVa, which has compounding

facilities in Sugar Land, Texas, and Bloomsbury, N.J., serving more than 2,200 hospital customers with over 280 product SKUs. “We placed our

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

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

first order with QuVa in January, right before the pandemic hit the United States,” Dickerson said. “By March and April, they were experiencing such demand that they were no longer able to bring on new customers because of the need to properly serve existing customers.” Vanderbilt initially outsourced only a handful of products to QuVa, including ephedrine, epinephrine and phenylephrine syringes, and phenylephrine and midazolam IV bags. But as the pandemic continued, more were added. “Fentanyl was an item that became challenging early on, and we were having difficulties procuring any of the vials for infusion we typically get from our standard wholesaler,” Dickerson said. “QuVa was able to step in then, which took a stressor off of us during that time frame.”

Funds Dry Up During Pandemic Before the pandemic, many hospitals and health systems, like Vanderbilt, were putting significant investments into pharmacy as one of their profit centers. However, with COVID-19 decimating the bottom line for many institutions, the availability of capital for major new investments, such as a 503B compounding facility, has dried up. “Of the CEOs and chief pharmacy officers I’ve spoken with, most of them say that prospectively trying to get into 503Bs probably isn’t in the works for at least another couple of years, financially speaking,” said Michael Souza, the CEO of New England Life Care (NELC), whose Advanced Compounding Solutions (ACS) 503B outsourcing facility is jointly owned by its 50-plus member hospitals (most in the Northeast). “We are experiencing an uptick in interest based on our model, so much so that we’ve created a joint venture with another system-owned 503B facility in Minnesota, and we are combining our efforts both to market to a broader base and provide more capacity for the increased demand we’re seeing,” said Keith Thomasset, PharmD, ACS’ vice president of clinical solutions and chief pharmacy officer. “I would say that this is at least partially attributable to pressures from the pandemic, especially for those hospitals that were considering developing their own 503Bs. But even pre-pandemic, the capital investment see 503B CHALLENGE, page 36

36 Policy

Pharmacy Practice News • November 2020

Sterile Compounding

503B CHALLENGE continued from page 35

and operating expenses associated with opening a 503B can get pretty scary if you’re going it alone.” Fagron Sterile Services US, another leading 503B outsourcing company, found early in the pandemic that it had to modify its production planning. “We had a significant increase, approximately 20%, in demand from our customers, with hospitals requiring new and different products or much greater quantities

‘We still do have outsourcing partnerships and always will. [Outsourcers] can have a portfolio of 50 items or more, but for smaller [in-house 503B] operations like ours, it doesn’t make sense to have all those products, especially if only one or two of our sites use them or the volumes are really low. There’s a place for both.’ —Kristina Bryowsky, PharmD of existing products for needs such as supporting high numbers of patients going on ventilators,” said Jason McGuire, who oversees operational and quality areas of

Fagron Sterile Services US. “They needed high quantities of narcotics like fentanyl and hydromorphone to sedate patients, and they just didn’t have the support

Read Pharmacy Practice News Anywhere, Anytime!

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within their facilities to provide the dosage forms and volumes they needed. Every day, there was something new that would pop up from health systems, and some of these products, quite frankly, we didn’t have immediately available,” McGuire said. “But we [were] still able to respond fairly quickly with something that would work and yet maintain a high level of quality.”

A Pioneer Partners Up The midwestern hospital system SSM Health, which operates more than two dozen hospitals and health centers in Wisconsin, Illinois, Oklahoma and Missouri, was the first health system to register as a 503B sterile compounder in 2014, and remains one of only a handful of such systems in the country. SSM Health currently produces about nine products in-house. Because operating rooms closed to elective surgeries during the height of the pandemic, SSM Health pharmacy director Kristina Bryowsky, PharmD, said her facility shifted production toward bags for the ICU and away from OR syringes. “We saw a reduction in volume overall because of the ORs, so we shifted the days we would have produced other products to make sure we stocked up heavily on IV products for the ICUs, so we never had a shortage of those bags. That was a big relief for our ICU team,” said Bryowsky, a Pharmacy Practice News editorial advisory board member. In December 2019, SSM Health had started its first round of testing to add fentanyl to its list of compounded products, but after the pandemic began, the system was unable to access active pharmaceutical ingredients (API) to complete the next two rounds of testing. Bryowsky said they will complete that testing before the end of the year, but in the meantime, to accommodate the high volume of fentanyl needed at the system’s larger hospitals, they use either an outsourcer or compound in-house under 503A’s internal <797> seven-day BUD limits. “Some of our bigger centers had allocations with larger outsourcers, but if you didn’t have that already, you weren’t going to get it during COVID-19,” Bryowsky said. “Because our ORs were closed and care had shifted to patients who were incredibly acute, the volume wasn’t as high. So we were able to spend the extra time to make internal batches of 300 bags with 2- or 5-mL vials, which is not

Policy

Pharmacy Practice News • November 2020

Sterile Compounding

Flexibility From the FDA

uring the COVID-19 pandemic, the FDA provided some flexibility for both 503B outsourcing facilities that produce large batches of product with or without prescriptions while adhering to current good manufacturing practices (CGMPs), as well as 503A entities, which are traditional compounding pharmacies that compound in accordance with patient-specific prescriptions and comply with U.S. Pharmacopeia (USP) standards. In April, the agency issued two guidance documents establishing temporary policies regarding the compounding of certain drugs. For 503Bs, the FDA said that under the current state of supply disruption, it would not take action against an outsourcing facility for compounding a drug that is considered essentially a copy of an approved drug, or for using bulk substances not on the FDA’s approved Bulks List if those drug products are used to treat COVID19 for hospitalized patients. The agency also would not pursue enforcement against 503Bs for not meeting CGMP requirements for product stability testing and establishment of an expiration date, provided the outsourcer used shorter default beyond-use dates (BUD)s as specified by the FDA. Furthermore, in an unprecedented move, 503As would be temporarily permitted to compound drugs in short supply for hospital patients with COVID-19 without a patient prescription. “They’ve flexed pharmacy,” said Eric Kastango, BSPharm, the vice president and managing partner at Kastango Consulting Group. “The 503Bs have capacity limits: There are only so many doses they can make and they only have so much ability to ramp up production to meet demand. With the COVID crisis and the number of patients who needed emergency medications, they could not keep up. So, the agency published a guidance of when a 503A can do compounding that is typically limited to a 503B, identifying half a dozen mostly critical care, anesthesia and pain management agents.” Still unknown: the question of when and how the FDA will ultimately implement its draft “one mile” rule, which allows 503A compounding hospital pharmacies to distribute compounded drugs to health care facilities owned and controlled by the same entity as the pharmacy, as long as they are located within a one-mile radius of the pharmacy. The rule, first released in draft form as part of the agency’s 2016 compounding guidance, is based on the reasoning that a central pharmacy sending compounded drugs beyond the one-mile limit would be operating like a 503B pharmacy but not regulated like one. In its April 2020 guidance, the agency made it clear that the rule was still in draft and would not be enforced at present. “The FDA has been saying for well over a year now that the new version is coming, and that they are considering all of the comments they’ve received,” said Mike Koch, the senior vice president of professional services for Central Admixture Pharmacy Services, a national network of outsourcing pharmacies. “They have also previously hinted that they may alter the one-mile radius either by making it time dependent, in terms of beyond-use dating, or by extending the radius. But it’s all just rumors right now, and I wouldn’t begin to hazard a guess on what they will ultimately say or their timing.”

—G.S.

something an outsourcer will do anyway.” Because of the shutdown of elective surgeries in both hospital ORs and ambulatory surgery centers, compounders such as Fagron also were able to free up some of their capacity and shift it to meet hospitals’ ICU needs. “It was still a bit of a challenge, especially as it relates to narcotics—you have to go to the Drug Enforcement Administration [DEA] and request access for more than your original quote,” McGuire said. “Fortunately, the DEA was very responsive and helpful, as was the FDA. For example, if there was a product that we had never created before within our facility, we might not have performed the full stability testing or validation around it. So we were

permitted to leverage our partner laboratories’ data available via R&D or the published literature, and then using FDA guidance, get something out there, even though it might have more limited dating. They were really trying to find ways for outsourcing facilities to be flexible during this extraordinary time, to meet patient needs while still maintaining our responsibility for the high quality of the products we produce.” The February closure of PharMedium, AmerisourceBergen’s compounding business, was a double whammy for hospitals in the Northeast, noted Stuart Hinchen, the co-founder and chief executive officer of QuVa. “The initial wave of COVID hit the Northeast particularly hard, and

that was also an area where PharMedium had been very strong,” Hinchen said. “So a lot of hospitals were really cut short, and we were getting four times the regular demand for certain products, particularly in critical care. We had to give preferential treatment to COVID-related products wherever we could. We looked at other inventory we had on the shelves, and where we had adequate reserves, slots that would have gone to that inventory were reallocated to COVID-related products. Throughout March and April, every day was a major production effort and there really was no playbook.” As changes in the pandemic have rippled throughout the country, along with reopenings of elective procedures, outsourcers have worked to keep up with shifting demand. “COVID-19 became less frantic in May, but then elective surgeries started to open up in June, so we went through an oscillation as the health networks were extremely keen to get those going again,” Hinchen said. “Then in the summer, COVID-19 cases spiked in the Sun Belt and we had dual pressures of both COVID-19 and elective surgeries.” QuVa, NELC/ACS and Fagron all have increased capacity to meet the changing demand. QuVa has added more than 100 people to its labor force this year, with more staffing planned in the immediate future. “We put on a third shift in our Sugar Land site, which handles the bulk of our compounding work, and five days a week we are running 24/7 with stopgap work over the weekend,” Hinchen said. The company’s 75,000-square-foot facility in New Jersey will double in size over the next 12 months, and a lease on a new facility in Sugar Land also will double the company’s current 75,000-square-foot footprint in Texas. Similarly, NELC/ACS has added weekend shifts and filled all its hoods on the weekday second shift.

A Need to Pivot Quickly Although NELC/ACS, like its non-hospital-owned competitors, experienced an early increase in demand for some supplies at the height of the pandemic, particularly products for patients on mechanical ventilation, Thomasset said there was never significant concern that they would not be able to meet demand. “We tend to keep at least three to four months’ worth of API on our shelves, so API shortages that affected some hospitals were not affecting us. The FDA had also provided guidance that we could compound sterile preparations from sterile API with a small extension beyond the current USP <797> BUD without

requiring studies. That gave us upwards of about a month’s worth of expiration.” (See sidebar.) McGuire said the biggest lesson for 503B compounders from the COVID-19 pandemic has been understanding how to pivot very quickly. “You need to have a culture in your business where people are willing to do whatever it takes to meet patients’ needs,” he said. “It was amazing to see how folks rallied around each other and made sure we did everything possible to get medicine out the door to wherever the needs were.” Vanderbilt is still in discussions about creating its own 503B facility—a conversation that Dickerson said will likely take several years—and does plenty of its own 503A compounding, with only about 10 products outsourced. But regardless of what happens with those plans, the medical center still will continue relationships with 503B compounding outsourcers. “Even aside from the pandemic, we know there are still some products that it doesn’t make financial sense for us to make in-house,” she said. “Some institutions still have fears associated with 503Bs, and frustrations with them because the consistency of product availability may not always be what people would hope. But in these critical situations, I cannot underscore enough the importance of having these [outsourcing] relationships, and even multiple relationships for redundancy.” Bryowsky agreed. “We still have outsourcing partnerships and always will. [Outsourcers] can have a portfolio of 50 items or more, but for smaller [in-house 503B] operations like ours, it doesn’t make sense to have all those products, especially if only one or two of our sites use them or the volumes are really low. There’s a place for both.” Eric Kastango, MBA, BSPharm, the vice president and managing partner at Kastango Consulting Group, cited cost as perhaps the biggest barrier to taking a DIY approach to 503B compounding. “[It] costs, by conservative estimates, $5 [million] to $15 million and three years to open your doors,” he said. “It’s not a quick fix, not just <797> on steroids. “Most of the people I have spoken with are going to multiple sources and have created relationships with more than one 503B,” Kastango added. “Most people can’t get by using just one 503B vendor, because they don’t all make the same products, or they are looking for supply redundancy. This pandemic has given us a new appreciation for just how important this unsexy part of pharmacy—compounding and distribution—really is.” —Gina Shaw The sources reported no relevant financial relationships beyond their stated employment.

38 Technology

Pharmacy Practice News • November 2020

Safe Handling

COVID-19 Prompts a Second Look at CSTDs I

n April, with COVID-19 cases increasing nationally, Cone Health oncology services in Greensboro, N.C., took a fresh look at closed system drugtransfer devices (CSTDs). The service, which operates five cancer care centers across the state’s North Central Piedmont region—with a sixth center slated to open in September 2021—had been tasked along with other Cone Health services to find ways to bolster operational effectiveness in light of the pandemic’s potential threat to health-system operations. Cone Health was not within an epicenter of coronavirus infections at that point, but organizational concern was rising over the likely revenue impact of a COVID-19 patient surge and about people losing health insurance and income due to local business closings. The aim was to get ahead of a possible crashing wave with a lean approach to costs, particularly of consumables. Medication use was an obvious target. “Drug costs were a huge driver, one of the largest cost centers out there,” said Andre D. Harvin, PharmD, the director of pharmacy oncology. For Cone Health’s cancer care clinics, which treat some 3,800 to 4,200 patients each year, medication use also meant the hefty costs associated with preparing and administering antineoplastics, including those associated

6 Steps For Vendor Evaluation

ost health systems have already integrated closed system drugtransfer devices (CSTDs) into their compounding and administration processes. But for those still weighing their options, Fred Massoomi, PharmD, a senior director at the pharmacy consulting firm Visante, offered six steps to aid in decision making.

A pharmacy technician compounds a hazardous medication using the BD PhaSeal Optima closed system drug transfer device. USP <800> requires CSTDs for administering antineoplastic compounds, but “recommends” the devices in preparing the drugs.

with disposable CSTDs and IV infusion bags and lines. Until April, the oncology clinics had been using BD’s PhaSeal CSTD system. “When COVID-19 hit, we saw it as an opportunity to sit down and say, ‘This is one of our more expensive consumables,’” Harvin said. “Should we reevaluate?” The answer was yes. The assessment that took place over the

Chemotherapy Robots an Aid In High Volume

ike many other health systems with high-volume oncology clinics, Cone Health centers employ robots and other automation technology to increase productivity and dose accuracy while further shielding technicians from harmful chemotherapy exposure. Two of the health system’s largest clinics, at Wesley Long Hospital, in Greensboro, N.C., and Alamance Regional Medical Center, in Burlington, N.C., deploy APOTECAchemo robots (Apoteca USA, an affiliate of Italy’s Loccioni industrial engineering company) to automate compounding of most An inside look at the Apoteca Chemo hazardous drugs. Cone Health’s robot as it performs a manipulation of other clinics are equipped with a hazardous medication. The platform APOTECAps, a guided automated uses barcode scanning, gravimetrics system that uses gravimetrics and a sterile environment to perform its to weight dose ingredients and compounding independently. ensure compounding accuracy. “Everything we compound we try to push through gravimetrics, whether hazardous or nonhazardous,” said Andre D. Harvin, PharmD, BCPS, the director of pharmacy oncology at Cone Health, in Greensboro. “We are actually in the midst of expanding [APOTECAps] because we don’t have it in every hood.” Other compounding automation companies competing in the same space include Equashield, Grifols’ Kiro Oncology and Omnicell. —B.B.

following weeks was similar to ones that other integrated health networks have initiated to comply with USP General Chapter <800>, which took effect in December. Budget dollars have typically played an outsized role in these discussions, said Patricia C. Kienle, RPh, MPA, the director of accreditation and medication safety for Cardinal Health. “If money wasn’t the issue, nobody would be talking about this. We’d all be doing it. “But people need to be safe,” added Kienle, who is also a member of the USP Compounding Expert Committee. “So USP <800> requires CSTD use for administration of Table 1 antineoplastics when the dosage form allows.” (It also “recommends” use of the device in preparing the drugs.) Kienle also noted that “the vast majority” of people she had spoken to had already acted to implement the USP employee safety standards (surveys of health systems support that). “There’s some utility for using [CSTDs] for other drugs, but that’s up to individual organizations to look at what works for them.” Kienle added that vetting the merits and potential weaknesses of prospective CSTDs should not be done independently by either pharmacy or nursing. “This is a team sport,” she stressed. “It needs to be coordinated in a system, and it cannot just be the cheapest one on the buying group contract.”

Coordination Is Key At Cone Health, team coordination was central to an evaluation that led to the deployment of a new CSTD system at the end of May. The investigation included virtual presentations from device makers, including BD, that were asked to demonstrate, via Zoom, what made their

Look at the FDA 510(k) clearance document. The idea is to see what the device was approved for and what information was submitted to the FDA to obtain clearance. It will provide a good understanding of the thoughts behind the device and how and why it was developed.

Go to company websites. These can be great resources for educational materials, as well as information on the size of the product portfolio for the device. If it has just a few pieces, it may not meet all of your needs.

Schedule a visit. If a candidate looks promising, spend time with a company representative, virtually if need be. The meeting needs to cover detailed information on the device and how it would work within your compounding and administration workflow.

Ask for a brief trial run. This is to allow pharmacists, technicians and nurses to see how well the device performs within your system. It really depends on your setup: how you use your primary engineering controls to move hazardous drugs through the compounding process and how well the device fits into nurses’ administration environment.

Ask additional questions about materials used in making the device. Find out how the device was tested to demonstrate conformance with National Institute for Occupational Safety and Health standards for preventing toxic emissions and pathogenic ingress. Has it been tested on the drugs that will be used with the device to ensure compatibility, and will there be any leaching or other issues that can occur with certain drugs?

Review all the materials sent to the FDA for clearance of the CSTD. This includes 510(k) letter, marketing clearance statements, comparative studies to the predicate devices, etc. —B.B.

CSTDs safer and easier to use—and to relate how much educational and other support would be forthcoming. Price was another consideration. Harvin said he also called peers at

Technology

Pharmacy Practice News • November 2020

Finance

Dose Round continued from page 1

In this prospective study, the researchers selected 24 high-cost and frequently used infusion drugs and created standardized dose-rounding rules that they then integrated into the Epic EMR system (abstract PM01). Any dose of these drugs calculated to be within 10% of the nearest vial size was automatically adjusted up or down to the nearest full vial, said Katie Eschenburg, PharmD, an infusion pharmacist at the Rogel Cancer Center at Michigan Medicine and a coauthor of the study. Physicians would then review the rounded dose to ensure they agreed with the rounding plan, and could opt out, if needed, Hough said. The 10% value was chosen based on HOPA guidance on dose rounding, which suggests adjusting the dose of many oncology drugs by 5% to 10% is unlikely to have a clinical effect. However, the effect of rounding on patients has not been well studied, Hough noted. From July 1, 2018 to June 30, 2019, more than 10,200 doses of the selected drugs were administered at Michigan Medicine, most patients in outpatient clinics. Half of the administered doses were rounded to the nearest vial size; of these, about 50% were rounded up and about 50% were rounded down, said Jacqueline Dela Pena, PharmD, a PGY-1 pharmacy practice resident at Michigan Medicine and co-author on the study.

other oncology organizations to hear about their experiences with CSTDs, including device failures, because, he noted, “these things happen.” But perhaps the most important input came from Cone Health’s end users themselves: the technicians and nurses. In the end, the nod went to BD’s Optima PhaSeal CSTD. It wasn’t that the other devices that were evaluated didn’t provide a high degree of compounding and administration safety; they did. The deciding factor, Harvin noted, was technicians’ and nurses’ comfort level based on their familiarity with PhaSeal and BD’s support system. He added that the newer Optima PhaSeal CSTD now uses a straight push-and-click action to connect with IV lines rather than the older device’s push-and-twist manipulation, which had prompted some complaints about repetitive motions needed to line up the red lines indicating secure connections. “We had to go through these evaluations very quickly,” Harvin said. “We went live with the new Optima PhaSeal system clinic by clinic, making sure each was ready to go. We saved the largest clinic here at Wesley Long Hospital for last. Everything was done by the end of May.”

Rounded doses led to about

$3.5 million in savings on outpatient infusions and

$130,000 in savings from inpatient infusions, resulting in about

$3.6 million saved overall. In all, the rounded doses led to about $3.5 million in savings on outpatient infusions and $130,000 in savings on inpatient infusions, resulting in about $3.6 million saved overall, Dela Pena said. The drugs associated with the highest annual savings were trastuzumab, which accounted for $756,000 in savings, and ipilimumab (Yervoy, Bristol-Myers Squibb), which accounted for $494,000 in savings. The study assumed the pharmacy used the smallest number of vials to fill each order, and there weren’t any dosing errors, Dela Pena said. It would have been extremely labor-intensive to review all 10,000-plus doses for inefficient vial use, but it’s also unlikely the pharmacy was 100% efficient, which could affect final cost savings, Hough noted. Dose rounding in and of itself is not a new idea, commented HOPA President David DeRemer, PharmD, the assistant director of clinical therapeutics at UF Health Cancer Center, in Gainesville, Fla. But automating the process is unique, said

Training Support Is Key Ryan Forrey, PharmD, the senior manager of Market Development for Hazardous Drugs at BD, said several factors need to be considered when selecting a CSTD. “From a clinical perspective, the things I think about are evaluating safety and performance of the CSTD as well as the ergonomics and ease of use, as well as the history and experience others have had with CSTDs.” What’s more, Forrey said, it’s not just the CSTD itself that needs to be evaluated. “There is monitoring and understanding your environmental conditions. Can your device manufacturer help with that?” He added: “How good are they in installing and implementing the device? You can have the best device in the world, but if you can’t implement it or train people and teach them how to use it, you’re not going to be successful.” —Bruce Buckley Massoomi reported he is a consultant for BD. Kienle reported she is a member of the USP Expert Compounding Committee; the views she expressed for this article are her own. The remaining sources reported no relevant financial relationships beyond their stated employment.

DeRemer, who was not involved with the study. “The integration of automatic dose rounding, within 10% of the original dose, into the electronic ordering system provides the opportunity for drug savings as well as reducing medication errors.” Automating the system removed all the back-end labor for the pharmacist because everything is integrated into the EHR, Dela Pena said. Because the system proved so successful, the project is ongoing and the researchers are testing other oncology agents to add to the rounding protocol, she said, adding that the team also is looking to implement dose-rounding beyond oncology drugs to other high-cost therapies, such as rheumatoid arthritis agents.

Hough, Dela Pena and Eschenburg plan to submit their study for publication. They said they hope this protocol could eventually help other institutions implement similar automatic systems and reap the cost savings. “I think the big key takeaways about this project are that a little up-front work on dose-rounding rules can be implemented into an EHR,” Hough said. “If institutions don’t have the ability to roll this out across all oncology medications, a review of the top 10 or 20 in the drug spend can still yield a very significant savings.” —Jillian Mock The sources reported no relevant financial relationships.

40 Tecnology

Pharmacy Practice News • November 2020

Supply Chain

ADC optimization, data mining among keys to success

Getting a Handle on Drug Inventory During COVID-19 T

he surge in demand for sedatives and other medications brought on by the peak of the COVID-19 pandemic presents lessons that pharmacists can learn for better drug inventory management, pharmacists said during a recent webinar sponsored by BD. The pandemic “has certainly challenged our society and health care system m in many ways, even in geographic areas that frequently managee natural disasters, such as fires or hurricanes, and have very experienced disaster managers,” said Doina Dumitru, PharmD, MBA, the senior director of medical affairs for BD, during a discussion on managing drug inventory during a pandemic. “The current crisis requires a new set of rules and playbooks.” One of the most serious issues to emerge has been employee safety, Dumitru said, which can be enhanced by limiting traffic in and out of facilities, including the pharmacy. During normal operations, pharmacy staff touch their drug inventory at least once a day whether ordering, refilling or other tasks, she said. During a pandemic, the safety strategy of reducing the number of trips to automated dispensing cabinets by increasing inventory of critical medicines limits staff exposure to highrisk areas of the hospital. In addition, Dumitru said, in a pandemic, supply needs can change very quickly—sometimes within hours. As facilities become overwhelmed with high-acuity patients requiring many interventions,

iitems such as swabs, IV lines and drugs can be depleted very quickly. So it’s important to keep a concise list of those critical supplies, she advised, and take inventory at least daily, if not more often. It also may be necessary to adjust par levels up for those drugs and supplies proactively, because historical par levels won’t be sufficient to meet the anticipated surge, she said. Some organizations reported four- to fivefold increases on inventory run rates for supplies. Finally, Dumitru said, leverage recent regulatory allowances to maximize all drug supplies on hand, such as centralizing some sterile compounding and distribution activities. Preplanning also can be helpful for pandemics when there is time, said W. Perry Flowers, RPh, MS, the vice president of medical affairs and Enterprise Medication Management for BD. “We [were fortunate] with this particular

Strategies for Managing Shortages During a Pandemic • Recognize that first-line therapy items might be in short supply and could be exhausted, and go to your pharmacy and therapeutics committee with recommended protocols and at least two approvable, substitutable items. This will include your first, second and third lines of therapy for antibiotics and antivirals. • Prepare to switch alternative therapies quickly, as usual therapies are depleted rapidly. • All alternatives should have usage guidelines, and information technology staff should be able to update drug libraries and order sets quickly as alternative drugs are stocked. • Clinicians such as physicians and nurses should be trained on how to order and administer alternative therapies. • Be prepared for large quantities of IV infusions, and adjust dosage form volumes accordingly. Larger bags of certain drugs, particularly those for sedation, will likely be needed. This allows nurses to limit the number of bag changes needed for these medications. • Calculate drug inventory at least daily, if not more often. Leverage any technology solutions your vendors may offer to allow par level changes to be made for automated dispensing cabinet. • Use all data available to create forecasts and projections for supplies; it’s one of the most powerful strategies in ensuring continuity of care for patients. Source: Doina Dumitru, PharmD, MBA.

‘I’m so grateful that the entire country didn’t surge at one time, because while New York and other hot spots needed a big spike in medications, other places like our state didn’t need as much. Now, unfortunately, it may be the reverse.’ —Erin R. Fox, PharmD pandemic to have a little bit of forewarning as to what might be coming,” Flowers said. Studying data from China, or New York’s response, for example, can give hospital leadership some clues what to expect, as can using data that can serve as a proxy for expected demand, such as reviewing statistics from the CDC comparing COVID-19–like illness to influenza-like illness and the percentage of related emergency department visits, to help with emergency preparedness. Overall, during COVID-19 surges, many hospitals ran low on supplies, not only medications and ventilators but items for supportive care, such as antiseptic mouth rinse for ventilated patients, Dumitru noted. By examining those shortages, a number of valuable lessons can be gleaned (sidebar).

A Different Kind of Shortage The pandemic presented an unusual situation with drug shortages due to a spike in demand, as opposed to those caused by manufacturing delays or other more common issues, commented Erin R. Fox, PharmD, BCPS, the senior pharmacy director of Drug Information and Support Services at the University of Utah Health, in Salt Lake City. “Usually a shortage is a really bad surprise, and you don’t have a lot of advance warning,” Fox said. “In this case, you could see the tsunami coming, but you may not have been prepared for it or you just did the best you could and hoped you were prepared for it.” It can be a knee-jerk reaction to try to order six months’ worth of all medications,

she added. But consider where you would store that much, and whether you really need it or are taking it from other hospitals that are in greater need. “I’m so grateful that the entire country didn’t surge at one time, because while New York and other hot spots needed a big spike in medications, other places like our state didn’t need as much. Now, unfortunately, it may be the reverse.” Try to prepare, and be data-driven if you can, she advised. Tally up your hospital’s preferred drugs, think about what your daily dose would be, and make calculations from there. Consider you may have limits in what you can order or what you can store. Work together as a team within your hospital to share resources. For example, her hospital’s anesthesia department was willing to make some changes to their practice to conserve propofol for the ICUs. The pandemic was made challenging by the many products that hospitals need, such as midazolam and fentanyl and some paralytics; some saw supply chain issues before the pandemic, Fox said. Another challenge has been in updating informatics systems to account for different dosage forms or strengths. During a previous morphine shortage when her hospital switched from syringes to vials, it took an estimated 100 hours of informatics work to make the changes, she said. To access a replay of the webinar, see bit.ly/2J9b6TJ. —Karen Blum The sources reported no relevant financial relationships.

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Health-system specialty pharmacies:

Lots of Data, but What Do Payors Want to Know? A

lthough health-system specialty pharmacies have access to an abundance of clinical and dispensing data, according to an expert who spoke during a session at the 2020 NASP Annual Meeting & Expo Virtual Experience, some pharmacies in outcomes-based contracts continue to ask payors the same question: What outcomes do they want to know about? That’s the “million-dollar question,” Bryan Schuessler, PharmD, MS, the director of home infusion and specialty pharmacy at Saint Luke’s Health System Kansas City, in Missouri, said during the session, a one-day pre-conference workshop on health-system specialty pharmacy. “What is it that people really want to see on that payor line? We’re not sure from payor to payor what’s valuable at this point.” Many other health-system specialty pharmacies that are drawing up outcomes-based contracts are likely to be in the same boat, finding that payors do not always know what outcomes they want to have measured as part of a

contract, Schuessler said. “Is a clinical outcome SVR [sustained virologic response] or is it days-to-therapy, or is it adherence?” he asked. Schuessler noted that his team draws on a large pool of data from the Saint Luke’s electronic health record system as well as dispensing and clinical documentation data from their retail and specialty pharmacies. “We’re documenting all these things. We’re following patients. We’re making notes. We’re collecting all these data, but … we’re still struggling to understand what [payors] want to see,” he said. At West Virginia University Hospitals, in

Specialty Pharmacies Offer Valuable Data to Stakeholders

range of stakeholders speaking at the NASP 2020 Annual Meeting & Expo Virtual Experience had a clear message for specialty pharmacies, whether embedded in health systems or stand-alone: We want your data. One presenter said data collected through prior authorizations, for example, can help manufacturers understand why some prescriptions are left unfilled. “Perhaps the diagnosis isn’t correct,” said Cheryl Allen, the principal consultant at Blue Fin Group. “Or maybe there’s a lack of education among the prescribers on the use of the drug.” In those cases, manufacturers can tailor their physician communication to ensure the drug is prescribed appropriately, Allen said. “The more we know about our patient’s journey, the better we are positioned to support them.” Any information that manufacturers can use to improve their grasp of the barriers that exist to medication use or prescription fulfillment “is really critical,” agreed Jenny Jackson, the head of strategy, specialty and strategic markets at UCB Pharmaceuticals, in Kansas City. “Without actionable data, you really lack the ability to

pivot or course-correct as necessary,” she said. “I can’t stress enough the value of that collaborative approach” between manufacturers and specialty pharmacies. Payors, too, place a premium on the data that specialty pharmacies gather, as Ryan Atkinson, PharmD, the senior director of specialty pharmacy strategy at Maxor National Pharmacy Services, a pharmacy benefit manager, said. While Maxor has a separate specialty pharmacy arm, the company’s two sides often work “synergistically,” he said. For example, Atkinson said the PBM uses data analytics to develop algorithms “that can identify specific trends in how a patient is taking their medications, when they’re getting their refills, and even relate it to their age, in some cases to their overall disease state, or to some of their comorbidities.” Those algorithms can help direct patients to clinical programs to optimize the safety and efficacy of a medication, he explained. —David Wild The sources reported no relevant financial relationships.

Morgantown, a lack of payor clarity on the question of outcomes led Louis Sokos, BS Pharm, MBA, the director of allied health solutions, specialty pharmacy services, to formulate what he believes is a universally applicable equation. Specifically, he said, demonstrating the impact of specialty pharmacies on both clinical outcomes and total cost of care for the health system is “a value proposition that I think any payor can see.” He stressed that health-system specialty providers have “to make sure we manage our patients as efficiently as we can and drive down costs overall … to make sure we’re a player in this

space.” For example, his specialty pharmacy looked at a group of the health system’s patients receiving antiviral medications and documented SVR rates that were higher than those of most nearby pharmacies outside their system, showing “a better return on investment” for payors, he said. Other health-system specialty pharmacies should take similar initiative and articulate what they believe to be the value of their services, suggested session moderator Erin Hendrick, the senior vice president of hospital strategy at Shields Health Solutions, headquartered in Stoughton, Mass. “We seem to have, as a collective, been very reactive to the data that’s been requested of us,” she said. Instead, Hendrick said, “I think there’s an opportunity for health systems to better define what we believe good specialty outcomes really are.” —David Wild The sources reported no relevant financial relationships.

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A Windfall in Savings From Biosimilars T

ransitioning patients taking infliximab to a biosimilar product and improving adherence to imatinib are among the strategies specialty pharmacists at Boston Medical Center Health System (BMC) used to help the system better use health care resources, according to a session at the 2020 NASP Annual Meeting & Expo Virtual Experience. The shift from originator infliximab to an infliximab biosimilar is forecasted to yield approximately $500,000 in annual savings, without compromising clinical outcomes, reported Alexander Pham, PharmD, BMC’s director of pharmacy strategy and business development. BMC’s specialty pharmacy successfully led the switch of 146 out of 151 eligible patients (97%) from the originator infliximab (Remicade, Janssen) to infliximab-dyyb (Inflectra, Pfizer) between March 2018 and June 2019 (J Manag Care Spec Pharm 2020;26[4]:410-416). As of October 2018, 56 patients (89%) continued with infliximab-dyyb after the transition. Of the 46 patients with 12 to 15 months of post-transition data, 38 (83%) remained on the biosimilar product. Sixty-three of 75 eligible patients (84%) with inflammatory bowel disease (IBD) transitioned from infliximab to infliximab-dyyb. In a subgroup of 40 patients with IBD who had available scores on the Harvey-Bradshaw Index or the Simple Clinical Colitis Activity Index from both before and after transition, 36 (90%) maintained remission. “This project represents one of many opportunities to reduce costs

without compromising outcomes, and it wouldn’t have been possible without the leadership of an advanced specialty pharmacy program and the insights that provides,” Pham said during the session, a one-day pre-conference workshop on health-system specialty pharmacy. “As more and more biosimilars come out, that represents a huge opportunity to decrease costs and an additional value point specialty pharmacy can bring to your institution,” said David Mitchell, PharmD, the pharmacist manager of specialty operations at UC Davis Health. He praised the BMC researchers for focusing not only on the cost containment aspect of the biosimilar switch, but also the outcomes that were achieved with new biosimilar products.

Improving Imatinib Adherence BMC’s specialty pharmacy program also successfully improved adherence to imatinib (Gleevec, Novartis) among patients with chronic myeloid leukemia. Adherence is a key driver of treatment success for this agent, Pham explained. “Patients who are adherent have a 76.7% five-year event-free survival rate, compared with just under 60% if you do not take the drug the right way,” he said, referring to results from a study in the American Journal of Hematology (2011;86[6]:471-474). BMC’s specialty pharmacy set an adherence goal for its patients receiving imatinib of a proportion of days covered (PDC) of 90% or higher. “Among the patients we observed at BMC specialty

Easing Off on Accreditation continued from page 1

of the day, the patient needs to get their medication. While that absolutely needs to be done right and up to quality standards, we have allowed accredited facilities to make changes where necessary during the pandemic.” The ACHC encourages its accredited pharmacies to document any deviations from normal practice imposed by pandemic-related challenges, preferably with a start date and a plan for reassessment at regular intervals, Pritchett said. “We have been having conversations daily with our customers about what is going on in their facilities. We had hoped that the impact of the pandemic would last only a few months, but the fact is that we don’t know when the end [will be] in sight.” Another accrediting body, URAC, has seen its accredited pharmacies affected by the pandemic, with the impact ranging all over the country as “hot spots”

have arisen and subsided, said Heather Bonome, URAC’s director of pharmacy. “We recognize that patient care has to be a top priority for these pharmacies, and if they need to prioritize that above a certain accreditation deadline, then that’s the right decision to make.” URAC developed a “temporary noncompliance template” for its accredited organizations to track such measures, Bonome said. “For example, if your telephone performance measures were not being met for a certain period of time because people were sick, the template provides you with what you need to report about when that started and what you did about it.” That template, as well as other measures, waivers and schedule changes, can be found in the COVID-19 section of URAC’s website. ACHC also has established a

pharmacy, the average PDC was 93.5%,” Pham said. However, he added, when they included patients using outside pharmacies, they “saw PDCs of 75% to 80%, and sometimes far lower.” Patients who achieved 90% or better adherence as measured by PDC had significantly improved health care resource utilization compared with those whose average PDC fell below 90%, as measured by annual average inpatient visits (0.4 vs. 4.1), total inpatient days (1.8 vs. 14.8), average length of stay in days (1.3 vs. 4.5), outpatient visits (30.2 vs 41.7), and total average cost per year ($58,000 vs. $107,000) (unpublished data). Underscoring the value of such initiatives, Mitchell told Pharmacy Practice News that “there are significant

economic and outcomes opportunities associated with h specialty pharmacy cy for an [integrated delivery ivery network]. In 2010, when we were preparing to launch our specialty program, the University HealthSystem Consortium had valued the average academic medical center specialty pharmacy opportunity at about $200 million, and that was 10 years ago, so you can imagine what that’s grown to today.” —Gina Shaw

COVID-19 section of its website. In the early months of the pandemic, accrediting organizations postponed many of their on-site surveys. “Some of that was driven by CMS [the Centers for Medicare & Medicaid Services], which asked accrediting organizations to do postponements, and some was state driven,” Pritchett said. “We pushed back deadlines thinking that things would come back in a few months. But when we began to realize that we didn’t know where this was headed, we began to implement virtual site surveys.” So far, the virtual surveys have been successful. “The technology is so fantastic, with the ability to share screens and share cameras, that it works very well and is rapidly becoming the norm,” Pritchett said. “We still prefer to do on-site surveys, and have done things to facilitate that when possible, such as using surveyors who live in the state to go directly to the pharmacies, but even those initiatives are difficult in the current situation.” URAC also put its on-site reviews on

hold, Bonome said. “We already had a good amount of experience with virtual reviews and a platform to do that in place, so it was pretty straightforward to move to fully virtual. For newly accredited pharmacies, we do intend to follow up with on-site observations as soon as appropriate. Month by month, we look to see how long we’re going to continue doing this. What we are stressing with everyone is that while things like due dates and expiration dates are important to adhere to, we want them to make sure they put patient care before filling out an application.” —Gina Shaw

Pham reported no relevant financial relationships. His co-authors Francis Farraye, MD, MSc, and Bhavesh Shah, RPh, reported financial relationships with companies including Janssen, Merck and Pfizer.

The sources reported no relevant financial relationships.

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Pharmacy Practice News (October 2020)

Articles inside

Outpatient antibiotic stewardship spreads its wings

TECHNOLOGY

An urban medical center tackles the opioid crisis

A $500K windfall from biosimilars

CLINICAL