April 2015 by McMahon Group

Bridging the gap between the hospital and alternate-site care Volume 4 • Number 2 • April/May 2015 • specialtypharmacycontinuum.com

In This Issue Business & Finance

A start-up specialty pharmacy embraces MHA clinical therapy management system.

An ‘unregulated environment’

How Wide Is the Safety Gap for Home Infusion?

Policy

Zarxio legal battle shows rough road ahead for biosimilars.

Clinical

8 10

IVIG and primary immunodeficiency. A hi-tech approach to boosting HIV drug adherence.

Home parenteral nutrition successes on tap at A.S.P.E.N.

Operations & Mgmt

19 20 22

SP network growing for new cystic ﬁbrosis Kitabis Pak. Avella, Sentry to partner on 340B guidance. Hospitals continue to make a splash in SP market.

Measuring Value Of Accreditation A Worthy Effort

ny specialty pharmacy can claim to provide “high-touch” patient care, with practitioners delivering safe, effective drug therapy along with the latest compliance tips to achieve the best possible clinical outcomes. The difference between claiming such expertise and actually proving it, however, is where specialty pharmacy accreditation comes in. The seal of approval comes with many benefits—as well as challenges, not the least of which is convincing the C-suite that the effort will yield a solid return on investment (ROI).

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Phoenix, Ariz.—With key specialty pharmacy players like Walgreens, CVS Caremark and Cardinal Health entering or expanding their investment in the home infusion therapy market, and infused drugs accounting for $35 billion of annual specialty drug spending, safety issues affecting home infusion have become increasingly important. However, there’s not a lot of national safety data specific to home infusion, according to Steve Kennedy, PharmD, the national director of infusion pharmacy services at Walgreens Infusion and Respiratory Services in Deerfield, Ill. “But the Institute of Medicine estimates that approximately 1.5 million preventable adverse drug reactions occur every year, and 20% of these are attributed to poor communication at transitions of care,” Dr. Kennedy said during a workshop on medication safety held during the National Home Infusion Association’s 2015 annual meeting. And if there’s a player in the specialty pharmacy market that exemplifies the challenges of transitions of care, specialty home infusion must be it—particularly, Dr. Kennedy said, because of the lack of electronic interfaces among systems.

see ACCREDITATION, page 16

Standardization Lessens CRBSIs In Oncology Pts

“We traditionally still rely on verbal communication and faxed information that contain the patients’ medical history, medication list, physicians’ orders, laboratory results, etc,” he said. “These faxes can be 10 to 15 pages of information that the home infusion pharmacist or specialty pharmacist must sort through to find the pertinent

Long Beach, Calif.—In patients receiving cancer treatment and home total parenteral nutrition (TPN), the risk for catheter-related bloodstream infections (CRBSI) can be reduced significantly by a standardized management approach, according to a study done in part with Coram CVS/specialty infusions services patients. “Home parenteral nutrition has gotten a bad reputation, mainly because of a high incidence of catheter-related infection, but this study shows we can significantly reduce that risk,” said lead researcher Pankaj Vashi, MD, the national clinical director of gastroenterology, nutrition and metabolic support

see INFUSION SAFETY, Y page 11

see CRBSIs, page 15

Technological Challenges

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Now Available: Specialty Pharmacy Continuum iPad App

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FDA Approval Unituxin approved for pediatric neuroblastoma. See page 17.

Send us a script. Let us impress you.

A different kind of Specialty Pharmacy. One patient at a time. One touch at a time. At Diplomat, we want our patients to thrive. That’s why we offer the tools and services to achieve adherence rates over 90%.1 It’s why we help patients find the financial assistance they need: over $55 million used in 2014.2 It’s why we’re service-oriented, with a 99% satisfaction rating among patients 3 and 97% among prescribers.4 “High-touch” isn’t a buzzword. For us, it’s a deep-seated belief. And at Diplomat, we take it to a whole new level. 1 2 3, 4

Reported Q4 2014 2014 Diplomat Third-Party Funding 2013 Diplomat Patient and Prescriber Surveys

Specialty Pharmacy Continuum • April/May 2015

BUSINESS & FINANCE

Building a Better Clinical Management System Las Vegas—Large, complex undertakings often have deceptively simple beginnings. Take, for example, a prescription for a specialty medication. With only a few keystrokes, a provider can order the drug and move on to the next patient. But for a specialty pharmacy (SP) tasked with dispensing that prescription, the work has just begun. Indeed, a cascade of interventions must be initiated to ensure that optimal clinical and financial outcomes are met. To help SP providers succeed in that task, Managed Health Associates Inc. (MHA) has developed computerized clinical support pathways that enable providers to interact with patients during telephone consults in a standardized, traceable manner. Patient education, drug adherence and adverse-event management are just a few of the areas that can be enhanced and documented, according to Stacey Ness, PharmD, RPh, the director of specialty clinical services at MHA, who described the system’s capabilities at the 2015 MHA Business Summit. MHA’s Clinical Therapy Management (CTM) modules cover a wide range of clinical conditions, including hepatitis C, HIV, rheumatoid arthritis (RA), oncology and disorders requiring immune globulin therapy. John E. Ford, RPh, the vice president of clinical services at Barnes Healthcare Services, a startup specialty pharmacy based in Valdosta, Ga., evaluated several systems before choosing CTM, he told Specialty Pharmacy Continuum. “There are two or three others we looked at,” he said. “They all have their benefits and drawbacks, but for us, a few features of CTM really stood out.” One of CTM’s main strengths, he said, is the fact that its clinical pathways and metrics are not primarily

based on information provided by a drug’s manufacturer. “The [MHA] system also draws on the published literature for all the main therapies and conditions it covers,” Mr. Ford said. “That’s not necessarily the case with some of the other [vendors] out there.”

‘We know that by creating [an electronic] action item, we need to go back and complete some aspect of the patient’s care after [the initial phone assessment is completed.]’ —Stacey Ness, PharmD, RPh Mr. Ford pointed to another benefit: Although CTM does a good job tracking medication possession ratios (MPRs) and other measures of adherence, it also enables his pharmacists to go beyond merely documenting that a drug has been taken: the system also helps them conduct detailed clinical assessments of patients and record baseline and follow-up symptoms. “MPRs are fine, but with the steadily rising costs of specialty medications, payors are going to start asking why they are spending all of this money on specialty medications,” he explained. “The only way we are going to justify those outlays is to show that our clinicians truly are helping patients and physicians achieve

better clinical outcomes. The MHA system helps us do that in an efficient manner.”

CTM Basics Dr. Ness outlined how CTM works when a patient has just received a new prescription for a specialty pharmaceutical. When the SP clinician first accesses the system, patient demographic information, prescriber information, a medication list, dispensing history and other key information “are all there,” she said. Once the clinician reviews that information, the initial telephone assessment with the patient can begin in earnest. One of the CTM screens contains a suggested script that first prompts the clinician to introduce the CTM program to the patient—“why we are calling them, what types of issues we are going to discuss with them, how frequently we will be calling them for follow-up etc.” The clinician then performs the relevant diseasestate assessment, focusing on several areas, including whether there are any comorbidities or allergies that may compromise care. In the case of RA—a condition Dr. Ness used as a model for demonstrating CTM—several injectable products are used, some of which contain latex. “We want to make sure that a latex allergy screening test was done so that patients don’t develop allergic skin reactions from the needle cover,” she explained. During the initial assessment, patients are also asked about the type, extent and location of their RA symptoms, with drop-down menus available to the clinician for documentation—for example, left shoulder pain, left elbow pain and so on. Patients also are asked to describe their pain using a comparative pain scale from 0-10.

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see CLINICAL MANAGEMENT, T page 4

EDITORIAL BOARD

ART/PRODUCTION STAFF

HOME INFUSION

Michele McMahon Velle, MAX Graphics/Creative Director

Jay Bryant-Wimp, RPh Owner/CEO Accurate Rx Pharmacy Columbia, MO

Frank Tagarello, Senior Art Director/Managing / Director, r MAX Graphics James O’Neill, Senior Systems Manager

Randy Fasnacht, RPh Director of Pharmacy Advanced Infusion Services Akron, OH

Dan Radebaugh, Director of Production and Technical Operations

Volume 4 • Number 2 • April/May 2015

specialtypharmacycontinuum.com

Marty Barbieri, Production Manager Brandy Wilson, Circulation Coordinator

SPECIALTY PHARMACY N. Lois Adams, MBA, RPh Chairman, President and CEO Freedom Pharmacy Orlando, FL Randy Falkenrath, MBA Senior Vice President CVS Health Woonsocket, RI

McMAHON PUBLISHING Michael Sicilian President, Managed Health Care Associates, Inc. Florham Park, NJ Donald J. Vidic, RPh, MBA Vice President of Operations and Pharmacy Services Walgreens Specialty Pharmacy Carnegie, PA

Stephanie Holliday, PharmD Clinical Pharmacy Specialist Prosperity Specialty Pharmacy Falls Church, VA Cindy Kunzendorf, PharmD General Manager Accredo/CCS Locations Elmhurst, IL Hetty Lima, RPh, FASHP Vice President of Specialty Infusion Services Diplomat Specialty Pharmacy Flint, MI

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Specialty Pharmacy Continuum • April/May 2015

BUSINESS & FINANCE

CLINICAL MANAGEMENT continued from page 3

A detailed medication history is also taken because it can yield valuable information about potential roadblocks to drug adherence. For example, “we want to assess if this is the first biologic for rheumatoid arthritis that they’ve taken or if they have been prescribed any other medications for their condition, and if so, why did they discontinue those agents,” Dr. Ness said. “That gives us a better understanding of where in their treatment cycle they are, so we can manage them appropriately.” As for the new specialty drug prescribed, the CTM system “will pull in key information for that particular drug therapy, which then serves as a guide for going through counseling points with the patient,” she said. “We review common side effects, what to expect from those side effects, how to mitigate them, what to do for more serious adverse events and when to notify the physician that their patient is having one of those events.” Several other points are covered during the initial assessment, including use of over-the-counter medications and herbal supplements; the patient’s mobility; other barriers to adherence, such as financial difficulties with copays; and scheduling conflicts. To underscore

the holistic approach that is taken with all patients, a screening for tobacco cessation is also done, she said. One particularly useful feature of the CTM program is an action items queue, Dr. Ness added. Whether it’s the need to schedule a clinic visit for that tobacco cessation effort or to make an appointment for a needed lab test, “we can create an electronic ‘sticky’ note that prompts our clinicians to follow up with the physician on those events,” Dr. Ness said. “It allows us to continue our assessment, but we know that by creating this action item, we need to go back and complete some aspect of the patient’s care after [the initial phone assessment] is completed.” Subsequent phone consults with the patient expand on the initial set of questions, Dr. Ness noted, including whether the RA symptoms have improved, where the patient is on the pain scale, and whether activities of daily living have been affected, such as days of work or school missed. “You are able to track and monitor how all of these parameters have changed over time and look at them using all of the outcomes-based reports our system can generate,” she said.

Beyond Clinical Management Clinical outcomes aren’t the only measures of success an SP provider has to demonstrate to keep getting competitive contracts. And that’s where the financial benefit of the CTM modules becomes evident, Dr. Ness said. There are a host of reports that the system can generate, such as those focused on adherence and persistency, which meet the business-related requirements of payors and manufacturers. Additionally, the reports can be used to respond to a request for proposal, which is a useful tool when competing for new business. The reports also can be an invaluable tool in building a case for SP accreditation, Dr. Ness said. Dr. Ford echoed that point, noting that Barnes Healthcare Services has a “pending” status for URAC accreditation. CTM’s reporting capabilities “really helped streamline the process of pursuing that accreditation,” he said. Given all of these capabilities, does it ever make

‘MPRs are fine, but with the steadily rising costs of specialty medications, payors are going to start asking tougher questions about how we are doing managing their patients.’ —John E. Ford, RPh

sense for an SP provider to build a CTM-type system itself, rather than outsource it to a company such as MHA? “Sure—some of the biggest specialty pharmacies have been doing that for several years now,” Mr. Ford said. “But I also know that it’s an incredibly complex undertaking to keep these clinical management systems up-to-date and working optimally.” He added that he knows of one provider who had been taking the DIY approach but who is now thinking of switching to an outside provider and purchasing clinical therapy management software.

Adaptability is Crucial SP providers that decide to buy a clinical management system should put a premium on adaptability, so that the program can adapt as their own data and reporting needs evolve, Mr. Ford stressed. For example, with RA, he noted, Barnes Healthcare Services is working toward leveraging CTM to record patients’ American College of Rheumatology symptom scores during evaluations. “The current CTM system doesn’t have a report for that,” he acknowledged. “But CTM gives me the framework to have my clinicians track that data to begin with.” —David Bronstein

UnitedHealth/OptumRx Snaps Up Catamaran an

nitedHealth Group announced that it will buy pharmacy benefits manager (PBM) Catamaran in a nearly $13 billion deal to merge Catamaran with UnitedHealth’s PBM, OptumRx. Assuming regulatory approval, the deal is expected to close sometime in the fourth quarter of this year. According to the Drug Channels Institute, the purchase will put the combined OptumRx/Catamaran behemoth hot on the heels of No. 2 PBM, CVS Health in total market share, with 22% of prescriptions compared with CVS’ 24%, and close behind No. 1 Express Scripts, with 29%. The new “Big Three” will now be far ahead of their nearest competitor, Prime Therapeutics, with 6%. “They will now be able to be much stronger competitors to Express Scripts and CVS,” said Yash Shah, the director of business development at ProMetrics, in an interview with Specialty Pharmacy Continuum. “From that point of view, it’s a pretty good

thing. BriovaRx [Catamaran’s specialty pharmacy] and Optum are both rapidly growing and trying to get more manufacturers’ limited-distribution business. The combined entity might give them more leverage.” “This is good for UnitedHealth and Catamaran,” agreed Stephen Lagano, MS, the founder and principal of industry consulting firm Altometrixs. “It gives them a lot more leverage against manufacturers and providers. They can push back on almost anybody. They will have greater ability to negotiate price and also get some efficiencies in their delivery.” But Mr. Lagano didn’t see the deal as necessarily such good news for consumers. “I’m a big fan of competition. Even though there are allegedly more efficiencies with consolidation, it seems like nothing gets passed down to the consumer the way you would anticipate. Consolidation makes it more challenging for all the players in the space:

manufacturers, providers, wholesalers and consumers.” Mr. Shah also points out that the “rosy picture” of new synergies made possible by the acquisition will take time to achieve. “Briova, as an entity, has 14 specialty pharmacies throughout the country. Those pharmacies are on one IT [information technology] system and able to coordinate patient care. Integrating Briova’s IT system with Optum’s will have challenges, and that could mean hiccups in servicing all stakeholders: physicians, payors, manufacturers and patients.”

More Consolidation In more specialty pharmacy acquisition news, the Memphis-headquartered discount chain Fred’s Inc., will spend $66 million to buy Reeves-Sain Drug Store Inc.—a deal largely motivated by the desire to acquire ReevesSain’s specialty pharmacy operation, EntrustRx.

Fred’s, which operates 661 general discount stores as well as more than 360 pharmacies, expects to gain many advantages from acquiring EntrustRx, including accreditation and access to expanded specialty networks, expertise in different disease states, access to limited-distribution medications and a model for a scalable retail experience, according to Fred’s CEO Jerry Shore. EntrustRx’s main therapeutic lines include oncology, hepatitis C, multiple sclerosis, rheumatology and growth hormones. —Gina Shaw

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Specialty Pharmacy Continuum • April/May 2015

POLICY

Injunction Against Zarxio Biosimilar Denied A U.S. District Court judge has denied Amgen’s motion forr a preliminary injunction to prevent Sandoz from marketingg its Neupogen biosimilar Zarxio, the first biosimilar drug to be approved by the FDA under the new Biologics Price Competition and Innovation Act (BPCIA). In its suit, Amgen argued that Sandoz should have provided its Biologic License Application and manufacturing plans within 20 days after the FDA’s acceptance of its application last July; it also claimed that Sandoz should have given six months’ notice of its plans to market the drug. U.S. District Court Judge Richard Seeborg held that the so-called “patent dance” provision of the BPCIA is optional, not mandatory. “It is … evident that Congress intended merely to encourage use of the statute’s dispute resolution process in favor of litigation, where practicable, with the carrot of a safe harbor for applicants who otherwise would remain vulnerable to suit,” he wrote. He concluded: “As the 12-year exclusivity period for Neupogen long ago expired, there exists no substantive bar to market

entry for Sandoz’s biosimilaar filgrastim—and, consequently, no basis on which Amgen is entittled to injunctive relief or other rem medies for disadvantages it may suffeer due to market competition from Saandoz.” David Galardi, PharmD, the cofounder of the biotech and health care consultancy Apogenics, said that this ruling is just another step in what will be a “rocky road for the foreseeable future” for biosimilars. “At this point, it appears that Sandoz is free to launch the product with five days’ notice whenever they want, at risk,” he said. “That could happen five days from now, or they could make a business decision to wait and let the litigation play through.” Dr. Galardi predicted that Sandoz will hold its cards for now, but will likely

harmacy pay-for-performance is here to stay which in turn makes demonstrating healthcare delivery excellence more important than ever. That’s why forward thinking pharmacy owners like Byron Yoshino of Pharmacare in Hawai’i have utilized The Compliance Team’s* Exemplary Provider® “EP” accreditation since 2007. Today, The Compliance Team offers pharmacies a full line-up of Exemplary Providerbranded accreditation programs including ones for Specialty, Community, Infusion, Sterile & Non-sterile Compounding, LTC, DMEPOS and Retail Clinic.

launch the drug if an appeals court upholds Mr. Seeborg Seeborg’ss ruling. “II think they’ll wait for the next appeal. If they win that, I won’t be surprised if they then launch the product at risk, and reserve any payments they might have to make if they lose on a later appeal. But this is going to be a drawn-out process.”

Hurdles Outlined at Symposium That sentiment was echoed by several stakeholders during the “Biosimilars and Follow-on Biologics 2015 Americas” symposium presented by Paradigm Global Events. Several barriers to entry were cited, including naming confusion

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due to the absence of FDA guidance on nomenclature, questions over bioequivalency and prolonged litigation. Liz Fuller, a consultant with the international law firm Bird & Bird LLP, said the lawsuit filed by Amgen must be clearly resolved before Zarxio can enter the market—a process that “could take years,” she told symposium attendees. Such legal wrangling, she added, is not surprising, given the lack of clear direction in the key BPCIA provisions. State substitution laws are another gray area regarding biosimilars that may complicate adoption of the products. Most states have passed laws that allow traditional generic drugs to be substituted for the reference product by a pharmacist without physician approval. Such laws exist because the FDA considers traditional generics to be therapeutically equivalent to their branded counterparts. Under the BPCIA, in contrast, only an interchangeable biotech product—not a biosimilar—is considered therapeutically equivalent. As a result, every state will need to pass legislation outlining the circumstances under which pharmacists may

Byron Yoshino President/CEO Pharmacare Hawaii Infusion/Specialty and LTC Pharmacy DMEPOS

Specialty Pharmacy Continuum • April/May 2015

POLICY

substitute biosimilars. A half-dozen states already have enacted laws variously limiting pharmacists from substituting biosimilars without physician notification and/or approval. Similar bills are pending in several other states.

A Compromise on Substitution? Generic and branded drug industry organizations have been battling the issue, but last year agreed on compromise model language (http://goo.gl/zKNQZo) on several fronts. For example, under the revisions, substitution would be allowed without prior notice or approval if the pharmacist enters the substituted product information into the patient’s electronic medical record, interoperable pharmacy record or faxes or telephones the information to the prescriber. “The electronic record is the best way to go,” agreed Bruce Leicher, general counsel, Momenta Pharmaceuticals, a Cambridge, Mass.-based company that develops biosimilars and generic versions of complex drugs. But manufacturers need to remain cautious, noted Kevin M. Nelson, a partner at Duane Morris, a law firm based in Chicago. That’s because states may pass more restrictive laws, “which will be a disincentive to biosimilars development,” he said.

‘I think [Sandoz will] wait for the next appeal. If they win that, I won’t be surprised if they then launch the product at risk.’ —David Galardi, PharmD designation. These will likely include switching studies, but because they are costly (more than $50,000 per patient), experts expect companies will not pursue the designation. Richard DiCicco, co-founder of Harvest Moon Pharmaceuticals USA Inc., a Falls Church, Va.-based company that manufactures

complex generic drug products and biologicals, noted that biosimilar manufacturers are frequently able to boost production yields and make other improvements to pioneer biologicals. Many believe these “biobetter” or “biosuperior” products will be preferable because biosimilars can be marketed

only after patents expire on the reference product, which in the case of the BPCIA is 12 years. “From the biosimilar developer’s standpoint, they may consider just doing a stand-alone development or developing a biobetter,” Ms. Fuller said. “After all, these products will already have been on the U.S. market for 12 years.” —Gina Shaw, Ted Agres None of the sources reported any relevant ﬁnancial conﬂicts of interest.

You can see the difference.

Naming Confusion Not Helping Another obstacle is the absence of FDA guidance on naming. Brand-name drug companies want the nonproprietary names of reference products (such as filgrastim or erythropoietin) to be different from those used by biosimilars to avoid confusion and facilitate tracking in case of adverse events. Biosimilar companies argue that this will only confuse patients and physicians more. They note that European and other countries require pioneer products and biosimilars to use the same International Nonproprietary Name (INN). “Unique naming suggests that biosimilars are not biosimilar. A unique biosimilar name could make a label misleading because it suggests a clinically meaningful difference when there is none,” Mr. Leicher said. Indeed, nearly three-fourths of pharmacists in a recent survey said they would feel confident or very confident substituting an interchangeable biosimilar for the reference biologic if the two products shared the same nonproprietary name ((J Manag Care Spec Pharm 2015;21[3]:188-195). The FDA has yet to issue draft guidance on the matter, and has designated “filgrastim-sndz” as the “placeholder nonproprietary name” for Sandoz’s just-approved filgrastim. The agency plans to issue draft guidance on the naming issue “in the near future.” FDA also expects to issue draft guidance sometime this year on the clinical studies needed for the interchangeable

Introducing the no latex, transparent Easypump®. There s an obvious difference to B There’s B. Braun Braun’ss new Easypump elastomeric infusion system system. Its silicone material is clear, making it easier to inspect for particulates after filling. Additionally, Easypump is not made with natural rubber latex, minimizing patient concerns over discoloration and allergies. Its patented sliding core ensures the pump reservoir is filled and contracts in a consistent, concentric manner. This can lead to fewer patient calls and a smoother homecare experience. Contact your B. Braun sales representative today, or visit BBraunEasypump.com

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Specialty Pharmacy Continuum • April/May 2015

CLINICAL

Navigating a wide array of choice can be a challenge

IG Products Require a Rational Selection Process T

he number of IV and subcutaneous immune globulin (IVIG, SQIG) products has been steadily expanding, thanks in part to the growing array of immunodeficiencies, autoimmune disorders, neuropathies and inflammatory disorders against which these agents have demonstrated or suggested benefit. For clinicians, selecting the optimal agent is not limited to understanding the indications of the available products, which vary, but recognizing characteristics that affect safety, tolerability and convenience. “There used to be only one [SQIG] available in the United States but now there are several options. The number of IVIG products has also increased, but none of these should be considered interchangeable. Understanding the differences is essential to increase the opportunity for benefit and reduce the risk for adverse events,” said Jerry Siegel, PharmD, a clinical associate professor at Ohio State College of Pharmacy, in Columbus. An expert on immune globulins, Dr. Siegel has often updated Specialty Pharmacy Continuum readers on the proper use of these products. Hospital and specialty pharmacy formularies are unlikely to stock every IG product, but this type of selection may not be necessary. For IVIG, Dr. Siegel estimated that several of the most well-established agents perform well in 80% or more of inpatients. He advised selecting one of these products as a “workhorse” while remaining familiar with alternatives for patients who have a relative contraindication, are not responding adequately or do not tolerate the initial choice. Independent of route of administration, IG products vary by a lengthy list of characteristics, including concentration, volume, osmolality and additives in the stabilizing agents, such as amino acids or sugars. Concentration and volume are important variables to achieve treatment goals, but the effect of many of the other characteristics on reaching those goals is difficult to judge because of limited comparative trials. However, some characteristics do deserve consideration when individualizing therapy for safety.

Comorbidities a Guidepost In particular, the choice of IG should be influenced by the presence of comorbidities, according to Dr. Siegel. For example, products with glucose should be avoided in patients with diabetes. Additionally, products with high sodium content may be inappropriate in patients with renal impairment or congestive heart failure. Dr.

Siegel also noted that IG products with high osmolality are often poorly tolerated in those with a history of migraine. In avoiding risks to specific patient populations, improved product labeling may help. Individualizing therapy to minimize risks is particularly important for patients expected to remain on an IG product indefinitely.

Initiating IG therapy, increasing the dose or switching from one to another typically represents the period of highest risk for adverse events. According to Dr. Siegel, rate of infusion is the single most important factor for modifying risk for intolerability. “The faster that the immune globulin is infused, the greater the chance of a reaction,” Dr. Siegel explained. He cautioned that each patient is unique not only for the rate at which they can tolerate an IG infusion but also for the maximum tolerated dose. Infusion reactions can occur even for doses and rates previously tolerated. For this reason, Dr. Siegel encouraged a conservative approach to infusions and incorporation of appropriate rate escalations. “In a patient who reports chills during an infusion, the worst thing to do is to first get a blanket, Dr. Siegel said. “Adverse reactions can often be controlled by slowing or splitting the dose but not by pushing through the dose,” He cautioned that intolerance is frequently misattributed to allergic reactions, which are uncommon. When rate reductions do not control reactions adequately, switching patients to an alternative IG is an appropriate strategy, because failure to one agent does not predict failure to another, he noted. In some individuals, the best alternative to IVIG is an SQIG formulation. Injections may or may not be perceived

by the patient as offering greater convenience over an infusion, but SQIG formulations are typically better tolerated, Dr. Siegel noted. In SQIG regimens, lower doses are administered more frequently, flattening the fluctuations in peak concentrations, which can circumvent dose-related adverse events, such as headaches, he explained. “For children, SQIG eliminates the need for catheters and PICC [peripheraln lly inserted central catheter] lines, which may be a consideration, but the major m aadvantage for most individuals is the rreduction in peak plasma levels,” Dr. Sieggel said. HyQvia (Baxter), a recent entry aamong SQIG options, now employs a novel mechanism that permits larger voln umes of IG to be infused and absorbed, u providing a strength and dosing flexp iibility approaching IVIG formulations ((BioDrugs 2014;28[4]:411-420), Dr. Siegel rreported. But he stressed that despite tthose large volumes, HyQvia preserves tthe advantage of lower peak concentrattions relative to IVIG formulations. Injection site reactions are a common phenomenon in patients using m SQIG products, occurring in up to 90% S of patients when they initiate therapy ((J Clin Immunol 2006;25[3]:265-273). In the majority of patients, these reactions are limited to mild swelling and redness that resolve in 24 hours. For those with more bothersome or persistent reactions, more injections administered at lower volumes may be a solution, Dr. Siegel pointed out. But he added that rotating injection sites and avoiding areas of inflammation are simple steps to reduce risk for serious reactions. Due to injection site reactions, SQIG is generally contraindicated for patients with idiopathic thrombocytopenic purpura or others prone to hematoma formation.

Acute vs. Chronic Therapy Overall, SQIG is best characterized for most indications as a maintenance therapy. “In patients with an urgent need for rapid induction of an immune globulin, such as an individual with Stevens-Johnson syndrome or a necrotizing skin disease, the [better] choice is an IVIG formulation, to ensure that an adequate concentration is reached rapidly,” Dr. Siegel said. IG formulations are blood products with a theoretical risk for viral transmission, but Dr. Siegel believes that the processes used to eliminate pathogens, although varying by manufacturer, are reliable. The clinical relevance of these processes is essentially confined to how the specific solvents employed influence tolerability.

“At least three different methods are now used by every manufacturer to eliminate risk for a viral transmission. They are not the same but they are all effective,” he said. “Some hospitals still require infusion of immune globulins through an in-line filter set, but there is no need for it with current purification processes.”

Data Sometimes Lacking Immune globulins have shown benefit or promise in a large number of diseases, but approved indications remain limited. For some diseases, confirmatory clinical trials may never be conducted, and this is problematic for patients who respond to an IG product and then are denied reimbursement for chronic treatment. According to Dr. Siegel, there have been several examples of grassroots efforts to win reimbursement in such cases. “It was only in 2009, that an indication was provided for the treatment of CIDP [chronic inflammatory demyelinating polyradiculonephropathy],” Dr. Siegel observed. He noted that this condition had been widely and successfully treated with IG since the 1980s, but reimbursement, if it was provided at all, was obtained at the regional level or on a case-by-case basis. “This can be a very frustrating situation when patients are clearly benefiting,” said Dr. Siegel, who recommended publishing cases and joining with others attempting to document benefit in orphan diseases. Cooperative groups can be invaluable for collecting the data required to convince regulators and payors to fund treatment. In patients with a chronic disease who respond to IG therapy, clinicians should be sensitive to the burden of an indefinite course of treatment, according to Dr. Siegel. He suggested that support groups might help some individuals cope with their condition and their therapy both through practical exchange of information and empathy. Although patients can derive reassurance from others who share their challenges, Dr. Siegel said that support groups benefit from the participation of a health care professional who can control dissemination of misinformation. “The goal is to help patients lead a normal life,” Dr. Siegel said. “For those whose disease is well controlled on IG, we want their therapy to revolve around their life rather than having their life revolve around the therapy.” —Ted Bosworth Dr. Siegel disclosed a consulting contract with Amgen, a teaching contract with Kedrion and a research contract with CSL Behring.

Take a bite out of G-CSF acquisition costs Based on whole esale acquissition cost (WAC C) of o alll sho ort rt-a -act -a c in ct i g GG-CS CSF F pr prod oduc od ucts uc t ts as of November 11, 201 0 3. 3 WAC AC rep pre ese sent ntss pu nt publ blis bl ishe is he ed ca cata talo log gue gu g e or lisst pr pric ices es and n may not represent acctual tra ansa a tion ac o al pri r ce es. s. Ple leas ase e co con ntac actt yo your urr sup uppl plie er fo forr ac actu tual al pri r ce c s. s

GRANIX® is an option in short-acting G-CSF therapy » A 71 7 % red ducttio ion n in dur urat a ion at ion off sev ever ere e ne neutrro openia a vs placebo (1.1 days vs 3.8 8 da d ys, p<0 0.0 000 001) 11 – Effica c cy cy was eva valu uat ae ed d in a m mult mu ltin nat ational, m multice enter, randomized, controlled, Phase III study of chem motherapy-naïve patients tss witth hi hig g -ris gh-r gh iskk br brea east stt cance er receivving do oxorubicin (60 mg/m2 IV bo olus)/docetaxel (75 mg/m2)1 » Th he sa safe fe etyy of GR GRA A IX was esta AN ablishe ed in 3 Phase III trials,, with 680 p patients receiving g chemotherapy py for either breast 1 ca anccer er,, lu lung ng g can nce er, or non-Ho odgkin lympho oma (N NHL) » No Now w of offe ferri fe ring ng a new e presentation for self-ad dministration

Indication » GR G AN ANIX IX is a le leukocyte ocyte growth factor indicat indicated ted forr reduction in the duration of severe ne neutropenia eutropenia in p patients atients w th non wi onm mye oid malig myel gnancies receiving myelosuppresssive anticancer drugs associated with a clinically significant i ci in cide denc nce e of febrile neu utropenia.

Important Safety Information » Sple Sp eni n c ru upture: Splen nic rupture, including fatal cases, can occur following the administrattion of human granulocyte colo co lony ny-stimulating facttors (hG-CSFs). Discontinue GRAN NIX and evaluate for an enlarged spleen or sp s le enic rupture in pati pa tien e ts who report up pper abdominal or shoulder pain after receiving GRANIX. » Ac Acut ute resspiratory disttress syndrome (ARDS): ARDS ca an occur in patients receiving hG-CSFs. Evaluate pa p tients t who wh o de d ve elop fever and d lung infiltrates or respirator o y disstress after receiving GRANIX, forr ARDS. Disco c ntinue GRANIX X in patients with ARDS. » Al A lergic reactions: Serrious allergic reactions, including anaphylaxis, can occur in patientts receiving hG G-CSF S s. Reactions n ca an occurr on initial exp exposure. posure Permanentlyy discontinue GRANIX GRA ANIX in patients with serious allergic reac actions. tions D Do o no n t not administe er GRANIX to patients with a histo ory of serious allergic reactions to o filgrastim or pe egfilgr g astim. » Use e in pa atients with sickle cell disease: Severe and sometimes fatal sickle e cell crises can occur in pa patients with sickkle cell diseasse receiving hG-CSFs. Consider the potential risks and benefits prrior to the administration of GRAN NIX X in patients with sickle cell disease. Discontinu ue GRANIX X in patients undergoin ng a sickle cell crisis. » Capillary leak syndrome (CLS): CLS can occur in patients receiving hG-CSFs and iss charac a teriize z d by hyp ypote ensiion o , hypoalbuminemia, edema and hemoconce entration. Episodes vary in freque ency, severity and may be life f -thre eatening if treatme ent is delayed. Patients who develop symptoms of CLS should be closelyy monitored and d re ece c ivve sttanda dard r symptoma atic treatment, which may include e a need for intensive care. » Potential for tumor growth stimulatory effects on malign g ant cells: The granulocyte colony-stimullating fa actor o (G-CSF) re eceptor, through which GRANIX acts, has been fo f und on tumor ce ell lines. The pos o sibility tha hat GRAN NIX X acts as a grow wth factor for any tumor type, inclu uding myelo oid malignancies and myelodysplasia, diseasses e for which GRA ANIX is not app proved, cannot be excluded. » Most com mmon treatment-emergent adve erse e reaction: The most common n treatment-eme ergent ad dvers r e re ea action that occurred in patients treated with GRANIX at the recommended do d se with an incidence of at leastt 1% or gre eat e a er and two ti t mess more frequent than in the placebo group wass bone pain. Please see brief summary of Full Prescribin ng Information on adjacent page.

For more information, visit GRANIXhcp.com. Refe Re fere renc nce: e 1. GRA ANIX® (tbo-filgrastim) Injection Prescribing g Info orm r ation. North Wales, PA: Teva Pharmaceuticals; 2014.

©2015 Cephalon, Inc., a wholly-owned subsidiary of Teva a Pharmaceutical Industries Ltd. GRANIX is a registered trademark of Teva Pharmaceutical Industries Ltd. All rights reserved.. GRX-40582 January 2015.

Specialty Pharmacy Continuum • April/May 2015

CLINICAL

Sovaldi and Harvoni Pose Risk When Used With Heart Rx

he FDA has issued a warning that symptomatic bradycardia can occur when the common arrhythmia drug amiodarone is taken concurrently with either ledipasvir/sofosbuvir (Harvoni) or sofosbuvir (Sovaldi) and another direct-acting antiviral agent (DAA). The warning follows reports of one death from cardiac arrest and three

incidents of patients requiring a pacemaker to regulate arrhythmias after taking this drug combination. The FDA has instructed physicians not to prescribe either of these two hepatitis C (HCV) drugs, both of which are marketed by Gilead, combined with another DAA, to patients also taking amiodarone. If such a combination must be prescribed, the patient should be monitored in the hospital for the first 48 hours, and then daily at home or in the physician’s office for at least the first two weeks of treatment.

BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR GRANIX® (tbo-filgrastim) injection, for subcutaneous use SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE GRANIX is indicated to reduce the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Splenic Rupture Splenic rupture, including fatal cases, can occur following administration of human granulocyte colony-stimulating factors. In patients who report upper abdominal or shoulder pain after receiving GRANIX, discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture. 5.2 Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) can occur in patients receiving human granulocyte colony-stimulating factors. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS. 5.3 Allergic Reactions Serious allergic reactions including anaphylaxis can occur in patients receiving human granulocyte colony-stimulating factors. Reactions can occur on initial exposure. The administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine may reduce the severity of the reactions. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim. 5.4 Use in Patients with Sickle Cell Disease Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving human granulocyte colony-stimulating factors. Consider the potential risks and benefits prior to the administration of human granulocyte colony-stimulating factors in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis. 5.5 Capillary Leak Syndrome Capillary leak syndrome (CLS) can occur in patients receiving human granulocyte colonystimulating factors and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. 5.6 Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte colony-stimulating factor (G-CSF) receptor through which GRANIX acts has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded. 6 ADVERSE REACTIONS The following potential serious adverse reactions are discussed in greater detail in other sections of the labeling: UÊ -« i VÊ,Õ«ÌÕÀiÊQsee Warnings and Precautions (5.1)] UÊ VÕÌiÊ,iÃ« À>Ì ÀÞÊ ÃÌÀiÃÃÊ-Þ `À iÊQsee Warnings and Precautions (5.2)] UÊ -iÀ ÕÃÊ iÀ} VÊ,i>VÌ ÃÊQsee Warnings and Precautions (5.3)] UÊ 1ÃiÊ Ê*>Ì i ÌÃÊÜ Ì Ê- V iÊ i Ê Ãi>ÃiÊQsee Warnings and Precautions (5.4)] UÊ >« >ÀÞÊ i> Ê-Þ `À i [see Warnings and Precautions (5.5)] UÊ * Ìi Ì > Êv ÀÊ/Õ ÀÊ À ÜÌ Ê-Ì Õ >Ì ÀÞÊ vviVÌÃÊ Ê > } > ÌÊ i ÃÊQsee Warnings and Precautions (5.6)] The most common treatment-emergent adverse reaction that occurred at an incidence of at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group was bone pain. 6.1 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 clinical practice. GRANIX clinical trials safety data are based upon the results of three randomized clinical trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of patients were female, the median age was 50 years, and 86% of patients were Caucasian. In the lung cancer study, 80% of patients were male, the median age was 58 years, and 95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients were male, the median age was 55 years, and 88% of patients were Caucasian. In all three studies a placebo (Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim product were administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy for at least five days and continued to a maximum of 14 days or until an ANC of *10,000 x 106/L after nadir was reached.

This warning, although serious, is unlikely to have a major effect on the new HCV drugs going forward, said Zitter Health Insights’ Melinda Haren in an interview with Specialty Pharmacy Continuum.

Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-USapproved filgrastim product). Leukocytosis In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than 1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies. Additional Adverse Reactions Other adverse reactions known to occur following administration of human granulocyte colony-stimulating factors include myalgia, headache, vomiting, Sweet’s syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis and thrombocytopenia. 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody development in patients receiving GRANIX has not been adequately determined. 7 DRUG INTERACTIONS No formal drug interaction studies between GRANIX and other drugs have been performed. Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution. Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C Risk Summary There are no adequate and well-controlled studies of GRANIX in pregnant women. In animal reproduction studies, treatment of pregnant rabbits with tbo-filgrastim resulted in increased spontaneous abortion and fetal malformations at systemic exposures substantially higher than the human exposure. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data In an embryofetal developmental study, pregnant rabbits were administered subcutaneous doses of tbo-filgrastim during the period of organogenesis at 1, 10 and 100 mcg/kg/day. Increased abortions were evident in rabbits treated with tbo-filgrastim at 100 mcg/kg/day. This dose was maternally toxic as demonstrated by reduced body weight. Other embryofetal findings at this dose level consisted of post-implantation loss‚ decrease in mean live litter size and fetal weight, and fetal malformations such as malformed hindlimbs and cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic exposure (AUC) of approximately 50-90 times the exposures observed in patients treated with the clinical tbo-filgrastim dose of 5 mcg/kg/day. 8.3 Nursing Mothers It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GRANIX is administered to a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. 8.4 Pediatric Use The safety and effectiveness of GRANIX in pediatric patients have not been established. 8.5 Geriatric Use Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients were 65 years of age and older. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients. 8.6 Renal Impairment The safety and efficacy of GRANIX have not been studied in patients with moderate or severe renal impairment. No dose adjustment is recommended for patients with mild renal impairment. 8.7 Hepatic Impairment The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment. 10 OVERDOSAGE No case of overdose has been reported. ©2014 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. GRANIX is a registered trademark of Teva Pharmaceutical Industries Ltd. Manufactured by: Distributed by: Sicor Biotech UAB Teva Pharmaceuticals USA, Inc. Vilnius, Lithuania North Wales, PA 19454 U.S. License No. 1803 Product of Israel GRX-40581 January 2015 This brief summary is based on TBO-004 GRANIX full Prescribing Information.

“You have to expect that when a drug like this expands into the general population beyond clinical trials, things will develop, especially since we’re suddenly treating hepatitis C patients broadly who we’ve never treated before,” Ms. Haren said. “Sovaldi and Harvoni are curative therapies, and payors are already limiting them to the most at-risk patients. You’re balancing potential cardiac side effects against the risk for dying from hepatitis C. It’s a conversation that patients will have to have with their physicians about which risk is of concern to them.”

Hi-Tech Adherence Plan for HIV Funded

rug adherence is always a challenge in any specialty pharmacy. But in the case of HIV, where patients’ regimens can include dozens of drugs, compliance tools are in particular demand. VillageCare, a New York City–based nonprofit organization, may have the answer, based on a grant it just received from The Center for Medicare & Medicaid Innovation (CMMI). The center awarded VillageCare $8.7 million for a three-year project called Treatment Adherence through the Advanced Use of Technology. The initiative centers on an integrated mobile Web and app portal that offers a personalized medication adherence plan, social support, video sessions and text messaging.

“Anything and everything that can be done to improve patients’ access to care and their medication adherence is a good thing,” Tony Luna, the executive vice president for business development at Aureus Health Services, told Specialty Pharmacy Continuum. “This model seems like it could potentially work for a segment of the population living with HIV/AIDS. But we can’t also lose sight of the fact that there are a lot of people living with HIV who are disenfranchised and may not have the financial abilities to have access to reliable and regular tech devices. Those who are homeless, for example, are at even more risk for nonadherence, and it’s very important that we recognize as service providers that not all people living with HIV/AIDS have that consistent, reliable access to the tech tools that so many people take for granted.” He added, “Technology is just one piece of the overall adherence solution.” —Gina Shaw

Specialty Pharmacy Continuum • April/May 2015

CLINICAL

INFUSION SAFETY continued from page 1

data. And there usually is not a true clinician-to-clinician handoff, where the patient is clinically ‘talked through.’” Given the challenges of information technology security, and the fact that many hospitals and health systems are still struggling with implementing their own internal electronic health records, it’s not likely that an electronic solution to transitions of care from the hospital to the home infusion setting will be found soon. “We are seeing more electronic prescriptions, but not true exchanges of patients’ medical records,” Dr. Kennedy said. Instead, he noted, pharmacists and nurses on the home infusion team must make the extra effort to create their own internal “case conference” on each patient who comes under their care. “We need to take a more active role in the holistic care of each patient, versus just going in and treating the patient with their IV medications,” he stressed. Dr. Kennedy also advised caution in dealing with computerized drug utilization review. “Due to the nature of the medications we provide, we tend to get a lot of pop-up warnings of drug interactions,” he said. “For instance, a lot of our patients are on heparin flushes for their IV line. The system sees heparin and defaults to continuous or intermittent heparin used for anticoagulation, [rather than] a low-level, nontherapeutic flush concentration.” This kind of confusion can have tragic results: in 2006, three premature infants died at an Indiana hospital when they mistakenly received 10,000 units/mL (the anticoagulant dose) of heparin instead of the 10 unit/mL FlushLock concentration. “The systems are designed for the retail market or ‘textbook’ screening, and we often don’t fit, so [there is] a tendency to ignore the warnings because there are so many pop-ups,” Dr. Kennedy said. “But we need to review each of

these and not go on autopilot.”

Asking the Right Questions Getting a clear, updated assessment of the patient on home infusion often requires the home infusion pharmacist to complete a telephone interview with that patient or the caregiver. “That requires a different, higher level of skill and motivational interviewing on the part of the pharmacist to determine the patient’s status,” said Margherita C. Labson, RN, MS, the executive director for the Home Care Program at the Joint Commission. She praised the finely honed interviewing skills of specialty pharmacists she has seen in extracting the needed information. “At one home infusion specialty phar-

are a common cause of medication errors; in Pennsylvania, for example, one in 10 medication errors reported to the state is associated with providing the wrong drug to a patient. One in three of those errors is due to confusion between medications with similar names ((Patient Safety Advisory 2004; 1[4]:1-3.) The emphasis must be on making the patient safely independent, Ms. Labson noted. “We have to be aware of the human factor. Remember that we are delivering services in an unregulated environment—the patient’s home There is nothing on the books, for example, that even requires the patient to have refrigeration,” she pointed out, which clearly could pose safety issues with cold-chain medications.

‘You have to say, “I’m in charge of dispensing this product. I take this responsibility seriously. What do my team and I need to know?’” —Paula Zelle, PharmD, FASHP macy I visited, I heard the technician on the phone and she never asked a yes or no question,” she said. “I finally asked her why. She said, ‘They will never give you new information with a yes or no question—they’ll just confirm what you believe. So instead of saying ‘Did the doctor change any of your medication?’ it is better to ask, ‘Which medications did your doctor change?’ and have the patient tell you ‘None.’” Another interviewing technique Ms. Labson observed was asking the patient to spell the medication’s name. “They did this for two reasons: Sometimes the medication was a look-alike and soundalike, and one change in a letter made a big difference. Also, having to spell the name of the drug gets the patient to focus on the label and its instructions.” Look-alike/sound-alike drug names

“This requires a collective consciousness that at any given moment, especially when the caregiver is self-infusing without supervision, a medication error could occur.”

Speed Pressures Given the intense focus on “getting product out the door,” concentrating on patient safety is not always easy, according to Paula Zelle, PharmD, FASHP, a health care consultant with Infusion Consultant Services and Accreditation Resources in Canton, Ohio. “There is such a push from so many avenues— the provider, the hospital, the discharge planner—to get the drug to the patient as soon as they get home,” she said. “Because of that, many home infusion providers may accept an incomplete referral from the hospital—one that

FDA Launches Drug Shortages Mobile App

sk home infusion providers what keeps them up at night, and drug shortages likely will be at or near the top of the list. Whether it’s a shortage of immune globulins—a life-saving therapy that has had intermittent supply problems for years—or more recent access issues such as those involving IV electrolytes—a new high-tech solution may be at hand. In March, the FDA launched its first free mobile app specifically designed to speed public access to valuable information about all drug shortages. The app identifies current shortages, resolved shortages and discontinuations of drug products. Scarce supplies of medications can lead health care professionals to rely on alternative drug products, which may be less effective or associated with higher risks than the hard-to-find orginal treatment, according to the FDA. “The FDA understands that health care professionals

[such as] pharmacists need real-time information about drug shortages to make treatment decisions,” said Valerie Jensen, the associate director of the Drug Shortage Staff in the FDA’s Center for Drug Evaluation and Research. “The new mobile app ... will offer easier and faster access to important drug shortage information.” App users can search or browse by a drug’s generic name or active ingredient, and browse by therapeutic category. The app can also be used to report a suspected drug shortage or supply issue to the FDA. The agency developed the app as part of the FDA’s efforts outlined in the Strategic Plan for Preventing and Mitigating Drug Shortages. The app is available for free download on iTunes (for Apple devices) and the Google Play store (for Android devices) by searching “FDA Drug Shortages.” —SPC Staff

doesn’t have all the patient’s allergies, or all their medications, or that has a medication list current for the hospital but not for what they’re going home on. It’s a hard call to say you’re going to hold everything up because you don’t have information on an allergy, but you’d rather be doing that than later on wishing you’d had that information.” Dr. Zelle advises home infusion pharmacists to prioritize the data and fields that mustt be filled in before sending out a particular therapy—a task that, unfortunately, cannot be one-size-fits-all. “It might be different for each therapy. It might be different for each region,” she said. “As with aminoglycosides, or vancomycin, for example—there’s an art to tailoring those [drugs] and titrating them to the patient’s needs. If you’re near a teaching hospital, they might be more aggressive in that therapy. In a rural setting, you’re going to set your sights potentially much more conservatively. In some areas, depending on access to a major center or the physician’s experience, they might do a very high dose once a day, focused more on the trough than the peak, whereas in other areas, they’re worried about the peak and the trough.” That said, there are certainly key fields to start with. These include: • Patient’s medical history • True allergies • Current list of medications • Known interactions with what is being prescribed • Current laboratory results • Proper storage of drug (can the patient meet that requirement?) But other data that may seem obviously necessary might, in fact, not be— like the patient’s accurate height and weight. “Many drugs aren’t dosed specifically on weight, and height is insignificant,” Dr. Zelle said. “But then there are other drugs, such as chemotherapy, that are dosed specifically on weight—or on BMI [body mass index], so you need height and weight.” Instead of a set list of fields that must be filled in, she said the home infusion pharmacy team must take the time to assess each therapy and each patient individually, asking, “What is this therapy? What do I need right now, and what am I comfortable with learning in an ongoing assessment? “If you accept a sloppy referral over and over, you’ve taught the discharge planner to give you a sloppy referral,” Dr. Zelle said. “You have to say, ‘I’m in charge of dispensing this product. I take this responsibility seriously. What do my team and I need to know?’” —Gina Shaw The sources reported no relevant ﬁnancial conﬂicts of interest.

Specialty Pharmacy Continuum • April/May 2015

CLINICAL

A Roundup from A.S.P.E.N.

Insights and Innovations in Home TPN Long Beach, Calif.—It’s not often that a home infusion provider can help a patient with a challenging chronic gastrointestinal disease win a marathon, but that’s exactly what a Memphis, Tenn. practice reported at the American Society for Parenteral and Enteral Nutrition’s (A.S.P.E.N.) Clinical Nutrition Week 2015. In this roundup of abstracts from A.S.P.E.N, we also detail what may well be the first home strategy for reducing malnutrition in mechanically ventilated children, and a separate group’s efforts to reverse nutritional deficiencies in children with intestinal failure. Living an Active Life With TPN Individuals who rely on IV hydration or nutrition do not necessarily have to give up endurance sports, reported a team from the University of Tennessee (UT) Health Science Center and Methodist Healthcare, in Memphis (abstract 8). Emma Tillman, PhD, a research assistant professor in UT’s Department of Clinical Pharmacy and an avid marathon runner, was diagnosed with idiopathic gastroparesis in 2011. Her resulting weight loss and malnutrition necessitated starting IV hydration and then home TPN, and Dr. Tillman feared she would be unable to continue marathon running.

For short runs, hydration before, after or at both times was adequate, but a marathon would be too long to run without IV hydration. Dr. Tillman worked with the pharmacists at her home infusion company to develop a strategy. A traditional pump in a backpack proved too heavy, so they tested an Eclipse elastomeric infusion device (Halvard), used frequently for home infusion of antibiotics. “We chose a 500-mL ball [a self-squeezing, balloon-like reservoir for the solution] that infuses over roughly two hours, and it fit nicely in a fanny pack water-bottle pouch,” Dr. Tillman said.

During training, Dr. Tillman recorded her pre- and post-run weights, along with the ambient temperature, running distance and run duration. These data were used to calculate her sweat rate and estimate hydration volume during the marathon. “I then practiced several times in my 18- or 20-mile training runs with the device, and we determined that I would need a bolus of 240 mL at 13 miles, so I had someone from my home infusion company meet me to push fluid and then change the tubing, put in a new ball and send me on my way.” In July 2014, she completed her first marathon postdiagnosis, on a very hilly

Emma Tillman, PhD, who has idiopathic gastroparesis, was able to finish a marathon after being given a portable IV infusion device (visible in her fanny pack) that helped ensure adequate nutrition and hydration.

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CLINICAL

course in San Francisco. “It was slower than I planned, but I finished!” Dr. Tillman said this approach could be adapted for IV hydration and/or nutrition patients who want to pursue an active lifestyle. “I’ve talked to many other patients who say they’re scared to do the things they used to do, such as camping or hiking, but now they know that if it’s 80° out, they’ll be dehydrated if they’re out for more than two hours. If I can run a marathon [coordinated] with IV activities, someone else can do the other things they want to do with the help of an infusion device like this. If it’s something that’s really important to the person and their quality of life, we have to think outside the box to adapt their hydration and nutrition to let them [perform those activities].”

created for each patient; prescribed energy intake was increased in seven patients and decreased in six, based on feeding state, she reported. In patients classified as underfed, mean daily energy intake was significantly increased from baseline visit: 39.8 versus 44.4 kcal/kg per day ((P=0.03). Protein intake was increased in all patients. “The vast majority of patients were getting less than 1.5 g/kg of protein per day,” Dr. Martinez said. “Even with those prescribed a reduction in energy intake, we increased their protein in see HOME TPN, page 14

Live Life Fully

Malnutrition and Mechanical Ventilation

Gammaplex is proven protection • In 50 patients with PI*, no serious acute bacterial infections were reported during a 12-month trial with Gammaplex1 • In 35 patients with ITP† given two days of treatment with Gammaplex, 83% achieved WSH[LSL[ JV\U[Z _ 9/L by day 9 of the trial2

Gammaplex infusion rate can be increased every 15 minutes as tolerated1,3 Gammaplex is a pure IVIG product with favorable product characteristics4 • Low IgA content • Low percentage of aggregates • Viscosity similar to plasma * PI = primary immunodeficiency † ITP = immune thrombocytopenic purpura

In clinical studies, the most common adverse reactions with Gammaplex were headache, pyrexia, vomiting, fatigue, pain, nausea, hypertension, chills and myalgia. For more information visit www.gammaplex.com

Please see the Brief Summary of Prescribing Information, including boxed warning, on accompanying page.

IMPORTANT SAFETY INFORMATION Gammaplex® (immune globulin intravenous [human], 5% liquid) is indicated for the replacement therapy in adults with primary humoral immunodeficiency (PI). This includes, but is not limited to, the humoral immune defect in common variable immunodeficiency, X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome and severe combined immunodeficiencies. Gammaplex is also indicated for the treatment in adults with chronic immune thrombocytopenic purpura (ITP).

December 2014 US/Gx/1214/0020 Printed in USA

Children on long-term mechanical ventilation are at substantial risk for malnutrition, reported a research team from Harvard Medical School and Boston Children’s Hospital, and can benefit from individualized dietary interventions (abstract 15). The need for individualized approaches to nutrition in adult patients on longterm mechanical ventilation has been recognized for some time, noted Enid Martinez, MD, a pediatric critical care specialist at Boston Children’s. “But in pediatrics, the long-term mechanically ventilated cohort has been small, although it has been growing. They have special nutritional needs that we are just beginning to understand, and so far, we can find no published work on this. We can’t automatically apply to children what we do in adults, but we can learn from them.” The prospective interventional study involved 16 children with a variety of diagnoses, the most common being a neuromuscular disorder, such as muscular dystrophy or spinal muscular atrophy. During a baseline home visit, a multidisciplinary team, including a registered dietitian, a respiratory therapist and a physician, conducted a comprehensive nutritional and metabolic assessment to determine baseline dietary needs. Nine of the 16 children (56%) were found to be at risk for malnutrition, and the mean fat mass percentage was significantly higher in study patients compared with population norms (41.6% vs. 22.8%; P<0.0001). Eight of the 16 patients had protein intake below the recommended goals for their age. Four patients were classified as underfed and four as overfed. “That was surprising to us, because as this population of patients is not mobile, we would expect more of them to be overfed, but a larger group was underfed,” Dr. Martinez said. Individualized nutrition plans were

Thrombosis may occur with immune globulin products, including Gammaplex. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur in predisposed patients who receive immune globulin intravenous (lGIV) products, including Gammaplex. Patients predisposed to renal dysfunction include those with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. Gammaplex does not contain sucrose. For patients at risk of thrombosis, renal dysfunction or acute renal failure, administer Gammaplex at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.

Gammaplex is contraindicated in patients who have had a history of anaphylactic or severe systemic reactions to human immune globulin; an hereditary intolerance to fructose and in infants and neonates for whom sucrose or fructose tolerance has not been established; and IgA deficient patients with antibodies to IgA and a history of hypersensitivity.

agent. No cases of transmission of viral diseases or CJD have been associated with the use of Gammaplex.

Thrombotic events may occur following treatment with immune globulin products, including Gammaplex. Monitor patients with known risk factors for thrombotic events; consider baseline assessment of blood viscosity for those at risk of hyperviscosity.

Serious adverse reactions observed in clinical trial subjects with PI were thrombosis and chest pain. Serious ARs observed in clinical trial subjects with ITP were headache, vomiting and dehydration.

In patients at risk of developing acute renal failure, monitor renal function, including blood urea nitrogen (BUN), serum creatinine and urine output. Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV therapy. Aseptic meningitis syndrome (AMS) may occur infrequently with IGIV treatment. AMS usually begins within several hours to 2 days following IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. AMS may occur more frequently in association with high doses (2 g/kg) and/or rapid infusion of IGIV. Hemolysis and hemolytic anemia can develop subsequent to IGIV treatments. Patient risk factors that may be associated with development of hemolysis include high dose (>2 g/kg), non-O blood group, and underlying inflammatory state. Noncardiogenic pulmonary edema may occur in patients following IGIV treatment (i.e. transfusion-related acute lung injury [TRALI]). Monitor patients for pulmonary adverse reactions (TRALI). If TRALI is suspected, test product and patient’s serum for anti-neutrophil antibodies. Gammaplex is made from human plasma and may contain infectious agents, e.g. viruses and, theoretically, the Creutzfeldt-Jakob disease

In clinical studies, the most common adverse reactions with Gammaplex were headache, pyrexia, vomiting, fatigue, pain, nausea, hypertension, chills and myalgia.

Please refer to the Gammaplex Prescribing Information for full prescribing details.

REFERENCES 1. Moy JN, Scharenberg AM, Stein AR, et al. Clin Exp Immunol. 2010;162:510-515. 2. Dash CH, et al. PLoS ONE. 2014;9(6):e96600. 3. Gammaplexx® (Immune Globulin Intravenous [Human], 5% Liquid) Prescribing Information. Raleigh, NC: BPL Limited. 2014. 4. Data on file, BPL: December 2011

For product information and inquiries, please call (866) 398-0825 or email BPLinfo@LashGroup.com

Specialty Pharmacy Continuum • April/May 2015

CLINICAL

HOME TPN continued from page 13

order to optimize their energy to protein-to-fat ratio.” The group did not perform a cost analysis, but Dr. Martinez noted that the resources used are generally available in most children’s hospitals. “Bringing a team to the patient’s home for baseline and post-intervention evaluation as we did might not be feasible for all other institutions, but the multidisciplinary approach would be easy to adopt in chil-

Gammaplex

Immune Globulin Intravenous (Human), 5% Liquid BRIEF SUMMARY CONSULT FULL PRESCRIBING INFORMATION FOR COMPLETE PRODUCT INFORMATION WARNING: THROMBOSIS, RENAL DYSFUNCTION and ACUTE RENAL FAILURE Thrombosis may occur with immune globulin products, including Gammaplex. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur in predisposed patients who receive immune globulin intravenous (lGIV) products, including Gammaplex. Patients predisposed to renal dysfunction include those with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. Gammaplex does not contain sucrose. For patients at risk of thrombosis, renal dysfunction or acute renal failure, administer Gammaplex at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. INDICATIONS AND USAGE Primary Humoral Immunodeficiency (PI) - Gammaplex is an Immune Globulin Intravenous (Human), 5% Liquid indicated for replacement therapy in adults with primary humoral immunodeficiency (PI). Chronic Immune Thrombocytopenic Purpura (ITP) - Gammaplex is indicated for the treatment of adults with chronic immune thrombocytopenic purpura (ITP) to raise platelet counts. CONTRAINDICATIONS Gammaplex is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin. Gammaplex is contraindicated in patients with hereditary intolerance to fructose, also in infants and neonates for whom sucrose or fructose tolerance has not been established. Gammaplex is contraindicated in IgA-deficient patients with antibodies to IgA and a history of hypersensitivity. WARNINGS AND PRECAUTIONS Renal Dysfunction / Failure: Acute renal dysfunction/failure, osmotic nephropathy, and death may occur upon use of human IGIV products. Ensure that patients are not volume depleted before administering Gammaplex. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of Gammaplex and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing Gammaplex. Thrombotic Events: Thrombosis may occur following treatment with immune globulin products, including Gammaplex. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia / markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. For patients at risk of thrombosis, administer Gammaplex at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Hypersensitivity: Severe hypersensitivity reactions may occur. In case of hypersensitivity, discontinue Gammaplex infusion immediately and institute appropriate treatment. Medications such as epinephrine should be available for immediate treatment of acute hypersensitivity reactions. Gammaplex contains trace amounts of IgA (<10 μg/ mL). Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. Gammaplex is contraindicated in patients with antibodies against IgA and a history of hypersensitivity reaction.

dren who are admitted to the hospital, or at clinic visits.” Dr. Martinez suggested that the model could also be useful in a pediatric ICU setting. “We were able to identify that optimizing nutrition can modify body chemistry and respiratory function, and when a patient is hospitalized in a chronic subacute state, that’s an important time to make sure that nutrition is optimized for rehabilitation and lean body mass preservation.” Children with intestinal failure who are on long-term total parenteral

Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia: Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV therapy. It is critical to clinically distinguish true hyponatremia from a pseudohyponatremia that is associated with or causally related to hyperproteinemia with concomitant decreased calculated serum osmolality or elevated osmolar gap, because treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and a possible predisposition to thrombotic events. Aseptic Meningitis Syndrome (AMS): AMS may occur with IGIV treatment. AMS usually begins within several hours to 2 days following IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. AMS is characterized by the following signs and symptoms: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting. Cerebrospinal fluid (CSF) studies frequently reveal pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dL, but negative culture results. Conduct a thorough neurological examination on patients exhibiting such signs and symptoms, including CSF studies, to rule out other causes of meningitis. AMS may occur more frequently in association with high doses (2 g/kg) and/or rapid infusion of IGIV. Hemolysis: Gammaplex may contain blood group antibodies that can act as hemolysins and induce in vivoo coating of red blood cells (RBCs) with immunoglobulin, causing a positive direct antiglobulin test (DAT) (Coombs’ test) result and hemolysis. Delayed hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration and acute hemolysis, consistent with intravascular hemolysis, has been reported. The following risk factors may be associated with the development of hemolysis following IGIV administration: high doses (e.g., *2 g/kg), given either as a single administration or divided over several days, and non-O blood group. Closely monitor patients for clinical signs and symptoms of hemolysis, particularly patients with risk factors noted above. If clinical signs and symptoms of hemolysis or a significant drop in hemoglobin or hematocrit have been observed, perform confirmatory laboratory testing. If transfusion is indicated for patients who develop hemolysis with clinically compromising anemia after receiving IGIV, perform adequate cross-matching. Transfusion-related Acute Lung Injury (TRALI): Noncardiogenic pulmonary edema may occur in patients following IGIV treatment. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function and fever. Symptoms typically appear within 1 to 6 hours following treatment. Monitor patients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and the patient’s serum. TRALI may be managed using oxygen therapy with adequate ventilatory support. Volume Overload: Carefully consider the relative risks and benefits before prescribing the high dose regimen (for chronic ITP) in patients at increased risk of volume overload. Transmissible Infectious Agents: Because Gammaplex is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No cases of transmission of viral diseases or CJD have been associated with the use of Gammaplex. All infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare providers to BPL Inc. 1-866-3980825. Before prescribing Gammaplex, the physician should discuss the risks and benefits of its use with the patient. Laboratory Tests: After infusion of immunoglobulin, the transitory rise of the various passively transferred antibodies in the patient’s blood may yield positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test. Clinically assess patients with known renal dysfunction, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or those receiving nephrotoxic agents, and monitor as appropriate (BUN, serum creatinine, urine output) during therapy with Gammaplex. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with polycythemia, cryoglobulins, fasting chylomicronemia/markedly high triglycerides, or monoclonal gammopathies. Consider measuring hemoglobin or hematocrit at baseline and approximately 36 to 96 hours post infusion in patients at higher risk of hemolysis. If signs and/or symptoms of hemolysis are present after an infusion of Gammaplex, perform appropriate laboratory testing for confirmation. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and patient’s serum. ADVERSE REACTIONS Serious adverse reactions (ARs) observed in clinical trial subjects with primary humoral immunodeficiency (PI) were thrombosis and chest pain. Serious ARs observed in clinical trial subjects with immune thrombocytopenic purpura (ITP) were headache, vomiting and dehydration. The most common ARs observed in the PI clinical trial were headache (18 subjects, 36%), pyrexia (8 subjects, 16%), fatigue (6 subjects, 12%), nausea (6 subjects, 12%), hypertension (3 subjects, 6%), chills (3 subjects, 6%), myalgia (3 subjects, 6%), pain (4 subjects, 8%), and vomiting (3 subjects, 6%). The most common ARs observed in the chronic ITP clinical trial were headache (12 subjects, 34%), vomiting (8 subjects, 23%), nausea (5 subjects, 14%), pyrexia (5 subjects, 14%), pruritus (2 subjects, 6%) and arthralgia (2 subjects, 6%).

nutrition (TPN) are also at significant risk for nutritional deficiencies, reported a group from the University of California, Los Angeles, Department of Pediatric Gastroenterology. “This is much more common than I ever would have expected,” said contributing author Laura J. Wozniak, MD. “Approximately 86% of the children in our group had at least one deficiency.” The retrospective study analyzed the nutritional profiles of 65 children with intestinal failure who had been on TPN for more than six months. The most

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 clinical practice. Treatment of Primary Humoral Immunodeficiency: In a multicenter, open-label, non-randomized clinical trial, 50 subjects with PI received doses of Gammaplex ranging from 279 to 799 mg/kg every 21 days (mean dose 465 mg/kg) or 28 days (mean dose 458 mg/kg), for up to 12 months. Twenty-four subjects (48%) had an AR at some time during the clinical trial that was considered product-related. The total number of ARs during infusion or within 72 hours of infusion was 237 (a rate of 0.34 ARs per infusion). The percentage of Gammaplex infusions with one or more ARs within 72 hours of infusion was 21%. The upper bound of the 1-sided 97.5% confidence interval for this percentage was 24%, which was below the pre-specified upper limit of 40% for this safety endpoint. The most common ARs observed in this clinical trial were headache (18 subjects, 36%), fatigue (6 subjects, 12%), nausea (6 subjects, 12%), pyrexia (6 subjects, 12%), pain (4 subjects, 8%), hypertension (3 subjects, 6%), chills (3 subjects, 6%), myalgia (3 subjects, 6%) and vomiting (3 subjects, 6%). Two subjects experienced serious ARs (thrombosis and chest pain). Forty-seven of the 50 subjects enrolled in this clinical trial had a negative direct antiglobulin test (DAT) at baseline. Of these 47 subjects, 4 (9%) developed a positive DAT at some time during the clinical trial. However, no subjects showed evidence of hemolytic anemia. Table 1: Adverse Reactions (ARs*) Occurring in >5% of Subjects with PI Adverse Reactions

Subjects (%) PI [n=50]

Infusions (%) PI [n=703]

Headache

18 (36%)

53 (7.5%)

Pyrexia

7 (14%)

10 (1.4%)

Sinusitis

8 (16%)

9 (1.3%)

Fatigue

6 (12%)

9 (1.3%)

Nausea

6 (12%)

7 (1.0%)

Nasal Congestion

5 (10%)

3 (0.4%)

Pain

4 (8%)

5 (0.7%)

Vomiting

3 (6%)

3 (0.4%)

Chills

3 (6%)

5 (0.7%)

Hypertension

3 (6%)

4 (0.6%)

Insomnia

3 (6%)

3 (0.4%)

Muscle spasms

3 (6%)

2 (0.3%)

Myalgia

3 (6%)

3 (0.4%)

Upper respiratory tract infection

3 (6%)

5 (0.7%)

*Adverse Reactions (ARs) are defined as treatment emergent adverse events which met any of the following criteria: (a) adverse events which began during an infusion of Gammaplex or within 72 hours of the end of an infusion, (b) adverse events considered by the investigator or sponsor to have been possibly, probably, or definitely related to administration of Gammaplex, (c) adverse events for which the investigator’s causality assessment was either missing or indeterminate. Treatment of Chronic Immune Thrombocytopenic Purpura: In a multicenter, open-label, non-randomized clinical trial, 35 subjects with chronic immune thrombocytopenic purpura were treated with a nominal dose of 1,000 mg/kg on each of two consecutive days (total dose 2,000 mg/kg). Doses of Gammaplex ranged from 482 to 1149 mg/kg on an infusion day. The median total dose per subject was 2035 mg/kg. All 35 subjects received at least one infusion of clinical trial drug, and all but one subject completed the first course of treatment. Twenty-four subjects (69%) reported at least one AR (103 in total); the most commonly reported being headache (12 subjects, 34%), vomiting (8 subjects, 23%), nausea (5 subjects, 14%), pyrexia (5 subjects, 14%), pruritus (2 subjects, 6%), dehydration (2 subjects, 6%) and arthralgia (2 subjects, 6%). Three subjects experienced a total of five serious ARs. Of the five serious ARs, one subject had three concurrently (vomiting, dehydration and headache) and two subjects each had one serious AR (headache). One of these latter two subjects discontinued from the clinical trial because of the severe headache. Table 2 lists the ARs in more than 5% of subjects. Based on a review of clinical and laboratory data, 4/35 subjects (11%) with drops in hemoglobin exceeding 2 g/dL following administration of Gammaplex were considered to have experienced suspected treatment-emergent hemolysis. Milder treatment-emergent hemolysis could not be excluded for an additional 7 subjects, giving a total of 11 of 35 subjects (31%) for whom hemolysis could not be excluded (not including an additional two subjects who lacked follow-up testing for hemolysis, so their hemolysis status was considered unassessable).

Occurring in >5% of

T Subjects with ITP Subjects (%) ITP [n=35]

Infusions (%) ITP [n=94]

Headache

Adverse Reactions

12 (34%)

15 (16%)

Vomiting

8 (23%)

9 (9.6%)

Nausea

5 (14%)

5 (5.3%)

Pyrexia

5 (14%)

7 (7.4%)

Pain

2 (6%)

2 (2.1%)

Abdominal pain upper

2 (6%)

2 (2.1%)

Nausea

6 (12%)

7 (1.0%)

Nasal Congestion

5 (10%)

3 (0.4%)

Gastritis

2 (6%)

2 (2.1%)

Contusion

2 (6%)

2 (2.1%)

Arthralgia

2 (6%)

2 (2.1%)

Cough

2 (6%)

2 (2.1%)

Anemia

2 (6%)

1 (1.1%)

Ecchymosis

2 (6%)

3 (3.2%)

Pruritus

2 (6%)

2 (2.1%)

Dehydration

2 (6%)

2 (2.1%)

Hypertension

2 (6%)

1 (1.1%)

Neck pain

2 (6%)

1 (1.1%)

*Adverse Reactions (ARs) are defined as treatment emergent adverse events which met any of the following criteria: (a) adverse events which began during an infusion of Gammaplex or within 72 hours of the end of an infusion, (b) adverse events considered by the investigator or sponsor to have been possibly, probably, or definitely related to administration of Gammaplex, (c) adverse events for which the investigator’s causality assessment was either missing or indeterminate. In neither of the above trials was there evidence of transmission of HBV, HCV, HIV and parvovirus B19. Postmarketing Experience: Because adverse reactions are voluntarily reported post-approval from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure. In addition to the adverse reactions identified in clinical studies, the following adverse reactions have been identified during postmarketing use of Gammaplex: Infusion reactions:: Dizziness, back pain, flushing; Respiratory:: Pulmonary embolism, dyspnea; Cardiovascular:: Myocardial infarction; Integumentary:: Rash, urticarial. The following adverse reactions have been identified during post-marketing use of intravenous immune globulins : Infusion reactions:: hypersensitivity (e.g., anaphylaxis), headache, diarrhea, tachycardia, fever, fatigue, dizziness, malaise, chills, flushing, urticaria or other skin reactions, wheezing or other chest discomfort, nausea, vomiting, rigors, back pain, myalgia, arthralgia, and changes in blood pressure; Renal:: Acute renal dysfunction/failure, osmotic nephropathy; Respiratory:: Apnea, Acute Respiratory Distress Syndrome (ARDS), TRALI, cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm; Cardiovascular:: Cardiac arrest, thromboembolism, vascular collapse, hypotension; Neurological:: Coma, loss of consciousness, seizures, tremor, aseptic meningitis syndrome; Integumentary: Stevens-Johnson syndrome, epidermolysis, erythema multiforme, dermatitis (e.g., bullous dermatitis); Hematologic:: Pancytopenia, l e u k o p e n i a , h e m o l y s i s , p o s i t i v e d i r e c t a n t i g l o b u l i n ( C o o m b s’ ) t e s t ; Gastrointestinal:: Hepatic dysfunction, abdominal pain; General/ Body as a Whole:: pyrexia, rigors DRUG INTERACTIONS: Transitory rise of the various passively transferred antibodies in the patient’s blood after infusion of immunoglobulin may yield positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test. Passive transfer of antibodies may transiently interfere with the immune response to live virus vaccines such as measles, mumps, rubella and varicella. Inform the immunizing physician of recent therapy with Gammaplex so that appropriate measures may be taken. Manufactured by: Bio Products Laboratory Limited Dagger Lane Elstree Hertfordshire WD6 3BX United Kingdom. US License No. 1811

common deficiency was vitamin D (67%), followed by copper (54%), iron (51%), zinc (51%) and selenium (17%). “These deficiencies can be attributed to the lack of oral and enteral absorption, as well as, in many cases, the effects of the underlying disease state on their bowels,” Dr. Wozniak said. “What they do take in orally may not be adequately absorbed. And of course, just the effects of chronic illness may contribute as well. These children are frequently in the hospital with line infections or undergoing surgeries, so they’re obviously not walking around and getting sun exposure.” The problem has been compounded by national shortages of many nutrients and trace elements for TPN. “It didn’t hit our kids as hard as our adults, because most pharmacies prioritize the children first and they have been able to get most of what they need,” Dr. Wozniak said. “But even though we are now fine with multivitamins, we still have spot shortages on some of the trace elements.”

Vigilence Urged Home infusion providers should assess key nutrient levels in children on TPN at least four times per year, and more frequently if indicated, Dr. Wozniak said. “I think most large centers with major TPN programs are generally diligent with this. But we know from shared patients who are under the care of outside providers, who may not see nearly as many of these cases, that these kids may not be assessed as much—certainly not four times per year.” If deficiencies are found in regular assessments, supplementation, as well as the frequency of nutritional testing should be increased. “Even when the guidelines set out by A.S.P.E.N. are followed, we still see that the majority of patients have deficiencies, so it’s important to check at that minimum frequency,” Dr. Wozniak said. “Where we get into trouble is with the patients who we forget to check, and then six or eight months go by and they’ve been deficient that long.” —Gina Shaw

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Specialty Pharmacy Continuum • April/May 2015

CLINICAL N ICAL

CRBSIs continued from page 1

at Cancer Treatment Centers of America (CTCA), Midwestern Regional Medical Center, in Zion, Ill. The study, which was presented at the American Society for Parenteral and Enteral Nutrition’s Clinical Nutrition Week (poster M9), assessed the efficacy of two standardized interventions: an intensive education and compliance effort, in which patients received detailed pre-discharge teaching by a team of nurses, dietitians and a dedicated case manager before going home with parenteral nutrition; and once at home, a standardized catheter maintenance protocol. The 241 adult oncology patients in the study received home TPN from Coram CVS/specialty infusions services and active treatment at CTCA from Jan. 1, 2012 to Dec. 31, 2013. The first two days of infusion were done at the hospital, during which patients were given verbal instruction, written educational material and a DVD. “We have them watch an educational DVD while they are getting their infusion, ask them if they have any questions, and then they go home with the DVD,” Dr. Vashi said. “Before they go home, we ask our patients to go over all the steps starting from how they are

going to handle the TPN bags (refrigerate them, keep them away from other food), to how they are going to add the nutrients to the bags/wash their hands, etc. Then a home health nurse goes to the patient’s home for the first couple of days and shows the patient how to do it. By then, the patient has usually become quite familiar with the process and can follow the protocol very strictly.”

Strict Aseptic Techniques The catheter care protocol included a strict aseptic flushing and dressing change procedure; weekly sterile dressing changes with use of ChloraPrep (CareFusion); and the application of MicroClave connectors (ICU Medical) and SwabCaps (Excelsior Medical) on all lumens that were not in use. The home health nurse performed a weekly assessment that provided details about the patients’ clinical status and compliance with catheter care and TPN, as well as the catheter status. The most common malignancies were stage III/IV colorectal, pancreatic and gynecologic cancer, and the average length of therapy was 70 days. The bulk of patients had an implanted port (51%) or a peripherally inserted central line (46%), with only 3% having a tunneled catheter. The incidence of CRBSIs was 0.47 per 1,000 catheter-days, which is

significantly ig ifi tl lless th than th those reported t d in the literature. For example in a study of patients with a variety of diseases, including HIV, cancer and heart disease, who were receiving home infusion therapy, rates of CRBSI varied from 0.16 to 6.77 per 1,000 catheter-days, depending on risk factors ((Ann Intern Med 1999;131[5]:340-347), he pointed out. In another study, the CRBSI rate was 4.49 per 1,000 catheter-days in pediatric hematology/oncology patients admitted to a hospital ((J Microbiol Immunol Infect 2014.pii:S1684-1182[14]00164-9). Cancer patients, who are often immunocompromised, are particularly susceptible to CRBSI when receiving treatment and/or parenteral nutrition. Up to

Vitamin D and Cancer Link? LONG BEACH, CALIF.—Is it time to add vitamin D supplements to the home infusion regimens of prostate and lung cancer patients? Some practitioners have already taken this step, based on the substance’s ability to inhibit apoptosis, inflammation and other processes linked to cancer, not to mention data showing a beneficial effect on survival. But two new studies presented at Clinical Nutrition Week, sponsored by the American Society for Parenteral and Enteral Nutrition, have cast doubt on the need for the supplement. “When a patient comes in with advanced lung or prostate cancer, whatever damage has been done is already done; trying to actively correct vitamin D levels might not make sense” based on the new data, said Pankaj Vashi, MD, the national clinical director of gastroenterology, nutrition and metabolic support at Cancer Treatment Centers of America (CTCA), Midwestern Regional Medical Center, Zion, Ill., who was involved with both studies. In the first study (poster M10), 125 patients with newly diagnosed stage IV prostate cancer underwent a baseline serum evaluation of vitamin D (25-hydroxyvitamin D) levels before receiving any treatment at CTCA between January 2008 and December 2011. At the time of diagnosis, vitamin D levels were deemed deficient (<20 ng/mL) in 25.6% of patients, insufficient (20-32 ng/mL) in 39.2% and sufficient (>32 ng/mL) in 35.2%. Patients were e followed prospectively until May 2014, and all were alive at least 60 days after serum collection. At the time of the analysis, 39.2% of patients had died and there was no association between the pretreatp ment vitamin D levels and d overall survival (OS). The study y was published onlin ne in PLoS S One on March 16. M

In the second study (poster M11), 270 patients with newly diagnosed stage III/IV non-small cell lung cancer (NSCLC) underwent a vitamin D evaluation before receiving any treatment between January 2008 and December 2010. Investigators followed patients prospectively until July 2014. Almost 80% of the patients had stage IV disease at diagnosis. Adenocarcinoma (73.3%) and squamous cell carcinoma (21.9%) were the two most common histologic subtypes. At the time of diagnosis, 43.7% of patients were classified as deficient in vitamin D, 31.5% were deemed insufficient and 24.8% were classified as sufficient. At the time of the analysis, 91.1% of patients had died, and the researchers found no association between vitamin D status and OS. Kimmie Ng, MD, MPH, a physician at Dana-Farber Cancer Institute, in Boston, recently led a 1,043-patient study that demonstrated higher pretreatment levels of vitamin D are associated with markedly improved progressionfree survival and OS in patients receiving treatment for metastatic colorectal cancer (2015 Gastrointestinal Cancers Symposium, abstract 507). Dr. Ng said the two new studies were well conducted, but pointed out they had very small patient numbers. “Therefore, I am not surprised that they were unable to find an association between 25(OH)D [25-hydroxyvitamin D] levels and survival,” Dr. Ng said. “Although the advanced nature of the cancer could have played a role in the lung cancer study, it is not a likely explanation for the results of the prostate study, [because] the median survival of those patients was long, at 40 to 50 months. It is also possible that the role of vitamin D is different in lung and prostate cancers than it is in colorectal cancer.” —K.O. Drs. Vashi and Ng reported no relevant ﬁnancial conﬂicts of interest.

63% off patients ti t undergoing d g i g home h TPN have at least one CRBSI in a year ((Aliment Pharmacol Ther 2006;24[8]:12311240). Moroever, the infections can have a two-pronged negative effect: They are associated with high morbidity and mortality and they come with a steep price tag, between $25,000 and $45,000 per infection (Clin Infect Dis 2011;52[9]:e162-e193). Dr. Vashi said the low infection rates in his study should reassure clinicians who want to recommend TPN, which can be very valuable. Malnutrition is common in patients with cancer and is associated with reduced quality of life (QoL), increased incidence of complications, decreased efficacy of treatment and reduced life expectancy. TPN can diminish some of these problems and has been shown to significantly improve QoL, even in certain advanced cancer patients ((BMC Cancer 2014;14:593). An Italian study also showed low rates of CRBSI are achievable in patients receiving home TPN. In the study of 254 such patients, half of whom were on active treatment, the CRBSI rate was 0.35 per 1,000 catheter-days with an “optimally managed” TPN program (J ( Parenter Enteral Nutrr 2011;37:375-383)

Oncology Pharmacist’s Take “The results of this study are significant because the cost of CRBSIs is so high, the infections require hospitalization and can lead to mortality, and the drugs used for treatment are expensive,” said Robert Ignoffo, PharmD, a professor of clinical pharmacy at Touro University California and a clinical professor emeritus at the University of California, San Francisco, who was not involved with the study. “Anytime you can standardize a prophylactic treatment, it leads to optimal control of the problem. Pharmacy departments and home infusion providers should promote the use of standardized catheter care protocol.” —Kate O’Rourke Drs. Vashi and Ignoffo reported no relevant ﬁnancial conﬂicts of interest.

Specialty Pharmacy Continuum • April/May 2015

OPERATIONS & MANAGEMENT

ACCREDITATION continued from page 1

The case for accreditation is a hard one to make—at least initially—because the endorsement doesn’t have an immediate impact on a specialty pharmacy provider’s bottom line. But the value is there, it can be documented and it is an effort worth making, according to Andrew Maddigan, the marketing manager of the Accreditation Commission for Health Care. “You just can’t prescribe a $5,000 a month medication to somebody and keep your fingers crossed hoping that they will take it,” Mr. Maddigan said. “You need to have a pharmacy that has the infrastructure to be able to commit to managing these patients and one that has demonstrated that its facility is engaging with providers—and be able to prove it.”

The Basics of Accreditation Accreditation is a review of the specialty pharmacy’s policies, procedures, processes, patient care services and out-

Mahaney, BSPharm, MBA, the executive director of the Center for Pharmacy Practice Accreditation (CPPA), based in Madison, Wis. The CPPA is a partnership established by the American Pharmacists Association, the National Association of Boards of Pharmacy and the American Society of Health-System Pharmacists that was formed in part to oversee accreditation of pharmacy practice sites. “Accreditation is a way of showing patients, health care providers, payors and manufacturers that the pharmacy is performing at a level much above what is required by regulation,” Ms. Mahaney said. Accreditation also provides the specialty pharmacy with a way to distinguish itself by its commitment to continuous quality improvement, added Heather Bonome, PharmD, the director of the Pharmacy Segment at URAC. The business office should consider two areas when evaluating the ROI of becoming an accredited specialty pharmacy provider: Will the accreditation process improve patient care and can

‘If a specialty pharmacy wants access to certain revenue streams, they have to accept the expense of accreditation.’ —Andrew Maddigan

comes that is performed by an independent, external body, which will compare that specialty pharmacy against national quality, care and business operation standards, Mr. Madiggan explained. Going through the accreditation process will enable the specialty pharmacy to develop or enhance policies and procedures, and provide documentation that substantiates that the pharmacy offers exemplary care and service that will improve patient outcomes, added Lynnae

they use this accreditation to their advantage by demonstrating to payors, providers and manufacturers that they are “exemplary,” explained Sandra Canally, RN, the president of The Compliance Team, a health care accreditation organization headquartered in Spring House, Pa. “Are they taking data and showing measures about how their operation is [functioning] at a higher level?” If they can demonstrate the superiority of their operation, then specialty

‘Accreditation is a way of showing patients, health care providers, payors and manufacturers that the pharmacy is performing at a level much above what is required by regulation.’ —Lynnae Mahaney, BSPharm, MBA pharmacy accreditation can make a direct contribution to the bottom line, Ms. Mahaney said, because payors and manufacturers will be more likely to contract with a specialty pharmacy that is accredited, and patients will be more likely to return if care is good and satisfaction is high. “If a specialty pharmacy wants access to certain revenue streams, they have to accept the expense of accreditation,” added Mr. Maddigan. The expense is justified, he said, because by pursuing the endorsement, providers are “opening up the possibility for some pretty significant revenues, and they are also benefitting in terms of their organization becoming more efficient and better trained, which positively impacts patient outcomes.” Besides the actual cost of the accreditation, which depends on several factors, such as how big the pharmacy is, how many locations it has, the number of specialty products it dispenses, how many patients it serves and staffing size, the specialty pharmacy must account for the staffing hours that will be needed to achieve accreditation.

Not a Time for Delegation This is not an activity that can be dumped on the desk of an administrative assistant or pharmacy technician to do in his or her spare time; pharmacy resources must be dedicated to the process, and the person must be able to spend at least four hours a week preparing for the accreditation, according to Ms. Canally.

How To Choose an Accreditation Body

ome business offices might suggest choosing an accreditor strictly based on price. Not so fast, the experts said. There are many criteria to consider and steps to take when choosing an accreditor. 1. Do a needs assessment. Before you choose an accreditor, review your own operations and see where you might be deficient. If you were started by a group of pharmacists who might be great at patient care, but not so good on the business side, you might want an accreditor that focuses more on the operations and business. If you were started by a venture capitalist, you might want one that concentrates on patient care. 2. Do your research. The next step is to go on all of the accreditors’ websites and take a look at their policies and standards, pricing and other basic information. Are they truly an independent body? Do you understand the standards and what is expected of you? Are they transparent? How were the standards developed? Who developed

them? How often are they updated or reviewed? 3. Dig a bit deeper. Look at how they handle the preparation process. What type of educational opportunities do they provide? Just as if you were shopping online, an educated consumer would also do well to consider the experience of others. Contact some of the accredited pharmacies, not just those listed as “in process” on the website and ask them what they thought of the process. Was the survey helpful? Did the overall process offer value commensurate with the cost? 4. Consider the contract. Does the manufacturer or third-party payor want a specific accreditation(s) before it will award a contract for distributing a given specialty medication? 5. Keep the end goal in mind. Regardless of which accrediting body you choose, expect to come out of the process a stronger operation that delivers superior patient care. —M.R.

Sometimes more time is needed, depending on the protocols and policies that are already in place and whether the pharmacy has ever gone through the process before, Dr. Bonome added. The preparation process can take months, so be prepared to invest the time. Once the decision is made and the accrediting body is chosen, the specialty pharmacy must obtain copies of the standards that it must meet. These are usually on the accreditor’s website and often include checklists and other selfassessment tools to help the pharmacy to determine next steps. In some cases, a new policy or protocol will have to be created; in others, existing ones will need some tweaking.

Points of Differentiation Although each accrediting body might focus more on a particular area, say operations, than another, they all review just about every area of the pharmacy, from staffing and training to patient care and follow-up. Each area must meet the standards before accreditation will be granted, Ms. Canally noted. The specialty pharmacy should look at itself the way the accreditor would and review all areas of its business and care model. The accreditor might look at employment records, quality metrics, licenses, written policies and protocols, patient care, education and follow-up, to name just a few areas of interest. Most of the accreditors appoint a “navigator,” someone the specialty pharmacy team can approach while preparing for accreditation. The navigator should be able to answer questions and offer guidance. Others offer online tools and regularly scheduled conference calls with the accreditor for feedback and education. Dr. Bonome suggested that specialty pharmacies take advantage of those resources. “We take an educational approach to accreditation,” she said. “So throughout the process, the applicant is encouraged to take advantage of the webinars, workshops and other tools and programs that provide the opportunity for gaining additional knowledge and understanding of the accreditation standards and process.” Once the pharmacy believes it is ready, the evaluation starts. An accreditor reviews all the documentation and metrics to see if they meet

Specialty Pharmacy Continuum • April/May 2015

OPERATIONS & MANAGEMENT

the standards. Then, he or she makes a site visit to see how the standards are implemented. The accreditor will review more documentation, licenses, mission statement, and might even talk to some staff members. Does a particular pharmacy technician know how to use the pharmacy information system to ensure a medication is delivered safely? What kind of follow-up does the pharmacy do to maintain medication adherence? What happens if there is an adverse event? Do they understand a drug’s Risk Evaluation and Mitigation Strategy program? What is the pharmacy’s harassment policy? If staff members don’t know the answers, do they know where to find the information? After the site visit, the accreditor issues a report and determines whether the pharmacy can be accredited. If there are minor deficiencies, the pharmacy may correct them. If there are major deficiencies, the pharmacy will fail the accreditation and will have to reapply. After accreditation is awarded, the pharmacy must provide organizational updates that affect standard compliance or scope of accreditation as they occur, verify that it has continually adhered to the accreditation guidelines via an annual attestation and fulfill a commitment to reporting pharmacy outcomes measures, Dr. Bonome explained. Some pharmacies hire an outside consultant to help them through the process, but Ms. Canally warned that they should make sure this person is actually helping them get ready for the site visit, not explaining what the standards mean. Standards should be understandable, she said. In fact, all the information should be transparent, added Ms. Mahaney. All of the accreditation experts agreed that some specialty pharmacies

FDA APPROVAL Unituxin Approved For Pediatric Neuroblastoma

he FDA has approved dinutuximab (Unituxin, United Therapeutics), in combination with granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2) and 13-cisretinoic acid (RA), to treat children with high-risk neuroblastoma who are partial responders to previous chemotherapy. The recommended dose and schedule for dinutuximab is 17.5 mg/m2 per day as a diluted IV infusion over 10 to 20 hours for four consecutive days for up to five cycles. Patients require IV treatment with opioids before, during and for two hours after the dinutuximab infusion to mitigate neuropathic pain. Patients also require prehydration and premedication to decrease the risk for hypotension and serious infusion reactions. Dinutuximab is a monoclonal antibody containing a combination of mouse and human DNA.

‘Throughout the [accreditation] process, the applicant is encouraged to take advantage of the webinars, workshops and other tools and programs [to gain] additional knowledge and understanding of the accreditation standards and process.’ —Sandra Canally, RN will seek more than one accreditation, and there is debate among them about

whether such a strategy has merit. They all felt that their organization’s

standards were rigorous enough that a pharmacy should only need one seal of approval. However, there can be a financial reason for passing more than one accreditation process; some payors and manufacturers demand accreditation from a certain accreditor before awarding contracts, Mr. Maddigan pointed out. If the pharmacy wants a chance at that contract, he noted, it needs to have that accreditation. But take heart, he said: The second time is usually easier. —Marie Rosenthal

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Specialty Pharmacy Continuum • April/May 2015

Q & A MEDI-DOSE The following advertorial is provided by Medi-Dose. It is designed to support the advertisement presented below.

MILT 4 Q: MILT 3.0 has been the industry-leading solution for labeling and barcoding unit-dose medications for years. Why did you decide to create a new version of this program?

A: MILT 3.0 has been extremely well received by pharmacists in facilities of all kinds and sizes. We would have continued to add features and enhancements indefinitely. But with 64-bit Windows becoming popular, the existing code had to be rewritten to support it. Rather than just reconfiguring MILT 3.0 for 64-bit, we chose to use the knowledge we gained working with so many pharmacists and rewrote the program to even better suit their specific needs.

Q: So the new version, MILT 4, requires 64-bit Windows? A: No, MILT 4 works with either 64- or 32-bit Windows. Furthermore, it can even be installed

on the same computer where MILT 3.0 is currently installed.

Q: How easy is it to move from MILT 3.0 to MILT 4? A: MILT 4 lets you import all your users, log history and formulary information from MILT 3.0. All of the features of MILT 4 (both those from MILT 3.0 and the new ones we’ve added) have been arranged to best simulate the workflow in a pharmacy.

Q: Which enhancements will make the most difference for pharmacists and staff?

A: The faster printing, cleaner fonts and easier interface will be the most obvious improvements for existing users. One of the most asked-for features is the ability to have different date calculations associated with specific medications. MILT 4 will automatically calculate the appropriate beyond-use date each time someone opens that medication. Another requested feature is the ability to be prompted for specific data, like a lot number, each time a medication is selected. Both of these features allow pharmacists to guide their staff toward completing the packaging task correctly, but still allow for intervention when special occasions arise.

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MILT 4 is the newest version of Medi-Dose's industry M leeading labeling and bar coding software. Every feature oof this custom-written program was specifically ddesigned to accommodate the needs of healthcare pprofessionals. With our large variety of laser and direct thermal labels, you can clearly identify and easily bar th code all medications.

A: That’s right. The pharmacist can configure everything from the type of information to be collected, to the rules for how barcodes are created, to easily limiting or expanding the access that staff members have to features within the program, ensuring that those choices are enforced. Labels for each medication type can be customized, and packaging logs and reports can retrieve desired information about the work that has been done.

Q: Is there a network version of MILT 4? A: MILT 4 is sold as an unlimited individual-site license. You can install the program on as many computers as you need. It’s easy to share your database with all the computers in just a standard folder on the network—no server installation is required.

Q: Can MILT 4 create advanced barcodes? A: MILT 4 allows you to include up to seven pieces of information in a 1-D or 2-D barcode, and to include identifiers that distinguish each piece of information. For example, you can create a barcode incorporating an NDC number, expiration date and lot number. If your barcode medication administration (BCMA) or point-ofcare (BPOC) systems can accommodate it, MILT 4 can generate it.

Q: What types of labels does MILT 4 support? A: We have a complete line of thermal and laser labels designed specifically for pharmacy and nursing use. From moisture-resistant, tamper-evident labels for sealing solids in our blisters, to butterfly and flag shapes for syringes, to labels small enough for unit-dose suppositories and large enough for IV bags, Medi-Dose/EPS and our MILT 4 software make it easy to label and barcode any medication.

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Specialty Pharmacy Continuum • April/May 2015

OPERATIONS & MANAGEMENT

Breathe Easier: SP Network Growing For CF Kitabis Pak

he distribution network is growing for PARI’s new cystic fibrosis (CF) treatment Kitabis Pak, a copackaging of Tobramycin Inhalation Solution (drug) and a trademarked reusable nebulizer, used to treat patients with bacterial infection by Pseudomonas aeruginosa.

for Kitabis Pak, which is PARI’s first drug approved in the United States, told Specialty Pharmacy Continuum. “We really want to change the patient experience for people with CF. They struggle enough with their disease and they don’t need a hassle when they take medication.” Given those struggles, “we can’t have a specialty pharmacy that doesn’t give the patient any more value than a regular retail pharmacy,” Ms. Zimmerman said. “We want pharmacies that really care for the patient and add value.”

Diplomat Part of Distributor Network For Cosentyx At press time, 21 specialty pharmacies had officially been approved to distribute Kitabis Pak, including Diplomat Pharmacy Inc., and several Walgreens community and specialty pharmacies. “We are still negotiating and signing with other specialty pharmacies, but we already have a pretty solid network that covers all 50 states,” Jan Zimmermann, the portfolio manager

he legal team at Novartis will not allow the company to publicize which specialty pharmacies will be distributing its new psoriasis drug secukinumab (Cosentyx), but one that’s definitely on the limited-distribution panel is Diplomat Specialty Pharmacy. Diplomat announced on March 4 that it would be distributing the drug, which was approved by the FDA in January to treat moderate to

severe plaque psoriasis in adults. Secukinumab is the first approved drug to target the interleukin-17 pathway, “and given its clinical results,

we’re excited to be able to offer it,” Gary Kadlec, Diplomat’s president, told Specialty Pharmacy Continuum. “Psoriasis is an issue that causes real ramifications in the lives of millions of patients and families. We’re ready to offer the support they need to address their symptoms, successfully stay on therapy and achieve their treatment goals.” Michelle Bauman, a Novartis spokesperson, noted that the company “does not have an exclusive contract with one Specialty Pharmacy, but rather uses a network of contracted specialty pharmacies to distribute Cosentyx. The specialty pharmacies were determined by a number of factors, including clinical expertise, patient education, service, treatment monitoring and support.” The safety and efficacy of secukinumab were established in four randomized, placebo-controlled, Phase III clinical trials with 2,403 participants with

plaque psoriasis who were candidates for systemic therapy or phototherapy. The researchers examined secukinumab 300 and 150 mg. Secukinumab met all primary and key secondary end points, including Psoriasis Area and Severity Index (PASI) 75 and 90 and Investigator’s Global Assessment modified 2011 (IGA) 0/1 responses, showing significant skin clearance at week 12. PASI measures the redness, scaling and thickness of psoriatic plaques, and the extent of involvement in each region of the body. Treatment efficacy is assessed by the reduction of the score from baseline (i.e., a 75% reduction is known as PASI 75 and a 90% reduction is known as PASI 90). Because secukinumab is an immune modulator, patients may have an elevated risk for infection. Serious allergic reactions have been reported with the use of secukinumab. Caution should be exercised when considering the use of secukinumab in patients with a chronic infection or history of recurrent infection, and in patients with active Crohn’s disease. The most common side effects include diarrhea and upper respiratory infections. see INDUSTRY NEWS, page 20

achc.org

ACCREDITATION IN YOUR FIELD SPECIALTY PHARMACY

ACHC offers a range of pharmacy compliance solutions that facilitate the highest level of patient safety through robust quality standards. ACHC Pharmacy accreditation includes: Comprehensive Offerings—Specialty, Community Retail, Long Term Care, Infusion, PCAB Compounding, and DMEPOS Broad Program Acceptance—Most US Third-Party Payors and Medicare in all 50 States Industry-Specific Surveyors—All pharmacy surveys are conducted by a licensed pharmacist

ISO 9001:2008 Certiﬁed CMS Approved

Specialty Pharmacy Continuum • April/May 2015

OPERATIONS & MANAGEMENT

INDUSTRY NEWS continued from page 19

Avella and Sentry Partner To Help Hospitals on 340B

vella Specialty Pharmacy has announced a partnership with Sentry Data Systems to help hospitals and health systems manage their participation in the federal 340B drug discount program. Sentry serves as a third-party administrator for many entities covered under 340B; with a proprietary technology platform, it helps the hospitals and health systems navigate the program’s

often thorny compliance, audit and inventory requirements. Under the new partnership, Avella will provide all the fulfillment of specialty medications for Sentry’s clients. “They do all of the validation and administrative support, while we will provide all the clinical support of the patient and the drug fulfillment,” Nancy McCutcheon, Avella’s senior vice president for strategic sales, told Specialty Pharmacy Continuum. “We have access to many limited-distribution drugs that many other pharmacies, especially specialty pharmacies, do not, as well as a track record of excellence in patient care.” The partnership is not an exclusive relationship for either company, Ms. McCutcheon said, and there are no estimates available as to how many

covered entities will be served under the new partnership. Given the complex requirements of the 340B program—and the growing number of audits being conducted— the need for compliance help is clear. The Health Resources and Services Administration (HRSA), which administers the 340B program, has stepped up its oversight, and conducting onsite audits is just one of the new “integrity

initiatives” that it has implemented in the past few years. Audits started in fiscal year 2012, and the number of audits conducted continues to increase each year. The audits assess participants’ compliance with program guidance and ensure that products are not being diverted to ineligible patients. As of late 2014, nearly 250 audits had been performed, according to an HRSA spokesperson. More are expected in 2015. Any covered entity that fails to comply with 340B program rules may be required to refund the discounted monies to the manufacturers or be removed from the program, and they will be subject to a second audit the following year, according to the agency. —Gina Shaw

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McMahon Group Acknowledges Exemplary Staff ff takes a moment to review the past year and celebrate the achievements of its various departments and the company overall. McMahon Group’s print and digital properties enjoyed signiﬁcant successes during 2014, often ft advancing d i in i both b th readership d hi andd reevenues.

2014

The following employees were singled ouut as exemplary at this year’s annual celebration. We thank them, and we thank our readerrs for their continued enthusiasm for our medical journalism, which has made many of our publications the best read in their specialty.

SUPPORT/ART/PRODUCTION/IT/FINANCE

This award is for a commingled groupp of several vital departments within the company, without any onee of which the company would not thrive, and as such there are two recipients of this award. MARTIN BARBIERI is the production manager for several of the company’s newsmagazines—a coomplicated task, which he accomplishes seamlessly month after month.

KWA ANGHEE CHUNG is senior lead developer in the IT Department, havinng input in all things digital, including our various websites, internnal content management systems, and apps, to name a few.

EDITOR OF THE YEAR

SALES ACHIEVEMENT AWARD tor among the publication,

copy and projects editorial staffs. KEVIN HORTY Y won for his editorial dirrection of General Surgery News, the best-read publication in general surgery. His contributions have included an important effort to enhance our Web-based video offerings.

MATTTHEW SPOTO is senior account manager for Gastrroenterology & Endoscopy News, the best-read publication in gastroenterology. This award celebrates creative thinking to enhance sales and customer service.

SALESPERSON OF THE YEAR

THE MCMAHON GROUP PARTNERS’ AWARD

RICHARD TUORTO, the senior groupp publication director for Anesthesiology News and Pain Mediicine News, both of which are the best-read publications in their fiields, earned this award for the ninth year in a row for generatinng the most revenue in the calendar year.

ROSA ANNE MCMAHON is a partner and co-founder of the comppany and the wife of CEO Ray McMahon. For many years she was personally involved in financial oversight, but nowadays she continues to do what she has done expertly from the very beginning: supporting the CEO and family members working at the company!

THE MCMAHON GROUP PERSON OF THE YEAR RICHARD TUORTO, this year’s Salesperson of the Year, was voted Person of the Year by McMahon Group employees for his longstanding excellence in both sales and publication management.

Specialty Pharmacy Continuum • April/May 2015

OPERATIONS & MANAGEMENT

Hospitals Continue Move Into Specialty Pharm Anaheim, Calif.—It may not be time to worry about health systems grabbing a major chunk of the specialty pharmacy market, but the trade channel continues to make steady gains in becoming more of a key player in this highly competitive landscape. Those gains were in evidence at the 2014 Midyear Clinical Meeting of the American Society of Health-System Pharmacists (ASHP), where several hospital leaders offered details on their strategies for building solid specialty pharmacy businesses. In many cases, those efforts are succeeding even when the hospitals are denied access to some specialty medications and payor plans, and the effect on the hospital’s revenue has been dramatic. Just ask JoAnn Stubbings, BSPharm, the assistant director of specialty pharmacy services at the University of Illinois (UI) Hospital & Health Sciences System, Chicago. Two years ago, UI specialty drug revenues stood at just $8 million, according to Ms. Stubbings, who spoke at the ASHP meeting. By the end of 2014, she reported, that figure had jumped by more than fourfold, to $35 million—the result of both a 144% gain in dispensed prescriptions, to 4,555, and a sharp escalation in specialty drug prices. What’s more, Ms. Stubbings said, the gains were achieved using existing facilities and with only a minimal increase in dispensing and call center staffs, which grew from 2.125 full-time equivalents in 2012 to 4.25 last year. How was this accomplished? By focusing on what Ms. Stubbings called “lowhanging fruit,” such as the open-access payors—mainly Medicaid and Medicare Part D—and the medications that manufacturers and distributors are willing to make available to all qualified specialty pharmacies. It helped, she said, to have a specialty pharmacy model that played to UI’s strengths in coordinated care and access to patients’ electronic medical records. “It really works,” Ms. Stubbings told Specialty Pharmacy Continuum. “You don’t have to build a new building. You can start it in your own pharmacy.

Start it small, pilot it and grow. The biggest investment is in people.” Don Carroll, MHA, BSPharm, the senior director of specialty pharmacy at Cleveland Clinic, in Ohio, agreed that the UI approach is “one potential strategy for getting started. There is definitely growth in those areas, and it definitely is substantial. You can build a viable business model based on any-willingprovider payors and also on the drugs that are currently accessible.”

perceived advantage in capturing and reporting national patient usage and outcomes data. That perception has led to the migration of more than half of the UI specialty pharmacy’s privately insured prescriptions to external specialty pharmacies, according to Ms. Stubbings, even as the UI pharmacy has managed to fill virtually all Medicaid and Medicare Part D prescriptions. That loss is of increasing concern because of the large number of targeted medicines coming to market over the next decade. IMS Health reported in 2014 that the specialty drug pipeline was “bulging” with just under 700 products in development (http://goo.gl/Vw97kC).

‘I’m very bullish on health systems getting into [the specialty pharmacy] business. The fastest-growing individual membership in NASP is the hospital sector.’ —James E. Smeeding, RPh, MBA But Mr. Carroll also noted that Cleveland Clinic’s start-up approach to specialty pharmacy was very different from the University of Illinois’ “start small and grow” strategy. “We did the opposite,” he said. “We had to start big because there is so much volume here.” He added that it was important for all hospital and health-system pharmacy practices “to at least make a very serious assessment about what specialty pharmacy can bring to their marketplaces. What would be their investment to get in? What kind of value proposition can they consistently show in their marketplace? How can they make a difference? Because I do think the opportunities are out there.” At UI, Ms. Stubbings said specialty pharmacy volume has grown despite the continuing loss of patient prescriptions to outside specialty pharmacies. Such entities, she noted, are favored by many private insurers and pharmaceutical manufacturers because of their

A PBM’s Approach

here certainly is no lack of players in the specialty pharmacy market, and each sector tends to emphasize its “high touch” approach to patient care. Michael Zeglinski, BS Pharm, the senior vice president of specialty pharmacy at Catamaran Corp., Pittsburgh, noted that BriovaRx, his company’s specialty pharmacy, “employs a holistic approach to serving patients with complex specialty conditions. Our pharmacists and nurses are an educational resource for patients, a 24/7 support system and a trusted adviser to the patient’s care team.” As for the benefits of being a specialty pharmacy within a PBM, “we can see any comorbidities the patient may have, as we are able to see all of their prescription information, and help them better manage their overall health,” he said, with a support model “that helps engage patients and provides them with a wealth of knowledge and resources as it relates to their treatments.” —B.B.

Restricted access can also have a serious impact on patient care. “These are high-risk drugs,” Ms. Stubbings said. “They can be managed to some extent by phone, but there is a lot of value in face-to-face communication and in having access to the medical record.”

Efficacy Data Needed The next step for the UI specialty pharmacy, Ms. Stubbings said, is to gather evidence showing that because of its ability to promptly handle prior authorizations and other hurdles that often slow patient treatment, it is able to get crucial medications to patients faster than an outside specialty pharmacy. “We know these patients,” Ms. Stubbings said. “We have access to their medical records. We can get them their medications the same day, delivered to their homes if needed. It would be very hard, in contrast, for them to be served by a company that is 2,000 miles away that doesn’t know their needs.” The pharmacy hopes the results from its new study will persuade insurers and manufacturers to ease policies that restrict specialty drug access and payments. “If this helps to convince them, that’s great,” Ms. Stubbings said, “but frankly, I see a trend to continued restricted access.” If that is the case, she added, a health system should at least be paid for the clinical work that is done to support the drugs dispensed from other parts of the country. Currently, she said, financial support for the specialty pharmacy’s clinical services comes

entirely from margins on medications dispensed internally. For this reason, Ms. Stubbings said, the health system has had to end serviceintensive call center support—including prior authorizations and medication assistance—for patient prescriptions filled by outside specialty pharmacies. “We still obviously provide all medical and pharmacy services in the clinics,” she said, “but in the call center, we only provide services for the prescriptions we can fill.”

Gaining C-Suite Support James E. Smeeding, RPh, MBA, the executive director of the National Association of Special Pharmacy, disputed the notion that remotely located specialty pharmacies are at a disadvantage to health systems in communicating with patients. Most specialty pharmacies, he said, use interactive technology tools, such as iPads along with applications, such as Apple’s Face Time “to communicate very effectively” with patients. The biggest challenges for hospitals, he said, is to gain C-suite support for the large investments required to establish a full-service specialty pharmacy, as well as to create the data collection and reporting mechanisms “required to get limited distribution from manufacturers and in-network opportunities from payors.” Still, Mr. Smeeding said, “I’m very bullish on health systems getting into [the specialty pharmacy] business. The fastest-growing individual membership in NASP is the hospital sector.” —Bruce Buckley Ms. Stubbings, Mr. Smeeding, Mr. Carroll and Mr. Zeglinski reported no relevant ﬁnancial conﬂicts of interest.

Video Exclusive For more insights into a health-system’s strategy for expanding their specialty pharmacy offerings, click on the 2D barcode to access an exclusive video interview with JoAnn Stubbings, BSPharm.

BRIEF SUMMARY OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Kabiven and Perikabiven safely and effectively. See full prescribing information, including Boxed Warning, for Kabiven and Perikabiven available at www.KabivenUSA.com. KABIVEN® (Amino Acids, Electrolytes, Dextrose, and Lipid Injectable Emulsion), for intravenous use Initial U.S. Approval: 2014 PERIKABIVEN® (Amino Acids, Electrolytes, Dextrose, and Lipid Injectable Emulsion), for intravenous use Initial U.S. Approval: 2014 WARNING: DEATH IN PRETERM INFANTS See full prescribing information for complete boxed warning • Deaths in preterm infants have been reported in literature. • Autopsy findings included intravascular fat accumulation in the lungs. • Preterm and low birth weight infants have poor clearance of intravenous lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion. INDICATIONS AND USAGE Kabiven and Perikabiven are each indicated as a source of calories, protein, electrolytes and essential fatty acids for adult patients requiring parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. Kabiven and Perikabiven may be used to prevent essential fatty acid deficiency or treat negative nitrogen balance in adult patients. Limitation of Use: Not recommended for use in pediatric patients < 2 years, including preterm infants, because the fixed content of the formulation does not meet nutritional requirements in this age group.

DOSAGE AND ADMINISTRATION

WARNINGS AND PRECAUTIONS

• Kabiven is for intravenous infusion only into a central vein • Perikabiven is for intravenous infusion into a central or peripheral vein • Recommended dosage depends on clinical status, body weight and nutritional requirements • Kabiven adult dosage: 19 to 38 mL/kg/day (0.63 to 1.26 g/kg/day of amino acids, 1.85 to 3.71 g/kg/day of dextrose, 0.74 to 1.48 g/kg/day of lipid) • The maximum infusion rate for Kabiven is 2.6 mL/kg/hour (corresponding to 0.09 g/kg/hour of amino acids, 0.25 g/kg/hour of dextrose, the limiting factor, and 0.1 g/kg/hour of lipid) • Perikabiven adult dosage: 27 to 40 mL/kg/day (0.64 to 0.94 g/kg/day of amino acids, 1.83 to 2.71 g/kg/day of dextrose, 0.95 to 1.4 g/kg/day of lipid) • The maximum infusion rate for Perikabiven is 3.7 mL/kg/hour (corresponding to 0.09 g/kg/hour of amino acids, 0.25 g/kg/hour of dextrose, the limiting factor, and 0.13 g/kg/hour lipid) • The recommended infusion period is 12 to 24 hours

• Hypersensitivity reactions: Monitor for signs or symptoms and discontinue infusion if reactions occur • Infection, fat overload, hyperglycemia and refeeding complications: Monitor for signs and symptoms; monitor laboratory parameters

DOSAGE FORMS AND STRENGTHS • Kabiven and Perikabiven are sterile, hypertonic emulsions in a three-chamber container. The individual chambers contain one of the following: amino acids and electrolytes, dextrose, or lipid injectable emulsion, respectively • Kabiven is available in four sizes 2566 mL, 2053 mL, 1540 mL and 1026 mL • Perikabiven is available in three sizes 2400 mL, 1920 mL and 1440 mL CONTRAINDICATIONS • Known hypersensitivity to egg, soybean proteins, peanut proteins, corn or corn products, or to any of the active substances or excipients • Severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides >1000 mg/dL • Inborn errors of amino acid metabolism • Cardiopulmonary instability • Hemophagocytic syndrome

ADVERSE REACTIONS The most common adverse reactions to Kabiven (>3%) are nausea, pyrexia, hypertension, vomiting, decreased hemoglobin, decreased total protein, hypokalemia, decreased potassium and increased gamma glutamyltransferase. The most common adverse reactions to Perikabiven (> 3%) are hyperglycemia, hypokalemia, pyrexia and increased blood triglycerides. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC, Vigilance & Medical Affairs at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONS Coumarin and coumarin derivatives, including warfarin: Anticoagulant activity may be counteracted; monitor laboratory parameters USE IN SPECIFIC POPULATIONS Renal Impairment: Patients on hemodialysis or continuous renal replacement therapy may require additional supplementation to meet nutritional requirements. If required, adjust the volume of Kabiven or Perikabiven administered based on serum electrolyte levels and ﬂuid balance.

Si plify Now available Kabiven® and Perikabiven® Fresenius Kabi’s three-chamber bags for parenteral nutrition contain: • Amino Acids and Electrolytes • Dextrose • Lipids (Intralipid® 20% IV Fat Emulsion) www.KabivenUSA.com. To order, call 1-888-386-1300. Kabiven and Perikabiven three-chamber bags must be activated prior to infusion. For activation instructions see DIRECTIONS FOR ACTIVATING THE BAG in the prescribing information available at www.KabivenUSA.com. Neither Kabiven nor Perikabiven is recommended for use in pediatric patients < 2 years, including preterm infants because the ﬁxed content of the formulations do not meet the nutritional requirements in this age group. WARNING: DEATH IN PRETERM INFANTS

See full prescribing information for complete boxed warning • Deaths in preterm infants have been reported in literature. • Autopsy ﬁndings included intravascular fat accumulation in the lungs. • Preterm and low birth weight infants have poor clearance of intravenous lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion. Known hypersensitivity to egg, soybean proteins, peanut proteins, corn or corn products, or to any of the active substances or excipients. Monitor patient closely for signs and symptoms of infection, hypertriglyceridemia, hyperglycemia and refeeding complications. Monitor laboratory parameters for alterations in electrolytes, liver and renal impairment, ﬂuid status and coagulation parameters. Adjust rate and dose of Kabiven and Perikabiven according to clinical status. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC, Vigilance & Medical Affairs at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see Brief Summary of Prescribing Information, including Boxed Warning, for Kabiven and Perikabiven on the following page.