Spring 2013 - Specialty Pharmacy Continuum by McMahon Group

Bridging the gap between the hospital and alternate-site care Volume 2 • Number 2 • Spring 2013 • specialtypharmacycontinuum.com

In This Issue Operations & Mgmt

Price not the key to a successful payer– specialty pharmacy partnership.

Helping To Close the Gaps in Specialty Care

Goads & Games Can Bolster Med Adherence

Part 1: Holistic patient management

San Diego—The staggering $317 billion that medication nonadherence costs our health care system each year can be chipped away at if pharmacists encourage proper medication use, an expert told attendees of the Academy of Managed Care Pharmacy’s (AMCP) 25th Annual Meeting and Expo. “None of the medicines we develop, none of our efforts to make sure these medicines are accessible to patients, none of the guidelines we create, none of these matter if we don’t actually get the medicine into a patient’s body,” said

‘ The Wheel’ keeps clients’ drug spend in check.

N ASP panel: There is strength in numbers from SP stakeholder collaboration.

Disease State Spotlight

A stepwise guide to IVIG product selection and use.

•

Clinical

Payers, providers need to be ready for Actemra in wake of positive studies.

Policy

K ynamro for HoFH gets SP distribution; FDA keeping close eye on drug.

Corporate Spotlight Medi-Dose/EPS see page 21

see ADHERENCE, page 17

Programs Cut Specialty Drug Spending in Half

San Diego—Specialty pharmacists are well positioned to narrow the significant and persistent gaps in patient care, experts told attendees of the National Association of Specialty Pharmacy’s Inaugural Specialty Pharmacy Conference. According to Diane Sullivan, vice president of the Payer and Channel Group at Pfizer Specialty Care, and the moderator of a roundtable discussion on the topic, approximately 55% of all patients in this country are receiving inadequate care. “It’s been 10 years since this number was first reported and we have the same gaps in patient care today,” said Ms. Sullivan, referring to a study from 2003 showing that preventive, acute and chronic care fell below evidence-based guidelines in 45% of patients (N Engl J Med 2003;348:2635-2645) and a more recent study showing that there have been no significant improvements in patient care since (Express Scripts 2012 Drug Trend Report). In light of the frequency of interactions between specialty pharmacists and patients as well as the contribution of specialty pharmacists to improving medication adherence rates, there is a significant opportunity to raise the bar for patient care, Ms. Sullivan suggested. “Seventy percent of our specialty products are distributed and managed by specialty pharmacists, and for three of our products, it’s 100%. So, we really rely on the expertise of specialty pharmacy,” she said. “We know that from an adherence perspective, a patient will actually have a better experience with specialty pharmacy than with retail, where adherence rates are 8% lower.”

mployers who use multiple cost management programs to control their spending on specialty drugs spend an average of 50% less on these medications annually than employers whose specialty spending is totally unmanaged, according to a recent study by Express Scripts. Specialty pharmacy is expected to account for one of every four dollars spent on prescription medications by next year, and utilization management programs often are depicted as a critical element in controlling the runaway growth rate of specialty spending. But the actual impact of utilization management on spending is still being determined.

see CARE GAPS, page 18

see SPENDING CUTS, page 8

•

The Book Page Remington: An Introduction to Pharmacy

•

Special Report

Loyd V. Allen (Editor)

Understanding Key Differences Between Biosimilars and Small Molecule Generics

See page 25.

See insert after page 14.

Evidence based. Patient proven.

Product Features FDA approved indications1 : s Chronic inﬂammatory demyelinating polyneuropathy (CIDP) s Primary immunodeﬁciency (PI) for both IV and SC administration s Idiopathic thrombocytopenic purpura (ITP)

Product properties1 : s No sugar s Optimal pH of: (4.0-4.5) s IgA content: average of 46μg/mL s Only trace amounts of sodium s Close to physiologic osmolality: (258 mOsm/kg)

Easy to use1 : s Latex-free packaging s Tamper-evident vials (cap overwrap) s Vials available in 1, 2.5, 5, 10, and 20 g s Long 3-year shelf life; room temperature storage* * Up to 6 months at any time during 36-month shelf life.

Important Safety Information Gamunex-C, Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified, is indicated for the treatment of primary humoral immunodeficiency disease (PI), idiopathic thrombocytopenic purpura (ITP), and chronic inflammatory demyelinating polyneuropathy (CIDP). Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients. Patients predisposed to renal dysfunction include those with any degree of preexisting 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. Gamunex-C does not contain sucrose. For patients at risk of renal dysfunction or failure, administer Gamunex-C at the minimum concentration available and the minimum infusion rate practicable. Gamunex-C is contraindicated in individuals with acute severe hypersensitivity reactions to Immune Globulin (Human). It is contraindicated in IgA deficient patients with antibodies against IgA and history of hypersensitivity. Gamunex-C is not approved for subcutaneous use in patients with ITP or CIDP. Due to the potential risk of hematoma formation, Gamunex-C should not be administered subcutaneously in patients with ITP. Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV therapy. Thrombotic events have been reported in association with IGIV. Patients at risk for thrombotic events may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization and/or known or suspected hyperviscosity. There have been reports of noncardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury (TRALI)], hemolytic anemia, and aseptic meningitis in patients administered with IGIV. The high dose regimen (1g/kg x 1-2 days) is not recommended for individuals with expanded fluid volumes or where fluid volume may be a concern. Gamunex-C is made from human plasma. Because this product is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. After infusion of IgG, 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. In clinical studies, the most common adverse reactions with Gamunex-C were headache, fever, chills, hypertension, rash, nausea, and asthenia (in CIDP); headache, cough, injection site reaction, nausea, pharyngitis, and urticaria with intravenous use (in PI) and infusion site reactions, headache, fatigue, arthralgia and pyrexia with subcutaneous use (in PI); and headache, vomiting, fever, nausea, back pain, and rash (in ITP). The most serious adverse reactions in clinical studies were pulmonary embolism (PE) in one subject with a history of PE (in CIDP), an exacerbation of autoimmune pure red cell aplasia in one subject (in PI), and myocarditis in one subject that occurred 50 days post-study-drug infusion and was not considered drug related (in ITP). Please see adjacent page for brief summary of Gamunex-C full prescribing information. 1. GAMUNEX-C package insert. Research Triangle Park, NC: Grifols Therapeutics Inc.; 2010.

For more information: Grifols, Inc. Customer Service: 888 325 8579 Fax: 323 441 7968

Grifols, Inc. 5555 Valley Boulevard, Los Angeles, 90032 CA - USA Tel. 888-GRIFOLS (888 474 3657) www.grifolsusa.com

Printed in USA.

September 2012

GX116-0912

GAMUNEX®-C

• Thrombotic events have occurred in patients receiving IGIV therapy. Monitor patients with known risk factors for thrombotic events; consider baseline assessment of blood viscosity for Immune Globulin Injection (Human) 10% those at risk of hyperviscosity.

Caprylate/Chromatography Puriﬁed

• Aseptic Meningitis Syndrome (AMS) has been reported with GAMUNEX-C and other IGIV treatments, especially with high doses or rapid infusion.

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to • Hemolytic anemia can develop subsequent to IGIV therapy due use GAMUNEX®-C safely and effectively. See full prescribing to enhanced RBC sequestration. Monitor patients for hemolysis information for GAMUNEX-C. and hemolytic anemia. GAMUNEX-C, [Immune Globulin Injection (Human) 10% • Monitor patients for pulmonary adverse reactions (transfusionCaprylate/Chromatography Puriﬁed] related acute lung injury [TRALI]). Initial U.S. Approval: 2003 • Volume overload WARNING: ACUTE RENAL DYSFUNCTION and FAILURE See full prescribing information for complete boxed warning. • Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients. • Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. GAMUNEX-C does not contain sucrose. • For patients at risk of renal dysfunction or failure, administer GAMUNEX-C at the minimum concentration available and the minimum infusion rate practicable.

• GAMUNEX-C is made from human plasma and may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease agent. • Passive transfer of antibodies may confound serologic testing. ----------------------------ADVERSE REACTIONS---------------------------• PI – The most common adverse reactions ( 5%) with intravenous use of GAMUNEX-C were headache, cough, injection site reaction, nausea, pharyngitis and urticaria. The most common adverse reactions ( 5%) with subcutaneous use of GAMUNEX-C were infusion site reactions, headache, fatigue, arthralgia and pyrexia.

• ITP – The most common adverse reactions during clinical trials (reported in 5% of subjects) were headache, vomiting, fever, -------------------------INDICATIONS AND USAGE------------------------nausea, back pain and rash. GAMUNEX-C is an immune globulin injection (human) 10% liquid • CIDP – The most common adverse reactions during clinical indicated for treatment of: trials (reported in 5% of subjects) were headache, fever, chills, hypertension, rash, nausea and asthenia. • Primary Humoral Immunodeficiency (PI) To report SUSPECTED ADVERSE REACTIONS, contact Talecris • Idiopathic Thrombocytopenic Purpura (ITP) Biotherapeutics, Inc. at 1-800-520-2807 or FDA at • Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) 1-800-FDA-1088 or www.fda.gov/medwatch. ----------------------------CONTRAINDICATIONS-------------------------------------------------------DRUG INTERACTIONS---------------------------• Anaphylactic or severe systemic reactions to human • The passive transfer of antibodies may transiently interfere with immunoglobulin the response to live viral vaccines, such as measles, mumps • IgA deficient patients with antibodies against IgA and a history and rubella. Passive transfer of antibodies may confound of hypersensitivity serologic testing. ---------------------WARNINGS AND PRECAUTIONS--------------------• IgA deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions. Have epinephrine available immediately to treat any acute severe hypersensitivity reactions. • Monitor renal function, including blood urea nitrogen, serum creatinine, and urine output in patients at risk of developing acute renal failure. • GAMUNEX-C is not approved for subcutaneous use in ITP patients. Due to a potential risk of hematoma formation, do not administer GAMUNEX-C subcutaneously in patients with ITP. • Hyperproteinemia, with resultant changes in serum viscosity and electrolyte imbalances may occur in patients receiving IGIV therapy.

--------------------USE IN SPECIFIC POPULATIONS -------------------• Pregnancy: no human or animal data. Use only if clearly needed. • Geriatric: In patients over 65 years of age do not exceed the recommended dose, and infuse GAMUNEX-C at the minimum infusion rate practicable.

Talecris Biotherapeutics, Inc. Research Triangle Park, NC 27709 USA U.S. License No. 1716

08939771/08939782-BS Revised: October 2010

Specialty Pharmacy Continuum • Spring 2013

OPERATIONS & MANAGEMENT

Selling SP Services on Price? Think Again. Las Vegas—When choosing a specialty pharmacy partner, payers will no longer be focusing primarily on price—or at least they shouldn’t be, said Michael Einodshofer, RPh, MBA, the director of utilization management for Walgreens, at the 18th annual Pharmacy Benefit Management Institute Drug Benefit Conference. “If you are a health plan or employer, you absolutely need to negotiate a competitive transactional price with your specialty pharmacy, but you can’t just stop there. We’ve seen a pretty substantial year-by-year erosion in pricing to the point where all the specialty pharmacies will come out right around the same price for the same product, all other things being equal.” The differentiators between specialty pharmacies now become more complex. “We recommend that plans start asking harder questions: What clinical programs do you have in place to keep members compliant with a drug? What utilization programs do you have in place to make sure we’re eliminating waste associated with specialty pharmacy use?” Of course, all specialty pharmacies claim that they have utilization management and clinical management programs, but not all are created equal. “Payers should be prepared to ask for

from utilization management programs. Clinical programs, which focus on managing the patient and keeping the prescribing physician in the loop with regard to the patient’s care, generate their ultimate savings over the long term by maximizing clinical outcome. “It’s a macro shift: You’re increasing drug

informed as to what to do should an adverse event occur.” Utilization management, on the other hand, is much more transactional in nature and realizes more immediateterm savings by minimizing the cost to treat. “Some of these things can be very straightforward, but have very important implications to the cost of care,” Mr. Einodshofer said. He took the time in his presentation to dive deeper into several examples of how simple but effective utilization management can generate significant cost savings with

‘What makes a specialty pharmacy is not access to … [specialty] products, but rather the programs they build around helping patients manage their drug therapy and underlying disease.’ —Michael Einodshofer, RPh, MBA

evidence, and specialty pharmacies should be prepared to provide evidence showing how intensely they’re intervening on these opportunities,” Mr. Einodshofer said. That means providing samples of reporting and details of program operation, and quantifying the effects of clinical programs separately

costs through driving greater medication compliance, but subsequently achieving a better clinical response which decreases downstream medical costs related to surgeries, inpatient admissions and excess emergency room use,” he said. “There’s a lot of work regarding drug interactions, the patient’s comfort level with the drug and keeping the patient

no adverse clinical effect. One example: Simply ensure a patient’s weight is appropriate for the dosage of a prescribed drug. The psoriasis drug ustekinumab (Stelara, Janssen) comes in either 90- or 45-mg doses, with average annual wholesale prices of approximately $62,000 and $31,000, respectively. The weight

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Volume 2 • Number 2 • Spring 2013

SPECIALTY PHARMACY

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Specialty Pharmacy Continuum • Spring 2013

OPERATIONS & MANAGEMENT would improve with a once-daily dosage as well. “There’s a difference between a specialty pharmacy and a pharmacy that dispenses specialty products,” Mr. Einodshofer concluded. “Many will dispense specialty medications because they are able to, but what makes a specialty pharmacy is not access to those products, but rather the programs they build around helping patients manage their drug therapy and underlying disease.” —Gina Shaw Examples of inappropriately ordered medications that present potential opportunities for savings through utilization management strategies.

threshold for the higher dose is 220 pounds, and Mr. Einodshofer pointed out that there is no evidence for increased efficacy deriving from a higher starting dose in patients who weigh less than that. “In an unmanaged population, we’ll still see patients who are appropriate for the 45-mg dose coming in with a prescription for 90 mg,” he said. “We will intervene with the physician and recommend lowering the dose. If we’re successful, that’s a $31,000 annual savings.” Etanercept (Enbrel, Pfizer), approved for a variety of specialty indications, also is used for psoriasis, at a dosage of 50 mg subcutaneously twice a week for three months, then reduced to weekly after the third month. “A lot of the overdosing of Enbrel we intervene on isn’t because the prescriber made a clinical error in writing the primary prescription—he wrote it for 2 times a week times three months—but rather because he then put three refills on the script—essentially an administrative error.” If a patient presents such a refill at any pharmacy without a utilization management program, the pharmacist will almost certainly refill the original twice-weekly prescription, rather than the recommended step-down, once-weekly dose. “That’s a $2,600 overcharge for the payer, and more drug than the patient truly needs for that month of therapy and thereafter,” he said. A third example: The oral chemotherapy drug everolimus (Afinitor, Novartis), approved by the FDA for a number of oncology indications, including advanced renal cell carcinoma and certain advanced breast cancers, comes in four different strengths, including a 2.5- and a 7.5-mg tablet. “The cost difference between three 2.5mg pills daily and just one 7.5 mg tablet daily is $17,000 a month,” Mr. Einodshofer said. Although Walgreens hasn’t studied this specifically, he noted that it also stands to reason that adherence

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Specialty Pharmacy Continuum • Spring 2013

OPERATIONS & MANAGEMENT

Tool Keeps the Wheels on Drug Spend in Check Las Vegas—Taking a one-size-fits-all approach to managing specialty pharmaceuticals is a prescription for failure, according to Peter Wickersham, the senior vice president in charge of cost of care at Prime Therapeutics, which helps Blue Cross Blue Shield manage a $12 billion drug spend. To be successful, a more tailored approach is needed—one that reflects the particular requirements of a given medication or disease state, Mr. Wickersham said during the 18th annual Pharmacy Benefit Management Institute Drug Benefit Conference. To help guide this process, Mr. Wickersham created The Wheel, a diagram that illustrates “in a compact yet comprehensive way” the strategies that Prime Therapeutics deploys to optimize customers’ spending on specialty drugs. He recently put The Wheel through its paces helping a client that experienced an unexpectedly sharp increase in drug costs. The client, which he dubbed “Acme Manufacturing,” a Midwest Fortune 500 company with nearly 20,000 plan members, was caught offguard by the spending spike because the firm had a very strong track record of earlier, successful pharmacy benefit management. In 2011, for example, Acme had saved $420,000 using drug utilization management alone and kept its pharmacy spending below average. “They had done everything right,” Mr. Wickersham said. And then it all changed. Between the fourth quarter of 2011 and the fourth quarter of 2012, Acme’s pharmacy spending spiked by 12.1%—nearly six times the increase seen by Prime’s overall book of business. Fully half of the growth was attributable to just two employees: one with hemophilia who incurred more than $500,000 in total spending, and one with kidney disease treated with repository corticotropin injection (Acthar Gel; Questcor Pharmaceuticals) at a price tag of $597,000 that year. In response, Mr. Wickersham used The Wheel as a visual tool to remind him that in challenging cases such as the one above, a full suite of management strategies can be brought to bear in any effort to optimize spending: channel management, utilization management, contracting activities and coordination of care. Applying The Wheel approach in managing the Acme case study led to a more rational use of the high-cost medicines and yielded significant savings, he noted. For each category, Mr. Wickersham said, although there may be potential savings by using each of these tools, there often is a particular part of the wheel to focus on. “Hemophilia is very different from autoimmune disease, for example. So what’s the best way to manage this class in distribution? Is it utilization management, with prior authorization, step therapy and quantity limits? Or is it care management, with coordination of care and disease and case management?” Benefit design and formulary, Mr.

Figure. The Wheel graphic depicts “in a compact yet comprehensive way” the tools that Prime Therapeutics deploys to optimize customers’ spending on specialty drugs, according to Peter Wickersham, the senior vice president in charge of cost of care at the benefits management company.

‘The big three categories take up 16% to 20% at most. And then, it’s sliver after sliver after small sliver, for lots of different conditions that drive the [specialty] spend.’

—Peter Wickersham

Wickersham said, form the foundation for The Wheel (Figure). He cited the autoimmune drugs etanercept (Enbrel, Amgen) and adalimumab (Humira, Abbott) as examples. “Simply putting a preferred drug on the formulary drives market movement, allowing lower prices to be negotiated with the manufacturer. You can also use utilization management or benefit design to drive this.” Why the need for such a multitiered, customizable approach? In a word: variability. Few disease states fall neatly into either the medical or the pharmacy benefit, which makes collaboration and coordination critical. And although the top three categories in specialty spend— autoimmune, injectable oncology drugs and multiple sclerosis—haven’t changed in recent years, a shifting array of other categories account for anywhere from

several million to nearly $200 million in spending each year. “If you put a pie chart up representing all of the specialty spend, the big three categories take up 16% to 20% at most,” Mr. Wickersham said. “And then, it’s sliver after sliver after small sliver, for lots of different conditions that drive the spend. This is not the blockbuster era of blood pressure or cholesterol-reducing agents. The spend is spread across a multitude of classes, and you have to have specific approaches in all of those classes.” But it doesn’t end there. In some cases, specialty pharmacy also requires management of individual drugs, not just drug classes, Mr. Wickersham said. “You need in-depth knowledge of pharmacology to understand the nuances of treatment. Frequently, there is a lack of interchangeability between these drugs. There’s a big

potential for off-label usage, and there are different administration needs.”

More Strategies Detailed Mr. Wickersham cited several additional strategies to keep in mind when managing the specialty drug category: Be flexible when it comes to channel management. He said that Prime Therapeutics does not necessarily take the approach, for example, that all specialty spend should go through a central specialty pharmacy. “Clearly, there is an advantage to specialty over retail pharmacy when it comes to specialty meds,” he said. “But in some cases, it’s better to allow these prescriptions to flow through the physician’s office and try to manage them through that channel. While many pharmacy benefit managers prefer to drive everything through a central specialty pharmacy because they make the greatest margin that way, we try to do it differently, choosing the best channel for the Blues [Blue Cross Blue Shield] plan and the patient based on what that therapeutic class is telling us.” Know the stakes. At every specialty pharmacy conference, the numbers behind the staggering growth of specialty pharmacy are presented. Still, it’s worth repeating, Mr. Wickersham noted. Specialty will permanently alter the pharmacy spending landscape. “Prime projections show that at the current rate of increase, close to 50% of all drug spending will be specialty by 2018,” he noted. “If combined specialty costs are roughly $25 PMPM [per member per month] today, by 2018 they will exceed $40 PMPM. Previous, widely used estimates predicted specialty would hit this point in 2030.” Thus, the stakes are high for managing this huge growth area well, he stressed. Ask the right questions. Ending his presentation, Mr. Wickersham posed a list of key questions for employers to ask themselves regarding their specialty pharmacy spend: 1. Are my employees using a dedicated specialty pharmacy? 2. Am I using management to support safe medication use and drive savings? 3. How well does my pharmaceutical benefits management company work with my health plan to ensure consistency and communication? 4. Am I receiving transparent price protection, rebate and other manufacturer revenue? 5. Am I talking with my pharmaceutical benefits management company and health plan about site-of-care optimization? 6. Are my benefits aligned across pharmacy and medical? —Gina Shaw

Specialty Pharmacy Continuum • Spring 2013

OPERATIONS & MANAGEMENT

Top-Down Versus Bottom-Up Trend Management Las Vegas—The traditional approach to managing specialty pharmacy is top-down: identifying what drugs cost most, both by unit cost and utilization, identifying the top disease states, and developing a cost management strategy focused on these large trend drivers. But at the 2013 Pharmacy Benefit Management Institute conference, Renee Rayburg, RPh, the manager of clinical pharmacy at OptumInsight, suggested that focusing myopically on these cost areas may lead payers and pharmacy benefit managers to miss smaller savings opportunities that collectively can add up to significant dollars. More than 600 specialty medications are currently in the pipeline, many targeting rare and orphan diseases. The average annual cost of therapy for one of these drugs is approximately $150,000. “Insurers need to understand these new drugs and the conditions they treat, assess how they will impact their membership, and have management strategies in place,” Ms. Rayburg said. For example, ivacaftor (Kalydeco, Vertex), approved by the FDA in January 2012, is the first drug that targets the genetic underpinnings of cystic fibrosis (CF). The drug is approved only for

patients with the specific G551D CFcausing mutation (about 4% of 70,000 people with CF worldwide), and its price tag is very high—pushing $300,000 annually. With Kalydeco’s sales predicted to reach $352 million this year and nearly double that by 2019, Ms. Rayburg noted that it behooves the savvy insurer to know how many members it has with CF and plan accordingly.

Other High-Ticket Medications Kalydeco doesn’t lack for company. Between 2008 and 2012, four drugs were approved to treat hereditary angioedema (HAE), which affects fewer than 30,000 individuals in the United States. Three of the drugs are approved to treat acute attacks and cost around $2,500 per dose. The fourth, ViroPharma’s Cinryze (C1 esterase inhibitor [human]), is the only one approved to prophylactically treat HAE; at an annual cost of $350,000, it ranked fourth on a 2012 Forbes list of the world’s most expensive drugs. “Three of these drugs are paid under the medical benefit and one, Firazyr [Shire; icatibant], under the pharmacy benefit,” Ms Rayburg said. Thus, “there are many opportunities for misdiagnosis as well as inconsistencies in billing and benefits, and misunderstandings about dosage.” She pointed to one year of utilization and costs in a large commercial plan covering more than

a million lives. “In one year, they had 80 members on a specialty drug for HAE at a total cost of $14 million. [At that high cost], you want to make sure everything is managed appropriately.” One particularly effective bottomup strategy that can realize significant savings is to be prepared for generic specialty drugs as they come to market. “New generics are billed with the same J-code as the brand,” Ms.

Rayburg explained. Because there is always a two-quarter lag before the average sales price (ASP) is updated when a new generic comes on the market, payers need to adjust reimbursement models accordingly. For example, when the FDA approved generic oxaliplatin, “vendors within health plans using J-codes that had reimbursement set to pay on brand were losing money.” Finally, Ms. Rayburg said, payers

should be aware of the net cost of specialty drugs and encourage the use of the lowest net cost products. But she added an important caveat. Whether top-down or bottom-up, utilization management “shouldn’t mean creating barriers for the patient or the provider. What we want is the right medication, at the right dose, for the right length of time, for the right diagnosis, for the right patient.” —Gina Shaw

Introducing BIVIGAM®

For Uncompromised Living™ BIVIGAM® [Immune Globulin Intravenous (Human), 10% Liquid] is indicated for the treatment of primary humoral immunodeﬁciency (PI). • 64% of study participants did not miss any days of work or school1 • 2.3 days/patient/year out of school or work1 • Sugar-free, 10% liquid preparation • BIVIGAM is manufactured in the USA for US providers and patients

BOXED WARNING: ACUTE RENAL DYSFUNCTION AND FAILURE Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur with the administration of Immune Globulin Intravenous (Human) (IGIV*) products in predisposed patients. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. BIVIGAM does not contain sucrose. For patients at risk of renal dysfunction or failure, administer BIVIGAM at the minimum dose recommended and the minimum infusion rate practicable. See full Prescribing Information for complete boxed warning. BIOTEST and the BIOTEST & Design marks are trademarks and/or registered trademarks of BIOTEST AG. BIVIGAM is a trademark of Biotest Pharmaceuticals Corporation. This information is intended only for residents of the United States. *IVIG is also known as IGIV, Immune Globulin Intravenous (Human)

Reference: 1. Wasserman RL, Church JA, Stein M, et al. Safety, efﬁcacy and pharmacokinetics of a new 10% liquid intravenous immunoglobulin (IVIG) in patients with primary immunodeﬁciency. J Clin Immunol. 2012. doi:10.1007/s10875-012-9656-5.

For more infor mation, visit

www.BIVIGAM.com 10190-90-IGG-040312_R00

Specialty Pharmacy Continuum • Spring 2013

OPERATIONS & MANAGEMENT

SPENDING CUTS continued from page 1

In the study, which was presented at the National Business Group on Health’s (NBGH) Business Health Agenda 2013 conference, Express Scripts analyzed the specialty drug spending of 60 employer clients who collectively represented more than 5 million individuals with pharmacy benefits. The employers were separated into three categories: unmanaged (members could get specialty medications from any

pharmacy, and the employer used no utilization management programs), somewhat managed (members were required to use a specialty pharmacy exclusively, and the employer used one utilization management program), or tightly managed (exclusive use of a specialty pharmacy plus at least two utilization management programs). Specialty drug spending by “unmanaged” employers jumped by an average of 27.8% per member per year. “Tightly managed” employers kept that spending in check, keeping the increase to 13.6%.

BIVIGAM [Immune Globulin Intravenous (Human), 10% Liquid] Rx only Brief summary: Consult the full prescribing information for complete product information WARNING: ACUTE RENAL DYSFUNCTION AND ACUTE RENAL FAILURE Use of Immune Globulin Intravenous (IGIV) products, particularly those containing sucrose, has been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death1,2. Patients at risk of acute renal failure include those with any degree of pre-existing renal insufficiency, diabetes mellitus, advanced age (above 65 years of age), volume depletion, sepsis, paraproteinemia, or receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. BIVIGAM does not contain sucrose. For patients at risk of renal dysfunction or failure, administer BIVIGAM at the minimum dose recommended and the minimum infusion rate practicable. Indication and Usage: BIVIGAM is an Immune Globulin Intravenous (Human), 10% Liquid, indicated for the treatment of primary humoral immunodeficiency (PI). Contraindications: BIVIGAM is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin. BIVIGAM is contraindicated in IgA deficiency patients with antibodies to IgA and a history of hypersensitivity. Warnings and Precautions: Thrombotic Events: Thrombotic events may occur following treatment with IGIV products. Patients at risk include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known/suspected hyperviscosity. 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 judged to be at risk of developing thrombotic events, administer BIVIGAM at the minimum rate of infusion practicable. Hypersensitivity: Severe hypersensitivity reactions may occur with IGIV products, including BIVIGAM. In case of hypersensitivity, discontinue BIVIGAM infusion immediately and institute appropriate treatment. Medications such as epinephrine should be available for immediate treatment of acute hypersensitivity reactions. BIVIGAM contains trace amounts of IgA ( 200 micrograms per milliliter). Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. BIVIGAM is contraindicated in IgA deficient patients with antibodies against IgA and a history of hypersensitivity reaction. Acute Renal Dysfunction and Acute Renal Failure: Acute renal dysfunction/failure, osmotic nephrosis, and death1,2 may occur upon use of human IGIV products. Ensure that patients are not volume depleted before administering BIVIGAM. 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 BIVIGAM and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing BIVIGAM. In patients who are at risk of developing renal dysfunction, because of pre-existing renal insufficiency or predisposition to acute renal failure (such as diabetes mellitus, hypovolemia, overweight, use of concomitant nephrotoxic medicinal products or age of >65 years), administer BIVIGAM at the minimum infusion rate practicable. Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia: Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV therapy, including BIVIGAM. 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 infrequently with IGIV treatments including BIVIGAM. 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: IGIV products, including BIVIGAM, may contain blood group antibodies that can act as hemolysins and induce in vivo coating of red blood cells (RBCs) with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis. Delayed hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration,13 and acute hemolysis, consistent with intravascular hemolysis, has been reported. Monitor patients for clinical signs and symptoms of hemolysis. If these are present after BIVIGAM infusion, perform appropriate confirmatory laboratory testing. If transfusion is indicated for patients who develop hemolysis with clinically compromising anemia after receiving IGIV, perform adequate cross-matching to avoid exacerbating ongoing hemolysis. Transfusion-Related Acute Lung Injury (TRALI): Noncardiogenic pulmonary edema may occur in patients following IGIV treatment14including BIVIGAM. 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 antineutrophil antibodies in both the product and the patient’s serum. TRALI may be managed using oxygen therapy with adequate ventilatory support. Transmissible Infectious Agents: Because BIVIGAM is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No cases of transmission of viral diseases or CJD have been associated with the use of BIVIGAM. All infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Biotest

Even the “somewhat managed” employers reined in spending nearly as well as the tightly managed group, holding the increase to 16.7%. (By comparison, Express Scripts’ 2012 Drug Trend Report found that the overall increase on specialty spending was 18.4% in 2012.) The study did not specifically assess individual utilization management programs, such as step therapy, prior authorization and drug quantity management. “This study shows that the specialty spend is not just something that happens to you. You can make decisions relative to

Pharmaceuticals Corporation at 1-800-458-4244. Before prescribing BIVIGAM, the physician should discuss the risks and benefits of its use with the patient. Monitoring Laboratory Tests: 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 BIVIGAM and at appropriate intervals thereafter. Because of the potentially increased risk of thrombosis with IGIV treatment, 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. If signs and/or symptoms of hemolysis are present after an infusion of BIVIGAM, perform appropriate laboratory testing for confirmation. If TRALI is suspected, perform appropriate tests for the presence of antineutrophil antibodies in both the product and patient’s serum. Interference with 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. ADVERSE REACTIONS:Serious adverse reactions observed in clinical trial subjects receiving BIVIGAM were vomiting and dehydration in one subject. The most common adverse reactions to BIVIGAM (reported in 5% of clinical study subjects) were headache, fatigue, infusion site reaction, nausea, sinusitis, blood pressure increased, diarrhea, dizziness, and lethargy. Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in clinical practice.In a multicenter, openlabel, non-randomized clinical trial, 63 subjects with PI, on regular IGIV replacement therapy, received doses of BIVIGAM ranging from 254 to 1029 mg/kg (median dose 462.8 mg/kg) every 3 weeks or 4 weeks for up to 12 months (mean 317.3 days; range 66 – 386 days). The use of pre-medication was discouraged; however, if subjects required pre-medication (antipyretic, antihistamine, or antiemetic agent) for recurrent reactions to immune globulins, they were allowed to continue those medications for this trial. Of the 746 infusions administered, 41 (65%) subjects received premedication prior to 415 (56%) infusions. Fifty-nine subjects (94%) had an adverse reaction at some time during the study. The proportion of subjects who had at least one adverse reaction was the same for both the 3- and 4-week cycles. The most common adverse reactions observed in this clinical trial were headache (32 subjects, 51%), sinusitis (24 subjects, 38%), fatigue (18 subjects, 29%), upper respiratory tract infection (16 subjects, 25%), diarrhea (13 subjects, 21%), cough (14 subjects, 22%), bronchitis (12 subjects, 19%), pyrexia (12 subjects, 19%), and nausea (9 subjects, 14%). Adverse reactions (ARs) are those occurring during or within 72 hours after the end of an infusion. In this study, the upper bound of the 1sided 95% confidence interval for the proportion of BIVIGAM infusions with one or more temporally associated adverse reactions was 31%. The total number of adverse reactions was 431 (a rate of 0.58 ARs per infusion). Seven subjects (11.1%) experienced 11 serious ARs. Two of these were related serious Table:Adverse Reactions (ARs) (within 72 hours after the end of a BIVIGAM infusion) in 5% of Subjects No. Subjects No. Infusions With ARs Reporting ARs ARs (% of Subjects) (% of Infusions) [n=63] [n=746] Headache 27 (43%) 115 (15.4%) Fatigue 15 (24%) 59 (7.9%) Infusion Site Reaction 5 (8%) 5 (0.7%) Nausea 5 (8%) 8 (1.1%) Sinusitis 5 (8%) 5 (0.7%) Blood Pressure Increased 4 (6%) 5 (0.7%) Diarrhea 4 (6%) 4 (0.5%) Dizziness 4 (6%) 4 (0.5%) Lethargy 4 (6%) 4 (0.5%) Back Pain 3 (5%) 3 (0.4%) Blood Pressure Diastolic 3 (5%) 5 (0.7%) Decreased Fibromyalgiaa 3 (5%) 17 (2.3%) Migraine 3 (5%) 8 (1.1%) Myalgia 3 (5%) 4 (0.5%) Pharyngolaryngeal Pain 3 (5%) 3 (0.4%) a Symptoms occurring under pre-existing fibromyalgia ARs (vomiting and dehydration) that occurred in one subject. One subject withdrew from the study due to ARs related to BIVIGAM (lethargy, headache, tachycardia and pruritus). All 63 subjects enrolled in this study had a negative direct antiglobulin (Coombs’) test at baseline. During the study, no subjects showed clinical evidence of hemolytic anemia. No cases of transmission of viral diseases or CJD have been associated with the use of BIVIGAM. During the clinical trial no subjects tested positive for infection due to human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). There was a single positive finding for parvovirus (B19 virus) during the study. This subject came in contact with acute B19 virus from working at a school greeting children where a child was reported to have symptomatic Fifth's disease. There was no cluster (no other cases in other subjects) of B19 virus transmission with the IGIV batch concerned. DRUG INTERACTIONS Live Virus Vaccines: Immunoglobulin administration may transiently impair the efficacy of live attenuated virus vaccines such as measles, mumps, rubella, and varicella because the continued presence of high levels of passively acquired antibody may interfere with an active antibody response. The immunizing physician should be informed of recent therapy with BIVIGAM so that appropriate measures may be taken.

your specialty drug benefit plan that control the trend on a going-forward basis,” said Ben Slen, the senior director of market development at Express Scripts. “And although plans and employers who are managing specialty aggressively are having a significant impact on these trends, there is still a lot of opportunity even within these tightly managed groups to do more. Many of them are probably only managing 30% to 40% of the specialty drugs they could manage, even within the pharmacy benefit picture.”

Rarer Conditions a Challenge Utilization management on the medical benefit side, where many specialty drugs for rarer conditions are prescribed (and where unit cost is a big driver), is much more challenging. For example, drugs in this setting are subject to prior authorization only about 5% of the time, largely because most contracts between plans and providers don’t have a provision for prior authorization under the medical benefit. “Nearly 50 percent of specialty drug costs are billed on the medical side of the plan benefit, where it’s difficult to apply these solutions,” Mr. Slen said. But, he noted, there are other options for intervening, such as site-of-care optimization. “We can steer many of these patients out of hospital outpatient sites and to settings that entail a lower cost while providing care that is just as effective or more effective, such as infusion centers or home care.” Utilization management also appeared to improve adherence in multiple sclerosis, oral oncology and autoimmune disorders during the Express Scripts study. “The tightly managed group achieved a 5% to 10% higher adherence rate than a matched sample of patients in the unmanaged set of clients ... so they were getting better results for their specialty dollar,” Mr. Slen said. “We saw an 80% to 90% adherence rate on key classes. And with some of these conditions, like hepatitis C, the new therapies are curative and can leave the patient with a zero viral load at the end of the treatment cycle. With a lower adherence rate, patients may miss the chance to be cured of the disease, and worse, end up needing a costly liver transplant down the road.” These results concur with what other organizations are seeing, said Melinda Haren, the senior director of access strategies at Zitter Health Insights. “For example, payers believe that stricter requirements for prior authorization in oncology are here to stay. We’ve found that they save between 1% and 10% of the annual cost of a drug. On a $100,000-a-year cancer drug, that’s a significant savings. Combining that with step therapy/trial and failure and other options can drive a pretty good volume through your preferred agent and garner savings.” —Gina Shaw

Specialty Pharmacy Continuum • Spring 2013

OPERATIONS & MANAGEMENT

Alignment Between Stakeholders Needed To Improve Care San Diego—Health care reform, which is changing “the way we do business,” is compelling specialty pharmacy to demonstrate its value as part of a collaborative approach. A multi-stakeholder panel discussed this at the National Association of Specialty Pharmacy’s Inaugural Specialty Pharmacy Conference. Industry experts are still trying to understand the roles and responsibilities each stakeholder will be taking on in achieving the primary goal of health care reform: optimal patient care at the lowest price, according to Randy Vogenberg, PhD, RPh, a principal at the Institute for Integrated Healthcare, in Sharon, Mass., and a managing principal and cofounder of Bentelligence, a health care consulting firm in Monroe, Conn.

services sometimes offered by specialty pharmacies, such as managing clinical guidelines and managing pri-

or authorization approvals, are less important to payers, largely because they already handle these tasks themselves, Mr. Zitter said. “Specialty pharmacy wants to add more value, but payers by and large say they don’t really use these additional services very much,” he noted. So, specialty pharmacies need to add value in other ways that address increasing costs, low adherence or that influence

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other quality metrics, he said. In his opinion, the imperative to do so is critical. “My advice is to add value or be eaten,” Mr. Zitter cautioned. “Not all stakeholders are going to thrive or even survive in the new environment. The most successful stakeholders are going to have to do better in managing costs while not compromising, and ideally even improving, patient care. Increasingly, this

•

see ALIGNMENT, page 10

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Defining the Special In Specialty Pharmacy? Specialty pharmacists may increase medication adherence rates and improve other measures and outcomes, but unless stakeholders first understand what specialty pharmacy is, the strengths of the industry may be for naught, Dr. Vogenberg suggested. He pointed to a 2011 nationwide employer survey that he helped conduct, which found approximately 75% of respondents did not know what specialty pharmacy meant (Figure). “Lots of what we talk about from a pharmacy perspective goes over their heads,” he said. “So, we need to begin by looking at what the knowledge level of the stakeholders is.” Sajid Syed, MS, RPh, president of Acro Pharmaceutical Services in Sharon Hill, Pa., agreed. “People still are not sure what’s so special about specialty pharmacy,” Mr. Syed said. According to Mr. Syed, one strength specialty pharmacists need to emphasize is their ability to improve medication adherence. “We need to educate stakeholders primarily about our ability to improve appropriate utilization. Payers don’t want to see a costly specialty medicine sitting at home. They are looking for pharmacies that can ensure appropriate utilization and optimal adherence,” Mr. Syed said. Mark Zitter, CEO of Zitter Health Insights, a research firm with offices in New Jersey and California that focuses on how payers influence use of life science products, said that the rising number of specialty drugs is burdening this stakeholder population. In turn, they are looking for ways to reduce related costs. What can specialty pharmacies do about this? “Payers rely on specialty pharmacies for things like lower drug prices, reducing waste and distribution,” he explained. However, other

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Specialty Pharmacy Continuum • Spring 2013

OPERATIONS & MANAGEMENT

Ig Nursing Group Eyes Certification Program Association prepares for second national conference As immunoglobulin (Ig) therapies are used to treat an increasing number of disorders in patients, the development of a certification program for Ig nurses is generating support. There are few educational and training opportunities to help nurses strengthen their skills and knowledge of complex Ig procedures. Indeed, most Ig nurses are self-taught, and/or learned from a colleague who also was self-taught. The Immunoglobulin Nursing Society (IgNS) is working to change all that by creating a certification program, along with standards of care and guidelines, and by organizing annual national conferences to help train Ig nurses. “We are developing a certification program that will assess, validate and document the clinical competence and knowledge of nurses who manage and administer Ig therapy, which is now used in a growing number of clinical indications,” said Luba Sobolevsky, PharmD, the program

ALIGNMENT

patient advocacy organizations and medical societies. It also will feature a dedicated portal for knowledge sharing between all health care professionals, where members and non-members alike can post questions and make comments.

National Conferences Helping IgNS Gain Momentum

director of the IgNS, based in Los Angeles. “When it launches in February 2014, it will be the first national certification program to recognize Ig nursing as a specialty, and will result in the standardization of the Ig nursing practice and a higher level of professionalism.” IgNS also is relaunching its website. It will offer an Educational Resources Center containing continuing education programs, recorded sessions from its national conferences and a professional resources area with information on

2011

Dr. Sobolevsky is expecting more than 300 attendees at the group’s second national conference, scheduled for Sept. 20-22, in Dallas. “We’ll offer the latest news on Ig products and pipeline, developments in disease-state management, advanced practice workshops on administration of IV and subcutaneous Ig, reimbursement and advocacy, and interdisciplinary collaboration,” said Dr. Sobolevsky.

Pharmacist Collaboration Key The conference is open to all health

2012

continued from page 9

will be done in collaboration with other stakeholders.”

Heading Toward Greater Collaboration According to Atheer Kaddis, PharmD, a senior vice president of sales and business development at Diplomat Specialty Pharmacy, several market trends are pushing specialty pharmacies to increase collaboration with other stakeholders. “We’re seeing products and patients crossing all channels, and this requires us to work together,” he said. For example, specialty pharmacy services are considered not only under the pharmacy benefits category but also are being classified by some payers as medical benefits. Dr. Kaddis said pharmacy benefits managers (PBMs) and payers are hoping that adding specialty pharmacy to the medical benefit category will keep costs down. The change is requiring specialty pharmacies to work more closely with providers, he said. Another reason for collaboration is that use of specialty and limited distribution drugs is outpacing that of traditional medications, Dr. Kaddis said. In light of this, non-specialty pharmacies will be increasingly turning to specialty drug dispensing. “Today, we have retail, health-system, long-term care, home-infusion and specialty pharmacy,” he said. “But over time we’ll all revert to being just pharmacies. We’ll be under the same umbrella and we’ll all work together with other pharmacies.” Dr. Kaddis said the increased spend-

10%

22% Low

53% 25%

Above average

Medium High

49% 37%

Average High Very little

care professionals, but the programs are accredited for—and especially relevant to—Ig nurses and pharmacists. “The team approach is important because nurses and pharmacists make decisions together relating to patients’ Ig therapy,” Dr. Sobolevsky said. “From which product, administration system and ancillary supplies to use; to management and documentation of adverse reactions; to advocating for patients regarding product access and reimbursement issues—it’s really both the pharmacists and nurses working together that drives the field forward.” Jerry Siegel, PharmD, FASHP, a clinical associate professor at the Ohio State University College of Pharmacy, in Columbus, and a leader in the Ig community who has trained both nurses and pharmacists, agrees that the two professions benefit from collaboration.

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see IG NURSING GROUP, page 19

are receiving a specialty drug,” she noted. “There are advantages to using specialty pharmacies over retail. I think specialty staff [members] have an understanding of what it takes to manage a patient. They have the services that go along with specialty drug use, whereas retail pharmacies might not.”

Entering Unknown Territory

ing on costly specialty pharmaceuticals is pushing payers to select those services that can ensure appropriate use of specialty drugs. “I think we’ve been focusing on the costs and management of specialty drugs, but we haven’t spent enough time managing the specialty patient,” Dr. Kaddis asserted. “There needs to be a paradigm shift.” A strength specialty pharmacies can capitalize on in their collaborative relationships is patient education. According to Jann Rigell, RPh, the vice president of specialty payer account management and clinical services at Accredo, this aspect of care is increasingly important to PBMs, who see it as a way of improving outcomes and reducing costs. “We believe that better educated patients make better choices,” Ms. Rigell said. “Our patients have access to therapeutic resource centers, which include pharmacists, pharmacy assistants and trained nurses.” Patients knowledgeable about their disease and their medications are more

likely to have better medication adherence, a critical measure for PBMs such as Express Scripts, which owns Accredo Specialty Pharmacy, she added. “We think adherence is the name of the game,” she said. “It improves care and reduces waste. This is getting more and more important as new specialty drugs are emerging, more individuals are receiving appropriate diagnoses and more patients are seeking new life-sustaining drugs.” Accredo also is using educational initiatives for other stakeholder groups, Ms. Rigell added. “On the payer side, it’s about giving payers the tools they can use to influence prescribers and patients to encourage them to make the best pharmacy choices,” she noted. What is the best pharmacy choice? For Ms. Rigell and other PBMs, services such as adherence interventions and formulary management are particularly important. “We do want patients to go through the specialty pharmacy channel if they

The stakeholder panel seemed to be in unanimous agreement that the cost and outcome-related pressures that are accompanying the accountable and value-based care model are demanding closer stakeholder collaboration. However, Dr. Vogenberg said it remains to be seen what that collaboration will look like. “If we’re changing the whole way we’re doing business, we have to change everything we do,” said Dr. Vogenberg. “We’ll have to figure out how we can better align our incentives, for one.” The well-being of the patient—the most important health care stakeholder with the least say—has to be at the center of the future of care, he said. “The government is looking to the commercial sector for transformative innovations, to do things differently, and to achieve better alignment between stakeholders with the goal of good patient care, because everybody recognizes that if the patient doesn’t benefit, it’s not worth societal cost,” he concluded. “This is our time. If we don’t do something now, we’re going to be stuck with the same old patchwork that we’ve been working with for the last 30 years.” —David Wild

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Specialty Pharmacy Continuum â&#x20AC;˘ Spring 2013

CLINICAL

DISEASE STATE SPOTLIGHT

IVIG Medication Safety: A Stepwise Guide to Product Selection and Use IVIG frequently is divided into 4 categories. First-line use is either FDAor compendia-approved. Second-line indications have grade B evidence; IVIG often is used for these indications when first-line therapy has failed or is not tolerated. Third-line indications are restricted to when other therapies have failed, and the evidence for these indications often is limited to openlabel studies, small sample sizes, or case reports. Fourth-line indications have no evidence or have evidence showing that use of IVIG either has anecdotal benefit at best or is potentially detrimental, and IVIG should not be used for these indications. Guidelines from the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology provide further information on the appropriate use of IVIG.1

Jerry Siegel, PharmD, FASHP Clinical Associate Professor The Ohio State University College of Pharmacy Columbus, Ohio

ver the past 30 years, intravenous immunoglobulin (IVIG) has been used for the treatment of primary immunodeficiency disorders and numerous autoimmune diseases. During this time, manufacturers have worked to enhance the safety profile of these products, with improvements in purification and stabilization. Additionally, through observation over years of treating patients, clinicians have improved patient tolerability of IVIG therapy. Appropriate selection and use of IVIG products can reduce the rate of IVIG-associated adverse events (AEs). The IVIG safety overview shown in Figure 1, and the information presented in Figures 2 through 8 and Tables 1 and 2, is designed to help maximize the safe use of IVIG and reduce the AEs associated with the infusion of these products.

Matching the Right Product To the Right Patient Clearly, various components of an IVIG formulation can affect patients differently. Medical history and patient risk factors, such as contraindications, age, and comorbidities, must be

IVIG Ordered and Approved

Patient education

Matching the right product to the right patient

Dosing considerations

Product selection from available products

weighed carefully against each productâ&#x20AC;&#x2122;s criteria to ensure that an appropriate product is selected and severe AEs are avoided. Just as patients receiving IVIG differ, so too do IVIG products. Health care providers must make critical clinical decisions concerning the appropriate product selection for each patient. Table 1 shows how various IVIG characteristics could affect specific patient risk factors.

Consider patient factors (contraindications, age, comorbidities, precautions) and product factors (volume, osmolality, IgA content, sodium content, sugar content, stabilizer, and pH)

Figure 1. IVIG safety overview. IgA, immunoglobulin A; IVIG, intravenous immunoglobulin

Contraindications

Table 1. Clinical Considerations: Matching the IVIG With the Patient Profile Patient Risk Factors

IVIG Characteristics Volume Load

Cardiac impairment

Renal dysfunction

Sugar Content

Sodium Content

Osmolality

Anti-IgA antibodies Thromboembolic risk

IgA

X X

Prediabetes

Geriatric patients

Neonates/pediatrics

IgA, immunoglobulin A; IVIG, intravenous immunoglobulin

Some patients have an immunoglobulin (Ig) A deficiency. Most often, this is caused by a failure of the bone marrow or a lack of thymus production of IgA. In more rare circumstances, IgA deficiency is caused by an anti-IgA antibody. In this situation, infusion of IgA could potentially cause anaphylaxis. Normally, this only occurs when the anti-IgA antibody is IgE-derived. Despite the rarity of this occurrence, patients need to be evaluated, and the IVIG product with the

Specialty Pharmacy Continuum • Spring 2013

CLINICAL

Patients With IgA Deficiency

Caution: monitor patient very carefully; infuse very slowly; use product with low IgA content

Patient Population

Consider the risks and benefits associated with administration of IVIG to these patients

Neonatal patients

pH concerns: local phlebitis at infusion site, metabolic acidosis if rapid highvolume infusion

Figure 2. IgA deficiency. a

IgA-deficient patients with antibodies to IgA are at greater risk for developing severe hypersensitivity and anaphylaxis.

IgA, immunoglobulin A

Caution: limit volume infused

Geriatric patients

Caution: watch for sodium and osmolar load causing hyperviscosity

Caution: cardiac, renal, or pulmonary insufficiency may be present

Caution: limit volume infused

Caution: watch for sodium, sugar, and osmolar load causing hyperviscosity

Figure 3. Age considerations.

lowest IgA content should be selected if the benefits of IVIG outweigh the risk associated with its use in such patients (Figure 2).

Patient With Diabetes Mellitus Caution: avoid products that can increase insulin requirement

Age

The effects of age need to be considered when IVIG is prescribed (Figure 3). Geriatric patients aged 65 years and older require additional monitoring and screening to prevent adverse reactions to IVIG. The increased likelihood of comorbid disease is higher in this patient population. Additionally, sensitivities to sugars, salts, and hyperosmolar infusions are more likely to cause IVIG intolerance in geriatric patients. In neonates, the infusion volume must be minimized. Additionally, the solution’s pH also must be considered. Low pH is important for stability of some products, but it can cause phlebitis in an infant’s small peripheral veins. Although the products are buffered and their pH is not of concern in adults, acidic pH may be problematic in neonates receiving IVIG. Slow infusions should resolve any concerns about metabolic acidosis. Finally, because the total blood volume in neonates is so small, the infusion of hyperosmolar, hyperviscous fluids can lead to hemolysis.

Glucose stabilizers: increase insulin requirement and must be avoided or accounted for

Sucrose stabilizers: do not increase glucose level in the blood

Maltose stabilizers: do not increase glucose level in the blood

Amino acid stabilizers: do not increase glucose level in the blood

Caution: maltose can cause false-positive reading with certain glucose monitoring devices (glucose dehydrogenase pyrroloquinoline quinoneor glucose-dye-oxidoreductase-based monitoring systems) a

Patient With Renal Insufficiency

Preexisting renal insufficiency (any degree), diabetes mellitus, >65 years, volume depletion and dehydration, sepsis, paraproteinemia, therapy with concomitant nephrotoxic drugs

Ensure that patients are adequately hydrated before starting the IVIG infusion

Assess and monitor patients’ serum creatinine, blood urea nitrogen, and urinary output

Prefer noncarbohydrate– stabilized IVIG if available

Slow infusion rate to minimal rate: for sucrose-stabilized products, maximum rate is 2 mg/kg/min

Use IVIG with isotonic osmolality (~300 mOsm/L)

Comorbidities

Comorbid conditions may determine which IVIG product is most appropriate for individual patients (Figure 4).2 In patients with diabetes mellitus, the biggest concern is the stabilizer agents used to prevent IgG aggregation. Although glucose directly affects the insulin requirement, complex sugars such as sucrose and maltose have no

Patient With Past History of MI, DVT, PE, or Thrombotic Disorder

Consider baseline assessment of blood viscosity for those at risk for hyperviscosity

Slow infusion rate

Use IVIG with isotonic osmolality (~300 mOsm/L)

Lower the dose infused per infusion

Text continues on page 14

Figure 4. Product selection based on comorbidities: DM, renal insufficiency, past history of MI, DVT, PE, or thrombotic disorder. DM, diabetes mellitus; DVT, deep vein thrombosis; MI, myocardial infarction; PE, pulmonary embolism a

For more information on false-positive readings with certain monitoring devices, see reference 2.

Specialty Pharmacy Continuum â&#x20AC;˘ Spring 2013

CLINICAL

Text continued from page 13

influence on these requirements (see Product Features Potentially Affecting Tolerability, page 14). Renal insufficiency also should be considered when IVIG products are administered. IVIGinduced renal insufficiency and acute renal failure were noted first with use of IVIG products stabilized with sucrose. This issue can occur with any carbohydrate-stabilized IVIG, and a related black box warning is part of all IVIG package inserts. Renal risk factors should be part of the standard review for all patients prior to IVIG product selection. Other safety measures called for in patients with renal insufficiency are using a slow infusion rate and using products that are close to iso-osmolar. Finally, although the exact relationship between IVIG and thrombotic AEs is not fully understood, it is recommended that the infusion rate be slowed, the dose administered during any given infusion be lowered, and iso-osmolar IVIG products be used in patients with a history of thrombotic events or disorders. Precautions

Various other factors require clinicians to use caution when prescribing IVIG (Figure 5). Aseptic meningitis. Aseptic meningitis is a post-infusion AE. Although the patient with this disorder will exhibit a severe headache with accompanying nuchal rigidity, lumbar puncture will not show evidence of infection. If the patient does not provide information about a previous IVIG administration, the connection might not be recognized. Patient education is imperative. Switching the product may not always result in improvement of this AE. If the benefit of IVIG therapy outweighs the risk in such patients, use of iso-osmolar IVIG products with a lower dose and a slower rate of administration is warranted. Hemolysis. Hemolysis is a rare AE associated with IVIG and anti-IgD administration. The mechanism and risk factors for this reaction are not

Aseptic Meningitis

May occur 5 to 7 days post-infusion; educate patients about the relationship of symptoms to IVIG

Hemolysis

Monitor patients for hemolysis and hemolytic anemia

Sodium Considerations

Aseptic meningitis syndrome may occur, especially with high doses or rapid infusion

Hemolysis can develop subsequent to IVIG treatments due to enhanced red blood cell sequestration

Changing IVIG products may prevent the syndrome; use low isotonic osmolality product, lower dose, and slower infusion rate

Educate patients about the signs of hemolysis

Increase post-infusion monitoring for at-risk patients

Sodium concentrations need to be carefully considered in the following settings: patients with cardiac conditions, renal insufficiency, or thromboembolic risk factors; geriatric patients; neonatal patients (neonates must be managed using oxygen therapy with adequate ventilatory support)

Precautions

TRALI

If TRALI is suspected, test for antinuclear antibodies in patient and IVIG product

Volume Considerations

Monitor patients for pulmonary adverse reactions and TRALI

Patients with TRALI may be managed using oxygen therapy with adequate ventilatory support

Infusion volumes need to be carefully considered in the following settings: patients with cardiac conditions, pulmonary edema, or thromboembolic risk; geriatric patients; neonatal patients

Figure 5. Clinical factors requiring caution when IVIG is used. TRALI, transfusion-related acute lung injury

clear. Patients need to be aware of postinfusion signs of hemolysis. Hematuria may cause a darkening of the urine within a few hours of IVIG administration and can serve as an early warning sign of hemolysis. Sodium considerations. The sodium concentration of IVIG products can vary from 0% to 1.8%. It is important to know the amount and concentration

of sodium being infused. The choice of diluents is a factor for reconstitution of lyophilized products. Lyophilized products that already have sodium chloride are of particular concern. Liquid IVIG products normally do not contain sodium chloride. Transfusion-related acute lung injury (TRALI). This syndrome is characterized by severe respiratory distress, pul-

monary edema, hypoxemia, and fever, with normal left ventricular function. Because TRALI can be associated with significant morbidity and mortality, monitoring for it is important in patients receiving IVIG products. Volume considerations. If a patient weighing 100 kg receives 1 g/kg of a 5% IVIG, the volume infused would be 2,000 mL. This volume of fluid, especially if

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Specialty Pharmacy Continuum • Spring 2013

CLINICAL hyperosmolar, could cause numerous problems for the patient. Cardiac, pulmonary, and renal dysfunctions raise particular concern. In neonates, because the total blood volume is small, the volume of infused IV fluid can affect the neonate’s metabolic state. Higher-concentration but iso-osmolar solutions of IVIG are best suited for these patients.

Product Features Potentially Affecting Tolerability Besides possible clinical efficacy and safety effects, different manufacturing steps also may affect product characteristics that determine tolerability. IVIGs vary with regard to formulations, concentrations, osmolalities, IgA content, pH, and sodium and sugar contents (Table 2). Some IVIG preparations contain sugar as a stabilizer (Table 2 and Figure 6). Glucose, sucrose, and sorbitol also have been used. Other IVIG products do not contain any sugar. Even though sorbitol may not increase the glucose level in the blood, it is metabolized to fructose. Caution needs to be exercised with patients who have hereditary fructose intolerance. A small population of patients may have hyperprolinemia and should not receive products stabilized with proline. Volume load (rate of infusion) also can affect tolerability.

Dosing and Rate Considerations Dosage Selection

Originally, IVIG was indicated only as replacement therapy for IgG-deficient patients with primary immunodeficiency disorders. Doses ranged from 150 to 250 mg/kg. Evaluation of outcomes and measurement of IgG serum levels revealed that this dose range was suboptimal to achieve an IgG level greater than 600 mg/dL. Doses for replacement therapy usually are in the range of 400 to 500 mg/kg, administered every 3 to 4 weeks. For immunotherapy, such as for idiopathic thrombocytopenic purpura and chronic inflammatory demyelinating polyneuropathy, the dosage can be much higher but normally is 2,000 mg/kg per

Table 2. Pharmaceutical Aspects of IVIG: Osmolality/Osmolarity, Sodium Content, and Stabilizer Product

Osmolality/Osmolarity

Sodium Content

Stabilizer

Bivigam Biotest (liquid 10%)

≤510 mOsm/kg

100-140 mEq/L

Glycine

Carimune NF CSL Behring (lyophilized)

In water: 3%, 192 mOsm/kg; 6%, 384 mOsm/kg; 12%, 1,074 mOsm/kg In saline: 3%, 498 mOsm/kg; 6%, 690 mOsm/kg; 12%, 1,074 mOsm/kg

0%, water; 0.9%, NS

Sucrose

Flebogamma 5%, 10% DIF Instituto Grifols (liquid 5% and 10%)

327±4.5 mOsm/kg (5%); 342±7.2 mOsm/kg (10%)

Trace (<3.2 mmol/L)

5% sorbitol (polyol)

Gammagard Baxter Healthcare (liquid 10%)

240-300 mOsm/kg

No sodium added

Glycine

Gammagard S/D Baxter Healthcare (lyophilized 5%)

636 mOsm/L

0.85%

2% glucose, glycine

Gammaked Grifols Therapeutics (distributed by Kendrion)

264±4 mOsm/kg

Trace (<7 mEq/L)

Glycine

Gammaplex Bio Products (liquid 5%)

420-500 mOsm/kg

30-50 mmol/L

Sorbitol, glycine, polysorbate 80

Gamunex-C Grifols Therapeutics (liquid 10%)

264±4 mOsm/kg

Trace (<7 mEq/L)

Glycine

Octagam, Octapharma (liquid 5%)

310-380 mOsm/kg

≤30 mmol/L

10% maltose

Privigen CSL Behring (liquid 10%)

240-440 mOsm/kg

Trace

Proline

treatment course. If the patient is able to tolerate it, a dosage of 1,000 mg/kg per day for 2 days will result in a rapid response. Some patients may need a lower dosage regimen spread out over time to minimize AEs. Volume considerations must be evaluated with regard to patient age, comorbidities, and so forth (Figure 7).3 Dosing in Obese Patients

Clinicians often are concerned with

proper dosing of IVIG for patients who are morbidly obese. IVIG product registration studies used actual body weight to calculate the final dose; however, morbidly obese patients usually are excluded from study populations. In most situations, actual body weight should be used, but when the patient’s weight is greater than 100 kg or body mass index is greater than 30 kg/m2, an adjustment of dosing weight may be required.

Rate Determination

Each product has a recommended rate of infusion that should be followed. When starting therapy, an initial rate that allows for observation and monitoring over a 15- to 30-minute period should be used. The rate should be increased as defined and then a third escalation should be implemented to determine the patient’s maximum tolerated rate. AEs can occur at any time, Text continues on page 16

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Specialty Pharmacy Continuum • Spring 2013

CLINICAL

Text continued from page 15

Stabilizer Considerations

Sorbitol: does not increase glucose level in blood

Maltose: dose not increase glucose level in blood

L-proline: does not increase glucose level in the blood

Caution: sorbitol is metabolized to fructose; avoid in patients with hereditary fructose intolerance

Caution: maltose is derived from corn syrup and should be avoided in patients with corn allergy

Caution: contraindicated in patients with hyperprolinemia

Glycine: does not increase glucose level in blood

Figure 6. Considerations for various stabilizers used in IVIG products.

Initial Dose and Rate Selection (Most indications: 2,000 mg/kg per course of therapy) a

Dosing weight determination

In most cases, use ABW

400 mg/kg over 5 days OR 500 mg/kg over 4 days OR 1,000 mg/kg over 2 days

If >100 kg or BMI >30 kg/m2, calculate IBW

ABW – IBW x 0.5 + IBW = dosing weight

Dosing rate determination Follow manufacturer’s guidelines c

Always escalate rate through 3 phases

Reduce rate if AEs occur

Use premedications if AEs occur

Figure 7. IVIG dose and rate selection steps. a

Doses are customized per patient for maintenance dosing.

For more information on dosing in obese patients, see reference 3.

See full prescribing information for each product for rate guidelines.

Stop infusion if AEs don’t subside

Determine patient’s maximum tolerated rate

Patient Consultation

Verify patient knowledge of the following: • Specific IVIG brand being used • Most recent IVIG dose they received • IVIG rate escalation used and tolerance they exhibited previously • Premedications they require • Risk factors they have • Infusion-related and delayed AEs they have experienced

Figure 8. Patient education and documentation steps. AEs, adverse events

Conclusion Further comparisons of IVIG products can be found in “Immune Globulins: Therapeutic, Pharmaceutical, Cost, and Administration Considerations.”4 Because of the varying characteristics, certain products may not be well tolerated by or recommended for particular patient populations. Additionally, individual patient tolerability may differ between certain products. Therefore, much care and consideration need to be taken when selecting a particular IVIG for a particular patient. When treating patients with IVIG therapy, an important component is patient education about the brand being used, the rate escalation, risk factors they may have, their tolerance of the product, and any AEs they may have experienced. Another important component is documentation in the patient’s medical record of the IVIG brand used, infusion rate, patient risk factors, and tolerance (Figure 8). A stepwise approach that considers all of the components listed in the figures and tables will help promote the safe use of IVIG and reduce the adverse reactions commonly associated with the infusion of these products.

References

ABW, actual body weight; AEs, adverse events; BMI, body mass index; IBW, ideal body weight

Documentation in medical record Note brand, rate, risks, and tolerance

and slowing the rate should be the first strategy. Additionally, the administration of antidotes may be required. On subsequent infusion, specific premedications may be administered to improve patient tolerability. During any situation when slowing the rate does not immediately reduce the AE, the IVIG should be stopped and treatment administered.

1. Orange JS, Ballow M, Berger M, et al. Position statement on the appropriate use of intravenously administered immunoglobulin (IGIV). http://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20 and%20Parameters/IGIV-2005.pdf. Accessed April 11, 2013. 2. Bronstein D. FDA issues warning on glucose test strips. Pharmacy Practice News. 2009;36:3. http://www.pharmacypracticenews.com/ index.asp?section_id=61&show=dept&issue_ id=560&article_id=13863. Accessed April 11, 2013. 3. Siegel J. IVIG FAQs. Immunoglobulins and obesity. Pharmacy Practice News. 2010; 37(1):8-9. 4. Siegel J. Immune globulins: therapeutic, pharmaceutical, cost, and administration considerations. Pharmacy Practice News. 40(1 suppl):1-8. http://www.pharmacypracticenews.com/ViewArticle.aspx?d=Specia l+Edition+%2f+Educational+Reviews&d_ id=63&i=January+2013&i_id=921&a_id=22490. Accessed April 11, 2013. Dr. Siegel has a research agreement with CSL Behring.

Specialty Pharmacy Continuum â&#x20AC;˘ Spring 2013

CLINICAL

ADHERENCE continued from page 1

Yelena Yankovskaya, PharmD, a fellow in managed markets at Mayes College of Healthcare Business and Policy at the University of the Sciences, in Philadelphia. â&#x20AC;&#x153;As pharmacists, I think we have a great opportunity to save lots of money both for our patients and ourselves if we improve adherence.â&#x20AC;? The financial toll of nonadherence is striking: $317 billion in health care expenditures are attributable to preventable disease-related complications, Dr. Yankovskaya said, referring to data from Express Scriptsâ&#x20AC;&#x2122; 2011 Drug Trend Report. A lack of symptoms is one predictor of nonadherence, but complex treatment regimens, a lack of confidence in the treatment or the care provider, the presence of mental illness and high treatment cost also are associated with poor adherence, Dr. Yankovskaya said. â&#x20AC;&#x153;By using what we already know about an individual from electronic health records and claims data, we can intervene proactively,â&#x20AC;? Dr. Yankovskaya said. â&#x20AC;&#x153;Tailored interventions using a predictive model that takes variables into account can address particular problems that can lead to nonadherence.â&#x20AC;?

Tailoring Interventions To Reduce Cost Barriers When cost is a barrier, for example, pharmacists can mail patients a â&#x20AC;&#x153;loss aversion letter,â&#x20AC;? outlining the financial costs of nonadherence, Dr. Yankovskaya said. She pointed to a study conducted by Express Scripts that showed that mailing such a letter increased adherence by 8.8%, compared with a 7% improvement when no letter was sent out. â&#x20AC;&#x153;This may be a modest increase but it is still an increase,â&#x20AC;? Dr. Yankovskaya said. â&#x20AC;&#x153;Considering the costs of nonadherence, any improvement is important.â&#x20AC;? Furthermore, she added, â&#x20AC;&#x153;a letter-mailing intervention may seem resource-intensive, but it is not as expensive as setting up a case management team.â&#x20AC;? Another way of addressing cost barriers is to work with insurers to create a â&#x20AC;&#x153;value-based insurance design,â&#x20AC;? Dr. Yankovskaya said. This might include reducing or completely waiving a patientâ&#x20AC;&#x2122;s copay or lowering the cost of preventative physician visits, she explained. In one study including more than 35,000 patients with diabetes, waiving copays increased adherence rates by approximately 6% (Health Aff 2008;27:103-112).

Who Knew Adherence Could Be Fun? Dr. Yankovskaya pointed to a novel adherence interventionâ&#x20AC;&#x201D;aimed at reducing the number of accidentally missed dosesâ&#x20AC;&#x201D;that strikes a lighter

note. â&#x20AC;&#x153;Gamification uses game elements and game design techniques to make adherence into something fun,â&#x20AC;? she explained. Although most attendees had not heard of the term â&#x20AC;&#x153;gamification,â&#x20AC;? an informal poll at the AMCP session revealed that many in the audience were enrolled in a

reward points program, which is a gamification strategy used by companies to encourage purchases and brand loyalty. According to Dr. Yankovskaya, a gamification strategy like a rewards program can lure customers into â&#x20AC;&#x153;going out of their way to do certain things that they might not otherwise do.â&#x20AC;?

Health care stakeholders are only starting to apply gamification to tackle nonadherence, but Dr. Yankovskaya believes it could prove effective in increasing adherence, particularly in the growing population of younger patients with chronic diseases. One example of gamification used to address nonadherence is the free iPhone application, Mango Health, which Dr. Yankovskaya encouraged pharmacists to use with their patients. The application rewards patients with

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see ADHERENCE, page 18

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Specialty Pharmacy Continuum • Spring 2013

CLINICAL

CARE GAPS continued from page 1

Courtesy: Biologics, Inc.

Thus, Ms. Sullivan started the conversation for the specialty pharmacy attendees and subsequent speakers at the roundtable discussion identified three main areas where they believe specialty pharmacists can help narrow the substantial gap: following a more holistic care model, providing better transitional support, and improving communication with patients and other care providers. The latter two areas will be covered in the second part of this two-part series.

Holistic Care To achieve true holistic care, specialty pharmacists need to cultivate a relationship that addresses more than simply medication management issues, said speaker Daniel Duffy, MBA, the chief business development officer at Biologics, Inc., an integrated oncology services company in Cary, N.C. “Since we follow a high-touch model of care and are in frequent contact with the patient, we are in a good position to impact them through a relationship that hinges on trust and empathy,” he said. “It’s an overwhelming experience for anyone who’s been diagnosed with cancer to be bounced around the care system with its many gaps and communication inconsistencies, and patients can be very anxious” (Figure). The holistic pharmacist–patient relationship should include discussion and assessment of quality-of-life issues, Mr. Duffy said. This type of engagement with “the whole patient” can empower patients and provide them with an opportunity to take control of their own care, he said. Adding to this point, Mr. Duffy said that the initial phone call with the patient is perhaps the most critical point of a holistic relationship. “Just engaging the patient to start with is a really big gap,” he said. “When the initial conversation does take place, patients might not be in a state of mind to really take everything in. They either have a new diagnosis, which can be a shocker to them, or their disease has progressed to the point of needing a

ADHERENCE continued from page 17

gift cards that can be redeemed at popular stores and also moves patients through different “levels,” depending on how adherent they are to their medication schedule. The app also includes a drug reference library, which patients can use to educate themselves about drug-related adverse events and drug interactions. “I can assure you you’ll be hearing more

Figure. The “whirling dervish” graphic points to potential gaps in care for oncology patients as they get bounced around disjointed segments of the health care system.

Monitoring ‘the full gamut of medications the patient is receiving means providing a more robust and holistic degree of care management.’ —David Calabrese, RPh, MHP

specialty drug. So you need to take into account their emotional state. If you get this first inch right, you’ll get the next mile right.” Getting that first contact right means ensuring that patients are not distracted and have enough time to talk, Mr. Duffy said. He urged pharmacists to conduct a

comprehensive patient assessment that includes “the clinical, financial and emotional side of care.” He recommended structuring the initial conversation and introducing key points first and providing more information as the conversation proceeds. “There’s only so much the patient can retain, given that they have a

about this approach,” Dr. Yankovskaya predicted, noting that pharmacists can learn more about gamification through a free online course at www.coursera.org. Eric Wee, PharmD, a postgraduate year 1 managed care pharmacy resident at CVS Caremark in Irving, Texas, has a particular interest in medication adherence and believes technologybased tools like Mango Health “can definitely play a big role in increasing adherence in the near future. The main issue with nonadherence is that

patients simply forget to take their medication,” Dr. Wee told Specialty Pharmacy Continuum. “Therefore, the best way to address the issue of nonadherence is to remind the patient to take their medication at the right time. From pill bottles that glow, vibrate, ring or beep, to iPhone apps that remind patients to take their medication, to the concept of gamification, I think technology can address the issue of nonadherence in an effective manner.” The toolbox of adherence-promoting

new diagnosis, a new drug, they’re dealing with a new delivery model and maybe they have new financial burdens that they hadn’t signed up for,” he said. “You can’t give them everything they need to know right away.” In terms of medication management, expanding the model of care from a narrow to a holistic approach also should include assessment of more than just the specialty drug the patient is receiving and the specific illness it is being prescribed for, said David Calabrese, RPh, MHP, vice president and the chief pharmacy officer at Catamaran, in Lisle, Ill. He suggested widening the purview of what specialty pharmacists typically see as their role in clinical care. “Specialty pharmacists are in an excellent position to screen for comorbidities on a routine basis,” Mr. Calabrese noted. This means anticipating the occurrence of specific comorbidities that emerge over time with a particular illness, he explained. For example, multiple sclerosis patients are at risk for depression, whereas those with inflammatory diseases such as rheumatoid arthritis often also experience conditions such as hypertension, hyperlipidemia and cardiometabolic diseases. Mr. Calabrese said that close monitoring gives specialty pharmacists “an opportunity to better triage and manage the overall care of the patient. The value of more comprehensive monitoring and intervention is that it also permits better selection and use of the right drugs based on what outcomes and adverse events the patient is actually experiencing or is anticipated to experience,” he said. “We can also use this aspect of care to better promote and differentiate the value of our services and [provide] new ones. I think we can take our services to a much higher level.” Monitoring “the full gamut of medications the patient is receiving means providing a more robust and holistic degree of care management,” Mr. Calabrese said. Mr. Duffy highlighted the need for improved and rapid detection of adverse events as a way of improving a patient’s quality of life, minimizing health care costs, and adding more value to

interventions means pharmacists can choose one or more approaches that are most appropriate for an individual patient, Dr. Yankovskaya concluded. “Different strategies are effective for different patients. There is no single solution. There might be something that works best for one patient, but not another.” —David Wild Drs. Yankovskaya and Wee reported no relevant financial conflicts of interest.

Specialty Pharmacy Continuum • Spring 2013

CLINICAL specialty pharmacy services. The health care burden of adverse events is such that approximately half of all cancer patients undergoing treatment will visit the emergency room for care that can be provided outside of this setting (J Clin Oncol 2011;29:2683-2688). “We are often the patient’s most frequent point of contact, so we can bring in the physician to mitigate any complications or adverse events if we appropriately collect patient information and monitor them frequently,” he said. While specialty pharmacists should

OpS & MGMT

IG NURSING GROUP continued from page 10

Dr. Siegel has no affiliation with the IgNS, but he supports a certification program for Ig nurses. “Everyone understands that you need to be certified to be a chemotherapy nurse, but Ig can be equally dangerous if given by a nurse who doesn’t understand it,” he said.

Safety Concerns Cited Every patient has a maximum tolerated rate of infusion, and a skilled nurse knows how to escalate safely, Dr. Siegel noted. Infusing a patient too rapidly can lead to adverse events such as headache, fever, chills and muscle aches. Rapid infusion also can cause renal insufficiency and thromboembolic disorders in patients with comorbidities such as diabetes, or a history of thrombosis. “Whether a patient can tolerate an Ig product may have more to do with the nurse than the product,” he said. “If a patient receiving Ig gets chills, an untrained nurse will respond by getting a blanket instead of turning down the rate of infusion. By the time they get back with the blanket, chills may have escalated to rigors.” Dr. Siegel pointed to a case where both the patient and nurse were in a hurry to get home, so the nurse turned up the infusion rate. The patient had a severe reaction and ended up in the ER. Another particularly dangerous practice is leaving an Ig patient unattended, Dr. Sobolevsky said. She knows of companies that sends nurses out to infuse patients in their home who will leave one patient unmonitored and drive to a second patient’s home to set up another infusion. “It’s critically important to stay with patients and monitor them throughout infusions,” she said “because adverse events can happen anytime.” Commenting on the new group, Kelly Bertolazzi, the Northeast regional Ig manager at Walgreens Infusion Services, said, “There’s a huge body of knowledge we need to get into the hands of nurses, and IgNS is helping to do that.” —Dana Hawkins-Simons

Initially ‘patients might not be in a state of mind to really take everything in....So you need to take into account their emotional state. If you get this first inch right, you’ll get the next mile right.’

—Daniel Duffy, MBA

take on the onus of more regular patient check-ins, Mr. Duffy also noted that patients need to take on their share of responsibility and should contact their specialty pharmacy as soon as possible, if an adverse event occurs. For this to happen, he said, pharmacists need to

establish a personal relationship with patients. “Instead of having the communication process only be time-driven, it should also be event-driven,” he said. “The high-touch care that patients receive should include them calling you when they have an event.”

In summary, Mr. Duffy said, “the longitudinal nature of our relationships with our patients gives us an opportunity to improve the quality of their care and take significant costs out of the system.” —David Wild

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CORPORATE SPOTLIGHT

ften, the most effective means of communication between health care professionals is through labeling. In order to meet this vital need for both pharmacy and nursing, Medi-Dose/EPS has specifically designed labels for every need from solids to liquids, syringes to ampules, IV lines and bags to insulin and suppositories. Plus, with our MILT 3.0 software, you can design your labels any way you want. In addition to being able to use graphics, special fonts, tall man lettering, shapes—even logos and symbols—to better identify your medications, MILT 3.0 has been designed to easily create bar codes with the information your bar code–enabled point-of-care and bar-code medication administration systems require. Popular 1-D and 2-D bar code formats can be created with NDC numbers, expiration dates, lot numbers and special codes. Here are some additional labeling systems we offer, with details on how they can help your facility improve medication handling and safety:

Lid-Label Cover Sheets, designed for use with the MediDose packaging system, maintain security for your medication while providing ample drug identification area. A moisture-resistant foil layer and an aggressive, tamperevident, FDA-acceptable adhesive combine for an effective moisture barrier for your medication. Yet the label’s innovative design yields an easy-to-open package. When used with our Medi-Cup PLUS Blisters, you can place up to one-year beyond-use dating on your packages. LiquiDose Labels provide a unique, tamper-evident labeling solution for all your liquid medication identification needs. The label’s versatile 1˝ × 3˝ size lends itself to a variety of uses—medication bottles, bin identification, log report books—just to name a few. Available for laser/inkjet or direct thermal printers, the label’s unique cross-hair cut design facilitates tamper evidence. MINI LiquiDose Labels were designed for labeling syringes, ampules and small packages. They also can be used to re-label and re–bar-code medication packages to accommodate specific needs. The label’s 7/16˝ × 1 ¼˝ size can comfortably accommodate five lines of text and a bar code. Available for laser/ inkjet or direct thermal printers, the label’s size makes them ideal for you to create your own Auxiliary Warning Labels. LiquiDose Butterfly Flag Labels have a distinctive twowing design so they can be wrapped around syringes, ampules or oddly shaped containers. Each wing has a labeling area to accommodate multiple lines and a bar code. Laser Butterfly Flag Labels are available in six colors, with or without ORAL imprint. Direct Thermal Butterfly Flag Labels are specially coated for added durability. LiquiDose Flag & Receipt Labels have a large, two-sided printing area with a long, thin strip that allows you to attach the label to any item, no matter how small or large. Each Flag Label also includes a Receipt Label that can be used for your charts or dispensing records. LiquiDose Flag & Receipt Labels are available in two sizes for laser and direct thermal printers. LiquiDose Square Labels solve a complicated problem elegantly. The 1-D bar codes required by most pharmacy systems are hard to scan on small items. With the LiquiDose Square Label, you simply turn the label 90 degrees so the bar code and text run along the curve of the item instead of around it, making both easier to read. All three sizes—1.00,˝ 1.33˝ and 2.66˝—are available for laser and direct thermal printers.

You name it. At Medi-Dose/EPS, there’s a label for that!

AT A GLANCE Address 70 Industrial Drive Ivyland, PA 18974 Phone: (800) 523-8966 Fax: (800) 323-8966 E-mail: info@medidose.com Web site: www.medidose.com

Products ®

Medi-Dose (Solid) and TampAlerT® (Liquid) Oral Unit-Dose Packaging Medi-Cup® PLUS packaging for extended beyond-use dating MILT® by Medi-Dose unit-dose and bar-coding software LiquiDose® labeling, IV additive and filtration products Nultraviolet® ultraviolet light inhibitant bags Steri-Dropper sterile ophthalmic dropper bottles High Alert and IV Line Tracing Labels Resealable bags, bottles and other pharmacy supplies and disposables

Specialty Pharmacy Continuum • Spring 2013

CLINICAL

Home Nutrition Services Boost Outcomes Phoenix—Clinical interventions for patients on home enteral nutrition (HEN) and home parenteral nutrition (HPN) not only can improve patient care but also can save significant health care dollars by preventing hospitalizations, according to a study by Walgreens Infusion Services that was presented at the American Society for Parenteral and Enteral Nutrition’s Clinical Nutrition Week conference. During a three-month period early in 2012, a multidisciplinary nutrition support team comprising nurses, pharmacists and dietitians managed 373 interventions among 2,770 patients, potentially saving an estimated 429 hospital days and $850,000 in health care dollars from hospitalizations. The interventions were not new, explained Noreen Luszcz, RD, MBA, CNSC, the lead study author and the nutrition program director for Walgreens Infusion Services. But as home infusion companies and other health care institutions face challenges in justifying their existence, she and others at Walgreens became concerned about the future of home infusion and thought it would be important to track interventions to demonstrate the value of the

home nutrition support team. Among HPN patients, for example, the team performed 70 interventions to manage electrolyte imbalance. In those cases, Ms. Luszcz said, the dietitians would notice if a patient’s labs looked irregular and would contact the patient’s physician to discuss an amended regimen, preventing further declines in health. “If you don’t have close monitoring of patients, you don’t notice changes that could potentially lead to negative outcomes,” Ms. Luszcz said. “Things can worsen and all of a sudden they’re calling the doctor and hearing ‘Go straight to the ER.’” For the study, registered dietitians tracked clinical interventions at 16 Walgreens Infusion Services offices, with 2,500 HEN patients and 270 HPN

patients on service at the time. The 373 interventions recorded—performed by the dietitian or in conjunction with other team members—included correcting overfeeding and underfeeding, preventing dehydration, reducing or eliminating diarrhea, managing hyperglycemia, managing electrolyte imbalances, transitioning patients from HPN to oral eating and starting patients on HPN. To qualify for inclusion in the study, interventions had to be based on sound clinical judgment, backed by best practices, initiated by a member of the team and documented in the patient’s medical record. The team intervened 192 times for HPN patients, including 39 interventions to prevent dehydration, 26 interventions to write a formula order and 20

‘Home nutrition support teams continue to provide a vital role in assuring the most appropriate, cost-effective provision of home parenteral and enteral nutrition.’ —Noreen Luszcz, RD, MBA, CNSC Table 1. Cost Savings for Key Home Enteral Nutrition Clinical Interventions Intervention (type)

Interventions (n)

Average Days of Hospitalization

Hospital Days Saved

Health Care Dollars Saved ($2,000/day)

Managed electrolyte imbalance

$18,000

Managed hyperglycemia

$12,000

Prevented dehydration

$76,000

Reduced/eliminated diarrhea

$68,000

Total hospital days/dollars saved

$174,000

Table 2. Cost Savings for Key Home Parenteral Nutrition Clinical Interventions Intervention (type)

Average Days of Interventions (n) Hospitalization

Hospital Days Saved

Healthcare Dollars Saved ($2,000/day)

Managed electrolyte imbalance

210

$420,000

Managed hyperglycemia

$96,000

Prevented dehydration

$156,000

Initiated parenteral nutrition in the home safely

$12,000

Total hospital days/dollars saved

342

$684,000

interventions to correct underfeeding. The team intervened 181 times for HEN patients, including 78 interventions to write a formula order, 47 interventions to correct underfeeding and 19 interventions to prevent dehydration. The study authors estimate that for HEN patients, they saved 87 hospital days at an average hospitalization cost of $2,000 per day, for a total savings of $174,000 (Table 1). For HPN patients, they estimate having saved 342 hospital days and $684,000 (Table 2). The team used online Healthcare Cost and Utilization Project data from the Agency for Healthcare Research and Quality to estimate average days of hospitalization for each of the medical conditions, and a 2009 article from Pharmaceutical Commerce (http://tinyurl.com/c8ljquj) about home infusion reimbursement to estimate average daily hospitalization costs. Beyond saved hospitalization dollars, the benefits for many patients include avoiding hospital-acquired infections and retaining the ability to work, Ms. Luszcz added. “What we set out to [prove], we did,” she said. “Home nutrition support teams continue to provide a vital role in assuring the most appropriate, costeffective provision of home parenteral and enteral nutrition.”

Kudos for Study Gordon Sacks, PharmD, the head of the Department of Pharmacy Practice at Auburn University’s Harrison School of Pharmacy in Alabama, told Specialty Pharmacy Continuum that he thought the Walgreens Infusion Services study was well done. But he said he was surprised to see that the team did not track catheter-related infections, the No. 1 reason he has found most home infusion patients are readmitted to the hospital. Dr. Sacks added that he also would have been interested to see more details about the types of electrolyte imbalances managed by the team. Ms. Luszcz responded by pointing out that catheter-related infections are tracked as an ongoing quality assurance process and thus were not included in these proactive clinician interventions. Future studies may further tease out the electrolyte imbalances, she noted. David Franklin, the president and CEO of Advanced Care Consulting Services, who formerly served on the board of directors for the National Home Infusion Association, commented that “the [study] methodology appears sound, the costs estimated are reasonable and the references are solid, which lends additional credibility.” —Karen Blum

Specialty Pharmacy Continuum • Spring 2013

CLINICAL

Trial Results May Boost Actemra Prescribing Tocilizumab prescribing may be set to increase following strong results from two controlled trials of the biologic. Findings from one placebo-controlled study showed an 85% response rate after 12 weeks of treatment for refractory systemic juvenile idiopathic arthritis (SJIA), and a large head-to-head trial showed that the interleukin-6 (IL-6) receptor blocker was more effective than adalimumab (Humira, Abbott) as monotherapy for severe rheumatoid arthritis (RA). Gary Rice, RPh, MS, MBA, the vice president of clinical programs for Diplomat Specialty Pharmacy, said the research adds to a growing body of evidence supporting the efficacy of tocilizumab [Actemra, Genentech] for the two indications. “I think these studies make a very good case for tocilizumab to be used more often and I expect they will generate lots of interest in the drug,” commented Mr. Rice, who was not involved in the studies. In the SJIA trial, 112 children with the illness received 12 weeks of twicemonthly infusions of either tocilizumab or placebo in a double-blinded fashion (N Engl J Med 2012;367:2385-2395). This was followed by a 40-week openlabel phase during which all patients were offered the drug. Children weighing 30 kg or more received tocilizumab 8 mg/kg; those weighing less than 30 kg received 12 mg/kg. The results showed that 85% (64 of 75) of tocilizumab recipients experienced at least a 30% improvement in three or more of the six core SJIA variables defined by the American College of Rheumatology (ACR). In contrast, 24% of placebo recipients (nine of 37) met this criterion (P<0.001). At the 52-week point, 80% of patients who received tocilizumab had at least a 70% improvement and no fever, 59% had at least a 90% improvement and 48% had no active arthritis. Approximately half of the patients were able to discontinue oral glucocorticoids by the study end date, the researchers found. “Many of these patients had already tried and failed other biologics and still showed rapid and profound improvement in both the systemic and arthritis aspects of the SJIA,” co-investigator Daniel Lovell, MD, MPH, the associate director of the Division of Rheumatology at Cincinnati Children’s Hospital Medical Center, told Specialty Pharmacy Continuum. He predicted that “in the future, IL-6 and/or IL-1 blocking biologics may become first-line therapy and SJIA patients will be able to completely avoid the need for systemic corticosteroid therapy.” The second study strengthening the drug’s record was a double-blind trial comparing 24 weeks of tocilizumab with adalimumab as monotherapy in patients with severe RA (Lancet 2013; doi: 10.1016/S0140-6736(13)60250-0. [Epub ahead of print]). Those researchers used the Disease Activity Score

(DAS) 28 to measure RA disease activity in 28 joints and found significantly greater mean reductions in scores among the 163 tocilizumab patients

than in the 162 adalimumab recipients (mean DAS28 change from baseline: –3.3 for tocilizumab vs. –1.8 for adalimumab; P<0.0001).

Safety a Concern Although the studies demonstrate impressive efficacy in both severe disease states, tocilizumab-related adverse events (AEs) are common. In the SJIA study, there were 159 drug-related AEs during the double-blind phase, including 60 infections, two of which were serious. In both the SJIA and RA studies, tocilizumab also was associated with

•

see ACTEMRA, page 24

Specialty Pharmacy Continuum • Spring 2013

CLINICAL

ACTEMRA

and macrophage production. Character- a Risk Evaluation and Mitigation istic presenting symptoms include non- Strategy (REMS) including a commucontinued from page 23 FILE SLUG STATUS & HISTORY nication plan. Genentech also recomremitting high fever, lymphadenopathy, CURRENT FILE: SPC OPT-IN.INDD 1ST PROOF LAYOUT APPROVED PROOF 1: 11/1 EDITOR: DAVID INITIALS AND DATE ART FRANK REV 1: neutropenia (mostly grade 3), elevated hepatosplenomegaly, pancytopenia, mends monitoring patients for ALT, liver DIRECTOR: REV 2: FULL NAME OF SENIOR EDITOR alanine aminotransferase (ALT) levels, dysfunction, hypertriglyceridemia and lipid, platelet and neutrophil changes, REV 3: PROJECT EDITOR REV 4: lowered PROJECT platelet counts and increased COPYhyperferritinemia. “Clinicians need to although the FDA does not call for this. REV 5: NO. EDITOR 6: low-density lipoprotein (LDL) choles- SALEScontinue to be vigilant forREVthese Genentech is providing rheumatoloserious REVISION # PROOF 1 terol levels. Notably, there also were PRODUCTION complications in SJIA patients receiving gists with most of the educational mateLAYOUT DATE/ APRIL 22, 2013 2:13 PM TIME instancesEDITORIAL of macrophage activation syn- CIRCULATION tocilizumab or other interleukin inhibi- rials directly, but specialty pharmacists DATE/TIME drome (MAS) and severe cardiopulmo- tors,” Dr. Lovell said. are required to distribute medication TRIM SIZE COMMENTS: KEYWORDS: nary disease in the SJIA study, Dr. Lovell guides to patients, Mr. Rice said. COLOR SPECS REMS Requirement Minimal said. MAS, which may not be well known “Our role is really to inform and eduFILE PATH SPC OPT-IN.INDD The potential for significant AEs cate,” he added. “The REMS requireto clinicians, is a rare but often fatal disorder thought to result from excess T cell has prompted the FDA to implement ment is not onerous, and there are real-

ly no other operational adjustments we need to make to dispense the drug.” Mr. Rice echoed Dr. Lovell’s comments that tocilizumab may eventually become a first-line treatment for SJIA and RA, but he suggested that prescribers’ familiarity with anti-tumor necrosis factor (anti-TNFs) agents may slow this process. Still, since tocilizumab can be used for multiple indications, this may increase physicians’ comfort level with it and its attractiveness to them, he said. Mr. Rice added that the latest ACR RA treatment guidelines recommend that anti-TNF drugs be administered as first-line biologic treatments (Arthritis Care & Res 2012;64:625-639).

An Alternative To ‘Buy-and-Bill’

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Rebekah Hanson, PharmD, a clinical liaison pharmacist for Specialty Pharmacy Services at the University of Illinois Hospital and Health Sciences System and a clinical assistant professor of pharmacy practice at the University of Illinois at Chicago College of Pharmacy, said that the findings from the SJIA study in particular are “very encouraging.” She told Specialty Pharmacy Continuum that rheumatologists may turn to tocilizumab “sooner and use it more aggressively as second- or third-line biologic for RA with inadequate response, and possibly as first-line treatment for more severe or rapidly progressive cases of SJIA.” Dr. Hanson said specialty pharmacies are an attractive alternative to the “buy-and-bill” route in light of the need to coordinate tocilizumab refills with scheduled infusion-center visits, provide special storage, and consider physician billing concerns. Health system specialty pharmacies or those with an integrated infusion center can strengthen their value proposition by conducting the tocilizumab-specific laboratory monitoring suggested by the manufacturer, she said. “Our health system prescribers now rely on our institution’s specialty pharmacy service to do all of the safety monitoring for biologics, both prior to initiation and for the duration of treatment,” Dr. Hanson said. For pharmacies with an infusion center component, she emphasized the importance of developing a strong relationship with the prescriber’s office. “Have a direct line of communication with the prescriber in case rapid intervention is necessary.” —David Wild

Diplomat Specialty Pharmacy reported a contractual relationship with Genentech. Dr. Lovell reported that he has served as a consultant or advisory board member for Amgen, AstraZeneca, Centocor, Roche, Novartis, UBC and Forest. Dr. Hanson reported no relevant financial conflicts of interest.

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Essential Microbiology for Pharmacy and Pharmaceutical Science

Geoff Hanlon; Norman Hodges February 18, 2013 This text is an essential study guide for undergraduates studying microbiology modules on degree courses in pharmacy and the pharmaceutical sciences. It distills the subject down into the essential elements that pharmacists and pharmaceutical scientists need to know.

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ORDER ONLINE For pricing, a more complete review and easy ordering with a credit card, go to McMahonMedicalBooks.com. We can supply any medical book in print, so if you don’t find the book you want, email your request with billing information to RMcMahon@McMahonMed.com. If you are an author and would like your medical book featured in this book section, contact Ray McMahon, Publisher, at RMcMahon@McMahonMed.com.

Information Technology in Pharmacy: An Integrated Approach

Stephen Goundrey-Smith October 5, 2012 This book provides a concise and practical general introduction to pharmacy IT, discusses issues surrounding the adoption of technology and how technologies may be used by the pharmacy profession to exercise new professional roles and achieve new professional aspirations.

Katzung & Trevor’s Pharmacology Examination and Board Review, 10th Edition

Anthony Trevor; Bertram Katzung; Susan Masters; Marieke Knuidering-Hall October 9, 2012 This book delivers a clear, concise review of fundamental concepts backed by more than 1,000 review questions and answers. The chapterbased approach facilitates use with course notes or larger texts.

Mosby’s Drug Reference for Health Professions

Mosby April 15, 2013 From Abilify to Zyrtec and nearly every drug in between, Mosby’s Drug Reference for Health Professions is the must-have portable drug handbook for every current or aspiring health professional in the field today. This updated edition features concise, reliable information that is easy to navigate, with alphabetically listed monographs for over 900 generic drugs, including 4,500 trade-name drugs for both U.S. and Canada.

PharmPrep: ASHP’s NAPLEX Review, Fourth Edition

Lea Eiland; Diane Ginsburg May 10, 2011 Using real patient cases accompanied by questions that address all NAPLEX® competency statements, the new edition gives you the flexibility to review information by specific disease state and provides 78 sample cases, as well as calculations and law review sections. As drug therapy becomes more complex, PharmPrep has continued to update and revise cases so they reflect contemporary clinical practice.

Remington: An Introduction to Pharmacy

Loyd V. Allen May 31, 2013 Remington: An introduction to Pharmacy is a companion to the 22nd edition of Remington: The Science and Practice of Pharmacy. It addresses the core concepts in the field of pharmacy, providing a broad overview of key pharmaceutical science and practice-related topics.

Roadmap to Postgraduate Training in Pharmacy

P. Brandon Bookstaver; April D. Miller; Celeste N. Rudisill; Kelly M. Smith February 5, 2013

Roadmap to Postgraduate Training in Pharmacy provides the information and expertise pharmacy students need to make confident, informed decisions regarding residency programs, fellowships and additional degrees.

Stockley’s Drug Interactions Pocket Companion 2013

Karen Baxter; Claire L. Preston January 10, 2013 This conveniently sized quick reference continues to provide the busy health care professional with a trustworthy, affordable and practical clinical reference on drug interactions and their management. It draws on the wealth of clinically evaluated, evidence-based information on drug– drug, drug–herb and drug–food interactions that is presented in the latest revalidated updates of the full reference work, Stockley’s Drug Interactions. SPC0513

Specialty Pharmacy Continuum • Spring 2013

POLICY

Antisense Makes Sense for Rare Lipid Disorder Mipomersen, the new antisense drug from Isis Pharmaceuticals and approved by the FDA under orphan drug status in January to treat homozygous familial hypercholesterolemia (HoFH), will be distributed exclusively through specialty pharmacies. Officials with Genzyme, the company that is marketing mipomersen as Kynamro, have confirmed that Walgreens, CVS Caremark and Accredo are the three specialty pharmacies that will supply the drug. Familial hypercholesterolemia (FH) is an autosomal dominant disorder that causes extremely high cholesterol levels. If a person inherits only a single mutated gene for FH, he or she will have the more common heterozygous FH (HeFH). That form, in fact, is one of the most common life-threatening genetic disorders, affecting about one in 500 people. The more severe and much rarer HoFH, which affects only about one in a million people, occurs when genetic mutations are inherited from both parents, according to the FH Foundation. “Kynamro was approved by the FDA because really, there weren’t any good options for these patients in the past. Patients can present at a very young age and are at high risk for heart attacks and even heart-related death,” said Carol Vuceta, the director of biopharmaceutical development at Walgreens Specialty Pharmacy. Ms. Vuceta added that in the past, physicians used high-dose statins or other cholesterol-lowering drugs, as well as strategies such as low-density lipoprotein apheresis to manage HoFH. But those interventions “all come with their own problems and none of them really work well in this population.” Administered as a weekly injection, mipomersen (along with other lipidlowering medications and diet) impairs the creation of the lipid particles that ultimately give rise to low-density lipoprotein cholesterol (LDL-C), according to the FDA’s approval notice for the drug. In a clinical trial of 51 patients with HoFH, LDL-C levels fell by about 25% during the first 26 weeks for

Plunger

Needle

Juxtapositioned With Juxtapid

Syringe

Kynamro packaging includes instructions for use that help explain how to self-administer the single-use, prefilled syringe formulation of the drug.

patients who received the drug. But the drug’s effectiveness comes with its own price: potentially severe liver toxicity. The FDA has approved mipomersen with a black box warning of possible liver abnormalities that could lead to progressive liver disease. The approval also is accompanied by a Risk Evaluation and Mitigation Strategies (REMS) program, which mandates prescriber and pharmacy certification and documentation of safe-use conditions. “The REMS program requires monitoring of liver enzymes, particularly in the beginning of therapy,” Ms. Vuceta said. Patients prescribed mipomersen must first receive baseline liver function tests, which will be repeated monthly for the first year of treatment. “After the first year, liver function

monitoring may be reduced to every three months,” she noted. Patients also receive extensive education about their disease, including tips for recognizing the signs of potential liver toxicity. The FDA has mandated no fewer than four postmarketing studies—a sign that the agency is keeping a close watch on this new class of drugs. The required studies include the development of a sensitive assay that binds double-stranded DNA; a study to detect antibodies to double-stranded DNA in patients using mipomersen; a longterm registry; and an enhanced pharmacovigilance program to monitor adverse events, particularly cancers, liver abnormalities and immune-mediated reactions. Ms. Vuceta said that because HoFH is so rare and often underdiagnosed,

More Antisense Molecules on the Horizon

fter nearly two decades of research, the market for antisense molecules may be poised for significant expansion. More than a dozen antisense products are in advanced stages of clinical study, analysts say, and many are from the portfolio of Isis Pharmaceuticals, which recently saw its first antisense molecule, mipomersen (Kynamro), approved by the FDA. “This is the end of the beginning for antisense,” Stanley Crooke, Isis Pharmaceuticals’ CEO, recently told Nature Medicine. The Kynamro approval, he noted,

the initial number of patients who may be treated with mipomersen could be quite low. However, she noted that the availability of this new treatment may help increase awareness and earlier diagnosis of, and treatment for, patients with HoFH. Mipomersen represents the first major commercial approval for the class of gene-silencing drugs known as antisense. Isis has more than a dozen other antisense drugs in the pipeline.

“is a critical step in the final validation of this technology.” Still, the company isn’t resting on its laurels. ISI-SMNrx, an intrathecal drug for patients with spinal muscular atrophy (SMA), continues to progress through clinical trials. (The condition is caused by a genetic defect that impairs production of a protein required for proper neuromuscular growth and function.) In a study of 28 patients designed to assess safety and tolerability, no significant adverse

events or dose-limiting toxicities were observed in patients treated with ISISMNrx. Although the ISIS-supported study was not designed to test efficacy, improved muscle function was documented in subjects who were given the highest study dose of the drug, according to data presented at the 2013 annual meeting of the American Academy of Neurology, in San Diego. Given the rare nature of SMA— approximately 30,000 total patients in the United States, Europe and Japan are

Mipomersen isn’t the only HoFH drug approval that hopefully will boost awareness of the disorder. In December 2012, Aegerion Pharmaceuticals’ Juxtapid (lomitapide) got the nod, also receiving orphan drug status. Industry analysts say there are several potentially important distinguishing features between the two drugs. Price is one potentially telling differentiator. Genzyme has set the price of Kynamro at $176,000 per patient per year, compared with $295,000 per patient per year for Juxtapid. The two products also differ in mode of delivery: Kynamro is given as a once-weekly injection versus Juxtapid, which is an oral agent taken once daily. Whether these differences will have a major impact in how the two drugs are perceived and used by clinicians remains to be seen. “Both Kynamro and Juxtapid are a welcome addition to the treatment of patients with HoFH,” said Matthew K. Ito, PharmD, a professor of pharmacy practice at Oregon State University College of Pharmacy, in Portland. “Statins are only minimally effective in lowering LDL-C in these patients,” noted Dr. Ito, who is the president-elect of the National Lipid Association. “In addition, LDL apheresis is not universally available throughout the country, which makes access difficult for many patients.” —Gina Shaw

affected—ISI-SMNrx may be poised for specialty pharmacy distribution. Several other companies have antisense molecules in development. Sarepta Therapeutics (formerly AVI BioPharma) is developing eteplirsen, a compound to treat Duchenne’s muscular dystrophy. And the ALS Association’s Translational Research Advancing Therapies for ALS (TREAT ALS) program is backing a drug that has been shown in preliminary trials to be a safe and effective therapy for amyotrophic lateral sclerosis. —SPC Staff

Another Successful Year For the McMahon Group

2012

Once a year, the McMahon Group takes time out to recognize the best of an outstanding group of employees. Now into its fifth decade, the company continues to publish best-read medical newspapers and must-view medical websites covering several clinical areas, and also creates medical education platforms for physicians, nurses and pharmacists. All of which proves yet again that a company powered by talented people will necessarily generate success.

Here is a review of the winners of the 2012 employee awards: MANAGEMENT/SUPPORT/IT/FINANCE/PRODUCTION

MANAGEMENT/SUPPORT/IT/FINANCE/PRODUCTION

Each year employees are asked to select two outstanding members representing these diverse departments. The first winner was DIANE LODISE, who is both the director of facilities management, overseeing the facilities owned by the company, and the conventions coordinator, planning the many details of our extensive convention coverage.

The second winner was HYONG KWON, the company’s development manager for IT, for his continuing efforts in improving the company’s digital presence.

MAX GRAPHICS PERSON OF THE YEAR

MOST IMPROVED SALESPERSON OF THE YEAR

BLAKE DENNIS was recognized for her excellence as art director for Anesthesiology News as well as her graphic design of a variety of special projects. Blake is dedicated to creating the most visually appealing projects possible.

BRIAN HIGGINSON, publication director for Gastroenterology & Endoscopy News, was recognized for the increase in that publication’s sales in 2012, which in part led to one of its most profitable years ever. His dedication to his clients’ needs and understanding of their products ensure his continued success in sales.

ASSOCIATE/SENIOR/PROJECTS EDITOR OF THE YEAR

MANAGING EDITOR OF THE YEAR

Editorial director of the special projects division, KATHERINE REIDER was recognized for her contributions as an editor and for providing leadership and direction to the members of the department. Her diplomacy skills and focus on process have helped ensure that projects are developed with the highest level of accuracy and in a timely manner. Katherine also was recognized for her 10 years of service at McMahon.

GEORGE OCHOA was voted editor of the year for his efforts and dedication to McMahon Group through his exemplary writing and editing. His stories appear in every McMahon Group publication and on every website and provide the managing editors with articles that exemplify editorial excellence.

SALES ACHIEVEMENT AWARD

SALESPERSON OF THE YEAR

The publication director for General Surgery News, MICHAEL ENRIGHT, was selected for this award in recognition of his strong commitment to his clients and his innovative thinking to create unique marketing platforms, which included the publication’s first international edition as well as the initiation of a website video arcade.

For an unprecedented seventh year in a row, RICHARD TUORTO earned the salesperson of the year award. Unlike the other awards, which are decided by peer votes, this award is presented to the individual who brings in the most revenue in the calendar year. Richard manages the Anesthesiology News and Pain Medicine News teams as senior group publication director.

THE MCMAHON GROUP PERSON OF THE YEAR

PARTNERS’ AWARD

The top award each year is for the person of the year, which goes to the employee who goes above and beyond the call throughout the year. JEANNIE MOYER, associate director of human resources, received the honor this year. Jeannie oversees personnel and works tirelessly to provide the best possible atmosphere for employees each day. She is integral to helping McMahon Group continue to grow every year.

From time to time, the partner-owners of the company recognize the contributions of those who have had a significant effect on the company’s success through the years. The 2012 award was given to WARD BYRNE, who served as publication director for Anesthesiology News for several years, starting in the early 1990s. He was responsible for the excellent growth of that newspaper, which today dominates the market. Ward eventually left McMahon Group to start what would be an 11-year career working at a medical education company, after which he returned to his true love — teaching. Today, Ward teaches special education in the New Jersey school system.

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