Summer 2013 by McMahon Group

Bridging the gap between the hospital and alternate-site care Volume 2 • Number 3 • Summer 2013 • specialtypharmacycontinuum.com

In This Issue Clinical

URAC executive makes the case for SP accreditation.

Strategies for fixing a fragmented health care system.

Multiple sclerosis: oral and injectable agents square off.

Savings With Biosimilars: A Promise Yet To Pay Off

Advances in multiple myeloma therapies.

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Technology

Tips for ensuring cold-chain product integrity.

Operations & Mgmt

Home infusion can take the strain off busy EDs.

Policy

Where are we on the biosimilars approval pathway?

10 Elements payors should look for in a specialty pharmacy

The View From The Payor Side Las Vegas—How are health plans approaching the growing specialty spend? Burt Zweigenhaft, CEO of OncoMed360 and the moderator of a panel on payor perspectives at this year’s Armada Specialty Pharmacy Summit, put that question to a group of industry experts after leading with a perspective of his own: “Whenever they say it’s not about the money, it’s all about the money.” Costs are definitely a driver for payors, and the changing landscape resulting from health care reform, and particularly the rise of accountable care organizations

Disease State Spotlight

Managing specialty spending:

Orlando, Fla.—National drug spending could be cut by $250 billion between 2014 and 2024 if only 11 biosimilar versions of current best-selling biologics are approved during those 10 years, Express Scripts has forecasted (www.lab.express-scripts.com). The company’s vice president of research and analysis, Sharon Frazee, said her team’s projection is based on a “uberconservative” model and suggested the savings could even be higher. “There are 92 patent expiries coming up,” said Ms. Frazee. “We only included the 11 that we believe are certainly going to have competitor biosimilars come to market.” The analysis, which was presented at the Express Scripts Outcomes Symposium, compared a scenario in which 11 generic versions of current best-selling

biologics (Table, page 22) would be available between 2014 and 2024 with one in which only the branded biologics would be available. In the biologics-only scenario, spending on the 11 drugs was estimated to increase from $33.6 billion in 2014 to $121 billion in 2024. In contrast, if the 11 biosimilars included in the other scenario were to receive FDA approval, spending in 2024 would be $81.3 billion, Express Scripts predicted. The cumulative savings between 2014 and 2024 would be $250 billion if these 11 biosimilars were approved, Express Scripts estimated (Figure, page 22). Although the savings could be higher than the forecast predicts, Molly Burich, MSc, a market analyst not involved in the research, said in an interview that

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see SPENDING, page 24

Accreditation Initiative Gets Mixed Reviews

ommunity pharmacies—including those that provide specialty pharmacy services—will soon face the decision of whether to become accredited by the Center for Pharmacy Practice Accreditation (CPPA), by URAC, or to forgo accreditation, at least for now. Supporters of the new push for accreditation claim it will raise the overall quality of the profession, whereas opponents argue it is duplicative of existing state and federal laws, and overly burdensome in terms of cost, time and effort. This area began to heat up last summer, when both URAC (formerly known as the Utilization Review Accreditation Commission) and CPPA, the most recent entrant into the accreditation arena, held

see BIOSIMILARS, page 22

•

see ACCREDITATION, page 18

The Book Page 2013 Oncology Pharmacy Preparatory Review Course

FDA Watch

ACCP

Denosumab (Xgeva, Amgen) gets new indication

See Page 27.

See page 9.

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

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GAMUNEX® X®-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 (ⱖ5%) with intravenous use of GAMUNEX-C were headache, cough, injection site reaction, nausea, pharyngitis and urticaria. The most common adverse reactions (ⱖ5%) 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 ⱖ5% 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 ⱖ5% 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 • Summer 2013

Q&A

Ask the Expert: Terri Smith Moore of URAC

The Value of Specialty Pharmacy Accreditation T

he increasing number of patients in need of specialty pharmaceutical products has boosted interest in specialty pharmacy accreditation. Terri Smith Moore, PhD, RPh, the senior manager of product development at URAC (formerly the Utilization Review Accreditation Commission), recently discussed her group’s specialty pharmacy accreditation program with Specialty Pharmacy Continuum.

SPC: When did you first launch your program? Dr. Moore: We came out with the first version in 2007. We regularly look at our standards to see if anything needs to be modified. They were reviewed and updated in 2010, and they’re up for review again later this year. SPC: What types of pharmacies are interested in specialty pharmacy accreditation? Dr. Moore: Any organization looking for ways to be recognized for their quality specialty pharmacy services [is interested]. It runs the gamut from single proprietor, independent pharmacies to multi-

chain mega-pharmacies, so that means entities like Walgreens or CVS Caremark as well as the corner pharmacy. Typically, they’re pharmacies with a general, community-based pharmacy practice. SPC: How does the growth of specialty pharmacy affect the outlook for accreditation? Dr. Moore: The first therapeutic categories that fell under specialty pharmacy were in the areas of oncology, rheumatoid arthritis, hemophilia, HIV/AIDS and multiple sclerosis. But now there are more and more transplant patients taking specialty pharmaceuticals. Infertility is another new area that’s evolving.

Any pharmacy that dispenses medications may also want to provide specialty pharmacy products and services. So there’s tremendous potential for the growth of specialty pharmacy accreditation. For example, there was a pharmacy near a hospital with a large number of hemophilia patients. The pharmacist decided to concentrate on these complex therapies, and that prompted him to want to get specialty pharmacy accreditation. SPC: What are the benefits of accreditation? Dr. Moore: Pharmacists as well as payors recognize that accreditation sets the seal of approval in terms of pharmacy organizations. We hopefully can get consumers and patients to also better recognize the value of an accredited pharmacy for their specialty products and services. Payors in particular are becoming more interested, largely because many specialty pharmacy products are expensive and require special distribution and handling. Manufacturers want the integrity and quality of the products maintained. So payors are asking, how do we know which providers to entrust our specialty pharmacy patients with?

Having accreditation assures them of the quality of these pharmacies. SPC: Do you have any new initiatives coming up? Dr. Moore: We’re looking into offering dual applications for similar accreditations. For example, specialty pharmacy and mail service pharmacy have a lot in common so could be offered together. SPC: What elements do you consider during the specialty pharmacy accreditation process? Dr. Moore: We look at infrastructure, management and staff, information technology, customer service, drug utilization management and pharmacy operations: how they handle an order from the time it comes from a prescriber to the processing of an order and the distribution of product. But perhaps the most important [capability] we consider is patient management, including ducation and counseling. It’s one thing that differentiates specialty pharmacy from general pharmacy practice. With specialty pharmaceuticals, the need for patient-centered services is

•

see ASK THE EXPERT, page 26

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HOME INFUSION

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/ Director, r Frank Tagarello, Senior Art Director/Managing MAX Graphics James O’Neill, Senior Systems Manager Dan Radebaugh, Director of Production and Technical Operations

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

Volume 2 • Number 3 • Summer 2013

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SPECIALTY PHARMACY

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HEALTH-SYSTEM PHARMACY

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Specialty Pharmacy Continuum • Summer 2013

CLINICAL

Closing the Gaps in Specialty Care Part 2: Fixing a fragmented health care system San Diego—When 18 providers are involved in the care of a single patient, opportunities for poor communication and coordination are almost inevitable. For Daniel Duffy, the chief business development officer at Biologics, Inc, an integrated oncology services company in Cary, N.C., this situation is laden with gaps in communication and weighs heavily on already anxious patients. Given those practice realities, Mr. Duffy said, “one of our priorities should be to try and create efficiencies in how the care team communicates with the patient.” “The health care system is oftentimes fragmented, and there are large numbers of providers and practitioners who are very specialized and therefore work in silos,” Mr. Duffy told attendees of the first National Association of Specialty Pharmacy’s Inaugural Specialty Pharmacy Conference. “As a result, there is a lack of communication and data integration between them,” he said. Biologics’ patient management experience shows that cancer patients see approximately 18 caregivers in a oneyear course of treatment, and more complex patients see additional providers. In the worst-case scenario, patients in contact with this many providers might reach their communication capacity and decide to avoid all telephone contact with their providers, cautioned Keith McGee, the vice president of business development at US Bioservices. “If everyone jumps in and the patient receives multiple phone calls, they might not know who’s calling and why they are calling,” Mr. McGee said. “Some patients can get very confused and stop picking up the phone.”

Know Who, When and Why According to Mr. McGee, specialty pharmacists can help minimize excessive and redundant communication by identifying which providers are contacting their patients and working with them to ensure each call has a distinct and valuable message. “Knowing who is communicating with the patient, when they are going to engage with the patient and being clear on the talking points are key to creating a seamless experience for the patient,” he said. “And if you find a flag in the information, that should prompt discussion between other stakeholders, communicate it back to the other parties.” David Calabrese, RPh, MPH, the vice president and chief pharmacy officer at Catamaran in Lisle, Ill., also spoke at the meeting and said a complaint he frequently hears from providers is that they are in the dark regarding the care their patients are receiving from other providers. Their concerns range from worries about the possibility that a patient has fallen out of appropriate care altogether, to worries of inappro-

Table. Ways To Enhance Oral Communication With Patients Limit teaching objectives Use simple sentences and plain language Limit to two or three teaching points at a time Give many examples to illustrate teaching points Repeat and summarize Encourage questions

priate or duplicative medication prescribing from another provider. One project Mr. Calabrese is undertaking to improve communication back and forth between providers is a formalized care transitions support program that pays particular attention to what is shared between patients and all providers during the transition from one setting to another (sidebar). “When the patient is entering a care setting, our web-based provider portal can enable the care setting to access a full profile of the patient’s most upto-date prescription history. Then, at discharge, we collect similar information back from the hospital as part of the discharge summary,” he explained. Within one to three days of discharge, he added, they contact the patient, his or her caregiver, or both, and assess whether the patient has filled his or her prescriptions. They also conduct a complete medication review and reconciliation and counsel the patient on appropriate medication use. “From there, automated programming—which is part of our claims adjudication system—tracks patient refill patterns,” Mr. Calabrese explained. “The minute they are more than 48 hours late

Catamaran Program Identifies and Notifies Stakeholders of Risk Factors

he goal of Catamaran’s pilot program is to identify patterns in drug use and medical claims activity as well as patient demographic traits that are associated with a heightened risk for rehospitalization, explained David Calabrese, RPh, MPH, the company’s vice president and chief pharmacy officer. “For example, one thing we’re doing is looking at patients’ drug histories prior to hospitalization to see whether there’s anything in that history, whether it be use of a particular medication or lack of adherence, that might have led to the hospitalization,” he said. Mr. Calabrese noted that a growing number of specialty pharmacies that are adding data warehouses to their infrastructure could do the same type of analyses and expand their care management to deliver “a more holistic set of services. Integrated data warehousing capabilities allow you to combine medical records, pharmacy claims activity, lab data and care management data and then to use those to coordinate patient care and improve provider communication,” Mr. Calabrese explained. Ultimately, if projects like Catamaran’s prove that specialty pharmacies can reduce the risk for rehospitalizations and improve other outcomes through information sharing with other stakeholders, “pharmacy benefits managers and specialty pharmacies will be able to help drive the type of added value that our rapidly evolving health care system is desperately striving toward.” —D.W.

Use participatory learning to enhance long-term memory of the information and to check patient’s comprehension Organize your information and present the most important messages at the beginning and again at the end Be positive and encouraging Create a shame-free environment and offer assistance when needed Use “teach-back” or “show-back” techniques to assess and ensure understanding Adapted from J A Pharm Assoc. 2009;4:e132-e149.

in filling a prescription, we communicate back out to the care manager, provider, patient or caregiver so that appropriate intervention can ensue.” To be sure, choosing to coordinate and monitor what other providers are doing can be politically delicate; as Biologics’ Mr. Duffy told meeting attendees, “we’re not there to direct care but we’re definitely there to support the coordination of the care determined by the treating team.” Ultimately, specialty pharmacies that choose to take on the task of improving what is relayed between providers and patients emphasize that they are working toward the shared goal of all providers: enhancing the experience and the health of the patient. “The patient doesn’t care if the system is complex,” James Hopsicker, RPh, the vice president of pharmacy services at MVP Health Care, in Schenectady, N.Y., said at the meeting. “They just want to know that their needs are going to be met. It’s our job to work together to make sure that we narrow the gaps and make that happen.” —David Wild Mr. Calabrese, Mr. Duffy, Mr. Hopsicker, and Mr. McGee reported no relevant ﬁnancial conﬂicts of interest.

For Part 1 of this series, go to http://goo.gl/8KObS.

Specialty Pharmacy Continuum • Summer 2013

CLINICAL

Immunoglobulins and Obesity: Dosing Considerations Jerry Siegel, PharmD, FASHP

’ve been involved with the development and management of intravenous immunoglobulin (IVIG) therapy for more than 30 years, and questions about the optimal use of IVIG are emailed to me on an almost daily basis. Many of those queries touch on safety issues, such as the review and monitoring of adverse reactions. I want to make this column as relevant as possible, so please send me your questions on IVIG therapy via email to Jerry.siegel.rx@gmail.com (cc: spceditor@mcmahonmed. com), and I will do my best to answer them. Each quarter, we’ll choose the most compelling question or patient case and use it as the basis for my column.

: How do you dose intravenous immunoglobulin in morbidly obese patients? A: For more than 30 years, intravenous immunoglobulin (IVIG) has been used as replacement therapy for patients with primary immunodeficiency.1 More recently, the product has been used for a wide array of autoimmune-mediated diseases and for the treatment of antibody rejection in solid organ transplantation.2,3 IVIG works via several mechanisms of action including the modulation of the Fc receptors of phagocytic cells, complement activation, inhibition of cytokine release, and interaction with B- and T-cell receptors.4

would result in a significant decrease in Australia’s IVIG use, and thus cost.6 This applies in other countries as well,

Clinical Associate Professor The Ohio State University College of Pharmacy Columbus, Ohio

and several other US and international groups have evaluated and made recommendations supporting the use of IBW.

However, if you start with IBW dosing, it is vital that you pay attention to

•

see IVIG DOSING, page 20

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Debate About Dosing IVIG is supplied in lyophilized and liquid dosage forms and is supplied as vials with varying increments. Different manufacturers provide 1-, 2.5-, 3-, 5-, 6-, 10-, 12-, 20-, 25-, and 30-g vials.5 The concentrations of IVIG are usually 5%, 6%, or 10%, depending on the reconstitution or liquid product selected. The dose of IVIG prescribed varies depending on the indication, but the appropriate dosing regimen in obese patients has long been unclear; studies have traditionally excluded this population.2,3 Recently, there has been a national and international debate about the “ideal” way to dose IVIG by weight. The drivers for this controversy have not been evidence-based studies definitively showing that using actual body weight (ABW) for dosing calculations will have a negative effect on outcome; rather, there has been concern among practitioners that the higher doses of immunoglobulin given to morbidly obese patients dosed using ABW may result in a higher risk for adverse events than that observed with dosing based on ideal body weight (IBW). Over the years, IVIG shortages also have influenced decisions about appropriate indications and dosing. There also are cost pressures that may weigh into the decision. A utilization review by the Australian Red Cross evaluated patients treated in that country between 2006 and 2009: 37.2% weighed at least 80 kg, 26% weighed at least 90 kg, and 12.6% weighed at least 100 kg. With 75.8% of the IVIG population being greater than 80 kg, changing to IBW dosing

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Specialty Pharmacy Continuum • Summer 2013

CLINICAL

No Consensus on Crowded MS Drug Field Las Vegas—When the American Academy of Neurology (AAN) published its five “Choosing Wisely” recommendations earlier this year, recommendation No. 4 was the following: “Don’t prescribe interferon-β or glatiramer acetate [Copaxone, Teva] to patients with disability from progressive, nonrelapsing forms of multiple sclerosis [MS].” Several prominent neurologists with expertise in MS criticized the recommendations soon after they were published online in the Feb. 20, 2013 edition of Neurology (doi: 10.1212/ WNL.0b013e31828aab14). The specialists clearly were miffed at the proscription against the two injectable MS drugs, posting multiple comments on the “WriteClick” section of Neurology’s website. “This is an oversimpli-

fied recommendation that we strongly feel needs to be more nuanced,” argued representatives of the AAN’s Multiple Sclerosis Working Group. “Progressive MS patients with superimposed relapses can still benefit from these agents....” As the controversy over the “Choosing Wisely” recommendations continues (sidebar), there is a need for guidance on how the “tried-and-true” injectable medications should be used, as well as how

they stack up against a new generation of oral agents, according to Janet Nguyen, PharmD, BCPS, the vice president of network strategies for ModernHEALTH Specialty Pharmacy. At the recent Armada Specialty Pharmacy Summit, Dr. Nguyen offered some insights into the drug class and how it is affecting cost and other aspects of MS care. Dr. Nguyen began with an overview of the new generation of MS drugs, start-

‘It’s a crowded class, but we still need more options. MS is a very personal and individualized disease.’ —Janet Nguyen, PharmD, BCPS

MS Expert Offers Insights Into ‘Choosing Wisely’ Controversy

obert Lisak, MD, Parker Webber Chair in Neurology at Wayne State University in Detroit and one of the MS Section members who raised concerns about the “Choosing Wisely” recommendations, outlined some of the issues that derailed consensus on this drug class during an interview with Specialty Pharmacy Continuum. “We do have evidence to indicate that [interferon-β and glatiramer acetate] are not particularly effective in a new, untreated patient with secondary or progressive MS, unless they have superimposed relapses or enhancements,” Dr. Lisak said. “But there are no randomized studies in patients who’ve become secondary progressive while already on one of these drugs, to see whether or not they get worse faster if you take them off it. Such a study would be almost impossible to do, but without that study and without more clarity on who we are calling progressive, you can’t say that staying on one of these drugs isn’t slowing progression somewhat in these patients.” Commenting on the three market newcomers, the oral medications are likely to reduce, but not eliminate, the market for the tried-and-true selfinjectables, Dr. Lisak noted. “There are people who are willing to stay with the self-injectables if they’re doing well,” he said. In addition to the short-term adverse-event profile for the newer drugs, he pointed out that the self-injectables also have the advantage of at least a decade or more of additional long-term safety data. “We know that nothing serious has come out about glatiramer acetate since the 1980s, and even longer with the interferons. You can’t say that about these newer drugs, with data going back only 10 years or even less.” Another problem in comparing the self-injectables with the newer oral agents: There actually have been very few headto-head studies. Fingolimod’s relapse rate beat that of a self-injectable formulation of interferon-β1a (Avonex, Biogen Idec) in a direct comparison trial, but dimethyl fumarate, on the other hand, has not yet been directly pitted against other existing MS medications in any major clinical trial. As for the current state of the imbroglio over the “Choosing Wisely” recommendations, it was eventually determined that AAN’s Multiple Sclerosis Working Group that criticized the recommendation had, in fact, not actually seen the text, due to an oversight by AAN staff. The recommendation is now under review; as of mid-June, AAN representatives told Specialty Pharmacy Continuum, a decision had yet to be made on whether or not to revise the guideline. —G.S.

ing with the first oral medication for the disease, fingolimod (Gilenya, Novartis), which entered the market in 2010, and continuing with oral teriflunomide (Aubagio, Genzyme), approved in fall 2012, and oral dimethyl fumarate (Tecfidera, Biogen Idec), approved in March 2013. Prescribers are still weighing the competing benefits and drawbacks of these three market newcomers, she noted. Fingolimod has the best efficacy data, with an annual reduction in relapse rate of 54% in the two-year FREEDOMS study that led to its FDA approval, compared with a generally accepted 49% for dimethyl fumarate (the average of two trials) and 31% for teriflunomide, which is not significantly greater than the established 30% for the old standby self-injectables, she pointed out. “Lots of physicians remain reluctant about fingolimod”—a hesitation that is often due to the cardiac side effects documented in the clinical trials, Dr. Nguyen said. “This drug may end up being used more often in a younger population, where the cardiovascular risks are not so significant.” (Biphasic bradycardia after the first dose of the drug was found in the clinical trial data, and the FDA has recommended that all patients starting fingolimod be monitored with hourly heart rate and blood pressure testing for at least six hours after the first dose. The FDA also recommends that the drug not be used for patients with certain preexisting heart conditions.) Teriflunomide, on the other hand, does not appear to have significant cardiovascular risks; however, it is a pregnancy category X drug, meaning that it may cause significant birth defects, Dr. Nguyen noted. Data presented at the 2012 meeting of the AAN indicated that 10 women who carried pregnancies to term after firsttrimester exposure to the drug had no structural or functional deficits in their newborns. (However, because 21 other women who became pregnant while on teriflunomide chose to terminate their pregnancies, and an additional nine experienced spontaneous miscarriage, these data are inconclusive at best). Teriflunomide continues to carry a boxed warning for women who are pregnant or trying to become pregnant, and a pregnancy registry has been established to monitor outcomes in women who accidentally become pregnant while taking teriflunomide. Given all of this, Dr. Nguyen posits that it will more likely be used in an older population. And there’s no consensus from the neurology community as to what’s best. “We surveyed prominent neurologists from across the country and their opinions differed,” Dr. Nguyen said. Neurologists from one major center said that they were

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‘The oral medications are likely to reduce, but not eliminate, the market for the tried-and-true self-injectables.’ —Robert Lisak, MD sure that oral medications would become first-line therapy and the self-injectables would become dinosaurs. “Another group said no, the self-injectables are the mainstay, we have 20 years’ experience with them and we know they work. And there was a middle group that said self-injectables are important but don’t work for

FDA Watch

Denosumab Approved for Giant Cell Tumor of Bone

n June 13, the FDA approved a new indication for denod sumab (Xgeva, Amgen): treat-ment of adultss and skeletally mature adolescents with giant cell tumor of bone (GCTB), a rare and usually noncancerous disease. Administered by subcutaneous injection, denosumab is indicated only in cases where GCTB is unresectable or where surgical resection is likely to result in severe morbidity, such as losing a limb or joint, according to an FDA press release. Denosumab is the first FDA-approved treatment for GCTB, an Amgen press release stated. A receptor activator of nuclear factor κ-B ligand inhibitor, denosumab is already indicated for preventing skeletal-related events when cancer has spread to the bones. “Today’s approval of Xgeva provides a needed treatment option for patients with GCTB who are not surgical candidates or who would otherwise have to undergo extensive, life-altering surgery,” according to Richard Pazdur, MD, the director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. The FDA approved denosumab, which has orphan product designation, following a priority review. According to Amgen and FDA press releases, the safety and effectiveness of denosumab for GCTB were established in two openlabel trials enrolling patients with GCTB that was recurrent or unresectable, or for which surgery would lead to severe morbidity. Of the 187 patients evaluated, 47 (25%) had an objective response, with an estimated median time to response of three months. Of those patients, 51% (24) had an eight-month duration of response. In three patients, with an average follow-up period of 20 months, disease progression occurred after an objective response. Safety was evaluated in 304 patients who received at least one dose of denosumab for GCTB. The most common adverse events were arthralgia, headache, nausea, fatigue and pain in the back or extremity. The most common serious adverse events were osteonecrosis of the jaw and osteomyelitis. —George Ochoa

everyone. It’s a crowded class, but we still need more options. MS is a very personal and individualized disease.”

Impact on Cost Although questions thus remain regarding the optimal drug regimen for MS, a clearer picture has emerged on the

effect the newer generation of drugs is having on the cost of treating the chronic condition. The spend on all three drugs is predicted to double, or nearly so, by 2017, according to Dr. Nguyen, from $1.2 billion in 2012 to $2.7 billion in 2017 for fingolimod; from an anticipated $389 million in 2016 to $917 million in 2017 for teriflunomide; and from an expected $1.7 billion in 2015 to $2.6 billion by 2017 for dimethyl fumarate. In a study by Adelman et al, researchers quantified the cost burden of MS and found that direct and indirect costs

associated with the disease ranged from $8,528 to $54,244 per patient per year ((J Med Econ 2013;16:639-647). Some 77% of those were direct costs, and the majority of those costs comprised prescriptions. Given the MS marketplace, these figures don’t indicate that any of these medications have been immediate blockbusters, Dr. Nguyen pointed out. “Health plans are being very cautious about these drugs,” she said, “perhaps because they want to see what other data [emerge].” —Gina Shaw

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DISEASE STATE SPOTLIGHT

Advances in Multiple Myeloma Therapies Michelle T. Martin, PharmD, BCPS, BCACP Clinical Pharmacist, Assistant Professor

Rebekah L. Hanson, PharmD, BCPS, BCACP Clinical Liaison Pharmacist, Specialty Pharmacy Services Assistant Professor

Andrew Crawford, PharmD Assistant Director, Ambulatory Care Pharmacy Manager Outpatient Oncology Pharmacy

University of Illinois Hospital and Health Sciences System University of Illinois at Chicago College of Pharmacy Chicago, Illinois

Multiple myeloma (MM), a plasma cell malignancy, is the second most common hematologic cancer. The estimated number of new cases diagnosed in the United States in 2013 is anticipated to be 22,350, and the number of deaths is projected to be 10,710.1 MM occurs more frequently in men, those of African American descent, and the elderly. The median age of diagnosis is approximately 70 years old.1 Previous exposure to radiation and a family history of MM may increase risk. The diagnosis of MM is based on symptoms, laboratory tests, imaging studies, and bone biopsy tests.2 Staging of the disease typically is based on multiple factors, including blood levels of M protein, calcium, hemoglobin, β2 microglobulin (β2M), and albumin, as well as the degree of damage in the bone (Table 1).2 Poor prognosis is asso-

ciated with stage III disease, advanced kidney dysfunction, older age, high levels of serum β2M, and changes in chromosome 13. Survival from time of diagnosis ranges on average from 2 to 5 years, based on historical studies. Various growth factors are elevated in patients with MM and are suspected in the pathogenesis of the disease

Table 1. Staging for MM Stage I

Treatment Options The combination of melphalan and prednisone (MP) was the main treatment for more than 20 years and is still used as primary therapy in combination with a third agent.2,6,7 With MP alone, complete remission is rare, overall survival (OS) is less than 3 years, and

Table 2. Growth Factors in the Pathogenesis of MM International Staging System

Growth Factor

Role in Pathogenesis

Small number of myeloma cells found

Serum β2M <3.5 mg/L and serum albumin level >3.5 g/L

bFGF

Promotes angiogenesis

IGF-1

Secreted by BMSCs and osteoblasts Increases growth, survival, cellular migration, drug resistance

IL-6

Produced by BMSCs and osteoblasts Major role in growth and survival, triggers proliferation of myeloma cells Elevated serum levels associated with poor prognosis

NF-κB

Regulates adhesion molecules in myeloma cells Increases cell survival

RANKL

Increased osteoclast activity

TNF-α

Produced by myeloma cells and BMSCs Increased in MM Increases binding of myeloma cells to BMSCs

VEGF

Produced by BMSCs and myeloma cells Production enhanced by IL-6, TNF-α Triggers growth and migration of myeloma cells Promotes angiogenesis Prevents antigen presentation to immune cells

Moderate number of myeloma cells found Features are not classified as stage I or stage III

III

(MGUS). Patients with MGUS should be observed closely, but typically no treatment is necessary.2 However, MGUS is a pre-myelomatous condition, and approximately 1% of patients with MGUS per year will go on to develop MM.1 When malignant plasma cells accumulate, the growth of a tumor called a plasmacytoma can result. A single tumor is categorized as a solitary plasmacytoma and usually can be treated with radiation or surgery; when serum M protein is detectable at a level of at least 30 g/dL, when abnormal plasma cells encompass 10% or more of the bone marrow, or when both conditions are present, the condition is categorized as MM.7 Patients with asymptomatic MM, also referred to as “smoldering” myeloma, may not require treatment for several years.2,6,7 Patients with symptomatic or active MM generally require therapy consisting of chemotherapy and immunomodulating agents for primary and maintenance therapy, stem cell transplant for those who are candidates, supportive treatments, radiation, and surgery.2,6,8

Durie-Salmon Staging System

All of the following must be present: • Hemoglobin level >10 g/dL • Bone x-rays normal or max 1 area of bone damage • Blood calcium levels <12 mg/dL • Small amount of M protein in blood or urine II

(Table 2).3-5 The interaction of myeloma cells with the normal bone marrow micro-environment plays an important role in their survival, growth, migration, and resistance to drugs. MM plasma cells cause destruction of healthy bone and increased tumor growth, resulting in numerous complications, including end-organ damage. Most patients present with signs and symptoms of one or more of the following complications: bone pain and lesions, bacterial infections, renal insufficiency, hypercalcemia, anemia, blood hyperviscosity, and, less frequently, neurologic symptoms.3 To understand treatment for MM, it is necessary to recognize the physiologic and diagnostic parameters of the disease. Plasma cells are a type of white blood cell that originate in the bone marrow.3 They are largely responsible for the production of antibodies, which play a critical component in immune function. For reasons that are not entirely defined, a single chromosomal DNA mutation can result in the development of a single abnormal plasma cell that survives apoptosis and divides to form additional clones.3,6,7 Instead of producing regular immunoglobulins, these malignant plasma cells begin producing a surplus of monoclonal antibody proteins (M proteins). A high level of M proteins in the blood without detected bone disease is termed monoclonal gammopathy of unknown significance

Large number of myeloma cells found One or more of the following must be present: • Hemoglobin level <8.5 g/dL • Blood calcium levels >12 mg/dL 3+ areas of bone destroyed • Large amount of M protein in blood or urine

β2M, β2 microglobulin Adapted from reference 2.

Neither stage I or III, ie, either: serum β2M level >3.5 and <5.5 mg/L (any albumin) orr serum albumin level <3.5 g/L and β2M <3.5 mg/L Serum β2M >5.5 mg/L

bFGF, basic fibroblast growth factor; BMSC, bone marrow stromal cell; IGF, insulin-like growth factor; IL, interleukin; MM, multiple myeloma; NF-κB, nuclear factor-κB; RANKL, receptor activator of NF-κB ligand; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor Based on references 3-5.

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Table 3. Selected Targeted Therapy for MM Bortezomib (Velcade, Millennium)

Carfilzomib (Kyprolis, Onyx)

Lenalidomide (Revlimid, Celgene)

Pomalidomide (Pomalyst, Celgene)

Thalidomide (Thalomid, Celgene)

Approved indication

Patients who have relapsed after ≥2 prior therapies (bortezomib and immunomodulator therapy)

Patients who have received ≥1 prior therapy; use in combination with dexamethasone

Patients who have received ≥2 prior therapies including lenalidomide and bortezomib and progressed on or within 60 d of last therapy

Newly diagnosed MM; use in combination with dexamethasone

Drug properties

Reversible inhibitor of the chymotrypsinlike activity of 26S proteasome; half-life: 9-15 h

Tetrapeptide epoxyketone 20S proteasome inhibitor, with antiproliferative and proapoptotic activities; half-life: <1 h

Thalidomide analog with immunomodulatory, antiangiogenic, and antineoplastic properties; half-life: 3.5 h

Thalidomide analog with immunomodulatory antineoplastic effect; half-life: 7.5 h

Inhibits angiogenesis, has anti-inflammatory and/or immunomodulatory properties; half-life: 5-7 h

Common AEs

Hypotension, rash, constipation, diarrhea, anorexia, nausea, vomiting, anemia, arthralgia, myalgia, asthenia, dizziness, headache, insomnia, peripheral neuropathy, cough, dyspnea, fever

Peripheral edema, rash, anorexia, constipation, diarrhea, nausea, anemia, neutropenia, thrombocytopenia, asthenia, dizziness, dyspnea, fatigue

Peripheral edema, abdominal pain, constipation, diarrhea, dyspepsia, loss of appetite, nausea, vomiting, weight loss, arthralgia, back pain, cramps, muscle weakness, dizziness, headache, insomnia, tremor, blurred vision, asthenia, dysuria, fatigue, fever; increased risk for DVT and PE, AF, Stevens-Johnson syndrome, angioedema

Peripheral edema, rash, anorexia, constipation, diarrhea, nausea, vomiting, thrombocytopenia, anemia, lymphocytopenia, neutropenia, back pain, headache, cough, dyspnea, upper respiratory tract infection, fatigue, fever

Weight change, edema, dry skin, rash, diarrhea, constipation, indigestion, nausea, leukopenia, asthenia, dyspnea, pneumonia, fatigue, fever, muscle weakness, hypocalcemia, peripheral neuropathy; increased risk for DVT and PE, AF, Stevens-Johnson syndrome, angioedema

Drug interactions

St. John’s wort, phenytoin, phenobarbital, dual CYP3A4 and P-glycoprotein inhibitors, CYP3A4 inhibitors, CYP3A4 inducers

None

Itraconazole, digoxin

P-glycoprotein inhibitors, strong CYP1A2 inhibitors, CYP3A4 inducers, CYP3A4 inhibitors, dual CYP3A4 and P-glycoprotein inducers, dual CYP3A4 and P-glycoprotein inhibitors

Docetaxel, dexamethasone, midazolam, cyclosporine

Contraindications

Hypersensitivity to bortezomib, boron, or mannitol

None, but precautions related to organ systems

Black box warnings: Embryo-fetal toxicity, hematologic toxicity (significant neutropenia and thrombocytopenia), VTE

Black box warnings: Embryo-fetal toxicity, VTE

REMS requirement

Yes

Additional patient counseling points

Maintain adequate fluid intake to avoid dehydration; report new or worsening cardiopulmonary symptoms and dehydration

Maintain adequate fluid intake to avoid dehydration; report symptoms of congestive heart failure, angina, or hepatotoxicity; use contraception during and 4 wk after treatment

Report signs/symptoms of VTE, myelosuppression, or peripheral neuropathy; take drug with water; use contraception and do not donate blood or sperm during and 4 wk after treatment

Take drug at approximately the same time each day without food (≥2 h before or after a meal); use contraception and do not donate blood or sperm during and 4 wk after treatment; do not smoke cigarettes during therapy (may reduce efficacy)

Immediately report signs/symptoms of Stevens-Johnson syndrome/toxic epidermal necrolysis/ thromboembolism; take drug at bedtime at ≥1 h after evening meal; use contraception and do not donate blood or sperm during and 4 wk after treatment; do not drink alcohol while taking drug

Drug

AE, adverse event; AF, atrial fibrillation; CYP, cytochrome P450; DVT, deep vein thrombosis; MM, multiple myeloma; PE; pulmonary embolism; REMS, Risk Evaluation and Mitigation Strategy; VTE, venous thromboembolism Based on references 2 and 11-16.

Look for more Disease State Spotlights in upcoming issues • HIV/AIDS

• Hemophilia/Von Willebrand’s Disease

• Rheumatoid Arthritis

• Inflammatory Bowel Disease/Crohn’s Disease

• Melanoma

• Chronic Lymphocytic Leukemia

Specialty Pharmacy Continuum • Summer 2013

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Table 4. REMS for MM Drug

Lenalidomide

Pomalidomide

Thalidomide

Manufacturer contact information

1-908-673-9000

1-888-423-5436

www.celgene.com

http://www.revlimidrems.com/

http://www.pomalystrems.com/

http://www.thalomidrems.com/

http://www.fda.gov/downloads/Drugs/ DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM222644.pdf

http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM339450.pdf

http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM222649.pdf

Link to medication guide

http://www.fda.gov/downloads/Drugs/ DrugSafety/ucm111335.pdf

http://www.fda.gov/downloads/Drugs/ DrugSafety/UCM340163.pdf

http://www.fda.gov/downloads/Drugs/ DrugSafety/UCM222363.pdf

Access

Restricted to contracted pharmacies (list available at www.celgene/PharmacyNetwork); contracted pharmacies must verify that a valid RevAssist Program authorization number is written on each prescription by calling an automated system to receive a confirmation number; patients and prescribers must enroll in RevAssist program and sign a Patient–Physician Agreement Form

Restricted to contracted pharmacies (list available at www.celgene/PharmacyNetwork); contracted pharmacies must verify that a valid Pomalyst REMS Program authorization number is written on each prescription by calling an automated system to receive a confirmation number; patients and prescribers must enroll in Pomalyst REMS program and sign Patient–Physician Agreement Form

Restricted to pharmacies that are certified in the S.T.E.P.S Program; specially certified pharmacies must verify that all prescriptions have an authorization number; patients must complete and sign a Patient Registration/ Patient–Physician Agreement Form and prescribers must complete and sign a Prescriber Registration application as part of S.T.E.P.S. Program

Monitoring

Pregnancy testing must be conducted for women of childbearing potential

Record keeping

Each Revlimid prescription dispensed including confirmation number received from Celgene Customer Care Center

Link to REMS guide

Prescriptions and authorization numbers

Corresponding completed Pomalyst REMS Education and Counseling checklist

Corresponding completed RevAssist Education and Counseling checklist Dispensing restrictions

28-d supply maximum; authorization numbers valid for prescriptions to be filled within 7 d of last pregnancy test for women of childbearing potential and 30 d for all other patients; there must be 7 d or less remaining on existing prescription; medication guide must be dispensed

28-d supply maximum; telephone prescriptions and automatic refills prohibited; authorization numbers are valid for prescriptions to be filled within 7 d of last pregnancy test for women of childbearing potential and 30 d for all other patients; there must be 7 d or less remaining on existing prescription; medication guide must be dispensed

28-d supply maximum (provided in blister packs) may be dispensed at a time; telephone prescriptions and automatic refills prohibited; authorization numbers are valid for prescriptions to be filled within 7 d of last pregnancy test for women of childbearing potential and 30 d for all other patients; there must be 7 d or less remaining on existing prescription; medication guide must be dispensed

MM, multiple myeloma; REMS, Risk Evaluation and Mitigation Strategy Based on references 22-24.

myelotoxicity is a common complication. In the mid-1980s, the combination of vincristine, doxorubicin, and dexamethasone (VAD) was introduced as an alternative to MP for the treatment of MM.6 OS did not improve, but this regimen was shown to be less myelotoxic than MP. In the 1990s, thalidomide’s role as an anti-myeloma agent was identified.9,10 Thalidomide’s lack of myelosuppression, acceptable side-effect profile, effectiveness as maintenance monotherapy, and ability to improve response, remission, and event-free survival when combined with standard therapy led to its widespread use9,10 and redefined the treatment and ongoing management of MM. Although no cure for MM exists, advances in medicine have decreased the severity of the disease. Newer targeted agents improve survival, decrease pain, and cause fewer complications than older drugs (Table 3).2,11-16 Two such agents— carfilzomib and pomalidomide—were

approved by the FDA since 2012. Carfilzomib, a selective irreversible proteasome inhibitor, induces apoptosis and cell-cycle cessation in myeloma cell lines, including some that are resistant to bortezomib or lenalidomide.17,18 This agent offers another option for treatment to patients with progressing, refractory disease with older treatment. Carfilzomib also has been used in bortezomib-naive patients who have used 2 alternate treatments.19 A clinical trial is currently recruiting patients to compare the combination of melphalan, prednisone, and either carfilzomib or bortezomib in transplant-ineligible, treatment-naive patients.20 Pomalidomide is a thalidomide analog that offers increased antineoplastic activity and decreased adverse events compared with thalidomide, as well as efficacy in patients who failed to respond to lenalidomide, another thalidomide analog.21 Pomalidomide’s use in combination with low-dose dexamethasone significantly improved progression-free survival over high-dose

dexamethasone in patients with relapsed or refractory MM.21 Patients who have failed treatment with lenalidomide and bortezomib now have pomalidomide as an option for treatment. These new agents and other targeted therapies have improved treatment outcomes for many patients with MM. Several other chemotherapy agents are used in the treatment of MM; for a complete list of regimens, refer to the National Comprehensive Cancer Network guidelines.2

Importance of Monitoring Monitoring is another essential component of optimal MM therapy. Patients should have blood and tissue tests and imaging during the initial diagnosis period, and throughout treatment to monitor for toxicity and response. Pregnancy testing and monitoring for venous thromboembolism is a mandatory part of treatment with lenalidomide, pomalidomide, and thalidomide.22-24 See Table 4 for

additional Risk Evaluation and Mitigation Strategy (REMS) details. Table 5 lists basic monitoring for patients; specific monitoring varies based on treatment selection.25

Patient Education The pharmacist plays an important role as part of the interdisciplinary health care team, especially in the education of patients about the side effects of MM treatment. It is important to discuss the complexity of MM with patients as well as the goals, duration, and cost of treatment. Patients also should be educated on the course and progression of MM, and its effects on quality of life. Clinical trials often are recommended for patients, and it is important that the risks and benefits are presented clearly to the patient. In addition to medications for MM, patients will need several other pharmacologic agents for associated issues (Table 6). Additionally, caregivers play an important role in the lives

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CLINICAL

of these patients, and they should be encouraged to learn about the treatment so they can assist the patient.

Conclusion The prognosis for patients with MM continues to improve with new advancements in medicine. Pharmacy plays an important role in the management of MM due to the highly regulated distribution, monitoring parameters, severity of drug interactions, and adverse-event profile for the agents used for its treatment.

in multiple myeloma progression. J Biomed Biotechnol. 2012;2012:157496. 5. Kuehl WM, Bergsagel PL. Molecular pathogenesis of multiple myeloma and its premalignant precursor. J Clin Invest. 2012;122(10):3456-3463. 6. Barlogie B, Shaughnessy J, Tricot G, et al. Treatment of multiple myeloma. Blood. 2004;103(1):20-32. 7.

Chou T. Multiple myeloma: recent progress in diagnosis and treatment. J Clin Exp Hematop. 2012;52(3):149-159.

8. Bruno B, Rotta M, Giaccone L, et al. New drugs for treatment of multiple myeloma. Lancet Oncol. 2004;5(7):430-442.

9. Singhal S, Metha J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341(21):1565-1571. 10. Strasser K, Ludwig H. Thalidomide treatment in multiple myeloma. Blood Rev. 2002;16(4):207-215. 11. Dolloff NG, Talamo G. Targeted therapy of multiple myeloma. Adv Exp Med Biol. 2013;779:197-221. 12. Bortezomib [package insert]. Cambridge, MA: Millennium Pharmaceuticals; 2012. http:// www.velcade.com/files/pdfs/velcade_prescribing_information.pdf. Accessed June 28, 2013. 13. Carfilzomib [package insert]. South San Fran-

cisco, CA: Onyx Pharmaceuticals; 2012. http:// www.kyprolis.com/Content/pdf/PrescribingInformation.pdf. Accessed June 28, 2013. 14. Lenalidomide [package insert]. Summit, NJ: Celgene Corporation; 6/2013. http://www. revlimid.com/pdf/MCL_PI.pdf. f Accessed June 28, 2013. 15. Pomalidomide [package insert]. Summit, NJ: Celgene Corporation; 2013. http://www.pomalyst.com/docs/prescribing_information.pdf. Accessed June 28, 2013. 16. Thalidomide [package insert]. Summit, NJ: Celgene Corporation; 2/2013. http://www. thalomid.com/pdf/Thalomid_PI.pdf. Accessed June 28, 2013.

References 1. American Cancer Society. Multiple myeloma. http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf. Accessed June 23, 2013. 2. National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology. Multiple myeloma. Version 2.2013. http://www. nccn.org/professionals/physician_gls/pdf/ myeloma.pdf. Accessed June 23, 2013.

Unit Do s Bar Cod e, in Pharma g, c Nursing y & Supp Experts ly !

3. Sirohi B, Powles R. Multiple myeloma. Lancet. 2004;363(9412):875-887. 4. Manier S, Sacco A, Leleu X, Ghobrial IM, Roccaro AM. Bone marrow microenvironment

Table 5. Sample Monitoring for MM Management Complete blood counts with differential Complete metabolic panel Urine tests Bone marrow biopsy Bone densitometry Computed tomography Magnetic resonance imaging Positron emission tomography MM, multiple myeloma Based on references 2 and 24.

Table 6. Adjunctive Treatment for MM Patients Bisphosphonates for bone health Pain medication for bone pain Treatment of hypercalcemia

Vaccinations to prevent, and antibiotics to treat infection Anticoagulants (if on lenalidomide or thalidomide) Plasmapheresis for hyperviscosity Fluids to prevent kidney damage MM, multiple myeloma Based on reference 2.

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Specialty Pharmacy Continuum • Summer 2013

CLINICAL

17. Vij R, Siegel DS, Jagannath S, et al. An openlabel, single-arm, phase 2 study of singleagent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib. Br J Haematol. 2012;158(6):739-748. 18. Siegel DS, Martin T T, Wang M, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma.

Blood. 2012;120(14):2817-2825. 19. Vij R, Wang M, Kaufman JL, et al. An openlabel, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012;119(24):5661-5670. 20. ClinicalTrials.gov. Phase 3 study of carfilzomib, melphalan, prednisone vs bortezomib, melphalan, prednisone in newly diagnosed multiple myeloma (CLARION). Identifier

NCT01818752. http://clinicaltrials.gov/show/ NCT01818752. Accessed June 28, 2013. 21. Leleu X, Attal M, Arnulf B, et al. Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: Intergroupe Francophone du Myélome 2009-02. Blood. 2013;121(11):1968-1975. 22. Lenalidomide REMS guide. http://www. revlimidrems.com. Accessed June 28, 2013.

23. Pomalidomide REMS guide. http://www.pomalystrems.com. Accessed June 28, 2013. 24. Thalidomide REMS guide. http://www.thalomidrems.com. Accessed June 28, 2013. 25. National Comprehensive Cancer Network. Multiple myeloma: NCCN guidelines for patients. http://www.nccn.org/patients/ patient_guidelines/myeloma/index.html#/1/. Accessed June 23, 2013.

Figure. UI Health oncology pharmacy services workflow. ETASU, elements to assure safe use; PA, prior authorization; REMS, Risk Evaluation and Mitigation Strategy; UI, University of Illinois

Health-System Pharmacy Approach to Management of MM

reatment regimens for MM and other cancers are intricate and require highly trained health care personnel for proper management. Given the complexity of oncology regimens as well as the need for close patient supervision and follow-up, multidisciplinary teams of health care providers facilitate optimal outcomes. Most health systems take an interdisciplinary team approach to the management of chemotherapy and targeted oncology treatments. At the University of Illinois (UI) Hospital and Health Sciences System, the members of this team consist of oncologists, nurses, medical assistants, clinical oncology pharmacists, and a centrally located outpatient oncology pharmacy comprised of clinical staff pharmacists and pharmacy technicians. The health-system pharmacists, both in clinical and operational roles, are vital in the management of oncology medications and the patients using them (Figure). Pharmacists treating patients with MM must consider the following factors: regimen type (intermittent, continuous, or both), pill burden, drug interactions/ food interactions, side effects, laboratory monitoring, medication administration requirement, and REMS. Some of the clinical oncology pharmacist’s responsibilities include medication consultations, patient drug therapy needs assessments, patient follow-ups and education, and lab monitoring. Clinical oncology pharmacists work in conjunction with the oncologists, the infusion clinic, and the outpatient oncology pharmacy to ensure patients can access the medications they need and use them safely and effectively. The oncology pharmacy provides patient education, refill management, and ongoing support to manage these needs. Additionally, benefits can be complicated and often involve medical benefits, pharmacy benefits, or both. The majority of medications require prior authorizations, which due to the cycling nature of the regimens, may require renewals at varying intervals. Often these medications are expensive and patients may need support obtaining copay or financial assistance. Some of the newer oral anti-myeloma agents have REMS mandates and require training and certifications to be implemented effectively. The UI Health oncology pharmacy assists in coordinating REMS requirements from the patient to the prescriber (Table 4).

As additional new oral anticancer medications become approved, it has become even more important for institutions with cancer services to have an effective outpatient system in place to manage specialty medications via a multidisciplinary collaborative model. Patient follow-up, the ability to access medications, effective REMS and other aspects of safe use management, and communication with prescribers are imperative. Challenges certainly exist for health systems working in the specialty pharmacy arena. Because high copays can eliminate certain medications as options for some patients, medication assistance program services are a priority. Insurance lockouts and restricted networks have a significant effect on patient management. The turnaround time from prescribing to start of therapy as well as communication between health care providers and the patient can be threatened when one or more prescriptions in a regimen must be dispensed outside of the health system. To ensure the integrity and stability of medications, many health systems limit or restrict brown-bagging and white-bagging so access to the medication can be affected or delayed. Additionally, increasing restrictions on product distribution has become a risk for this type of a multidisciplinary collaborative model. Health-system pharmacies offer an ideal setting for REMS with or without elements to assure safe use (ETASU) and other aspects of medication safety management, in part because of their access to the patients’ medical records, ability to coordinate and confirm important pretreatment laboratory values, direct access to the prescribers for quicker intervention for side effects or deviations in labs, and access to compliance histories with the dispensing records. When medications have restricted pharmacy distribution requirements, pharmacies outside of a health system may lack the capabilities just described, and may not be able to manage safe use to the same degree as the integrated pharmacy. Despite these challenges, health systems and other institutions that offer this type of interdisciplinary oncology service are poised to have a significant effect on ongoing outpatient management of chemotherapy and other targeted oncology treatments as the treatment of MM continues to evolve.

Specialty Pharmacy Continuum • Summer 2013

TECHNOLOGY

Temperature Checks Add Safety to Cold Chain Las Vegas—Specialty pharmacies must err on the side of caution and replace rather than ship a refrigerated medication if the entire cold chain is not validated, but new strategies such as temperature indicators take some of the guesswork out of the process and help ensure product integrity, while reducing costs and waste. That’s why Amherst, N.Y.-based RelianceRx Specialty Pharmacy, which shipped nearly 50,000 packages last year, began using temperature indicators in its packages. “If it’s triggered, [the medicine is] done. This tool empowers clinical pharmacists on [use or reship] decisions,” said Jody Miller, MBA, RelianceRx’ co-founder and former CEO, who recently left RelianceRx to become a partner in Monarch Specialty Group, in Chicago. The paper/wax indicators change color outside of a safe temperature zone, and assure confidence in the medication’s safety when unchanged. “The health plan and PBM [pharmacy benefit manager] are happy—they know it’s a good dose. Pharmacists get their data point, and the pharmacy polishes its

brand with patients,” said Mr. Miller. “Without the indicator, physicians might see a regimen failure and not know why. It could lead to another stay in the hospital, or a switch to a more expensive drug,” Bill Bailey, RPh, COO of the PBM Citizens Rx, in Edwardsville, Ill., told Specialty Pharmacy Continuum. “Also, we’re seeing more RFP [request for proposal] questions from vendors about what the PBM does to ensure safe delivery of the medications they mail directly to patients. The temperature indicators show how the specialty pharmacies selected take an extra step.” At a panel discussion that addressed cold chain management strategies for specialty pharmacies during the 2013 Armada Specialty Pharmacy Summit, Mr. Miller said that within five months,

‘You must understand the true capabilities of your pharmacy’s [cold-chain] packaging methodologies. There’s a big difference delivering in upstate New York versus the heat of Texas.’ —Jody Miller, MBA

RelianceRx broke even on a year’s use of paper/wax temperature indicators, which cost approximately $1 each. Estimating that the pharmacy loses an average of $3,000 per reshipment, Mr. Miller determined that the company saved over the first year because medicine “didn’t have to be reshipped simply because we weren’t sure.” Mr. Bailey, who moderated the Armada session, presented initial findings from an ongoing joint research study that is monitoring 6,000 specialty medication shipments per week. The study, which is being conducted by Mr. Bailey and Mr. Miller as well as panelists Gary Hutchinson, the president of the PBM Modality Solutions, and Ron Krawczyk, the managing partner at the consulting firm Blue Fin Group, began in early 2012 and is expected to last into autumn 2013. Key responses from patients so far include: • 54% expressed concern that medicine shipped to them was too warm or too cold. • 96% feel a source that ships with a temperature indicator “shows concern

Specialty drugs requiring refrigeration Specialty drugs requiring no refrigeration

40%

60%

Figure. of all specialty drugs requiring temperature control, 2015 (projected).

for my safety.” • 96% want a temperature indicator in the box with every medication shipment.

•

see COLD CHAIN, page 16

Ensuring Safe Delivery of Specialty Medications Phyllis Lin, PharmD Clinical Staff Pharmacist Wood Street Pharmacy Chicago, Ill.

niversity of Illinois Hospital and Health Sciences System (UI Health) Wood Street Pharmacy began shipments of specialty medications to patients in 2007. Due to the nature and cost of specialty medications, which the pharmacy now ships on a daily basis, several quality control measures have been implemented to ensure that the drugs are maintained at a stable temperature during storage University of Illinois clinical staff and transit. pharmacists Kyle Mork, PharmD, and To maintain medication stability, Phyllis Lin, PharmD, prepare a medication all refrigerators that store medicaorder for temperature-sensitive shipping. tions in the pharmacy are continuously monitored using a monitoring service to ensure that the temperature of the refrigerator is maintained between 36 and 46 F. Any deviations in temperature are sent via text message to UI Health Wood Street Pharmacy administration, so the cause of temperature change can be quickly determined and fixed. Refrigerated medications are individually labeled and packaged with two cold packs in Styrofoam containers that are specially measured to closely fit the medication package size. The average cost of the cold shipping container including cold packs is $6 to $9 per shipment. Upon delivery to the patient, UI Health Wood Street Pharmacy requires patient identification and signature to ensure that medications are not given to the wrong person or left sitting

outside. The delivery service coordinates with UI Health Specialty Pharmacy Services in cases when the recipient cannot be reached, so that medications can be returned to refrigeration if needed. To ensure that specialty medication temperatures are maintained between 36 and 46 F in transit, UI Health Wood Street Pharmacy recently performed several tests using electronic temperature monitors. The tests were done during the summer, when outside temperatures ranged from 85 to 93 F. Temperature monitors were placed in insulated Styrofoam packaging with two cold packs and a demo medication kit and then mailed to UI Health Wood Street Pharmacy employees within a range of seven to 32 miles from the shipping point. Medications were packaged at 3 p.m. the day before being shipped and were due to be received between 8 a.m. and 5 p.m. the next day. During package transit time, the package temperature was monitored and recorded via computer at five-minute intervals. Computer downloads showed that package temperature levels did not fluctuate significantly during this time, staying between the range of 36 and 46 F. Upon receiving their packages, UI Health Wood Street Pharmacy employees completed a survey regarding the temperature outside that day, the time of package receipt and the temperature inside the package. At the completion of these tests, it was determined that UI Health’s cold-chain shipment practices resulted in a safe and stable temperature range. Since the development of a standardized procedure for the shipment of refrigerated specialty medications, no medications have been wasted because of unregulated temperatures. UI Health Wood Street Pharmacy continues to periodically test the temperature of its refrigerated medication package shipments by sending refrigerated packages and temperature monitors to test subjects. Future tests are planned for the winter months to ensure that medication temperatures do not fall below 36 F. The next initiative is to begin testing green shipping containers made of recycled materials that are 100% biodegradable. In addition to being environmentally friendly, these green shipping containers also may offer a cost savings.

Specialty Pharmacy Continuum • Summer 2013

TECHNOLOGY

COLD CHAIN continued from page 15

• 71% would be “very concerned” if their insurer switched their deliveries from a source that ships with a temperature indicator to one that does not. The panelists could not peg a percentage of specialty pharmacies that use temperature indicators, but pointed to a “vast gap” between those that do and those that should—especially, they said, because operators often are unaware of how well the boxes they use perform on cold-chain integrity. “You must know this, independent of manufacturer claims. And you must understand the true capabilities of your pharmacy’s packaging methodolo-

gies,” said Mr. Miller. “There’s a big difference delivering in upstate New York versus the heat of Texas.” Mr. Bailey explained it’s not just the boxes that are used, but also the positions within them of ice packs, baffling and the medications themselves that help determine a package’s ability to maintain cold-chain integrity. “It’s often a matter of tweaking and adding the safety net of an indicator,” he said. A white paper presented by Mr. Hutchinson at the Armada session detailed results of a thermal performance study conducted by Modality Solutions. The paper, The Cold Hard Facts: What You Need to Know About Thermal Shipping Technologies, revealed that “none

‘Without [a temperature] indicator, physicians might see a regimen failure and not know why. It could lead to another stay in the hospital, or a switch to a more expensive drug.’ —Bill Bailey, RPh

of the five tested thermal packaging systems typically used by specialty pharmacies … maintained the specified temperature in the first 24 hours.”

Why the Urgency? “In five years, 50% to 60% of drugs in use will be specialty drugs, and 60% of them will require temperature control

in shipping [Figure]. Manufacturers will decide how to handle these drugs, and if your processes aren’t in place, you may not be able to handle or acquire them,” predicted Mr. Bailey. “Also,” he said, “physicians will direct scripts to specialty pharmacies they know do a good job.” —Al Heller

OPERATIONS & MANAGEMENT

Managing the specialty spend:

A Picture of Emerging Trends Las Vegas—“Traditional approaches” like prior authorizations and step therapy are not providing a total solution to reducing the increasing costs of specialty medicationss, said Avalere Health’s Leigh Anne Bruhn at the 2013 Armada Specialty Pharmacy Conference. “There is a lot of space for innovation in benefit design and utilization management.” In a new report funded by Janssen Biotech and presented at Armada, Avalere described eight key areas of interest related to access to specialty pharmaceuticals identified by survey respondents from national and regional health plans, integrated delivery systems, pharmacy benefit managers, employer coalitions and self-insured employers. These include: 1. Delivery system changes 2. Payment system changes 3. Site-of-care optimization 4. Clinical pathways 5. Medication adherence 6. Innovative contracting arrangements 7. Benefit design and utilization management 8. Medical and pharmacy integration Survey respondents reported that they were engaged in more than 800 individual activities spanning these eight “opportunity areas” to manage specialty drugs, Ms. Bruhn said. Not surprisingly, national health plans were further along the path to implementing strategies in most of these eight areas than were regional plans or integrated delivery systems. For example, all of the eight areas were ranked as at least “emerging” by the vast majority of national health plans, with many of them having wellestablished strategies, particularly in the areas of site-of-care optimization

and medication adherence. “But no one approach is dominating on siteof-care optimization,” Ms. Bruhn observed. Case management and managing access through prior authorizations were the most common activities, but many other strategies, like differential cost-sharing and expanded use of home health services, also were frequently cited.

to be perceived as emerging opportunities (100% of plans in the South h agreed with thiis) than in the Westt and the Northeast. Benefit design and utilization management were more likely to be per-

‘Across the board, provider acceptance was the most common critical success factor cited for all activities—above collaboration with stakeholders, patient acceptance and employer support.’ —Leigh Anne Bruhn On the other hand, a significant percentage of regional plans (40%) ranked site-of-care optimization as a strategy that was not yet present at all for them; the most common emerging strategies were delivery system changes, clinical pathways, benefit design and utilization management. For their part, integrated delivery systems were well along the way in clinical pathways (with 88% ranking this area “established”) and medical and pharmacy integration (70% “established”). The picture changes somewhat by region. In the Midwest and South, payment system changes were more likely

ceived as emerging in the West and Midwest than in the Northeast, where innovative benefit design is more established.

Taking the Next Step Health plans are looking for new solutions beyond prior authorizations and step therapy, said Maria Lopes, MD, formerly of Blue Cross Blue Shield and now the chief medical officer for CDMI, a leading medical and pharmacy benefit management company. “Although there’s a lot of activity in oncology, areas like rheumatoid arthritis, hepatitic C and rare diseases are consuming more

b budget dollars—which means that a smaller number of patients represent more and more of their annual costs,” Dr. Lopes said. “That means that plans want to go beyond ‘right patient, right drug’ to p dettermining if the drug is wo orking for that patient. They wan want clinical pathways that are not just about the drug, but also involve things like a patient functional assessment that can tie back to a more meaningful discussion between the patient and the provider about their response to the drug.” Across the board, among all plans, several areas emerged as “promising”—expandable and likely to succeed. The top three on this list were payor–provider contracts for a center of excellence, episode of care bundled payments (with or without quality measures) and reauthorization to continue drug therapy. And there was one thing on which everyone—all types of plans, as well as employers and pharmacy benefit managers—seemed to agree: Providers hold the key to acceptance of any of these strategies. “Across the board,” Ms. Bruhn said, “provider acceptance was the most common critical success factor cited for all activities—above collaboration with stakeholders, patient acceptance and employer support.” —Gina Shaw

Specialty Pharmacy Continuum • Summer 2013

OPERATIONS & MANAGEMENT

ACCREDITATION continued from page 1

public comment periods on proposals to establish accreditation programs for community pharmacies—from independents, chains and mail-order pharmacies, to outpatient pharmacies associated with health systems and hospitals. More recently, CPPA released consensus-based standards in an attempt to identify pharmacies focused on advancing patient care, safety and quality. Additionally, the group is looking into establishing a set of accreditation standards specifically geared toward specialty pharmacies, according to the group’s executive director, Lynnae Mahaney, BSPharm, MBA, FASHP, who briefly discussed the potential initiative during an interview at the inaugural meeting of the National Association of Specialty Pharmacy (NASP), in San Diego. If CPPA goes ahead with specialty pharmacy accreditation, it will be competing yet again with URAC, which established standards for specialty pharmacy accreditation in 2007. But a URAC executive stressed that the organization is well positioned for staying on top. “Our specialty pharmacy program is robust, and has some similarities with our proposed community pharmacy program,” said Terri Smith Moore, PhD, RPh, the senior manager of product development at URAC. “Interestingly, there are community pharmacies that also provide specialty pharmacy services or are looking to provide them.” Gary Cohen, interim executive director of the Specialty Pharmacy Certification Board, which is developing a Certified Specialty Pharmacist credential for individual practitioners, said he is a proponent of both CPPA and URAC. Mr. Cohen added that he hopes the community pharmacy accreditation programs result in improved quality with lower costs. But he said he has concerns about the voluntary nature of the programs offered. “It will be interesting to see how insurance payors respond,” Mr. Cohen said, adding that in specialty pharmacy, some payors now require accreditation for reimbursement. “What is ‘voluntary’ now, may become mandatory,” he stressed.

Strong Base of Support Ms. Mahaney said members of her organization felt a strong need to establish professional standards for community pharmacy practice that come from within the pharmacy profession. “We have direct access to the professionals who have the best knowledge about how services should be provided—that’s one of our distinguishing factors,” she said. “CPPA’s standards were developed and vetted by the major stakeholders in community pharmacy practice.”

‘We have direct access to the professionals who have the best knowledge about how services should be provided—that’s one of our distinguishing factors.’ —Lynnae Mahaney, BSPharm, MBA

The NCPA also believes the standards are focused on subjective procedures and goals—which leaves members to wonder how compliance with the draft standards will be measured. Yet another concern is that although accreditation is voluntary at this point, it may become a requirement in the future. “Ultimately, NCPA is concerned that (accreditation) would become a carrot for larger entities, but a stick for smaller independent businesses,” the letter stated.

‘A Market Standard’

‘If I’m going to use a pharmacy, I want one that’s meeting a high standard. It’s the same as choosing a cardiologist [or] a hospital ... I would want the one that has passed the test of an external review.’ —Douglas J. Scheckelhoff, MS The importance of instituting a community pharmacy accreditation program reflects the ongoing shift from a dispensing mode of practice to one that is more focused on clinical services and improving patient outcomes, Ms. Mahaney noted. Many pharmacy practices are providing services and programs that CPPA wants to see grow, such as immunization, patient adherence and smoking cessation programs. “What we’re doing matches up with what’s going on in the U.S. health care environment,” she said. “There’s a huge demand and need for the type of costeffective quality care that pharmacists can provide.” To help pharmacies through the accreditation process, Ms. Mahaney said she is willing to speak at state association meetings and talk with group purchasing organizations and community pharmacy alliances. Also, CPPA’s website (www. pharmacypracticeaccredit.org), which went live in July, will provide information on continuous quality improvement tools, best practices and literature references, Ms. Mahaney said. The group also plans to add instructional offerings such as webinars to the website.

URAC an Established Player Dr. Moore explained what she sees as the distinguishing factor between her group and CPPA. “We don’t align with one particular segment. We represent

and work with [a cross-section] of stakeholders because community pharmacies touch a variety of players—consumers to payors,” Dr. Moore said. “Is that an advantage? Let the marketplace decide.” Dr. Moore also pointed to URAC’S experience in the field of health care accreditation. “URAC historically has tremendous experience in the accreditation space, developing standards and operational processes that truly meet the needs of an organization,” she said. “We have a long-standing track record in [this market] with our pharmacy benefit management, specialty pharmacy and mailservice pharmacy accreditations.” Dr. Moore said most of URAC’s proposed standards focus on the patient care services that community pharmacies should provide, such as comprehensive medication management, adherence consultations, immunizations, wellness and health screenings, and chronic disease management. However, some community pharmacy groups, such as the National Community Pharmacists Association (NCPA), oppose CPPA and URAC’s push to establish accreditation programs. The NCPA sent letters outlining its concerns about the programs to both organizations. The group argues that the programs are costly, duplicate current state and federal laws and regulations, and rely largely on documentation of policy and procedures instead of actual practice improvements.

Douglas J. Scheckelhoff, MS, the vice president of the American Society of Health-System Pharmacists (ASHP) Office of Professional Development, agreed that, over time, payors are likely to look to accreditation to verify that the level of services offered meets their standards. “There comes a point where it becomes the market standard to have accreditation status,” Mr. Scheckelhoff said. “If I’m going to use a pharmacy, I want one that’s meeting a high standard. It’s the same as choosing a cardiologist, a hospital or any other medical service. I would want the one that has passed the test of an external review.” In the meantime, CPPA and URAC are moving forward with their accreditation programs. URAC is doing more testing and validation before it releases its community pharmacy standards. “We don’t have a specific launch date, but we’re aggressively ... working on our program,” Dr. Moore said. CPPA’s accreditation program documents are drafted, and Ms. Mahaney said she anticipates opening application for accreditation in July. Both organizations understand that some community pharmacies believe that the accreditation process can be overly taxing and provides no guidance. But Dr. Moore said URAC takes an educational and interactive approach to the process that can be transformational. “Accreditation allows organizations to step back and look at themselves more deeply. It allows them to get recognition from payors or those that look closely at quality,” she said. “We want organizations to benefit from the experience and find the process rewarding and helpful.” Ms. Mahaney agreed that “accreditation can be an administrative burden, and we’re mindful of that by harmonizing our standards with existing quality standards and other accreditation standards such as the ASHP community pharmacy residency. But we firmly believe accreditation is the right thing to do, because our first obligation is to take care of patients.” —Dana Hawkins-Simons Ms. Mahaney, Dr. Moore and Mr. Scheckelhoff declared no relevant ﬁnancial conﬂicts of interest.

Specialty Pharmacy Continuum • Summer 2013

OPERATIONS & MANAGEMENT

Home Infusion Can Take Strain Off EDs Dallas—Home infusion providers seeking to build partnerships with hospitals will be more successful in diverting less-acute patients from the emergency department (ED) to triage offsite if they address ED physicians’ concerns about quality, liability, and patient safety and satisfaction. “There’s not a lot of knowledge among ED physicians about external infusion and home care providers,” said Susan C. Westgate, MSW, who has been analyzing ED operations at Sinai Hospital in Baltimore, where she works as a social worker in the Palliative Care Department. “There is kind of a disconnect between the services that the outpatient world is capable of supplying and what the inpatient world knows about them.” For example, private infusion providers tend to view their work on a case-bycase basis, whereas hospital EDs function more by volume, Ms. Westgate noted during a presentation at the National Home Infusion Association’s 2013 annual conference. And when patient volume increases, the pressure to admit patients also increases. “External infusion providers need to understand this culture and be able to address issues such as volume, surges and speed of treatment as well as ways to reduce admissions and prevent unnecessary readmissions,” she said. Ms. Westgate explained that liability and medical malpractice concerns heavily influence patient care and admission decisions, and, therefore, infusion providers should address those issues with hospital officials up front. “When ED physicians and care management feel confident around this point, they are more likely to endorse alternative clinical interventions,” she noted.

ED Overcrowding According to recent studies, ED visits increased in the United States by about 25% between 1997 and 2007, and 5.6% in 2008 alone ((JAMA 2010;304:664-670; JAMA 2012;307:511-512). According to the American Hospital Association, the number of EDs decreased by 27% from 1990 to 2009 (JAMA ( 2011;305:19781985). A report by Rand Health, released in May, points to the lack of attention that has been paid “to the growing role that EDs play as gateways to inpatient treatment” (http://www.rand.org/pubs/ research_reports/RR280.html). Furthermore, these decisions to admit ED patients are not made consistently according to acute care criteria, noted Ms. Westgate. For example, it is often easier to admit a patient than to determine other ways to triage, especially when knowledge of alterative outpatient interventions is limited. Increasingly, however, hospitals are being pressured to reduce unnecessary readmissions and control costs, especially when patients are uninsured or underinsured, as is often

the case in the ED. By addressing these concerns, infusion providers can demonstrate how triaging patients outside of the ED can reduce overcrowding and even improve the hospital’s bottom line. For example,

hospitals lose revenue when a less-acute patient is using resources that a more acute patient could be using. “So if you have six beds or triage bays filled with patients who could be triaged away from the system to allow more acute patients

to come in with, say, stroke or cardiac arrest, the opportunity cost becomes huge,” Ms. Westgate explained.

An Elusive Goal However, experts noted that although diverting patients from the ED to home services is logical in theory, it can be elusive in practice. “For health care systems, the goal is always to make sure that patients receive appropriate care in the appropriate setting. Although we work hard to educate physicians and other

•

see HOME INFUSION, page 20

Specialty Pharmacy Continuum • Summer 2013

OPERATIONS & MANAGEMENT

HOME INFUSION continued from page 19

referral sources about the various types of care available and resources within the system, this goal can be difficult to achieve,” said Carrie Koenig, an assistant vice president at MedStar Visiting Nurse Association and MedStar Health Infusion, in Elkridge, Md. “It’s rare to get patients referred to home infusion from the emergency department.” MedStar Health operates 10 hospitals and medical centers in Washington, D.C. and suburban Maryland. Not even MedStar’s physicians are familiar with MedStar’s home infusion company. “If someone goes to the ED with an infection and gets prescribed seven days of IV antibiotics, it is more likely that the

‘[Infusion providers] need to think about removing as many barriers as possible from the ED physician or care manager, so they can triage patients away from the ED and to their homes.’ —Susan C. Westgate, MSW physician will admit the patient for at least a few days rather than refer him [or her] directly into home care to receive antibiotic therapy at home,” Ms. Koenig told Specialty Pharmacy Continuum. MedStar is making efforts to educate its physicians and new residents about the availability of home care and infusion services, she said. Because the provision of home infusion services costs far less than ED care, shifting the site of care may benefit hospitals

financially as they become more involved in accountable care, bundled payments or other reform strategies that either fix or cap patient payments. MedStar did not specifically address how this trend may affect its operations going forward, but Ms. Koenig noted that the company has opened a number of urgent care centers and plans to open more during the next two years to reduce ED visits by lessacute patients. But Ms. Westgate noted that in addi-

tion to costing less and reducing hospital readmissions, home infusion services also result in greater patient satisfaction scores in surveys—another important driver as payors increasingly tie reimbursements to quality of care and patient experience. Infusion providers need to think strategically and proactively about what they can do to help EDs, Ms. Westgate added. “Perhaps they can network with payor sources or troubleshoot on the front end, compared with trying to solve problems on the back end,” she said. “They need to think about removing as many barriers as possible from the ED physician or care manager, so they can triage patients away from the ED and to their homes.” —Ted Agres

CLINICAL

IVIG DOSING continued from page 7

clinical outcome and adjust the dose accordingly. At the Cleveland Clinic, dosing and use guidelines for IVIG dosing follow 3 key points. First, the dose of IVIG is calculated based on IBW, not ABW. If the person is 30% to 40% above IBW, then an adjusted body weight will be used, making it important to have the current weight of the patient. Second, the total dose of IVIG should be no more than 2 g/kg (eg, 0.4 g/ kg per day for 3 to 5 days or 1 g/kg per day for 2 days). All doses greater than 1 g/kg must be approved by the Drug Information Center. Third, IVIG should not be dosed any more frequently than every 4 to 6 weeks.7 The policy at Hospital Corporation of America is to base all doses of IVIG (except for in neonates) on patient’s IBW and round to the nearest whole vial size.8 IVIG dosing adjustment also has been evaluated in pregnancy. Canadian investigators studied the pharmacokinetics of IVIG before and during pregnancy in healthy women with poor obstetrical

Table 1. Equations IVIG Dosing Calculation = Adjusted Body Weight = IBW + 0.5 (actual body weight – IBW)

histories and found that with a weightadjusted dosage of IVIG, drug exposure, based on area under the curve calculations, was maintained at the pre-pregnancy level. This team recommended “a weight-adjusted dosage of IVIG during the first and second trimesters.”9 The Department of Health of the United Kingdom clinical guidelines for immunoglobulin use dose-determining weight (DDW) derived from IBW for patients who are morbidly obese.10 The Ohio State University Medical Center uses an approach that takes into account the pharmacokinetic properties of the drug, as well as the product packaging variability to dose IVIG in obese patients. Although IVIG has been shown to have very little distribution into the fat,11 there is an increased volume of distribution (Vd) in patients with obesity due to their increased volume of body fluids. Thus, although in general, IVIG should be dosed using ABW W in patients weighing up to 100 kg with a body mass index (BMI) less than 30 kg/m2, in obese patients, an adjusted body weightt should be used to account for the increased Vd into their extra body fluids, without accounting for the increase in fat. It is recommended that dosing be calculated

BMI = 703 × [(264 lb)/(64 in. × 64 in.)] = 45 kg/m2 Because the patient’s BMI is greater than 30 kg/m2, the IVIG should be dosed using an adjusted body weight. To calculate an adjusted body weight, first calculate the patient’s IBW. IBW = 45.5 × [2.3 × (64 in. – 60 in.)] = 54.7 kg Using that IBW, an adjusted body weight can then be calculated. Adjusted body weight = IBW (54.7 kg) + 0.5 × (actual body weight [120 kg] – IBW [54.7 kg]) = 87.4 kg To calculate the total dose, the dose that the physician ordered (500 mg/kg) is then multiplied by the adjusted body weight (87.4 kg), yielding 43,700 mg, or 43.7 g. For a calculated dose of 43.7 g, the dose should be rounded to 42 g. After dose escalation, the maximum tolerated infusion rate was 2 mg/kg per hour. The infusion rate of a 6% preparation in this case would be calculated as follows: The maximum tolerated infusion rate: (2 mg/kg per minute) × adjusted body weight (87.4 kg) × (1 g/1,000 mg) × 700 mL/42 g (6 g/100 mL in 6% preparation, ie, 700 mL/42 g) × (60 min/1 h) = 174.8 (175) mL per hour.

Table 2. Examples of Dosing of IVIG in Morbidly Obese Patients

BMI = 703 × (weight in pounds/height in inches2) IBW (kg) for males = 50 + [2.3 × (height in inches – 60)]

using an adjusted body weight if a patient has a BMI of 30 kg/m2 or higher, or if the patient’s ABW is more than 20% over his or her IBW. A practical and cost-efficient formula for dosing IVIG in morbidly obese patients using an adjusted body weight can be calculated considering the equations in Table 1.10 The dosing equation in the Table will provide values that account for the extra Vd in obese patients. It is not uncommon for calculated doses to fall between vial sizes. Such doses should be rounded to the nearest whole vial size available to prevent unnecessary waste. Generally, the goal is to target the rounded doses to be within 10% of calculated doses. The dosing equation in Table 1 provides values that easily can be rounded to manufacturer’s vial sizes. Table 2 demonstrates the importance of dosing patients with obesity using an adjusted body weight. In the first example, IVIG is ordered for a 5-ft 4-in., 120-kg woman with primary immunodeficiency. The ordering physician considers giving the patient a dose of 500 mg/ kg. To calculate the dose of drug that the patient will require, her BMI must be calculated first. Patient’s weight = 120 kg × 2.2 = 264 lb Patient’s height = 64 in.

Height, in.

Weight, kg

Dosing BW, kg

BMI

% Body Weight Above IBW

Dose Using Actual BW, g

Dose Using Adjusted BW, g

Patient

Dose

Female 48 y

500 mg/kg

120

87.4

37.5

43.7

If 6-g, use 7 vials (42 g) 6% solution = 700 mL

Male 24 y

1,000 mg/kg

150

116

45.2

150

116

If 20-g, use 6 vials (120 g) 10% solution = 1,200 mL

IBW (kg) for females = 45.5 + [2.3 × (height in inches – 60)] IVIG Adjusted Body Weight = IBW + 0.5 (actual body weight – IBW) IBW, ideal body weight; IVIG, intravenous immunoglobulin

No. Vials Needed For Rounded Adjusted BW Dose

BMI, body mass index; BW, body weight; IBW, ideal body weight

Specialty Pharmacy Continuum • Summer 2013

CLINICAL

The second example also highlights the importance of using an adjusted body weight in the dosing of IVIG in patients who are obese. IVIG is ordered for a 6-ft 2-in., 150-kg male professional football player for the treatment of idiopathic thrombocytopenic purpura. The dosing options vary from 400 mg/kg per day for 5 days to 500 mg/kg per day for 4 days or 1,000 mg/kg per day for 2 days. At the highest dose-per-day option (1,000 mg/kg per day), he would receive 150 g of IVIG per day if the ABW were used. If a 5% solution were used, this would be 3,000 mL of IVIG fluid per day (5 g/100 mL in 5% preparation, ie, 3,000 mL/150 g). The volume and time for infusion may be difficult for the patient to tolerate. To address this problem, a 10% solution is selected for administration. Additionally, because his BMI is greater than 30 kg/m2 and the ABW is more than 20% above the patients’ IBW, the IVIG should be dosed using an adjusted body weight. To calculate an adjusted body weight, first calculate the patient’s IBW. IBW = 50 + [2.3 × (74 in. – 60 in.)] = 82.2 kg Adjusted body weight = 82.2 kg + 0.5 × (150 kg – 82.2 kg) = 116 kg Using adjusted body weight (116 kg), the calculated dose of IVIG is 116 g, and this dose should be rounded to 120 g, allowing for the use of six 20-g vials. At a maximum infusion rate of 2 mg/kg per minute, the rate would be 140 mL per hour, not the 180 mL per hour that would be calculated using actual body weight. The maximum tolerated infusion rate: (2 mg/kg per minute) × adjusted body weight (116 kg) × (1 g/1,000 mg) × 1,200 mL/120 g (10 g/100 mL in 10% preparation, ie, 1,200 mL/120 g) × (60 min/1 h) = 140 mL per hour.

appropriate dose for each patient should be based on the patient demographics and monitoring of clinical outcomes, with dosage adjustments made as needed.

kee, IL: CSL Behring LLC; June 2012.

References

4. Crow A, Lazarus A. The mechanisms of action of intravenous immunoglobulin and polyclonal anti-D immunoglobulin in the amelioration of immune thrombocytopenic purpura: what do we really know? Transfus Med Rev. 2008;22(2):103-116.

1. Boros P, Gondolesi G, Bromberg JS. High dose intravenous immunoglobulin treatment: mechanisms of action. Liver Transpl. 2005;11(12):1469-1480.

5. Siegel J. Intravenous immune globulins: therapeutic, pharmaceutical, administration, and cost considerations. Pharmacy Practice News. 2013;40(1 suppl):1-8.

2. Privigen Immune Globulin Intravenous (Human) 10% Liquid [package insert]. Kankakee, IL: CSL Behring LLC; May 2012.

6. http://www.transfusion.com.au/sites/default/ files/Aston%20Less%20is%20the%20new%20 more.pdf.

3. Immune Globulin Intravenous (Human), Carimune NF, Nanofiltered [package insert]. Kanka-

Standard Cleveland Clinic Foundation clinical practice.

8. IVIG HCA Pharmacy Protocol. www.ashp. org/s_ashp/.../DShort_IVIGHCAPharmacyProtocol.doc. 9. Ensom MH, Stevenson MD. A two-center study on the pharmacokinetics of intravenous immunoglobulin before and during pregnancy in healthy women with poor obstetrical histories. Hum Reprod. 2011;26(9):2283-2288. 10. Wemperis J, Lunn M, Jones A, et al. National Health Service. Clinical guidelines for the use of immunoglobulin use: second edition update. https://www.gov.uk/government/uploads/ system/uploads/attachment_data/file/153238/ dh_131107.pdf.pdf. 11. Koleba T, Ensom MH. Pharmacokinetics of intravenous immunoglobulin: a systematic review. Pharmacotherapy. 2006;26(6);813-827.

Specialty Pharmacy Strategic Business Exchange

The Future of Specialty Pharmacy

Meets at the Alamo

Conclusion IVIG should be dosed using adjusted body weight in obese patients to account for distribution into extra body fluids. Adjusted body weight should be used if a patient has a BMI of 30 kg/m2 or greater or if the patient’s ABW is more than 20% over IBW. At our institution, we recommend using the equation, adjusted body weight = IBW + 0.5 × (ABW – IBW) for ease of calculation. More important than using IBW or ABW for IVIG is the clinical outcome. For replacement therapy, monitoring the IVIG level and the clinical response of prevention of infections is the most important outcome and will vary from patient to patient. For immunomodulation, the ideal dose is not known and IVIG levels are less important than outcome. For ITP, the surrogate marker is the platelet count, whereas for neurologic disorders such as chronic inflammatory demyelinating polyneuropathy, it is the patient’s performance level. Guidelines for determining the most

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Bio-ethical issues in Specialty Pharmacy

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Specialty Pharmacy Continuum • Summer 2013

POLICY

continued from page 1

the figure also could be lower than the analysis suggests. “This report assumes biosimilars will be discounted at 30% relative to their branded competitors, but the thinking over the past few years has led to an erosion of this number down to between 20% and 25%,” said Ms. Burich, the assistant director of Reimbursement Strategy and Health Policy at Xcenda, an AmerisourceBergen Consulting Services company based in Charlotte, N.C.

Biosimilar Landscape Currently Hazy One reason expectations have been curbed is that the FDA may create an onerous biosimilar approval pathway, Ms. Burich said. Manufacturers might be required to submit extensive preapproval data and conduct postmarketing studies. Express Scripts did not take the costs of gathering these data into consideration when constructing its 30% discount rate, Ms. Frazee said. Instead, Express Scripts based the discount assumption on the historical costs of biosimilars, including those available in Europe. Other costs that could bite into any savings include those associated with distributing drugs and providing physician reimbursement assistance and patient support programs. “All of these elements will require a big investment on the part of biosimilar manufacturers and will have a significant impact on the discounts they can offer,” she said. Both Ms. Burich and Ms. Frazee agreed

‘If there was any doubt in my mind that a biosimilar was not as effective as the biologic, I would choose the branded drug.’ —Leonard Zwelling, MD, MBA that the extent to which a biosimilar will be used interchangeably with its branded competitor will mean the difference between small and large savings. Express Scripts assumed that 55% of the 11 biosimilars included in its model will be used interchangeably by payers and physicians by 2020, primarily in patients newly prescribed a biologic treatment. However, the degree of interchangeability could be lower or higher, Ms. Burich said. “Interchangeability is a critical unknown and could have a huge impact on overall savings,” Ms. Burich noted. She said payor behavior will likely follow what the FDA says and that, based on preliminary guidance, the administration will likely be conservative in granting interchangeability, at least initially. “But if biosimilar manufacturers can offer huge discounts, payors may go ahead and mandate that a biosimilar be used in new patients, at least,” she noted.

Physicians Protest Against High Cost of Biologics Hagop Kantarjian, MD, the chairman of the Leukemia Department at the University of Texas MD Anderson Cancer Center in Houston, who, along with 120 chronic

140 Without biosimilars With biosimilars Savings

120

100

Dollars (in millions)

BIOSIMILARS

0 2012

2014

2016

2020

2022

2024

Figure. Projected U.S. spending on 11 specific biologics. Source: Express Scripts

myeloid leukemia (CML) experts, recently published an article protesting against the high cost of biologics ( (Blood 2013 April 25. doi:10.1182/ blood-2013-03-490003), told Specialty Pharmacy Continuum that the FDA needs

Table. Drugs Included in Express Scripts’ 10-Year Biosimilar Savings Model Brand

Generic

Manufacturer

Approval

Patent Expiration

2012 Sales

Avastin

Bevacizumab

Genentech

02/06/2004

06/18/2019

$2,662,842,000

Epogen

Epoetin alfa

Amgen

06/01/1989

05/26/2015

$2,254,245,000

Herceptin

Trastuzumab

Genentech

09/25/1998

08/27/2019

$1,837,693,000

Humira

Adalimumab

AbbVie

12/31/2002

12/31/2016

$4,505,380,000

Intron A

Interferon alfa-2a

Merck

06/04/1986

08/26/2020

$94,009,000

Neulasta

Pegfilgrastim

Amgen

01/31/2002

10/20/2015

$3,472,988,000

Neupogen

Filgrastim

Amgen

02/20/1991

11/10/2013

$1,007,172,000

PegIntron

Peginterferon alfa-2b

Merck

01/19/2001

08/26/2020

$121,828,000

Procrit

Epoetin alfa

Janssen Products

06/01/1989

05/26/2015

$1,127,024,000

Remicade

Infliximab

Janssen Biotech

08/24/1998

09/04/2018

$3,796,422,000

Rituxan

Rituximab

Genentech

11/26/1997

07/05/2015

$3,183,625,000

Sou ce Express Source: p ess Scripts Sc ptts

2018

to implement an accelerated approval process. “Of course safety concerns need to be addressed, but they also shouldn’t delay in getting biosimilars to market,” he said. However, Dr. Kantarjian’s colleague, Leonard Zwelling, MD, MBA, a professor of medicine and pharmacology at MD Anderson, wants biosimilar manufacturers to conduct safety and efficacy studies before their product receives FDA approval. “In malignant diseases, where the first pass is critical, you want to come at the disease with your best guns first,” said Dr. Zwelling, who also has a research interest in health policy and economics. “If there was any doubt in my mind that a biosimilar was not as effective as the biologic, I would choose the branded drug.” Dr. Zwelling admitted that extensive clinical data requirements could discourage manufacturers from developing biosimilars altogether. In that case, he said, “the likelihood that big savings could result from biosimilars is about zero.” —David Wild Drs. Kantarjian and Zwelling and Ms. Burich reported no relevant ﬁnancial conﬂicts of interest.

Specialty Pharmacy Continuum • Summer 2013

POLICY

Biosimilars Face Hurdles; None Expected Soon Las Vegas—“The biosimilars game is a long game, a very long game, indeed.” So write the editors of Nature Biotechnology in the magazine’s April 5 online edition. This assessment neatly sums up the view of what’s coming with biosimilars shared by experts at the 2013 Armada Summit conference. In other words, despite the fact that in early 2012, the FDA established a new approval pathway aimed at getting these follow-on biologics to market, it still could be several years before the first such product becomes available. The obstacles to getting a biosimilar to market are “huge,” said David Galardi, PharmD, the co-founder of the health care consulting firm Apogenics, during a session on the topic at the conference. “Biologics, by definition, are hard to make,” he said. “I can’t just go buy a tablet press and pour powder in there and watch it pour off some machine.” Unlike traditional small-molecule generic drugs, such as the current oral generic drugs, biosimilar versions of large molecule drugs (biologics) will require successful clinical trials to get to FDA approval. “For the standard generic drug application, a 505( j) filing, there’s no trial required,” Dr. Galardi noted. “It’s effectively just a pharmacokinetics one-to-one analysis. But the filing for a biologic is a 301(k), which requires a full efficacy and safety workup, which means a clinical trial.” Developers of the innovator biologics also will have a much bigger advantage over their imitators than is the case with small-molecule generics, Dr. Galardi added. “The litigation process for biosimilars is substantial. Effectively, the ‘bio-sponsor’ must disclose to the innovator their application and their manufacturing process, providing a clear advantage to the innovator company. [The innovator company] also likely will have a lower cost of production and deep roots in the supply

chain for raw materials. Innovators are smart. Expect them to become aggressive in defending their turf.” Another obstacle for biosimilars is that providers initially may be reluctant to switch to these products, more so than is the case with small-molecule generics. “Vigilance to immunogenicity and related adverse events is an important safety concern with biologics,” Dr. Galardi noted. “Say you’ve had Mary on a particular drug and she’s tolerant, and somebody else comes along and says, ‘try anotherr drug that looks similar.’ Mary ggoes to the infusion center and codes. Think that’s possible? Abso olutely. It happens.” When biosimilars ffinally do come to market, they most m likely will be covered under the medical benefit. “They’re large molecules, which with feew exceptions get injected or infused into veins, although some are subcutaneous,” Dr. Galardi said. “In 64% of cases, thaat’s [covered by] the medical benefit. That means that biosimilars will live in the world of ASP [average sales price]] reimbursement, because th he path of least resistance for a Medicare patient with an injjectable drug is Part D, which gives g you more flexibility as

‘Biologics, by definition, are hard to make. I can’t just go buy a tablet press and pour powder in there and watch it pour off some machine.’ —David Galardi, PharmD to who can dispense the drug.” Biosimilars are almost certain to upset the current cost structure of specific biologics. “Supply and demand curves will shift,” Dr. Galardi predicted. “Unlike small-molecule generics, they will face a more complex pricing environment.” For example, inexperienced bio-sponsors may price a

What the FDA Is Saying About the Biosimilar Approval Pathway

n a statement issued to Specialty Pharmacy Continuum’s sister publication Pharmacy Practice News on May 22, a representative from the FDA’s Center for Drug Evaluation and Research said, “the type and amount of data and information that will be sufficient to demonstrate biosimilarity will be determined on a program-specific basis.” The spokesperson noted that the FDA was still reviewing public comments on the subject and has yet to finalize three draft guidances. The agency still needs to decide how to develop future policies on biosimilars, the statement said, including guidance on what clinical pharmacology data it needs from manufacturers to show biosimilarity to a reference product. “We will be able to provide meaningful advice on the scope and extent of necessary animal and human testing after a thorough review of data from structural and functional analyses [for a given product],” the FDA statement said. “Additional animal and clinical studies should be designed to address residual uncertainty about the biosimilarity between the two products to ensure such testing is appropriately targeted.” Draft guidance on the development and approval of biosimilars can be found at http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ Biosimilars/default.htm). —D.W.

product in a way th hat means providers cannot achieve th he necessary cost recovery to support their use. On the other hand, experiencced innovators may make the mistake of contracting more aggressively than neceessary, thus cannibalizing their existingg product’s potential prematurely. “Wh hat if you change yo our contract terms in anticipation of a biosimilar—and then it doesn’t come out?” Dr. Galarrdi said. Theree’s a lot of savings potential from biosimilars, butt it won’t be the same kind of numbers that were realized with h generics because biosimilars are not as closely related to the innovato or drug as traditional generics are to their branded counterparts, accordiing to Mike Ellis, Walgreens’ corporat corporate vice president for specialty pharmacy and infusion. “There’s a reason they’re called biosimilars and not bioexacts,” said Mr. Ellis during another session at Armada. “I talked to a couple of large pharmaceutical companies, and they’re modeling about 40% off [the original product], not 80% like the generics were.” “These aren’t generic substitutes,” agreed Helen Sherman, PharmD, the vice president of clinical pharmacy consulting at Solid Benefit Guidance. “They will be a brand. But, in any case, despite all the press about biosimilars, I haven’t heard of one solid example indicating that there is a biosimilar coming out anytime soon.” —Gina Shaw

Specialty Pharmacy Continuum • Summer 2013

POLICY

SPENDING continued from page 1

(ACOs) and the new health care exchanges, has put increasing pressure on payors to adapt and increase efforts to lower the overall cost of care. Both Mike Ellis, the corporate vice president for specialty and infusion at Walgreens, and Michael White, PharmD, the director of clinical pharmacy for Blue Cross and Blue Shield of Tennessee, agreed that this increasing pressure under the new landscape is keeping them up at night.

Recognizing the potential of ACOs to address costs, specialty pharmacy is even getting involved with them. In January, Walgreens became the first pharmacy to create an ACO. In fact, Walgreens created three, with affiliated physician groups in New Jersey, Texas and Florida. Under the program, Walgreens pharmacists will be integrated into patient care teams, Mr. Ellis said. One factor complicating costs and reimbursement for payors is that the specialty spend often is still managed in silos— retail, pharmacy and medical—said Helen

Sherman, a vice president at Solid Benefit Guidance, which advises both health plans and self-insured groups encompassing about 35 million members. “That’s a little myopic ... and it means that although there’s a lot published on specialty spending, I think it’s impossible to get our arms around the medical side. ... The figures [indicating] that the medical side represents 30% to 40% of specialty, I believe [are] an underestimate.” Site-of-care optimization is another big area of focus for payors trying to reduce spending, but it often leads to

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ballooning costs elsewhere, Ms. Sherman said. “Right now, it’s being done either through voluntary case management or prior authorization using member contract language that includes something about the ‘least costly site of care.’ But ... when you do take the care out of the physician office or the outpatient setting, … [providers may] just make up that revenue in different ways. I haven’t quantified that, but I’m confident it happens.” That’s an example of the law of unintended consequences, said Dr. White. “We decided that we needed to curb the [physician] buy and bill,” he said. “But now [physician] groups are being purchased by hospitals, and we’re being charged double what we were in a [physician’s] office.” To help address cost concerns, Blue Cross and Blue Shield of Tennessee, like many other payors, is taking a hands-on approach to managing what has historically been a hands-off arena: oncology. “These $100,000 orals have to be managed very well,” said Dr. White. One aspect of oncology reimbursement that has payors concerned is that in at least 25 states and the District of Columbia, oral oncology parity laws now require insurers to provide coverage for oral cancer drugs that is equivalent to that for infused drugs. In states without such laws, oral medications are usually covered under the pharmacy benefit, with coinsurance, rather than the medical benefit/copay formula for most infused cancer drugs, which usually translates into substantially higher costs to the patient. But Dr. White suggested that such laws, like site-of-care optimization, could have unintended consequences. “There was active legislation in Tennessee and we went before the legislature … to explain … how much more the state of Tennessee would be paying for its own insurance benefits with these $100,000 oral therapies … they were convinced not to move forward” with the legislation. Although they do not advocate the parity legislation, payors still want to leave decisions up to the physician when both oral and infusible medications are available, according to Dr. White. “We’re not in the business of practicing medicine. If the physician thinks an oral medication is superior and has a patient who is compliant, or who is in a setting where compliance is not a factor, OK. If not, then [the patient] can come into the office and get the infusion, or get it at home.” “Competition, whether within a class or care setting, is good,” said Mr. Ellis. “I spend a lot of time with patient advocacy groups, and I constantly hear, ‘who are you to limit my choices and tell me what the best way is to take this medication?’ Competition is what this economy was built on, and it can lower the cost of care.” —Gina Shaw

Specialty Pharmacy Continuum • Summer 2013

POLICY

Debating the Merits of Copay Offsets Are these assistance programs bad for specialty pharmacy? Las Vegas—The number of drug copayoffset programs has skyrocketed over the past several years, and although patients, doctors and pharma have embraced these programs, some payors and pharmacy benefit managers argue that copay offsets shift costs, may increase overall health care costs and suppress the use of specialty pharmacy. Both of those points of view were well represented during a lively debate at Armada’s 2013 annual meeting, moderated by Zitter Health Insights’ Mark Zitter. As of the end of 2012, about 500 pharmaceutical brands were participating in copay-offset programs, according to a study released in December by New Jersey-based Alliance Life Sciences Consulting Group. That roughly meshes with data from Zitter Health Insights’ Co-Pay Offset Monitor, released in mid-2012, which found that at that time there were 419 copay-offset programs from 440 unique brands (a copay program can be applied to more than one brand, and vice versa). During the session, Mr. Zitter shared a “heat map” of the areas of the country with the highest copay offsets (Figure). “Not surprisingly, the highest copay offsets for a drug like Enbrel [etanercept; Amgen/Pfizer] are found in the regions of the country where they have the most restrictive prior authorizations,” he said. “They’re used more where payor restrictions are greatest.” Patients love these programs, naturally, because they help patients defray the cost of medications. Doctors love them because they help doctors get (and hopefully keep) patients on medications they believe will benefit their patients. And manufacturers love them because they drive brand loyalty. But payors and pharmacy benefit managers (PBMs) are skeptical of these programs, arguing that they just shuffle around costs and push pricey brand-name drugs while driving traffic away from more affordable generics. “Based on current trends, copay coupons will increase prescription drug costs by $32 billion over the next 10 years for employers, unions and other plan sponsors,” argued United Healthcare in a web section aimed at consumers. Mr. Zitter framed the discussion from the patient’s point of view: “Drug costs are 11% of total health care spend, but 43% of a patient’s out-of-pocket cost,” he noted. Depending on a drug’s tier, the average copay for prescription medication ranges from $10.67 for a tier 1 drug, to $29.64 for tier 2, $54.72 for tier 3 and $132 for tier 4. “The median income in the United States is between $45,000 and $50,000,” Mr. Zitter pointed out, adding that because “the

HUMIRA (max benefit: $6,000)

average American takes home less than $1,000 a week, $20 or $30 or $40 out of pocket for a drug for one person matters. People without a lot of money have to pay a lot for these drugs—so why not help them out with these copay offsets?”

Should Patients Carry A Higher Cost Load? However, patients are not paying anywhere near the true cost of these medications, countered Steve Avey, the vice president of specialty pharmacy with PBM MedImpact, arguing that taking most of the burden of paying for prescriptions off the patient has helped to spike costs. Before widespread employer-subsidized health insurance, he said, patients “paid for it all and the average prescription cost was $15. As soon as third parties started paying for drugs, the costs escalated substantially. In the old days, pharma used to do focus groups on ‘How much would you be willing to pay for a drug that did X?’ They don’t do that anymore, because members aren’t paying for the costs of these drugs.” (Thirdparty payment isn’t the only factor here, of course. The increasing cost of drug development—up 7.4% each year according to DiMasi et al in the Journal of Health Economics in 2003—also has contributed significantly to skyrocketing costs.) Mr. Avey also said that most benefits have a maximum out-of-pocket level for medications, usually between $100 and $150 per month, and a maximum annual out-of-pocket ceiling. “At a certain level, you’ll have no copay left whatsoever,” he said. “We’re not insensitive to the fact that these are substantial amounts of money. But the member has to pay some share.” The most controversial copay-offset program, Mr. Zitter noted, has been for Lipitor, which has a direct generic equivalent. “That confuses people,” said Mr. Avey. “We’re trying to get the industry to move to generics in general, if they’re indeed as effective as a brand name, but you confuse people if in this one case you’re trying to get a brand name to be used.” PBMs such as MedImpact “go to a great deal of effort to assess all therapies within a class, analyze evidence and come up with the most appropriate brand-name medication and incentivize people to use [it],” Mr. Avey said. “But when the pharmaceutical companies come out on TV and say, ‘go get this medication, here’s a free trial,’ that disrupts our program of using good evidence to understand where this therapy fits. And then they start on a free trial, get one or two fills, and then all of a sudden they have a copay of $150

•

see COPAY, page 26

ENBREL (max benefit: $8,000)

CIMZIA (max benefit: $11,000)b

PA zone of high payor restriction

Figure. RA copay programs offset majority of copay dollars.a

57.8% + 53.34%-57.87% 38.30%-53.34%

Mean copay program dollar utilization for select RA agents, Q412. Data based on more than 525,000 scripts processed through specialty pharmacies, representing 25% of national specialty pharmacy claims. Data based only on patients who had copays. Copay programs are used more where payor restrictions are greatest. Rich program benefits and poor tier positioning drive higher Cimzia program utilization. Source: Zitter Health Insights’ Co-pay Offset Monitor, 2013

17.12%-38.30% 1%-17.12% (Max annual benefit)

Specialty Pharmacy Continuum • Summer 2013

POLICY

ASK THE EXPERT

10 Elements for Payors To Consider When Selecting a Specialty Pharmacy

continued from page 4

more complex, because the therapies are more complex. There’s a need to make sure patients understand their condition and their therapy. There’s a great emphasis placed on monitoring patient adherence and working closely with patients to reach the optimal goals of therapy.

Avella Specialty Pharmacy recently issued a white paper guiding payors in the selection of a specialty pharmacy. Although the paper includes a section about Avella, it mostly offers general advice, specifying 10 criteria.

SPC: Should specialty pharmacy accreditation be mandated? Dr. Moore: It makes sense that any payor would tend to gravitate to an organization that meets a certain high level of quality. The fact that payors are looking more for accreditation makes each organization decide where it wants to position itself in the marketplace. I would hope that pharmacies could see accreditation as a positive way to demonstrate the high quality of their organizations. Yes, it requires some work and commitment. But at the end of the day, most groups we work with tell us how much they appreciate the process, because it made them better. Our standards provided them with a set of guidelines, a roadmap. Accreditation helps increase the quality of health care.

Access to limited distribution drugs

Specialty pharmacies should have a good relationship with drug manufacturers, so that the pharmacy will be trusted to dispense their drugs.

Specialty medication therapy management

Specialty pharmacies should help patients adhere to drug regimens, using counseling, educational materials, technology (e.g., text messaging), support groups, etc.

Customer service

Patients and payors should be supported with such services as around-the-clock clinical support and thorough knowledge of financial aid programs.

Accreditation

Accreditation by an independent agency, such as URAC or the Pharmacy Compounding Accreditation Board, helps distinguish a specialty pharmacy.

Quality

Specialty pharmacies should have a department to monitor and improve quality.

Waste management

Because specialty pharmacy drugs are expensive, specialty pharmacies should have programs to manage waste (eliminating auto-refills, setting reasonable quantity limits, etc).

Data management/reporting

Specialty pharmacies should be able to capture relevant data and issue reports.

Cost containment

Specialty pharmacies should offer competitive pricing and be able to issue price discounts.

Internal resources

Support services (prior authorization services, billing resources, legal/regulatory oversight, account management, marketing, formulary management, etc) must be available for patients as well as payors, pharmacy benefit managers and physicians.

Corporate history, community standing and distinctions

A specialty pharmacy should stand out because of its rich history (e.g., collaboration on scientific projects).

—Dana Hawkins-Simons

COPAY

of cost savings for the plan—68% was because the patient actually paid a higher price.” A copay card helps “defray the patient’s higher costs” for those who can and are willing to pay. But, he noted that 10% of the patients switched to a lowercost drug and 33% left with no medication. “Although I understand trying to get patients to use lower-cost alternatives, often instead they will walk away with nothing.” Mr. Avey expressed concern that copay-offset programs may be limiting the use of specialty pharmacy. “We

continued from page 25

or $200 and they want the doctor to fill out a prior authorization to get them an exception.” But decision making about prescriptions at a population-based level isn’t always effective for the individual, said Jeff Krol, the senior director for managed markets at Avanir Pharmaceuticals. “[Express Scripts International] did a study showing what happened when copays were raised. There were a lot

want these products filled at a specialty pharmacy, where studies show that adherence is much better,” he said. “But copay assistance programs keep more people in retail settings. There’s less follow-up and adherence is worse, so pharmacy is working against itself.” In fact, United Healthcare has announced that pharmacies in its Specialty Pharmacy Designated Network will no longer redeem manufacturer-sponsored coupons as an offset to member cost-sharing payments for six specialty drugs—the multiple scle-

rosis therapies interferon β-1b (Extavia, Novartis) and fingolimod (Gilenya, Novartis), the transplant agent mycophenolate mofetil (Cellcept Genentech), the tumor necrosis factor inhibitor adalimumab (Humira, AbbVie), and the hepatitis therapies boceprevir (Victrelis, Merck) and peginterferon alfa-2b ( PegIntron, Merck). “I’m not sure we’re ready to do that,” Mr. Avey said, but he noted that “there is enough angst in the industry that you have a large health plan that is.” —Gina Shaw

Read Specialty Pharmacy Continuum Anywhere, Anytime! 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.

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

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

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

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

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

Corporate Spotlight Medi-Dose/EPS see page 21

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.”

•

see CARE GAPS, page 18

The Book Page Remington: An Introduction to Pharmacy

see ADHERENCE, page 17

Programs Cut Specialty Spend Growth in Half

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 SPENDING CUTS, page 8

Special Report

Loyd V. Allen (Editor)

Understanding Key Differences Between Biosimilars and Small Molecule Generics

See page 25.

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