Specialty Pharmacy Continuum Spring 2012 - Digital Edition by McMahon Group

Bridging the gap between the hospital and post-discharge care

In This Issue Ask the Expert

For smaller operators, how to get into a limited drug distribution network.

Volume 1 • Number 2 • Spring 2012

Reports from the PBMI conference

Cost Containment In Specialty Pharmacy

Q&A

Jay Mirtallo, MS, RPh, on why nutrition needs to be a higher priority.

Practice Proﬁle

The Apothecary Shops applies a personal touch to disease management.

Operations & Mgmt

New study underscores savings potential of alternate-site infusions.

Clinical

Anti-EGFRs linked to increased risk for thromboembolic events.

Disease State Spotlight

UIC Specialty Pharmacy’s primer on managing hepatitis C patients.

Excelera Eyes Market Growth For Hospitals

everal health systems have made the foray into the specialty pharmacy market. But with their limited scale and lack of national exposure, it is difficult for them to convince manufacturers and insurers that they can supply medications and patient management programs at a reduced cost, and also deliver the utilization and outcomes data that Pharma needs for research and marketing. Now some health systems are tackling the size challenge. A group led by Fairview Health System in Minnesota and Henry Ford Health System in Michigan has established a national network of hospital pharmacies called ExceleraRx, LLC

•

Scottsdale, Ariz.—Specialty pharmacy medications represent a significant source of pharmacy costs for most employers trying to keep their pharmacy benefits in check. Although they make up fewer than 20% of overall prescriptions today, according to Medco Health Solutions’ 2011 trend report, specialty drug spending saw a 22% increase in its total market share between 2008 and 2010 and further growth is predicted for the coming decade. The nonprofit accrediting body URAC has predicted that specialty drugs will make up the majority of new drug approvals in coming years and will account for approximately 40% of a health plan’s drug spending by 2020. With numbers like these, it’s little wonder that specialty pharmacies are emphasizing cost containment initiatives. Such initiatives were key topics in many of the presentations at the Pharmacy Benefit Management Institute’s 2012 Drug Benefit Conference in February. For example, Walgreens has a number of cost containment strategies for its specialty pharmacy program, such as compliance management, divided dispensing and site of care optimization (related article, page 11). Aggressive management of patient compliance/adherence is one such initiative, Michael Einodshofer, director of utilization management for Walgreens Specialty Pharmacy told Specialty Pharmacy Continuum. In addition to influencing patient outcomes (Table, page 11), compliance can have a huge affect on cost. Mr. Einodshofer noted that Walgreens has preliminary results showing that a compliant

•

see CONTAINMENT, page 10

Educational Review Medication Errors: A Year in Review by ISMP See specialtypharmacy continuum.com

see EXCELERA, page 8

Breadth of problem is ‘scary’

Do MTX Drug Interactions Fall Below Radar?

dangerous interaction between proton pump inhibitors (PPIs) and methotrexate that prompted the FDA to issue a warning late last year represents just the tip of the iceberg of potentially serious interactions that can occur when common medications are given concomitantly with methotrexate. “It’s pretty scary how many of these interactions there are,” said Ali McBride, PharmD, clinical pharmacy specialist at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital in St. Louis.

•

see INTERACTIONS, page 17

The Book Page Fundamentals of Pharmacognosy and Phytotherapy, Second Edition Michael Heinrich See page 27.

The PROOF is everywhere you look GAMUNEX- C has proven efﬁcacy and patient outcomes in CIDP, PI, and ITP*1

Important Safety Information for GAMUNEX-C 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 pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. 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 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). *CIDP=Chronic inflammatory demyelinating polyneuropathy; PI=Primary immunodeficiency; ITP=Idiopathic thrombocytopenic purpura. Reference: 1. Data on file, Grifols. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see adjacent page for brief summary of GAMUNEX- C full Prescribing Information.

To get GAMUNEX-C call 1-888-MY GAMUNEX (694-2686) USA Customer Service: 1-800-243-4153 www.gamunex-c.com

GAMUNEX®-C

Immune Globulin Injection (Human) 10% Caprylate/Chromatography Puriﬁed

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

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

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

• ITP – The most common adverse reactions during clinical trials (reported in 5% of subjects) were headache, vomiting, fever, -------------------------INDICATIONS AND USAGE------------------------nausea, back pain and rash. GAMUNEX-C is an immune globulin injection (human) 10% liquid • CIDP – The most common adverse reactions during clinical indicated for treatment of: trials (reported in 5% of subjects) were headache, fever, chills, hypertension, rash, nausea and asthenia. • Primary Humoral Immunodeﬁciency (PI) • Idiopathic Thrombocytopenic Purpura (ITP) • Chronic Inﬂammatory Demyelinating Polyneuropathy (CIDP)

To report SUSPECTED ADVERSE REACTIONS, contact Talecris Biotherapeutics, Inc. at 1-800-520-2807 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

----------------------------CONTRAINDICATIONS-------------------------------------------------------DRUG INTERACTIONS---------------------------• Anaphylactic or severe systemic reactions to human • The passive transfer of antibodies may transiently interfere with immunoglobulin the response to live viral vaccines, such as measles, mumps • IgA deﬁcient patients with antibodies against IgA and a history and rubella. Passive transfer of antibodies may confound of hypersensitivity serologic testing. ---------------------WARNINGS AND PRECAUTIONS--------------------• IgA deﬁcient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions. Have epinephrine available immediately to treat any acute severe hypersensitivity reactions. • Monitor renal function, including blood urea nitrogen, serum creatinine, and urine output in patients at risk of developing acute renal failure. • GAMUNEX-C is not approved for subcutaneous use in ITP patients. Due to a potential risk of hematoma formation, do not administer GAMUNEX-C subcutaneously in patients with ITP. • Hyperproteinemia, with resultant changes in serum viscosity and electrolyte imbalances may occur in patients receiving IGIV therapy.

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

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

08939771/08939782-BS Revised: October 2010

Specialty Pharmacy Continuum • Spring 2012

IN BRIEF

Mergers in the News Divisive Express Scripts Medco merger proceeds; Walgreens seeks to acquire some of BioScrip

fter an eight-month investigation, in a 3-to-1 vote, the Federal Trade Commission (FTC) voted to close its investigation of the Express Scripts acquisition of pharmacy benefit manager (PBM) Medco Health Solutions, allowing it to proceed. In its statement, the FTC majority explained that their investigation “revealed a competitive market for PBM services characterized by numerous, vigorous competitors who are expanding and winning business from traditional market leaders. The acquisition of Medco by Express Scripts will likely not change these dynamics: The merging parties are not particularly close competitors, the market today is not conducive to coordinated interaction, and there is little risk of the merged company exercising monopoly power.” However, in a dissenting opinion, Commissioner Julie Brill expressed her concern that “this $29 billion merger—between two of the largest three pharmacy benefit management providers—is a game-changer. I have reason to believe that this merger is, in fact, a merger to duopoly with few efficiencies in a market with high entry barriers—something no court has ever approved.”

Ms. Brill has asked the FTC to retrospectively study the effects of the merger after three years. In the meantime, in late March, pharmacy trade groups brought forth a suit challenging the merger and seeking to undo it. In turn, Express Scripts has asked the suit to be dismissed. On April 10, a U.S. District Court heard arguments from both sides. As of press time, the judge’s ruling on the case was still pending. The merger creates a huge PBM that is estimated to control one-fourth of the prescriptions in the United States, according to Atlantic Information Services (AIS). The next largest competitor, CVS Caremark, has approximately half the market share of the new behemoth (12.74%), according to AIS. In a separate deal, Walgreens, the PBM arm of which has a 1.45% market share, seeks to buy BioScrip’s 30 specialty pharmacies in 16 states, as well as its specialty and mail service pharmacy businesses. Walgreens will reach an additional 500,000 HIV, oncology and transplant medication patients if the deal closes in April 2012 as expected. The purchase, said Walgreens president and CEO Greg Wasson, will allow the chain’s “core drugstore business ... [to] provide specialty pharmacy

Ask the Expert

solutions” to its patients. These businesses will add to the estimated $6 billion in annual sales Walgreens generates from 11 specialty pharmacies it already operates, according to Deborah Weinswig, from Citi Investment Research. She noted for comparison that CVS Caremark operates 44 specialty pharmacies that produce $11.7 billion in annual sales. The chain’s agreement to buy portions of BioScrip makes sense to pharmacy industry consultant Bruce Kneeland of Royersford, Pa. “Walgreens, like all of the major retail operators, continues to look for the next engine that will drive it forward,” he told Specialty Pharmacy Continuum. “No question the promise of specialty pharmacy is too big to ignore. With Walgreens’ success in infusion, and with its announced intention to be aggressive in building its own PBM, this is a logical avenue for them to pursue.” —Al Heller, Sarah Tilyou

some of the larger manufacturers who have set up limited distribution networks, so that we can get a piece of that business?

: You should definitely pursue these opportunities. In fact, we recently were in the same exact position and were able to convince a very large manufacturer that we could in fact meet all of its requirements as a select distributor for its orphandrug medication. Once we began to participate, we absolutely fulfilled all of those criteria and it has been a major boost to our bottom line. Just be sure you are not overpromising: Take a very careful look at exactly what is expected of you in the relevant contracts. You sometimes get only one opportunity to show that you can play in the big leagues, and if you come through, it could well be a game-changer for your company. But if you falter, that is hard to overcome.

Randy Fasnacht, RPh, director of pharmacy, Advanced Infusion Services, Akron, Ohio

: If we have very skilled clinicians and database managers on staff who can meet the typical criteria set for specialty pharmacy distributors—e.g., patient and physician registries, outcomes tracking, reporting requirements, etc., is it worth pitching our capabilities to

EDITORIAL BOARD

ART/PRODUCTION STAFF Michele McMahon Velle, MAX Graphics/Creative Director

HOME INFUSION

Frank Tagarello, Senior Art Director/Managing Director, MAX Graphics

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

James O’Neill, Senior Systems Manager Dan Radebaugh, Director of Production and Technical Operations

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

Marty Barbieri, Production Manager

Volume 1 • Number 2 • Spring 2012

Brandy Wilson, Circulation Coordinator

McMAHON PUBLISHING

SPECIALTY PHARMACY

Raymond E. McMahon, Publisher and CEO, Managing Partner

Cindy Kunzendorf, RPh, MBA General Manager Accredo/CCS Locations Elmhurst, IL N. Lois Adams, RPh, MBA Chairman, President and CEO Freedom Pharmacy Orlando, FL Stephanie Holliday, PharmD Clinical Pharmacy Specialist Prosperity Specialty Pharmacy Falls Church, PA

Randy Falkenrath Senior Vice President CVS Caremark

smtilyou@mcmahonmed.com

Van Velle, President, Partner

Kevin Horty, Don Pizzi, Adam Marcus, Cynthia Gordon, Kate O’Rourke, Contributing Editors

Matthew McMahon, General Manager, Partner

HEALTH-SYSTEM PHARMACY

James Prudden, Group Editorial Director

Ernest R. Anderson Jr, MS, RPh System Vice President of Pharmacy Steward Health Care System Boston, MA

Robin B. Weisberg, Manager, Editorial Services

REIMBURSEMENT

David Kaplan, Group Publication Director dkaplan@mcmahonmed.com

Bonnie Kirschenbaum, MS Breckenridge, CO

Lauren Smith, Michael McMahon, Michele McMahon Velle, Rosanne C. McMahon, Partners

Elizabeth Zhong, Associate Copy Chief

MCMAHON PUBLISHING MCMAHONMED.COM

SALES

Sales, Production and Editorial Offices: 545 West 45th Street, 8th Floor, New York, NY 10036. Telephone: (212) 957-5300.

Matt Spoto, Account Manager mspoto@mcmahonmed.com

Michael Sicilian President, Managed Health Care Associates, Inc. Florham Park, NJ

David Bronstein, Editorial Director davidb@mcmahonmed.com Sarah Tilyou, Senior Editor

Alina Dasgupta, Classified Advertising adasgupta@mcmahonmed.com

Copyright © 2012 McMahon Publishing, New York, NY 10036. All rights reserved. Specialty Pharmacy Continuum (ISSN 0886-988x) is published quarterly by McMahon Publishing. Periodicals postage paid at New York, NY, and at additional mailing offices. POSTMASTER: Send address changes to Pharmacy Practice News, Circulation Dept., 545 W. 45th St., 8th Floor, New York, NY 10036.

WANT TO SUBSCRIBE? CHANGE YOUR ADDRESS? HERE’S HOW

your address change directly with Specialty Pharmacy News, Circulation Dept., 545 W. 45th St., 8th Floor, New York, NY 10036. You can also fax your request to (212) 977-3645, or send it via email, circulation@mcmahonmed. com. If you are not a hospital pharmacist but would like to receive Specialty Pharmacy News, please send a check for $70.00 (U.S.) or $90.00 (outside U.S.) for a year’s

subscription payable to Specialty Pharmacy News to McMahon Publishing, 545 West 45th St., 8th Floor, New York, NY 10036. Please allow 8 to 12 weeks for delivery of the first issue. Individual issues are $7.00 (U.S.) or $10.00 (outside U.S.). McMahon Publishing is a 39-year-old, first-generation, family-owned publishing company dedicated to providing

medical professionals with essential, up-to-date news. As the second largest publisher of medical newspapers, McMahon produces Anesthesiology News, Clinical Oncology News, Gastroenterology & Endoscopy News, General Surgery News, Infectious Disease Special Edition, Pain Medicine News, Pharmacy Practice News and Rheumatology Practice News.

EDITORIAL STAFF

Selected U.S. hospital pharmacists and healthcare personnel receive Specialty Pharmacy News free of charge. If you are a hospital pharmacist and do not receive the publication, you must add your professional address or make

A family-owned medical publishing and medical education company. McMahon publishes seven clinical newspapers and several annual or semiannual Special Editions.

David Nathanson, Account Manager dnathanson@mcmahonmed.com

Specialty Pharmacy Continuum • Spring 2012

Q & A

Making Nutrition a Higher Priority Malnutrition can have a tremendous influence on health care outcomes for patients with many different disease states. Jay Mirtallo, MS, RPh, BCNSP, FASHP, director of the MS in Health-System Pharmacy at The Ohio State University College of Pharmacy, in Columbus, discusses some of the implications of malnutrition and what specialty pharmacists and other health care providers can do to improve nutritional care. Q: How common is malnutrition among hospitalized and home care patients? ( A: A classic article by Butterworth (Nutr Today 1974;9:4-8) demonstrated what he called the skeleton in the closet—that more than 50% of patients on medical wards had some form of malnutrition. In subsequent surveys and evaluations conducted in hospitals, nursing homes and home care settings, we find the same percentage of patients with malnutrition as Butterworth identified more than 30 years ago. When we interview people on our medical staff, they say nutrition is very important, but they admit they have been poorly trained to deal with it. It’s often under their radar. Nutrition often is overlooked, and if you don’t look for it, you won’t even know it’s there. Q: What are some of the most concerning implications of malnutrition in these environments? A: In most cases, the consequences of malnutrition are somewhat similar to those of the underlying disease. But without recognizing that, clinicians often don’t know if malnutrition is contributing to the disease process and they don’t have a sense of a patient’s ability to recover once they leave the hospital. Patients with malnutrition just don’t fare as well as well-nourished patients and they have a poorer prognosis. This adds to overall health care costs.

needed follow-up assessments often are not done. A couple of weeks down the road, that patient can suffer from inadequate nutrition. Q: Are clinicians generally becoming more cognizant and proactive regarding malnutrition? A: We know that clinicians, in whatever specialty, don’t advance or improve their

probably going to be significantly different when they move to a floor, and different when they move to rehabilitation or an extended-care facility, and when they return home. But what often happens is that there’s no re-evaluation at those transition points when nutritional requirements change. That’s a big problem. The formula that’s appropriate for the ICU is not appropriate at home. Individuals receiving nutritional

Q: What can be done to make nutrition a higher priority?

‘My challenge to home-care specialists is this:

A: I have tried to emphasize, especially in specialty pharmacy, that clinicians need to learn some nutrition-related skills. You don’t have to be a dietitian, but you have to realize that malnutrition is common in any patient population—cardiac patients, diabetic patients, the critically ill and even the general patient population. Any clinician who consults with patients should pay attention to nutrition and make sure the patient is well nourished. They should notice things such as a patient who hasn’t eaten in three or four days. In a hospital setting, nutrition staff often conducts nutrition assessments when a patient enters the hospital, and then every seven days. But when a patient moves within the hospital and transitions out of the hospital,

Do you feel you have enough knowledge to be able to avoid a significant [adverse] event?’ skills or knowledge with regard to nutrition once they finish their training programs unless they have a special interest in it. For instance, clinicians trained in the 1980s will continue to dose calories the same way they did during training, so eventually they will nutritionally overdose most patients. This is something specialty pharmacists can look for. One of the more problematic areas is during patient transitions within components of the health system. We don’t do well during transitions of care. If a patient has a nutrition care plan set up in the ICU, the dosing they need is

supplements need to be reassessed periodically for what they’re receiving and how they’re responding to therapy, but many such patients don’t get reassessed. One risk, for example, is that home care patients gain too much weight because they receive too high a caloric dose. Q: What are the pros and cons of starting a patient on parenteral nutrition (PN) at home? A: The pros are that these patients stay at home and out of the institutional health care system, and that a small group of clinicians is establishing care and seeing

these patients. In some cases, that might work out fine. However, my bias is that it is not a best practice, because patients who receive inadequate nutrition are at high risk for refeeding syndrome, which can cause lethal complications, including cardiopulmonary arrest. During the first 24 to 72 hours of any type of supplemental feeding, there’s a risk for refeeding syndrome. If that patient is at home, you don’t have the ability to monitor his or her condition or response to therapy, or deal with an acute event. That’s a significant negative for starting PN at home. My challenge to home care specialists is this: Do you feel you have enough knowledge to be able to avoid a significant [adverse] event? Do you understand the nuances of refeeding syndrome? I’ve spent more than 30 years in this field and know the risk factors for refeeding syndrome, but I am still surprised that some patients I wouldn’t have predicted get it. Out of thousands of patients, refeeding syndrome might occur in only two or three. If it occurs in the hospital, you can respond to it quickly and the consequences won’t be as severe. If it happens at home, the patient can easily wind up in the emergency room or ICU, or could die because they can’t be treated quickly enough. Q: How have you adjusted to the shortages of nutritional products that have occurred over the past couple of years? A: There are 19 individual components that go into PN, and all but one of them have been in shortage—sometimes prolonged shortage—at some point over the past two years. The most critical shortages now are of electrolytes. To accommodate shortages, especially for patients at home, we have to use alternatives, but that can lead to problems: The patient has gotten used to a routine; now they’re out of that routine and using a product they’re not familiar with, so the potential for error is significant. To stretch or conserve products that are in short supply, we sometimes have to give patients half of their dose, with the idea that some is better than none. But eventually, that will lead to nutritional deficiencies, creating a disease in itself. We’ve focused most of our efforts on educating clinicians about providing adequate levels of electrolytes, how to deal with alternatives, and what to look for to identify deficiency symptoms. If patients don’t receive a normal dose, eventually a deficiency will occur, but we can’t predict when or to what extent. —Reported by Steve Frandzel Mr. Mirtallo reported that he is a consultant for B. Braun.

Specialty Pharmacy Continuum • Spring 2012

PRACTICE PROFILE

The Apothecary Shops: A Personal Touch Unlike specialty pharmacies owned by pharmacy benefits managers (PBMs) with vast call centers, The Apothecary Shops (TAS) use clinical and sales teams that apply a personal touch in disease management. The strategy has helped the company build trust with hospitals, physicians and their patients—and achieve impressive gains in market share. A 30-person field sales staff helps the Phoenix-based operator stay in close contact with clinical teams at major academic teaching hospitals such as Duke, Vanderbilt, Stanford, Cleveland Clinic and the University of California, Los Angeles. Indeed, closeness with physicians has helped drive TAS’s rapid growth—revenues increased to $330 million in 2011 from $210 million in 2010, according to the company. “Relationships with physicians are key to the continuum of care,” said president Keith L. Cook, RPh. “The sales team adds to our clinical care coordinators and pharmacists as important points of contact who help ensure providers and their

apy infusion to more oral anticancer drugs taken at home over the past few years has created opportunities for the company to gain their foothold in oncology. The 2011 launches of the oral drugs tilaprevir (Incivek, Vertex) and boceprevir (Victrelis, Merck) created similar opportunities in managing outpatients with chronic hepatitis C. In the case of HIV and organ transplant patients, the inroads made by TAS are understandable, Mr. Cook said. “Hospitals typically lack the facilities to manage [these] outpatients, so they seek a specialty pharmacy to help improve outcomes and prevent rehospitalizations,” he explained.

How the Process Works

For small and rural hospitals, specialty pharmacy is ‘their assurance a patient is not going to fall through the cracks when discharged; that everything you’ve done with the patient in the hospital is continued when they leave the hospital.’ —Keith L. Cook, RPh

Medication Adherence Tool

he wholesale division of The Apothecary Shops (TAS) recently piloted a program with Novartis and Vitality to help boost drug compliance among patients diagnosed with chronic myeloid leukemia and malignant stromal tumors. Vitality markets GlowCaps, an electronic pill-bottle top that automatically alerts patients at their dosage time via a flashing light and an audible alert. If patients don’t open the bottle and (presumably) take their medication within one hour of the alerts, the GlowCap chimes a reminder for one hour. If patients still fail to open the bottle, they are automatically reminded with a telephone call to take their pill. TAS pharmacists can tap into the wireless GlowCaps system, which records data on a secure Vitality network, to monitor patients’ drug compliance. If a TAS pharmacist notices that a patient has not achieved an optimal adherence level, the clinician can educate the patient on the importance of adherence. TAS said it is not yet able to release specific data on the degree to which the GlowCaps initiative has improved drug compliance. But the specialty pharmacy operator did confirm that the wireless medication reminder technology improved patient adherence and persistence with the Novartis drugs Tasigna (nilotinib) and Gleevec (imatinib). TAS said it is discussing the potential use of the GlowCaps system with other pharmaceutical manufacturers, building on this pilot and its prior experience using GlowCaps with organ transplant patients. In a separate study of patients taking antihypertensive medications conducted in 2009 by a division of Partners Healthcare, a health-system based in Boston, up to 95% of patients who used the GlowCaps reminder system adhered to their prescribed medication regimen, compared with 45% in a control group that did not use the electronic compliance aid. The study has not yet been published, according to Vitality. People who don’t take their medicines as prescribed cost the U.S. health care system an estimated $290 billion in avoidable medical spending every year, according to a report released by the New England Healthcare Institute in 2009. That’s up 161% from the year 2000. The research findings note that one-third to one-half of all patients do not take their medications properly. The report can be seen at http://www.nehi.net/uploads/full_report/pa_ issue_brief__final.pdf —A.H.

staffs know who we are.” Far from its 1996 launch with a focus on fertility treatments, TAS now includes 15 retail sites located next to the medical centers and physician groups they serve, plus a 25,000-squarefoot national distribution center in Phoenix; a Sacramento facility that primarily ships oncology medications to eight Northwestern states; and a separate wholesale business. More than 75% of TAS business is generated by the company’s involvement in oncology and infectious disease, primarily HIV and hepatitis C. TAS also has clinical experts working in solid organ transplant support, fertility, rheumatologic and dermatologic inflammatory diseases, ophthalmology, veterinary medicine and pharmaceutical compounding. This structure appeals to clinicians and patients, according to Mr. Cook, because they get to know the TAS pharmacists and support staff servicing them. “Whenever [patients] call, they deal with the same people. We’re organized by disease state. It’s a much warmer, high-touch personal model than a true managed care–driven specialty pharmacy,” he said. Changes in the medication marketplace had a major influence on where TAS decided to specialize. For example, a shift from hospital-based chemother-

TAS starts to manage and support a referred patient by reviewing clinical notes and laboratory results supplied by providers. During one recent patient consultation, a metastatic breast cancer patient prescribed capecitabine and IV chemotherapy (docetaxel) revealed that she also took warfarin for atrial fibrillation and drank green tea daily. Noting the potential for green tea to interfere with the metabolism of certain chemotherapy agents and blood thinners, the clinical pharmacist contacted both the patient’s oncologist and primary care clinician to stop the green tea and discuss drug monitoring parameters, according to Eric Sredzinski, PharmD, AAHIVE, vice president of clinical affairs for TAS. During ongoing patient care, TAS clinical pharmacists review medications and check for adverse effects, and aim to foster adherence with technology such as GlowCaps (sidebar, “Medication Adherence Tool”) and textmessage refill reminders. TAS also coordinates patient care with hospitals month by month because patients return there for follow-up laboratory checks and appointments. When necessary, TAS recommends provider interventions that could prompt an office or emergency department visit, a reduction or cessation of medicine, or over-the-counter management of an adverse reaction, Dr. Sredzinski explained.

Forging Tighter Connections To help further tighten continuity of care, pharmacists from the TAS retail sites provide education on a wide variety of clinical topics, including updates on immunosuppressant therapy for organ transplant patients and “Club Meds,” HIV classes that review the basics of the disease, adverse effects of drug therapy and updates on current

Specialty Pharmacy Continuum • Spring 2012

PRACTICE PROFILE therapies, noted Dr. Sredzinski, who is also pharmacy program director of the company’s AIDS drugs assistance programs. TAS pharmacists also cover topics that can help patients cope with the high cost of medications, such as copay assistance resources. These types of outreach efforts are especially valuable in rural and regional hospitals, where specialty pharmacy is “their assurance a patient is not going to fall through the cracks when discharged; that everything you’ve done with the patient in the hospital is continued when they leave the hospital,” Mr. Cook said. Maintaining a strong connection with patients thus is critical to TAS’ strategy—as is the company’s outreach to hospitals. TAS collaborates with larger institutions in various ways. For example, at the Cleveland Clinic, TAS organized a multidisciplinary advisory board for a manufacturer to discuss the treatment pathways for hepatocellular carcinoma. Additionally, because TAS compounds topical mechlorethamine for patients diagnosed with cutaneous T-cell lymphoma, the hospitals at Vanderbilt, Duke and Stanford use TAS to manage these patients for them. Some of TAS’ collaborations with hospitals focus on research. At the University Medical Center of Tucson, for example, TAS has been involved in two clinical trials—one a placebo-

controlled trial of methylphenidate in pediatric patients with attentiondeficit/hyperactivity disorder, and another to study the effectiveness of an intervention toolbox to promote immunosuppressant therapy adherence in adult renal transplant patients. (TAS is the primary referral pharmacy for solid organ transplants at the medical center.) TAS also has conducted research with the University of Arizona’s College of Pharmacy, in Tucson, to assess the affect of the company’s clinical

programs on patient outcomes. Preliminary data from the study, presented at the 2011 American Transplant Congress in Philadelphia (abstract 1139), suggested that behavioral interventions could significantly improve the medical possession ratio (MPR; a measure of prescription adherence) in renal transplant recipients. At baseline, the mean MPR in the intervention group was 0.74 ±0.25, versus 0.91 ±0.22 at six months (P<0.05). No statistically significant differences in MPRs were found within the control group.

Asked to provide further data on how TAS interventions affect patient outcomes and rehospitalization rates, Mr. Cook said that accumulating such data is “an industry challenge. We only see our own data related to how long we keep a patient on therapy. We don’t always see the medical benefit. Generally, if we keep a patient on therapy and they adhere, we expect to see a decreased spend on the medical side— fewer hospitalizations, relapses and recurrences.” —Al Heller

Using Retail Software for Your Specialty Pharmacy?

Additional Strengths

here are several additional operational areas that distinguish The Apothecary Shops from other providers, according to Todd Speranzo, vice president of marketing: • TAS secures insurance preauth– orizations for patients before the hospital discharges them, unburdening the nursing staff from this arduous task. • TAS secures financial assistance from foundations or manufacturer copay cards when needed; it obtained $5 million for patient aid in 2011. • Clinical pharmacists can be reached 24/7.

Specialtyy Pharmacy rmacy macy rrequires Specialized Software. Software CPR+ is sspecialty pharmacy software. + Comprehensive clinical & therapy management + Powerful reimbursement tools for medical and pharmacy claims with prior authorization tracking + Super-efficient workflow management designed specifically for Specialty Pharmacy CPR+ fits your Specialty Pharmacy business – no hammer required.

• Clinical care teams are dedicated to each specialty. This is especially important in oncology, where more orders are being written for off-label use, and where proof for preauthorizations is needed before medications can be dispensed. • Clinical pharmacists comprise more than 18% of TAS staff. —A.H.

Schedule a one hour, no-obligation demo and find out why hundreds of Specialty Pharmacies trust CPR+.

www.cprplus.com/specialized

866-277-4876

Specialty Pharmacy Continuum • Spring 2012

OPERATIONS & MANAGEMENT

EXCELERA continued from page 1

that aims to unite at least 20 large, integrated health systems in an effort to win a greater share of the specialty pharmacy business now going to more established companies. Excelera launched in early April with a new Web site (excelerarx.com). At press time, the company was concentrating on converting more of the health systems that have signed letters of intent into active members. “We’re at the point now where everything is hitting on all cylinders,” said Daniel Kus, BS Pharm, RPh, vice president, Ambulatory Pharmacy Services at Henry Ford Health System, which operates an active specialty pharmacy. Mr. Kus said the timing was right for the Excelera initiative. Some health systems, he noted, already have lost a sizeable portion of their most vulnerable and complex patients to other specialty pharmacies because of limited distribution drug arrangements. The losses are occurring even as health systems—many of which have launched or are setting up accountable care organizations—remain at risk for their patients’ total medical and pharmacy care costs. “Right now, we’re not able to provide pharmacy care for probably 30% to 40% of our patients who leave our health system,” Mr. Kus said. “Their insurance either mandates that they go to a different specialty pharmacy or, for some drugs, they may be able to go to a retail network.”

A Hybrid Approach Its founders say Excelera’s integrated delivery network represents a new hybrid model that centralizes functions such as patient call centers and data aggregation while decentralizing the delivery of specialty medications to patients within their own health networks. “The model where care is delivered locally is where we feel care is delivered best,” said David Stibbe, Excelera’s vice president of strategic markets. Mr. Kus said the model differs from others that “may have a network of specialty pharmacies, but [require] you to send the prescription to one place and all those prescriptions get dispensed from there.” The Excelera approach, Mr. Stibbe said, avoids the fragmented and sometimes delayed care that occurs when patients are forced outside of their care orbits to get the medicines they need for difficult-to-treat conditions. With this model, he added, “We believe we’ll be able to deliver better care and better outcomes for our patients and reduce costs.” One advantage that Excelera’s founders believe sets it apart from large commer-

The Excelera initiative ‘intuitively makes sense. But you have to ask yourself, why would health plans and other payers be moving specialty drug management away from [hospitals] if in fact it is such an intuitive solution?’ —Randy Falkenrath, CVS Caremark cial specialty pharmacies is the access it provides health system caregivers to complete patient medical records as well as to the collective expertise and research of medical thought leaders throughout the coalition’s various medical centers. “We believe that we are more oriented and equipped to be able to have standardized pharmacy protocols for hepatitis C, multiple sclerosis, rheumatoid arthritis” and other complex chronic diseases “no matter where the patient is in the country,” Mr. Kus said. Additionally, he said, Excelera offers a centralized data management system capable of aggregating the clinical data that providers, payers and manufacturers are seeking in their efforts to improve patient outcomes and to reduce overall health care costs. Mr. Kus said one of the key areas he discusses frequently with drug manufacturer executives is the gap in information they’re receiving on specialty drug utilization and management in hospitals and often in physicians’ offices. “Specifically,” he added, “they’re now concerned about [a lack of data on] drugs being used in accountable care organizations.” Mr. Kus said Excelera’s data management system, located in Minneapolis, “is a very robust system that is going to allow us to collect information that is accurate and valuable to the manufacturers and payers, and, we believe, well above what is currently being delivered by any specialty pharmacy network in the country. I believe it’s going to be a substantial differentiator in the marketplace.” More than 20 health systems have signed letters of intent to join the Excelera network, according to Mr. Kus, but he declined to be specific because of nondisclosure agreements. As for the types of members Excelera is looking for, officials declined to be specific, but did note that they want large health systems with specialty pharma-

cies capable of delivering the clinical services and information payers demand. The University of Maryland Medical Center in Baltimore is one health system that is still weighing its specialty pharmacy options. But Gary A. Stewart, MS, RPh, assistant director of pharmacy, believes that a collective approach gives participants more leverage in their bid to retain the specialty pharmacy patients being lost to limited distribution drug arrangements. “Now,” he said, “instead of 30 or 300 institutions developing their own [systems], the strategy is to use one centralized data management process to aggregate outcomes information and support the delivery of products and effective clinical management services at the institutional level, and through that technology, you can deliver the expertise to clinically get more engaged with these patients.”

CVS Caremark’s Take Randy Falkenrath, senior vice president of specialty pharmacy at CVS Caremark, said the attempt by Excelera to form a coalition to overcome the loss of specialty pharmacy patients by individual health systems “intuitively makes sense.” But he added, “You have to ask yourself, why would health plans and other payers be moving specialty drug management away from [hospitals] if in fact it is such an intuitive solution?” One reason, Mr. Falkenrath said, is that health systems have not been “very visible in the specialty pharmacy community. When you look at materials today that identify specialty pharmacies, you tend not to see these pharmacies listed. When you go to organizations like PCMA [Pharmaceutical Care Management Association—the trade association representing pharmacy benefit managers], you don’t see these pharmacies participating in that industry association and collaboration.” Additionally, Mr. Falkenrath said, “you

don’t see any publications from them about outcomes analyses. They don’t provide the kind of robust payer-required reporting tools to look at utilization information, outcomes information and patient management information within their specialty pharmacy systems.” Mr. Falkenrath compared the “silence or lack of visibility” of specialty pharmacy health systems with the performance of more established specialty pharmacy providers. The latter, he said, deliver “more well-defined examples of the clinical services and support ... [and the] reporting capabilities they provide back to the payer, whether it’s a health plan or an employer.” Such feedback “is a required part of the specialty pharmacy business model,” he said. “It may be that the Fairviews and others do that, but you don’t see any evidence of that.” Kyle Skiermont, PharmD, director of specialty infusion operations at Fairview Pharmacy Services (part of a large regional hospital network), said that he agreed “to some extent” with Mr. Falkenrath’s comments about health system specialty pharmacy’s lack of national visibility. But Dr. Skiermont took issue with the implication that Fairview’s clinical services were not as robust as those of national specialty pharmacies and that it was not providing payers with the utilization and outcomes information that they require. “We do provide these services and report to a number of payer customers on a quarterly basis,” he said, adding that publication of some data had been done through Fairview, “but it is not going to be the same kind of media splash that it’s going to be with a large national player.” Dr. Skiermont said that while “we’re not as visible in the national specialty pharmacy community, we’re more visible in the provider community and in our local regional markets. All of the payers in our [region] know Fairview Specialty Pharmacy very well, as do all of our regional and local pharmaceutical representatives. On a national level, it’s not that we are completely unknown, but clearly we are not known in the same sense as a CVS Caremark or Walgreens.” As for the larger question of whether health systems bring value as a new entrant into specialty pharmacy, David S. Fasching, president of Excelera, said that is definitely the case. “Health systems have an enormous new opportunity to improve quality of care, value and financial performance by retaining their complex patients for specialty pharmacy,” Mr. Fasching said. He added that by providing local integrated coordinated care, the hospital-based specialty pharmacy model “can reach new levels of specialty pharmacy quality and value.” —Bruce Buckley

Specialty Pharmacy Continuum • Spring 2012

OPERATIONS & MANAGEMENT

Hand Hygiene Critical for Clean Compounding New Orleans—Harmful microorganisms can find their way to patients when staffers do not follow best practices when compounding sterile preparations, according to a study by pharmacists at at NewYork-Presbyterian Hospital, in New York City. To reduce the transmission of pathogens, the hospital launched a plan to improve compliance among pharmacy staffers who make compounded drugs in IV admixture clean rooms. “We wanted to reduce the potential risk of transmission from the staff who are making sterile products for patients,” said Vickie L. Powell, MS, RPh, FASHP, site director of the pharmacy and co-author of the study. “That can happen in many ways, such as not washing your hands and then touching the compound you’re making. Numerous organisms can grow and potentially be transmitted. We decided that even though we put people through extensive training about sterile compounding safety, we would conduct random cultures of gloved fingers to see how clean they were as a way to monitor, evaluate and document compliance.” Random culturing revealed that only 30% of the approximately 100 staff members had no colony-forming units of microorganisms growing on their gloved fingertips before beginning compounding procedures. (The microbes detected included Corynebacterium, coagulasenegative Staphylococcus, Micrococcus, Pseudomonas, Streptococcus, and Kytococcus.) The results, presented in December at the 2011 Midyear Clinical Meeting of the American Society of Health-System Pharmacists, suggested inadequate compliance with procedures as described by US Pharmacopeia (USP) Chapter <797> on sterile compounding Staff members who were noncompliant—as judged by microbial growth on their cultures—were required to undergo re-education and training on proper procedures, a process that took about a week. “We have them review videos and conduct one-on-one instruction, then we observe them at their work, which is followed by another culture,” Ms. Powell said. “I think people are inclined to do the right thing, but sometimes they take shortcuts if you’re not watchful.” Ongoing monthly monitoring, which includes random cultures and training, has resulted in compliance with USP <797> and Joint Commission medication management standards, Ms. Powell noted. Since the program’s initiation in 2010, 95% of the pharmacy staff’s cultures have been free of microbial growth. The team concluded that “strict adherence to proper hand washing and sterile compounding procedures decreases microbial growth and virtually eliminates the risk for nosocomial infections from

compounded admixtures. Developing strict policies and procedures can ensure quality outcomes for our patients.” Angela Cassano, PharmD, president of Pharmfusion Consulting in Midlothian,

Va., said she is encouraged by New-York Presbyterian’s dedication to taking USP <797 seriously. “I’m not surprised to see that in this study, compliance rates among staff increased after a formalized program was put in place,” she added. “When employees see that you’re serious about an initiative, you’re likely to get greater buy-in. Going from 30% compliance to 95% is significant and shows that their efforts have been very effective.”

Dr. Cassano added that managers who are responsible for compounding operations often assert that the only way to effectively reduce contamination is to invest millions in rebuilding the clean room, but this program shows clearly that a difference can result from a structured training program, and more importantly, regular compliance oversight. —Steve Frandzel

The Path to Providing Services and Solutions that Improve Access to Specialty Pharmaceuticals and Enhance Patient Care Begins Here. + Expand your

Clinical Focus

+ Improve Adherence & Persistency

+ Proﬁle Your Business

+ Measure

Patient Outcomes

+ Address

Reimbursement Challenges

+ Save with

Contract Pricing

+ Report &

Analyze Data

Get Ready for the Future Today! Contact Managed Health Care Associates, Inc. P 800.642.3020 x2870 • info@mhainc.com • www.mhainc.com

Specialty Pharmacy Continuum • Spring 2012

OPERATIONS & MANAGEMENT

CONTAINMENT continued from page 1

cohort of patients with multiple sclerosis (MS) experienced medical costs that were almost 40% lower than those of patients who were noncompliant. He said the company hopes “to release the full data and analysis later this year.” When assessing compliance, one of the factors to look at is the medication possession ratio (MPR), which measures the percentage of time a patient has access to medications. “It’s been shown to be a good proxy for compliance with treatment,” Mr. Einodshofer said. He noted that Walgreens has found that patients with MS who are not in an active disease management program within their pharmacy have a

63% MPR compared with a 92% MPR among those who are managed. He noted that the difference is even more dramatic among patients with rheumatoid arthritis: 50% MPR for unmanaged patients versus 93% MPR for those who are managed. So what are the keys to aggressive patient management in specialty pharmacy? Knowing when patients are due for refills, reaching out to them ahead of time to either ensure that the refill is completed or document why they are electing not to receive it and coordinating with physicians on new prescriptions to ensure that therapy remains uninterrupted, according to Mr. Einodshofer. Importantly, “patient management also involves asking the right clinical questions,” such as whether

‘People have been talking about integrating specialty and medical pharmacy with traditional forever, but I think the time has come.’ —Kjel Johnson, PharmD, BCPS, FCCP

patients are experiencing side effects and whether they understand how to take their medication, he stressed. “You need to develop an appropriate array of questions by therapeutic class and specifically by drug, to help you identify any possible problems or lack of understanding with the medication that could contribute to noncompliance. … There’s a lot more to it than simply dispensing medications.” Another cost containment initiative that Walgreens has found effective is its oral oncology split-fill program. The sad reality is that between 20% and 30% of patients on certain oral oncolytics will discontinue therapy after their first month—sometimes due to intolerable side effects, and sometimes because they have passed away, according to Mr. Einodshofer. If the full month’s supply of the drug is dispensed at the beginning of the month, the payer has already paid for the drug that remains unused. “For certain products that are very high cost—between $4,000 and $12,000 per month—we simply split the first 30 days of medication” into two parts, he said. “We then follow up to ensure that the second half of dispensing, and the next month, is necessary prior to shipping.”

Where the Costs Are

‘To control costs, we need to shift from a model in which the margin is associated with drug reimbursement to a quality-based payment program.’

—Surya Singh, MD

Everyone knows that oncology drugs are the 600-pound gorillas of cost in specialty pharmacy. In a presentation on the challenges of oncology benefit management as cancer becomes a chronic disease, Surya Singh, MD, CVS Caremark’s vice president for medical benefit management, pointed out that 53% of medical pharmacy spending is in the oncology sphere, dwarfing other types of products (11% of medical pharmacy spending is for autoimmune therapies, 4% immune therapies and 32% is “all others,” according to CVS Caremark’s 2010 Enterprise Analytics). Although MS medications such as natalizumab (Tysabri, Biogen Idec/Elan) come with a high price tag, about 90% of them are managed under the pharmacy benefit, whereas 81% of oncology drugs are managed under the more costly medical benefit, according to data from Express Scripts’ 2010 Drug Trend Report presented by Dr. Singh at the meeting. “The rate of growth for the expenditures on oncology drugs ranges from 15% to 30% annually,” added Dr. Singh. Even with Medicaid’s shift to average sales price (ASP)-plus pricing from average wholesale pricing (AWP) in 2005, there is an enormous variability in drug pricing based on local market dynamics. In a survey conducted by the Zitter Group, 31% of respondents were paying at least ASP plus 11%, significantly higher than the rate of ASP plus 6% dictated by Medicaid (the Zitter Group’s Managed Care Oncology Index,

Summer 2011). Dr. Singh told Specialty Pharmacy Continuum that the problem with the current “buy-and-bill” approach to oncology drug pricing, in which doctors purchase a drug and then sell it to insurers with a markup, is that it creates misaligned incentives. “Markup-based reimbursement, whether it’s AWP or ASP, encourages the use of more expensive drugs in almost any case,” Dr. Singh said. “To control costs, we need to shift from a model in which the margin is associated with drug reimbursement to a quality-based payment program.” Dr. Singh offered the example of a patient with KRAS wild-type metastatic colorectal cancer. Under the current “buy-and-bill” model (with ASPbased reimbursement), one possible treatment (regimen A) costs the health plan approximately $18,000, and another (regimen B) just over $14,000, with the physician being reimbursed about $430 more for prescribing regimen A. Under a quality performance program (QPP), however, the physician would be incentivized to prescribe regimen B when clinically appropriate, and would be given a “quality bonus”—in this case, approximately $400. That $400 makes up most of the difference between what the physician would earn for prescribing drug A versus B, and still costs the payer significantly less. “Overall,” said Dr. Singh, “on this single patient example, QPP reduces health plan drug costs by $4,434.74, or 24%. It’s relatively straightforward math.”

Channel Management Channel management is another way to contain costs for specialty pharmacy drugs. Costs drastically vary depending on whether a drug is self-administered and paid under a pharmacy benefit, or clinician-administered and paid under a medical benefit, according to Kjel Johnson, PharmD, BCPS, FCCP, senior vice president of strategy and business development for Magellan Pharmacy Solutions. “Obviously, the first way to cut costs is through channel management: where possible, you keep the … prescription out of [the] medical benefit and within pharmacy,” Dr. Johnson said. When dealing with specialty prescriptions that are self-administered and fall under the pharmacy benefit, the key cost containment strategies involve formulary management and utilization management, which go hand in hand. “In this setting, formulary management is not a yes-or-no proposition,” Dr. Johnson said. It’s important to drive formulary choice, he added. “If the physician calls and requests Remicade [infliximab, Janssen], ask if they have tried Enbrel [etanercept, Amgen/Pfizer] or Humira [adalimumab, Abbott] first. If they haven’t, they should.”

Specialty Pharmacy Continuum • Spring 2012

OPERATIONS & MANAGEMENT

Alternate-Site Infusions Can Reap Big Savings Scottsdale, Ariz.—Moving specialty pharmacy infusions from the costliest sites of therapy to less expensive locations—a practice known as site-of-care optimization—can achieve savings of as much as 60%, according to a study conducted by Walgreens Specialty Pharmacy. The top 10 most expensive infused specialty medications include eight chemotherapy drugs and two non-chemotherapy agents—infliximab (Remicade, Janssen) for rheumatoid arthritis and psoriasis, and natalizumab (Tysabri, Elan) for multiple sclerosis. Walgreens’ analysis of the cost data for these 10 medications found that, on average, the drugs in a hospital setting cost 86% more than at alternate sites, such as a physician’s office or freestanding infusion suite. Additionally, costs directly related to the administration of those drugs at a hospital are approximately double what they would be in the outpatient facility. “With very few exceptions, any product that’s being infused at an outpatient facility within a hospital can be transferred to an alternate site

On the other hand, when physicians are administering drugs in their offices, several factors come into play. According to Dr. Johnson, physicians are able to directly purchase specialty drugs from manufacturers for 15% less than specialty pharmacies and then they can then keep the drug on the shelf until the patient buys it from them at the time of administration. When a physician orders a drug for a specific patient from a specialty pharmacy, it is usually done a couple of days in advance of treatment. As explained above, with certain specialty oncolytics, the patient ends up not receiving therapy at least 20% of the time. “Either they’re too sick to take chemo, their lab values are wrong, their benefits expire—in any case, it gets thrown into a box and you can either give it to an indigent patient or throw it away. The doctor cannot return it. But the payer has already paid,” Dr. Johnson said. So, it appears that the physicians have the advantage of being able to hold the product on their shelves until administration and they can obtain the product for less money if they purchase directly. However, Mr. Einodshofer said it’s not cut and dried. He acknowledged that some drugs can be purchased by physicians at a cost slightly below a pharmacy’s acquisition cost, due to various manufacturer pricing strategies, but that’s not always the case. “The drug mix prescribed influences whether or not, on a net basis, physicians truly have any purchasing advantage over a

hospital setting, but other than that, most patients can get their infusions elsewhere, Mr. Einodshofer noted. For the most part, he added, chemotherapy drugs can be given safely in the physician’s office or at an infusion suite. “The key is having specialty

‘There can be up to a 60% price difference between the hospital and alternate sites.’ —Michael Einodshofer

of care,” said Michael Einodshofer, director of utilization management for Walgreens Specialty Pharmacy, who presented the data at the Pharmacy Benefit Management Institute’s

(PBMI) 2012 Drug Benefit Conference in February. A patient who has had past anaphylactic reactions to a particular infusion may be too highrisk to receive therapy outside the

Table. Effect of Nonadherence on Patient Outcomes Approximately 40% of patients overall and approximately 50% of those with chronic diseases fail to take their medication as directed. Up to 69% of medication-related hospital admissions are caused by poor medication adherence (at a cost upward of $100 billion per year). As many as 25% of total hospital and nursing home admissions are the result of poor adherence. A patient with substandard adherence has three times as many doctor visits per year and averages $2,000 more per year in costs than adherent patients. Based on URAC specialty pharmacy white paper. the patient-centered outgrowth of specialty pharmacy. https://www.urac.org/Whitepaper/PQM-Specialty_Pharmacy.pdf, IMS Health Inc. Understanding and improving adherence for specialty products. 2010, and Center for Health Transformation.

trained nurses and other health care professionals who are very experienced in infusion,” he noted. Other infusion medications, including infliximab, natalizumab and another expensive therapy, IV immunoglobulin

•

see BIG SAVINGS, page 12

office if they choose to do so but that spares them the double burden of purchasing high-cost drugs and the need to bill the patient for copays or coinsurance. “A structured program encouraging MD offices to use a specialty pharmacy vendor for drug procurement can help prevent this unintended consequence,” he suggested. Walgreens Specialty ships millions of dollars’ worth of specialty drugs to physician offices every week. “These physicians have the drug arrive just prior to the patient’s appointment, yet are alleviated from having to bill the payer for the drug, bill the patient for their copay and purchase and keep inventory of the drug,” Mr. Einodshofer said.

The Future Is in Integration

specialty or retail pharmacy,” he said. Additionally, Mr. Einodshofer pointed out that purchasing products directly creates storage and administrative

problems for physicians. The key, he said, is for payers to offer providers a drug procurement method that allows physicians to infuse in their

The future of specialty pharmacy, Dr. Johnson suggested, is part of an integrated pharmacy benefit management approach. “You need a pharmacy benefit manager [PBM] overseeing all benefits, all drugs, all sites of service, and that’s the approach we take,” he said. “If you have rheumatoid arthritis, for example, that PBM can validate that you’re on methotrexate, make sure you get Enbrel or Humira first-line and then a doctor-administered therapy second-line, and keep you out of the hospital for infusion. People have been talking about integrating specialty and medical pharmacy with traditional forever, but I think the time has come.” —Gina Shaw

Specialty Pharmacy Continuum • Spring 2012

OPERATIONS & MANAGEMENT

BIG SAVINGS continued from page 11

(IVIG), can be safely and cost-effectively offered not only at physician’s offices and infusion centers but also in the home setting and within retail pharmacies specially equipped to provide infusion services, according to Mr. Einodshofer.

employees on an expensive medication to reap the cost savings needed to put in a small center. “The costs of infliximab are between $20,000 and $60,000 a year. There can be up to a 60% price difference between the hospital and alternate sites; even if it’s just 40% less to deliver that product in your own suite, just one or two patients can more than justify the cost of your

‘My concern is whether or not this type of environment has been independently studied and shown to be one that could be safe and effective in administering medications such as chemotherapy.’ —Rebekah Hanson, PharmD Additionally, he said, “A lot of employers, especially those with concentrated employment bases, are putting in health suites on site. The patients can get their infusion as part of their workday so they don’t have to take a personal day, and the cost is lower for the employer and they get better [worker attendance.]” It seems counter-intuitive to think that putting in an entire health suite for employees could actually save an employer money, but Mr. Einodshofer claims that it only takes one or two

infrastructure.” Walgreens headquarters has its own infusion suite; Mr. Einodshofer said that other corporate clients have established such facilities as well, although he doesn’t have permission to share names. Around the country, Walgreens also has nearly 100 infusion suites within its retail and infusion pharmacy locations. Some are actually dedicated facilities, former physician’s offices that have been converted to dedicated infusion suites staffed by nurse practitioners. This model allows

for more complex infusions, such as chemotherapy. In other cases, there is dedicated space within a Walgreens in-store facility, where a nurse will meet a patient at a scheduled infusion time. “Infusions that can be done in the home are also great candidates for in-store infusion. Those that are more complex and currently in the domain of physician or hospital can almost entirely be transitioned to free-standing suites,” Mr. Einodshofer said.

A Model Worth Emulating? Is that a model that other specialty pharmacies could, or should, consider replicating? Walgreens has a big bricksand-mortar advantage with well over 8,000 points of care throughout the country. But the infrastructure isn’t the most important key to the success of a pharmacy-owned infusion facility; nursing capabilities are. “You need nurses that are very experienced, professional and know how to do these administrations, otherwise everything is going to fail,” Mr. Einodshofer observed. CVS Caremark is at least considering the strategy, said Randy Falkenrath, senior vice president of specialty pharmacy for the company. “I agree with the concept: For cost-effective, clinically effective sites of service, site-of-

Site-of-Care Considerations For IV Immunogloblin Delivery Jerry Siegel, PharmD, FASHP Clinical Associate Professor The Ohio State University College of Pharmacy Columbus, Ohio

hen deciding the appropriate site of care for a patient receiving intravenous immunoglobulin (IVIG), several factors must be considered. First and foremost is safety. Has the preparation been compounded within the guidelines of USP 797 to insure sterility of the prepared product? Is this the first IVIG infusion for the patient or a change in IVIG product? Has the nursing staff been trained on the infusion and risks associated with IVIG? If this is the first time a patient is receiving IVIG, the infusion should be given in a hospital or other setting where emergency care is readily available. Nurses and others involved in the infusion must have the proper training to recognize and treat IVIG-related adverse reactions. The costs associated with IVIG infusion must be considered from more than one perspective. The facility may be able to purchase the product at a favorable price, but the setting may result in a higher copay for the patient. If the infusion clinic is under the provider status of a facility eligible for 340b pricing, the financial advantages can be significant, but the drugs much be purchased by the facility. “Brown-bagging,” the practice in which a drug is delivered to the patient by the specialty pharmacy and is brought into the infusion center for administration should be avoided, since the pedigree and storage of the product cannot be guaranteed. “White-bagging,” the practice in which the specialty pharmacy delivers drug to the infusion center prevents the infusion center from profiting on the drug costs and the center is expected to survive on the infusion charge alone. Thus, references to “lower” costs that may be achieved in some specialty settings may not be accounting for the costs passed on to the patients and the facilities responsible for administration.

care optimization makes total sense.” Indeed, he said, prior to the mid-1990s, Caremark actually had an infusion suite business. It divested from that in 1996, but is looking at returning to the model. “We’re evaluating the opportunity to expand our infusion capability to provide more options, whether it’s at our sites or a strategic partner’s infusion sites.” What do hospital pharmacists think about this plan? Rebekah Hanson, PharmD, BCPS, clinical pharmacist and clinical liaison for specialty pharmacy services at the University of Illinois at Chicago, is intrigued. “My concern is whether or not this type of environment has been independently studied and shown to be one that could be safe and effective in administering medications such as chemotherapy,” she said. “I do like the business model, if the savings is legitimately that high, but I would be hesitant to support it until we could see more evidence that it’s safe and that everything related to the infusion, such as labs, can be appropriately taken care of.” (The results presented at PBMI are based on Walgreens’ internal analysis. Mr. Einodshofer noted that the company is now reviewing the data in order to present it to peer-reviewed publications.) —Gina Shaw

Specialty Pharmacy Continuum • Spring 2012

OPERATIONS & MANAGEMENT

Increased Copays Result in Fewer Filled Prescriptions Plans should consider $100 ‘breaking point’ when setting specialty copays Scottsdale, Ariz.—The trend of dramatically raising copays to cover the cost of specialty medications could endanger patients’ health by causing them to discontinue necessary prescriptions, according to a presentation at the Pharmacy Benefit Management Institute’s Annual Drug Benefit Conference. Patients taking a specialty drug for multiple sclerosis (MS) or rheumatoid arthritis (RA) whose benefit plan began requiring them to pay 20% of the cost— up to $200—were nearly twice as likely to stop taking the drug as those whose plans continued to limit out-of-pocket expenses to $40 per prescription, according to a study led by Patrick P. Gleason, PharmD. “The concern is that people are going to stop [taking] their medications,” said Dr. Gleason, director of clinical outcomes assessment at Prime Therapeutics, a pharmacy benefit management company, and adjunct associate professor at the University of Minnesota College of Pharmacy in Minneapolis. “It’s not just that they switch—they stop.” The tendency of benefit plans to shift more costs to members in the form of higher out-of-pocket costs took off a few years ago as a way to encourage patients to opt for less-expensive alternatives and reduce plan expenses, Dr. Gleason told Specialty Pharmacy Continuum. For many benefit plans, specialty drugs, which can cost thousands of dollars per year, are of particular concern, said Dr. Gleason. One of every 200 medication users, or 0.5%, takes specialty drugs, but specialty drugs repPRINT RECOMMEND E-MAIL COMMENT resent 18% ofSHAREall expenditures. In some cases, the cost shifting was abrupt, he said. “You would go from most people filling a drug for an average of $40, then in a single day it moved to $200.” To investigate the effect of this change, Dr. Gleason and his colleagues PRINT

RECOMMEND

E-MAIL

COMMENT

What’s Your View?

RECOMMEND

E-MAIL

COMMENT

Should copay levels be adjusted to affect drug compliance? Are there other strategies that your specialty pharmacy is using to boost adherence that you’d like to share with your colleagues? Send replies to

spceditor@mcmahonmed.com

investigated patients whose benefits

plan changed dramatically in January 2008 and compared them with patients whose plans did not change at that time. Among those whose plans changed, including 59 patients who were taking specialty drugs for MS or a tumor necrosis factor (TNF) blocker for RA, copays for specialty drugs that had been a maximum of $40 rose to 20% of

the cost of the drug, or a maximum of $200. After 90 days on the new plan, Dr. Gleason and his team compared patients affected by the copay change with 120 patients who were taking the same specialty drugs but whose copays did not change. They found that 20% of those whose

•

see COPAY, page 16

Specialty Pharmacy Continuum • Spring 2012

POLICY

Boceprevir Does Not Play Well With Ritonavir-boosted HIV Protease Inhibitors

he FDA recently warned that drug interactions between the hepatitis C virus (HCV) protease inhibitor (PI) boceprevir (Victrelis, Merck) and certain ritonavir-boosted HIV PIs may reduce the effectiveness of these medications when they are used together. The HIV PIs specified are atazanavir (Reyataz, Bristol-Myers Squibb), lopinavir (Kaletra, Abbott) and darunavir (Prezista, Janssen). According to the FDA, a drug interaction study showed that taking boceprevir in combination with one of these drugs reduced blood levels of the HIV medications and boceprevir in the body. The boceprevir label will be updated to reflect these drug interactions. Another HCV PI, telaprevir (Incivek, Vertex), already carries warnings about drug interactions with HIV PIs. The FDA’s action was based on data presented on March 6 at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) from researchers at Merck (Hulskotte E et al, paper 771LB). Investigators evaluated drug interactions between boceprevir and ritonavir-boosted HIV PIs in 39 healthy adults. Blood samples were analyzed for pharmacokinetic characteristics of HIV PIs, ritonavir and boceprevir. The

researchers found that boceprevir in combination with ritonavir-boosted atazanavir, darunavir and lopinavir resulted in reduced steadystate exposures of the HIV medications. Darunavir and lopinavir, but not atazanavir, lowered boceprevir exposure. However, another study, presented on the same day at CROI (Sulkowski M et al, abstract Q-175), came to a different conclusion. This study evaluated the efficacy of boceprevir in patients co-infected with HIV and HCV genotype 1 who were not previously treated for HCV. Patients were treated with HIV PIs and also received boceprevir in combination with peginterferon alfa-2b/ribavirin (B/PR; n=64) or peginterferon alfa-2b/ribavirin (PR; n=34) alone. In an interim analysis, sustained virologic response at week 12 was achieved in 61% of

patients in the B/PR group compared with 27% of patients in the PR group. The rates of HIV breakthrough (defined as HIV RNA >50 copies/mL at two consecutive visits) were 4.7% (three of 64) for patients who received boceprevir and 11.8% (four of 34) for those who did not. “Although this study included a small number of patients, it did not demonstrate an increased rate of HIV breakthrough in patients receiving boceprevir plus HIV protease inhibitors compared with subjects receiving protease inhibitors alone,” said Kristen Marks, MD, assistant professor of medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York City, and investigator, Cornell Clinical Trials, who was not involved in the study. “However, further study is needed to determine if HCV and HIV protease inhibitors can

be safely used together.” “There has been considerable concern about the off-label use of these drugs and how they are used in patients with retroviral infections,” said Andrew Talal, MD, MPH, associate professor of medicine and associate medical director, Center for the Study of Hepatitis C, Weill Cornell Medical College, New York City. “I am pleased by the release of these data.” Dr. Talal said he would hold off initiating combination therapy with boceprevir and ritonavir-boosted HIV PIs in a patient with HCV–HIV co-infection who had not already been started on such therapy. As for patients who have already been started on the combination, the FDA alert recommends they should be closely monitored for HCV treatment response and potential HCV and HIV virologic rebound. Dr. Marks said that she would make decisions about whether to continue treatment with boceprevir and a ritonavir-boosted HIV PI on a case-bycase basis. “For example,” she said, “if a patient has been on combination therapy for half a year and is doing well with respect to both HIV and HCV, I would leave them on it.” —George Ochoa

Dr. Talal has received research and consulting fees from Merck. Dr. Marks reported no relevant conﬂicts of interest.

FDA Approves Peginesatide for Anemia From Chronic Kidney Disease

n late March, the FDA approved the new erythropoiesis-stimulating agent (ESA) peginesatide (Omontys, Affymax/ Takeda) to treat anemia due to chronic kidney disease (CKD) in adult patients on dialysis. Peginesatide is administered once a month, less frequently than other ESAs for this indication. It is also the first ESA approved by the FDA for this indication to be manufactured by a company other than Amgen. (One medication in this class, epoetin alfa [Procrit], is distributed by Centocor Ortho Biotech, but is manufactured by Amgen.) Peginesatide “represents the first new

FDA-approved and marketed ESA for this condition since 2001,” noted Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement. “This new drug offers patients and health care providers the convenience of receiving ESA therapy just once per month instead of more frequent injections.” Two randomized, multicenter clinical trials demonstrated the safety and efficacy of peginesatide in patients with CKD who were on dialysis, according to the FDA. The open-label trials randomly selected patients with hemoglobin levels

initially stabilized by the ESA epoetin alfa (N=1,608) to receive either peginesatide once monthly or to continue their current epoetin alfa treatment. Peginesatide was shown to be as safe and effective as epoetin in maintaining hemoglobin levels within the studies’ prespecified range of 10 to 12 g/dL. The most common adverse events observed in 10% or more of dialysis patients treated with peginesatide were diarrhea, vomiting, hypertension

FDA Approves Two Pancreatic Enzyme Products

he FDA has approved Ultresa (pancrelipase) and Viokase (pancrelipase), two pancreatic enzyme products marketed by Aptalis Pharma U.S. Inc. The two new products, intended to aid food digestion, are only the fourth and fifth pancreatic enzyme products approved by the FDA, and, according to the agency, will help ensure adequate supply of the medications. Ultresa is a delayed-release capsule used to treat children and adults with cystic fibrosis or other conditions that

prevent patients from digesting food normally because of exocrine pancreatic insufficiency. Viokase, taken in combination with a proton pump inhibitor, is used to treat adults who cannot digest food normally. Adults with chronic pancreatitis, or those who have had a pancreatectomy, may not digest food normally because of lack

of enzymes or because enzymes are not released into the bowel. Viokase’s safety and efficacy in children has not been established, according to the FDA. “The approvals of Ultresa and Viokase, along with the other approved pancreatic enzyme products, allow health care providers to prescribe the product that is most appropriate for the estimated 200,000 patients in the United States who have pancreatic insufficiency,” Julie Beitz,

and arthralgia. According to the drug’s prescribing information, peginesatide should not be used in patients with CKD who are not receiving dialysis, in patients with cancer-related anemia or as a substitute for red blood cell transfusions in patients who require immediate correction of anemia. —Based on FDA and Affymax/Takeda press releases

MD, director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research, Beltsville, Md., said in a statement. Unapproved pancreatic enzyme products had been available for decades. As of April 28, 2010, however, manufacture and distribution of such products was no longer permitted by the FDA, the agency noted. Besides Ultresa and Viokase, the other FDA-approved pancreatic enzyme products are Creon (Abbott), Pancreaze (Janssen), and Zenpep (Eurand). Pancreatic enzyme products are not interchangeable. —Based on an FDA press release

Specialty Pharmacy Continuum • Spring 2012

POLICY

Hecoria, for Transplant Recipients, Now Available as Branded Generic

ow available in U.S. pharmacies, Hecoria is the first generic tacrolimus that can be prescribed by its brand name, according to its distributor, Novartis. An AB-rated generic therapeutic bioequivalent to Prograf (tacrolimus), Hecoria is an immunosuppressant approved for the prophylaxis of organ rejection in patients receiving allogeneic liver or kidney transplants. As a branded generic, Hecoria offers a cost savings while presenting an option for physicians who want their patients to receive the same brand of tacrolimus at every refill, said Novartis. Available in 0.5-, 1- and 5-mg capsules, Hecoria has its brand name printed on the capsule. “Hecoria complements our extensive portfolio of transplant immunosuppressant medications, and underscores our ongoing commitment to delivering a broad range of treatment options to our customers and their patients,” said Usman Azam, MD, head of U.S. Medical & Drug Regulatory Affairs, Novartis Pharmaceuticals, East Hanover, N.J., in a statement. The FDA approval of Hecoria was based on comparative, randomized, single-dose, two-way crossover, bioavailability studies of tacrolimus and Prograf 5-mg capsules in healthy volunteers following a standard meal and under fasting conditions. The results demonstrated that tacrolimus and Prograf capsules are bioequivalent under fed and fasting conditions. According to Novartis, health plans will generally reimburse patients for Hecoria as an AB-rated generic and generally will make the medication available to patients at a generic price. Through its Patient Assistance Program, Novartis is offering the same level of financial support for Hecoria as for other branded Novartis products. For information about the Novartis Patient Assistance Program, visit www.patientassistancenow.com. For more information about Hecoria, including potential adverse events and drug–drug interactions, see the full prescribing information, available at www.hecoria.com. —Based on a press release from Novartis

New Indication Approved for Etravirine: Resistant Pediatric Patients

he FDA has approved etravirine (Intelence, Janssen) to be administered in combination with other antiretroviral (ARV) medications for HIV infections in treatment-experienced pediatric patients (6 to <18 years old) who have failed to respond to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other ARVs. The approval, which follows FDA priority review of Janssen’s supplemental New Drug Application, expands the etravirine indication and makes it the only NNRTI indicated for use in these treatment-resistant patients, according to a news release from Janssen. The drug had previously been approved for ARV treatment–experienced adults who are infected with HIV strains that are resistant to an NNRTI and other ARVs. The approval includes a new 25-mg dose to allow for weight-based dosing in pediatric patients weighing at least 35.2 lb. The 25-mg tablet is expected to be available in the first half of May, Janssen stated. The approval is based on 24-week data from the PIANO (Pediatric trial with INTELENCE as an Active NNRTI Option) study, which evaluated the pharmacokinetics, safety, tolerability and efficacy of etravirine in combination with other ARVs in ARV–experienced pediatric patients aged 6 to <18 years. Etravirine should be taken orally following a meal. For patients unable to swallow the tablets whole, the tablets may be dispersed in a

glass of water and then added to other liquids such as milk or orange juice. The use of grapefruit juice, warm liquids or carbonated beverages should be avoided. In 2009, the FDA notified health care professionals of revisions to the Warnings and Precautions section of the prescribing information for etravirine. The new warnings were based on postmarketing reports of cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and hypersensitivity reactions characterized by rash and sometimes organ dysfunction, including hepatic failure. Etravirine therapy should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop. —George Ochoa

ISMP: CMS storage standards flawed

Drug Expiration Rules Exacerbate Drug Shortages Some parenteral medications in critically short supply may be needlessly discarded because of inconsistencies in the guidelines issued by the Centers for Medicare & Medicaid Services, according to the Institute for Safe Medication Practices. The CMS guidelines aim to provide a standard for measuring health care organization performance. The problem for pharmacies, ISMP noted, is that although its guidelines advise pharmacists to rely on standards and recommendations from professional organizations regarding how long injectable drugs may be used after they are removed from vials and manipulated, CMS continues to use FDAapproved manufacturer drug labeling as the basis for determining product life. The manufacturer labeling information on expiration dates, however, may be inadequate, missing or even outdated, according to ISMP (Medication Safety Alert! Jan. 26, 2012). For pharmacies torn between relying

strictly on the CMS interpretive guidelines for deciding whether to throw away a scarce medication or following fresh evidence supporting extended dating, the decision often may be colored by the fear of citation by a surveyor from the Joint Commission or state health department. In January, the ISMP fielded a survey to find out how pharmacists are dealing with the challenge. Although the final results are not yet completed, ISMP’s president, Michael R. Cohen, RPh, MS, ScD, FASHP, said an early look showed that “without a doubt, people are throwing things out as a result of not allowing the extended dating.” Dr. Cohen said ISMP had “spoken to CMS on this issue and they are defi-

nitely willing to look into seeing what they might be able to do to address it.” Patrick Conway, MD, chief medical officer for CMS and director of the Office of Clinical Standards and Quality, responded by stating that “CMS is actively working with our colleagues in the FDA and CDC to identify options available to practitioners to address the challenge of drug shortages within existing laws and regulations. We continue to welcome suggestions by ISMP and other experts as well seek methods

to alleviate the shortage while also ensuring that unsafe medications do not reach patients.” Pharmacists are extremely cautious about admitting to extending the dating of some drugs in short supply, even if supported by newer literature. “You can’t be quoted in print and have a surveyor come back and haunt you,” said one pharmacy director. However, a safe harbor for determining appropriate injectable medication use and storage may be strict adherence to United States Pharmacopeia (USP) Chapter <797> guidelines. Dr. Cohen said that “if the scientific literature supports extended dating and you’re still sticking within the USP Chapter <797> guidelines for dating, it makes sense to me not to necessarily worry about whether you’re going to get cited or not.” —Bruce Buckley

Specialty Pharmacy Continuum • Spring 2012

OPERATIONS & MANAGEMENT

ASHP Urges Tougher Action Against Drug Shortages On April 6, the American Society of Health-System Pharmacists (ASHP) and 24 other health care organizations sent a letter to the Senate Committee on Health, Education, Labor, and Pensions to urge changes in draft legislation that would take a tougher stand against drug shortages. Heightened efforts to address the drug shortage are sorely needed, according to ASHP members. “The number of drug shortages has significantly increased over the last four years,” ASHP CEO Paul W. Abramowitz, PharmD, FASHP, said in a statement. “This is a public health crisis that is putting patients at risk.” Representing patients, clinicians and hospitals, the signers of the letter responded to a draft of a bill aimed at addressing drug shortages as part of the proposed reauthorization of the Prescription Drug User Fee Act. High among the requests in the letter is the institution of civil monetary penalties, or another enforcement mechanism, to ensure that drug manufacturers comply with the requirement to report production interruptions or product discontinuations. “We are concerned that a requirement lacking enforcement isn’t really a requirement,” the letter states. The letter also recommends that clinicians, patients and supply chain members be included in the task force

created by the legislation to promote inter- and intra-agency coordination, planning and decision making. The FDA should receive additional resources to address drug shortages, and the language requiring the agency to provide public notification about shortages should be strengthened, according to the letter. The FDA and Drug Enforcement Administration should work collaboratively, with appropriate flexibility, in developing quotas for manufacturers producing controlled drugs, the letter states. In addition to recommending changes, the letter expressed support for certain aspects of the draft legislation, such as inclusion of biologics and biosimilar products in the draft bill.

At HOPA Meeting, FDA Addresses Drug Shortage In an earlier development, at the annual meeting of the Hematology/Oncology Pharmacy Association, Emily Thakur, RPh, senior program management officer at the FDA’s Center for Drug Evaluation

and Research Drug Shortage Program, said the agency has taken several steps to address drug shortages. These include working with firms to address issues, asking other manufacturers to increase production if possible and, in some cases, temporarily importing product from overseas. In 2011, temporary importation was allowed for foscarnet, ethiodol, thiotepa, norepinephrine, levoleucovorin and leucovorin. In 2012, liposomal doxorubicin and methotrexate have so far been imported. Most recently, the FDA has allowed importation of LipoDox (Sun Pharma) from India as an alternative to Doxil. Since President Obama signed an executive order in October, the number of FDA staff assigned to address the drug shortages has grown from four to 11, Ms. Thakur said. The FDA has attempted to expedite applications related to drug shortages, such as those that involve new manufacturers, increased expiry, increased capacity, new raw material sources or changes in specifications. The agency also has made greater efforts to work with manufacturers regarding quality problems. “The way we show flexibility is using regulatory discretion, so that we can allow a manufacturer of a medically necessary product to still allow product out that has minor, low-risk issues to it,” Ms. Thakur said.

COPAY continued from page 13

plan did not change had stopped taking the two specialty drugs examined in the study. Dr. Gleason did not consider that “surprising” because it is typical for some patients to stop or switch their medications. But among the people whose plans had changed, 35.6% had stopped filling their prescriptions for specialty medicines. In other words, those whose copayments dramatically increased were nearly twice as likely to stop using their medicines. After members complained, the plan changed again in May 2008, and the outof-pocket maximum was reduced from $200 to $100. Dr. Gleason and his colleagues found that several weeks after that change, patients in the new plan were just as likely to be on the same prescriptions as before the initial change in January as those who had experienced no change in their benefits. “In other words,” said Dr. Gleason, “when the cost share decreased to $100, people reinitiated [use of their medications].” This finding is consistent with his previous research published in the October 2009 issue of the Journal of Managed Care Pharmacy (15:648-

‘The research points benefits managers to a [copay] number that balances the need to ensure patient responsibility and the negative effect of nonadherence.’

—Jody Miller, MBA, Reliance Rx

658), which found that patients start abandoning specialty medication prescriptions for MS and RA when the out-of-pocket costs exceed $100 per prescription, said Dr. Gleason. “Research suggests $100 represents a ‘breaking point’ of some kind,” he said. He recommended that plans try to control costs and influence member choices by creating two tiers for spe-

cialty medicines: preferred, with a maximum out-of-pocket cost of up to $100 per prescription, and nonpreferred, which would range from $125 to $200 per prescription. Plans can further manage costs by establishing preferred pharmacy networks that provide deeper specialty medication discounts, and ensuring there is a care management service to make sure patients don’t

Since the executive order requiring manufacturers to notify the FDA of possible shortages was issued, the agency has had a sixfold increase in notifications, according to Ms. Thakur. The increased notification, she added, has allowed more time for backup plans to be created. But even with these measures, pharmacists don’t seem terribly optimistic about the drug supply. “If it is a generic, sterile injectable, it has been, is now or will be in shortage in the near future, and that has been the experience we have been suffering with for several years now on an escalating basis,” Dwight Kloth, PharmD, FCCP, BCOP, director of pharmacy at Fox Chase Cancer Center, Philadelphia, said in an interview with Specialty Pharmacy Continuum. In a recent editorial in the Journal of Clinical Oncology, Michael Link, MD, past president of the American Society of Clinical Oncology and other experts pointed out that “manufacturers have little incentive to produce drugs with low profit margins and often shift their resources to drugs for which higher profit margins can be anticipated.” Unless things change, the rollercoaster drug shortage problem looks to be the new normal. —George Ochoa, Kate O’Rourke continue to receive drugs if they have to stop them because of side effects, for instance. “These medications should be thought of differently from traditional medications,” he said. The project is “an excellent and rigorous study that adds to the discussion” about how to deal with the cost of specialty drugs without discouraging patients from taking necessary medications, said Jody Miller, MBA, CEO of Reliance Rx, a regional specialty pharmacy. “We see these issues of cost every day in practice in our specialty pharmacy, so we know they are real.” It’s helpful to identify a strategy that reduces the risk that patients will stop therapy, he added, such as limiting copays for preferred specialty drugs to $100. “The research points benefit managers to a number that balances the need to ensure patient responsibility and the negative effect of nonadherence.” Today, MS drugs and TNF blockers typically come with programs from the manufacturer to help patients with copays, often bringing them down to $5, noted Mr. Miller. Ensuring that patients have access to these programs will further reduce the financial burden and improve adherence. —Alison McCook

Specialty Pharmacy Continuum • Spring 2012

CLINICAL

INTERACTIONS continued from page 1

The FDA warning noted that administering a PPI in conjunction with IV methotrexate could lead to elevated serum levels of the IV agent, potentially resulting in methotrexate toxicity. The warning cited case reports and pharmacokinetic studies. In addition to PPIs, other drugs that can delay the elimination of methotrexate from the body, potentially with toxic consequences, include: nonsteroidal antiinflammatory drugs (NSAIDs), salicylic acid (aspirin) and many antibiotics, including penicillin, vancomycin and amoxicillin. “We’ve had several cases of methotrexate toxicities,” Dr. McBride said. “We treat a lot of acute leukemic and lymphoma patients who require highdose methotrexate. With this drug, we use a high dose, and you have to maintain the patient’s urine pH at greater than 7.0 in order to maximize the elimination of the drug and prevent any toxic side effects.” But patients taking PPIs, NSAIDs, antibiotics and/or aspirin may have a difficult time maintaining that pH, he noted. The signs of acute methotrexate toxicity include severe vomiting, diarrhea, and mucositis; low white cell and/or platelet counts; and renal failure. These risks are still present with the low doses of the drug used to treat rheumatoid arthritis (RA), but they are likely to be less well understood, experts note. “Patients with rheumatoid arthritis are also commonly taking NSAIDs as well,” said Robert Ignoffo, PharmD, professor of pharmacy at Touro University College of Pharmacy in Vallejo, Calif. “And if you’re taking an NSAID, you may also be taking a PPI because you have GI [gastrointestinal] side effects from the NSAIDs. So you have a double whammy—the NSAID and the PPI both interact with the methotrexate to delay its elimination.” As for the FDA alert, “I think the [agency] is on the mark here in issuing it,” Dr. Ignoffo said, adding that he wouldn’t be surprised if pharmacists and prescribing physicians were missing methotrexate interactions at least 10% of the time. “It may go unnoticed if the patient doesn’t have an extreme reaction.” Drug–drug interactions may not be the only problem with methotrexate therapy. Anything that increases the acidity of urine may impair elimination of the drug, such as carbonated beverages. A 2010 case report in the British Journal of Clinical Pharmacology (2010;70:762-764) found that unexplained low urinary pH in a lymphoma patient being treated with high-dose methotrexate was resolved in part by the elimination of cola drinks from the patient’s diet. In St. Louis, Dr. McBride had a similar experience. When a patient who was

scheduled for an acute lymphocytic leukemia regimen could not be started on the treatment because of a suboptimal pH range, “we found out he was constantly drinking huge containers of Pepsi. We told him to switch to water; he did, and his pH levels resolved.” The dose and duration of methotrexate therapy that trigger toxic drug interactions have yet to be determined, according to Dr. McBride. “That’s the question everyone is still trying to figure out,” he said. “There are case reports where someone taking a low dose of

methotrexate for rheumatoid arthritis has signs of toxicity even with only two to four weeks of NSAIDs.” Until such questions are resolved, experts recommend a high degree of caution when prescribing the drug combinations—not just for the patient’s safety but also to avoid the high cost of complications. Fortunately, getting access to a rescue drug, known as glucarpidase, may soon get easier. On Jan. 17, the FDA approved the medication (Voraxaze, BTG plc) for the treatment of toxic plasma methotrexate concentrations in patients with

delayed methotrexate clearance due to impaired renal function. The approval “represents a significant gain in the limited arsenal for treating methotrexate toxicity,” said Leigh Boehmer, PharmD, BCOP, clinical pharmacist in medical oncology at Barnes-Jewish. Dr. Ignoffo stressed the need for heightened awareness when treating patients with cancer and RA. “These drugs should be put on the checklist of red-flag items prior to the administration of methotrexate in any form.” —Gina Shaw

Connected Sales Reps = MORE Referrals! With CPR+ Web Portal, your Sales Reps can connect to the real-time CPR+ data they need to make more effective sales calls, build better relationships and maximize their productivity. From anywhere, anytime, they can: View & Edit Contact Information - Physicians, Case Managers, Discharge Planners, etc. Schedule Appointments and Create “To Do’s” Schedule, View and Conduct “Calls-to-Make” Document & Review Call Notes Instantly See Past Referrals by Contact Person and More!

Best of all, every Sales Appointment, Call, To Do and Sales Note is totally integrated into CPR+, the industry’s leading business management solution. New patient referrals are the lifeblood of your business. In today’s competitive environment, you need every advantage you can get.

Get a Demo in the next 30 days and you could win an iPad® and 3 months of Web Portal FREE – Call Today!

www.cprplus.com/sales

866-277-4876

Specialty Pharmacy Continuum • Spring 2012

CLINICAL

Anti-EGFR Agents Confer Increased Risk for Thromboembolic Events

ome anti-epidermal growth factor receptor (EGFR) agents used as targeted therapies in the treatment of advanced cancers—in particular, cetuximab (Erbitux, Bristol-Myers Squibb/ Lilly) and panitumumab (Vectibix, Amgen)—are associated with an increased risk for thromboembolic events compared with controls, according to a recent meta-analysis. The analysis, performed by a team of researchers at the medical oncology unit of the Azienda Ospedaliera Treviglio-Caravaggio in Italy, set out to assess the incidence of and relative risk for arterial thromboembolic events (ATEs) and VTEs associated with this

class of agents, which has been used increasingly in recent years in a variety of advanced cancers, including head and neck, colorectal, renal and lung cancers, among others. Although research has indicated that use of these agents can lead to the development of ATEs and VTEs in some patients,

the incidence and level of risk associated with their use remains unknown. The authors, who published their findings in the Annals of Oncology (2012 Jan 11. [Epub ahead of print]), analyzed 13 studies encompassing 7,611 patients undergoing therapy with anti-EGFR agents, including bevacizumab (Avastin, Genentech), cetuximab, erlotinib (Tarceva, Genentech), gefitinib (Iressa, AstraZeneca), sorafenib (Nexavar, Bayer/Onyx), panitumumab and sunitinib (Sutent, Pfizer). Overall, the use of anti-EGFR agents increased the risk for VTEs by 32% in patients with advanced solid tumors, the researchers found. In 11

studies that included 7,073 patients, the relative risk for VTEs in patients treated with an anti-EGFR agent was 1.32 compared with control patients (P=0.01). In five studies that included 3,030 patients, the relative risk for ATEs in patients treated with an anti-EGFR agent was 1.34 (P=0.11). Additionally, the authors found that the relative risk for VTEs was higher among those treated with monoclonal antibodies (1.34; P=0.01) than among those treated with tyrosine kinase inhibitors (1.16; P=0.65). Cetuximab and panitumumab carried the highest risk for ATEs and VTEs (1.61; P=0.006) within the anti-EGFR class in settings for which they are currently approved. On the other hand, the authors found that erlotinib and gefitinib did not carry an increased risk for thrombotic events.

Multi-kinase Inhibitor Regorafenib on Horizon for Colorectal Cancer

AN FRANCISCO—A first-in-class drug that jumped straight from a Phase I to a Phase III trial is expected to be approved in patients with refractory metastatic colorectal cancer (mCRC). The Phase III data, presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, has shown that treating this patient population with regorafenib (Bayer) increased median overall survival by 1.4 months. “The vast majority of colorectal cancer patients with metastatic disease are in a palliative situation,” having failed a wide range of standard therapies, according to investigator Axel Grothey, MD, professor of oncology at Mayo Clinic, in Rochester, Minn. Regorafenib could offer these patients a much-needed therapeutic option once the FDA approves the drug, Dr. Grothey said. The Phase III CORRECT trial included patients with mCRC disease progression during or within three months after the last administration of approved standard therapy, including fluoropyramidine, oxaliplatin, irinotecan, bevacizumab (Avastin, Genentech) and, if KRAS wild type, cetuximab (Erbitux, BMS/Imclone) or panitumumab (Vectibix, Amgen). The double-blind multicenter trial recruited 760 patients within the first 10 months. Patients were randomized in a 2-to-1 fashion to regorafenib (160 mg orally once daily) plus best supportive care (BSC) or placebo plus BSC. Placebo and regorafenib were given for three weeks on, one week off, until disease progression. The median overall survival, the primary end point of the trial, was 6.4 months in patients receiving regorafenib and 5.0 months in patients receiving placebo (hazard ratio, 0.77; P=0.0052). The results come from a prespecified interim analysis after 74% of events were reported. The median progression-free survival (PFS) was also improved in the regorafenib arm (1.9 vs. 1.7 months; hazard ratio 0.49; P<0.000001).

The efficacy of regorafenib was driven by improvements in stable disease (44.8% vs. 15.3%) and reductions in progressive disease (49.5% vs. 80.0%), rather than complete responses, of which there were none, or partial responses (only a minor improvement for regorafenib [1.0 vs. 0.4]) (all P<0.000001). <0.000001). “The strength of this drug is clearly more in delaying tumor progression than in inducing tumor responses,” Dr. Grothey said. Adverse events were managed with dose delays and reductions. There were few grade 4 events. Patients discontinued therapy slightly more often in the active arm because of treatment-related

adverse events (8.2% vs. 1.2%). Marlo Blazer, PharmD, BCOP, specialty practice pharmacist, outpatient oncology, Arthur G. James Cancer Hospital

& Richard J. Solove Research Institute, The Ohio State University, Columbus, said that she “is optimistic” about regorafenib’s approval, given the drug’s activity when compared with placebo. That’s especially the case, Dr. Blazer noted, given the fact that such efficacy was not demonstrated in single-agent trials assessing bevacizumab and sunitinib in this clinical setting. However, “that optimism is cautiously applied,” she stressed, “due to the increased risk of grade 3 rash (including hand-foot syndrome), fatigue, diarrhea and hypertension” documented in the trial. —Kate O’Rourke

Most C. difficile Infections Linked to Health Care Settings but Not Necessarily Hospitals

verall, 94% of Clostridium difficile infections (CDIs) are related to health care exposures, with 75% of these infections occurring among patients outside the hospital, such as patients who were recently discharged, patients receiving outpatient therapy and nursing home residents, according to a recent report from researchers at the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep 2012;61:157-162). Despite the known association between CDI and hospitals, the researchers found that 52% of CDIs treated in hospitals were present on admission. Some cases occurred in patients who had recently transitioned between health care settings, the investigators noted. For example, 20% of hospital-onset CDIs occurred in recent residents of nursing homes. Also, 67% of infections that had their onset in nursing homes occurred in patients who were recently discharged from an acute care hospital. Data for the MMWR paper was generated using 2010 population-based surveillance data from the CDC’s Emerging

Infections Program, in which 10,342 CDIs were identified. The researchers also used data from the CDC’s National Healthcare Safety Network, an Internet-based surveillance system, and from CDI prevention programs in Illinois, Massachusetts and New York. According to the study’s authors, CDI incidence rates, mortality rates and medical care costs have reached historic highs, despite the fact that many of the infections can be prevented. They called for more to be done to prevent CDIs and suggested that infection control programs and antibiotic stewardship be extended to non-hospital settings. “State health departments and partner organizations have shown leadership in preventing CDIs in hospitals and can prevent more CDIs by extending their programs to cover other health care settings,” the authors concluded. “Clinicians and other health care providers, as well as inpatient and outpatient health care facilities, [and] state and federal public health officials … could benefit from increased collaboration in preventing CDIs.” —George Ochoa

Specialty Pharmacy Continuum • Spring 2012

CLINICAL

International Group Issues Recommendations For Treatment of Pediatric MS

he International Pediatric Multiple Sclerosis Study Group (IPMSSG) has issued a consensus statement on pediatric multiple sclerosis (MS), providing treatment recommendations for first- and secondline therapy (Mult Scler 2012;18:116-127). In a field where practitioners face “challenges in recommending the most appropriate therapy,” according to the authors, the statement offers recommendations from a global network of neurologists, scientists, clinicians, and representatives of MS societies and other groups. Restricting its recommendations to relapsing forms

of pediatric MS, the IPMSSG recommended that “all pediatric patients with MS … be considered for treatment with either a beta-interferon or glatiramer acetate [Copaxone, Teva] as first-line therapy.” The statement added that children with a first demyelinating attack with features highly associated with MS may benefit from initiation of therapy. When receiving a beta-interferon, children should be titrated to as full a dose as tolerated, using adult titration schedules for guidance, the statement advised. Clinical practice with glatiramer acetate is to initiate at full dose. The statement proposed a working definition for inadequate treatment response (after a minimum of six months on full-dose therapy with full compliance): an increase in or no reduction in relapse rate, or new T2 or contrast-enhanced lesions based on magnetic resonance imaging (MRI) compared with the pretreatment period; or at least two confirmed relapses (clinical or MRI) within a period of 12 months or less. When inadequate treatment response occurs, the options include switching between first-line therapies and changing to a second-line agent. Because of the lack of adequate studies of second-line therapies in pediatric MS, the IPMSSG wrote that the choice to switch to one “will depend on patient characteristics and a collaborative informed decision made by the physician, family, and patient.” Among second-line therapies, the statement noted the potential benefits of natalizumab (Tysabri, Elan) but warned of the risk for progressive multifocal leukoencephalopathy. Pediatric use of mitoxantrone is discouraged because of its risk profile. The statement underscores the “considerable experience” with cyclophosphamide in pediatric autoimmune diseases other than MS while pointing out the paucity of relevant studies with rituximab (Rituxan, Genentech) and fingolimod (Gilenya, Novartis). The statement also discussed emerging MS therapies and made recommendations regarding the evaluation of investigational agents in pediatric MS. —George Ochoa

Potential First-in-Class Hepatitis C Vaccine Enters Phase I/II Trials

preventive vaccine against hepatitis C virus (HCV) that would potentially be the first in that class is entering a Phase I/II clinical trial, according to the Basel, Switzerland-based biopharmaceutical company Okairos. This is the first multicenter, double-blinded, randomized, placebo-controlled trial of a vaccine to prevent HCV infection, the company stated. The trial, born of collaboration between Okairos and the National Institute of Allergy and Infectious Diseases, will be conducted by co-principal investigators from Johns Hopkins University and the University of California, San Francisco. The Phase I/II trial follows promising Phase I results published in January in Science Translational Medicine (2012;4:115ra1). In that study in healthy volunteers, the T-cell–based preventive vaccine was safe and well tolerated, and, the authors reported, it was shown possible “to generate very strong, broad, long-lasting, and functional T-cell responses against HCV in healthy donors using an adenovirus-based approach.” The Phase I/II trial will test the vaccine’s potential effectiveness in protecting against chronic HCV infection. Enrolling 350 subjects, the trial will begin with an interim Phase I analysis of safety and immunogenicity data in a subset of the participants. The study’s primary end points will measure the incidence of chronic HCV infection, and the vaccine’s safety and tolerability. Okairos’ HCV vaccine is based on a technology platform that uses proprietary, chimpanzee-derived adenovirus vectors to stimulate a robust T-cell response against selected antigens. —Based on an Okairos press release and the article in Science Translational Medicine

Adverse Effects Cause Patient Noncompliance

rug toxicity is the primary cause of the high rates of noncompliance associated with long-term adjuvant endocrine therapy, according to results from a prospective, open-label Phase III clinical trial published in the February issue of the European Journal of Surgical Oncology (2012;38:110-117).

The IDEAL (Investigation on the Duration of Extended Adjuvant Letrozole) trial was designed by a team of researchers from the Netherlands to identify the factors associated with treatment discontinuation among patients with hormone receptor (HR)–positive postmenopausal early breast cancer undergoing therapy with aromatase inhibitors (AIs), such as letrozole (Femara, Novartis). The goal of the study was to assess noncompliance in the first 2.5 years of extended adjuvant therapy. The authors defined noncompliance as “early discontinuation of letrozole for all reasons, excluding death or recurrence.” The research was supported by an educational grant from Novartis Oncology. Researchers randomized 1,262 patients to receive either 2.5 or five years of adjuvant therapy with letrozole. In all, 1,215 of the patients in the study population had at least one dose of the study drug during the follow-up period, and most (1,069 patients) started treatment within six months of the discontinuation of prior adjuvant endocrine therapy, with tamoxifen, AIs or a sequence of both. Within the 2.5-year follow-up period, the overall noncompliance probability was 18.4%. Median follow-up time was 1.88 years for compliant patients and 1.11 years for noncompliant patients, respectively (P=0.003). The highest discontinuation rates were reported during the first six months of therapy with letrozole (49.7%). The vast majority of patients (85.1%) discontinued treatment due to adverse events (AEs), the most common of which included musculoskeletal, neurologic and dermatologic disorders. Further analysis of the study population revealed that patients previously treated with tamoxifen/AI sequential therapy had “the lowest probability” of treatment discontinuation at 2.5 years of follow-up compared with those whose prior endocrine therapy was tamoxifen or AIs alone (P=0.004). According to the authors, patients with longer treatment-free intervals (between initial endocrine therapy and adjuvant endocrine therapy) also were more likely to be noncompliant during adjuvant therapy with letrozole (P=0.011).

Spotlight On Our Very Best As 2011 drew to a close, the McMahon Group bestowed honors on several employees within its talented workforce. Throughout the year, McMahon’s portfolio of clinical news magazines maintained readership numbers that solidiﬁed their best-read status, and sales revenues increased despite a challenging economic climate. The diverse talents and collaborations among McMahon’s staff allowed the company to maintain its position as a trusted source of news and educational initiatives. McMahon’s publishing success was on display both in print and on the Web sites of its publications and custom media platforms.

2011

Here is a look at those recognized for their unique contributions during 2011.

SUPPORT/PRODUCTION/IT/FINANCE PERSON OF THE YEAR:

GRAPHIC DESIGNER OF THE YEAR:

Employees were asked to select the two most outstanding members from these departments. The ﬁrst winner was JOHN CABA, software developer, for his tireless devotion toward improving the company’s digital platforms.

The second winner was ROSA DIMICCO, accounting associate, for diligently ensuring that freelance writers and key opinion leaders are paid in a timely manner for their exceptional work.

JEANETTE MOONEY won the award in recognition of her creative talents as art director for Pain Medicine News, along with her superb layout designs for a host of Special Reports and custom newsletters.

MOST IMPROVED SALESPERSON OF THE YEAR:

SPECIAL PROJECTS EDITOR OF THE YEAR:

NEWSMAGAZINE EDITOR OF THE YEAR:

Each member of the sales staff seeks to improve throughout the year; however, one inevitably displays accelerated growth. DAVID NATHANSON, account manager, managed to do just that across several publications in 2011.

SETH KANDEL was voted best projects editor for his exemplary work on numerous custom media programs for medical industry clients as well as his management of the editorial in Infectious Disease Special Edition.

DONALD PIZZI, managing editor of Pain Medicine News, was recognized for the excellence of his news coverage throughout 2011. Under Don’s discerning eye, the magazine offers a comprehensive resource for clinicians involved in the management of pain.

SALES ACHIEVEMENT AWARD:

SALESPERSON OF THE YEAR:

DAVE KAPLAN, publication director of Pharmacy Practice News, was the 2011 winner in this category. Dave has proven himself to be an innovator among his peers by championing exciting new platforms and marketing opportunities for his many clients.

Whereas the other awards are decided by a jury of one’s peers, this honor is bestowed on the one salesperson who brings in the most revenue. For a record-breaking sixth year in a row, the winner was RICHARD TUORTO, senior group publication director for Anesthesiology News and Pain Medicine News. Richard’s dedication to his clients’ marketing needs and intimate knowledge of their products enable him to reach the zenith of sales proﬁciency year after year.

PERSON OF THE YEAR

PARTNERS AWARD

PERSON OF THE YEAR 2011:

PARTNERS SPECIAL RECOGNITION AWARD 2011:

This award recognizes the cream of the crop, and MARY LOU CAMPANELLA, chief financial officer, was the 2011 Person of the Year. Mary Lou has been able to streamline the company’s finances by thwarting inefficiencies and highlighting excess expenditures. Her constant professionalism, hard work and keen eye for detail have proven to be invaluable commodities that are greatly appreciated by her peers.

The partners of McMahon Publishing occasionally present an award to someone who has contributed to the success of the company over many years of service. This year’s winner was URBAN S. MULVEHILL, who has provided legal services to the company since 1983. He became a partner at his law ﬁrm, O’Neill DiManno and Kelly, in 1980 after having served as a trial lawyer for several years at the U.S. Department of Justice. Urban’s relaxed demeanor and sage advice over the past three decades have been greatly appreciated.

Specialty Pharmacy Continuum • Spring 2012

CLINICAL SPOTLI G HT ON HE P A T I T I S

Use of Direct-Acting Antiviral Agents for

Treatment of Hepatitis C Michelle T. Martin, PharmD, BCPS, BCACP Clinical Pharmacist Clinical Assistant Professor

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

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

Hepatitis C virus (HCV) is the most common blood-borne infection in the United States.1 The Centers for Disease Control and Prevention estimates that HCV affects approximately 4 million Americans, or 1.3% to 1.9% of the US population.2-5 These estimates do not include homeless, incarcerated, or institutionalized patients, so the estimate is conservative. Hepatitis C infection is estimated to cause about 12,000 deaths annually in the United States.6 More Americans are infected with and die from HCV than from HIV.7 HCV is the leading reason for liver transplant, and the leading cause of end-stage liver disease, liver-related death, and hepatocellular carcinoma.8,9 The progression of HCV over time is shown in the Figure.10 These sequelae of HCV carry a tremendous and growing financial burden. The annual cost of HCV treatment is expected to increase from $30 billion in 2009 to $85 billion in 2028.11

HCV is a single-stranded, enveloped RNA virus from the Flaviviridae family of the Hapacivirus genus. The virus was first discovered in 1989 and a sensitive HCV antibody blood test to detect it was developed and in use by July 1992.12 Approximately 15% to 25% of patients who are exposed to HCV will clear the virus and eliminate the infection; the remaining 75% to 85% of patients will develop chronic HCV. Table 1 lists the risk factors and modes of transmission for HCV. 13 Recent screening initiatives have been directed at patients born between 1946 and 1964 who are the most likely to be infected with HCV due to tainted blood transfusions and injection drug use.2,14 The goal of HCV treatment is eradication of the virus, which is denoted by a negative viral level 24 weeks after completion of treatment, known as sustained virologic response (SVR). Available treatment for HCV is successful in up to 80% of patients, depending on the HCV genotype.13,15-18 Six main

genotypes have treatment recommendations in the United States, and several subtypes exist.19 Genotype 1 accounts for approximately 75% of cases; genotypes 2 and 3 account for approximately 20% of cases; and genotypes 4 to 6 account for a small, yet increasing number of cases due to the nation’s expanding cultural diversity.20 Vaccines are under investigation, but thus far have not been successful because of the heterogeneity of the virus and its rapid mutation. Pegylated interferon (pegIFN) alfa-2a (Pegasys, Genentech) or alfa2b (Peg-Intron, Schering-Plough) and ribavirin (RBV) were the former standards of care for genotype 1, and these are the only 2 medications FDAapproved to treat HCV genotypes 2 to 6.21-23 PegIFN is self-administered

once weekly via subcutaneous injection. Pegasys dosing depends on renal function, and Peg-Intron dosing depends on weight and renal function. RBV is dosed orally twice daily and works in conjunction with PegIFN. It is not effective as monotherapy for the treatment of HCV. Ribavirin dosing depends on weight, renal function, and genotype.

New Antiviral Agents The first direct-acting antiviral (DAA) agents, telaprevir (Incivek,

•

see HEP C, page 22

Table 1. Risk Factors And Modes of HCV Transmission 15%-25%

Intranasal drug use IV drug use Hemodialysis

75% -85%

HIV or hepatitis B virus co-infection 20%

Occupational exposure

3%-6% per year

Perinatal transmission Injections with used/ contaminated needles

1%-4% per year

Blood transfusions or solid organ transplant (prior to July 1992) Clotting factors (prior to 1987)

0.5

Approximate Time, y

Figure. Progression of HCV. ESLD, end-stage liver disease; HCC, hepatocellular carcinoma; HCV, hepatitis C virus Based on reference 16.

Tattoos, acupuncture, or body piercing with unsterilized instruments Sexual transmission (multiple sex partners, men who have sex with men, or history of STDs) IV, intravenous; STD, sexually transmitted disease Based on reference 13.

Specialty Pharmacy Continuum • Spring 2012

CLINICAL

Table 2. Protease Inhibitor Adverse Drug Reactions, Monitoring, and Management

HEP C continued from page 21

Vertex) and boceprevir (Victrelis, Schering-Plough), were approved for HCV genotype 1 in May 2011.24,25 Each protease inhibitor (PI) must be used in combination with pegIFN and RBV. Monotherapy with these agents is associated with rapid virologic resistance and treatment failure. Prior to approval of these new agents, dual therapy with pegIFN and RBV had resulted in SVR rates of 38% to 54%.16-18 The overall SVR rates with use of the PIs as part of triple therapy for treatment-naive HCV genotype 1 patients in Phase III clinical trials was 75% with telaprevir and 66% with boceprevir.26,27 The SVR rates vary based on a patient’s treatment history (lower rates for previous null-responders and partial-responders compared to relapsers) and stage of fibrosis (lower SVR rates for patients with cirrhosis compared with patients with less fibrosis). The PIs prevent the virus from cleaving the polyprotein into smaller proteins, and thus interfere with the virus’ ability to replicate.28 They both have a fixed dose and are given every 8 hours. Doses are not decreased for any reason. In clinical trials of HIV-coinfected patients, higher doses of telaprevir have been used with specific antiretroviral agents including efavirenz (Sustiva, Bristol-Myers Squibb), but this combination is not yet FDA-approved.29 Telaprevir must be administered with food containing 20 g of fat to ensure proper absorption, while boceprevir must be administered with food containing at least 100 calories. It is important to discuss with patients the importance of co-administration with food (and importance of healthy food choices) as imperative for proper absorption so patients understand the reasoning and adhere to proper dosing. Several adverse effects can occur with the PIs (Table 2). Boceprevir can cause anemia, headache, dysgeusia, and nausea. Telaprevir can cause anemia, anorectal irritation, diarrhea, dysgeusia, nausea, pruritis, and rash.24,25 These medications also have numerous drug–drug interactions because they are cytochrome P450 3A4 substrates and inhibitors. HCV treatment and duration depends on the patient’s HCV genotype (Table 3).13,15,24,25 Treatment of HCV genotype 1 with triple therapy is complex for both patients and provid-

Adverse Drug Reactions

Monitoring

Management

Nausea

Patient report

• Eat bland foods • Eat small frequent meals • Take oral antiemetics

Rash/dry skin/ itching

Physical exam, patient report

• Use topical corticosteroids • Use topical moisturizing creams and emollients • Avoid alcohol-based products • Wear loose-fitting clothing • Ensure adequate hydration • Take oral antihistamines

Anorectal irritation

Physical exam, patient report

• Use topical corticosteroids, anesthetics, witch hazel, emollients, and skin protectants • Use wet toilet paper

Diarrhea

Patient report

• Take oral anti-diarrheals • Make diet and fiber intake adjustment

Hemolytic anemia

Complete blood count with differential at weeks 2, 4; then every 4 wk or as clinically indicated

• Dose-reduce ribavirin • Add erythropoietin-stimulating agent

Based on references 24 and 25.

Table 3. HCV Treatment Options Based on Genotype Genotype

Treatment Options

Treatment Length

Stopping Points

pegIFN and RBV plus PI (BOC or TVR)

• 24-48 wk • Response-guided therapy with PI • Previously up to 72 wk with pegIFN and RBV

• At week 4 and 12 if VL >1,000 IU/mL (TVR) • At week 12 if VL >100 IU/mL (BOC) • At week 24 if VL detectable (any course of treatment)

2 and 3

pegIFN and RBV

24 wk

Week 12 if null-responder

pegIFN and RBV

48 wk

Week 12 if null-responder, week 24 if nonresponder

5 and 6

pegIFN and RBV

Typically 48 wk

Week 12 if null-responder, week 24 if nonresponder

BOC, boceprevir; pegIFN, pegylated interferon; PI, protease inhibitor; RBV, ribavirin; TVR, telaprevir; VL, viral load Based on references 13,15,24, and 25.

ers. Non-cirrhotic patients with genotype 1 who are naive to HCV treatment are eligible for response-guided therapy (potentially a shortened duration of treatment of 24 weeks for telaprevir-based regimens, and 28 weeks for boceprevir-based regimens) if they achieve an extended rapid virologic response, or negative virus level at weeks 4 and 12 of treatment with telaprevir, or a negative viral level at weeks 8 and 12 for patients with boceprevir.24,25 Patients with cirrhosis, and treatmentexperienced patients who were nullresponders must undergo the entire 48 weeks of treatment for both PI regimens.13,15,24,25 Telaprevir is started with pegIFN and ribavirin and triple therapy lasts for 12 weeks, then the patient continues pegIFN and ribavirin for 12 or 36 weeks, depending on the previously mentioned factors. Boceprevir-based regimens always start with 4-week pegIFN and RBV lead-in, and boceprevir is added for triple therapy after completion of the lead-in. Naive, non-cirrhotic patients

with a detectable virus level at week 8 will have 32 weeks of triple therapy and 48 weeks of total treatment. Cirrhotic or previous null-responders start with a 4-week lead-in and complete 44 weeks of triple therapy with pegIFN, RBV, and boceprevir. Relapsers from previous treatment have differing lengths of therapy depending on viral response and PI regimen (Tables 4 and 5).24,25 If patients have a detectable viral level at week 24 on either PI regimen, all HCV treatment must be discontinued. Several other DAA agents are in clinical trials.29 The treatment of HCV is poised to change radically over the next decade.

Patient Considerations Selection of PI depends on provider and patient preference, insurance coverage and affordability, length of treatment, and side-effect profile. Patients with difficulty adhering to medication regimes may prefer telaprevir, as it has a shorter duration of treatment than boceprevir. Patients with comorbid skin

conditions or hemorrhoids may prefer boceprevir as it does not exacerbate these conditions. Patients with comorbid obesity or lipid disorders may have difficulty with the fat intake requirement with telaprevir. Table 6 details additional comparisons of the PIs.

Conclusion HCV treatment requires a team of health care professionals who are dedicated to the management of the disease. Open communication among providers, patients, and pharmacy personnel is imperative in the coordination of patient-specific HCV treatment. It requires intensive monitoring and patient education to ensure optimal patient outcomes. Due to the advent of complex new antiviral agents, clinical pharmacists have a unique opportunity to improve outcomes in the HCV treatment population. Drs. Martin and Hanson reported no relevant financial disclosures. You can contact the authors at: mmichell@uic.edu and Rhanso2@uic.edu.

Specialty Pharmacy Continuum â&#x20AC;˘ Spring 2012

CLINICAL

C: an age wave of disease burden. Am J Manag Care. 2005;11(suppl 10):s286-s295.

Table 4. Telaprevir-based Regimens

Stage of Fibrosis

Previous HCV Treatment

Noncirrhotic

Naive

Cirrhotic

Naive

Week 4

Week 12

Week 24

Length of Triple Therapy, wk

Undetectable

When To Stop TVR

When To Stop pegIFN and RBV

Week 12

Week 24

Undetectable

<1,000 IU/mL

Week 48

<1,000 IU/mL

Week 48

Noncirrhotic

Previous relapser Undetectable or partial responder <1,000 IU/mL

Undetectable

Week 24

<1,000 IU/mL

Week 48

Cirrhotic

Previous null-responder

<1,000 IU/mL

Week 48

<1,000 IU/mL

HCV, hepatitis C virus; pegIFN, pegylated interferon; RBV, ribavirin; TVR, telaprevir Based on reference 24.

Week 24

Length of Triple Therapy, wk

When To Stop When To pegIFN Stop BOC and RBV

Undetectable

Week 28

<100 IU/mL

Week 36

Week 48

Previous HCV Treatment

Week 8

Week 12

Noncirrhotic

Naive

Undetectable

Detectable

13. Ghany MG, Strader DB, Thomas DL, Seeff LB. American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335-1374. 14. McGarry L, et al. The impact of birth-cohort screening for hepatitis c virus (HCV) compared with current risk-based screening on lifetime incidence of and mortality from advanced liver disease in the United States. DDW 2011; abstract 477. 15. Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB. American Association for the Study of Liver Diseases. An update on treatment of genotype 1 chronic hepatitis C virus infection. Hepatology. 2011;54(4):1433-1444. 16. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347(13):975-982.

Table 5. Boceprevir-based Regimens

Stage of Fibrosis

12. Houghton M. The long and winding road leading to the identification of the hepatitis C virus. J Hepatol. 2009;51(5):939-948.

Cirrhotic

Naive

Any level

<100 IU/mL

Week 48

Noncirrhotic

Previous relapser or partial responder

Undetectable

Week 36

Detectable

<100 IU/mL

Week 36

Week 48

Cirrhotic

Previous null-responder

Any level

<100 IU/mL

Week 48

BOC, boceprevir; HCV, hepatitis C virus; pegIFN, pegylated interferon; RBV, ribavirin Based on reference 25.

17. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358(9286):958-965. 18. Hadziyannis SJ, Sette H Jr, Morgan TR, et al for PEGASYS International Study Group. Peginterferonalpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346-355. 19. Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural history, treatment and prevention of hepatitis C. Ann Intern Med. 2000;132:296-305. 20. Nainan OV, Alter MJ, Kruszon-Moran D, Gao FX, Xia G, et al. Hepatitis C virus genotypes and viral concentrations in participants of a general population survey in the United States. Gastroenterology. 2006;131:478-484. 21. Pegasys [package insert]. South San Francisco, CA: Genentech USA, Inc.; 2011. 22. PegIntron [package insert]. Whitehouse Station, NJ: Schering Corporation, a subsidiary of Merck & Co., Inc.; 2011.

Table 6. Protease Inhibitor Comparison Protease Inhibitor

Boceprevir

Telaprevir

Length of triple-therapy treatment

24, 32, or 44 wk

12 wk

Cost per 4-wk supply

Approximately $4,400

Approximately $16,000

Pill burden

4 capsules every 8 h

2 tablets every 8 h

Packaging

28 bottles containing 12 capsules

4 boxes of 7 blister cards containing 3 sections, each with 2 tablets

Administration

With food: 100 calories

With food: 20 g of fat

References 1. World Health Organization. Hepatitis factsheet. Available at: http://www.who.int/ mediacentre/factsheets/fs164/en. Accessed April 1, 2012.

Disease Burden from Viral Hepatitis A , B, and C in the United States. http:// www.cdc.gov/hepatitis/PDFs/disease_burden. pdf. Accessed April 1, 2012.

JW, Holmberg SD. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med. 2012;156(4):271-278.

2. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705-714.

5. Institute of Medicine. Hepatitis and liver cancer: A national strategy for prevention and control of hepatitis B and C. http://www.iom. edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-andControl-of-Hepatitis-B-and-C.aspx. Accessed April 1, 2012.

8. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol. 2007;13(17):2436-2441.

3. Centers for Disease Control and Prevention. Division of Viral Hepatitis - Statistics and Surveillance 2009. http://www.cdc.gov/ hepatitis/HCV/StatisticsHCV.htm. Accessed April 1, 2012.

6. Wise M, Bialek S, Finelli L, Bell BP, Sorvillo F. Changing trends in hepatitis C-related mortality in the United States, 1995-2004. Hepatology. 2008;47:1-8.

10. Pyenson, B., Fitch, K., Iwasaki, K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Seattle, WA: Milliman, Inc.; 2009

4. Centers for Disease Control and Prevention.

11. McHutchison JG, Bacon BR. Chronic hepatitis

Ly KN, Xing J, Klevens RM, Jiles RB, Ward

9. Kim WR. The burden of hepatitis C in the United States. Hepatology. 2002;36(Suppl):S30-S34.

23. Copegus [package insert]. South San Francisco, CA: Genentech USA, Inc.; 2011. 24. Incivek [package insert]. Cambridge, MA: Vertex Pharmaceuticals Inc.; 2011. 25. Victrelis [package insert]. Whitehouse Station, NJ: Schering Corporation, a subsidiary of Merck & Co., Inc.; 2011. 26. Poordad F, McCone J Jr, Bacon BR, et al for the SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1195-1206. 27. Jacobson IM, McHutchison JG, Dusheiko G, et al for the ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364(25):2405-2416. 28. Schlutter J. Therapeutics: new drugs hit the target. Nature. 2011;474:S5-S7. 29. KE Sherman, JK Rockstroh, DT Dieterich, et al. Telaprevir combination with peginterferon alfa-2a/ribavirin in HCV/HIV coinfected patients: 24-week treatment interim analysis. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011); November 4-8. 2011; San Francisco, CA. Abstract LB-8.

â&#x20AC;˘

see HEP C, page 25

Specialty Pharmacy Continuum • Spring 2012

CLINICAL continued from page 23

Health System Approach to Specialty Pharmacy Services

There are several advantages to integrated specialty pharmacy services. As part of the health care team, the clinical pharmacist has direct access to medical records, pharmacy records, and prescribing physicians. This allows for continuity of care between clinicians by minimizing handoffs and other communication delays, and gives the patients the opportunity to see multiple members of their care team in the same visit. Unique to this service model, the patient has 3 different dispensing options to meet their needs: pharmacy pick up, mail order, or our most used option, in-clinic pickup. Timing is everything with HCV therapy, so the ability to coordinate labs, refills, and clinic visits is extremely valuable to ensure accuracy in reading and monitoring lab results and improve overall outcome. Additionally, the clinical pharmacist has immediate access to the team of physicians if complications occur, resulting in quicker interventions and resolutions. Additionally, through a collaborative practice agreement, the clinical pharmacist can modify treatment regimens to address such problems. The treatment of HCV revolves heavily around precise therapy management, which can be difficult when the medications are dispensed outside the health system. The use of external pharmacy fulfillment puts the majority of the coordination responsibilities on the patients who are already overwhelmed with the daily regimens. Most patients have little knowledge of or do not understand the need for a PA, particularly for those as multifaceted as HCV PAs. When the dispensing of the medication occurs outside the health system, it introduces additional complications in managing PA renewals. This is due to the onus it may put on the patient to reliably coordinate refills with enough lead time to identify and renew expired or expiring PAs. This can lead and has led to interruption in therapy with a significant risk for causing poor outcome. With the implementation of more plan lockouts and changes in network status, this is becoming a growing challenge for the health care team. Health systems should consider expanding specialty pharmacy operations to patients with HCV to improve coordination and continuity of care, increase patient satisfaction, and contribute to improved patient outcomes.

Specialty Pharmacy Service Call Center

Specialty Clinic Pharmacist

Specialty Clinic Physician

ealth systems that specialize in the diagnosis and treatment of hepatitis C have a unique opportunity to expand their specialty pharmacy service through the provision of therapy management, continuous monitoring, and assurance of continuity of care. The University of Illinois Hospital & Health Sciences System takes an integrated specialty pharmacy approach to the management of treatments for hepatitis C. The structure is built around a clinical pharmacist–managed program incorporated into an outpatient specialty clinic that focuses on liver-related diseases. As part of a multidisciplinary team, a clinical pharmacist works with the physicians, nurses, and medical assistants in the treatment of the patients. The clinical pharmacist performs multiple functions including education of patients and their representatives, screening for individuals who qualify for treatment, developing and initiating individualized treatment plans, and providing ongoing follow-up and management of the patients once they are started on therapy. This ongoing management includes lab monitoring and interventions, sideeffect management, lifestyle education and assessment, regimen adherence and coordination of refills, and also serving as a mentor for the patients (Figure). The clinical pharmacist works with the health system’s specialty pharmacy service to initiate and obtain prior authorization (PA) requests, handle prescriptions, and monitor adherence through refill management. With current hepatitis C treatments, one of the most challenging aspects of initiating therapy can be securing and renewing PAs for reimbursement; it is not uncommon to obtain multiple PAs for each patient throughout the course of treatment as well as to submit required clinical information at certain benchmarks to maintain coverage. Additionally, there is a lack of standardization for PAs among the different third-party payers in terms of number of pages or number of forms needed, degrees of clinical detail requested, and time to process and approve the request. Because most payers require PAs for HCV medications, having a dedicated specialty pharmacy team with prior authorization expertise is essential.

Figure. University of Illinois Hospital & Health Sciences System: integrated specialty pharmacy approach for the management of hepatitis C. © 2012 University of Illinois Hospital & Health Sciences System. All rights reserved.

Look for our next Disease State Spotlight by a non-hospital–based specialty provider in our summer issue.

Specialty Pharmacy Continuum • Spring 2012

CLINICAL

Patient Case

Time

Hepatitis C Virus Level

Hemoglobin, ANC, g/dL cells/mcL

Platelets/ mL

Total Bilirubin, mg/dL

ALT, U/L

AST, U/L

changes. The patient denied missing doses of HCV treatment, and denied alcohol consumption during treatment.

M is a 55-year-old man with Baseline 585,040 IU/mL 16 3,100 218,000 1.1 95 54 history of hepatitis C virus (HCV) genotype 1a, with a baseWeek 4 Not detected 13.5 1,600 199,000 1 34 31 line viral load of 585,040 IU/ Length of Treatment Week 12 Not detected 12 1,400 251,000 0.9 23 24 mL upon presentation. He had TM’s HCV level was grade 2, stage I to II disease After Not detected 12.2 1,500 219,000 0.6 31 27 undetectable at weeks on liver biopsy 3 months earWeek 24 4 and 12, so he qualified lier. He had not been previously ALT, aspartate aminotransferase; ANC, absolute neutrophil count; AST, alanine aminotransferase for a total of 24 weeks treated for his HCV. His physiHCV treatment using cian referred him to the clinical response-guided therpharmacist for HCV treatment apy. TVR treatment always ends at 12 weeks, but with a protease inhibitor (PI). The clinical pharmatwice daily, and TVR 750 mg orally every 8 hours patients continue pegIFN and RBV for either 12 or cist evaluated the patient’s medical history and inter- with 20 g of fat. He completed 12 weeks of TVR, 36 weeks, depending on the viral response, previviewed him to verify readiness for treatment. and then continued treatment with pegIFN and ous treatment response, and extent of liver fibroThe specialty pharmacy team evaluated the RBV. He completed 24 weeks of pegIFN and RBV sis. If the patient had cirrhosis, or if the patient had patient’s insurance for HCV medication coverage. treatment. been a null-responder to treatment with pegIFN TM’s prescription insurance required PAs for both No erythropoietin-stimulating agents or granuloand RBV in the past, the total length of treatment pegylated interferon (pegIFN) and ribavirin (RBV) cyte colony-stimulating factors were needed durwould have been 48 weeks instead of 24 weeks. but not telaprevir (TVR). Some insurance compaing his treatment, and the doses of RBV and pegIFN The patient had an end-of-treatment response nies did not require PAs for the PIs for the first few remained unchanged throughout his course of therwith an undetectable HCV level at the completion months after they were on the market, but many apy. If the patient had experienced anemia durof 24 weeks of treatment. His hemoglobin, absolute now do. The clinical pharmacist completed the PAs. ing treatment, the dose of RBV could have been neutrophils, and platelets were within an acceptable TM’s insurance plan also required that a specialty decreased (but not stopped entirely if he was takrange during treatment. His liver enzymes improved mail-order pharmacy fill his prescriptions. After ing TVR). The dose of TVR is never adjusted durwith elimination of the viremia. The patient’s careful coordination with the outside pharmacy and ing treatment, and the duration is always 12 weeks. HCV level was checked at 12 and 24 weeks after the patient, the medications were sent directly to If the patient had experienced severe neutropenia completion of treatment to assess for SVR. If the patient’s home. He was instructed to bring the or thrombocytopenia, the pegIFN dose could have the patient’s HCV level is still undetectable at 24 medications to his first clinic visit for education and been decreased during treatment, but not stopped weeks after completing HCV treatment, it will be treatment initiation, and the patient verbalized his entirely if he was still taking RBV or RBV and a PI. considered a cure. understanding not to start the medication on his The patient tolerated treatment well. He experiUse of PIs in HCV genotype 1 offers select patients own prior to his clinic appointment with the clinical enced fatigue and shortness of breath with exeran opportunity for a shortened duration of HCV pharmacist and physician due to the intense education; mild fevers, chills, headaches, and body aches treatment. Patients without cirrhosis respond better tion required prior to HCV treatment. with pegIFN injections; minor anal irritation; and minto HCV treatment, and this particular patient was an TM was started on HCV (pegIFN) alfa-2a 180 mcg imal injection site irritation and erythema. He did example of an ideal virologic response to treatment. subcutaneously every week, RBV 600 mg orally not experience a rash, and had no significant mood

We’re in a

position

to fill your

position

For classified advertising: contact Alina Dasgupta 212-957-5300 x338 adasgupta@mcmahonmed.com

Specialty Pharmacy Continuum • Spring 2012

CLINICAL

New Indication Sought for Methylnaltrexone Researchers recommend the agent for opioid-induced constipation in patients treated for nonmalignant pain Virtually all the data on methylnaltrexone (Relistor, Salix/Progenics) seem to confirm the drug can bring fast, effective and relatively side effect–free relief to patients suffering from opioid-induced constipation. The drug’s potential significant adverse events are gastrointestinal (GI) perforation and abdominal pain, but these do not appear to be a large concern. The subcutaneous form of methylnaltrexone, an opioid antagonist, was approved by the FDA in April 2008 for add-on therapy for patients receiving palliative care for advanced illnesses and those who have opioid-induced constipation but have not responded sufficiently to laxatives. Salix Pharmaceuticals is now seeking an indication for patients with nonmalignant pain based on data from 2011, and is conducting Phase III trials of oral methylnaltrexone. The 2008 approval was based largely on two randomized, placebo-controlled studies funded by Progenics, one of which was later published in The New England Journal of Medicine (Thomas J. 2008;358:2332-2343). The results demonstrated that 48% and 52% of patients, respectively, treated with one or two to four daily injections of methylnaltrexone had a rescue-free bowel movement (RFBM)—laxation without the use of a rescue laxative—within four hours. The respective rates for patients receiving placebo were 15% and 8%, respectively (P<0.001, for both comparisons). Moreover, the median time to laxation was significantly shorter among patients receiving methylnaltrexone compared with placebo. Results of a recent randomized controlled trial indicate that approximately 30% of injections of subcutaneous methylnaltrexone in patients with chronic, noncancer pain and opioid-induced constipation treated once a day or once every other day had an RFBM within four hours of treatment (Michna E. J Pain 2011;12:554-562). The four-week trial involved 150 patients randomized to 12 mg of subcutaneous methylnaltrexone daily, another 148 randomized to 12 mg of subcutaneous methylnaltrexone every other day and 162 given daily placebo injections. The results indicate the medication is effective and also safe, although the patients in the methylnaltrexone groups suffered from more abdominal pain, nausea, diarrhea and hyperhidrosis than did the placebo subjects. A post hoc analysis of the trial published three months later showed that 42.3% of patients responded to at least two of the first four daily treatments, and those patients averaged 4.8 RFBMs per week compared with two RFBMs per week among the other 57.7% of subjects (Michna E. Pain Med 2011;12:1223-

1230). Both analyses were funded by Progenics. Edward Michna, MD, lead investigator of both studies, said that their “results show that if a patient responds early on, it’s a good sign that they’re going to continue responding.” Dr. Michna, director of the Pain Trials Center and assistant professor at Harvard Medical School, Boston, noted that “Progenics asked for the post hoc analysis because [the company] wanted to find out which patients have the highest chance of success, since it’s an expensive medication.”

suspected mechanical GI obstruction. In 2010, the FDA issued a warning on methylnaltrexone because cases of GI perforation were reported in patients with complex confounding factors, such as cancer, GI malignancy, GI ulcer, and Ogilvie’s syndrome, who received methylnaltrexone and medications, such as bevacizumab (Avastin, Genentech), nonsteroidal anti-inflammatory drugs and steroids. The FDA stated that physicians should use methylnaltrexone with caution in patients with known or suspected lesions of the GI tract, and that patients who develop severe, persistent and/or

‘For opioid-induced constipation, methylnaltrexone’s almost like a diagnostic test, because if patients present with constipation as their gastrointestinal disorder and also are put on narcotics for something else, I may not know if the constipation is related to the narcotics or not. But if they respond to methylnaltrexone, then it’s likely narcotic related.’ —Douglas Drossman, MD Another Progenics-supported study, published in February 2011 (Expert Opinion Drug Metab Toxicol 2011;7:227-235), confirmed that when methylnaltrexone is administered subcutaneously it has a high bioavailability at therapeutic dose levels. It also has a terminal half-life of eight to nine hours, is metabolized only to a limited extent before being excreted and has a limited number of drug–drug interactions. “The onset of activity is fairly quick, and the practical half-life is short—in fact, the clinically relevant half-life is only two to three hours because the concentration drops so quickly after that,” confirmed Robert Israel, MD, senior vice president of medical affairs, Progenics, Tarrytown, N.Y., and senior author of The New England Journal of Medicine paper. “That means that you don’t get accumulation if you give it according to the instructions on the label, and you can give it as often as daily.” However, methylnaltrexone is contraindicated in patients with known or

worsening abdominal symptoms should be advised to discontinue therapy and immediately notify their physicians. Several specialists weighed in on why methylnaltrexone may produce certain side effects. In a letter to the editor of the Journal of Opioid Management, Xiulu Ruan, MD, director of clinical research at Physicians’ Pain Specialists of Alabama, PC, in Mobile, cited a study that showed another peripherally restricted opioid antagonist, naloxone methiodide, “when administered subcutaneously, blocked the antinociception of systemically and centrally administered methadone” (He L. J Pain 2009;10:369-379). Methadone is dependent on peripheral opioid receptors, and Dr. Ruan indicated that these data strongly support the argument that peripheral opioid receptors also may play an important role in antinociception. “From an evolutionary standpoint, it seems more conceivable that the plethora of opioid receptor types expressed

in the gut serve not only to modulate motility of the smooth muscles of the bowel but also to participate in antinociception,” Dr. Ruan said. “I wonder what the outcome would be when patients on methadone for analgesia were given methylnaltrexone and alvimopan.” Douglas Drossman, MD, professor and co-director of the Center for Functional GI & Mobility Disorders, University of North Carolina Health Care System, Chapel Hill, said Dr. Ruan’s explanation is plausible, especially based on related research he is conducting on narcotic bowel syndrome (Grunkemeier DM. Clin Gastroenterol Hepatol 2007;5:1126-1139). This condition leads to abdominal pain from narcotics, which activates glial cells and upregulates pain. However, Dr. Drossman noted, he has not seen abdominal pain develop de novo in any patients he has treated with methylnaltrexone, and that he has found it be quite effective, “although I am cautious when using it in patients who have predominant abdominal pain with their constipation.” “For opioid-induced constipation, methylnaltrexone’s almost like a diagnostic test, because if patients present with constipation as their gastrointestinal disorder and also are put on narcotics for something else, I may not know if the constipation is related to the narcotics or not. But if they respond to methylnaltrexone, then it’s likely narcotic-related,” said Dr. Drossman. Overall, however, experts appear optimistic about methylnaltrexone, not only for terminally ill cancer patients but also for those with chronic, nonmalignant pain. Tarun Mullick, MD, gastroenterologist at Rush–Copley Medical Center, in Chicago, commented that methylnaltrexone “will be useful for patients who have chronic pain issues or even have been on narcotics recently for diseases like pancreatitis. In addition, those patients with cancers of any type often are on narcotics. Thus this medicine can be useful in that case.” Dr. Mullick noted that health care providers caring for patients on this medication should “make sure the patient has no signs of mechanical bowel obstruction. In these patients, this medicine is contraindicated. Finally if there are any signs of worsening pain with this medicine, one may have to stop the medication. Naturally, methylnaltrexone, while helping with the narcotic induced constipation, can cause a reversal of effects of narcotics and increase pain.” —Rosemary Frei, MSc

The bookstore division of

mCmahonmediCalbookS.Com an online bookstore

order bookS online

The book Page

Visit our site to get a FREE financial planning audio CD!

PubliSher’S ToP PiCkS of The monTh on mCmahonmediCalbookS.Com These books and thousands more...

2012–2013 Top 300 Pharmacy Drug Cards Jill M. Kolesar; Lee Vermeulen

McGraw-Hill, January 12, 2012 This book is a fun, fast way to learn essential information about the top 300 drugs. Essential for pharmacy school courses and NAPLEX preparation.

Scan here for our complete catalog of medical books.

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

Basic & Clinical Pharmacology, 12th Edition Bertram Katzung; Susan Masters; Anthony Trevor

McGraw-Hill, December 13, 2011 Organized to reflect the syllabi in many pharmacology courses and in integrated curricula, this book covers the important concepts students need to know about the science of pharmacology and its application to clinical practice. Selection of the subject matter and order of its presentation are based on the authors’ many years of experience teaching this material to thousands of medical, pharmacy, dental, podiatry, nursing and other health science students.

Clinician’s Pocket Drug Reference 2012 Leonard Gomella; Steven Haist; Aimee Adams

Fundamentals of Pharmacognosy and Phytotherapy, Second Edition

Michael Heinrich Elsevier/Churchill Livingstone, April 11, 2012 This landmark textbook provides useful and fascinating insights into the history, botany, chemistry, phytotherapy and importance of medicinal plants in some of today’s health care systems. It brings together relevant data from numerous sources and provides cutting-edge information relevant to pharmacists, pharmacognocists, complementary practitioners, doctors and nurses alike.

Handbook on Injectable Drugs: 16th Edition Lawrence A. Trissel

ASHP, October 27, 2010 All 349 monographs have been updated in this edition, including six new monographs. For each monograph, compatibility, stability, storage and preparation data have been referenced and presented.

Managing Anticoagulation Patients in the Hospital: The Inpatient Anticoagulation Service

Michael Gulseth

McGraw-Hill, November 17, 2011

ASHP, June 15, 2007

This book has everything you need to know when prescribing and administering more than 1,000 of the drugs most often used in medical practice.

The first guide to providing systematic anticoagulation care in inpatient settings, this resource is written for pharmacists who practice in or are developing, implementing and maintaining an inpatient anticoagulation service.

Drug Facts and Comparisons 2012 Facts & Comparisons

Lippincott Williams & Wilkins, October 17, 2011 The health care professional’s first choice for comprehensive, authoritative and timely drug information for more than 60 years. Drugs are divided into related therapeutic or pharmacological groups for easy comparison.

Understanding Pharmacy Calculations, 2nd Edition Teresa A. O’Sullivan

APhA, March 1, 2012 Written in easy-to-understand language and emphasizing practical calculations that pharmacists do every day, this revised and updated edition of Understanding Pharmacy Calculations guides student pharmacists through the sometimes overwhelming introduction to the subject. SPC0412

READY TO USE. READY TO BUY. READY TO SELL. Amiodarone: the drug your customers know. And now, for the very ﬁrst time, it’s available from Baxter Healthcare Corporation in a manufacturer-prepared, ready-to-use, premixed form – the way your customers want it.

S U I T A B L E F O R : S U R G E R Y C E N T ER S - EMS When you offer Nexterone, you offer a valuable drug with convenience. Premixed Nexterone eliminates admixing time when there’s not a second to waste. It also has a shelf life measured in years, not hours. And that means your customers can store it in crash carts until the instant it’s needed.* Your customers are ready for Nexterone. Are you ready to make it available to them? Contact your Baxter sales representative to ﬁnd out more. *Store in carton to protect from light until ready to use.

NEXTERONE.COM

Baxter, Galaxy, Nexterone and the Sphere Graphic are trademarks of Baxter International Inc.

Medication Delivery

111616 11/11