Winter 2013 - Specialty Pharmacy Continuum by McMahon Group

Bridging the gap between the hospital and alternate-site care

Volume 2 • Number 1 • Winter 2013

specialtypharmacycontinuum.com

In This Issue Ask the Expert

Suzanne Tschida, PharmD, of OptumRx-United Healthcare, on managing transplant patients taking oral immunosuppressant therapy.

Policy

9 12

Limited distribution network set for Gattex, a newly approved treatment for short bowel syndrome. New Medicare legislation paves the way for at-home IVIG therapy.

Operations & Mgmt

Will non-pharmacy dispensing sites cut into specialty pharmacy market?

Disease State Spotlight

Pulmonary arterial hyptertension: current and future treatment trends.

Clinical

26 New column! IVIG FAQ, by Jerry Siegel, PharmD

Is There Room for Two New Trade Associations?

A ‘Tipping Point’ For Specialty Rx Spend Looming

NASP, SPAARx square off for the future of specialty pharmacy representation

ommunity pharmaccists have the National Communityy Pharmacists Association (NCPA)). Pharmacists practicing in hosp pittals and HMOs have the Ameeriican Society of Health-Syystem Pharmacists (ASHP)). Pharmacists involved in n managed care have the Academy of Managed Care Pharmacy (AMCP). Now, after years of rapid growth—but no trade group of its own— — specialty pharmacy haas no less than two new asssociations seeking to repressen nt the interests of its stakeeho olders. The first group emergged d last fall, with the launch of th he National Association of Specialtyy Pharmacy (NASP). On Jan. 31, Arm mad da Health da Care joined the party by an nnouncing the formation of the Speccialty lty Pharmacy Association of America (SPAARx). Whether sparks will indeed fly once these two groups begin to compete for members remains to be seen; for now, representatives of each group declined to go on the record about the other’s foray into the association arena. But in background interviews, a certain level of distrust between the two organizations was clear. Phil Hagerman, RPh, CEO of Diplomat Specialty Pharmacy and a founding member of NASP, did offer this observation: he said he wasn’t expecting the SPAARx announcement. “We found it surprising, as Armada has been around for many years and I never heard this was part of their plans.” Mr Hagerman also added a word of caution: “I believe having a second association enter the [specialty pharmacy] space will cause some confusion.”

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see NASP, SPAARx, page 16

New Product

pending on specialty medications increased by 22.6% during the first three quarters of 2012 compared with the same time period in 2011, according to the inaugural Drug Trend Quarterly report, released by Express Scripts in late November. And although those numbers may appear to be good news for the industry, some analysts say there may be a price to pay in the not-too-distant future. “From our surveys of payer panels, we are consistently hearing the theme that we’ve got to do something about the spiraling costs of specialty medications,”

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see COST TRENDS, page 14

High-Tech Tools For Improving Specialty Med Rx Websites, social media and mobile apps gaining traction

variety of new web-based initiatives are helping patients to manage disorders typically treated with specialty pharmacy medicines. To illustrate the many types of tools and what they involve, here’s a closer look at initiatives in three therapeutic areas: HIV, hemophilia and hereditary angioedema (HAE). In some cases, the initiatives promote screening and patient compliance with medications, while others focus on increasing communication

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see WEB TOOLS, page 7

The Book Page

Cometriq approved for metastatic thyroid cancer

Internal Medicine: A Guide to Clinical Therapeutics Monica L. Miller, Rebecca L. Attridge, Rebecca Moote, Laurajo Ryan

See page 10.

See page 25.

Evidence based. Patient proven.

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

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

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

Important Safety Information Gamunex-C, Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified, is indicated for the treatment of primary humoral immunodeficiency disease (PI), idiopathic thrombocytopenic purpura (ITP), and chronic inflammatory demyelinating polyneuropathy (CIDP). Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients. Patients predisposed to renal dysfunction include those with any degree of preexisting renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. Gamunex-C does not contain sucrose. For patients at risk of renal dysfunction or failure, administer Gamunex-C at the minimum concentration available and the minimum infusion rate practicable. Gamunex-C is contraindicated in individuals with acute severe hypersensitivity reactions to Immune Globulin (Human). It is contraindicated in IgA deficient patients with antibodies against IgA and history of hypersensitivity. Gamunex-C is not approved for subcutaneous use in patients with ITP or CIDP. Due to the potential risk of hematoma formation, Gamunex-C should not be administered subcutaneously in patients with ITP. Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV therapy. Thrombotic events have been reported in association with IGIV. Patients at risk for thrombotic events may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization and/or known or suspected hyperviscosity. There have been reports of noncardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury (TRALI)], hemolytic anemia, and aseptic meningitis in patients administered with IGIV. The high dose regimen (1g/kg x 1-2 days) is not recommended for individuals with expanded fluid volumes or where fluid volume may be a concern. Gamunex-C is made from human plasma. Because this product is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. After infusion of IgG, the transitory rise of the various passively transferred antibodies in the patient’s blood may yield positive serological testing results, with the potential for misleading interpretation. In clinical studies, the most common adverse reactions with Gamunex-C were headache, fever, chills, hypertension, rash, nausea, and asthenia (in CIDP); headache, cough, injection site reaction, nausea, pharyngitis, and urticaria with intravenous use (in PI) and infusion site reactions, headache, fatigue, arthralgia and pyrexia with subcutaneous use (in PI); and headache, vomiting, fever, nausea, back pain, and rash (in ITP). The most serious adverse reactions in clinical studies were pulmonary embolism (PE) in one subject with a history of PE (in CIDP), an exacerbation of autoimmune pure red cell aplasia in one subject (in PI), and myocarditis in one subject that occurred 50 days post-study-drug infusion and was not considered drug related (in ITP). Please see adjacent page for brief summary of Gamunex-C full prescribing information. 1. GAMUNEX-C package insert. Research Triangle Park, NC: Grifols Therapeutics Inc.; 2010.

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

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

Printed in USA.

September 2012

GX116-0912

GAMUNEX® X®-C

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

Caprylate/Chromatography Puriﬁed

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

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

• GAMUNEX-C is made from human plasma and may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease agent. • Passive transfer of antibodies may confound serologic testing. ----------------------------ADVERSE REACTIONS---------------------------• PI – The most common adverse reactions (ⱖ5%) with intravenous use of GAMUNEX-C were headache, cough, injection site reaction, nausea, pharyngitis and urticaria. The most common adverse reactions (ⱖ5%) with subcutaneous use of GAMUNEX-C were infusion site reactions, headache, fatigue, arthralgia and pyrexia.

• ITP – The most common adverse reactions during clinical trials (reported in ⱖ5% of subjects) were headache, vomiting, fever, -------------------------INDICATIONS AND USAGE------------------------nausea, back pain and rash. GAMUNEX-C is an immune globulin injection (human) 10% liquid • CIDP – The most common adverse reactions during clinical indicated for treatment of: trials (reported in ⱖ5% of subjects) were headache, fever, chills, hypertension, rash, nausea and asthenia. • Primary Humoral Immunodeficiency (PI) To report SUSPECTED ADVERSE REACTIONS, contact Talecris • Idiopathic Thrombocytopenic Purpura (ITP) Biotherapeutics, Inc. at 1-800-520-2807 or FDA at • Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) 1-800-FDA-1088 or www.fda.gov/medwatch. ----------------------------CONTRAINDICATIONS-------------------------------------------------------DRUG INTERACTIONS---------------------------• Anaphylactic or severe systemic reactions to human • The passive transfer of antibodies may transiently interfere with immunoglobulin the response to live viral vaccines, such as measles, mumps • IgA deficient patients with antibodies against IgA and a history and rubella. Passive transfer of antibodies may confound of hypersensitivity serologic testing. ---------------------WARNINGS AND PRECAUTIONS--------------------• IgA deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions. Have epinephrine available immediately to treat any acute severe hypersensitivity reactions. • Monitor renal function, including blood urea nitrogen, serum creatinine, and urine output in patients at risk of developing acute renal failure. • GAMUNEX-C is not approved for subcutaneous use in ITP patients. Due to a potential risk of hematoma formation, do not administer GAMUNEX-C subcutaneously in patients with ITP. • Hyperproteinemia, with resultant changes in serum viscosity and electrolyte imbalances may occur in patients receiving IGIV therapy.

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

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

08939771/08939782-BS Revised: October 2010

Specialty Pharmacy Continuum • Winter 2013

CLINICAL

Infusion Providers Phone Home, Improve Care Las Vegas—Conducting detailed follow-up phone calls with patients on home infusion therapy shortly after they start selfadministering medications can help identify and prevent potentially dangerous, costly medical errors, according to an executive at BioScrip, Inc., a national provider of home infusion services. Using a telephone data collection tool they developed, BioScrip providers found that more than 10% of new patients had at least one potentially significant issue within 24 to 72 hours of starting home infusion therapy, including breaching aseptic technique with the IV catheter, not flushing the IV catheter and uncontrolled pain. All the issues were resolved by re-educating the patient or the caregiver, contacting the prescriber, communicating with a home health nurse and/or delivering any missing supplies. Presenting the results at the American Society of Health-System Pharmacists 2012 Midyear Clinical Meeting, Cathy Johnson, RPh, the national director of clinical pharmacy operations for BioScrip, in Cincinnati, said, “The data showed that 10% to 15% of patients [on home infusions] have a serious issue, and if you can solve that early on, you can

keep those patients [at home] instead of them being readmitted to the hospital,” she said. “It also reduces stress on the health care system.” Ms. Johnson said that home infusion could be described as “hospitallike care in a home setting.” Patients “have an intravenous catheter that has direct access to their bloodstream, with its inherent risk factors, and the medications have significant side effects. For good clinical care, follow-up with patients is a smart thing to do.” Based on her knowledge of common issues that confuse home infusion therapy patients, Ms. Johnson wrote a series of 13 questions for company pharmacists and support personnel to ask patients when following up with them by telephone. The questions, which were added to the company’s patient management software in April 2012, included asking patients

Table. Home Infusion–Related Challenges Patients, n (N=296)

Problems Reported Serious breaches of aseptic technique involving the IV catheter, risking bloodstream infections

One or more missed doses

Redness and/or swelling at the IV insertion site; difficulty infusing medication through the IV catheter

Improper flushing of IV catheters

Home-based care was delayed by several days

Prescribed antibiotic not filled due to cost concerns

‘The data showed that 10% to 15% of patients [on home infusions] have a serious issue, and if you can solve that early on, you can keep those patients [at home] instead of them being readmitted to the hospital.’ —Cathy Johnson, RPh to describe how they were using their infusion medications, if they were having any difficulties with their IV catheter, if there was any fever or pain not controlled by medication, and if they

had any questions or concerns about their care. Ms. Johnson and her colleagues collected data from 296 patients being

•

see PHONE HOME, page 24

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HOME INFUSION

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SPECIALTY PHARMACY CONFERENCE

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Specialty Pharmacy Continuum • Winter 2013

CLINICAL

Ask the Expert: Suzanne Tschida, PharmD

Specialty Pharmacy Adds Value To Oral Immunosuppressive Therapy A

United Healthcare study has documented the pivotal role that specialty pharmacy plays in optimizing care, reducing overall treatment costs and improving therapy adherence of renal transplant patients taking oral immunosuppressant medications. The research measured how clinical management programs at specialty pharmacy add value beyond what patients experience acquiring these medications at conventional retail pharmacies, according to Suzanne Tschida, PharmD, BCPS, the vice president of specialty benefit & outcomes strategy at OptumRx, in Irvine, Calif. Dr. Tschida, the lead author of the study, which appears in the Jan./Feb. issue of the Journal of Managed Care Pharmacy y (2013;19:26-41), highlighted its key findings in a recent interview with Specialty Pharmacy Continuum. She also spoke about the complexities that patients face in adhering to oral immunosuppressant regimens, especially if they have comorbidities such as diabetes or hypertension and take perhaps a dozen medications per day, or if they are adolescent or pediatric patients, who often find complying with their drug regimens to be particularly challenging.

SPC: In conducting background research for your study, did you come across any other studies that pointed to adherence challenges in this patient population? Dr. Tschida: Of course; medication adherence or compliance is a well-recognized problem in transplant medicine, although concrete solutions are a bit harder to find. Basically, we found, in looking at the literature, that between 20% and 70% of patients in the transplant population do not adhere to therapy—the rate varying with definitions of adherence measures and study populations.1-7 Moreover, the rate of nonadherence is highest at one to three years post-transplant, but it may happen at any point during lifelong therapy.1, 8-9 SPC: Turning to your study, what was your approach and key results? Dr. Tschida: We propensity-matched one cohort of 519 United Healthcare members who filled at least 80% of their renal transplant immunosuppressant medication prescriptions at the specialty pharmacy in our specialty program, with another cohort of 519 United Healthcare members who filled at least 80% at retail pharmacies. The patients were matched on measures of health status, comorbid conditions and time since transplant using claims data. We tracked medical benefit claims and prescription drug claims for members taking oral formulations of cyclosporine, tacrolimus, mycophenolate and sirolimus. We measured primary outcomes, such as overall costs, total outpatient costs, total medical costs and pharmacy costs. Overall, we found that the specialty pharmacy program group showed consistent cost savings and higher therapy adherence: • 15% lower total mean cost during the first follow-up year—$24,315 versus

$27,891 (P=0.03) • 42% lower transplant-related medical costs—$5,9600 versus $8,486 ((P=0.04) • 32% less transplant-related medical costs—$5,259 versus $7,685 ((P=0.02) • More transplant-related prescriptions dispensed—18.67 versus 17.90 ( <0.05) (P • A higher weighted medication possession ratio—0.87 versus 0.83 ( =0.001). (P Interestingly, despite the fact that adherence was higher, transplant medication costs were significantly lower in the specialty pharmacy group. And that’s due to a negotiated competitive discount drug rate. Several other important outcomes were improved in the specialty pharmacy–managed group. For example, although not significant, there were lower hospitalizations, lower inpatient and outpatient medical costs, and shortened inpatient lengths of stay. SPC: Which aspects of the specialty pharmacy care program led to these outcomes? Which steps are most important to implement? Dr. Tschida: We empower members to manage their medications and take ownership of their conditions. Upon discharge from a transplant center, we can allow the center or a local pharmacy to [dispense] a grace fill if a patient needs immediate access to drugs. We notify patients of the requirements to obtain refills through a designated specialty pharmacy network. Upon first prescription fill by OptumRx, our specialty pharmacy, we teach patients extensively about how we’ll work with them clinically to screen for other gaps in therapy, comorbid conditions, potential drug–drug interactions or therapeutic duplication, and we also give them 24/7

access to a specialty-trained pharmacist who can help with medication questions and issues. Prescription refills are limited to a monthly supply to support our oversight of adherence, so we structure a call five to seven days prior to the due date to discuss any patient questions or problems and screen for adherence issues. While updating the clinical assessment on the call, a pharmacist stresses the transplanted organ failure risk if there is a medication nonadherence. We aim to oversee care without being too intrusive, so once we determine that a patient is clinically stable on the medications, we continue to provide adherence oversight, but the in-depth telephonic clinical assessments may be less frequent. We also screen for medication issues through medication reviews and questions during dispensing. SPC: What can be projected from this study to other areas of specialty management? Dr. Tschida: We’ve seen similar outcomes in improving medication adherence and clinical results and lowering medical service costs through our specialty pharmacy programs in oral oncology, rheumatoid arthritis, multiple sclerosis and HIV/AIDS. We’re excited about building our ability to reach and touch patients [using tools] such as web-based enhancements and emails when appropriate, because many patients are young, healthy, working and computer-savvy. SPC: What are the lessons here for specialty pharmacy readers? Dr. Tschida: Specialty medications are a significant market force today. This will continue because the pipeline is robust. Having the specialty expertise within a

therapeutic category to oversee patients and intervene ultimately drives the value of better medical outcomes. We’ve seen improvements in compliance and adherence, as well as the downstream benefits of better outcomes and savings. As an extension of the clinical team—physicians, nurses, surgeons and pharmacists—specialty pharmacy can help make sure patients achieve their best outcomes with their medication regimen.

References 1. Chisholm-Burns MA, Spivey CA, Garrett C, et al. Impact of clinical pharmacy services on renal transplant recipients’ adherence and outcomes. Patient Prefer Adherence. 2008;2:287-292. 2. Butler JA, Roderick P, Mullee M, et al. Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review. Transplantation. 2004;77:769-776. 3. Greenstein S, Siegal B. Compliance and noncompliance in patients with a functioning renal transplant: a multicenter study. Transplantation. 1998;66(12):1718-1726. 4. Chisholm MA, Vollenweider LJ, Mulloy LL, et al. Renal transplant patient compliance with free immunosuppressive medication. Transplantation. 2000;70(8):1240-1244. 5. Chisholm MA, Mulloy LL, DiPiro J. Comparing renal transplant patients’ adherence to free cyclosporine and free tacrolimus immunosuppressant therapy. Clin Transplant. 2005;19(1):77-82. 6. Bullington P, Pawola L, Walker R, et al. Identification of medication non-adherence factors in adolescent transplant patients: the patient’s viewpoint. Pediatr Transplant. 2007;11(8):914-921. 7. Dobbels F, Ruppar T, De Geest S, et al. Adherence to the immunosuppressive regimen in pediatric kidney transplant recipients: a systematic review. Pediatr Transplant. 2010;14(5):603-613. 8. Farney AC, Doares W, Kaczmorksi S, et al. Cost-effective immunosuppressive options for solid organ transplantation: a guide to lower cost for the renal transplant recipient in the USA. Immunotherapy. 2010;2(6):879-888. 9. DaVanzo JE, Dobson A, Kirby RF. Assessing the cost of dispensing immunosuppressive drugs to Medicare transplant recipients—an update. A report prepared for the transplant Pharmacy Coalition by The Lewin Group. April 15, 2007. http://www.regulations.gov/ contentStreamer?objectId=0900006480ca477 f&disposition=attach ment&contentType=pdf. Accessed February 5, 2013. Dr. Tschida’s co-investigators included William H. Shrank, MD, MSHS, an assistant professor of medicine at Harvard Medical School, Boston; Brett Sahli, PharmD, OptumRx; and Saad Aslam, PhD, PharmD and Tanvir Khan, MS, from Optuminsight, United Health Group’s data analytics division. Portions of this Q&A are based on content from a presentation by Dr. Tschida at the 2012 annual meeting of the Academy of Managed Care Pharmacy, in San Francisco.

Specialty Pharmacy Continuum • Winter 2013

TECHNOLOGY

WEB TOOLS continued from page 1

between doctors and patients, or educate patients about their disease.

Using Facebook and Twitter To Raise Awareness According to the Centers for Disease Control and Prevention (CDC), more than 1.1 million people in the United States are living with HIV infection. Yet, nearly 20% of those HIV-positive patients aren’t aware of their status and can unknowingly spread the virus to others. In Chicago, statistics on the disease are far worse: HIV rates in some neighborhoods have climbed to a staggering 53%, and more than 20,000 people are living with the disease, according to the CDC. Thus, efforts to promote awareness of HIV testing and treatment are sorely needed.

‘Programs like Need2Know can help educate and empower people to get [HIV] tested and treated, and if the results are positive, to help manage their disease.’ —Glen Pietrandoni, RPh The AIDS Foundation of Chicago (AFC), in partnership with Abbott Laboratories, is answering that need by using social media platforms such as Facebook and Twitter (#Need2KnowHIV) to educate patients about the immunodeficiency disease and encourage conversations about testing and treatment. Nearly 6,000 people were exposed to the campaign during the first week of the program’s launch (Nov. 27 to Dec. 3), and hundreds of them liked, shared or retweeted AFC’s message, according to the group. “We’re aiming to drive awareness and spark conversation, and ultimately prompt more people to get tested early and monitor their status regularly if they are living with HIV,” said Johnathon E. Briggs, MPH, the chief officer of external relations at AFC. “What sets Need2Know HIV apart from other HIV testing campaigns is that it highlights the importance of diagnosing HIV in its earliest stages,” Mr. Briggs said. He added that the program also emphasizes “ongoing viral load molecular testing for those living with HIV.” In a separate campaign, pharmacists

at Walgreens began offering free HIV testing in selected markets. It’s part of an innovative CDC program aimed at helping reduce the stigma of HIV. Hundreds of people have been tested at selected community pharmacies and retail clinics in Chicago; Lithonia, Ga.; and Washington, D.C. since the initiative launched last June. “We are very supportive of any initiatives that help people learn their HIV status. Programs like Need2Know can help educate and empower people to get tested and treated, and if the results are positive, to help manage their disease,” said Glen Pietrandoni, RPh, AAHIVP, the senior manager of HIV/AIDS and hepatitis, at Walgreens. “Both traditional face-to-face conversations and social media can be instrumental to making a meaningful difference.”

Engaging Physicians Hereditary angioedema is a rare but serious autosomal dominant genetic disease characterized by episodes of extreme swelling. HAE may affect the face, extremities, gastrointestinal tract or—most dangerously—the larynx. The larynx can swell, closing the airway and leading to asphyxiation and death. ViroPharma, Inc., hopes to raise awareness about the daily and long-term effects of the emotional burden of the disease with their “Moments Missed” campaign (www. momentsmissed.com). The goal is to help initiate ongoing and meaningful conversations between physicians and patients about how HAE may affect the work, school and social lives and the mental state of patients. The emotional effects of HAE oftentimes aren’t discussed with physicians. “The idea for this campaign arose from conversations we’ve had with patients in the past,” said Bianca Jay, ViroPharma’s senior product manager for HAE. “Many patients can recall not only several specific instances where they had to miss a dance or their child’s school play because of their HAE, but also how days lost to HAE have drastically impacted their decisions regarding school, work, friends, vacations or work travel.” Managing HAE often involves evaluating the frequency and severity of a patient’s attacks, and using this information to determine the most appropriate therapeutic regimen. But HAE also can have a devastating psychological impact—producing feelings of

Boehringer Ingelheim Launches Hepatitis C Web Portal

oehringer Ingelheim recently launched a website, HepCRedefined.com, to help improve the lives of people with hepatitis C virus (HCV) infection. Created in collaboration with HCV community advocates and health care providers, the portal offers a range of interactive resources that can be shared via social media channels, embedded on other websites or viewed on various smart devices. “The more we empower ourselves to learn about the challenges associated with HCV, the better we will be able to provide patient management and come closer to a cure for this disease,” said Steve Smith, the vice president of established brands at Boehringer Ingelheim, in a statement. Some of the tools available on the portal include: • a comprehensive and interactive checklist to help patients manage the care and treatment of their condition; • a key facts page on HCV mortality; • at-a-glance information cards designed to debunk myths surrounding HCV; and • a community “C-pledge,” where patients, health care providers and caregivers can take an oath to redefine the experience of living with HCV and the way it is perceived. “The entire HCV community is in need of simple tools and resources to talk about the disease in an informed, supportive way,” said Michael Ninburg, the executive director of the Hepatitis Education Project, in a statement. “There is information about HCV across the web, but HepCRedefined.com is designed to aggregate straightforward and accurate information in a single, virtual destination.” According to the Centers for Disease Control and Prevention, an estimated 16,000 cases of acute HCV and an estimated 3.2 million people with chronic HCV infection were recorded in the United States in 2009. —Maureen Sullivan

anxiety, anger, frustration, loneliness and depression. It also can adversely change a patient’s quality of life through their lack of productivity and inability to plan for the future due to the fear of HAE attacks. ViroPharma, which markets Cinryze

(C1 Esterase Inhibitor [Human]), an FDA-approved drug for HAE, conducted market research with physicians managing HAE patients to help determine what approach would be most beneficial. “We wanted this

•

see WEB TOOLS, page 8

Specialty Pharmacy Continuum • Winter 2013

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WEB TOOLS continued from page 7

program to speak to physicians on a clinical level, but also to be true to the real experiences patients have lived with,” Ms. Jay said. Momentsmissed.com was designed to provide an interactive experience and illustrate specific, real-life examples of HAE patients struggling with the disease. The website also offers additional information on the disease and its treatment, and provides resources to help doctors begin a conversation with patients by having them take an “emotional burden survey.” ViroPharma also deployed the Moments Missed campaign through journal advertising to reach more physicians. The U.S. Hereditary Angioedema Association (HAEA) provided positive feedback on the overall message and intent of the Momentsmissed.com campaign, according to Ms. Jay.

‘I like the simplicity of the [momentsmissed. com] infographic and the succinctness of the HAE questionnaire.’ —Hetty A. Lima, RPh Other stakeholders in the HAE community agree that the initiative raises awareness about the disease, while helping relieve some of the embarrassment and stigma of HAE. The campaign succeeds in other ways as well. “I like the simplicity of the infographic and the succinctness of the HAE questionnaire,” said Hetty A. Lima, RPh, FASHP, the vice president of specialty infusion and rare diseases at Diplomat Specialty Pharmacy, in Flint, Mich. “I’m going to incorporate some of their quality-of-life questions into our HAE clinical assessments.” Ms. Lima also sees value in the social component of the ViroPharma initiative. “At Diplomat, we have a comprehensive clinical care management program. We ask HAE patients if they’ve missed any days of school or work due to their disease. However, we haven’t asked patients how the disease impacts their social and family life,” she said. “So, this is definitely something we’ll be looking at further.”

Tracking Treatment Details With a Mobile App HemaGo is a mobile application that helps patients with hemophilia and their caregivers to monitor not only the details of treatment—including medi-

cations, dosing and bleed information—but also the effect of hemophilia on patients’ lives. The app also is designed to provide this detailed information to the patient’s health care team as well, according to Rich Halpern, the senior brand manager for BioPharm Marketing at Novo Nordisk, which developed the HemaGo app. Any patient with a bleeding disorder can use the app, regardless of what medications he or she is taking, Mr. Halpeern noted. (In contrast, some of the other apps that have been developed for bleeding disorders only are available to patients who use a manufactur-

er’s product to treat the disorder.) The HemaGo app offers multiple profiles so that more than one family

‘Adherence Estimator’ Helps Boost Drug Compliance

any patients don’t take their medicines as directed, resulting in more hospitalizations and emergency department admissions, and higher risks for mortality. Improving patient adherence to medications would not only save lives but also would reduce expenditures because the problem costs nearly $300 billion annually in the United States. One way to address this serious public health problem is to identify patients at greatest risk for not taking their medicine. Researchers at Merck conducted two studies involving thousands of patients to do just that (Clin Therr 2009;31:2584-2607; Curr Med Res Opin 2009;25:215-238). They discovered three primary reasons why patients wouldn’t take their prescriptions: They didn’t understand why the medication was needed and weren’t committed to using it; they were worried about the potential side effects and long-term safety of the drugs; and they were concerned about the cost of the medications. Merck used this information to develop the Adherence Estimator, a free, three-question survey that quickly gauges a patient’s willingness to take a newly prescribed medicine. The compliance tool then provides patients with information directed at their specific concerns. “With the patient’s responses to the survey in hand, health care professionals are able to have better conversations with patients about their prescribed medicines,” said Jamie Rosati, the leader of Merck’s adherence team. “We believe improved communication between providers and patients is a key to improving adherence.” Mr. Rosati said Merck doesn’t track the number of times physicians use the Adherence Estimator. “But we often hear from providers who like it,” said Mr. Rosati, who added that the resource also can be useful to pharmacists. “Pharmacists can play a critical role in improving adherence to medications. They are highly accessible to patients and well positioned to consult with physicians or other health care professionals when concerns are raised about treatment plans.” The online version of the Adherence Estimator is available at https://www. merckengage.com/rxforhealth/adherence-estimator.aspx. The latest development regarding this tech tool is the addition of a widget, which allows providers to deploy the tool on their health system’s internal website for easy access and use with patients. Health care professionals now have the option to administer the survey in a doctor’s office or pharmacy, have patients access it on mobile devices, or email the survey to their patients to complete at home. —D.H.

memb ber can use the tool. It tracks medications, doctor’s appointmentts, factor use, pain scores, and rreason for and type of infusion. It also notes the location and durattion of bleeding events and the efffect of the bleeding episode on the individual’s work or o school life. In fact, “HemaGo has the most comprehensive array of features of all of the apps available in the bleeding disorder community,” Mr. Halpern said. “HemaGo is the only aapp that combines all the features in one place.” Patients can create treatment logs, bleed logs and quality-of-life reports to share with a patient’s health care team at Novo Nordisk’s “Changing Possibilities in Hemophilia” website (www.changingpossibilities-us.com/ HemaGo). The app also syncs to this website. HemaGo is available for free on both iPhone and Android platforms. For those who don’t have a mobile device, the app’s tools also are freely available from the website for use on a computer. HemaGo was developed with the participation of Novo Nordisk’s Consumer Council, which is composed of patients with bleeding disorders. Novo Nordisk said it has had very positive feedback from hemophilia patients and their caregivers. “Since mobile devices have become an important part of people’s lives both professionally and personally,” Mr. Halpern said, “we’ve found that utilizing this technology can help us reach patients in a new, engaging way.” —Dana Hawkins-Simons

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Limited Distribution Network for New Short Bowel Drug

n Dec. 27, NPS Pharmaceuticals, Inc., announced the establishment of a network of specialty home infusion providers to distribute its newly approved short bowel syndrome treatment, teduglutide (rDNA origin, Gattex). The contracted providers in the limited distribution network—including Accredo Health Group, Inc.; BioScrip, Inc.; Coram, LLC; ThriveRx; and Walgreens Infusion Services—will not only dispense teduglutide but also will provide clinical services to support its use in reducing patients’ dependence on parenteral nutrition and intravenous fluids, according to a press release from NPS Pharmaceuticals. Steve Kennedy, PharmD, the national director for infusion pharmacy services at Walgreens Infusion Services, said the company was chosen as a contracted provider of teduglutide because of “our nationwide presence and ability to provide clinical support. We’re one of the nation’s largest providers of infusion services—we have more than 70 infusion pharmacies and 100 alternate treatment sites nationwide. That’s important in caring for the patients: to have a local presence and be close to the patient.” A network of 1,400 clinical experts, including pharmacists, nurses and dietitians who are available to visit patients, “provides high-quality, high-touch services,” Dr. Kennedy said. He also pointed to Walgreens Infusion Services’ multidisciplinary approach to caring for patients as an important benefit. “We educate patients on the proper use of Gattex, continually monitor their progress and coordinate care with the physician.” Initially, a nurse visits the patient to provide injection training, after which teduglutide is self-administered subcutaneously, he noted. Weekly telephone contact continues discussion of oral intake, urine output, weight, general nutritional status and lab results. “We’ll use this information to confirm if the patient is doing well and can be weaned or decreased from parenteral nutrition and intravenous hydration, because Gattex had helped them absorb more nutrients.” Walgreens Infusion Services also provides insurance coverage support and assistance, dietary education and nutrition-support journals to help patients monitor fluid and nutrient intake and overall nutritional status. Additionally, Dr. Kennedy noted, the division can provide any other infusion therapy that a patient may need.

First Major Advance in Nearly A Half-Century Teduglutide, a novel, recombinant analog of human glucagon-like peptide 2, a protein involved in rehabilitation of the intestinal lining, is the first major long-

term treatment advance for short bowel syndrome in nearly 40 years, according to NPS Pharmaceuticals An injection administered once daily, teduglutide helps improve intestinal absorption of fluids and nutrients, reducing frequency and volume of parenteral nutrition, according to an FDA press release. The safety, efficacy and tolerability of teduglutide were evaluated in two randomized, placebo-controlled clini-

cal trials and two extension studies. Designed to quantify the number of patients who achieved at least a 20% reduction in the volume of weekly parenteral nutrition after 20 and 24 weeks of treatment (clinical response), the trials showed that 46% and 63% of patients, respectively, treated with teduglutide achieved a clinical response compared with 6% and 30% of patients treated with placebo, respectively.

The most common side effects of teduglutide identified in the clinical trials were abdominal pain, injection site reactions, nausea, headaches, abdominal distension and upper respiratory tract infection. A postmarketing study is required to evaluate teduglutide’s potential for increasing the risk for colorectal cancer and other conditions. —George Ochoa

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First Antidiarrheal Drug for Patients With HIV/AIDS Approved

Diarrhea is common in patients with n the last day of 2012, the FDA approved crofelemer (Fulyzaq, HIV/AIDS and is a frequent reason for Salix Pharmaceuticals) for symp- discontinuing or switching antiretrotomatic relief of noninfectious diar- viral therapies. Crofelemer is the first rhea in patients with HIV/AIDS who FDA-approved antidiarrheal drug for are receiving antiretroviral therapy, these patients. according to an FDA press release. A botanical prescription drug derived

from the Croton lechleri plant, crofelemer release tablet, taken orally twice daily. is believed to act by blocking chloride The FDA approval of crofelemer is secretion, thereby reducing the high-vol- based on a randomized, multicenter, ume water loss that occurs in patients double-blind study with placebo-conwith HIV-associated diarrhea, according trolled (one-month) and placebo-free to press release from Salix. The recom- (five-month) arms that evaluated 374 mended dosage is one, 125-mg delayed- HIV-positive patients receiving stable

Diplomat Named Exclusive Distributor of New Thyroid Ca Drug

n Dec. 3, Diplomat Specialty Pharmacy was announced as the exclusive specialty pharmacy distributor for cabozantinib (Cometriq, Exelixis), a newly approved treatment for progressive, metastatic medullary thyroid cancer (MTC). According to a press release issued jointly by the two companies, Exelixis chose Flint, Mich.-based Diplomat as the exclusive distributor for the drug because of Diplomat’s “commitment to high-touch patient care.” This type of exclusive arrangement is occurring more frequently, according Diplomat CEO Phil Hagerman, RPh. “This is becoming more of a common channel for orphan or ultraorphan drugs such as Cometriq (a little over 1,000 patients). It makes sense due to the complex and unique nature of the therapy.” FDA’s review of the kinase inhibitor cabozantinib was completed in six months under the FDA’s priority review program, in place for drugs that may offer major treatment advances or provide a treatment when no adequate therapy exists. Cabozantinib received orphan-product designation because it is intended to treat the rare MTC. The safety and effectiveness of cabozantinib were established in a clinical trial of 330 patients with

MTC, according to an FDA press release. Although treatment with cabozantinib did not extend patients’ lives, patients on the drug lived an average of 11.2 months without tumor growth, compared with an average of four months for patients taking placebo. Twenty-seven percent of patients on cabozantinib had reductions in tumor size that lasted an average of nearly 15 months, compared with no reductions in tumor size for patients taking placebo. Although its initial target population is small, cabozantinib could expand its list of indications in the future. “It could become one of the major players in the cancer arsenal,” said Mr. Hagerman. “This drug has extensive opportunities for additional indications based on subsequent studies,” agreed Gary Rice, RPh, MS, MBA, the vice president of clinical services, at Diplomat. The prescribing information for cabozantinib includes a boxed warning about perforations and fistulas and severe, sometimes fatal, hemorrhage. Common side effects, according to the FDA press release, include diarrhea; inflammation or sores of the mouth; hand-foot syndrome; weight loss; loss of appetite; nausea; fatigue; oral pain; graying or loss of hair color; bad taste; new or worsening high blood pressure; and abdominal pain and constipation.

For Diplomat, the process of becoming the exclusive specialty pharmacy for cabozantinib has been long and ongoing, said Mr. Hagerman. “We’ve been working with Exelexis for over a year. We started talking when the drug was in late Phase II.” Education has played a major part. “Every person at Diplomat involved in this therapy has gone through an extensive program of specific training for Cometriq.” Mr. Hagerman said, “We won this business with a broad array of services,” including “an intense, exhaustive process to insure every appropriate patient has access to the drug” and “therapy patient care management programs [that] were customdesigned between Exelixis and Diplomat.” He added, “In the care management process, we have multiple touchpoints in which we follow up with the patient, when we anticipate side effects and when it’s time for a new supply of medication.” Mr. Rice said, “We can help patients minimize and manage side effects through such means as education and over-the-counter medication to treat or minimize the severity of the side effects. We also communicate with the patient’s physician regarding the patient-reported side effects, so that the physician is aware of the side effects and can discuss with the patient next steps in treatment.” —George Ochoa

FDA Approves Auto-Injector for MS Drug

he FDA has approved Rebif Rebi- introduces an enhancement that improves dose (interferon β-1a), a single-use ease of use, it makes a difference,” Rick auto-injector for the self-administration Miller, RPh, MBA, the director of speof Rebif, a disease-modifying drug for cialty clinical services for Walgreens Spethe treatment of relapsing forms of mul- cialty Pharmacy, in Carnegie, Pa., told tiple sclerosis (MS). Specialty Pharmacy Continuum. The approval was announced on Jan. 3, Compared with an earlier autoby EMD Serono, Inc., a subsidiary of injector, Rebiject II, preparation with Merck KGaA, and Pfizer Inc, co-mar- Rebif Rebidose is minimized, which makes the self-administration process keters of Rebif in the United States. In a 12-week, Phase IIIb, open-label, more straightforward, Mr. Miller noted. single-arm study, Rebif Rebidose was “The manufacturer has preassembled evaluated for ease of use, patient satis- the [newer] device for the patient,” he faction and acceptability, and functional explained. As a result, “Rebif Rebidose reliability. Patients with relapsing MS, is ready to use right out of the box [after who were receiving Rebif 44 mcg three allowing the product to come to room times weekly for more than 12 weeks, temperature].” He added, “Since there’s continued MS therapy using Rebif Rebi- no manipulation of the medication dose for 12 weeks. The results showed required, this new dosage form can help that the majority of the patients found improve adherence to therapy.” Rebif Rebidose easy to use. The specialty pharmacy can bring “Anytime a pharmaceutical company value to the use of Rebif Rebidose, Mr.

Miller said, particularly with regard to patient education. “Patients need education on proper injection techniques,” as well as on “general counseling tips, such as rotating injection sites throughout the body.” Walgreens has developed a ConnectedCare MS program, which is designed to aid in the clinical management of MS patients. The company also has a program in place to treat those patients taking Rebif Rebidose, Mr. Miller noted. At Walgreens Specialty Pharmacy, Specialty pharmacists also can assist pharmacists provide education via tele- with insurance coverage and access to the phone before the patient receives the product, managing adverse events and product. The pharmacist educates the discussing the importance of adherence. patient “on proper site preparation and “With multiple sclerosis,” Mr. Miller said, on how to prepare the drug for adminis- “medications can only delay disease protration,” he said. “Rebif is a refrigerated gression, but this will only happen with product and should be brought to room proper adherence to therapy.” temperature prior to injection to minimize injection discomfort.” —George Ochoa

If you are a Hizentra patient or caregiver

Get connected through

Scan this code with your smart phone or log on to Hizentra.com/V2V to view stories from Voice2 e Voice graduates like Cindy to see what it’s all about! Cindy

Voice2Voice is a peer-to-peer support program Find out what a Voice2Voice advocate from CSL Behring, the maker of Hizentra. can do for you. 2Voice connects Hizentra patients and caregivers with advocates who have direct experience with Hizentra and know what it’s like to live with primary immunodeﬁciency disease (PIDD).

A Voice2Voice advocate is someone you can share your story with. They can help answer your non-medical questions* and connect you to helpful resources. In addition, Voice2Voice advocates can share their own real-life treatment stories and offer encouragement as only someone who’s “been there” can do.

Sign up for Voice2Voice. You can enroll online at Hizentra.com/V2V or call 1-877-355-IGIQ (4447) for assistance. *Voice2Voice 2 advocates are not healthcare professionals or medical experts. For medical questions, please contact your physician. Individuals appearing in the Voice2Voice 2 videos are compensated by CSL Behring LLC for their time and/or expenses.

Important Safety Information Hizentra treats various forms of primary immunodeﬁciency (PI) in patients age 2 and over. Hizentra should not be used if you have had serious negative reactions to immune globulin (Ig) preparations or a deﬁciency of an Ig known as IgA. Because Hizentra contains the amino acid proline as stabilizer, patients with hyperprolinemia (too much proline in the blood) should not take Hizentra. Infuse Hizentra under your skin only; do not inject into a blood vessel. Allergic reactions can occur with Hizentra. If your doctor suspects you are having a bad allergic reaction or are going into shock, treatment will be discontinued. Immediately tell your doctor or go to the emergency room if you have signs of such a reaction, including hives, trouble breathing, wheezing, dizziness, or fainting. Please see additional Important Safety Information on next page. Please see brief summary of full prescribing information for Hizentra on adjacent pages.

For people with PIDD

Hizentra is the Ig therapy that’s deliberately designed for SubQ use

Sign up for Voice2Voice. Log on to Hizentra.com/V2V to get connected with an experienced Voice2Voice advocate for helpful peer-to-peer support. Hizentra.com/V2V

Backed by the expertise of CSL Behring, Hizentra 20% is currently being used by more than 10,000 patients and providers,1 a number that’s growing every day UÊ Hizentra helps keep IgG levels stable with low-volume self-infusions —The ﬁrst and only 20% lg concentration delivers a consistent level of protection against infection —Individualized dosing means you can have conﬁdence that you are getting the dose that’s right for you

Important Safety Information (continued) Tell your doctor about any side effects that concern you. Your doctor will monitor for potentially serious reactions that have been seen with Ig treatment, including thrombotic events (blood clotting); aseptic meningitis syndrome (brain swelling); osmotic nephropathy (a kidney condition); hemolysis (a blood problem) and transfusion-related acute lung injury. The most common drug-related adverse reactions in the clinical trial for Hizentra were injection-site reactions (swelling, pain, redness, heat or itching); headache; back pain; diarrhea; tiredness; cough; rash; itching; nausea and vomiting. Hizentra is made from components of human blood. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated. Vaccines (such as measles, mumps and rubella) might not work as well if you are using Hizentra. Before receiving a vaccination, tell the healthcare professional that you are being treated with Hizentra. Also tell your doctor if you are pregnant or nursing, or if you plan to become pregnant. Please see brief summary of full prescribing information for Hizentra on adjacent pages. You are encouraged to report negative effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Reference: 1. Data on File. Available from CSL Behring as DOF HIZ-003.

Hizentra is manufactured by CSL Behring AG and distributed by CSL Behring LLC LLC. Hizentra is a registered trademark of CSL Behring AG. Voice2Voice 2 is a service mark of CSL Behring LLC. ©2012 CSL Behring LLC 1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA www.CSLBehring-us.com www.Hizentra.com HIZ05-12-0062b 6/2012

Specialty Pharmacy Continuum • Winter 2013

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antiretroviral therapy with a history of diarrhea lasting one month or longer. The primary end point of the study was defined as the proportion of patients having no more than two watery bowel movements per week. Investigators found that significantly more patients taking crofelemer experienced a clinical response compared with those taking placebo (17.6% vs. 8%, respectively). Some patients had a persistent antidiarrheal effect for 20 weeks. Statistically significant reductions from baseline to the end of the double-blind

Crofelemer (Fulyzaq, Salix Pharmaceuticals) is derived from the Croton lechlerii plant.

period also were observed for the number of watery bowel movements per day and daily stool consistency score among patients taking crofelemer compared with those taking placebo. Furthermore, crofelemer showed significantly greater efficacy compared with placebo in subgroup analyses of duration of diarrhea, baseline number of daily watery bowel movements, use of HIV protease inhibitors and CD4 cell count. “In addition, the Phase III study showed that Fulyzaq did not influence the efficacy or safety of the patients’

Hizentra®, Immune Globulin Subcutaneous (Human), 20% Liquid Initial U.S. Approval: 2010 INFORMATION FOR PATIENTS These highlights do not include all the information needed to use Hizentra safely and effectively. See full prescribing information for Hizentra. -----------------------------------INDICATIONS AND USAGE---------------------------------Hizentra is an Immune Globulin Subcutaneous (Human) (IGSC), 20% Liquid indicated for the treatment of primary immunodeficiency (PI) in adults and pediatric patients 2 years of age and older. INFORMATION FOR PATIENTS This patient package insert summarizes important information about Hizentra. Please read it carefully before using this medicine. This information does not take the place of talking with your healthcare professional, and it does not include all of the important information about Hizentra. If you have any questions after reading this, ask your healthcare professional. What is the most important information I should know about Hizentra? Hizentra is supposed to be infused under your skin only. DO NOT inject Hizentra into a blood vessel (vein or artery). What is Hizentra? Hizentra (Hi – ZEN – tra) is a prescription medicine used to treat primary immune deficiency (PI). Hizentra is made from human plasma. It contains antibodies, called immunoglobulin G (IgG), that healthy people have to fight germs (bacteria and viruses). People with PI get a lot of infections. Hizentra helps lower the number of infections you will get. Who should NOT take Hizentra? Do not take Hizentra if you have too much proline in your blood (called “hyperprolinemia”) or if you have had reactions to polysorbate 80. Tell your doctor if you have had a serious reaction to other immune globulin medicines or if you have been told that you also have a deficiency of the immunoglobulin called IgA. Tell your doctor if you have a history of heart or blood vessel disease or blood clots, have thick blood, or have been immobile for some time. These things may increase your risk of having a blood clot after using Hizentra. Also tell your doctor what drugs you are using, as some drugs, such as those that contain the hormone estrogen (for example, birth control pills), may increase your risk of developing a blood clot. How should I take Hizentra? You will take Hizentra through an infusion, only under your skin. Make sure that the infusion is not into a blood vessel. You will place up to 4 needles into different areas of your body each time you use Hizentra. The needles are attached to a pump with an infusion tube. It usually takes about 60 minutes to do one infusion. You will need to have infusions once a week. Do not use Hizentra by yourself until you have been taught how by your doctor or healthcare professional.

HIV medications,” said Bill Forbes, PharmD, Salix’ executive vice president of medical research and development and chief development officer. The most common adverse reactions in patients taking crofelemer were upper respiratory tract infections, bronchitis, cough, flatulence and elevated bilirubin concentration. Crofelemer is not intended for the treatment of infectious diarrhea; infectious etiologies of diarrhea should be ruled out before a patient is started on crofelemer. —SPC Staff

What should I avoid while taking Hizentra? Vaccines may not work well for you while you are taking Hizentra. Tell your doctor or healthcare professional that you are taking Hizentra before you get a vaccine. Tell your doctor or healthcare professional if you are pregnant or plan to become pregnant, or if you are nursing. What are possible side effects of Hizentra? The most common side effects with Hizentra are: Redness, swelling, itching, and/or bruising at the injection site Headache/migraine Nausea and/or vomiting Pain (including pain in the chest, back, joints, arms, legs) Fatigue Diarrhea Stomach ache/bloating Cough Rash (including hives) Itching Fever and/or chills Shortness of breath Dizziness Tell your doctor right away or go to the emergency room if you have hives, trouble breathing, wheezing, dizziness, or fainting. These could be signs of a bad allergic reaction. Tell your doctor right away if you have any of the following symptoms. They could be signs of a serious problem. Reduced urination, sudden weight gain, or swelling in your legs. These could be signs of a kidney problem. Pain, swelling, warmth, redness, or a lump in your legs or arms. These could be signs of a blood clot. Numbness or weakness of an arm or leg or one side of your face. Sudden confusion, or trouble speaking or understanding. Bad headache with nausea, vomiting, stiff neck, fever, and sensitivity to light. These could be signs of a brain swelling called meningitis. Brown or red urine, fast heart rate, yellow skin or eyes. These could be signs of a blood problem. Chest pains or trouble breathing. Fever over 100ºF. This could be a sign of an infection. Tell your doctor about any side effects that concern you. You can ask your doctor to give you more information that is available to healthcare professionals. How do I use Hizentra? Infuse Hizentra only after you have been trained by your doctor or healthcare professional. Revised: October 2011

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Medicare Act Paves Way for Home IVIG Infusions New legislation signed into law last month by President Obama will give Medicare patients with primary immunodeficiency disease (PID) the opportunity to receive immunoglobulin (Ig) infusions at home. The Medicare IVIG Access Act (HR 1845) provides for a three-year demonstration project examining the provision of Medicare coverage for items and services required for home infusion of intravenous immunoglobulin (IVIG) therapy for up to 4,000 Medicare beneficiaries with a diagnosis of PID. Coverage of such items and services is to begin within a year of the act’s passage. Until that time, Medicare reimbursement only covers the cost of the Ig product itself, and not the costs associated with infusion in the home, such as pumps and nursing services, which has effectively precluded home infusion for Medicare patients. “This news will open up a rational way to provide care and decrease the risks and burdens associated with traveling to a treatment center for infusion therapy with IVIG,” said Jerry Siegel, PharmD, FASHP, a clinical associate professor at The Ohio State University College of Pharmacy, in Columbus. Because it eliminates “the burdens of finding and traveling to a treatment site, waiting for product preparation, and being exposed to other patients who may be carriers of infection, home care allows the patient to carry on in a more ‘normal’ lifestyle,” he said. Dr. Siegel stressed, however, that special “care must still be exercised.” Both the infusion nurse and the patient must be educated about the common signs and symptoms often encountered during treatment, he said. “Headache, fever and chills are the most common intolerances, but they can be easily controlled by lowering infusion rates or administering simple premedications such as

Immunoglobulin FAQs Jerry Siegel, PharmD, kicks off his new question-andanswer column with some tips for managing adverse reactions. See page 26.

acetaminophen or diphenhydramine.” (See Dr. Siegel’s FAQ column on IVIG, which focuses on managing adverse reactions, on page 26.)

Out-of-Pocket Savings ‘Exciting’ Amy Clarke, RN, the program manager for specialty infusion services at Diplomat Specialty Pharmacy, in Flint, Mich., agreed that “it’s exciting that Medicare patients potentially won’t have to pay as much out of pocket for immunoglobulin therapy,” but she also expressed caution. “My biggest concern is safety,” she said, noting that the shift in reimbursement puts “a huge onus of education on the specialty pharmacy, which could be very challenging.” Ms. Clarke discussed some steps specialty providers can take to minimize problems and maximize outcomes for patients receiving IVIG infusions at home. Providers will need to make sure that they have the background and training to manage patients receiving Ig therapy, particularly the nurses who will be involved in administering the therapy. “Traditional nursing agencies are not trained in infusion,” she said, adding that some providers will not have the expertise to administer a first dose, so that may have to be done in a hospital or other facility with experience. Once a patient has received a first dose safely, there are additional factors to consider, including where the patient lives and the emergency medical response in that area, patient comorbidities, such as congestive heart failure because of fluid considerations and diabetes, renal status and patient age. “IVIG and subcutaneous immunoglobulin should be a very high-touch model,” Ms. Clarke said. (Although the act specifies IVIG, Ms. Clarke noted that current Medicare reimbursement also covers subcutaneous Ig products but not the supplies required for administration.) Although the act only provides for reimbursement during the three-year demonstration period, in a press release on the act’s passage, the Immune Deficiency Foundation, a national patient advocacy organization for patients with PID, predicted that the demonstration project would show the cost-effectiveness of home infusions of IVIG therapy in patients with PID, “thus paving the way for a permanent fix to this issue.” In fact, the Department of Health and Human Services is required to file an interim report within three years of

‘It’s exciting that Medicare patients potentially won’t have to pay as much out of pocket for immunoglobulin therapy.’ —Amy Clarke, RN enactment of the act and a final report one year after completion of the demonstration, analyzing the appropriateness of implementing a new Medicare payment methodology for IVIG. The demonstration project has implications beyond IVIG, according to Hetty Lima, RPh, FASHP, the vice president of specialty infusion and rare diseases at Diplomat. Ms. Lima predicted that the outcome of the demonstration project has “huge potential to trickle down and pave the way for coverage of related nursing and supplies for other home infusion therapies, such as IV antibiotics and parenteral nutrition, under Medicare as well.” Additionally, she said the project could possibly “open the way for coverage of an expanded list of diagnostic indications,” such as neurologic conditions. One neurologic condition being evaluated is Alzheimer’s disease. Baxter is supporting trials evaluating Gammagard Liquid in patients with Alzheimer’s and the results to date have been favorable, said Ms. Clarke. “Once Alzheimer’s comes into the picture,” she said, “it’s going to push pharmacists’ capability, and it’s going to be important to make sure that pharmacists are comfortable with gerontology and how immunoglobulin therapy affects that.”

Ms. Clarke said that the demonstration project leaves a lot of questions unanswered. For example, it’s not clear whether Medicare coverage ultimately will extend beyond PID to other approved indications, such as chronic inflammatory demyelinating polyneuropathy and Kawasaki’s disease. Additionally, coverage determinations on unapproved indications such as Alzheimer’s disease, aplastic anemia, immune-related neutropenia, and others are also unclear. It’s also not evident whether Medicare patients would be responsible for any out-of-pocket costs or copays for Ig therapy, or whether there would be differences in reimbursement between patients who have only Medicare Part B versus those who also have Part D coverage. In the meantime, Dr. Siegel noted, PID “patients who are stable clinically and have not exhibited adverse reactions are prime candidates for IVIG home infusion, and now for the first time the type of coverage will not limit this patient-preferred method of administration.” —Sarah Tilyou Dr. Siegel reported that he is a speaker for Amgen.

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COST TRENDS continued from page 1

said Melinda Haren, the director of access strategies for The Zitter Group, a health care consultancy firm. Ms. Haren was quick to point out, however, that data from the new report don’t paint a uniform picture of soaring prices. Each category seems to tell its own tale of spending trends—some rather stable, others spiking significantly, and not all due to the same market conditions.

‘From our surveys of payer panels, we are consistently hearing the theme that we’ve got to do something about the spiraling costs of specialty medications.’ —Melinda Haren Top-line results yielded few surprises. Rheumatoid arthritis and autoimmune conditions, multiple sclerosis and cancer continued to be the 800-pound gorillas of the specialty pharmacy spend; at 28.7%, 20.9% and 17.4%, respectively,

each accounts for more of the total pie than the next four indications combined (growth deficiency, 4.1%; anticoagulation, 3.8%; respiratory conditions, 3.3%; and pulmonary arterial hypertension, 3.2%; Table, page 15).

But looking at leading specialty drugs by spend trend paints a different picture. Spending on all therapy classes within specialty pharmacy was up over the previous year—no surprise there— but not for the same reasons. Spending on hepatitis C drugs, for example, was up a whopping 117%, but the vast majority of that increase was due to utilization (100%) rather than unit cost ( just 17%). That, of course, traces back to the mid-2011 approval of two drugs in the first new class of drugs for hepatitis C since 2001—Merck’s Victrelis (boceprevir) and Vertex’s Incivek (telaprevir)—although that picture may change with a continuing litany of bad news from the FDA on Incivek, culminating in a black box warning being issued Dec. 19, after two patients developed fatal skin rashes.

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Multiple sclerosis (MS) drugs, in contrast, showed almost static utilization (a 0.4% increase), while unit costs climbed 17.3%. That’s the highest overall increase in unit cost for any therapy class in the specialty basket, with the exception of respiratory conditions, which saw the introduction of the nearly $300,000-per-year ivacaftor (Kalydeco, Vertex), a breakthrough therapy for cystic fibrosis. The MS spike can be traced, at least in part, to the fall 2010 introduction of Novartis’ Gilenya (fingolimod), the first once-daily pill approved by the FDA for reducing the number of relapses in people with relapsing forms of the disease, with its $48,000 price tag. “The introduction of new medications used to treat MS likely pushed drug costs for all medications in this class even higher,” the Express Scripts report stated. “Manufacturers of conventional MS medications may be struggling to maintain profits as they compete with popular new drugs that are gaining market share. As a result, prices of older medications may also be increased so that they do not appear inferior to the newer, more expensive medications.” The year-by-year increase in specialty spending for 2012 is actually not any greater than in past years, according to Sharon Frazee, PhD, MPH, the vice president for research and analysis at Express Scripts. “In any given year, the increase in specialty utilization usually ranges between 3% and 10%, and unit costs usually increase by around 13% to 15%.” This year’s spend increase, at 9.4% for utilization and 13.3% for unit cost, falls squarely within that ballpark. But specialty pharmacy’s growing share of the market (and its even larger dominance of the pipeline) has started to make people sit up and take notice. “Back in the day when specialty was

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OPERATIONS & MANAGEMENT

only 10% of total per-member, per-year spend, payers would say that the trend was high, but they didn’t worry about it too much because the actual dollars weren’t that high spread across the entire membership,” Dr. Frazee said. “But now, specialty is making up about 20% of the total spend, and payers know that specialty medications are only used by about 2% of the total [patient] population.”

Where’s the Pressure on Pricing? The continued increase in the specialty pharmacy “spend” can be partly explained by another distinguishing feature of this market: The usual pressures that have led to cost reduction in the traditional pharmacy market haven’t worked in specialty, Ms. Haren noted. “In the traditional world, more drugs for an indication means lower costs,” she said. “But in the specialty space, the agents still do not compete in the same way as, say, β-blockers. There’s not a lot of clinical reasoning as to which β-blocker you should choose, so it becomes a question of physician preference in combination with what the patient will have to pay. If you add another β-blocker to the category, then, it tends to drive prices down.” For most specialty medications, in contrast, there are in fact significant differences that can affect prescriber choice. Take boceprevir and telaprevir, for example. “There are clinical reasons to choose one agent over another,” Ms. Haren said. “There are differences in side-effect profile, length of therapy and frequency of monitoring.”

Table. Top Ten Specialty Therapy Drug Classes, Ranked By % of Total Spend

Therapy Class

% of Total Specialty Spend

Rheumatoid arthritis/autoimmune conditions

28.7%

Multiple Sclerosis

20.9%

Cancer

17.4%

Hepatitis C

4.9%

Growth Deficiency

4.1%

Anticoagulants

3.8%

Respiratory Conditions

3.3%

Pulmonary Arterial Hypertension

3.2%

Hemophilia

2.9%

Enzyme Deficiency

2.0%

Other

8.8%

‘If these spending trends continue over the next two to three years, there will be some dramatic fallout from this. Patients can’t afford it, insurers can’t afford it, and the government will not assume that exposure.’ —Richard Jay, PharmD Even in an indication such as breast cancer, for which there are multiple specialty medications, there is little direct competition because of clear

differentiation between different agents on the market. “They all treat a different type and stage of breast cancer,” Ms. Haren explained. “Meta-

static? Phase II? Can you do surgery first?” Those points of differentiation “[don’t] leave much room for pricing

•

see COST TRENDS, page 17

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NASP, SPAARx continued from page 1

Armada Health Care founder and president Robert Irene countered by saying that the SPAARx effort has in fact been in discussion mode, if not outright development, for some time. “A lot of people we work with in the industry were calling for Armada to take the lead in forming an association,” he said. “We have the expertise to form organizations and the skills on the business side. It’s a unique opportunity in health care to go from zero to having a full association just with a management change.” Mr. Irene said that SPAARx is the next logical outgrowth of the Armada conference, which has grown from a couple of dozen people networking around a table ten years ago to an anticipated attendance of more than 2,500 at this year’s meeting. But it is that bully pulpit—plus Armada’s position as a major specialty pharmacy provider—that has some critics worried about potential conflicts of interest in SPAARx’s efforts to be a trade association advocate for all comers. Mr. Irene downplayed such concerns. “SPAARx will be completely vendor-neutral and run separately from Armada, with its own board of directors and committee members,” he said. Although the board “is in the

process of forming,” he added, no official appointments have yet been made. He also stressed that Armada will reap no financial gain from the association. The company currently is subsidizing SPAARx, but expects that membership dues will ultimately fund the group, he noted.

NASP Begins To Take Shape Given its two-month lead time over SPAARx, it’s not surprising that more details are known about NASP. Although the composition of its board is still in flux, NASP has named an acting executive director—Town Total CEO Mike Nameth, RPh, MBA, former executive vice president of Walgreens’ Specialty Pharmacy business unit— and a chief executive officer—Gary M. Cohen, BSPharm, RPh, recently the publisher of Specialty Pharma Journal. In fact, NASP got its start during meetings of advisory boards for the journal. “Executives from CVS [Caremark], Walgreens, Diplomat, Express Scripts—they all took note of the fact that there was no specific platform for specialty pharmacy,” Mr. Cohen said. “All the meetings they were attending were hosted either by a specific specialty pharmacy or by a more general pharmacy organization, and they didn’t have longevity toward addressing the specific needs of the specialty pharmacy market.” NASP’s first major initiative will be

What Is Spe·cial·ty Phar·ma·cy?

espite rapid growth—or perhaps because of it—there still isn’t a clear, established definition of what exactly specialty y pharmacists and pharmacies do, and how those efforts translate into value for the provider, payer and patient. That’s why one of the first tasks the newly formed National Association of Specialty Pharmacy (NASP) has taken on is to better define these activities. At one time, “specialty pharmacy” almost exclusively dealt with self-injectable biologics, specifically monoclonal antibodie es such as those used to treat cancer, rheumatoid arthritis and mu ultiple sclerosis. But the list of specialty pharmaceuticals is much broader today. For example, the Academy of Managed Care Pharmacy defines specialty pharmacy drugs as “medications [that are] generally prescribed for people with complex or ongoing medical conditions such as multiple sclerosis, hemophilia, hepatitis and rheumatoid arthritis. These medications also typically have one or more of the following characteristics: [they are] injected or infused (but some may be taken by mouth); [they have] unique storage or shipment requirements; additional education and support [is] required from a healthcare professional; [and the drugs are] usually not stocked at retail pharmacies.” Diplomat’s Phil Hagerman, RPh, suggested a simpler definition: “It’s complicated, expensive stuff.” So how does that definition translate into the role of the specialty pharmacy and specialty pharmacist? “From a clinical perspective, the definition of specialty pharmacy should be driven by the clinical needs of the medication and its associated conditions,” said OptumRx’s Suzanne Tschida, PharmD. “Specialty pharmacy requires clinicians who are specifically trained in these disease states to provide a high level of guidance and oversight to maintain compliance, ensure appropriate use and get the best outcomes.” Any definition of specialty pharmacy cannot be formulation-specific, Dr. Tschida added. “Specialty pharmacy medications could be oral, inhalation, selfinjectable or even topical,” she noted. And specialty pharmacy can involve either the prescription or the medical benefit side, Mr. Hagerman noted. “Obviously, oral oncolytics, an example of the prescription side, are the heart of specialty pharmacy today. But what about the medical benefit side, where physicians in some cases are starting to be less involved? That can involve specialty pharmacy as well.” —G.S.

‘[At Diplomat], we’re spending millions on technology to create business intelligence tools and better track outcomes, but we’re still just one voice. That’s where NASP comes in: to aggregate that information and validate it nationwide.’ —Phil Hagerman, RPh

The Path to Certification

n most health professions, certification is an essential marker of a clinician’s specialized training and experience. And because all pharmacists these days enter their profession with PharmD degrees, specialty certification is a way for professionals to distinguish themselves in a crowded field. The Board of Pharmacy Specialties offers certification in eight pharmacy areas: ambulatory care, critical care, nuclear, nutrition support, oncology, pediatric, pharmacotherapy and psychiatry. (There are also added qualifications, subspecialties of sorts, in cardiology and infectious disease within the pharmacotherapy specialty.) But specialty pharmacy is becoming more and more of a subspecialty field, according to NASP CEO Gary Cohen, RPh, BSPharm. The same impetus behind the creation of NASP also has spurred the parallel creation of a separate certification organization, The Specialty Pharmacy Certification Board (SPCB; www.spcboard.org). “The SPCB and the NASP are separate board-governed, non–member-owned, not-for-profit organizations. Each organization has autonomy in both its roles and policy making,” said Mr. Cohen, who added that he serves as interim executive director for the SPCB but has no vote in its policies, procedures or guidelines. One of the certification board’s first undertakings has been to define the role of a specialty pharmacist, using a Role Delineation Study (RDS), which is now being reviewed and evaluated by a survey population of approximately 1,000 specialty pharmacists. Once that step is complete, an independent panel of subject matter experts will author the questions for the examination. In February, the certification board will vote on the amount of experience, continuing education hours and requirements for both certification and recertification. “The certification board’s role is to develop and provide standards for testing, not to educate,” Mr. Cohen explained. NASP, in contrast, will take a leading role in specialty pharmacy education. The group has partnered with the Specialty Pharma Education Center, an online postgraduate continuing education school for specialty pharmacists. The center is developing certificate programs in more than 20 therapeutic categories, as well as a prototype course that pharmacists can take to prepare for the examination. Developed with input from some 75 faculty members representing more than 15 schools of pharmacy, the center will be “the most comprehensive online postgraduate pharmacy ‘school’ out there,” Mr. Cohen said. —G.S.

a national conference in San Diego, April 2-3, immediately preceding the AMCP’s 25th annual meeting (and in collaboration with that organization). The speaker list was nearly complete at press time, according to Mr. Cohen; the planned agenda includes sessions on the immunoglobulin and hepatitis C therapy categories, panel discussions on gaps in care and how specialty channels and stakeholders can align goals and contribute to improving patient care and outcomes, and a case-study session on the integration of technologies that can improve outcomes in specialty pharmacy.

Seeking Validation Mr. Hagerman said that NASP’s most important role will be to help specialty pharmacy validate its model and outcomes. “We offer a tremendous amount of high-touch services and are expected to raise the bar dramatically over our retail partners, but as an industry we haven’t done a great job in quantifying [those efforts],” he said. “To get fair-market value fees for what we’re doing to keep patients healthy and on therapy longer, we need to get our arms around outcomes.” He added that at Diplomat, “we’re spending millions on technology to create business intelligence tools and bet-

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COST TRENDS continued from page 15

pressures that could drive down costs, she noted. Just as in the old Schoolhouse Rock song, three seems to be the magic number for achieving such pricing pressure. “You need three drugs that treat exactly the same disease, with a same delivery system and very similar efficacy and safety to be able to go to a manufacturer and say, ‘You need to give me a new contract and drop the price or I’m going with one of the other two,’” Ms. Haren said. That tipping point may be approaching with specialty medications for some diseases. Refractory chronic myelogenous leukemia could be the first, with dasatinib (Sprycel, BristolMyers Squibb), nilotinib (Tasigna, Novartis) and the new drugs ponatinib (Iclusig, ARIAD Pharmaceuticals) and bosutinib (Bosulif, Pfizer) competing against imatinib (Gleevec, Novartis). Human growth hormone is another area where there is critical-mass bioequivalency, and some rare diseases now also have three specialty products. Gaucher’s is a prime example, with three injectable medications approved for this disease: taliglucerase alfa (Elelyso, Pfizer/Protalix), velaglucerase alfa (VPRIV, Shire) and imiglucerase (Cerezyme, Genzyme). The abbreviated licensure pathway for “biosimilar” drugs established by the Affordable Care Act may not be sufficient to spur significant further

ter track outcomes, but we’re still just one voice. That’s where NASP comes in: to aggregate that information and validate it nationwide.” Suzanne Tschida, PharmD, BCPS, the vice president of specialty benefit & outcomes strategy at OptumRx, also underscored the benefits of having an organization that can facilitate and support outcomes research. “Being able to track and report outcomes is going to help us not only justify the use of specialty pharmaceuticals but also to help evolve the clinical context for these medications,” Dr. Tschida said. “I think NASP will really be an important forum for us to establish outcome measures, address issues of cost and affordability, maintain access to these medications and develop innovative new ways for them to be available.” Mr. Hagerman said he hopes NASP can serve another important function—as a conduit for process improvement. It’s hard to do research and compare outcomes when information

Two Firsts for Drug Report

revious drug-trend reports from Express Scripts have compared annual data without quarterly breakdowns; the new report offers quarterly data for the first time. Another first: the report now combines data from both ExpressScripts and Medco. To access the report, visit http://digital.turn-page.com/i/95262

movement in that direcction, becaause of the inteellectual property req quirements placed on manufacturers, Dr. Frazee F noted. “[It has] worked in Europe and d Asia, but they have different markets and different requirements. Lots of people are calling for changes to make it more competitive and so that biosimilar manufacturers don’t essentially have to hand over all their intellectual property to competitors in order to do business.”

2014 a Tipping Point For Specialty Pricing Pressures In 2014, the market likely will experience a competitive tipping point in one of the most significant specialty areas: rheumatoid arthritis. “AstraZeneca and

Novartiis are both filing for oral drugs soon. AstraZen neca anticipates filing in the second half of next year, and Novarttis is saying sometime in 2 2014,” Ms. Haren said. “Thaat would mean three oral agents competing in an already crowded market.” Crowded, indeed. The three oral medications would be in a battle with five subcutaneous agents and three IV agents, Ms. Haren noted. Thus, “payers will have plenty of choice among RA agents.” In fact, “RA may be the first market where you’ll see some significant winners and significant losers.” Another way to apply pressure to the spiraling cost of specialty pharmacy may be found on the physician end. “Back in the 1980s and 1990s, with oral drugs, we saw that if you can put phy-

‘I’m happy that [Armada has] decided that [their] meeting really should be moving away from a special-interest group to an association model.’ —John Musil, PharmD systems don’t speak the same language, he noted, adding that “right now, the industry is fairly disjointed with regard to technology. We’re all working on different data sets and different platforms, which means that it’s difficult to get everybody on the same page when new drugs are announced. It would be great to work together to identify or develop a common data language that would allow everybody a base level of connectivity.” NASP “also can help physicians and care management organizations recognize the value of specialty pharmacy services—not just to ensure reimbursement, but to help the specialty pharmacy model survive and thrive in a world

of accountable care organizations and health insurance exchanges.” That’s a key goal, Mr. Cohen noted. “NASP’s mission will be to enhance knowledge about specialty pharmacy, improve and optimize delivery of specialty pharmacy products and enhance both health and economic outcomes in the care of specialty pharmacy patients. It’s all about improving care, both in terms of outcomes and economics.”

Support for SPAARx Initiative As for the more recent Armada initiative, John Musil, PharmD, CEO and founder of Avella (formerly The Apothecary Shops), said that he has been urging Armada to pursue an asso-

sicians at financial risk for prescribing decisions, that certainly influences behavior in terms of trending toward a preferred product,” said Richard Jay, PharmD, the chief pharmacy officer at Ventegra, a managed care contracting services organization. “We’re doing a lot of that with some California medical groups now: They assume the risk of specialty injectables. That’s one of our niches in the marketplace to help manage the specialty spend.” “Something obviously is going to have to give,” Dr. Jay added. “You can shift costs to the patients to some extent, but at some point it’s going to be unsustainable. If these spending trends continue over the next two to three years, there will be some dramatic fallout from this. Patients can’t afford it, insurers can’t afford it, and the government will not assume that exposure.” —Gina Shaw

ciation for a number of years. “I’m happy that they have decided that [their] meeting really should be moving away from a special-interest group to an association model,” he said. Will there be room for two specialty pharmacy associations? “That is an excellent question,” Dr. Musil said, adding that there already are multiple pharmacy associations, both nationally as well as locally and regionally. “I think it’s ultimately who puts the best products out there: educational pieces, clinical programs, access to services for membership. That’ll ultimately work itself out.” “I applaud anybody who tries to take the lead in creating associations,” Dr. Musil added. “It is not easy to get pharmacists to join a group and be active members. I’m glad that people are recognizing that the specialty space is truly a unique area in pharmacy and focusing more efforts on it.” —Gina Shaw

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OPERATIONS & MANAGEMENT

Are Oncologists Coming After Your Business? W

ith oral oncology drugs making up nearly one-third of the oncology pipeline—a percentage that is only expected to grow—many oncology practices are investigating their options for dispensing these medications in-house. The obvious and more common solution is to set up an in-house dispensing pharmacy within the practice. In such a dispensing model—and another approach that does not even require the direct presence of a supervising pharmacist—specialty pharmacy gets cut out of the equation. So, this trend is something that the specialty pharmacy industry is watching closely. The first step in being prepared to react to these new dispensing models is to understand the extent to which they currently are in play, according to pharmaceutical channels expert Adam Fein, PhD, founder of Pembroke Consulting. “In the oncology world, about 300 to 400 practices have their own pharmacy licenses, with about 100 of them being very successful as a business proposition,” Dr. Fein said. “The more successful practices have a pharmacy director and are dispensing significant volume to their patients.” But as noted, there’s also been a smaller, quieter movement among community oncologists to pursue an alternative strategy. Instead of establishing a full-scale dispensing pharmacy within their practices, some oncologists are setting up “non-pharmacy dispensing sites” (NPDS), which under the laws of some states permit the physician to dispense medications without the involvement of a pharmacist. Non-pharmacy dispensing sites are nothing new in medicine. A search of the National Provider Identification (NPI) database reveals thousands of physician practices categorized as NPDS. “This model has been around for at least 15 years, but until recently, most of the sites have been primary care providers, pediatricians and internists, who primarily dispense antibiotics or more common prescription medications,” said Kirby Eng, RPh, the director of Medical Benefit Management at CVS Caremark. “Oncologists are more recent additions to the NPDS model.” It’s often assumed that the primary motivation for an oncology practice to set up an NPDS is financial. Third-party payers are increasingly dissatisfied with the buy-and-bill model, Dr. Fein said, and the increasing shift in oncology from infused IV medications to oral specialty therapies has meant a corresponding movement in coverage from the medical benefit to the pharmacy benefit. “Unlike infused or injected medications, writing a prescription for an oral

medication by an oncologist does not generate any revenue unless they dispense,” Mr. Eng said. It’s true that revenue plays a role in the decision to establish an NPDS, said Brandon Tom, the director of oral specialty pharmaceuticals at McKesson Specialty Health, which along with AmerisourceBergen is one of the two biggest players in helping oncology practices set up an NPDS. “The projection is that by 2014, overall revenue from oral oncolytics should double from 7 billion to almost 14 billion [dollars]. Physicians know that they want to get into that business.”

Not a Cash Cow Setting up an NPDS doesn’t mean an oncology practice is planting a money tree in its office. “I haven’t heard of a practice anywhere in the country that’s saying they’re making much money on this,” said Dawn Holcombe, the executive director of the Connecticut Oncology Association. “The margins just

patient is taking that drug exactly how they should be in order to maximize effectiveness, you’d rather give them that drug in the office than send it to Walgreens or have them go home and wait for a mail-order prescription.” Ms. Holcombe added that oral oncolytics, as potentially toxic systemic drugs, require significantly more physician oversight than, say, a course of antibiotics. “When you dispense three weeks’ worth of pills, which is most convenient for pharmacies, you run the risk of dispensing more than the patient can tolerate. That’s a problem you’re less likely to have if the physician is dispensing and can stay on top of how the drug is affecting the patient.” The complex oncology patient also is much more likely than patients on other types of scripts to require last-minute care modifications. “On the day a patient arrives for treatment, his health status may have changed, which requires the doctor to change what he had planned to

Regional Medical Center, in Yuma, Ariz. “These patients in particular tend to have multiple physicians and multiple things wrong with them. The true benefit of pharmacy practice is that if you have one place where you are getting your prescriptions filled, checks and balances are in place—protection

‘At the end of the day, payers will continue to look for ways to prefer specialty pharmacy managing high-cost oral oncology drugs.’ —Kirby Eng, RPh that goes away when you go to physician dispensing. It may be more convenient, but the benefits of a typical pharmacy system and the data it has may be lost.” Physician practices also are likely to stock a much smaller formulary than any pharmacy, no matter how small. ‘My formulary here is probably 3,000 items, where a physician dispensing from a machine in his office probably has only 30 to 40 drugs,” Mr. Van Hassel said. “That limits them as to what medications the patient may have access to.”

Building an NPDS: The Process

‘The projection is that by 2014, overall revenue from oral oncolytics should double from 7 billion to almost 14 billion [dollars]. Physicians know that they want to get into that business.’ —Brandon Tom aren’t there.” So why do it? “Because they can better manage the patient from a compliance standpoint, and it’s easier for them to monitor how well the patient is doing on a particular drug.” Oral oncology is rapidly becoming very fragmented, Mr. Tom pointed out. “If specialty oncolytics are managed under the pharmacy benefit, they can go through three channels: the physician’s office, mail-order specialty or retail specialty. If you’re a community oncologist and you want to make sure that your

do,” Ms. Holcombe noted. “There may be a dose increase or decrease or a switch to a different drug. If the physician had ordered that drug under the specialty pharmacy model, and it had arrived the day before, there would then be a perfectly good drug that would have the patient’s name on it, which now has to be thrown away. That’s a horrendous waste.” But there are downsides to physician dispensing for the oncology patient, cautioned Tom Van Hassel, PharmD, the director of pharmacy at Yuma

So how does an oncology practice establish itself as an NPDS? First, they must determine whether or not it’s the right dispensing model for them. In a few states, like Massachusetts, Montana and New York, physicians are barred from dispensing medications altogether. Other states require a dispensing license, and still others require the office to register as a retail pharmacy and have a pharmacist dispense the drugs. “In Connecticut, the physician may dispense medications, either oral or infused, as long as they count the pills, put them in the bottle, put the top on the bottle and hand them to the patient,” Ms. Holcombe said. “The physician has to be the one doing everything a pharmacist would do and cannot employ a pharmacist, pharmacy tech or nurse to do any of those steps for them.” In states that do allow physician dispensing without setting up as a full dispensing pharmacy, the NPDS model can be more economical because it does not fall under as many staffing, licensing and audit requirements that may be placed on true retail pharmacy sites by the state’s board of pharmacy. However, an NPDS may not be accepted

Specialty Pharmacy Continuum • Winter 2013

OPERATIONS & MANAGEMENT

by all the insurers in a given region, Mr. Tom pointed out. “Some pharmacy benefit managers don’t recognize an NPDS as eligible for contracts,” he said. “If you’re in a given market where 50% of insurers won’t recognize you, it may not make sense to set up as an NPDS.” Once a practice decides to adopt the NPDS model, solution providers like McKesson and AmerisourceBergen set them up with the infrastructure and technology they require, including: A pharmacy system that can adjudicate claims on the pharmacy benefit. “Most of our practices have never even thought about that before,” Mr. Tom said. “While some of the initial oral oncology drugs, like Xeloda [Genentech; capecitabine], are reimbursed on Part B similarly to an IV drug, commercial payers are now processing 90% of oral oncology meds on the pharmacy benefit, and that requires a new pharmacy system.” A managed care contracting solution. “Practices that set up as an NPDS will now need to get contracts with pharmacy benefit managers and payers that they’ve never had before,” Mr. Tom said. The final piece: an actual oral oncology distribution solution. “We’ve created a process where our community oncology practices can order oral oncology drugs—and non-oncology medications, like pain meds—through the same vehicle with which they order IV drugs.” Practices that set up under the NPDS model typically are not looking to generate a significant amount of profit from dispensing oral oncolytics, Mr. Tom added. “It doesn’t take a lot of up-front capital, infrastructure or workflow changes, and the physicians are really doing it for the patient convenience and comprehensive management factor.” There’s always a critical mass of prescriptions needed to justify taking the step into physician dispensing, be it as an NPDS or as a dispensing pharmacy. “It’s based on a variety of factors, including the reimbursement rates you’re getting and the therapeutic areas you most commonly see in practice, as well as your brand versus generic mix,” Mr. Tom noted. “Some practices just don’t have the volume to sustain a dispensing model.” Mr. Van Hassel suggests that most of the benefits of the NPDS model actually accrue to the third-party solution providers, not the physician or the patient. “They’re the ones who make the money. It bypasses the physician, bypasses the patient, and now there’s another third party that makes the profits,” he said. “From what I’ve seen, most physician offices get into dispensing for a short time and then realize that it’s an awful lot of work.” That workload is likely to be even higher for an oncology practice because of the added paperwork. “If you’re a true oncol-

‘The true benefit of pharmacy practice is that if you have one place where you are getting your prescriptions filled, checks and balances are in place—protection that goes away when you go to physician dispensing.’

—Tom Van Hassel, PharmD

ogy dispenser and primarily dispensing oral oncolytics, many of these can only be dispensed under a REMS [Risk Evaluation and Mitigation Strategies] protocol,” he pointed out. “That’s a lot of red tape

for relatively little benefit.” Most experts seem to agree that although the NPDS model is a growing one and thus something that bears watching by specialty pharmacy stake-

holders, it currently poses little threat to specialty pharmacies. “At the end of the day, payers will continue to look for ways to prefer specialty pharmacy managing high-cost oral oncology drugs,” Mr. Eng said. “Payers seek the consistency in clinical application, member engagement and drug fulfillment provided by specialty pharmacy providers. Although there may be some room for growth, the amount of physician dispensing for these oral oncology drugs will likely remain a small portion of the market.” —Gina Shaw

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Specialty Pharmacy Continuum • Winter 2013

CLINICAL

DISEASE STATE SPOTLIGHT

Current and Future Perspectives In Pulmonary Arterial Hypertension Rebekah Hanson, BS, PharmD, BCPS Clinical Liaison Pharmacist, Specialty Clinical Assistant Professor

Michelle Martin, PharmD, BCPS, BCACP Clinical Pharmacist Clinical Assistant Professor University of Illinois College of Pharmacy University of Illinois Hospital & Health Sciences System Chicago, Illinois

Pulmonary hypertension is characterized by an increase in the blood pressure of the lung vasculature that arises from an elevation in pulmonary vascular resistance (PVR).1 This increase in pressure may occur in the pulmonary arteries, capillaries, veins, or a combination of these.1,2 Pulmonary hypertension is organized into 5 groups, based primarily on etiology, each with different medical management strategies. When the elevation in pressure occurs predominantly in the pulmonary arteries, it is considered pulmonary arterial hypertension (PAH).3,4 The origin of PAH may be unknown or idiopathic, genetic, or secondary to a related disease associated with an increased risk for PAH (Table 1).4 Of these, connective tissue disease and congenital heart disease are the most common associated causes.5 PAH is uncommon, occurring in approximately 2.4 to 7.6 people per million per year; it is diagnosed up to three times more frequently in women than in men.2,5 It is a

progressive disease that has no cure and is associated with significant morbidity as well as premature death. If treated, patients with PAH have a median life expectancy longer than 7 years after diagnosis, but if they do not receive treatment, their life expectancy is less than 3 years.6,7 Studies over the last decade have further elucidated the underlying mechanisms of PAH and have led to

Table 1. Revised Classification of PH Group 1. PAH Idiopathic Heritable • Bone morphogenetic protein receptor type 2 • Activin receptor-like kinase type 1 • Unknown Drug and toxins-related Disease-related • Connective tissue disease • Congenital heart disease • Portal hypertension • HIV infection • Schistosomiasis • Chronic hemolytic anemia Persistent pulmonary hypertension of the newborn

multiple groundbreaking drug developments. Normal pulmonary circulation is one of high volume, low pressure and low resistance. In PAH, both pressure and resistance are increased due to genetic factors, environmental factors, or both.1,2,8-10 The result is that dysfunctional pulmonary smooth muscle endothelial cells create an imbalance in regulation of vascular tone, leading to a persistent state of vasoconstriction, inflammation, and abnormal endothelial proliferation.1,2 This causes elevated pulmonary resistance and pressure, the development of plexiform lesions, increased potential for thrombus formation, ventricular remodeling, and, ultimately, right ventricular heart failure and death. Three primary pathways implicated in the development of PAH are the nitric oxide (NO), endothelin, and prostacyclin pathways.1,2,8-12 The available PAH targeted drug therapies are summarized in Table 2.13-26

The diagnosis of PAH is complex and requires a team of highly skilled specialists (Table 3).11,12,27 To date, the only way to confirm the diagnosis of PAH is to conduct a right heart catheterization. Confirmatory values are a mean pulmonary artery pressure more than 25 mm Hg, PVR more than 3 Wood units, and a normal or near normal pulmonary capillary wedge pressure.28 Several tests are recommended as part of the initial workup to rule out or identify other causes.11,12,27 This is important for both diagnosis as well as assisting with treatment selection. Because of the specificity and complexity of diagnosis, it is recommended that all patients suspected of having PAH be referred for evaluation by a pulmonary hypertension specialist. Symptoms of PAH typically are nonspecific and often present like other health problems.29 Symptoms include dyspnea (most common), fatigue or weakness, exercise intolerance, palpitations, chest pain, and syncope. PAH can also be asymptomatic. PAH progression can be rapid if it is not treated.27 The disease often is misdiagnosed for years and most patients have significantly advanced symptomatology by the time of diagnosis. In fact, according to the US Registry to Evaluate Early And

Group 1’. Pulmonary veno-occlusive disease /pulmonary capillary hemangiomatosis Group 2. PH related to left heart disease Group 3. PH associated with lung diseases and/or hypoxemia Group 4. PH due to chronic thrombotic and/or embolic disease Group 5. PH with unclear or multifactorial mechanisms PAH, pulmonary arterial hypertension; PH, pulmonary hypertension Based on reference 4.

Micrograph of patient lung with pulmonary arterial hypertension.

Specialty Pharmacy Continuum • Winter 2013

CLINICAL

Table 2. Medications for the Management of PAH Medication

Approved Indication

Drug Properties

Drug Interactions

Contraindications/Safety

Initial dose: 2 ng/kg/min, titrated ≥q15min, until doselimiting effects or tolerance established. Maintenance dose: 1-2 ng/kg/min q1-2wk

Half-life: Short (<6 min) Common for drug class: Prior to reconstitution, Diarrhea, flushing, store vials at RT; after headache, jaw pain, dilution, stable for ≤8 h leg pain, nausea/ at RT, ≤24 h on ice, or vomiting, rash, ≤48 h if refrigerated reduced platelets, (Veletri is stable for site pain (SC), site ≤48 h at RT, or ≤5 d if infection (SC), refrigerated.); protect thrombus formation from light (IV), CVC infection (IV), sepsis (IV)

Anticoagulants, antihypertensives, antiplatelets, digoxin, diuretics, vasodilators

Contraindicated with CHF due to severe LVD; rebound PH can be fatal with abrupt withdrawal or large dose reduction; requires backup pump available at all times and an additional mixed medication reservoir ready in the event of pump malfunction; always initiate with close monitoring and trained personnel

Anticoagulants, antihypertensives, antiplatelets, diuretics, inhibitors or inducers of CYP2C8, vasodilators

Avoid abrupt withdrawals; increased risk for BSIs and sepsis; always initiate with close monitoring and trained personnel

Cough, diarrhea, dizziness, flushing headache, nausea, throat irritation and pain

Anticoagulants, antihypertensives, diuretics, inhibitors or inducers of vasodilators

Caution if underlying lung disease or symptomatic hypotension

Cough, dizziness, flushing, headache, hypotension, jaw pain, lightheadedness, nausea

Anticoagulants, antihypertensives, vasodilators

Caution if underlying lung disease or symptomatic hypotension; patients with a history of hyperreactive airway may be at increased risk for bronchospasm; use caution if pulmonary edema develops

Common: Elevated LFTs, flushing, headache, nasal congestion, peripheral edema, sinusitis Serious: Anemia, birth defects, CHF exacerbation, liver injury

Cyclosporine, glyburide, hormonal contraceptives, rifampin, ritonavir, sildenafil, statins, tacrolimus, warfarin

Contraindicated with pregnancy, cyclosporine or glyburide; caution with liver impairment, anemia, PVOD, fluid retention, and decreased sperm count; REMS for pregnancy, liver monitoring; available only through Tracleer Access Program (TAP)

Epoprostenol sodium (Flolan, GlaxoSmithKline; Veletri, Actelion; others)

WHO Group I PAH to improve exercise capacity (studied primarily in NYHA FC III-IV)

Treprostinil (IV, SC) (Remodulin, United Therapeutics)

WHO Group I PAH to diminish exercise-induced symptoms (studied primarily in NYHA FC II-IV) Patients requiring transition from epoprostenol

Initial dose: 1.25 ng/kg/min titrated to response SC: use undiluted drug; change pump medication reservoir every 72 h. IV: requires further dilution; change pump medication reservoir every 48 h; requires CVC

Half-life: ~4 h

Treprostinil (inhaled) (Tyvaso, United Therapeutics)

WHO Group 1 PAH to improve exercise ability (studied primarily in NYHA FC III)

Initial dose: 3 breaths (18 mcg) per treatment qid; increase by 3 breaths per treatment q1-2wk as tolerated to goal of 9 breaths per treatment qid

Half-life: ~4 h

Requires reconstitution and further dilution, CVC and continuous infusion pump; concentration is rate/dose-dependent

Requires use of Opti-Neb inhalation device Iloprost (inhaled) (Ventavis, Actelion)

Bosentan (Tracleer, Actelion)

Adverse Events / Complications

Dosing and Administration

WHO Group 1 PAH to improve composite end point of symptoms, exercise tolerance, and lack of deterioration (studied primarily in NYHA FC III-IV)

Administer undiluted, 1 ampule per treatment session Dose: 2.5 mcg x 1, then 5 mcg per dose if tolerated, 6-9 treatments/d; (20 mcg/ mL = 5 mcg dose only!)

WHO Group 1 PAH to improve exercise ability and decrease clinical worsening (NYHA FC II-IV)

Initial dose: 62.5 mg BID x 4 wk, increase to 125 mg BID thereafter; dose adjustments required for elevated LFTs, low body weight, and administration with ritonavir

Store unopened vials at RT; store opened vials ≤30 d at RT; administer undiluted drug SC for ≤72 h at RT and diluted drug IV for ≤48 h at RT

Packaged as 4 ampules per 1 foil pack; store at RT; discard after 7 d once foil opened; discard remaining solution from ampule after 24 h; protect from light Half-life: ~20 to 30 min Store at RT

Requires use of I-neb inhalation device Half-life: ~5 h Reaches steady state in 3-5 d; unaffected by food; metabolized by and inducer of CYP3A4 and CYP2C9, possibly CYP2C19; some autoinducer properties

BSIs, bloodstream infections; CHF, congestive heart failure; CVC, central venous catheter; CYP, cytochrome enzyme; FC, functional class; LFTs, liver function tests; LVD, left ventricular dysfunction; NYHA, New York Heart Association; PAH, pulmonary arterial hypertension; PDE, phosphodiesterase; PH, pulmonary hypertension; PVOD, pulmonary veno-occlusive disease; REMs, Risk Evaluation and Mitigation Strategy; RT, room temperature; SC, subcutaneous; SCD, sickle cell disease; WHO, World Health Organization Based on references 13-26.

Table continues on following page

Long-term PAH (REVEAL), the median time to a diagnostic right heart catheterization relative to symptom onset is nearly 3 years, and the majority of patients present with severe symptoms consistent with functional class III and IV (Table 4).3-5 Functional class has been shown to be a strong predictor of survival, making initiation of treatment paramount once a patient is diagnosed.12 Emerging evidence demonstrates that earlier intervention with treatment will

result in an improved outcome.12 No known cure exists, but several targeted therapeutic options are available to improve symptoms, slow clinical progression, and promote increased survival in PAH.29 The 3 main classes of medications are prostacyclins, endothelin receptor antagonists (ERAs), and phosphodiesterase type 5 inhibitors (PDE-5i). Agents are available in oral, inhaled, and infused dosage formulations. PAH treatments require specialized training to manage in

addition to specialized drug delivery and maintenance knowledge (Tables 2 and 5).13-26 The medications are expensive and have specific handling, monitoring, and reporting requirements. Many PAH medications are designated as limiteddistribution or restricted-access items and are obtainable only through selected dispensing specialty pharmacies. Ensuring insurance coverage and reimbursement for these products can be challenging and may require expert knowledge of

benefit verification. Several factors are examined when selecting initial treatment regimens for newly diagnosed patients. Some of these factors include disease severity and level of risk (Table 6), acute vasodilatory results during a right heart catheterization, concomitant diseases, a patient’s ability and support to manage the complexity of infused or inhaled therapies, and prescriber experience

•

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Specialty Pharmacy Continuum • Winter 2013

CLINICAL

Table 2. Medications for the Management of PAH Medication Ambrisentan (Letairis, Gilead)

Sildenafil (Revatio, Pfizer)

Tadalafil (Adcirca, Lilly)

Approved Indication

continued

Dosing and Administration

Drug Properties

WHO Group 1 PAH to improve exercise ability and delay clinical worsening (NYHA FC II-III )

Dose: Initiate at 5 mg/d, increase to 10 mg/d if tolerated Limit to 5 mg/d with cyclosporine

Effective half-life: ~9 h (unaffected by food)

WHO Group 1 PAH to improve exercise ability and delay clinical worsening (predominantly NYHA FC II-III)

Dose: 20 mg TID (oral), 10-mg TID (injection)

Half-life: ~4 h

WHO Group 1 PAH to improve exercise ability (studied primarily in NYHA FC II-III)

Absorption delayed by high-fat meals

Dose: 2 tablets (40 mg) daily in 1 dose; reduce dose with renal and hepatic impairment (20 mg daily); adjust dose with ritonavir

Metabolized by CYP3A and CYP2C19, substrate P-gp

Metabolized by CYP 3A4 and 2Cp (minor) Very selective for PDE-5 compared with other PDEs

Half-life: ~35 h in PAH (unaffected by food) >10,000-fold more potent for PDE-5 than other PDEs

Adverse Events / Complications

Drug Interactions

Contraindications/Safety

Common: Flushing, headache, nasal congestion, palpitations, peripheral edema, sinusitis Serious: Anemia, birth defects, CHF exacerbations

Cyclosporine, rifampin

Contraindicated with pregnancy; caution with fluid retention or PVOD. May decrease sperm count; may reduce hemoglobin; measure at baseline, after 1 mo, then periodically REMS for pregnancy; enroll in Letairis Education and Access Program (LEAP)

Common: Dyspepsia, epistaxis flushing, nasal congestion, nausea Serious: Fatality in children, hearing loss, hypotension, priapism, vaso-occlusive crisis, vision loss

Alcohol, α-blockers, antihypertensives, organic nitrates, potent CYP3A4 inhibitors

Avoid with SCD and PVOD; allergy; contraindicated with nitrates; increased mortality with high dose in children; sudden loss of vision or hearing, priapism

Common: Dyspepsia, flushing, headache, myalgia, nasal congestion Serious: Hearing loss, hypotension, priapism, vision loss

Alcohol, α-blockers, antihypertensives, organic nitrates, potent inducers or inhibitors of CYP3A4

Contraindicated for use with nitrates; caution with some cardiovascular diseases and PVOD; sudden loss of vision or hearing, priapism

PAH continued from page 21

with the agents. The ACCF/AHA 2009 Expert Consensus Document on PAH presents a treatment algorithm based on risk assessment and diagnostic exams that many specialists use to guide therapy.11 Treatment for PAH is goal-directed, and patients should be evaluated regularly to assess improvement in symptoms, exercise capacity, and hemodynamic measures, and to minimize adverse events (AEs) and other complications of treatment.11,12,27

Future Treatment of PAH Several novel therapeutic agents and pathways are undergoing clinical investigation for use in the treatment of PAH. The endothelin (ET-1) pathway has been well established in PAH treatment. The investigational agent macitentan (Opsumit, Actelion) is an oral dual (ETA and ETB) ERA with high lipophilicity that outperformed bosentan (Tracleer, Actelion) in animal models. The results of the largest PAH study to date, the Phase III SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve clinical outcome) were presented at CHEST 2012 (American College of Chest Physicians). Maciten-

tan in a 10-mg daily dosage reduced the risk for death from PAH by 33% and hospitalization for PAH by 50% compared with placebo. Macitentan also was associated with a functional improvement in 6-minute walking distance (6MWD) at 6 months. The medication was well tolerated, with fewer serious AEs than placebo. AEs included a decrease in hemoglobin and elevated liver function tests.30 Actelion submitted a new drug application for FDA approval in October 2012.31 The NO pathway helps PAH patients through vasodilation, inhibition of platelet aggregation, and vascular smooth muscle proliferation. Riociguat (Bayer), a first-in-class soluble guanylate cyclase (SGC) stimulator, is being studied in Phase III trials.32 In Phase II studies, including CHEST-1 in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and PATENT-1 in patients with idiopathic pulmonary arterial hypertension (IPAH), 56% of patients experienced AEs including dyspnea, headache, or hypotension.33-35 Another pathway used in PAH treatment is the prostacyclin pathway. Selexipag (Actelion) is an oral prostacyclin IP receptor agonist. A Phase II study found that twice-daily dosing was well tolerated and provided a 33% reduction in PVR compared

with placebo.36 The ongoing Phase III GRIPHON (Prostacyclin [PGI2] Receptor agonist in Pulmonary arterial Hypertension) trial has a primary end point of time to first clinical event.37 Oral treprostinil (Tyvaso/Remodulin, United Therapeutics) was evaluated in patients on ERAs and/or a PDE5i in the Phase III FREEDOM-C(2) study.38 The study did not meet its primary end point of improvement in 6MWD, and the new drug application for oral treprostinil, submitted in October 2012, was denied.39,40 Selective serotonin reuptake inhibitors (SSRIs) also have been investigated for treatment of PAH, with mixed results. A retrospective cohort study did not identify a significant benefit of using SSRIs in these patients, whereas a case–control study demonstrated that high-affinity SSRIs (sertraline, paroxetine, or fluoxetine) may provide protection from or reduce the risk for PAH.41,42 The 5-HT receptor antagonist terguride (Ergonex Pharma) is undergoing studies in rat PAH models.43 Gilead terminated trials to evaluate the diuretic cicletanine after a study failed to meet its primary end point of change from baseline 6MWD after 12 weeks of treatment.44 Remodeling of the pulmonary arteries in PAH has been shown to display

some characteristics that are similar to those of certain cancers. Therefore, platelet-derived growth factor (PDGF) targeting is a new pathway for PAH drug development. The tyrosine kinase inhibitor imatinib, which is approved for use in chronic myelogenous leukemia (CML), has reversed disease in rat PAH models and has reached Phase III trials.45 These trials compare imatinib with placebo, and also are evaluating its effect in combination with sildenafil and bosentan. Patients with scleroderma were shown to receive benefit in hemodynamic parameters at 24 weeks, and imatinib was able to suppress the upregulated PDGF in PAH patients.43 Increased doses did not improve efficacy and were associated with renal AEs.45 Nilotinib, the second-generation PDGF agent used for treatment-resistant CML, also has been studied in patients who failed to respond to other PAH therapies. It has a better AE profile than imatinib but was linked to QT interval prolongation.46 Nilotinib is in Phase II clinical trials, and one study has the primary end point of change in PVR.47

Pharmacist’s Role In PAH Management PAH is a complicated, progressive disease. The future treatment of PAH

Specialty Pharmacy Continuum • Winter 2013

CLINICAL

Table 3. Diagnostic and Monitoring Evaluation

Table 5. Potential Complications With Infused Therapies

Test

Purpose

Physical examination and history

To rule out suspected PH

Chest x-ray, electrocardiogram

To rule out suspected PH

• Accidental bolus

Echocardiogram

To evaluate RV function

• Bloodstream infection

Ventilation/perfusion scan

To screen for CTEPH

Overnight oximetry

To screen for sleep disorder or nocturnal hypoxia

• Delivery delay • Development of new symptoms • Dose-related side effects

Pulmonary function tests

To screen for obstructive or restrictive diseases, and to assess diffusing capacity

• Interruption in therapy

Blood work: ANA, LFT, HIV, BNP, UA, troponin

To screen for connective tissue disease, liver disease, and HIV; BNP: to measure RV failure and determine prognosis; UA, troponin: to determine prognosis

• Mixing error

6-minute walking distance

Right heart catheterization

To assess baseline exercise capacity and response to treatment, and to determine prognosis To confirm diagnosis, obtain baseline and ongoing hemodynamic profile, assess acute vasodilator response to CCB, and to determine CO/CI, PCWP, and RAP

ANA, antinuclear antibody; BNP, brain natriuretic peptide; CCB, calcium channel blocker; CI, cardiac index; CO, cardiac output; CTEPH, chronic thromboembolic pulmonary hypertension; LFT, liver function test; PCWP, pulmonary capillary wedge pressure; PH, pulmonary hypertension; RAP, right arterial pressure; RV, right ventricular; UA, uric acid Based on references 11, 12, and 27.

• Line infection • Patient noncompliance • Pump malfunction • Sudden worsening of symptoms • Supply misuse Based on references 22-24.

Table 6. Risk Determinants In PAH (ACCF/AHA)

• Evidence of RV failure • Hemodynamics from RHC

No limitation of usual physical activity; ordinary physical activity does not cause increased dyspnea, fatigue, chest pain, or presyncope

• RV dysfunction evident on echocardiogram

Mild limitation of physical activity; no discomfort at rest, but normal physical activity causes increased dyspnea, fatigue, chest pain, or presyncope

• Symptom progression

Unable to perform any physical activity at rest and possible signs of RV failure; dyspnea and/or fatigue may be present at rest, and symptoms are increased by almost any physical activity

6MWD, 6-minute walking distance; ACCF/AHA, American College of Cardiology Foundation/ American Heart Association; BNP, brain natriuretic peptide; CPET, cardiopulmonary exercise test; PAH, pulmonary arterial hypertension; RHC, right heart catheterization; RV, right ventricular Based on reference 11.

RV, right ventricular; WHO, World Health Organization Based on references 3 and 4.

is poised to improve greatly with the study of several new pharmacotherapeutic agents. The multitude of medications used for managing PAH underscores the value of the pharmacist as a provider in PAH treatment. Pharmacists make an important contribution to PAH patient care as part of an interdisciplinary team. The pharmacist’s role in PAH management includes advising on medication dosing and dilutions for infused therapies, providing recommendations for patient-specific considerations, identifying and preventing potential complications including serious drug interactions, and providing patient education and AE management. Pharmacists also assist with medication adherence, refill management, prior

authorizations, and specialty pharmacy coordination. With these actions, the pharmacist improves the patient’s experience, ensures safe use of PAH targeted therapies, and contributes to optimal outcomes. The commonly used medications for PAH (with the exception of sildenafil and tadalafil) are available only from a limited number of specialty pharmacy providers. The advantage of the specialty pharmacy model is convenience for manufacturers and providers when communicating with one or two pharmacies for all their patients and the presence of dedicated PAH teams at the specialty pharmacies. The disadvantages of this model are potential delays in therapy due to communication challenges between the health system,

3. Simonneau G, Galie N, Rubin L, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004;43(suppl 1):s5-s12. 4. Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54 (1 suppl):s43-s54. 5. Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension. Baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376-387.

• Functional class

2. Lourenço AP, Fontoura D, Henriques-Coelho T, Leite-Moreira AF. Current pathophysiological concepts and management of pulmonary hypertension. Int J Cardiol. 2012;155(3):350-361.

• CPET results

Description

Marked limitation of physical activity; no discomfort at rest, but less than ordinary activity causes increased dyspnea, fatigue, chest pain, or presyncope

1. Jain S, Ventura H, deBoisblanc B. Pathophysiology of pulmonary arterial hypertension. Semin Cardiothorac Vasc Anesth. 2007;11(2):104-109.

• BNP

Class

III

References

6. Benza RL, Miller DP, Barst RJ, Badesch DB, Frost, AE, McGoon MD. An evaluation of longterm survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142(2):448-456.

• 6MWD

Table 4. Summary of WHO Classification Of Functional Class in Pulmonary Hypertension

gency room visits, or hospitalizations; and total cost of care. Overall, there is potential for improved care of the patient with PAH, and health system pharmacists have an opportunity to be part of the team that develops new, coordinated models of care.

patient, and specialty pharmacy, and fragmentation of care, because the specialty pharmacies are not part of the health system network or the accountable care organization. To address these potential disadvantages, pharmacists at some health systems, including the University of Illinois Hospital & Health Sciences System, have developed innovative models that may lead to improved outcomes for patients with PAH. These models involve team-based direct patient contact, insurance benefit verification, start of therapy management, followup visits with the pharmacist for medication management, coordination with the health care team, and documentation in the electronic medical record. Outcomes to be measured include time to start of therapy; patient adherence; management of AEs; patient satisfaction; quality of life; utilization of resources such as doctor visits, emer-

D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991;115(5):343-349.

8. Park MH. Advances in diagnosis and treatment in patients with pulmonary arterial hypertension. Catheter Cardiovasc Interv. 2008;71(2):205-213. 9. Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med. 2004;351(16):1655-1665. 10. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351(14):1425-1436. 11. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension. J Am Coll Cardiol. 2009;53(17):1573-1619. 12. Vachiery JL, Yerly P, Huez S. How to detect disease progression in pulmonary arterial hypertension. Eur Respir Rev. 2012;21(123):40-47. 13. Tracleer (bosentan) tablets prescribing information. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; October 2012. 14. Ventavis (iloprost) inhalation solution prescribing information. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; August 2012. 15. Veletri (epoprostenol) for injection prescribing information. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; June 2012. 16. Adcirca (tadalafil) tablets for oral administration prescribing information. Indianapolis, IN: Eli Lilly and Company; March 13, 2012. 17. Letairis (ambrisentan) tablets, for oral use prescribing information. Foster City, CA: Gilead Sciences, Inc.; October 2012. 18. Flolan (epoprostenol) for injection prescribing information. Research Triangle Park, NC: GlaxoSmithKline; March 2011. 19. Revatio (sildenafil) tablets, for oral use; for oral suspension; injection, for intravenous use prescribing information. New York, NY: Pfizer Inc; August 2012.

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PAH continued from page 23

20. Remodulin (treprostinil) injection prescribing information. Research Triangle Park, NC: United Therapeutics Corporation; 2011. 21. Tyvaso (treprostinil) inhalation solution prescribing information. Research Triangle Park, NC: United Therapeutics Corporation; February 2011. 22. Roncesvalles A, Lee FW, Camamo J, Priestley G. Patient safety challenges in treprostinil therapy. Medsurg Nurs. 2008;17(2):101-106. 23. Kingman MS, Tankersley MA, Lombardi S, et al. Prostacyclin administration errors in pulmonary arterial hypertension patients admitted to hospitals in the United States: a national survey. J Heart Lung Transplant. 2010;29(8):841-846. 24. Kallen AJ, Lederman E, Balaji A, et al. Bloodstream infections in patients given treatment with intravenous prostanoids. Infect Control Hosp Epidemiol. 2008;29(4):342-349. 25. Kingman MS, Tankersley MA, Lombardi S, et al. Prostacyclin administration errors in pulmonary arterial hypertension patients admitted to hospitals in the United States: a national survey. J Heart Lung Transplant. 2010;29(8):841-846. 26. Kallen AJ, Lederman E, Balaji A, et al. Bloodstream infections in patients given treatment with intravenous prostanoids. Infect Control Hosp Epidemiol. 2008;29(4):342-349. 27. McGoon MD, Kane GC. Pulmonary hypertension: diagnosis and management. Mayo Clin

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treated by 14 infusion pharmacy sites during May and June 2012. About twothirds of the patients (197) were on antibiotic therapy, 16 received methylprednisolone, 15 were on parenteral pain management, 11 were parenteral nutrition patients, and the rest were

Proc. 2009;84(2):191-207. 28. Badesch DB, Champion HC, Sanchez MA, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 suppl):s55-s66. 29. Badesch DB, Abman SH, Simonneau G, Rubin LJ, McLaughlin VV. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines. Chest. 2007;131(6):1917-1928. 30. The Pharma Letter. Actelion files for US approval of Opsumit for PAH. http://www. thepharmaletter.com/file/117432/actelionfiles-for-us-approval-of-opsumit-for-pah.html. Accessed January 29, 2013. 31. ClinicalTrials.gov. Study of ACT-064992 on morbidity and mortality in patients with symptomatic pulmonary arterial hypertension. NCT00660179. http://clinicaltrials.gov/ ct2/show/NCT00660179. Updated October 23, 2012. Accessed January 29, 2013. 32. Ghofrani HA, Hoeper MM, Halank M, et al. Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Eur Respir J. 2010;36(4):792-799. 33. ClinicalTrials.gov. A study to evaluate efficacy and safety of oral BAY63-2521 in patients with pulmonary arterial hypertension (PAH) (PATENT-1). NCT00810693. http://clinicaltrials. gov/ct2/show/NCT00810693. Updated June 19, 2012. Accessed January 29, 2013. 34. ClinicalTrials.gov. A study to evaluate efficacy and safety of oral BAY63-2521 in patients with CTEPH (CHEST-1). NCT00855465.

receiving various other therapies. The team identified 44 problems. The most concerning ones included three patients making serious breaches of aseptic technique involving the IV catheter, risking bloodstream infections; three patients reporting one or more missed doses; eight patients having various problems related to their IV catheters, such as redness and/or

“When you see deficiencies, you’ve got to stop and ask yourself, ‘Why does this keep happening?’” —Hetty Lima, RPh, FASHP

http://clinicaltrials.gov/ct2/show/ NCT00855465. Updated August 6, 2012. Accessed January 29, 2013. 35. Ghofrani HA, Voswinckel R, Gall H, et al. Riociguat for pulmonary hypertension. Future Cardiol. 2010;6(2):155-166. 36. Simonneau G, Lang I, Torbicki A, et al. Efficacy, safety and tolerability of ACT-293987, a novel oral, non-prostanoid, prostaglandin I2 (IP) receptor agonist: results from a phase IIa study in pulmonary arterial hypertension (PAH). Am J Respir Crit Care Med. 2010;181:A2515. Abstract. 37. ClinicalTrials.gov. Efficacy and safety of oral UT-15C tablets to treat pulmonary arterial hypertension (FREEDOM-C2). http://clinicaltrials.gov/ct2/show/NCT00887978. Updated December 7, 2012. Accessed January 29, 2013. 38. ClinicalTrials.gov. ACT-293987 in pulmonary arterial hypertension. http://clinicaltrials.gov/ ct2/show/NCT01106014. Updated October 8, 2012. Accessed January 29, 2013. 39. Tapson VF, Torres F, Kermeen F, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/ or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. 2012. doi: 10.1378/ chest.11-2212. [Epub ahead of print] 40. United Therapeutics. UT-15C treprostinil diethanolamine sustained release tablets (oral treprostinil) [news release]. http://www.unither.com/oral-treprostinil-for-pah. Accessed January 29, 2013.

swelling at the IV catheter insertion site, or difficulty infusing the medication through the IV catheter; five not flushing the IV catheter correctly; seven with pain uncontrolled by medication; four reporting possible adverse drug effects; and two reporting that home-based care was delayed by several days. One patient could not afford the prescribed antibiotic, and the pharmacist was able to obtain orders from the prescriber for a less expensive drug.

Kudos for Reporting Outcomes Commenting on the findings, Hetty Lima, RPh, FASHP, the vice president of specialty infusion and rare diseases at Diplomat Specialty Pharmacy, in Flint, Mich., said that issues like the ones faced by patients in this study are fairly common, and following up with home infusion therapy patients by one method or another is “pretty much industry standard.” But, she added, “throughout the years, no one has come forward to report on their clinical outcomes, so I applaud them for that.” Still, she said she would have liked the researchers to delve deeper into why some of these concerns happened: Did the pharmacists talk above the patients’ level of understanding? Did the home nurses ensure the patients

41. Kawut SM, Horn EM, Berekashvili KK, et al. Selective serotonin reuptake inhibitor use and outcomes in pulmonary arterial hypertension. Pulm Pharmacol Ther. 2006;19(5):370-374. 42. Shah SJ, Gomberg-Maitland M, Thenappan T, Rich S. Selective serotonin reuptake inhibitors and the incidence and outcome of pulmonary hypertension. Chest. 2009;136(3):694-700. 43. Dumitrascu R, Kulcke C, Konigshoff M, et al. Terguride ameliorates monocrotaline-induced pulmonary hypertension in rats. Eur Respir J. 2011;37(5):1104-1118. 44. ClinicalTrials.gov. Study of cicletanine for pulmonary arterial hypertension (PAH). http://clinicaltrials.gov/ct2/show/ NCT00832507. Updated August 22, 2012. Accessed January 29, 2013. 45. Hatano M, Yao A, Shiga T, Kinugawa K, Hirata Y, Nagai R. Imatinib mesylate has the potential to exert its efficacy by downregulating the plasma concentration of platelet-derived growth factor in patients with pulmonary arterial hypertension. Int Heart J. 2010;51(4):272-276. 46. Duggan N, Bonneau O, Hussey M, et al. Comparison of effects of imatinib and nilotinib in a rodent model of pulmonary arterial hypertension. Am J Respir Crit Care Med. 2010;181:A6304. Abstract. 47. ClinicalTrials.gov. Efficacy, safety, tolerability and pharmacokinetics (PK) of nilotinib (AMN107) in pulmonary arterial hypertension (PAH). http://clinicaltrials.gov/ct2/ show/NCT01179737. Updated October 1, 2012. Accessed January 29, 2013.

understood how to administer the drug? Did the patients use appropriate aseptic technique? “When you see deficiencies, you’ve got to stop and ask yourself, ‘Why does this keep happening?’” Ms. Lima said. She said she also would have liked to see how the number of issues identified compared with benchmarks established by accrediting agencies like the Accreditation Commission for Health Care or the Joint Commission. Ms. Johnson said the study was intended “to simply provide a snapshot of the type of problems that might occur early in a patient’s home infusion care.” She noted that “teaching self-administration of a complicated IV therapy involves several knowledge areas featuring multiple steps, and accomplishing successful teaching during a time when the patient may still be feeling unwell can be challenging. The assessment tool is intended to reinforce anything the patient may have misunderstood or forgotten.” Regarding benchmarking, she said it was difficult to find published information with which a meaningful comparison could be made. “Future studies,” Ms. Johnson said, “may be able to provide more data that could eventually result in benchmarking.” —Karen Blum

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

This book presents in a logical and progressive format all the information that pharmacists and student pharmacists need to understand the purpose and processes of compounding. It covers basic guidelines, economic and technical factors that compounding pharmacists must consider and all aspects of good manufacturing practices for compounded medications.

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Managing Anticoagulation Patients in the Hospital: The Inpatient Anticoagulation Service

Michael Gulseth June 15, 2007 The first guide to providing systematic anticoagulation care in inpatient settings, this resource will be welcomed by all pharmacists who practice in or are developing, implementing and maintaining an inpatient anti-coagulation service.

Pharmacy and the US Healthcare System: Fourth Edition Michael Ira Smith; Albert I. Wertheimer; Jack E. Fincham

March 13, 2013 This book is a one-stop textbook of current information about the features of the US healthcare system. It covers the personnel and institu-tions, along with concise reports on trends, regulations policy and finance.

Stockley’s Drug Interactions Pocket Companion 2013 Karen Baxter, Claire L Preston

January 10, 2013 The conveniently sized quick-reference Stockley’s Drug Interactions Pocket Companion 2013 3 continues to provide the busy health care professional with a trustworthy, affordable and practical clinical reference on drug interactions and their management. It draws on the wealth of clinically evaluated, evidence-based information on drug–drug, drug– – herb and drug–food interactions that is presented in the latest revali-dated updates of the full reference work, Stockley’s Drug Interactions.

The APhA Complete Review for Pharmacy, Ninth Edition American Pharmacists Association

January 15, 2012 The NAPLEX® is the standard licensing exam that all U.S. pharmacy stu-dents must pass to practice pharmacy. It’s an arduous exam that tests a daunting range of knowledge. This book contains only the information most ost relevant e e a t to the t e exam, e a , summarized su a ed in abbreviated abb e ated bullet bu et format. o at SPC0213

Specialty Pharmacy Continuum • Winter 2013

CLINICAL

Intravenous Immunoglobulins FAQ:

Jerry Siegel, PharmD, FASHP

Managing Adverse Reactions

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

’ve been involved with the development and management of intravenous immunoglobulin (IVIG) therapy for more than 30 years. In fact, I was actually present at the bedside of the first patient to be infused with IVIG at the Ohio State University Hospitals. We waited with bated breath to see whether the patient developed an infusion reaction; fortunately, he did not, helping to usher in the modern-day era of safe, effective IVIG therapy. Still, questions about the optimal use of IVIG are emailed to me on an almost daily basis. Many of those queries touch on safety issues, such as the review and monitoring of adverse reactions. I want to make this column as relevant as possible, so please send me your questions on IVIG therapy via email to Jerry. siegel.rx@gmail.com (cc: spceditor@mcmahonmed.com), and I will do my best to answer them. Each quarter, we’ll choose the most compelling question or patient case and use it as the basis for my column.

: What are the key steps to take when managing an adverse reaction to IVIG?

A: When an adverse reaction occurs after administration of intravenous immunoglobulin (IVIG), it is important to determine whether the reaction was caused by the brand of IVIG, the manner in which it was administered, or other clinical factors. The most common adverse reactions associated with IVIG are headache, chills, and fever. By slowly escalating the infusion, monitoring for these events, and slowing the rate as necessary, you can ensure the infusions are more easily tolerated. Also, premedications such as acetaminophen and diphenhydramine will be useful for these types of reactions. The case in point is a patient who experienced “rigors” during the administration of IVIG. The reaction was so profound that the patient was very concerned about continuing therapy. Suspecting that the first brand of IVIG was the culprit, the physician requested a change in brand. Was this adverse reaction actually related to the particular product or to another factor? Rigors was described in the literature more than 100 years ago as an extreme exacerbation of chills leading to shaking and pain and convulsive-like muscle contractions.1 The phenomenon often is preceded by a feeling of cold running down the spine followed by pain, chills, shaking, and spasm. Fever often is the next phase of the event. Physiologically, an increase in prostaglandins is followed by cytokine release. Although the primary cause of rigors still is not well understood, it has been postulated that the rapid infusion of antibodies (IgG) in an IVIG infusion precipitates an antigen/antibody reaction that accelerates rapidly, causing rigors. The treatment of choice for rigors has historically been meperidine.2,3 However, because of the active metabolite normeperidine, there is increased risk for toxicity in the elderly and those with renal impairment, which may contraindicate its use.4

Other agents used to treat rigors include tramadol, fentanyl, and morphine.5-9 In the case of the patient discussed here, although there was no reason to believe that a change in brand would alleviate the risk for rigors, it was decided to try a different brand for the patient’s peace of mind. The package

returns? One option would be to consider using a nonsteroidal anti-inflammatory drug (NSAID), rather than acetaminophen, as a premedication because the NSAIDs are stronger prostaglandin inhibitors. Another possibility would be to use tramadol as an additional premedication. Because tramadol has been used for treatment of rigors, it is conceivable that it may have some benefit for prophylaxis.

The laboratory evidence of hemolysis includes having a hemoglobin drop of greater than 1 g/dL within 10 days of the infusion plus a positive direct antiglobin. Additionally, at least 2 other factors should be present, including: • reticulocyte count • lactate dehydrogenase • haptoglobin • serum bilirubin • hemoglobinemia • hemoglobinuria • significant spherocytosis When the combination of these clinical and laboratory findings is present, the likelihood that IVIG was the causative factor is much higher. It is always important to screen patients for risk factors, split large doses so that no more than 1 g/kg per day is infused, and monitor for and educate patients about signs and symptoms of hemolysis post-infusion. In high-risk situations, monitoring hemoglobin 48 to 72 hours post-infusion and selecting IVIG products with low-titer antibodies for isohemaglutinin A/B may be warranted.

References 1. Johnson G. A lecture on the pathology and treatment of rigors. Br Med J. 1868;4:369-370. 2. Raymo LL, Camejo M, Fudin J. Eradicating analgesic use of meperidine in a hospital. Am J Health Syst Pharm. 2007;64(11):1148,1150,1152. 3. Medical University of South Carolina. Guidelines for the appropriate use of meperidine. Charleston, SC: Medical University of South Carolina; 2008. 4. Meperidine hydrochloride [FR]. UNC drug formulary. Hudson, OH: Lexi-Comp, Inc.; 2008.

insert guidelines for infusion were followed, but after the first escalation, the patient again experienced rigors. The infusion was stopped, and meperidine was given immediately. After 60 minutes, the patient returned to baseline and the next decision to be made was whether to discontinue treatment. At this point, the pharmacist on the case recommended starting again at the beginning rate, escalating at 50% of the normal rate and waiting twice as long before continuing any further escalations. The patient tolerated the remainder of the infusion, but the escalation rate was limited to the half-dose increase for the remainder of the dose. The patient was instructed to return in 1 month for his next treatment. What approach should be taken when he

This case shows that changing to another brand of IVIG is not always the solution, and that rate adjustment and monitoring are essential. With some adverse reactions, the rate of infusion may have nothing to do with the event. If a patient has clinical and laboratory evidence of hemolysis following an infusion of IVIG, how can you tell if it is related to the IVIG? Some underlying patient factors to consider are the patient’s blood type (non–type O are at increased risk) and sex (women are at increased risk) and whether they have an underlying inflammatory condition. Other factors to consider are whether a high dose (>2 g/kg per day IVIG) was administered and whether products with high-titer IgG antibodies to isohemaglutinins A/B are used.

5. Kranke P, Eberhart L, Roewer N, Tramer MR. Pharmacologic treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials. Anesth Analg. g 2002;94(2):453-460. 6. Tsai YC, Chu KS. A comparison of tramadol, amitriptyline, and meperidine for postepidural anesthetic shivering in parturients. Anesth Analg. g 2001;93(5):1288-1292. 7.

Chan AM, Ng KF, Tong EW, Jan GS. Control of shivering under regional anesthesia in obstetric patients with tramadol. Can J Anesth. 1999;46(3):253-258.

8. de Witte J, Deloof T, de Veylder J, Housmans PR. Tramadol in the treatment of postanesthetic shivering. Acta Anaesthesiol Scand. 1997;41(4):506-510. 9. Pausawasdi S, Jirasirithum S, Phanarai C. The use of tramadol hydrochloride in the treatment of postoperative shivering. J Med Assoc Thai. 1990;73(1):16-20.

Dr. Siegel is a speaker for Amgen.

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Looking for a meeting that provides numerous opportunities to connect with peers and industry experts on topics related to Specialty Pharmacy? Search no further than the 2013 NHIA Annual Conference & Exposition—where you’ll find highly valuable educational and networking sessions focused on Alternate Site Infusion and Specialty Pharmacy, including: • An Executive Pre Conference* Session, titled “Assessing the Spe cialty Pharmacy Business Opportunity for Home Infusion Providers,” that begins with an overview of the state of the specialty pharmacy industry and addresses the risks, as well as the opportunities, that specialty drugs represent for the alternate site industry—in this pro gram, you’ll explore how to develop a business plan for a specialty program, from data requirements to drug access. • A Lunch Symposium, titled “New Drugs and Biologics— 2012,” returning for the 11th consecutive year at at tendee requests, that will review key clinical and reimbursement considerations for the most re cently approved parenteral drugs and biologic therapies—and also those oral agents with a potential to impact home infusion therapy services.

• A Roundtables Program on two separate evenings that provide a venue for industry peers to gather and discuss a large array of specific topics related to the alternate site and specialty pharmacy—one of the most well attended programs at the conference each year! • A Concurrent Track Session, titled “To Do or Not To Do? Crafting Drug Protocols for High Risk Therapies,” which will offer tools and insights into the development of drug protocols intended to edu cate staff and remediate provider risk. • Another Concurrent Track Session, titled “Biologic Therapies—Mech anisms of Action and Treatment Considerations,” will impart a com prehensive overview of the immune system relative to how each type of biologic therapy exerts its effect—as well as the most common ad verse reactions that have been reported and strategies for minimizing their occurrence.

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