March 2014

The Pharmacist’s News Source

pharmacypracticenews.com

Volume 41 • Number 3 • March 2014

Printer-friendly versions available online

in this issue UP FRONT

3

Student’s Corner: the ‘Five Ps’ of pharmacy assessment.

CLINICAL

4

Benchmarking helps hospitals boost outcomes, save scarce health-care dollars.

6

Hepatitis C rates slashed in liver transplant patients; results “practice-changing.”

16

Hospitals at the tipping point for more widespread CSTD adoption.

WEB EXCLUSIVE

Part 1 of a 2-Part Series

ASP Building Tips: Going Slow Yields Big Success Orlando, Fla.—“Learn to crawl before you walk and run,” was the first piece of advice Ed Eiland, PharmD, MBA, BCPS (AQ-ID), FASHP, dispensed to a room full of attendees at the American Society of HealthSystem Pharmacists 2013 Midyear Clinical Meeting eager to implement or strengthen their own antimicrobial stewardship program (ASP).

Based on $1.34 million in savings, a 25% drop in 30-day hospital readmissions and a nearly 50% drop in Clostridium difficile infections (CDIs) Dr. Eiland achieved with a revamped ASP at Huntsville Hospital, in Ala, the go-slow strategy can yield major dividends.

Phase 1 (2005-2007) His team’s first step in building the ASP was to assemble an antimicrobial management team (AMT), including pharmacists, infectious

•

see ASP BUILDING TIPS, page 8

Nearly $1 M in cost avoidance Radiofrequency Identification (RFID) reduces errors, speeds process of refilling drug trays.

See Technology section, pharmacypracticenews.com

EDUCATIONAL REVIEW

Administration of CV Drugs With Food and Grapefruit Juice See page 22.

Pharm Technicians Praised for Spot-on Med Reconciliation

New sterile compounding legislation:

Does Bill Have the Muscle To Stop Another NECC? B

y the end of 2013, a sigh of relief could be heard in some patient safety circles after newly passed legislation gave state and federal officials broadened oversight powers to regu ulate sterile compounders. With the new insp pection muscle bestowed on those officiaals, the chances of another New England Compounding Center (NECC)-type outbreeak killing or injuring hundreds of patien nts seemed significantly diminished.

The latest details on the results off those inspections, however, suggest that safety gaps still remain.

Of the 28 sterile compounding facilities that have registered with the FDA under the bill’s new “outsourcing facility” category, 13 had been inspected by the FDA ass of late February. That may not be surprisingg, given that it is still the early days of the leggislation’s rollout. The more striking findingg is that all but two of the inspected facilities w were issued Form 483s, which the agency send ds if its inspectors have observed “objectional conditions” at

•

see ANOTH HER NECC?, page 26

A Push for Practice Change Yields Big Payoff at U Kansas

Orlando, Fla.—Emergency department (ED) pharmacy technicians from several hospitals received praise at the American Society of HealthSystem Pharmacists 2013 Midyear Clinical Meeting for conducting medication reconciliations with up to 96% accuracy. The studies found that pharmacy technicians were able to detect a substantial number of

Chicago—Millions of dollars in new revenue. A 30 percentage-point gain in patient satisfaction score. A fourfold increase in the capture rate for pharmacist-completed admission histories and discharges. Any of those achievements would be impressive on its own. But scoring all three in less than a year’s time is a testament to the power of taking an entrepreneurial approach to practice change, according to Rick Couldry, MS, FASHP, the director of pharmacy at the University of Kansas Hospital, in Kansas City, Kan. At the American Society of Health-System Pharmacists’ (ASHP) annual leadership conference, Mr. Couldry described some of the key components of his strategy for revamping pharmacy operations. One effective strategy, he noted, is to tell compelling patient stories that communicate viscerally why a proposed practice model change is needed, and be prepared to answer the question of “So what?” by delivering measurable evidence of a program’s effect.

see ED TECHNICIANS, page 10

see BIG PAYOFF, F page 30

•

•

New Product Codonics, RIVA team up for safer labeling.

See Technology section, pharmacypracticenews.com

Because your patients have different needs… …Amgen supports a broad range of access programs INDEPENDENT CO-PAY FOUNDATIONS Amgen Assist can check the current funding status at different independent foundations for your office

MEDICARE

UNINSURED

COMMERCIALLY INSURED

THE SAFETY NET FOUNDATION The Safety Net Foundation provides products at no cost to eligible uninsured and underinsured patients THE NEULASTA/NEUPOGEN FIRST STEP™ PROGRAM The NEULASTA/NEUPOGEN FIRST STEP™ Program helps reduce out-of-pocket (OOP) costs for all eligible commercially insured patients.

Go to www.amgenfirststep.com for program eligibility and limitations

NEULASTA/NEUPOGEN NEULASTA FIRST STEP FIRST STEP PROGRAM PROGRAM ®

™

NEULASTA/NEUPOGEN FIRST STEP™ PROGRAM

*Please do not remove this sticker

($///$-,$JK<G( nnn%8d^\e=@IJKJK<G%Zfd

For more information regarding these programs, please call 1-888-4ASSIST or visit AmgenAssistOnline.com To enroll your patient into the Amgen FIRST STEP™ Co-pay Coupon Program call 1-888-65-STEP1 (1-888-657-8371) or visit amgenfirststep.com.

The NEULASTA/NEUPOGEN FIRST STEP™ Program MasterCard is issued by The Bancorp Bank pursuant to license by MasterCard International and this card may not be used everywhere Debit MasterCard is accepted. No cash or ATM access. MasterCard is a registered trademark of MasterCard International Incorporated. The Bancorp Bank; Member FDIC.

Amgen One Amgen Center Drive Thousand Oaks, CA 91320-1799

© 2014 Amgen Inc. All rights reserved. 77477-R1-V3 1-14

Up Front 3

Pharmacy Practice News • March 2014

Student’s Corner

Development of the ‘Five Ps’ of Pharmacy Assessment Paresh Kumar

100 92

PharmD Candidate

Michael J. Gonyeau, PharmD, FCCP, BCPS

80

77

52%

reported that the tool would be helpful to their practice

92% 77%

reported that the tool would be easy to learn

Northeastern University School of Pharmacy Boston, Massachusetts

Percent

Clinical Professor

T

he “five Ps” of pharmacy assessment tool is designed to guide students when they are analyzing the assessment component in the subjective- objective-assessmentplan (SOAP) process. The five Ps are patient, prescription, pharmacokinetics, problems (with drug therapy) and prevention. Our main objective was to develop and validate this tool through feedback from practicing pharmacists and pharmacy faculty to aid in the teaching and learning of the SOAP process in patient evaluation.

The five Ps assessment tool and a seven-item questionnaire were sent to practicing pharmacists and clinical pharmacy faculty, as separate cohorts, using Northeastern University’s continuing education network. At the end of both surveys, there was an open response section so survey participants could provide feedback on the strengths of the tool and opportunities for improvement. Participation in these surveys was voluntary, and

58

60

52

40

58%

20

would recommend the tool to P2 to P4 students and newly licensed pharmacists would recommend the tool to PGY1 residents

0

Figure. Pharmacist respondents’ evaluations of the five Ps tool. responses were anonymous.

Of the pharmacists responding to the survey (N=149), 52% agreed that the tool would be helpful to their practice, 92% agreed that it would be easy to learn and 77% reported that they would recommend the tool to newly licensed pharmacists and P2 to P4 students; fewer believed the tool would be helpful for postgraduate year 1 residents (58%) (Figure). Comments highlighted the tool’s concise algorithmic structure and ease of implementation in practice, and suggestions included improving the tool’s efficiency, considering the lack of time available to use it in some practice areas.

Of faculty respondents (n=12), 85.8%

supported using the tool as an adjunct educational technique to improve the teaching and learning processes related to the patient assessment section in the SOAP process. Overall, 71% agreed that the tool would be easy to learn and 85.7% agreed it would be easy to teach. Additionally, they indicated that use of the tool would likely improve student competence (62.5%), confidence (87.5%) and efficiency (62.5%) in patient assessment.

Faculty comments pointed to strengths such as the tool’s algorithmic approach, its effectiveness as a supplemental method for therapeutics courses and its usefulness for P4 rotations due to its easyto-remember mnemonic. Suggestions

for improvement included modifying the wording and addressing the potential confusion related to integrating the tool.

Survey results demonstrated that practicing pharmacists and clinical faculty positively support the use of the five Ps of pharmacy assessment tool as an adjunct teaching method for the assessment portion of the SOAP process. A study evaluating the effectiveness and benefit of this tool from the professional pharmacy student perspective is currently in progress at Northeastern and results can be expected by May 2014.

Mr. Kumar and Dr. Gonyeau reported no relevant financial conflicts of interest.

EDITORIAL BOARD

ART/PRODUCTION STAFF

ADMINISTRATION

Michele McMahon Velle, MAX Graphics/Creative Director

Robert Adamson, PharmD, Livingston, NJ

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

Ernest R. Anderson Jr., MS, RPh, Boston, MA

Volume 41 • Number 3 • March 2014 • pharmacypracticenews.com

ANESTHESIOLOGY/PAIN Julie A. Golembiewski, PharmD, Chicago, IL Melvin E. Liter, MS, PharmD, FASHP, Lexington, KY

INTERNAL MEDICINE

EDITORIAL STAFF

David S. Craig, PharmD, BCPS, Tampa, FL

Geoffrey C. Wall, PharmD, FCCP, BCPS, CGP, Des Moines, IA

Robert L. Barkin, MBA, PharmD, Chicago, IL

NUCLEAR PHARMACY

David Bronstein, Editorial Director davidb@mcmahonmed.com

BIOTECHNOLOGY

Jeffrey Norenberg, PharmD, Albuquerque, NM

Indu Lew, PharmD, Livingston, NJ

ONCOLOGY Robert T. Dorr, PhD, RPh, Tucson, AZ

CARDIOLOGY

Robert Ignoffo, PharmD, San Francisco, CA

s CT C. Michael White, PharmD, Storrs,

Sarah Tilyou, Senior Editor smtilyou@mcmahonmed.com Kevin Horty, Don Pizzi, Adam Marcus, Cynthia Gordon, Contributing Editors

Philip E. Johnson, MS, RPh, FASHP, Tampa, FL

CNS/PSYCHIATRY

Cindy O’Bryant, PharmD, Aurora, CO

Charles F. Caley, PharmD, Storrs, CT Lawrence Cohen, PharmD, FASHP, FCCP, Fort Worth, Texas Larry Ereshefsky, PharmD, San Antonio, T Texas

Ali McBride, PharmD, MS, BCPS, St. Louis, MO Sara S. Kim, PharmD, BCOP, New York, NY

James Prudden, Group Editorial Director Robin B. Weisberg, Manager, r Editorial Services Elizabeth Zhong, Associate Copy Chief

James O’Neill, Senior Systems Manager Dan Radebaugh, Director of Production and Technical Operations Marty Barbieri, Production Manager Brandy Wilson, Circulation Coordinator

McMAHON PUBLISHING Raymond E. McMahon, Publisher and CEO, Managing Partner Van Velle, President, Partner Matthew McMahon, General Manager, Partner Lauren Smith, Michael McMahon, Michele McMahon Velle, Rosanne C. McMahon, Partners

MCMAHON PUBLISHING MCMAHONMED.COM Sales, Production and Editorial Offices: 545 West 45th Street, 8th Floor, New York, NY 10036.

Telephone: (212) 957-5300.

Corporate Office: 83 Peaceable Street, Redding CT 06896

COMPLEMENTARY AND ALTERNATIVE MEDICINE

ORGAN TRANSPLANT PHARMACY

Cathy Rosenbaum, PharmD, Cincinnati, OH

Eric Tichy, PharmD, BCPS, New Haven, CT

SALES

CRITICAL CARE

PEDIATRICS

Judi Jacobi, PharmD, FCCM, Indianapolis, IN

Gretchen Brummel, PharmD, BCPS, Hudson, OH

David Kaplan, Group Publication Director dkaplan@mcmahonmed.com

INFECTIOUS DISEASES

REIMBURSEMENT

Steven J. Martin, PharmD, BCPS, FCCM, Toledo, OH

Bonnie E. Kirschenbaum, MS, FASHP, Breckenridge, CO

David P. Nicolau, PharmD, Hartford, CT

TECHNOLOGY

Robert P. Rapp, PharmD, Lexington, KY

Thomas Van Hassel, RPh, Yuma, AZ

Nancy Parker, Classified Advertising g Sales nparker@mcmahonmed.com

Copyright © 2014 McMahon Publishing, New York, NY 10036. All rights reserved. Pharmacy Practice News (ISSN 0886-988x) is published monthly by McMahon Publishing. Periodicals postage paid at New York, NY, and at additional mailing offices. POSTMASTER: Send address changes to Pharmacy Practice News, Circulation Dept., 545 W. 45th St., 8th Floor, New York, NY 10036.

WANT TO SUBSCRIBE? CHANGE YOUR ADDRESS? HERE’S HOW All U.S. hospital pharmacists should receive Pharmacy Practice News free of charge. If you are a hospital pharmacist and do not receive the publication, you must add your professional address or make your address change directly

with Pharmacy Practice News, Circulation Dept., 545 W. 45th St., 8th Floor, New York, NY 10036. You can also fax your request to (212) 977-3645, or send it via email, circulation@mcmahonmed.com.

If you are not a hospital pharmacist but would like to receive Pharmacy Practice News, please send a check for $70.00 (U.S.) or $90.00 (outside U.S.) for a year’s subscrip-

tion payable to Pharmacy Practice News to McMahon Publishing, 545 West 45th St., 8th Floor, New York, NY 10036.

Please allow 8 to 12 weeks for delivery of the first issue.

Individual issues are $7.00 (U.S.) or $10.00 (outside U.S.).

McMahon Publishing is a 42-year-old, first-generation, family-owned publishing company dedicated to providing medical professionals with essential, up-to-date news. As

the second largest publisher of medical newspapers, McMahon produces Anesthesiology News, Clinical Oncology News, Gastroenterology & Endoscopy News, General Surgery News, Infectious Disease Special Edition, Pain Medicine News, Pharmacy Practice News.

Rheumatology Practice News and Specialty Pharmacy Continuum.

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

Matt Spoto, Senior Account Manager mspoto@mcmahonmed.com

4 Clinical

Pharmacy Practice News • March 2014

Quality Improvement

Operating in a Vacuum? Try Benchmarking D

Better Anticoagulation, Lower LOS = Millions in Savings Robert Adamson, PharmD, the corporate vice president of clinical pharmacy services at Barnabas Health, a network of eight hospitals headquartered in Livingston, N.J., has been using benchmarking for several years. When asked for a benchmarking success story, Dr. Adamson did not hesitate. “Our anticoagulation initiative has enabled us to make a significant reduction in hospital length of stay [LOS], which has generated huge savings,” he said. “But even more importantly, it’s yielded major improvements in patient care.”

The effort began with the realization that too many patients at Barnabas Health were either super- or subtherapeutic while on warfarin therapy.

“That’s not good for two reasons: First and foremost, it can lead to excessive bleeds or clots, but it also delays discharge from the hospital because we can’t send anyone home until their INRs [international normalized ratios] are therapeutic,” Dr. Adamson said. “And those discharge delays quickly add up in terms of denied reimbursements.”

To improve anticoagulation therapy, the pharmacy quality improvement (QI) team began by searching the literature for a relevant benchmark that could guide its efforts. The team found several abstracts that were presented at the 2009 Midyear Clinical Meeting of the American Society of Health-System Pharmacists (ASHP), stating that approximately 90% of patients on warfarin should be therapeutic during their hospital stay. “When we started this journey four years ago, we were in the low 80th percentile,” Dr. Adamson said.

“So we had some work to do.”

The team soon found the primary cause of the gaps in therapeutic INRs: staff physicians who either did not order enough lab tests or, if they did order the tests, often neglected to check the results and factor them into warfarin dosing. To address that challenge, the team took a two-pronged approach. “For about half of the physicians, we got them to cede total control over warfarin management to pharmacy,” he said. “They would simply write, ‘manage warfarin patient as per pharmacy,’ and we would

ings in the four years we have had the program in place. And we would not have been able to accomplish this without benchmarking data leading the way.”

$0.18

Cost per Pharmacy-Adjusted Patient-Day

ecreased hospital length of stay, fewer reimbursement denials and better patient care are just a few of the benefits that several hospitals have achieved as a result of benchmarking.

The keys to success include matching the right analytical tool to a particular operational area and knowing that a mix of homegrown efforts and outside benchmarking sources may be needed.

$0.16 $0.14

A Good Place To Start $0.12 $0.10 $0.08 $0.06 $0.04 $0.02 $0.00

Baseline

Jul 13

Aug 13

Sep 13

Oct 13

PPI Utilization

Figure. PPI benchmarking initiative.

‘If you’re not benchmarking, you won’t be able to be proactive and stay ahead of [pharmacy practice] trends. That is not a position you want to be in, given the volatility in health care today.’

—Kathy Chase, PharmD take it from there—that is, order the required tests, monitor the patients and make dosage adjustments as needed.”

In the remaining cases, he noted, the physicians still wrote a detailed drug order, “but we were given the authority to write an order to draw the labs any time we felt they were needed to ensure optimal anticoagulation.”

The results of the initiative were striking, he noted. “Suddenly, we were looking at discharging a patient 18 to 20 hours earlier” than had been the case before the initiative, Dr. Adamson said. “And our therapeutic INR performance also shot up, to the point where today, about 95% of our patients have therapeutic INRs.”

IV to Oral Conversions Key To fully understand the cost savings that accrued from those efforts, Dr. Adamson pointed to the effects of a related anticoagulation benchmarking initiative at the health system. Most patients needing anticoagulation, he noted, are started on IV heparin. “When you convert them to oral warfarin in preparation for discharge, there is about a two- to three-day lag before warfarin becomes therapeutic,” he said. “That means you have to give them heparin and d warfarin concurrently.

The problem is we were not adding warfarin early enough to reach therapeutic levels and avoid delayed discharges.”

Indeed, in 2010, only 40% of IV anticoagulant patients at Barnabas Health were started on concurrent/conversion therapy in the first 48 hours of treatment, which often resulted in a six-day LOS. “So a lot of the insurers were actually downgrading our payments from an acute-care rate of $1,500 per day to the skilled nursing rate of $100 per day,” Dr. Adamson said. “That’s a $1,400 swing in reimbursement, per patient, in the six hospitals we were looking at. It was a huge financial hit to take.”

The fix, he noted, was to again enlist pharmacists to take a more active role in anticoagulation therapy—in this case, by working with physicians and intervening earlier in the course of therapy and to follow a timely anticoagulation conversion protocol.

By 2011, once those efforts were firmly in place, 71% of patients on IV heparin were converted to oral warfarin in the first 48 hours, for a decreased LOS of 1.3 days, Dr. Adamson said. By 2012, that rate increased to 80.5%, for an additional LOS decrease of 0.7 days compared with the previous year.

Those gains translated to significant savings: “Our ‘denial of days’ from payors has dropped dramatically, from several thousands of days denied to several hundred over a two-year period,” he said.

“That’s yielded millions of dollars in sav-

Dr. Adamson had a few pointers for hospitals that want to ramp up their benchmarking efforts. He first noted that no single benchmarking tool will suffice. In some cases, benchmarking data from professional groups such as ASHP or the American Hospital Association “will be your best bet,” he said.

ASHP is a particularly helpful resource for data on the inflation rate for drug purchases, he noted. “They can benchmark those rates across the entire country, which is very helpful in forecasting pharmacy budgets.” But for some clinical QI initiatives such as the anticoagulation effort at Barnabas Health, “you’ll probably have to take a do-it-yourself approach and find your own benchmarking resources, as we did.”

Dr. Adamson noted that he also has used the benchmarking services of outside consultants, as well as the major wholesalers such as Cardinal Health.

“They can be a very valuable resource on workforce statistics, as well as on how we may improve the way we use higher-cost medications,” he said. “The bottom line is to remember that there are multiple benchmarking resources out there.”

A Benchmarking Provider’s Take Kathy Chase, PharmD, director of drug cost control services for Cardinal Health’s Innovative Delivery Solutions business, which has been providing a variety of consulting services to health systems for about the last decade, said data analyis and benchmarking are particularly useful when hospitals use them to determine the best use of staff resources.

“Our goal is to help you determine where you should ideally be spending your time,” Dr. Chase said. “In other words, where can you get the biggest bang for your buck in terms of QI efforts?

It’s an incredibly important question, because so many hospitals have very limited staffs, and yet the list of things you’re potentially measured against and held accountable for just keeps growing.”

Dr. Chase offered several tips that hospitals should keep in mind when considering a benchmarking project: Don’t be too selective. “There’s no perfect hospital match out there to compare yourself to,” she said. “If you do your ‘sort’ based on finding a hospital that has, say, a neonatal intensive care unit, is a level III trauma center, has around 500 beds, is a teaching hospital etc., you’re just not going to end up with enough

Clinical 5

Pharmacy Practice News • March 2014

Quality Improvement sites to give you any useful basis for comparison. So we encourage our hospitals not to initially get too granular.”

Don’t get hung up on acquisition cost. Certainly, benchmarking can help a hospital determine if the price it is paying for its top-line pharmaceuticals is in line with nationwide trends. “And we all need to be responsible stewards of our pharmacy drug budgets,” Dr. Chase said. “Yet that initial cost is just a small piece of what you need to be looking at.”

She cited, as an example, a QI initiative that Cardinal Health has offered to many hospitals involving the use of alvimopan (Entereg, Cubist Pharmaceuticals), a drug indicated for gastrointestinal (GI) recovery following certain types of surgery. “Because this is a costly drug, it sometimes comes up as a red-flag item in pharmacy budgets,” Dr. Chase said. “However, if you take steps to ensure its proper use, you can reduce hospital length of stay—a claim of the manufacturer that we found to be true at the hospitals we work with on this initiative—and boost overall savings.

That’s key, especially if you’re operating in a DRG [diagnosis-related group] environment with fixed levels of reimbursement.”

Look at more than just one or two “high-ticket” items. Proton pump inhibitors (PPIs) are another drug class that lends itself well to benchmark-driven QI efforts, Dr. Chase said. In several hospitals she has recently worked with, there was a trend upward in the use of PPIs when compared with the previous year. Several contributing factors were identified, most involving use of the drugs for stress ulcer prophylaxis (SUP), whether it is indicated or not.

“The problem is that PPIs often are given to ‘all comers’ in the emergency department, which is not supported by the literature,” Dr. Chase noted. “And they are often not discontinued when patients transition from critical care to less intensive sites of care, where the literature has shown much less benefit.”

To ensure more proper use of PPIs for SUP, Dr. Chase and her colleagues combed the literature for data showing the best candidates for the treatment, as well as the best start and stop points for drug administration, and then established those benchmarks as goals for practice change at the target hospital. “We used several strategies, including talking with specific groups of physicians who were key prescribers of PPIs for SUP, such as ED [emergency department] physicians,” she explained. “We [also] did nurse and pharmacist training, because they can certainly have an impact on SUP usage rates. We hit care transition areas and had pharmacists involved at discharge to ensure that patients were not going

home with an unneeded prescription for PPIs. We know there are side effects to these medications, and in terms of overall efficacy, the data are just not there to continue them after discharge in all patients.”

Once these interventions were put in place, the return on the efforts soon became evident: In one hospital, the PPI cost per pharmacy-adjusted patient-day dropped by more than 50% (Figure).

Given these types of benefits from benchmarking, should the practice become more widespread? “Every hos-

pital needs to do benchmarking to at least some degree,” Dr. Chase said. “And that’s because nothing in the patient care setting is stagnant. Patient mix changes; efficacy data changes; the performance areas you will be judged on, either internally or externally, change.

“If you’re not benchmarking, you won’t be able to be proactive and stay ahead of those trends. That is nott a position you want to be in, given the volatility in health care today.”

—David Bronstein

More on the Web: Another Fan of Benchmarking Keith Thomasset, PharmD, the director of pharmacy at the Lahey Hospital and Medical Center, in Burlington, Mass., is another strong proponent of benchmarking.

In Web-exclusive coverage, Dr. Thomasset discusses his benchmarking strategies and how the practice has brought about improved, more cost-effective patient care at his health system.

Plus, Ali McBride, PharmD, gives a glimpse of the future direction benchmarking needs to take in order to be most effective in accountable care organizations and other newer care models.

IN ALPHA-1 ANTITRYPSIN AUGMENTATION THE FIRST AND ONLY

READY TO INFUSE

FEWER STEPS1

LIQUID GLASSIA1-4

NO RECONSTITUTION

SAFETY CONSIDERATION S1,5 Does not require reconstitution; reduces the risk for preparation errors

One ASHP recommendation to reduce preparation errors is to “dispense medications in ready-to-administer dosage forms whenever possible.”5 The American Society of Health-System Pharmacists (ASHP) Guidelines on Preventing Medication Errors in Hospitals

PRESCRIBE LIQUID GLASSIA TODAY. INDICATION FOR GLASSIA [ALPHA 1-PROTEINASE INHIBITOR (HUMAN)] GLASSIA is indicated for chronic augmentation and maintenance therapy in individuals with emphysema due to congenital deficiency of alpha1-proteinase inhibitor (Alpha1-PI), also known as alpha1-antitrypsin (AAT) deficiency.

• The effect of augmentation therapy with GLASSIA or any Alpha1-PI product on pulmonary exacerbations and on the progression of emphysema in Alpha1-PI deficiency has not been demonstrated in randomized, controlled clinical trials.

• Clinical data demonstrating the long-term effects of chronic augmentation and maintenance therapy of individuals with GLASSIA are not available.

• GLASSIA is not indicated as therapy for lung disease in patients in whom severe Alpha1-PI deficiency has not been established.

DETAILED IMPORTANT RISK INFORMATION FOR GLASSIA GLASSIA is contraindicated in immunoglobulin A (IgA) deficient patients with antibodies against IgA. Patients with selective or severe IgA deficiency and with known antibodies to IgA have a greater risk of developing severe hypersensitivity and anaphylactic reactions.

GLASSIA is contraindicated in individuals with a history of severe immediate hypersensitivity reactions, including anaphylaxis, to Alpha1-PI products.

Monitor vital signs continuously and observe the patient carefully throughout the infusion. If anaphylactic or severe anaphylactoid reactions occur, discontinue the infusion immediately.

GLASSIA is made from human plasma and may carry a risk of transmitting infectious agents, such as viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

GLASSIA should be administered at room temperature at a rate not greater than 0.04 mL/kg body weight per minute.

Administer GLASSIA within 3 hours of entering the vials.

Safety and effectiveness in patients over 65 years of age have not been established.

In the clinical studies, one subject experienced a treatment emergent serious adverse reaction (infective exacerbation of COPD), considered possibly related to treatment with GLASSIA due to its temporal association. The most common adverse reactions deemed possibly related to GLASSIA administration (>5%) were headache and dizziness.

Please see Brief Summary of Full Prescribing Information on the adjacent page.

References: 1. GLASSIA [Alpha1-Proteinase Inhibitor (Human)] Prescribing Information. Westlake Village, CA: Baxter Healthcare Corporation; June 2012. 2. ZEMAIRA [Alpha1-Proteinase Inhibitor (Human)] Prescribing Information. CSL Behring, LLC: Kankakee, IL; April 2013. 3. ARALAST NP [Alpha1-Proteinase Inhibitor (Human)] Prescribing Information. Baxter Healthcare Corporation: Westlake Village, CA; April 2010. 4. PROLASTIN-C [Alpha1-Proteinase Inhibitor (Human)] Prescribing Information. Talecris Biotherapeutics, Inc: Research Triangle Park, NC; January 2013. 5. ASHP guidelines on preventing medication errors in hospitals. American Society of Health System Pharmacists Web site. http://www.ashp org/s_ashp/docs/files/MedMis_Gdl_Hosp.pdf. Accessed June 18, 2013.

Baxter is a registered trademark of Baxter International Inc. Glassia is a registered trademark of Kamada Ltd.

February 2014

USBS/341/13-0003a

6 Clinical

Pharmacy Practice News â&#x20AC;˘ March 2014

Infectious Disease Results deemed â&#x20AC;&#x2DC;potentially lifesavingâ&#x20AC;&#x2122;

Hepatitis C Rates Slashed in Liver Transplant Patients Washingtonâ&#x20AC;&#x201D;The outlook for patients with hepatitis C undergoing liver transplantation got a lot sunnier with the results of two studies presented at The Liver Meeting 2013. In one study, researchers showed that the combination of sofosbuvir (Sovaldi, Gilead Sciences) and ribavirin used prior to transplantation prevented recurrence

GLASSIA No. of subjects: 33

Prolastin No. of subjects: 17

No. of subjects with adverse reactions1 (AR) (percentage of all subjects)

No. of subjects with adverse reactions1 (AR) (percentage of all subjects)

Cough

3 (9%)

4 (24%)

Reinfection of a transplanted liver is inevitable in patients who have HCV RNA-positive serum at the time of transplantation. Recurrence of HCV infection is the most common cause of mortality and graft loss following liver transplantation. Between 10% and 50% of transplant patients with recurrent HCV infection progress to cirrhosis within five years, and once cirrhosis is established, 42% of patients have graft failure within 12 months. Current therapies to treat HCV infection before and after liver transplantation have limited efficacy and are poorly tolerated, causing severe adverse reactions and significant interactions with immunosuppressive medications, according to Dr. Di Bisceglie.

Upper respiratory tract infection

3 (9%)

0 (0%)

Post-Transplant Sofosbuvir

Headache

3 (9%)

3 (18%)

Sinusitis

2 (6%)

1 (6%)

Chest discomfort

2 (6%)

0 (0%)

Dizziness

2 (6%)

0 (0%)

Michael Charlton, MD, a professor of medicine at Mayo Clinic in Rochester, Minn., presented a late-breaking abstract on the topic at The Liver Meeting. In this study, Dr. Charlton and his colleagues enrolled 40 patients with HCV infection who underwent liver transplantation between six and 150 months before study enrollment.

Patients were given 24 weeks of treatment with ribavirin plus sofosbuvir, a nucleotide polymerase inhibitor with potent antiviral activity against HCV genotypes 1 to 6.

Both treatment-naive and treatmentexperienced patients were included in the study; individuals with decompensated liver disease were excluded. The majority of patients had HCV genotype 1 (55%, 1a and 28%, 1b); the remainder had HCV genotype 3 (15%) or 4 (3%).

At the time of study analysis, 77% of patients had achieved SVR four weeks after treatment completion, and 12 of 13 patients for whom data were available at 12 weeks still had SVR. Dr. Charlton reported that there were no interactions between sofosbuvir and any immunosuppressive agents, including cyclosporine and tacrolimus, and no deaths, graft losses or episodes of liver rejection.

Adverse events (AEs) included fatigue (28%), headache (25%), arthralgia (23%), diarrhea (23%), cough (18%), nausea (18%) and anemia (15%). Grade 3/4 laboratory abnormalities occurred in 53% of patients and included decreased levels of lymphocytes (33%) and hemoglobin (20%), and hyperglycemia (10%).

of hepatitis C virus (HCV) infection in 64% of patients. Used after transplantation, the regimen resulted in a sustained virologic response (SVR) rate of 77% four weeks after treatment completion. â&#x20AC;&#x153;These studies are both very dramatic,â&#x20AC;? said Adrian Di Bisceglie, MD, the president elect of the American Association for the Study of Liver Diseases, who

Adverse Reactions1 Occurring in > 5% of Subjects During the First 12 Weeks of Treatment

GLASSIA [Alpha1-Proteinase Inhibitor (Human)] Brief Summary of Prescribing Information. Please see package insert for full prescribing information.

INDICATIONS AND USAGE Alpha1-Proteinase Inhibitor (Human), GLASSIA is indicated for chronic augmentation and maintenance therapy in adults with emphysema due to DPOHFOJUBM EFmDJFODZ PG BMQIB1-proteinase inhibitor (Alpha1-PI), also known as alpha1 BOUJUSZQTJO ""5 EFmDJFODZ â&#x20AC;˘ The effect of augmentation therapy with GLASSIA or any Alpha1-PI product on pulmonary exacerbations and on the progression of emphysema in Alpha1 1* EFmDJFODZ IBT OPU CFFO EFNPOTUSBUFE JO SBOEPNJ[FE DPOUSPMMFE DMJOJDBM USJBMT â&#x20AC;˘ Clinical data demonstrating the long-term effects of chronic augmentation BOE NBJOUFOBODF UIFSBQZ PG JOEJWJEVBMT XJUI (-"44*" BSF OPU BWBJMBCMF â&#x20AC;˘ GLASSIA is not indicated as therapy for lung disease in patients in whom severe Alpha1 1* EFmDJFODZ IBT OPU CFFO FTUBCMJTIFE

DOSAGE AND ADMINISTRATION

was not involved with the studies. â&#x20AC;&#x153;They signal a potential dramatic change in our practice of medicine related to hepatitis C and liver transplant.â&#x20AC;?

Sofosbuvir was approved to treat patients with HCV infection in December 2013, including patients with hepatocellular carcinoma awaiting liver transplantation to prevent HCV recurrence.

Adverse Event (AE)

â&#x20AC;˘ For Intravenous Use Only.

Hepatic enzyme 2 (6%) 0 (0%) â&#x20AC;˘ 6TF BTFQUJD UFDIOJRVF GPS BMM QSFQBSBUJPO BOE BENJOJTUSBUJPO TUFQT increased â&#x20AC;˘ *OTQFDU UIF WJBM PG (-"44*" 5IF TPMVUJPO TIPVME CF DMFBS BOE DPMPSMFTT 1 An adverse reaction is any adverse event which met any of the following criteria: UP ZFMMPX HSFFO BOE NBZ DPOUBJO B GFX QSPUFJO QBSUJDMFT %P OPU VTF JG UIF (a) an adverse event that began within 72 hours following the end of product infusion, QSPEVDU JT DMPVEZ or (b) an adverse event considered by either the investigator or sponsor to be at least â&#x20AC;˘ "ENJOJTUFS (-"44*" BMPOF EP OPU NJY XJUI PUIFS BHFOUT PS EJMVUJOH TPMVUJPOT possibly related to product administration, or (c) an adverse event for which causality â&#x20AC;˘ Administer product brought to room temperature within three hours of BTTFTTNFOU XBT NJTTJOH PS JOEFUFSNJOBUF FOUFSJOH UIF WJBMT Postmarketing Experience 5IF GPMMPXJOH SFBDUJPOT IBWF CFFO JEFOUJmFE EVSJOH QPTUNBSLFUJOH VTF PG Treatment of Congenital Alpha1 3URWHLQDVH ,QKLELWRU 'HĂ&#x20AC;FLHQF\ (-"44*" JO DMJOJDBM QSBDUJDF #FDBVTF UIFZ BSF SFQPSUFE WPMVOUBSJMZ GSPN The recommended dosage of GLASSIA is 60 mg/kg body weight B QPQVMBUJPO PG VOLOPXO TJ[F FTUJNBUFT PG GSFRVFODZ DBOOPU CF NBEF BENJOJTUFSFE PODF XFFLMZ CZ JOUSBWFOPVT JOGVTJPO %PTF SBOHJOH TUVEJFT The reactions, which have been chosen for inclusion due to either their VTJOH FGmDBDZ FOEQPJOUT IBWF OPU CFFO QFSGPSNFE 5IF SFDPNNFOEFE seriousness, frequency of reporting, possible causal connection to GLASSIA, EPTBHF PG NH LH UBLFT BQQSPYJNBUFMZ NJOVUFT UP JOGVTF 5IF PS B DPNCJOBUJPO PG UIFTF GBDUPST JODMVEF )FBEBDIF %ZTQOFB 'BUJHVF JOGVTJPO SBUF TIPVME OPU FYDFFE N- LH CPEZ XFJHIU QFS NJOVUF BOE /BVTFB

CONTRAINDICATIONS (-"44*" JT DPOUSBJOEJDBUFE JO JNNVOPHMPCVMJO " *H" EFmDJFOU QBUJFOUT XJUI BOUJCPEJFT BHBJOTU *H" GLASSIA is contraindicated in individuals with a history of severe immediate hypersensitivity reactions, including anaphylaxis, to Alpha1 1* QSPEVDUT

WARNINGS AND PRECAUTIONS Hypersensitivity to IgA (-"44*" NBZ DPOUBJO USBDF BNPVOUT PG *H" 1BUJFOUT XJUI TFMFDUJWF PS TFWFSF *H" EFmDJFODZ BOE XJUI LOPXO BOUJCPEJFT UP *H" IBWF B HSFBUFS SJTL PG EFWFMPQJOH TFWFSF IZQFSTFOTJUJWJUZ BOE BOBQIZMBDUJD SFBDUJPOT .POJUPS WJUBM TJHOT DPOUJOVPVTMZ BOE PCTFSWF UIF QBUJFOU DBSFGVMMZ UISPVHIPVU UIF JOGVTJPO IF ANAPHYLACTIC OR SEVERE ANAPHYLACTOID REACTIONS OCCUR, DISCONTINUE THE INFUSION IMMEDIATELY. Have epinephrine and other appropriate supportive therapy available for the treatment of any acute BOBQIZMBDUJD PS BOBQIZMBDUPJE SFBDUJPO Transmissible Infectious Agents Because this product is made from human plasma, it may carry a risk of transmitting infectious agents, such as viruses, and theoretically, the $SFVU[GFMEU +BLPC EJTFBTF $+% BHFOU 5IF SJTL PG USBOTNJUUJOH BO JOGFDUJPVT BHFOU IBT CFFO NJOJNJ[FE CZ TDSFFOJOH QMBTNB EPOPST GPS QSJPS FYQPTVSF UP certain viruses, by testing for the presence of certain current virus infections and by inactivating and removing certain viruses during the manufacturing process (see Description [11] in full prescribing information for viral reduction NFBTVSFT %FTQJUF UIFTF NFBTVSFT TVDI QSPEVDUT NBZ TUJMM QPUFOUJBMMZ USBOTNJU IVNBO QBUIPHFOJD BHFOUT 5IFSF JT BMTP UIF QPTTJCJMJUZ UIBU VOLOPXO JOGFDUJPVT BHFOUT NBZ CF QSFTFOU JO TVDI QSPEVDUT 5IF QIZTJDJBO TIPVME XFJHI UIF SJTLT BOE CFOFmUT PG UIF VTF PG UIJT QSPEVDU BOE EJTDVTT UIF SJTLT BOE CFOFmUT XJUI UIF QBUJFOU All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Kamada Ltd. at 1-866-GLASSIA or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

No seroconversions for hepatitis B or C (HBV or HCV) or human JNNVOPEFmDJFODZ WJSVT )*7 PS BOZ PUIFS LOPXO JOGFDUJPVT BHFOU XFSF SFQPSUFE XJUI UIF VTF PG (-"44*" EVSJOH UIF DMJOJDBM TUVEJFT

ADVERSE REACTIONS The serious adverse reaction observed during clinical studies with GLASSIA XBT FYBDFSCBUJPO PG DISPOJD PCTUSVDUJWF QVMNPOBSZ EJTFBTF $01%

The most common drug-related adverse reactions considered by the investigator to be at least possibly related to GLASSIA administration observed BU B SBUF PG JO TVCKFDUT SFDFJWJOH (-"44*" XFSF IFBEBDIF BOE EJ[[JOFTT

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C "OJNBM SFQSPEVDUJPO TUVEJFT IBWF OPU CFFO DPOEVDUFE XJUI (-"44*" *U JT also not known whether GLASSIA can cause fetal harm when administered UP QSFHOBOU XPNFO PS DBO BGGFDU SFQSPEVDUJWF DBQBDJUZ (-"44*" TIPVME CF HJWFO UP B QSFHOBOU XPNBO POMZ JG DMFBSMZ OFFEFE Nursing Mothers It is not known whether Alpha1 1* JT FYDSFUFE JO IVNBO NJML #FDBVTF NBOZ drugs are excreted in human milk, caution should be exercised when GLASSIA JT BENJOJTUFSFE UP B OVSTJOH XPNBO Pediatric Use 4BGFUZ BOE FGGFDUJWFOFTT JO QFEJBUSJD QBUJFOUT IBWF OPU CFFO FTUBCMJTIFE Geriatric Use Clinical studies of GLASSIA included 11 subjects of 65 years of age or PMEFS 5IJT OVNCFS PG TVCKFDUT XBT OPU TVGmDJFOU UP EFUFSNJOF XIFUIFS UIFZ SFTQPOE EJGGFSFOUMZ GSPN ZPVOHFS TVCKFDUT "T GPS BMM QBUJFOUT EPTJOH GPS HFSJBUSJD QBUJFOUT TIPVME CF BQQSPQSJBUF UP UIFJS PWFSBMM TJUVBUJPO 4BGFUZ BOE FGGFDUJWFOFTT JO QBUJFOUT PWFS ZFBST PG BHF IBWF OPU CFFO FTUBCMJTIFE

PATIENT COUNSELING INFORMATION â&#x20AC;˘ Inform patients of the early signs of hypersensitivity reactions, including IJWFT HFOFSBMJ[FE VSUJDBSJB DIFTU UJHIUOFTT EZTQOFB XIFF[JOH GBJOUOFTT IZQPUFOTJPO BOE BOBQIZMBYJT "EWJTF QBUJFOUT UP EJTDPOUJOVF VTF PG UIF product and contact their physician and/or seek immediate emergency care, EFQFOEJOH PO UIF TFWFSJUZ PG UIF SFBDUJPO JG UIFTF TZNQUPNT PDDVS â&#x20AC;˘ Inform patients that GLASSIA is made from human plasma and may contain JOGFDUJPVT BHFOUT UIBU DBO DBVTF EJTFBTF F H WJSVTFT BOE UIFPSFUJDBMMZ UIF $+% BHFOU &YQMBJO UIBU UIF SJTL PG (-"44*" USBOTNJUUJOH BO JOGFDUJPVT agent has been reduced by screening the plasma donors, by testing the donated plasma for certain virus infections, and by a process demonstrated to inactivate and/or remove certain viruses during manufacturing (see Warnings and Precautions 4ZNQUPNT PG B QPTTJCMF WJSVT JOGFDUJPO JODMVEF headache, fever, nausea, vomiting, weakness, malaise, diarrhea, or, in the DBTF PG IFQBUJUJT KBVOEJDF â&#x20AC;˘ Inform patients that administration of GLASSIA has been demonstrated to raise the plasma level of Alpha1-PI, but that the effect of this augmentation on the frequency of pulmonary exacerbations and on the rate of progression of FNQIZTFNB IBT OPU CFFO FTUBCMJTIFE CZ DMJOJDBM USJBMT #BYUFS JT B SFHJTUFSFE USBEFNBSL PG #BYUFS *OUFSOBUJPOBM *OD H (MBTTJB JT B SFHJTUFSFE USBEFNBSL PG ,BNBEB -UE H Baxter Healthcare Corporation, p Westlake Village, CA 91362 USA *TTVFE 0DUPCFS 64#4

Pre-Transplant Sofosbuvir Michael Curry, MD, the medical director for liver transplantation at Beth Israel Deaconess Medical Center, in Boston, presented an abstract on pre-

Clinical 7

Pharmacy Practice News • March 2014

Infectious Disease ‘These studies are both very dramatic. They signal a potential dramatic change in our practice of medicine related to hepatitis C and liver transplant.’

—Adrian Di Bisceglie, MD

vir, but pre-transplant patients received 48 weeks of treatment. “Transplant patients have to be on [sofosbuvir] for much longer,” she said, “and there is a huge concern among payors about the cost of therapy.”

—Kate O’Rourke

a post-transplant indication, clinicians “might meet resistance from third-party payors.”

Janet Nguyen, PharmD, BCPS, the vvice president of network strategies at ModernHEALTH, a Los Angeles-based

pharmacy services provider, agreed that third-party payors are looking closely at this. The duration of treatment for some transplant patients is a concern, she said. In clinical trials, post-transplant patients received 24 weeks of sofosbu-

Dr. Curry reported a financial relationship with Gilead. Drs. Charlton and Di Bisceglie reported receiving support from and serving as a consultant for Gilead. Dr. Nguyen reported no relevant financial conflicts of interest.

Committed to Meeting Patient Needs transplantation treatment with sofosbuvir. In this study, 61 patients with HCV infection were enrolled to receive sofosbuvir plus ribavirin until the time of liver transplantation, or up to 48 weeks.

The patient population included those infected with HCV genotypes 1a (39%), 1b (34%), 2 (13%), 3a (12%) and 4 (2%).

At the time of analysis, 44 patients were scheduled to receive a liver transplant; of these, 41 (93%) were negative for HCV infection (undetectable HCV RNA) and three were positive. (The remaining 17 patients stayed on treatment, were post-treatment and awaiting a transplant, had discontinued treatment or had liver cancer progression.)

Post-transplant virologic response (pTVR) rate at 12 weeks was 64%. The number of consecutive days with undetectable HCV RNA before transplantation was the strongest predictor of pTVR ((P<0.0001). On-treatment HCV RNA suppression was rapid.

Dr. Curry characterized the treatment as safe and well tolerated. Although 18% of patients experienced a serious AE, none of the AEs were deemed related to sofosbuvir: Laboratory abnormalities and AEs observed pre-transplantation were similar to those seen in the posttreatment study. Only 3% of patients discontinued treatment because of AEs.

‘Potentially Lifesaving’ Implications Dr. Di Bisceglie predicted that the studies will have an immediate effect on clinical practice. But he pointed out that clinicians will be more likely to use the medications after transplantation at first. “Its availability, combined with these data, will probably mean we are going to start treating patients after liver transplantation very quickly. This is a potentially lifesaving therapy, and I’m sure physicians will not want to wait until it is approved for this indication,” Dr. Di Bisceglie said. However, he added, until sofosbuvir’s label includes

For more than 20 years, Bedford Laboratories has been a leader in generic sterile injectables, providing high-quality, medically necessary medicines to patients in hospitals, clinics and oncology treatment centers across the U.S. and Puerto Rico. Founded in 1993, Bedford has one of the largest and most experienced generic injectable sales forces in the industry, and is one of the top three Abbreviated New Drug Application (ANDA) holders in the U.S. As we embark on our third decade, we look forward to continuing to meet your needs and ensuring that these critical medicines reach your patients.

Visit www.bedfordlabs.com for our latest Online Catalog and Customer Supply Update Report. For information and additional questions, please contact your Bedford Laboratories Sales Representative or our Client Services Team at 800.562.4797.

Bedford Laboratories™ | T 800.562.4797 | F 440.232.6264 | www.bedfordlabs.com

8 Clinical

Pharmacy Practice News • March 2014

Infectious Disease

ASP BUILDING TIPS continued from page 1

disease specialists, physicians and surgeons, and to establish the ASP’s guiding principles, noted Dr. Eiland, formerly the clinical practice and business supervisor in the Department of Pharmacy at Huntsville Hospital, an 881-bed community acute care regional hospital, and now the chief executive officer at Vital Care, Inc., a home infusion services provider located in Meridian, Miss.

“The first principle we decided on is that the first dose of an antimicrobial is the only documented dose to save lives,” he said. “While you can always discontinue or de-escalate anti-infective therapy on day 2 or 3, for every hour of delay in appropriate therapy when treating sterile site infections, there is an increase in mortality.”

The second principle was that the most expensive antimicrobial is the one that does not lead to the intended outcome or results in an adverse event, and the third principle was that antibiotic regimens should be initiated promptly, said Dr. Eiland.

To turn these tenets into measurable outcomes, the AMT established an anti-infective subcommittee tasked with identifying antimicrobials being overused at the hospital, as well as microbes that were developing resistance. Findings from ongoing analyses are published in an annual antibiogram publication and are presented during staff development meetings, along with other recommendations for proper antibiotic use, Dr. Eiland said.

A few initiatives the AMT launched in light of the first set of antibiogram

findings included establishing sepsis and pneumonia order sets and transitioning from IV to oral use of linezolid, voriconazole and levofloxacin.

“Focusing on a limited number of areas made it easier for us to measure clinical, quality and financial outcomes and to trumpet our successes, while learning from our difficulties,” Dr. Eiland said.

Indeed, the program’s effect on pharmacy spending within the first two years merited trumpeting: The institution’s annual antimicrobial purchasing dropped from $5.8 million before the ASP was implemented to $4.46 million with the program in place. “The question after the first stage is ‘how do you sustain the program and maintain the initial savings?’”

Dr. Eiland said. “You need to expand.”

Phase 2: Expanding the Program (2008-2010) In 2008, the AMT identified more areas where stewardship was needed.

The team also measured outcomes along the way, which allowed them to continue demonstrating the program’s effect. To improve the ease and accuracy of data collection, the AMT created a documentation system that allowed pharmacists to record each of their interventions (screenshot at right). “We also put a clinical alert system in place to identify pharmacist opportunities for antimicrobial interventions in real time,” said Dr. Eiland, adding that these interventions could then be correlated with outcomes in target patients.

Initiatives implemented during this second phase of the ASP included shifting prescribing patterns to the formulary-designated carbapenem and echinocandin and placing restrictions

Expert analysis:

Five Reasons To Like ASP Initiative Steven Martin, PharmD Professor and Chairman Department of Pharmacy Practice University of Toledo College of Pharmacy and Pharmaceutical Sciences Toledo, Ohio

T

his is a very well-developed and successful ASP initiative, with several keys to its success.

1. Getting buy-in. The Huntsville program achieved widespread buy-in from multiple stakeholders by establishing a multidisciplinary AMT. This allowed all stakeholders to weigh in and help select the program’s goals. Because they were invested in the program, they were motivated to champion it and help achieve its goals. Physician champions model appropriate behavior and, when their peers deviate from newly implemented policies, they can be crucial in working to bring about compliance.

At Huntsville Hospital, in Huntsville, Ala., pharmacists who participate in an antibiotic stewardship program use a documentation system (above) to record each of their interventions.

on the use of tigecycline and linezolid.

“Tigecycline and linezolid are static drugs and should be used based on their FDA indications, not for sterile site infections, as we had found they were often being used,” he said.

The team also developed a Clostridium difficile infection (CDI) clinical pathway aimed at improving the treatment and prevention of CDI. The project, which garnered a 2010 ASHP Best Practices Award, was developed because stool cultures were being used to determine CDI cures. “Physicians were not realizing that a negative test

Importantly, the multidisciplinary team also included infectious disease (ID) physicians. They are major players on any ASP team because they can identify problems that can be readily corrected.

2. Limiting the scope. Another thing they did right was to start the ASP with a limited scope. All too often, ASPs go after very difficult cultural changes first, which can lead to head-butting with physicians who are concerned with maintaining control over their turf. I think a successful ASP builds momentum on noncontroversial changes, and gains buy-in from multiple stakeholders who share in the success.

3. Tangible performance metrics. They made sure to measure performance using bite-sized and easily achievable goals and tangible metrics. It appears they have a robust data collection and reporting system that includes medication use information, financial data, as well as clinical information such as microbiology reports. A laser-like focus on outcomes that truly affect the institution in measurable ways provides results that all can champion, making the program’s necessity hard to argue with. And as a program expands to target more controversial prescribing habits—such as overuse of broad-spectrum therapies, avoidance of deescalation, or prescription of expensive and nonformulary agents—referring to those achievements and also

after a short treatment course was not a good predictor of cure,” Dr. Eiland said. “This led to abrupt and premature discontinuation of therapy prior to, or at, discharge, resulting in readmissions and colectomies.”

As part of the CDI initiative, Dr. Eiland’s team also persuaded hospital administrators to switch from enzyme testing to polymerase chain reaction (PCR) testing to identify suspected C. difficile as well as methicillin-resistant Staphylococcus aureus. “Although PCR is more expensive, we went from ordering

•

see ASP BUILDING TIPS, page 20

bringing in published evidence can provide a sound foundation on which to implement change.

4. Engaging the C-suite. The goals they chose also appeal to hospital administrators because they help move patients through the hospital, maximizing diagnosis-related group payments and refilling beds as soon as possible. By appealing to administrators, the ASP program guarantees future resources, and ensures it receives support from the C-suite even as hospital budgets tighten. One cannot underestimate the need to invest tangible resources in a program such as this.

5. A team approach. Although dedicated pharmacists manage the Huntsville program on a day-today basis, pharmacist residents and ID physicians provide assistance. The program may have started with just one pharmacist, but it rapidly expanded, and the number of ID physicians participating also increased as the program became successful. This is where the use of bite-sized measurable outcomes in the early phases of the ASP also comes into play: People want to join a winning team, and early success is a magnet for more resources.

Dr. Martin reported no relevant financial conflicts of interest.

AV N AI OW LA BL E

25 mg/mL & 50 mg/mL

Great tasting!

Each convenient onvenient Kit ccontains ontains everything you need to compound a l Vancomycin V i S l i prescription i i quickly i kl and d easily! il ! single Solution This new FIRST®-Vancomycin Oral Solution Kit is the quick, easy way to compound individual Vancomycin prescriptions.

Each Kit: Ŧ has everything needed to compound one prescription from one prescriber for one patient Ŧ contains pre-weighed, pre-measured ingredients to aid accuracy Ŧ bar-coded dispensing containers Ŧ saves prep, compounding and cleanup time Ŧ facilitates compliance with USP Chapter <795> Ŧ has a single NDC number that saves time and eliminates waste, also eases third-party reimbursement

FIRST® - VANCOMYCIN ORAL SOLUTION KIT ®

FIRST NDC #

STRENGTH

QUANTITY

65628-200-05

25 mg/mL

5 oz.

65628-200-10

25 mg/mL

10 oz.

65628-201-05

50 mg/mL

5 oz.

65628-201-07

50 mg/mL

7 oz.

65628-201-10

50 mg/mL

10 oz.

To learn more, call

1-800-461-7449 www.cutispharma.com

facebook.com/CutisPharma 68 Cummings Park, Woburn MA 01801 Tel: 781-935-8141 Fax: 781-935-8395

twitter/CutisPharma youtube.com/watch?v=rM8zI4ZxofA

10 Clinical

Pharmacy Practice News • March 2014

Critical Care

ED TECHNICIANS continued from page 1

errors included in ED nurse-obtained medication histories, heading off costly and harmful adverse events.

“Our program has been so successful that our technicians are often called to floors to obtain home medication lists for direct admissions,” said Colleen Teevan, PharmD, an ED clinical pharmacist at The Hospital of Central Connecticut

A Technician’s Med Rec Checklist From The Hospital of Central Connecticut 1. Introduce yourself as a pharmacy staff member and inquire as to the reason for the patient’s visit 2. Ask about and record allergies and reactions to: • Medications • Foods • Other 3. Record patient’s preferred pharmacy 4. Record name of patient’s primary care physician (PCP); communicate PCP’s name to admitting department 5. Obtain and record patient’s height and weight 6. Obtain medication history from any external pharmacies used.

7. Obtain patient’s medication list and last doses. Ask specifically about: • Prescription medications • Blood thinners (dabigatran [Pradaxa, Boehringer Ingelheim], rivaroxaban [Xarelto, Janssen], warfarin, aspirin) • Eye drops • Pain relievers • Patches • Inhalers • Creams or ointments • Any recent antibiotics • Sleep aids • Insulin or other injectables • Vitamins, supplements, or herbal medications • Anything taken once a week or once a month • Over-the-counter medications • Medication pumps (internal/external) 8. Call pharmacy/nursing home/ etc., as needed for clarification 9. Communicate any issues to providers

(THOCC), in New Britain (poster 5-148).

Dr. Teevan said the 22,000 patients admitted annually through THOCC’s ED more than justified hiring seven pharmacy technicians to provide around-theclock medication reconciliation services and an ED pharmacist to verify the accuracy of their work. Between late 2012, when the program was launched, and late 2013, the pharmacy technicians conducted more than 25,000 ED medication reconciliations, averaging roughly 250 per week. Documentation from the ED pharmacist who approved each list demonstrated that technians were accurate 96% of the time.

That number stands in contrast to the 66% accuracy rate for medication lists gathered by other ED health care providers at THOCC, noted Dr. Teevan.

“Having technicians document home medications using a structured approach ensures the same level of quality and completeness for every patient,” she said, referring to a checklist used by the ED pharmacy technicians (see sidebar at left) that has helped standardize the medication reconciliation process. “Practically nothing is missed, even during busy times, and the admitting team can rely on the quality of information they are receiving.”

Table. Frequency of Errors in Nurse Medication Lists at St. Vincent’s Medical Center

Category of Discrepancy

Discrepancies (N = 981)

Patients With Particular Discrepancy Type, % (N = 300)

Omitted medication

267

42.0

Omitted frequency

212

46.2

Omitted dose

157

47.6

Discontinued medication

117

31.1

Incorrect frequency

89

30.2

Incorrect dose

67

22.6

Omitted route

50

10.4

Incorrect formulation

12

5.2

Incorrect drug

9

3.8

PRN with no indication

1

0.5

PRN, as needed

‘Given how helpful the [pharmacy technician] medication reconciliation program has been in increasing patient safety and avoiding costs, we believe it would be beneficial to include the service for all admissions.’

—Katherine Kamataris, PharmD

Nearly $1 Million Saved An ED pharmacy technician at St. Vincent’s Medical Center-Riverside, in Jacksonville, Fla., also has been scrupulous in detecting and correcting errors in nurseobtained medication histories, helping avoid nearly $1 million in annual adverse event–related costs (poster 5-202).

Katherine Kamataris, PharmD, an emergency medicine pharmacist at St. Vincent’s Medical Center-Riverside, and her colleagues reviewed medical records from 300 patients admitted through the hospital’s ED between October 2012 and February 2013, after the pharmacy technician-conducted medication reconciliation service was initiated in June 2012. Patients included had been interviewed by a nurse at ED presentation as well as by a technician at the time of hospital admission, Dr. Kamataris noted. ED admissions outside of the specific technician’s 40-hour workweek were not included.

According to Dr. Kamataris, the pharmacy technician found and corrected 981 discrepancies in 70.7% (212 of 300) of medication histories compiled by nurses during the study period. (The Table presents the types of errors found.)

Nurses were most likely to err in documenting cardiovascular medications, she reported, with 52% of all cardiovascular drug entries in nurse histories containing one or more inaccuracies. Nurse-obtained history entries contained errors for the following additional drug types: pain relievers and muscle relaxants, 38.2%;

gastrointestinal medications, 27.8%; anxiolytics, sedatives and hypnotics, 19.3%; and psychiatric medications, 13.2%.

Because the study only included EDadmitted patients interviewed by both the pharmacy technician and nurses, Dr. Kamataris estimated the number of errors nurses made in their medication lists over 12 months is closer to 14,700.

Based on a conservative assumption that 3% of those errors would have resulted in an adverse event, she said pharmacy technicians helped avoid an estimated $962,543 in error-related treatment costs.

“Given how helpful the [pharmacy technician] medication reconciliation program has been in increasing patient safety and avoiding costs, we believe it

would be beneficial to include the service for all admissions,” Dr. Kamataris said.

Techs Versus Nurses Pharmacy technicians at Morton Plant Hospital, in Clearwater, Fla., have proven vastly more accurate than nurses in documenting use of high-risk antiplatelet and anticoagulant medications, according to Coleen Hart, PharmD, formerly a postgraduate year 1 pharmacy resident there (poster 3-073).

Dr. Hart reviewed 150 medication lists created by ED nurses between November 2011 and February 2012, and the same number of technician-conducted admission medication reconciliations, checking

•

see ED TECHNICIANS, page 21

ÂŽ

Superior Safety and Ease of Use

Introducing the safest Closed System Transfer Device for hazardous drugs

Safe

#OVERS MORE ROUTES OF EXPOSURE than alternative systems

s 4HE ONLY SYSTEM THAT PREVENTS SYRINGE PLUNGER CONTAMINATION RECENTLY IDENTIFIED AS A MAJOR ROUTE OF EXPOSURE TO HAZARDOUS DRUGS s #LOSED PRESSURE EQUALIZATION PREVENTS THE ESCAPE OF DRUG AND VAPORS s "Dry" connector remains free of drug residuals s 0REVENTS MICROBIAL INGRESS IN NON PRESERVED DRUG VIALS s #LINICALLY PROVEN TO ELIMINATE SURFACE CONTAMINATION

Simple

Faster and easier to use than any other system

s 4HE ONLY SYSTEM WITH A FULLY PREASSEMBLED SYRINGE AND CONNECTOR, REQUIRING NO FURTHER SETUP OR OFF THE SHELF SYRINGES s Easy-to-use single motion connectors

Closed s s s s

The most closed system on the market

4HE ONLY SYSTEM WITH ENCAPSULATED SYRINGE BARREL AND PLUNGER #LOSED INTERNAL PRESSURE EQUALIZATION BUILT INTO TO THE SYRINGE #ONNECTOR PERMANENTLY WELDED TO SYRINGE %NCAPSULATED PLUNGER THAT CANNOT BE PULLED OUT OF THE BARREL

In the all new EquashieldÂŽ II :

Air bubbles can be ejected back into the vial during drug withdrawal. The new generation PREVENTS MIGRATION OF DRUG TO THE BACK OF THE syringe at any time.

WWW EQUASHIELD COM

Indications and Usage NEXTERONE (amiodarone HCl) Premixed Injection is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. NEXTERONE also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with NEXTERONE, patients may be transferred to oral amiodarone therapy.

Use NEXTERONE for acute treatment until the patient’s ventricular arrhythmias are stabilized. Most patients will require this therapy for 48 to 96 hours, but NEXTERONE may be safely administered for longer periods if necessary.

Important Risk Information NEXTERONE (amiodarone HCl) Premixed Injection is contraindicated in patients with: • Known hypersensitivity to any of the components of NEXTERONE, including iodine • Cardiogenic shock • Marked sinus bradycardia • Second- or third-degree atrio-ventricular (AV) block unless a functioning pacemaker is available • NEXTERONE should be administered only by physicians who are experienced in the treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and benefits fi of amiodarone therapy, and who have access to facilities adequate for monitoring the effectiveness and side effects of treatment.

• Hypotension is the most common adverse reaction seen with intravenous amiodarone. In clinical trials, treatment-emergent, drug-related hypotension was reported in 16% (288/1836) of patients treated with intravenous amiodarone. Clinically significant fi hypotension during infusions was seen most often in the first several hours of treatment and appeared to be related to the rate of infusion. Monitor the initial rate of infusion closely and do not exceed the recommended rate. In some cases, hypotension may be refractory and result in a fatal outcome. Treat hypotension initially by slowing the infusion; additional standard therapy may be needed, including: vasopressors, positive inotropic agents and volume expansion.

• In 4.9% (90/1836) of patients in clinical trials, drug-related bradycardia that was not dose-related occurred while patients were receiving intravenous amiodarone for life-threatening VT/VF. Treat bradycardia by slowing the infusion rate or discontinuing NEXTERONE. Treat patients with a known predisposition to bradycardia or AV block with NEXTERONE in a setting where a temporary pacemaker is available.

• Elevations of blood hepatic enzyme values ALT, AST, GGT are commonly seen in patients with immediately life-threatening VT/VF. / In patients with life-threatening arrhythmias, the potential risk of hepatic injury should be weighed against the potential benefit of NEXTERONE therapy. Carefully monitor patients receiving NEXTERONE for evidence of progressive hepatic injury. In such cases, consider reducing the rate of administration or withdrawing NEXTERONE. • Like all antiarrhythmics, NEXTERONE may cause worsening of existing arrhythmias or precipitate a new arrhythmia. Monitor patients for QTc prolongation during infusion with NEXTERONE. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent.

• There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with intravenous amiodarone. Findings included pulmonary infi filtrates and masses on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure or death. Two percent (2%) of patients were reported to have acute respiratory distress syndrome (ARDS) during clinical studies involving 48 hours of therapy. Pulmonary toxicity including pulmonary fifibrosis is a well-recognized complication of long-term amiodarone use.

• Amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased T4 levels, decreased T3 levels, and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients. Amiodarone can cause either hypothyroidism or hyperthyroidism. Evaluate thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. Because of the slow elimination of amiodarone and its metabolites, high plasma iodide levels, altered thyroid function, and abnormal thyroid function tests may persist for several weeks or even months following NEXTERONE withdrawal.

• The most important adverse reactions were hypotension, asystole/cardiac arrest/pulseless electrical activity (PEA), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. The most common adverse reactions leading to discontinuation of intravenous amiodarone therapy were hypotension (1.6%), asystole/cardiac arrest/PEA (1.2%), VT (1.1%), and cardiogenic shock (1%).

• Drug Interactions • Since amiodarone is a substrate for CYP3A and CYP2C8, drugs/substances that inhibit these isoenzymes may decrease the metabolism and increase serum concentration of amiodarone.

• Amiodarone inhibits p-glycoprotein and certain CYP450 enzymes, including CYP1A2, CYP2C9, CYP2D6, and CYP3A. This inhibition can result in unexpectedly high plasma levels of other drugs which are metabolized by those CYP450 enzymes or are substrates for p-glycoprotein. HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with amiodarone have been associated with reports of myopathy/rhabdomyolysis. Limit the dose of simvastatin in patients on amiodarone to 20 mg daily. Limit the daily dose of lovastatin to 40 mg. Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required.

• Some drugs/substances are known to accelerate the metabolism of amiodarone by stimulating the synthesis of CYP3A (enzyme induction). This may lead to low amiodarone serum levels and potential decrease in effi ficacy. Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly.

Please see brief summary of Full Prescribing Information on the following pages.

Baxter Healthcare Corporation Deerfield, IL 60015

Drug Delivery.

Nexterone (amiodarone HCl)

For the way you pharmacy.

Premixed Injection It’s About Time.

Two-year shelf life Extended stability for greater convenience.

No admixing Helps minimize errors due to compounding.

Ready to use Because every second counts.

It’s the only cGMP manufacturer-prepared, premixed amiodarone on the market. Find out how Nexterone (amiodarone HCl) can help you.

Contact your Baxter representative to place an order at 888.229.0001. For more information on how Nexterone (amiodarone HCl) can enhance patient care, visit nexterone.com.

DESCRIPTION

PRODUCT CODE

STRENGTH/ VOLUME

CONCENTRATION

NDC #

PACK FACTOR (cartons/case)

2G3451

150 mg/100 mL

1.5 mg/mL

43066-150-10

12

2G3450

360 mg/200 mL

1.8 mg/mL

43066-360-20

10

NEXTERONE (amiodarone HCl) Premixed Injection

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

111932 07/13

NEXTERONE (amiodarone HCl) Premixed Injection for intravenous use Brief Summary of Prescribing Information. See PI for Full Prescribing Information.

1 INDICATIONS AND USAGE NEXTERONE is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy. NEXTERONE also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. During or after treatment with NEXTERONE, patients may be transferred to oral amiodarone therapy [see Dosage and Administration (2) in full prescribing information].

Use NEXTERONE for acute treatment until the patient’s ventricular arrhythmias are stabilized. Most patients will require this therapy for 48 to 96 hours, but NEXTERONE may be safely administered for longer periods if necessary.

4 CONTRAINDICATIONS NEXTERONE is contraindicated in patients with: • Known hypersensitivity to any of the components of NEXTERONE Premixed Injection, including iodine. Hypersensitivity reactions may involve rash, angioedema, cutaneous/mucosal hemorrhage (bleeding), fever, arthralgias (joint pains), eosinophilia (abnormal blood counts), urticaria (hives), thrombotic thrombocytopenic purpura, or severe periarteritis (inflammation around blood vessels).

• Cardiogenic shock.

• Marked sinus bradycardia.

• Second- or third-degree atrio-ventricular (AV) block unless a functioning pacemaker is available.

5 WARNINGS AND PRECAUTIONS NEXTERONE should be administered only by physicians who are experienced in the treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and benefits of amiodarone therapy, and who have access to facilities adequate for monitoring the effectiveness and side effects of treatment.

5.1 Hypotension Hypotension is the most common adverse reaction seen with intravenous amiodarone. In clinical trials, treatment-emergent, drug-related hypotension was reported as an adverse effect in 288 (16%) of 1836 patients treated with intravenous amiodarone. Clinically significant hypotension during infusions was seen most often in the first several hours of treatment and was not dose related, but appeared to be related to the rate of infusion. Hypotension necessitating alterations in intravenous amiodarone therapy was reported in 3% of patients, with permanent discontinuation required in less than 2% of patients.

Treat hypotension initially by slowing the infusion; additional standard therapy may be needed, including the following: vasopressor drugs, positive inotropic agents, and volume expansion. Monitor the initial rate of infusion closely and do not exceed the recommended rate [see Dosage and Administration (2) in full prescribing information].

In some cases, hypotension may be refractory and result in a fatal outcome [see Adverse Reactions (6.2) in full prescribing information].

5.2 Bradycardia and Atrio-ventricular Block In 90 (4.9%) of 1836 patients in clinical trials, drug-related bradycardia that was not dose-related occurred while they were receiving intravenous amiodarone for life-threatening VT/VF. Treat bradycardia by slowing the infusion rate or discontinuing NEXTERONE. In some patients, inserting a pacemaker is required. Despite such measures, bradycardia was progressive and terminal in 1 patient during the controlled trials. Treat patients with a known predisposition to bradycardia or AV block with NEXTERONE in a setting where a temporary pacemaker is available.

5.3 Liver Enzyme Elevations Elevations of blood hepatic enzyme values [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)] are commonly seen in patients with immediately life-threatening VT/VF. Interpreting elevated AST activity can be difficult because the values may be elevated in patients who have had recent myocardial infarction, congestive heart failure, or multiple electrical defibrillations. Approximately 54% of patients receiving intravenous amiodarone in clinical studies had baseline liver enzyme elevations, and 13% had clinically significant elevations. In 81% of patients with both baseline and on-therapy data available, the liver enzyme elevations either improved during therapy or remained at baseline levels. Baseline abnormalities in hepatic enzymes are not a contraindication to treatment.

Acute, centrolobular confluent hepatocellular necrosis leading to hepatic coma, acute renal failure, and death has been associated with the administration of intravenous amiodarone at a much higher loading dose concentration and much faster rate of infusion than recommended [see Dosage and Administration (2) in full prescribing information].

In patients with life-threatening arrhythmias, the potential risk of hepatic injury should be weighed against the potential benefit of NEXTERONE therapy. Carefully monitor patients receiving NEXTERONE for evidence of progressive hepatic injury. In such cases, consider reducing the rate of administration or withdrawing NEXTERONE. 5.4 Proarrhythmia Like all antiarrhythmic agents, NEXTERONE may cause a worsening of existing arrhythmias or precipitate a new arrhythmia. Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation, by intravenous amiodarone, of the QTc interval to 500 ms or greater. Although QTc prolongation occurred frequently in patients receiving intravenous amiodarone, TdP or new-onset VF occurred infrequently (less than 2%). Monitor patients for QTc prolongation during infusion with NEXTERONE. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent.

Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP , in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly [see Drug Interactions (7) in full prescribing information].

Amiodarone causes thyroid dysfunction in some patients, which may lead to potentially fatal breakthrough or exacerbated arrhythmias.

5.5 Pulmonary Disorders Early-onset Pulmonary Toxicity There have been postmarketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with intravenous amiodarone. Findings have included pulmonary infiltrates and masses on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure or death.

ARDS Two percent (2%) of patients were reported to have adult respiratory distress syndrome (ARDS) during clinical studies involving 48 hours of therapy.

Pulmonary Fibrosis Only 1 of more than 1000 patients treated with intravenous amiodarone in clinical studies developed pulmonary fibrosis. In that patient, the condition was diagnosed 3 months after treatment with intravenous amiodarone, during which time the patient received oral amiodarone. Pulmonary toxicity is a well-recognized complication of long-term amiodarone use (see package insert for oral amiodarone).

5.6 Loss of Vision Cases of optic neuropathy and optic neuritis, usually resulting in visual impairment, have been reported in patients treated with oral amiodarone. In some cases, visual impairment has progressed to permanent blindness. Optic neuropathy and neuritis may occur at any time following initiation of therapy. A causal relationship to the drug has not been clearly established. Perform an ophthalmic examination if symptoms of visual impairment appear, such as changes in visual acuity and decreases in peripheral vision. Re-evaluate the necessity of amiodarone therapy if optic neuropathy or neuritis is suspected. Perform regular ophthalmic examination, including fundoscopy and slit-lamp examination, during administration of NEXTERONE. 5.7 Long-Term Use There has been limited experience in patients receiving intravenous amiodarone for longer than 3 weeks. See package insert for oral amiodarone.

5.8 Thyroid Abnormalities Amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased T4 levels, decreased T3 levels, and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients. Amiodarone is also a potential source of large amounts of inorganic iodine and can cause either hypothyroidism or hyperthyroidism. Evaluate thyroid function prior to treatment and periodically thereafter, particularly in elderly patients, and in any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. Because of the slow elimination of amiodarone and its metabolites, high plasma iodide levels, altered thyroid function, and abnormal thyroid function tests may persist for several weeks or even months following NEXTERONE withdrawal.

There have been postmarketing reports of thyroid nodules/thyroid cancer in patients treated with amiodarone. In some instances hyperthyroidism was also present [see Adverse Reactions (6.2) in full prescribing information].

Hyperthyroidism and Thyrotoxicosis Hyperthyroidism occurs in about 2% of patients receiving amiodarone, but the incidence may be higher among patients with prior inadequate dietary iodine intake. Amiodarone-induced hyperthyroidism usually poses a greater hazard to the patient than hypothyroidism because of the possibility of thyrotoxicosis and arrhythmia breakthrough or aggravation, all of which may result in death. There have been reports of death associated with amiodarone-induced thyrotoxicosis. Consider the possibility of hyperthyroidism if any new signs of arrhythmia appear.

Identify hyperthyroidism by relevant clinical signs and symptoms, subnormal serum levels of thyroid stimulating hormone (TSH), abnormally elevated serum free T4, and elevated or normal serum T3.

Since arrhythmia breakthroughs may accompany amiodarone-induced hyperthyroidism, aggressive medical treatment is indicated, including, if possible, dose reduction or withdrawal of amiodarone.

Amiodarone hyperthyroidism may be followed by a transient period of hypothyroidism.

The institution of antithyroid drugs, Ƶ-adrenergic blockers or temporary corticosteroid therapy may be necessary. The action of antithyroid drugs may be especially delayed in amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid hormones stored in the gland.

Radioactive iodine therapy is contraindicated because of the low radioiodine uptake associated with amiodarone-induced hyperthyroidism.

When aggressive treatment of amiodarone-induced thyrotoxicosis has failed or amiodarone cannot be discontinued because it is the only drug effective against the resistant arrhythmia, surgical management may be an option. Experience with thyroidectomy as a treatment for amiodarone-induced thyrotoxicosis is limited, and this form of therapy could induce thyroid storm. Therefore, surgical and anesthetic management require careful planning.

Neonatal Hypo- or Hyperthyroidism Amiodarone can cause fetal harm when administered to a pregnant woman. Although amiodarone use during pregnancy is uncommon, there have been a small number of published reports of congenital goiter/hypothyroidism and hyperthyroidism associated with oral administration. Inform the patient of the potential hazard to the fetus if NEXTERONE is administered during pregnancy or if the patient becomes pregnant while taking NEXTERONE. Hypothyroidism Hypothyroidism has been reported in 2% to 4% of patients in most series, but in 8% to 10% in some series. This condition may be identified by relevant clinical symptoms and particularly by elevated serum TSH levels. In some clinically hypothyroid amiodarone-treated patients, free thyroxine index values may be normal. Manage hypothyroidism by reducing the NEXTERONE dose and considering the need for thyroid hormone supplement. However, therapy must be individualized, and it may be necessary to discontinue oral amiodarone in some patients.

5.9 Surgery Perform close perioperative monitoring in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction defects of halogenated inhalational anesthetics.

Nervous System: hallucination, confusional state, disorientation, and delirium, pseudotumor cerebri

5.10 Corneal Refractive Laser Surgery Advise patients that most manufacturers of corneal refractive laser surgery devices contraindicate corneal refractive laser surgery in patients taking amiodarone.

Respiratory: y bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates and /or mass, pleuritis

5.11 Electrolyte Disturbances Correct hypokalemia or hypomagnesemia whenever possible before initiating treatment with NEXTERONE, as these disorders can exaggerate the degree of QTc prolongation and increase the potential for TdP. Give special attention to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in patients receiving concomitant diuretics.

Thyroid: d thyroid nodules/thyroid cancer

6 ADVERSE REACTIONS 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In a total of 1836 patients in controlled and uncontrolled clinical trials, 14% of patients received intravenous amiodarone for at least one week, 5% received it for at least 2 weeks, 2% received it for at least 3 weeks, and 1% received it for more than 3 weeks, without an increased incidence of severe adverse reactions. The mean duration of therapy in these studies was 5.6 days; median exposure was 3.7 days.

The most important adverse reactions were hypotension, asystole/cardiac arrest/pulseless electrical activity (PEA), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. Overall, treatment was discontinued for about 9% of the patients because of adverse reactions. The most common adverse reactions leading to discontinuation of intravenous amiodarone therapy were hypotension (1.6%), asystole/cardiac arrest/PEA (1.2%), VT (1.1%), and cardiogenic shock (1%).

Table 4 lists the most common (incidence *2%) adverse reactions during intravenous amiodarone therapy considered at least possibly drug-related. These data were collected in clinical trials involving 1836 patients with life-threatening VT/VF. Data from all assigned treatment groups are pooled because none of the adverse reactions appeared to be dose-related.

Table 4: ADVERSE REACTIONS IN PATIENTS RECEIVING INTRAVENOUS AMIODARONE IN CONTROLLED AND OPEN-LABEL STUDIES (> 2% INCIDENCE) Study Event

Body as a whole Fever Cardiovascular System Bradycardia Congestive heart failure Heart arrest Hypotension Ventricular tachycardia Digestive System Liver function tests normal Nausea

Controlled Studies (n=814)

Open-Label Studies (n=1022)

Total (n=1836)

Body as a whole

Body as a whole 13 (1.2%)

Body as a whole 37 (2.0%)

24 (2.9%) Cardiovascular 49 (6.0%) 18 (2.2%) 29 (3.5%) 165 (20.2%) 15 (1.8%) Digestive System 35 (4.2%) 29 (3.5%)

Cardiovascular 41 (4.0%) 21 (2.0%) 26 (2.5%) 123 (12.0%) 30 (2.9%) Digestive System 29 (2.8%) 43 (4.2%)

Cardiovascular 90 (4.9%) 39 (2.1%) 55 (2.9%) 288 (15.6%) 45 (2.4%) Digestive System 64 (3.4%) 72 (3.9%)

Other adverse reactions reported in less than 2% of patients receiving intravenous amiodarone in controlled and uncontrolled studies included the following: abnormal kidney function, atrial fibrillation, diarrhea, increased ALT, increased AST, lung edema, nodal arrhythmia, prolonged QT interval, respiratory disorder, shock, sinus bradycardia, Stevens-Johnson syndrome, thrombocytopenia, VF, and vomiting.

6.2 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of amiodarone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: anaphylactic/anaphylactoid reaction (including shock), fever

Pancreatic: pancreatitis Renal:l renal impairment, renal insufficiency, acute renal failure

Vascular: r vasculitis 7 DRUG INTERACTIONS Since amiodarone is a substrate for CYP3A and CYP2C8, drugs/substances that inhibit these isoenzymes may decrease the metabolism and increase serum concentration of amiodarone.

Amiodarone inhibits p-glycoprotein and certain CYP450 enzymes, including CYP1A2, CYP2C9, CYP2D6, and CYP3A. This inhibition can result in unexpectedly high plasma levels of other drugs which are metabolized by those CYP450 enzymes or are substrates for p-glycoprotein.

HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with amiodarone has been associated with reports of myopathy/rhabdomyolysis.

Limit the dose of simvastatin in patients on amiodarone to 20 mg daily. Limit the daily dose of lovastatin to 40 mg. Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required.

Some drugs/substances are known to accelerate the metabolism of amiodarone by stimulating the synthesis of CYP3A (enzyme induction). This may lead to low amiodarone serum levels and potential decrease in efficacy.

Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Category D Reproductive and teratology studies performed in rabbits and rats at doses of up to 100 mg/kg per day (about 1.4 times the maximum recommended human dose on a body surface area basis) revealed no evidence of embryotoxicity at 5 mg/kg and no teratogenicity was observed at any dosage in rabbits.

Maternal toxicity and embryotoxicity were observed in rats in the 100 mg/kg group.

Use NEXTERONE during pregnancy only if the potential benefit to the mother justifies the risk to the fetus.

8.2 Labor and Delivery It is not known whether the use of amiodarone during labor or delivery has any immediate or delayed adverse effects.

8.3 Nursing Mothers Amiodarone and one of its major metabolites, desethylamiodarone (DEA), are excreted in human milk, suggesting that breast-feeding could expose the nursing infant to a significant dose of the drug.

8.4 Pediatric Use The safety and effectiveness of amiodarone in pediatric patients have not been established; therefore, the use of amiodarone in pediatric patients is not recommended.

8.5 Geriatric Use Clinical studies of amiodarone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Carefully consider dose selection in an elderly patient.

10 OVERDOSAGE There have been cases, some fatal, of amiodarone overdose. Effects of an inadvertent overdose of intravenous amiodarone include hypotension, cardiogenic shock, bradycardia, AV block, and hepatotoxicity.

Treat hypotension and cardiogenic shock by slowing the infusion rate or with standard therapy: vasopressor drugs, positive inotropic agents, and volume expansion. Bradycardia and AV block may require temporary pacing. Monitor hepatic enzyme concentrations closely. Amiodarone is not dialyzable.

Baxter Healthcare Corporation Deerfield, IL 60015 Baxter, Galaxy, Nexterone and the Sphere Graphic are trademarks of Baxter International Inc.

Cardiovascular: r hypotension (sometimes fatal), sinus arrest Dermatologic: toxic epidermal necrolysis (sometimes fatal), exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, skin cancer, pruritus, angioedema

Sourced from: 07-19-68-241 Rev. January 2012

Endocrine: syndrome of inappropriate antidiuretic hormone secretion (SIADH) Hematologic: pancytopenia, neutropenia, hemolytic anemia, aplastic anemia, thrombocytopenia, agranulocytosis, granuloma Hepatic: hepatitis, cholestatic hepatitis, cirrhosis Injection Site Reactions: pain, erythema, edema, pigment changes, venous thrombosis, phlebitis, thrombophlebitis, cellulitis, necrosis, and skin sloughing Musculoskeletal:l myopathy, muscle weakness, rhabdomyolysis

111923 04/13

16 Clinical

Pharmacy Practice News • March 2014

Drug Preparation Part 1 of a 2-Part Series

Are CSTDs at a Tipping Point in Nation’s Hospitals?

T

his year may well be the tipping point for closed system transfer devices (CSTDs) to gain more traction in U.S. hospitals.

Less than one-third of hospitals use these devices, which are self-contained systems that prevent the release of hazardous drugs or drug vapors by being leakproof and airtight. This lag exists despite studies that have shown the devices can significantly enhance worker and patient safety—a much-needed benefit, given the fact that in the case of health-care workers, approximately eigh million individuals a year may be exposed to hazardous drugs, according to the National Institute for Occupational Safety and Health.

One of the largest roadblocks to adoption of CSTDs has been the perceived high cost of the devices. But that soon may be changing, according to Firouzan “Fred” Massoomi, PharmD, FASHP, the pharmacy operations coordinator in the Department of Pharmacy Services at Nebraska Methodist Hospital, in Omaha.

“This year, as CSTD manufacturers offer new contracts and pricing strategies to hopitals, there is a sense of optimism that CSTDs may finally be poised to [achieve] much wider adoption,” Dr. Massoomi said. These cost reductions, he noted, are being driven by the fact that there are “more CSTD products on the market. That has forced the companies that sell them to work with health-systems … and Group Purchasing Organizations to establish contracts for best pricing.”

These contracts did not exist in the past, Dr. Massoomi noted. “Some people may not know they exist now, so I would hope that, when negotiating [CSTD] pric-

es, buyers continually look for contracts that offer efficiencies with pricing.”

It is also important to consider the nondirect cost savings that can accrue from CSTDs, he stressed. These include workflow efficiencies, minimizing work-related repetitive stress injuries, eliminating needlestick injuries, and increasing the ease and speed of compounding and administering products prepared with the devices.

in 2011 in conjunction with three other hospitals, showed that when the facilities used BD PhaSeal, along with proper aseptic technique, during the preparation of a single-dose vial, they were able to maintain product sterility for up to seven days versus the six hours achieved using methods that did not employ a CSTD. Before implementing the CSTD technology, “if the drugs in our partially filled vials weren’t used within six hours [as

significant strides in reducing contamination, whether they were using PhaSeal; ChemoClave, made by ICU Medical; or EQUASHIELD, made by Equashield. Dr. Massoomi has a broad base of experience with the devices. Since 2001, he noted, he and his colleagues have tested and used all of the leading CSTD brands. He said he let staff decide which device they prefer, adding that he is very pleased with all of them. “None are per-

‘In the very near future, it is my hope that CSTDs will be used for all sterile compounding products based on the benefits they provide for managing hazardous drugs and the potentials for vial optimization programs.’

—Firouzan Massoomi, PharmD, FASHP Lucy Moyer, RPh, the director of pharmacy operations at the University of Texas MD Anderson Cancer Center, in Houston, shared Dr. Massoomi’s enthusiasm for CSTD technology. The benefits of the devices are many, Ms. Moyer pointed out. Not the least of these is increased worker and patient safety. Devices such as PhaSeal (BD Diagnostics), which MD Anderson uses, prevent the escape of chemotherapy into the atmosphere and also prevent microbiologic contamination of single-dose vials, Ms. Moyer noted. In the process, the devices “keep the drugs inside sterile” and thus safe for reuse in multiple patients, she noted.

CSTDs also enable pharmacies to extend the period of time in which the stable drug contents of a partially used vial can be utilized, a process commonly known as Drug Vial Optimization (DVO), Ms. Moyer pointed out. Two independent DVO studies, done by MD Anderson

A pharmacy technician, working inside a biological safety cabinet, transfers chemotherapy medications using PhaSeal to prevent drug spills and air leaks. The system interfaces simultaneously with the newly introduced BD Cato workflow software.

per USP Chapter <797> guidelines], we threw them away, and chemo drugs are very expensive,” she said.

MD Anderson, which operates 17 pharmacies, 14 of which do high-volume compounding primarily of IV and chemotherapy IV medications, also did a drug-waste study to quantify the costsavings associated with DVO. The study, conducted in three of its pharmacies that compound hazardous drugs, found that before using PhaSeal for DVO, “we were throwing away $321,000 of partial vials” in a typical month, Ms. Moyer said. “After we began using PhaSeal in our DVO program, we reduced [that] waste to $175,000—a 45% decrease.”

Although technicians initially found PhaSeal awkward to use, she added, “within several weeks they became comfortable with the new technique and we actually found production time to be decreased. That was because variation in technique was reduced, vial pressure was now equalized, and they could be less concerned about leaks and vapors escaping during preparation.”

These positive outcomes are not a new occurrence at MD Anderson, Ms. Moyer noted. As the first hospital to deploy a CSTD system in the United States, almost immediately after PhaSeal was introduced in 1998, the health system has had ample time to study the technology and to evaluate its effects on patient and health-care worker safety. After PhaSeal was deployed, she noted, “our wipe studies showed a major reduction in contamination.” Today, wipe samples, done quarterly at MD Anderson, provide “conclusive evidence that using PhaSeal has virtually eliminated contamination from the production side, except when vials are dropped.”

All the hospitals interviewed by Pharmacy Practice News reported similar

fect; they all have gaps,” Dr. Massoomi said. “But they all have their strong points and make cleanrooms safer” than when the devices did not exist.

According to Dr. Massoomi, Nebraska Methodist Hospital uses both BD’s PhaSeal and ICU Medical’s ChemoClave/Spiros system. “In our pursuit of occupational safety, we will continue to review and test enhancements to existing devices and review new ones as they are made available,” he said.

Penn State Hershey Medical Center, in Hershey, Pa., is another site that chose to go with the ChemoClave system and began using the technology about a year ago. Lisa BracciniBarletta, MBA, RPh, the hospital’s director of Pharmacy, Outpatient Services, said her team will likely continue to evalate new products as they are made available but for now, they are pretty happy with ChemoClave. “We knew that this was going to be something that everyone understood,” Ms. BracciniBarletta said. “They wanted to use it and they felt comfortable using it.”

Hybrid Systems Spark Interest The emergence of new “hybrid” CSTD systems that work in conjunction with automation and pharmacy workflow software has also sparked new interest in the devices. These hybrid systems are creating new ways of incorporating CSTDs into pharmacy cleanrooms, endusers noted.

BD Diagnostics is introducing a new hybrid IV software workflow solution called BD Cato that interfaces PhaSeal with pharmacy management systems.

PhaSeal “protects the healthcare worker and ensures the sterility of the drugs being compounded,” while “BD Cato makes sure the correct drug is being

•

see CSTDs, page 19

Enoxaparin Sodium Injection, USP

WARNING: SPINAL/EPIDURAL / HEMATOMAS

See full prescribing information for complete boxed warning.

Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: • Use of indwelling epidural catheters • Concomitant use of other drugs that affect hemostasis, such as non-steroidal antiinflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants • A history of traumatic or repeated epidural or spinal punctures • A history of spinal deformity or spinal surgery.

• Optimal timing between the administration of enoxaparin sodium injection and neuraxial procedures is not known.

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. [see Warnings and Precautions (5.1) and Drug Interactions (7)].

Please see brief summary of full prescribing information including boxed warning on following page.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. www.us.sandoz.com © 2014 Sandoz Inc., a Novartis company. All rights reserved.

SDZ0434 02/2014

Available in 7 strengths in pre-filled syringes.

• 30 mg/0.3 mL pre-filled syringe 40 mg/0.4 mL pre-filled syringe 60 mg/0.6 mL pre-filled syringe 80 mg/0.8 mL pre-filled syringe 100 mg/1.0 mL pre-filled syringe 120 mg/0.8 mL pre-filled syringe 150 mg/1.0 mL pre-filled syringe • Sandoz is a member of the Novartis family of companies — a name you can trust for quality and reliability

Choose the full potential of generics.

Enoxaparin Sodium Injection, USP WARNING: SPINAL/EPIDURAL HEMATOMAS See full prescribing information for complete boxed warning.

Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: • Use of indwelling epidural catheters • Concomitant use of other drugs that affect hemostasis, such as non-steroidal antiinflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants • A history of traumatic or repeated epidural or spinal punctures • A history of spinal deformity or spinal surgery.

• Optimal timing between the administration of enoxaparin sodium injection and neuraxial procedures is not known.

Monitor patients frequently for signs and symptoms of neurological impairment.

If neurological compromise is noted, urgent treatment is necessary. [see Warnings and Precautions (5.1) and Drug Interactions (7)].

- - - - - - INDICATIONS AND USAGE - - - - - Enoxaparin sodium injection, USP is a low molecular weight heparin [LMWH] indicated for: • Prophylaxis of deep vein thrombosis (DVT) in abdominal surgery, hip replacement surgery, knee replacement surgery, or medical patients with severely restricted mobility during acute illness • Inpatient treatment of acute DVT with or without pulmonary embolism • Outpatient treatment of acute DVT without pulmonary embolism • Prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction [MI] • Treatment of acute ST-segment elevation myocardial infarction [STEMI] managed medically or with subsequent percutaneous coronary intervention [PCI] - - - - - - DOSAGE AND ADMINISTRATION - - - - - Indication

Dose

DVT prophylaxis in abdominal surgery

40 mg SC once daily

DVT prophylaxis in knee replacement surgery

30 mg SC every 12 hours

DVT prophylaxis in hip replacement surgery

30 mg SC every 12 hours or 40 mg SC once daily

DVT prophylaxis in medical patients

40 mg SC once daily

Inpatient treatment of acute DVT with or without pulmonary embolism

1 mg/kg SC every 12 hours or 1.5 mg/kg SC once daily*

Outpatient treatment of acute DVT without pulmonary embolism

1 mg/kg SC every 12 hours *

Unstable angina and non-Q-wave MI

1 mg/kg SC every 12 hours (with aspirin)

Acute STEMI in patients <75 years of age [For dosing in subsequent PCI, see Dosage and Administration]

30 mg single IV bolus plus a 1 mg/kg SC dose followed by 1 mg/kg SC every 12 hours (with aspirin)

Acute STEMI in patients ≥75 years of age

0.75 mg/kg SC every 12 hours (no bolus) (with aspirin)

• See recommended durations for enoxaparin sodium injection therapy • *See recommendations regarding transitioning to warfarin therapy • Adjust the dose for patients with severe renal impairment

- - - - - - DOSAGE FORMS AND STRENGTHS - - - - - 100 mg/mL concentration: Prefilled syringes: 30 mg/0.3 mL, 40 mg/0.4 mL Graduated prefilled syringes: 60 mg/0.6 mL, 80 mg/0.8 mL, 100 mg/mL 150 mg/mL concentration: Graduated prefilled syringes: 120 mg/0.8 mL, 150 mg/mL - - - - - - CONTRAINDICATIONS - - - - - Active major bleeding Thrombocytopenia with a positive in vitro test for anti-platelet antibody in the presence of enoxaparin sodium Hypersensitivity to enoxaparin sodium Hypersensitivity to heparin or pork products Hypersensitivity to benzyl alcohol [for multi-dose formulation only] - - - - - - WARNINGS AND PRECAUTIONS - - - - - Increased risk of hemorrhage: Use with caution in patients at risk Percutaneous coronary revascularization: Obtain hemostasis at the puncture site before sheath removal Concomitant medical conditions: Use with caution in patients with bleeding diathesis, uncontrolled arterial hypertension or history of recent gastrointestinal ulceration, diabetic retinopathy, renal dysfunction, or hemorrhage History of heparin-induced thrombocytopenia: Use with caution Thrombocytopenia: Monitor thrombocytopenia closely Interchangeability with other heparins: Do not exchange with heparin or other LMWHs Pregnant women with mechanical prosthetic heart valves and their fetuses may be at increased risk and may need more frequent monitoring and dosage adjustment

- - - - - - ADVERSE REACTIONS - - - - - Most common adverse reactions (>1%) were bleeding, anemia, thrombocytopenia, elevation of serum aminotransferase, diarrhea and nausea To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

- - - - - - DRUG INTERACTIONS - - - - - Discontinue agents which may enhance hemorrhage risk prior to initiation of enoxaparin sodium injection or conduct close clinical and laboratory monitoring - - - - - - USE IN SPECIFIC POPULATIONS - - - - - Severe Renal Impairment: Adjust dose for patients with creatinine clearance <30 mL/min Geriatric patients: Monitor for increased risk of bleeding Patients with mechanical heart valves: Not adequately studied Hepatic Impairment: Use with caution Low Weight Patients: Observe for signs of bleeding • Obese Patients: Not adequately studied. Observe for thromboembolism

Manufactured by Baxter Pharmaceutical Solutions LLC for Sandoz Inc., Princeton, NJ 08540 Rev. November 2013

Clinical 19

Pharmacy Practice News • March 2014

Drug Preparation

CSTDs

When used properly, the first-generation EQUASHIELD device eliminated such plunger contamination, he noted.

However, in extreme cases of misuse, contaminants could remain trapped between the back of the plunger and the syringe. EQUASHIELD II, Mr. Kriheli said, has a proprietary shield designed to prevent any access of drugs to the plunger, “completely eliminating such incidents of misuse.”

That feature, he noted, makes EQUASHIELD II “the only CSTD device that covers all routes of detectable hazardous drug exposure.”

continued from page 16

delivered and in the right dose,” noted Kevin Kelly, the company’s senior business director of pharmacy solutions.

BD Cato, Mr. Kelly added, also allows pharmacies “to create efficiencies by standardizing workflow, creating an automated documentation trail and speeding up the production process because it’s standardized and automated. These [enhancements] will all drive down costs.”

For more than a year now, MD Anderson has been using and evaluating BD Cato interfaced with PhaSeal. “Using PhaSeal to improve healthcare worker safety and better protect drug vial contents, along with Cato to ensure drug dose accuracy and improve workflow, is like a revolution in chemotherapy preparation,” Ms. Moyer said. “As far as medication safety, efficiency and inventory management, I haven’t seen anything like Cato.”

The need for a sophisticated and safe sterile compounding system is underscored by the extent and type of compounding being done at MD Anderson.

The health system processes 20,000 doses of IV chemotherapy medications a month; serves a large high-risk patient population; often dispenses narrow therapeutic index drugs with a challenging safety/efficacy profile; and often has to navigate look-alike/ sound-alike drugs that make chemotherapy management even more of a challenge, Ms. Moyer noted. What’s more, “weight-based dosing makes the process more complex and more subject to human error,” she said.

BD Cato has taken some of the strain out of those processes, she said, by bringing “standard operating procedures to every single dose production that we have. Every technician prepares the dosage exactly the same way every time. Reduction of variation always leads to better outcomes.”

MD Anderson also wanted a technology solution that could increase opera-

EQUASHIELD II has a proprietary shield designed to prevent access of drugs to the plunger, a feature meant to completely eliminate the potential for plunger contamination.

‘[There is] conclusive [wipe-sample] evidence that using [a CSTD] has virtually eliminated contamination from the production side, except when vials are dropped.’

—Lucy Moyer, RPh tional efficiencies and improve inventory management, and Cato delivers on all counts, Ms. Moyer noted. So far, benefits, after approximately one year of use in one of MD Anderson’s 14 compounding pharmacies include: • $111,000 saved in a year through direct labor cost reductions. “These are decreases in production time and decreases in pharmacists check time,” she said.

• $49,000 saved within 10 months through reduced errors during drug preparation. “If it’s prepared incorrectly, you can’t use the drug.”

• $46,500 saved in a year through indirect labor cost reductions. “We had been shuffling paper; we are paperless now.”

• $22,000 monthly saved via DVO and better vial management. “Cato tracks every vial and instructs the

ONB Designation May Hasten Reimbursement

A

ny hospital interested in adding CSTDs in its facilities should become familiar with how the devices are characterized by regulatory bodies.

There is a designation that a CSTD manufacturer can obtain for its devices by applying to the FDA for a product code, an ONB, that designates a CSTD as a device for transferring liquids to reduce hazardous drug exposures in specific workplace settings such as pharmacies or nursing areas. Two CSTDs currently have an ONB designation: PhaSeal (BD Diagnostics) has an ONB for compounding, and ChemoLock (ICU Medical) has an ONB for both compounding and administration.

The possibility exists that when CSTDs have an ONB code, hospitals “might be able to bill for reimbursement for using these devices as medical devices,” said Dr. Massoomi. “That’s what I would hope for. It would help recoup some of our investment costs.”

—L.P.

technicians to use stable vials first,” Ms. Moyer said, adding that Cato BD currently is tracking 28 drugs in just one of MD Anderson’s pharmacies.

“We have about 60 drugs this would be relevant for and 14 compounding pharmacies, so we have plenty of opportunities for more savings.”

There also have been medication safety enhancements, in addition to those already provided by PhaSeal alone. “Of the doses made, 3.78% were out of tolerance range,” Ms. Moyer said. “We could never have figured that out without Cato. We can tell exactly with Cato.”

MD Anderson is now in the process of implementing BD Cato throughout its institution. It will go into six more pharmacies this spring, Ms. Moyer noted.

EQUASHIELD: The Newest Entry Port Washington, N.Y.-based Equashield makes EQUASHIELD, the newest of the three leading CSTD brands, introduced to the U.S. market just three years ago, and currently in distribution in hundreds of hospitals. But management is already rolling out a secondgeneration system, EQUASHIELD II, described by Marino Kriheli, cofounder of Equashield and the inventor of EQUASHIELD, as “a one-step system including a syringe, preassembled with a connector and closed pressure equalization.” He said this makes the device “the fastest and easiest to use CSTD on the market.”

Some regular and CSTD syringe plungers can be contaminated by drug residue, according to Mr. Kriheli.

Montefiore Medical Center, in the Bronx, N.Y., was one of the first hospitals to install the first-generation EQUASHIELD three years ago and will be testing EQUASHIELD II when it ships this spring. To test the effectiveness of EQUASHIELD I, Montefiore did before-and-after surface wipe tests in both its pharmacy and nursing areas.

Roy Browne, PharmD, the director of Oncology Pharmacy Services at Montefiore, said trace amounts of chemotherapy on counter tops have been “completely eliminated.” He attributed that outcome to an EQUASHIELD adapter at the end of the IV tubing that replaced caps at the end of the tube. In the pharmacy, he said, “we significantly reduced the drips, leaks and spills that we used to experience when needles were pulled out of syringes.”

But, Dr. Browne explained, “if you were using bad technique, it was possible to get traces of drug fluids inside the space behind the plunger. EQUASHIELD II has improvements, a barrier, that prevents that from happening and we will be testing it as soon as we can.”

A clinical, nonsponsored study by researchers at the Cleveland Clinic ((J Oncol Practt 2013;19:99-104) comparing contamination one year before using EQUASHIELD I and one year after, showed “zero detections of contamination from all contamination sources,” Dr. Browne said.

Looking Ahead Whatever the particular CSTD system used, the benefits of the technology support more widespread use of the devices, noted Methodist Hospital’s Dr. Massoomi. Indeed, “In the very near future,” he said, “it is my hope that CSTDs will be used for all sterile compounding products based on the benefits they provide for managing hazardous drugs and the potential for vial optimization programs.”

—Liz Parks

Part 2, Next Issue: More details on ICU Medical’s CSTDs, plus the Chemo Safety System from CareFusion.

20 Clinical

Pharmacy Practice News • March 2014

Infectious Disease

ASP BUILDING TIPS continued from page 8

more than 300 enzyme tests monthly to 140 PCR tests per month, because PCR was more accurate in identifying these infections on the first test.”

Thanks to the CDI initiative, infection rates that were as high as eight cases per 10,000 patient-days before the initiative were brought down to an average of 4.1 cases per 10,000 patient-days one year later, Dr. Eiland said.

Collectively, the second-phase initia-

tives resulted in an estimated $296,775 in avoided costs during the two-year period, Dr. Eiland said. “By this point in the ASP, the longevity of the program led to a real sustained culture change in the prescribing of antimicrobials,” he added.

Phase 3 (2011-2013): Enhancing the Program Never resting on their laurels, in 2011 Dr. Eiland and his team searched for more ways to expand the ASP and to demonstrate further value. They devel-

oped a new initiative aimed at lowering infection rates among hospital patients receiving outpatient parenteral antibi-

LEADERS EXPLORE THE POSSIBILITIES

Leaders inquire. They map out all approaches in order to find the best route.

At the end of the day, they take the best path to their ultimate destination.

At Aesynt, we lead hand-in-hand to help our customers find that destination.

Our game-changing pharmacy automation and medication management solutions are helping hospitals and health systems improve outcomes, build stronger businesses and manage change in an evolving healthcare environment.

Discover your path with Aesynt.

Visit www.aesynt.com.

otic therapy (OPAT).

“We focused on OPAT because it is four to five times less expensive to treat an outpatient than an inpatient,” he said. “We also involved our PGY [postgraduate year] 1 students in the program, further reducing the cost of the program and providing them with a good learning experience.”

The initiative’s main element was creation of a standardized order form for infectious disease physicians to ensure OPAT patients were receiving appropriate anti-infective therapy. Dr. Eiland said implementation of the sets correlated with a decrease in infectionrelated 30-day readmissions in OPAT patients from 9.2% during the year before order sets were used to 6.9% within a year of their implementation.

Moreover, branching out into the OPAT niche led to a joint venture with a home infusion company to manage their clients, generating further revenue for the hospital.

Also during the third phase of the ASP’s implementation, Huntsville Hospital updated its sepsis protocols to reflect new guidelines, added PGY2 residents to carry out ASP duties and established criteria to help physicians determine which patients should receive fidaxomicin (Dificid, Cubist) for C. difficile-associated diarrhea (CDAD). Fidaxomicin was increasingly being used in combination with vancomycin and metronidazole, Dr. Eiland said. “We developed a five-point scorecard that included risk factors for CDAD to help direct appropriate therapy,” he explained.

Results from a retrospective, observational study of 60 patients treated during the year following the scorecard’s implementation were presented in a poster at the American College of Clinical Pharmacy’s 2013 annual meeting (poster 28), with the findings showing a 10-day cure rate of 98.4% after program implementation. Additionally, the 30-day recurrence rate of 10% in their patients compared favorably with the 12.7% to 15.4% 30-day recurrence rates reported in two large, Phase III trials ((N Engl J Med 2011;364:422-431; Lancet Infect Dis 2012;12:281-289).

—David Wild Dr. Eiland reported no relevant conflicts of interest.

Clinical 21

Pharmacy Practice News • March 2014

Critical Care

ED TECHNICIANS continued from page 10

them both against clinician notes and hospital pharmacy prescriptions.

She found that, in recording the last time patients had been administered an anticoagulant or antiplatelet, nurses were accurate only 13% of the time, whereas pharmacy technicians were correct in 76% of cases in their medication reconciliations ((P<0.001).

The potential consequences of such errors could be dire, Dr. Hart noted. “If a patient were to have a scheduled or unscheduled surgical procedure too soon after they received their anticoagulant and it had not been clearly documented, they could potentially have a serious or life-threatening bleed,” she said.

Dr. Hart added that the results of the study were all the more surprising, given the fact that pharmacy technicians were often asked to do medication histories on the more complicated patients. “As a result, we might expect that the technician group would make more errors,” she said. “However, the [overall] data actually showed the opposite. Despite having more complicated patients, 88% of the time the technician group had completely accurate medication histories vs. only 57% of the time by nurses” (Figure).

Pharmacy Technician (n=150)

12%

Nurses Welcomed the Help Dr. Hart’s report had the potential to anger ED nurses, who may have felt the results questioned the quality of their work. However, a survey Dr. Hart distributed to 27 of the ED nurses suggested otherwise. “All of the nurses said they would be happy if [pharmacy technicians] conducted every ED medication reconciliation and that it would leave them with more time to attend to other duties.”

Caryl Ann Mannino, BSN, RN, the director of Professional Practice/Magnet Project Director at Our Lady of Lourdes

Memorial Hospital, in Binghamton, N.Y., is an expert on the role of nurses in the medication reconciliation process.

She said her hospital has not formally compared the accuracy of nurse- and technician-conducted medication histories but, “from anecdotal comments and incidental medical record reviews,” there are more omissions, wrong doses and wrong frequencies in medication histories collected by nurses.”

Those errors are not surprising, Ms. Mannino noted. “Nurses are constantly interrupted, have multiple foci and are

often multi-tasking, whereas a [medication reconciliation technician] is focused on this one task—[medication reconciliation],” she said. Such technicians “have the time to contact external sources such as retail pharmacies and provider offices, while nurses most often rely on information provided by patients or [in their] records.”

—David Wild None of the researchers reported any relevant financial conflicts of interest.

TAP INT A FRES

SUPPLY Tap into Fresenius Kabi USA— your source for Acetylcysteine Solution n, USP.

88%

Nurse (n=150)

57%

43% Medical Information 800-551-7176 Customer Service 888-386-13 300 www.Fresenius-Kabi.us F i K bi

P=<0.0001

Correct

Incorrect

Figure. of medication lists obtained by pharmacy technicians and nurses.

A PROVEN RECORD OF RESPONSE. ©2013, Fresenius Kabi USA, LLC. All Rights Reserved. 0623-ACS-05-11/13

Soon to be flowing in more sizes.

22 Clinical

Pharmacy Practice News • March 2014

Educational Review

Guidelines for Administration of

Cardiovascular Medications With Food and Grapefruit Juice GRETCHEN L. D’ARCANGELO, BSPS

VINCENT F. MAURO, PHARMD, FCCP CCP

PharmD Candidate College of Pharmacy and Pharmaceutical Sciences The University of Toledo Toledo, Ohio

Professor of Clinical Pharmacy College of Pharmacy and Pharmaceutical S Science es Adjunct Professor of Medicine College of Medicine The University of Toledo Toledo, Ohio

I

n many clinics and pharmacies, patients often question whether medications should be taken with or without

food. This led the authors to research recommendations

for taking various cardiovascular medications with food.

The results of this search are contained within the table and are intended to be used as a quick aid for health care practitioners when they are prescribing or administering cardiovascular drugs, or are counseling patients taking these drugs.1-3 Information was collected primarily from the manufacturer-provided package inserts. In situations where the manufacturer did not provide recommendations on administration, the AHFS Drug Information online reference was used. If no information was available there, the final source consulted was Lexi-Comp’s online reference.

The focus of this research was to address the effect that food has on the direct gastrointestinal absorption and tolerability of specific medications. If it is recommended that a medication be administered with food, the preferred

time (ie, before, during, or after a meal) is presented, when available. We have included the most commonly used cardiovascular medications, providing recommendations regarding administration. Specific information on the presence of a grapefruit juice interaction also is included because it can lead to variable yet significant changes in drug concentrations and effects.

References 1.

McEvoy GK, ed. AHFS Drug Information 2012. Bethesda, MD: ASHP; 2011.

2. Lacy CF, Armstrong LL, Goldman MP, Lance LL, eds. Drug Information Handbook, k 20th Edition.

Hudson, OH: Lexi-Comp; 2011.

3. Seden K, Dickinson L, Khoo S, Back D. Grapefruit-drug interactions. Drugs. 2010; 70(18):2373-2407.

Table. Recommendations for Administration of CV Agents With Food, Grapefruit Juice Drug

Recommendation Regarding Food

Grapefruit Juice Interaction

Acebutolol

May be taken with or without food

No2

Aliskiren (Tekturna, Novartis) Aliskiren/Amlodipine (Tekamlo, Novartis) Ambrisentan (Letairis, Gilead)

Should be taken consistently with or without food but not with high-fat meals

Avoid combination; separation by several hours may reduce chance for interaction2 Avoid combination3

May be taken with or without food No2

Amiloride Should be taken with food Amiloride/HCTZ Amiodarone

Should be taken consistently with or without food

Avoid combination3

Amlodipine Amlodipine/atorvastatin Amlodipine/benazepril Amlodipine/olmesartan (Azor, Sankyo) Amlodipine/olmesartan/HCTZ (Tribenzor, Sankyo)

Avoid combination or limit consumption to small quantities2,3 May be taken with or without food Avoid combination3

Clinical 23

Pharmacy Practice News â&#x20AC;˘ March 2014

Educational Review

Table. Recommendations for Administration of CV Agents With Food, Grapefruit Juice Drug

Recommendation Regarding Food

Amlodipine/telmisartan (Twynsta, Boehringer Ingelheim)

May be taken with or without food

Amlodipine/valsartan (Exforge, Novartis)

Should be taken consistently with or without food

Aspirin

Administration with food may help prevent stomach upset1

Aspirin/dipyridamole (Aggrenox, Boehringer Ingelheim)

May be taken with or without food

Atenolol

No issue apparent regarding administration with or without food

Avoid combination3

Atorvastatin

No2

Avoid combination or limit consumption to small quantities2,3

Azilsartan (Edarbi, Arbor) Benazepril

Grapefruit Juice Interaction

No2 May be taken with or without food

Betaxolol

No2

Bisoprolol

Monitor for increased effects of bisoprolol2

Bosentan (Tracleer, Actelion)

Monitor for increased effects of bosentan2

Bumetanide

No issue apparent regarding administration with or without food

Candesartan

May be taken with or without food

Captopril

Should be taken 1 h before meals

Carvedilol

Should be taken with food to decrease risk for orthostatic hypotension

Chlorthalidone

Should be taken as a single dose in the morning with food

Cholestyramine

Should be taken with food

Cilostazol

Should be taken consistently either 30 min before or 2 h after breakfast and dinner

No2

Monitor for increased effects of carvedilol2

No2 Monitor for increased effects of cilostazol2

Clonidine May be taken with or without food Clopidogrel

No2

Colesevelam (Welchol, Sankyo)

Should be taken with food

Colestipol

Should be taken with plenty of fluids

Cyclosporine

All formulations should be taken consistently with or without food, but Neoral (Novartis) should not be administered with high-fat meals

Avoid combination3

Dabigatran etexilate (Pradaxa, Boehringer Ingelheim)

May be taken with or without food

Monitor for increased effects of dabigatran2

Digoxin

May be taken with or without food; however, meals high in bran fiber should be avoided

No2,3

Diltiazem

IR product should be taken before meals; no issue with long-acting product; however, Dilacor XR (Actavis) should not be taken with high-fat meals

Monitor for increased effects of diltiazem2,3

No2

Dipyridamole Disopyramide

No issue apparent regarding administration with or without food

No2

Dofetilide (Tikosyn, Pfizer) May be taken with or without food Doxazosin Dronedarone (Multaq, Sanofi-Aventis)

Monitor for increased effects of disopyramide2

Should be taken with food

Monitor for increased effects of doxazosin2 Avoid combination3 No2

Enalapril Eplerenone (Inspra, Pfizer)

May be taken with or without food

Eprosartan

Should be taken consistently with or without food

Ethacrynic acid

Should be taken after meals

No2

May be taken with or without food

Avoid combination or limit consumption to small quantities2,3

Dose adjustments are recommended; contact physician2

Ezetimibe (Zetia, Merck/Schering) Ezetimibe/simvastatin (Vytorin, Merck/Schering)

24 Clinical

Pharmacy Practice News â&#x20AC;˘ March 2014

Educational Review Table. Recommendations for Administration of CV Agents With Food, Grapefruit Juice Drug

Recommendation Regarding Food

Grapefruit Juice Interaction

Felodipine

Should be taken without food or with a light meal

Moderation of grapefruit juice ingestion may be needed2

Fenofibrate

May be taken with or without food (Antara [Lupin], Fibricor [AR Scientific], TriCor [AbbVie], Triglide [Shionogi], and TriLipix [AbbVie]); should be taken with food (Fenoglide [Santarus], and Lipofen [Kowa])

Flecainide Fluvastatin

May be taken with or without food

No2

Fosinopril Furosemide

No issue apparent regarding administration with or without food

Gemfibrozil

Should be taken 30 min before morning and evening meals

Guanfacine

IR and ER products may be taken with or without food, but ER products should not be taken with high-fat meals

Monitor for increased effects of guanfacine2

Hydralazine

Should be taken consistently with or without food

No2

Hydralazine/isosorbide dinitrate (BiDil, Arbor)

No issue apparent regarding administration with or without food

Monitor for increased effects of isosorbide2

Hydrochlorothiazide

May be taken with or without food; however, Microzide (Actavis) capsules should be taken consistently with or without food

Indapamide

No issue apparent regarding administration with or without food

Irbesartan

May be taken with or without food

Isosorbide

May be taken with or without food (mononitrate); no issue apparent regarding administration with or without food (dinitrate)

Monitor for increased effects of isosorbide2

Isradipine

No issue apparent regarding administration with or without food

Monitor for increased effects of isradipine2

Labetalol

Should be taken consistently with or without food

No2

No2

Lisinopril May be taken with or without food Losartan Lovastatin

Should be taken with food

Avoid combination3

Methyldopa No issue apparent regarding administration with or without food Metolazone Metoprolol

Should be taken consistently with or immediately after meals

Mexiletine

Should be taken with food

Midodrine

May be taken with or without food

Minoxidil

No issue apparent regarding administration with or without food

Moexipril

Should be taken 1 h before meals

No2

Monitor for increased effects of nadolol2

Nadolol May be taken with or without food Nebivolol (Bystolic, Forest)

No2

Niacin

No2

Niacin/lovastatin (Advicor, AbbVie)

Should be taken with food

Niacin/simvastatin (Simcor, AbbVie)

Avoid combination3 Avoid combination or limit consumption to small quantities2,3

Nicardipine

To ensure constant bioavailability, do not administer with high-fat meals; SR product should be taken consistently with or without food

Nifedipine

No issue apparent regarding administration with or without food with IR products; long-acting products should be taken without food

Nisoldipine

Should be taken either 1 h before or 2 h after a meal

Olmesartan (Benicar, Sankyo)

May be taken with or without food

Omega-3-acid ethyl esters

No issue apparent regarding administration with or without food

Pentoxifylline

Should be taken with food

Perindopril erbumine

Should be taken consistently with or without food

Avoid combination3

No2

Clinical 25

Pharmacy Practice News • March 2014

Educational Review

Table. Recommendations for Administration of CV Agents With Food, Grapefruit Juice Drug

Recommendation Regarding Food

Grapefruit Juice Interaction

Pindolol May be taken with or without food Pitavastatin (Livalo, Kowa) Potassium chloride

No2 Should be taken with food

Prasugrel (Effient, Lilly) May be taken with or without food Pravastatin

Monitor for increased effects of pravastatin2

Prazosin

No issue apparent regarding administration with or without food

No2

Propafenone

May be taken with or without food

Monitor for increased effects of propafenone2,3

Propranolol

Protein-rich foods increase bioavailability, so IR product should be taken without food to ensure constant bioavailability; long-acting product has no apparent issue regarding administration with or without food

No2

Quinapril

Should be taken consistently with or without food, but not with high-fat meals

Quinidine sulfate/quinidine gluconate

Should be taken with food

Monitor for increased effects of quinidine2

Ramipril

May be taken with or without food

No2

Rivaroxaban (Xarelto, Janssen)

When used for AF, should be taken with evening meals; when used for DVT prophylaxis after hip/knee surgery, may be taken with or without food

Monitor for increased effects of rivaroxaban2

Rosuvastatin (Crestor, AstraZeneca)

May be taken with or without food

No2

Sildenafil

May be taken with or without food, but not with high-fat meals

Monitor for increased effects of sildenafil2,3

Simvastatin

May be taken with or without food

Avoid combination or limit consumption to small quantities2,3

Sirolimus (Rapamune, Pfizer)

Should be taken consistently with or without food, but not with high-fat meals

Avoid combination3 No2

Sotalol Should be taken consistently with or without food Spironolactone

No2

Tacrolimus

Should be taken consistently with or without food, but not with high-fat meals

Avoid combination3

Tadalafil (Adcirca, Cialis, Lilly)

May be taken with or without food

Monitor for increased effects of tadalafil2,3

Telmisartan (Micardis, Boehringer Ingelheim)

May be taken with or without food

No2

Terazosin

No issue apparent regarding administration with or without food

No2

Ticagrelor (Brilinta, AstraZeneca)

May be taken with or without food

Monitor for increased effects of ticagrelor2

Ticlopidine

Should be taken with food

No2

Timolol

No issue apparent regarding administration with or without food

No2 Avoid combination2

Tolvaptan (Samsca, Otsuka) Torsemide

May be taken with or without food

No2 No2

Trandolapril

Monitor for increased effects of verapamil2

Trandolapril/verapamil (Tarka, AbbVie)

Should be taken with food

Triamterene (Dyrenium, Wellspring)

Administer after meals to avoid stomach upset

Triamterene/HCTZ

Administer after meals

Valsartan

Should be taken consistently with or without food

Verapamil

IR product has no apparent issue regarding administration with or without food; Calan SR (Pfizer) and Isoptin SR (Ranbaxy) capsules should be taken with food

Interaction unlikely to be clinically relevant3; monitor for increased effects of verapamil2

Warfarin

Should be taken consistently with or without food; efforts should be made to maintain a consistent dietary vitamin K intake

No2

No2

AF, atrial fibrillation; CV, cardiovascular; DVT, deep vein thrombosis; ER, extended-release; HCTZ, hydrochlorothiazide; IR, immediate-release; SR, sustained-release Based ased on o manufacturers’ a u actu e s package pac age inserts se ts unless u ess otherwise ott e w se noted. oted

26 Policy

Pharmacy Practice News • March 2014

Medication Safety

ANOTHER NECC?

‘[Sterile compounders] are reluctant to register with the FDA because they fear the possibility that the agency will come in and shut them down. The FDA has tremendous power.’

continued from page 1

the compounding facility. The Form 483s, which can be viewed on the FDA’s website (http://1.usa.gov/1h06JCj), listed several potential violations, including insufficient air filtration systems, failure to perform endotoxin testing on all finished sterile injectable drug products, and, in one case, an employee “dragging a full trash bag across the clean-room floor ... where aseptic processing activities [were occurring].”

—Tom Van Hassel, RPh, MPA The two facilities that were not issued Form 483s were last inspected by the agency eight and ten years ago, respectively, according to the FDA. Christian Hartman, PharmD, MBA,

who chaired a special commission on compounding in Massachusetts, where NECC was located, said he is encouraged that the FDA is aggressively inspecting such facilities and citing them for poten-

REMEDIES

tially unsafe manufacturing conditions (see sidebar for more details, page 28).

But he said he was troubled by the fact that so few compounders have stepped forward to register. That slow uptake, he noted, means that “facilities performing compounding similar to NECC are in some cases still going unregulated.”

Dr. Hartman did acknowledge that the National Association of Boards of Pharmacy (NABP) and state boards are working with the FDA to strengthen state-level oversight for facilities that do not register under the new category. As a result, “state laws and efforts are moving in the right direction to ensure safer compounding,” he said. “But they are not yet where they need to be.”

The Teeth in H.R. 3204

Risk Evaluation and Mitigation Strategies: an Employer-Driven CME Initiative for Efficacy and Safety

Follow the Blue Blu lueprint pri rint t

Complete Parts 1 and 2 to meet et the requirements of the FDA Blue Blueprint print fo forr Prescriber er Education fo for Extended-Release and Long-Acting Long-Acting Opioid Ana Analges Analgesics lgesics ics

Navigating g Opioid RE REMS MS

Navigating Na N avigating O Opioid REMS REMS

SUPPLEMENTARY SUPPLEMENTAR S UPPLEMENTARY UPPLEMENTAR U M NTA .5 C

LOW L OW BACK PAIN

A Virtual Patient Activity

A Virtual Patient Activity

MY FIRST-CHOI E IIS MY S

Now What?

What

As for the outsourcing sterile compounders that have voluntarily registered with the FDA, they are now subject to the rules of the Drug Quality and Security Act (DQSA) (H.R. 3204), which was signed into law by President Obama in November 2013 (see Pharmacy Practice News December 2013, page 1). Such facilities are expected to follow U.S. Pharmacopeial Convention (USP) Chapter <797> standards and are held to the same good manufacturing practices (GMPs) as large pharmaceutical manufacturers.

Although that high bar may be reassuring to purchasers and patients, it also might be scaring away outsourcing compounders that would potentially qualify under the new outsourcing facility category, according to Tom Van Hassel, RPh, MPA, the director of pharmacy at Yuma Regional Medical Center, in Yuma, Ariz., and former president of the Arizona State Board of Pharmacy. “People are reluctant to register with the FDA because they fear the possibility that the agency will come in and shut them down,” he said.

“The FDA has tremendous power.”

Mr. Van Hassel said most facilities that could qualify as outsourcing compounders will do so only if they are forced to, or if doing so would help them gain a market advantage. If more purchasers choose FDA-registered compounders, he noted, the reluctant majority also might opt to register.

State Boards Tighten their Grip

Enroll E nroll today today Release Date: May 9, 2013

www.REMEDIESCME.com

Expiration Date: May 9, 2014

AMA PRA Category 1 CreditsTM For information about the accreditation of this program, please contact Global at (303) 395-1782 or inquire@globaleducationgroup.com Jointly sponsored by Global Education Group and Applied Clinical Education

Supported by an educational grant from

The FDA and some state boards of pharmacy are actively promoting the benefits of registration. But states also have been working hard to meet a separate challenge that predates H.R. 3204: a lack of state resources available for policing sterile compounding facilities, noted Dr. Hartman, who is the senior director of clinical quality and patient safety at Wolters Kluwer Health, Pharmacy OneSource. “At the time of the NECC [crisis], our state board of pharmacy—and I think this is true of many state boards—was underfunded and did not have the appro-

Policy 27

Pharmacy Practice News • March 2014

Medication Safety priate board membership and training to carry out effective oversight,” he said.

“Compounding is an extremely complex process and the quality controls that have to be in place to make it safe are hard to identify, so facility inspectors need to have specialized training.”

Some relief has come as a result of the Special Commission on Compounding that Dr. Hartman chaired in 2012.

The commission, which was convened

by Massachusetts Gov. Deval Patrick, was charged with generating recommendations on statutory, regulatory and operational rules that would make compounding safer in that state. Following on the Special Commission’s recommendations, the state legislature increased the Massachusetts Board of Pharmacy’s budget from roughly $182,000 to $1.3 million.

Now the board has enough funding to train its staff and can carry out thorough inspections of facilities engaged in sterile compounding, Dr. Hartman said.

The Massachusetts state legislature also has handed the board more regulatory power to enforce manufacturing standards and it has put whistle-blower protection laws in place, so that “practitioners have the appropriate protections to raise alarm when facilities engage in unsafe practices,” he noted.

“I’m cautiously optimistic that the big compounding operations that could be involved in another NECC have now been identified,” Mr. Kastango said. “That’s half the battle—knowing who’s out there.”

‘State laws and efforts are moving in the right direction to ensure safer compounding. But they are not yet where they need to be.’

—Christian Hartman, PharmD, MBA these pharmacies were not doing what they claimed to be doing in their attestation,” he said.

The California Board of Pharmacy is also ramping up its enforcement efforts.

The board is expected to implement revised regulations on July 1, 2014, that

Filling the Communication Gap

are more closely aligned with requirements in USP Chapter <797>. The board also is providing specific training to its inspections on USP Chapter <797>. In the interim, California’s Department of Public Health has been busy inspecting pharmacies for USP <797> compliance.

Carmen Catizone, MS, RPh, DPh, the executive director of the NABP, said his organization is working diligently to address the gap in communication that was one of the root causes of the NECC catastrophe. “We’ve developed a single

•

see ANOTHER NECC?, page 28

Which is your favorite season?

Support Remains Uneven Unfortunately, not all state boards are receiving such support, according to Eric Kastango, RPh, MBA, the chief executive officer and president of Clinical IQ, LLC, a firm that provides training for compounding facility inspectors. In many states, he noted, “to change their pharmacy laws they need an act of legislature, and if you can’t get a sponsor who really cares or sees the need to make these changes, it can be a slow process.”

Nevertheless, Mr. Kastango said most state legislatures and boards of pharmacy are addressing the issue in “a systematic and multi-tiered way, which is exactly what we need them to do. In fact, I’ve been incredibly impressed with the veracity with which many of the big states have been [pursuing] this issue.”

For example, some state boards of pharmacy that until now have allowed compounders to operate without following USP Chapter <797> standards are working with legislators to put such a requirement in place, Mr. Kastango noted. And in states such as New Jersey and Massachusetts, boards of pharmacy have been flexing their new regulatory muscles, requiring licensees to complete attestations and following up with systematic audits by their newly trained inspectors or contracting out the survey process to the NABP. “I believe that at least six pharmacies received temporary cease and desist orders issued by the Attorney General’s office in New Jersey over the past several months because

WINTER

SPRING

SUMMER

PROPOFOL

At SAGENT we can supply you all year long!

PROPOFOL Injectable Emulsion USP 1%

www.SagentPharma.com All trademarks herein are the property of Sagent Pharmaceuticals, Inc.

©2014 Sagent Pharmaceuticals, Inc. 1852

T-11676

28 Policy

Pharmacy Practice News • March 2014

Medication Safety

ANOTHER NECC?

‘We’ve developed a single Web portal that state boards can access and where they can find all the information collected and housed on pharmacies across the country, including inspection reports on compounders.’

continued from page 27

Web portal that state boards can access and where they can find all the information collected and housed on pharmacies across the country, including inspection reports on compounders,” Dr. Catizone said. “State boards can now send their inspection reports in to the NABP and we immediately notify other states where that pharmacy is licensed or registered, as well as the states into which it supplies drugs.”

—Carmen Catizone, MS, RPh, DPh The NABP is also building a website by the end of 2014 which will list much of this information. The site “will include a list of non-FDA–registered compounders

and their inspection reports, when available,” Dr. Catizone noted.

Mr. Van Hassel agreed that the issue of interorganizational communication is a

priority area that needs to be addressed.

“At the time of the NECC crisis, there was really poor communication in every direction, between the FDA and individual boards of pharmacy, between boards of pharmacy in different states, and between the NABP and its state boards of pharmacies,” Mr. Van Hassel said. He thus commended the NABP for working with individual boards of pharmacy to develop the portal for sharing information.

Based on these and other actions recently taken by the NABP and state boards, “Everything is moving in the right direction to improve the quality and safety of compounded products,” Mr. Van Hassel stressed.

Progress, Not Perfection As the combined efforts of so many stakeholders continue to take shape,

Rationale, Reversal, and Recovery of Neuromuscular Blockade Part 1: Framing the Issues Case Study Harold is a 74-year-old man undergoing a video-assisted right upper lobectomy for stage I non-small cell lung cancer.

Current Symptoms • Dyspnea • Coughing with hemoptysis • Chest pain Vital Signs • Height: 177.8 cm (70”) • Weight: 65 kg (143 lb) Signi¿cant Medical History • Hypertension • Chronic obstructive pulmonary disease (moderate) Current Medications • Metoprolol succinate ER 50 mg/d • Tiotropium bromide inhalation powder Laboratory Results • 2-cm lesion in right upper lobe revealed on chest computed tomography (CT) scan; malignancy con¿rmed with needle biopsy • No abnormal bronchopulmonary or mediastinal lymph nodes; brain CT, isotopic bone scan, abdominal ultrasonography negative for distant metastases • Forced expiratory volume in the ¿rst second: 43.6% of predicted value (1.44 L) • Carbon monoxide diffusing capacity: 71.7% of predicted values (20.19 mL/min/mmHg) • Cardiac ultrasonography: normal pulmonary artery pressure (22 mm Hg) At induction, Harold receives propofol 1.5 mg/kg and rocuronium 0.6 mg/kg. During the procedure, movement of the diaphragm interferes with surgery.

This activity is jointly sponsored by Global Education Group and Applied Clinical Education.

Supported by an educational grant from Merck.

Applied Clinical Education is pleased to introduce a new interactive 3-part CME series featuring challenging cases in neuromuscular blockade.

Each activity will present a clinical scenario that you face in your daily practice. After reading the introduction to the case, consider the challenge questions, and then visit www.CMEZone.com/nmb1 to ¿nd out how your answers stack up against those of our multidisciplinary faculty panel.

Access the activities on your desktop, laptop, or tablet to explore the issues surrounding safe, effective, neuromuscular blockade and reversal via a unique multimedia learning experience and earn 1.0 AMA PRA Category 1 Credit.™ Participate in the coming months as well to complete the whole series and earn a total of 3.0 AMA PRA Category 1 Credits.™ This activity’s distinguished faculty Jon Gould, MD Glenn S. Murphy, MD Chief, Division of General Surgery Alonzo P. Walker Chair in Surgery Associate Professor of Surgery Medical College of Wisconsin Senior Medical Director of Clinical Affairs Froedtert Hospital Milwaukee, Wisconsin

Clinical Professor, Anesthesiology University of Chicago Pritzker School of Medicine Director Cardiac Anesthesia and Clinical Research NorthShore University HealthSystem Evanston, Illinois

Challenge Questions 1. What would you do next?

2. What potential postoperative risks does this patient face?

Access this activity at www.cmezone.com/nmb1

More Details On Form 483s

E

leven of the 13 sterile compounding outsourcers that have registered with, and been inspected by, the FDA were issued Form 483s.

The following conditions were among those specified in the Forms: ✔ “The production area air supply lacks an appropriate air filtration system.” ✔ “Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established. Specifically, there is no sterile filtration performed during the aseptic processing of sterile injectable drug products.” ✔ “We noted a rust colored build up of material behind the HEPA filter screen near the screen retaining bolts of hood #13.” ✔ “Laboratory controls do not include the establishment of scientifically sound and appropriate test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality and purity.” ✔ “Failure to utilize positive and negative controls or conduct growth promotion testing for the microbiological growth media used in the [REDACTED] monitoring of laminar airflow hoods, personnel glove monitoring, environmental monitoring, and media fills.” ✔ “Failed to investigate an estimated 22 lots with discrepant results for microbial testing. For ‘inconclusive’ results, your firm does not have an investigation, rationale or justification to support that these results are not sterility failures.”

According to the FDA, issuance of a Form 483 “does not constitute a final agency determination of whether any condition is a violation of the FD&C Act or any of its relevant regulations.”

Policy 29

Pharmacy Practice News • March 2014

Medication Safety ‘I’m cautiously optimistic that the big compounding operations that could be involved in another NECC have now been identified. That’s half the battle— knowing who’s out there.’

—Eric Kastango, RPh, MBA th he prescribing practitioner has determined that a compounded product is m necessary for the particular patient and n would provide a significant difference w .... as compared with the FDA-approved ccommercially available drug product.”

Mr. Kastango said sterile compounding is a risky process no matter how

purchasers looking for outsourced compounded drugs are still left wondering where to turn for reliably safe products.

“Ideally, you would only use drugs made by large drug manufacturers,” Mr. Van Hassel said. “These are consistently the highest-quality products—period.”

Many hospitals are choosing a different path—that is, to control their own quality processes and compound sterile products in-house, Mr. Van Hassel noted. However, the expense of doing so can be prohibitive, with construction of a clean room that meets USP Chapter <797> standards costing about $500,000, he pointed out, and the additional staff, materials and training present further costs. Even then, there is no guarantee of sterility.

“It’s a very detailed process,” Mr. Van Hassel emphasized.

He added a word of caution to hospitals that balk at such challenges and thus decide to continue purchasing products from outside compounding pharmacies: don’t solely rely on state and federal inspections as a basis for vendor selection. As thorough as those inspections might be, “If you’re using [an outsourcing] compounder, develop a formal relationship with them and go inspect their plants, get their FDA and board of pharmacy reports, and make sure you’re comfortable with their practice.”

The ASHP Foundation has developed a “Contractor Assessment Tool” for evaluating outsourcing compounders. The document can be accessed at http://bit.ly/MUcirp.

Still, no vetting process is fail-safe. In a statement to Pharmacy Practice News, the FDA said, “Purchasers of drugs compounded at a registered outsourcing facility that has had a recent satisfactory FDA inspection will have some assurance that the conditions at that facility met applicable standards at the time of the inspection … [however], FDA inspections are a snapshot in time, and conditions can change at any time.”

Like Mr. Van Hassel, the agency recommended using original FDA-approved medications if they are available, “unless

well it is regulated or how well suppliers are vetted. “As long as you’re taking things and aseptically manipulating them and as long as people are involved, there’s always the risk of contamination,” he said. “But with USP [Chapter] <797> compliance, proper inspections by trained individuals and adequate over-

Do more with less.

Cardinal Health Drug Cost Control Solution As you are forced to do a lot with a little, you want to make sure you use the right tool for the job. The Cardinal Health Drug Cost Control Solution achieves cost savings for hospitals and can significantly improve patient outcomes and decrease lengths of stay. Through the use of analytics to benchmark drug utilization by physician and DRG, we help hospitals implement and achieve savings of threeto-five percent — or more — on annual pharmaceutical expenses.

1.877.300.9180 cardinalhealth.com/innovativedeliverysolutions Call today to learn how to do more with less.

© 2014 Cardinal Health. All rights reserved. CARDINAL HEALTH, the Cardinal Health LOGO, and ESSENTIAL TO CARE are trademarks or registered trademarks of Cardinal Health.

All other marks are the property of their respective owners. Lit. No. 1ACP14-10659 (02/2014)

sight, the lion’s share of the risk can be mitigated out of the process.”

—David Wild Drs. Hartman and Catizone and Mr. Van Hassel reported no relevant financial conflicts of interest.

30 Operations & Management

Pharmacy Practice News • March 2014

Leadership ‘It was a big deal for the pharmacists to get comfortable with the fact that they were basically writing orders.’

BIG PAYOFF continued from page 1

Storytelling helped Mr. Couldry and his colleagues win organizational buyin for a new pharmacy-led medication reconciliation program that called for the addition of 12 full-time equivalents (five pharmacists, three residents and four technicians) and highlighted the pharmacy’s impact on reported quality outcomes.

The program integrated medication reconciliation into care transitions and pharmacists’ daily work, which enabled nurses and physicians to focus more on direct care and improving communication with patients about their medication.

The pharmacy-driven process provides tiered levels of support based on readmission risk, medication therapy complexity and individual patient needs, Mr. Couldry noted. Levels of support range from electronic reconciliation only, to individualized teaching with a personalized medication calendar.

In presenting the practice change proposal to leadership, Mr. Couldry related the case of a 51-year-old man with multiple chronic conditions for whom the clinical pharmacist made 19 changes to the medical record on admission, including six missing medications, eight incorrectly dosed drugs and five medications, listed as active, that the patient was no longer taking. The audible gasp when he told this story signaled that “I had made an emotional connection with most of the nurses and physicians in the room about what pharmacists do that’s important.”

According to Mr. Couldry, the proposed practice change initially generated

—Rick Couldry, MS, FASHP

concern among the pharmacists about their ability to handle the work. These concerns were allayed with the development of a system of shared responsibilities among all members of the pharmacy team. “The pharmacists oversee patients and coordinate services, pharmacy residents visit patients and perform the medication reconciliations, and pharmacy technicians and students provide support as needed,” he explained.

The medication reconciliation program has led to “transformational change in our thought process as clinicians,” Mr. Couldry said. The hospital’s electronic medical records system now allows pharmacists to make recommendations, correct dosages and perform other tasks before the physician sees the patient’s record. The process streamlines discharge, and physicians appreciate the pharmacists’ involvement, he noted.

“It was a big deal for the pharmacists to get comfortable with the fact that they were basically writing orders,” but they have adjusted, Mr. Couldry said.

As long as the physician signs off on the orders, the process falls within the bounds of pharmacy practice, he added.

Pharmacists now prepare orders as soon as they know a patient will be going home in 24 to 48 hours. “We no longer have to drop what we’re doing. That was a big practice model change for us.”

As a result of the increased focus on that new practice model, capture rates for pharmacist-completed admission histories and pharmacist-supported discharges (e.g., orders and patient education) soared: At baseline, in September 2012, the capture rate for those admission and discharge efforts was 22% and 0%, respectively. In June 2013, the rates increased to 94.4% and 80.7%, respectively, Mr. Couldry reported.

The pharmacy also found compelling data to show the program’s value after seven months. Although Hospital Consumer Assessment of Healthcare Providers and Systems scores for medication communication did not change, patient satisfaction with the discharge process rose from 62.5% in October 2012 to 92% in April 2013 (percent answering “always” to the question: “During this hospital stay, did you get information in writing about what symptoms or health problems to look out for after you left the hospital?”).

“Our organization has been able to determine no other significant change in the discharge process except for our medication reconciliation process change,” Mr. Couldry said. He added that compliance with the meaningful use standard for medication reconciliation increased from 78% at baseline to 95%.

25 September 2012 (baseline)

22.45

April 2013

Readmission Rate, %

20

18 97 18.97

19 4 19.4 17.33

16.67

16.67

15.91

15

10

5

4.35

0 Acute Myocardial Infarction

Chronic Obstructive Pulmonary Disease

Heart Failure

Pneumonia

Improvements in 30-day hospital readmission rates also were seen in several complex diseases, including acute myocardial infarction (18.97% at baseline vs. 4.35% in April 2013), heart failure (22.45% vs. 16.67%), pneumonia (19.4% vs. 16.67%) and chronic obstructive pulmonary disease (17.3% vs. 15.91%; Figure).

The pharmacy department engaged the hospital’s communications staff to deliver messages about the program through multiple channels, including email and Twitter. “Don’t overlook the importance of communication,” he stressed.

Embracing Specialty Pharmacy Mr. Couldry also reviewed the University of Kansas Hospital’s development of an oncology specialty pharmacy that generated $8 million in new revenue between September 2012 and June 2013, and garnered high satisfaction ratings from providers and patients. Noting that spending on specialty medications is likely to increase by 67% through 2015, he said specialty pharmacy is “a burning platform” for health-system pharmacists.

Although it can be a “tough sell” to senior leadership because of the sizable investment involved, specialty pharmacy holds enormous potential for health systems, according to James A. Jorgenson, RPh, MS, FASHP, the president of Hospitals & Health Systems for Visante, Inc., a consulting firm in St. Paul, Minn. “When you look at the definition of specialty pharmaceutical, it’s for complex patients with high-cost drugs. Those are exactly the patients that we’re concerned about with readmission. Why would I want to leave the care of patients to a whole variety of different providers while I’m on the hook for the readmission?” Mr. Jorgenson said, referring to Medicare payment cuts that are levied against hospitals that exceed targed readmission rates.

He noted lack of experience in the billing and reimbursement intricacies associated with specialty pharmacies as one of the key challenges facing many health systems. “It’s a lot more complex,” he said.

The evolving health care environment offers “a tremendous opportunity for us to be entrepreneurs to help our organizations take care of our patients and drive revenue to the hospital,” Mr. Couldry said. The key is to “step outside your comfort zone” in bringing pharmacy’s critical but often underappreciated contributions to the fore.

—Susan Birk Mr. Couldry and Mr. Jorgenson reported no relevant financial conflicts of interest.

COMING SOON: Figure. 30-Day readmission rates for core-measure patients.

More details on the University of Kansas Hospital’s specialty pharmacy build-out.

ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE

UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT UNIT

ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE

DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE DOSE

ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE ONE

AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND AND

ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY ONLY

0.5 mL each

An Innovative Non-Aerosol Unit Dose Topical Anesthetic Spray r .FFUT +PJOU $PNNJTTJPO 4UBOEBSE GPS UIF NPTU SFBEZ UP BENJOJTUFS GPSN BWBJMBCMF r 'BTU POTFU 4IPSU EVSBUJPO 7JSUVBMMZ OP TZTUFNJD BCTPSQUJPO r 6UJMJ[FT CBS DPEF NFEJDBUJPO BENJOJTUSBUJPO #$."

UP BDDPNNPEBUF QPJOU PG DBSF TDBOOJOH r 7JSUVBMMZ FMJNJOBUFT BEWFSTF FWFOUT SFTVMUJOH GSPN QSFWFOUBCMF NFEJDBUJPO FSSPST FOTVSJOH UIF i 3JHIUTu BSF NFU â&#x2C6;&#x161; 3JHIU %SVH â&#x2C6;&#x161; 3JHIU 1BUJFOU â&#x2C6;&#x161; 3JHIU %PTF â&#x2C6;&#x161; 3JHIU 3PVUF â&#x2C6;&#x161; 3JHIU 5JNF r 4JOHMF VOJU PG VTF QBDLBHJOH FMJNJOBUFT UIF QPUFOUJBM GPS DSPTT DPOUBNJOBUJPO r *ODSFBTFT CJMMJOH BDDVSBDZ BOE JNQSPWFT TVQQMZ DIBJO DPTUT ORDERING INFORMATION NDC#

AMERISOURCE BERGEN

CARDINAL HEALTH

MCKESSON

MORRIS & DICKSON

PRODUCT

$*/

)VSSJ$BJOF 0/&® 6OJU %PTF /PO "FSPTPM 4QSBZ #PY PG GM P[ N- FBDI

$*/

)VSSJ$BJOF 0/& 6OJU %PTF /PO "FSPTPM 4QSBZ #PY PG GM P[ N- FBDI

*G )VSSJ$BJOF 0/& JT OPU ZFU BWBJMBCMF UISPVHI ZPVS XIPMFTBMFS SFRVFTU JU CZ OBNF BOE /%$ /VNCFS +PJOU $PNNJTTJPO 4UBOEBSE .. &1

MAKE THE SWITCH TODAY. LLC

$BMM UP QMBDF ZPVS PSEFS PS SFRVFTU NPSF JOGPSNBUJPO XXX CFVUMJDI DPN )VSSJ$BJOF 0/& JT B SFHJTUFSFE USBEFNBSL PG #FVUMJDI® 1IBSNBDFVUJDBMT --$ )$0"

BD PhaSeal™ Closed System Transfer Device Protection Across the Continuum of Care

The BD PhaSeal™ System has been proven to prevent exposure to contents of hazardous drug vials during preparation, administration, and disposal.*

Take a closer look at the first FDA cleared CSTD indicated to reduce exposure to hazardous drugs

• Hazardous Drug protection throughout the continuum of care

• Protects the microbial state of vial contents** and cuts drug waste

• Reduces administrative admin nistrative burden of drug shortages to fo ocus on patient care

file at BD ** For drugs indicated as stable, a compounding pharm macy using the BD PhaSeal System and following g USP <797> may choose to use the vial contents for up to 168 hours. Follow your institution’s policies and USP <797> practice standards for compounding g sterile preparations in pharmacy.

BD, BD Logo and BD PhaSeal are trademarks of B Becton, Dickinson and Company. ©2014 BD. MSS0452 (10/13)

BD Medical 1 Becton Drive Franklin Lakes, N NJ 07417 www.bd.com/ph haseal