January 2014

The Pharmacist’s News Source

pharmacypracticenews.com

Volume 41 • Number 1 • January 2014

Printer-friendly versions available online

in this issue UP FRONT

3

Antibiotic, calcium channel blocker linked to kidney injury.

OPERATIONS & MGMT

4 9 13

High-cost cancer drugs point to a health care system in crisis.

Collaboration fuels a successful transition to CSTDs. Targeted medication reconciliation cuts 30-day readmissions.

CLINICAL

24 25 26

Liposomal bupivacaine boosts post-op pain relief.

Algorithm aims for safer, smarter codeine use.

Practice Pearl: a centralized approach to medication safety.

POLICY

28

What you need to know about the new OPPS payment rules.

EDUCATIONAL REVIEW

Immune Globulins: Therapeutic, Pharmaceutical, Cost, and Administration Considerations See insert after page 16.

Dashboard Tool Helps Avert Big Errors at VISN 21

Project IMPACT Extends Reach to High-Risk Patients

Orlando, Fla.—When a pharmacist-led committee at the Veterans Affairs Sierra Pacific Network (VISN 21) sat down to create an electronic health record (EHR)-based clinical Medication Safety Dashboard (MSD), they faced the unenviable task of sifting through roughly 400 EHR metrics and choosing the fraction they believed would lead to the widest improvements in safe medication use if targeted. As evidenced by the 113,000 patients spared potentially life-threatening drug-related complications during a three-year dashboard pilot period, their work has paid off.

The program’s success demonstrates that, although the sheer volume of “big data” can be overwhelming, managing and exploiting it can lead to striking outcomes, said William Owad, who presented the team with an American Society of HealthSystems Pharmacists (ASHP) Foundation Award for Excellence in Medication Use Safety at the 2013 ASHP

P

revious research initiatives such as the Asheville Project in North Carolina and the American Pharmacists Association (APhA) Foundation’s Project IMPACT studies have shown that when pharmacists assume a key role in empowering patients to manage their diabetes and other chronic conditions, patients’ health improves and the cost of care decreases.

But does the same pharmacistdriven model work for a large and far more challenging population, one that includes a high number of individuals who are mostly poor, uninsured and sometimes homeless? That was the question the APhA Foundation set out to explore three years ago, when it launched “Project IMPACT: Diabetes.”

It turned out that the answer was yes. Preliminary results released by the foundation showed that a group of more than 1,500 highrisk patients, many of them on

see BIG DATA, page 30

see IMPACT, T page 16

•

Med Rec Efforts Can Be Difference In Patient Safety Albuquerque, N.M.—Three studies presented at the American College of Clinical Pharmacy (ACCP) annual meeting offer fresh evidence that enlisting pharmacists in the medication reconciliation process can help patients avoid serious adverse drug events that prolong costly hospitalizations. In some cases, the interventions were deemed potentially life-saving.

One of the studies, a prospective,

•

see MED REC, page 14

•

A student pharmacist from Mountain States Health Alliance consults with a patient at Dispensary of Hope Pharmacy, a site of the Project IMPACT: Diabetes initiative.

In a Crystal Ball for Pharmacy, Profound Change Is a Constant Orlando, Fla.—A survey of pharmacy stakeholders from across the country suggests that health-system pharmacists should brace themselves for mounting financial pressures and expanding clinical responsibilities, among other big changes. The five-year Pharmacy Forecast, presented at the American Society of Health-System Pharmacists (ASHP) 2013 Midyear Clinical Meeting, also indicated that experts believe that hospital pharmacies will need to focus more on outpatient care and demonstrate their department’s influence on the hospital’s success.

David A. Zilz, MS, a clinical professor emeritus and former director of pharmacy at the University of Wisconsin Hospital and Clinics in Iola, said health-system pharmacy leaders need to develop and implement a strategic plan now more than ever. “Hospitals are being integrated into multihospital systems, and the model of care is changing from a siloed acute and community care approach to a longitudinal, continuum-ofcare model,” said Mr. Zilz, who moderated the ASHP session where the Pharmacy

•

see FORECAST, T page 22

New Product FDA Approves Sovaldi for Hepatitis C. See page 23.

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Up Front 3

Pharmacy Practice News • January 2014

Capsules

Antibiotic, Calcium Channel Blocker Combination Linked to Kidney Injury

P

atients who receive both clarithromycin and a calcium channel blocker are at increased risk for potentially fatal kidney injury, according to a recent study published online in the Journal of the American Medical Association (doi:10.1001/jama.2013.282426).

Researchers at the Western University, in London, Ontario, Canada, found that the coadministration of these drugs was associated with acute kidney injury, hypotension and an increase in overall mortality compared with patients who took azithromycin and a calcium channel blocker.

Clarithromycin, unlike azithromycin, is a potent inhibitor of the enzyme cytochrome P450 3A4 (CYP3A4). Amlodipine, diltiazem, verapamil and other calcium channel blockers also inhibit CYP3A4, and coadministration of these two enzyme inhibitors can lead to greatly decreased blood pressure—which, in turn, may result in kidney failure.

In a retrospective study of patient data obtained from the Ontario Drug Benefit Program database, which contains clinical information on every resident who

receives health care through Ontario’s governmental health insurance, the authors identified 96,226 patients who concurrently received clarithromycin and a calcium channel blocker. The 94,083 patients who were prescribed azithromycin and a calcium channel blocker provided a cohort for comparison. (The researchers did not include data for erythromycin treatments, which physicians in Ontario prescribe at less than one-twentieth the rate of clarithromycin.) Amlodipine was the most common calcium channel blocker used in both groups, prescribed to more than 50% of patients.

Although the overall risk was low, acute kidney injury was more common in the clarithromycin group than in those prescribed azithromycin (0.44% vs.

0.22%, respectively), with an absolute increased risk of 0.22% (95% confidence interval, 0.16%-0.27%).

Mortality among patients receiving clarithromycin therapy was almost twice as high as for azithromycin (1.02% vs. 0.59%, respectively).

On the label for clarithromycin, the FDA warns that bradyarrhythmias, hypotension and lactic acidosis

have been observed in patients who received concurrent verapamil. “It is concerning,” the study authors wrote, “that clarithromycin continues to be co-prescribed with calcium channel blockers despite previous studies” showing that there were problems. The researchers recommend that physicians prescribe an antibiotic that does not inhibit CYP3A4 when appropriate, or that patients hold their calcium channel blockers during clarithromycin treatment.

“For patients with mild-moderate hypertension, withholding the [calcium channel blocker] for a week or two would be unlikely to have a negative outcome,” said John Horn, PharmD, a professor of pharmacy at the University of Washington, in Seattle, who was not involved with the study. Patients taking calcium channel blockers for coronary artery disease or atrial fibrillation, however, should probably not interrupt their therapies, he said.

For those cases, the preferable option would be to use azithromycin or another antibiotic that does not inhibit CYP3A4 in place of clarithromycin.

—Ben Guarino

Table 1. Average Pain Scores in Patients Given Local Anesthetics Average Pain Scoresa

Group 1: 1% Lidocaine (n=50)

Group 2: 1% Buffered Lidocaine (n=50)

Group 3: 0.9% Bacteriostatic Normal Saline (n=50)

Overall (N=150)

Significance

Baseline

0.09

0.03

0.15

0.09

NS

Following anesthetic injection

2.81

1.64

2.05

2.10

P=0.023b 1 vs 2 = P<0.05 1 vs 3 = NS 2 vs 3 = NS

Following PIV insertion

1.81

1.81

3.05

2.19

P=0.005b 1 vs 2 =NSc 1 vs 3 = P<0.05c 2 vs 3 = P<0.05c

D

ue to a production error, the Table on page 19 of the December issue that accompanied the news article, “Reducing the Burn,” contained incorrect data.

The correct table appears on the right. The editors regret the error.

ANOVA, analysis of variance; HSD, honestly significant difference; NS, not significant; PIV, peripheral intravenous a

A difference of means of 1 in pain scores is considered clinically significant.

b

Kruskal-Wallis one-way ANOVA; P<0.05 is clinically significant.

c

Tukey Tukey’ss HSD test

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Volume 41 • Number 1 • January 2014 • pharmacypracticenews.com

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4 Operations & Management

Pharmacy Practice News • January 2014

Finance

Strategies To Rein in Oncology D Chicago—The staggering price tag of some oncology drugs points to a health care system that is out of control, the president of the Hematology/Oncology Pharmacists Association said at the group’s Inaugural Fall Practice Management Meeting.

Coupled with the added costs associated with chronic medication shortages, off-label medication use and unfunded regulatory mandates, hematology/oncology pharmacists have their hands full, Niesha Griffith, MS, RPh, FASHP, said. Ms. Griffith offered several strategies to help hematology/oncology pharmacists rein in these costs based on her experience as director of pharmacy and infusion services at the James Cancer Hospital (JCH) and Solove Research Institute at The Ohio State University, in Columbus.

Develop a high-dollar chemotherapy process. “Don’t just assume that because a medication is FDA-approved that the insurance company is going to pay for it,” Ms. Griffith said. JCH created a process to review patient benefits and determine coverage, which in some cases is assisted by the pharmaceutical company’s support program for the specific medication. “We also determine the patient’s financial obligation so we can let them know what to expect. This process not only helps us ensure payment, but, just as important, prevents any ‘expensive surprises’ for our patients.”

The addition of sipuleucel-T (Provenge, Dendreon) to the JCH formulary triggered the development of the hospital’s high-dollar chemotherapy process, according to Ms. Griffith. The hospital’s Hematology/Oncology Pharmacy & Therapeutics Subcommittee determines which agents will be managed under the program. This generally includes all medications costing more than $50,000 for a typical course of treatment. In addition to sipuleucel-T, the list currently includes ado-trastuzumab emtansine (Kadcyla, Genentech), omacetaxine mepesuccinate (Synribo, Cephalon), ipilimumab (Yervoy, Bristol-Myers Squibb), brentuximab (Adcetris, SeattleGenetics), eculizumab (Soliris, Alexion Pharmaceuticals) and pertuzumab (Perjeta, Genentech).

“The process enhances patient satisfaction,” Ms. Griffith noted. “Patients feel like they have some control over their treatment because they are involved in the decision making.” With the development of specific workflows for each medication at JCH, she added, “To date, there have been no write-offs for the medications when this process is used. Because of our investment in front-end resources, we are improving

our chances of getting paid for these very expensive medications.”

Be proactive to head off medication shortages. Ideally, such efforts should include a dedicated staff person who can stay on top of a “bread, butter and milk” list of agents with a history of shortages by keeping sufficient quantities on hand and stocking up before holidays, when some pharmaceutical manufacturers are known to stop production. “It’s been a different world for us having someone with responsibility for managing this,” she said.

Develop clear policies and processes for off-label medication use.

A multidisciplinary group of clinicians can best develop and oversee this process, Ms. Griffith noted. The goal here is to ensure that when off-label medications are used, it is done in a manner that is supported by clinical evidence and compendia, Ms. Griffith noted. The system should also seek payor approval when possible and peer review as necessary. “Without the appropriate buyin and institutional support, addressing off-label use can be a difficult task and lead to uncomfortable situations for pharmacists,” she said. “It’s important to communicate that safety and effectiveness are as much a consideration as cost and reimbursement.”

This type of program takes time to effectively implement and requires a significant amount of education and communication with the medical staff, Ms. Griffith added. As a result of those efforts at JCH, “our physicians are familiar with the policy and process and let us know in advance, as soon as they are considering prescribing an offlabel use,” she said.

In terms of specific steps involved, one of the first is for a physician to send a request for an off-label use to a clinical specialist pharmacist, who enters the request, the evidence-based literature and compendia support and the associated costs into a database.

“The physician’s main responsibility is to let us know they’re thinking of off label. We walk through the process, even if they’re only considering it, because sometimes it takes us up to two weeks to get approval from the payor,” Ms. Griffith said.

Entry of a request into the database triggers an email to the pharmacy director, the chair of the Hematology/Oncology Pharmacy & Therapeutics committee and dedicated nurses in the finance department. A nurse then contacts the payor to request predetermination (approval for off-label use) and reports the result back to the patient care team.

If the request is not approved, the clinical specialist pharmacist contacts one

of the medication assistance staff to determine availabillity of support programs for off-llabel use. If the payor does not approve the request (and a support program is not an option), the off-label use is then peer-reviewed by the disease-specific lead physician. p “If the lead says yees, then the head of the [hemaatology or oncology] division must m also approve,” Ms. Grifffith said.

“I get involved in almost all of the high-dol-

‘This process not only helps us ensure payment, but, just as important, prevents any “expensive surprises” for our patients.’

—Neisha Griffith, MS, RPh lar requests. Some also involve our chief financial officer.”

According to Ms. Griffith, the requests that involve peer review are few and far between. Because this system for vetting high-cost off-label medication use has been in place for several years “our physicians usually have a good understanding of the data and whether an off-label use is going to be covered,” she noted.

“Regardless, we go to the ends of the earth to get these medications paid for if we think it’s the right thing to do, even if it means writing it off, Ms. Griffith said, adding that “because we have such robust infrastructure in place, we actually have few denials and don’t write off very much [off-label therapy].”

Treatment plans at JCH containing off-label indications are clearly labeled as such to ensure adherence to the offlabel approval process, she added.

Standardize the ordering of medications. Standardizing the ordering of chemotherapy and supportive care can have a significant effect on the ability to control medication costs (including the use of off-label medications noted above), Ms. Griffith said. “As you move to electronic ordering, premedications and supportive care drugs that are specific to a regimen and reflective of your institutional guidelines can be built into comprehensive treatment plans.”

Make full use of medication assistance programs. Ms. Griffith recommends having dedicated staff that can navigate the complexities of the different assistance programs and effectively communicate the details of those prograns to patients and clinical staff. The individuals supporting these activities don’t have to

be pharmacists, she noted. At JCH, the medication assistance coordinators who handle these responsibilities have backgrounds as pharmacy technicians, social workers and financial counselors. However, because these staff members are likely to receive and transport medications, it is important to know whether your state regulations allow a medication assistance program to operate that is not supported by the pharmacy department.

In addition to programs that provide free medications for qualified patients, copay assistance foundations are available to help the underinsured. “With changes in health care, this patient population is likely to grow, further supporting the need for dedicated personnel to assist patients with accessing these programs,” she said.

Limit waste associated with compounding of high-cost chemotherapy products. Strategies that can be used include dose-rounding, standardizing administration times and use of closedsystem transfer devices to extend the expiration dating for chemotherapy single-dose vials up to seven days.

Educate your pharmacists about payor rules. “Most pharmacists never expected to become experts in accessing CMS [Centers for Medicare & Medicaid Services] coverage determinations, navigating various compendia or learning payor requirements, but if you work in oncology today, it’s becoming unavoidable,” Ms. Griffith said.

Make judicious use of personnel resources. Pharmacists don’t have to do everything in the pharmacy department.

“All of our budgets are being scrutinized because of our expensive medications

•

see STRATEGIES, page 8

40 g

Largest Vial Size Availablle !

In IVIg therapy

Privigen 40 g: An added measure of convenience Ready-to-use 10% IVIg liquid Simple choice s Provides the largest vial size of IVIg available

Simple storage s Occupies less shelf space than two 20-g cartons for more efďŹ cient storage

Simple administration s Reduces the number of vials to open and handle for infusions of 40 g or more

Important Safety Information Privigen is indicated as replacement therapy for patients with primary immunodeďŹ ciency (PI) associated with defects in humoral immunity, including but not limited to common variable immunodeďŹ ciency (CVID), X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeďŹ ciencies. Privigen is also indicated to raise platelet counts in patients with chronic immune thrombocytopenic purpura (ITP).

WARNING: THROMBOSIS, RENAL DYSFUNCTION AND ACUTE RENAL FAILURE t 5ISPNCPTJT NBZ PDDVS XJUI JNNVOF HMPCVMJO QSPEVDUT JODMVEJOH 1SJWJHFO 3JTL GBDUPST NBZ JODMVEF BEWBODFE BHF QSPMPOHFE JNNPCJMJ[BUJPO IZQFSDPBHVMBCMF DPOEJUJPOT IJTUPSZ PG WFOPVT PS BSUFSJBM UISPNCPTJT VTF PG FTUSPHFOT JOEXFMMJOH WBTDVMBS DBUIFUFST IZQFSWJTDPTJUZ BOE DBSEJPWBTDVMBS SJTL GBDUPST t 3FOBM EZTGVODUJPO BDVUF SFOBM GBJMVSF PTNPUJD OFQISPTJT BOE EFBUI NBZ PDDVS XJUI UIF BENJOJTUSBUJPO PG IVNBO JNNVOF HMPCVMJO JOUSBWFOPVT *(*7 QSPEVDUT JO QSFEJTQPTFE QBUJFOUT 3FOBM EZTGVODUJPO BOE BDVUF SFOBM GBJMVSF PDDVS NPSF DPNNPOMZ JO QBUJFOUT SFDFJWJOH *(*7 QSPEVDUT UIBU DPOUBJO TVDSPTF 1SJWJHFO EPFT OPU DPOUBJO TVDSPTF t 'PS QBUJFOUT BU SJTL PG UISPNCPTJT SFOBM EZTGVODUJPO PS SFOBM GBJMVSF BENJOJTUFS 1SJWJHFO BU UIF NJOJNVN EPTF BOE JOGVTJPO SBUF QSBDUJDBCMF &OTVSF BEFRVBUF IZESBUJPO JO QBUJFOUT CFGPSF BENJOJTUSBUJPO .POJUPS GPS TJHOT BOE TZNQUPNT PG UISPNCPTJT BOE BTTFTT CMPPE WJTDPTJUZ JO QBUJFOUT BU SJTL GPS IZQFSWJTDPTJUZ 4FF GVMM QSFTDSJCJOH JOGPSNBUJPO GPS DPNQMFUF CPYFE XBSOJOH Privigen is contraindicated in patients with history of anaphylactic or severe systemic reaction to human immune globulin, in patients with hyperprolinemia, and in IgA-deďŹ cient patients with antibodies to IgA, who have had hypersensitivity reactions. Patients with IgA deďŹ ciency and antibodies to IgA are at greater risk of severe hypersensitivity and anaphylactic reactions.

In patients at risk for developing acute renal failure, monitor urine output and renal function, including blood urea nitrogen and serum creatinine; discontinue if renal function deteriorates. Ensure that patients with preexisting renal insufďŹ ciency or otherwise predisposed are not volume-depleted and administer Privigen at the minimum rate of infusion practicable.

Thrombosis might occur with Privigen, even in the absence of known risk factors. Patients could also experience hyperproteinemia, increased serum viscosity, or hyponatremia; infrequently, aseptic meningitis syndrome (AMS) may occurâ&#x20AC;&#x201D;more frequently with high doses (2 g/kg) and/or rapid infusion.

Hemolysis, either intravascular or due to enhanced red blood cell sequestration, can develop subsequent to treatment. Risk factors include non-O blood group, underlying inďŹ&#x201A;ammation, and high doses.

Closely monitor patients for hemolysis and hemolytic anemia. Consider the relative risks and beneďŹ ts before prescribing high-dose regimen for chronic ITP in patients at increased risk of thrombosis, hemolysis, acute kidney injury or volume overload. Monitor patients for pulmonary adverse reactions and signs of transfusion-related acute lung injury (TRALI).

Privigen is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.

In clinical studies of patients being treated with Privigen for PI, the most common adverse reactions observed in >5% of subjects were headache, fatigue, nausea, chills, vomiting, back pain, pain, elevated body temperature, abdominal pain, diarrhea, cough, stomach discomfort, chest pain, joint swelling/effusion, inďŹ&#x201A;uenza-like illness, pharyngolaryngeal pain, urticaria, and dizziness. Serious adverse reactions were hypersensitivity, chills, fatigue, dizziness, and increased body temperature.

In clinical studies of patients being treated with Privigen for chronic ITP, the most common adverse reactions seen in >5% of subjects were headache, elevated body temperature, positive DAT, anemia, nausea, epistaxis, vomiting, increases in conjugated and unconjugated bilirubin, decreased hematocrit, and increased blood lactate dehydrogenase. A serious adverse reaction was aseptic meningitis syndrome (AMS).

Treatment with Privigen might interfere with a patientâ&#x20AC;&#x2122;s response to live virus vaccines and could lead to misinterpretation of serologic testing. Use in pregnant women only if clearly needed.

In patients over 65 or in any patient at risk of developing renal insufďŹ ciency, do not exceed recommended dose and infuse Privigen at the minimum rate practicable.

1MFBTF TFF CSJFG TVNNBSZ PG QSFTDSJCJOH JOGPSNBUJPO GPS 1SJWJHFO JODMVEJOH CPYFE XBSOJOH PO BEKBDFOU QBHF Privigen is manufactured by CSL Behring AG and distributed by CSL Behring LLC. Privigen is a registered trademark of CSL Behring AG. Š2013 CSL Behring LLC 1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA www.CSLBehring-us.com www.Privigen.com PVG13-11-0038

12/2013

6 Operations & Management

Pharmacy Practice News • January 2014

Leadership in Action

The Power of Your Thinking I

n the past three articles we have looked at the relationship between our thinking—that is, our actual brain function—and how that process affects our creativity, productivity and leadership. We looked at the importance of paying attention and focusing on the relevant, inhibiting the distractions and using our working memory of relevant information to make decisions. We also looked at the importance of a positive

emotional climate and why connections to others are vital. In this article, I concentrate on those aspects you have controll over as a leader to get results with your staff.

Our Brains Thrive on Control There are certain aspects of health care that you as a pharmacy leader have no control over. The government determines our reimbursement for the

Privigen® Immune Globulin Intravenous (Human), 10% Liquid Initial U.S. Approval: 2007

BRIEF SUMMARY OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Privigen safely and effectively. See full prescribing information for Privigen.

WARNING: THROMBOSIS, RENAL DYSFUNCTION AND ACUTE RENAL FAILURE See full prescribing information for complete boxed warning. @ Thrombosis may occur with immune globulin products, including Privigen.

Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors. @ Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. Privigen does not contain sucrose. @ For patients at risk of thrombosis, renal dysfunction or renal failure, administer Privigen at the minimum dose and infusion rate practicable.

Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.

------------------------------------INDICATIONS AND USAGE---------------------------------Privigen is an Immune Globulin Intravenous (Human), 10% Liquid indicated for the treatment of: D Primary humoral immunodeficiency (PI) D Chronic immune thrombocytopenic purpura (ITP) -------------------------------DOSAGE AND ADMINISTRATION----------------------------Intravenous Use Only Indication PI

Dose

Initial Infusion Rate 0.5 mg/kg/min (0.005 mL/kg/min)

Maintenance Infusion Rate (as tolerated) Increase to 8 mg/kg/min (0.08 mL/kg/min)

200-800 mg/kg (2-8 mL/kg) every 3-4 weeks ITP 1 g/kg (10 mL/kg) for 0.5 mg/kg/min Increase to 4 mg/kg/min 2 consecutive days (0.005 mL/kg/min) (0.04 mL/kg/min) D Ensure that patients with pre-existing renal insufficiency are not volume depleted, and discontinue Privigen if renal function deteriorates.

D For patients at risk of renal dysfunction or thrombosis, administer Privigen at the minimum dose and infusion rate practicable.

--------------------------------DOSAGE FORMS AND STRENGTHS------------------------Privigen is a liquid solution containing 10% IgG (0.1 g/mL).

---------------------------------------CONTRAINDICATIONS ----------------------------------D History of anaphylactic or severe systemic reaction to human immune globulin

cost of care and drugs, as well as what is and is not covered. Pharmacy leaders deal with issues daily that are out of their control. Our response to the circumstances, however, is in our control. We must constantly think, given these conditions, about how pharmacy can advance the care of patients and the profession of pharmacy. The real question for you as a leader is how to give the people in your department a

D Hyperprolinemia (Privigen contains the stabilizer L-proline) D IgA-deficient patients with antibodies to IgA and a history of hypersensitivity ------------------------------WARNINGS AND PRECAUTIONS------------------------------D IgA-deficient patients with antibodies to IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions.

D Monitor renal function, including blood urea nitrogen and serum creatinine, and urine output in patients at risk of developing acute renal failure.

D Thrombosis may occur with immune globulin products, including Privigen.

D Hyperproteinemia, increased serum viscosity, and hyponatremia may occur.

D Aseptic meningitis syndrome (AMS) may occur, especially with high doses or rapid infusion.

D Hemolysis that is either intravascular or due to enhanced red blood cell sequestration can develop subsequent to Privigen treatments. Risk factors for hemolysis include high doses and non-O blood group. Closely monitor patients for hemolysis and hemolytic anemia.

D Monitor patients for pulmonary adverse reactions (transfusion-related acute lung injury [TRALI]).

D Carefully consider the relative risks and benefits before prescribing the high dose regimen (for chronic ITP) in patients at increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload.

D Privigen is made from human blood and may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

------------------------------------ADVERSE REACTIONS------------------------------------D PI – The most common adverse reactions, observed in >5% of study subjects, were headache, fatigue, nausea, chills, vomiting, back pain, pain, elevated body temperature, abdominal pain, diarrhea, cough, stomach discomfort, chest pain, joint swelling/ effusion, influenza-like illness, pharyngolaryngeal pain, urticaria, and dizziness. Serious adverse reactions were hypersensitivity, chills, fatigue, dizziness, and increased body temperature.

D Chronic ITP – The most common adverse reactions, observed in >5% of study subjects, were headache, elevated body temperature, positive direct antiglobulin test (DAT), anemia, nausea, epistaxis, vomiting, blood bilirubin unconjugated increased, blood bilirubin conjugated increased, blood total bilirubin increased, hematocrit decreased, and blood lactate dehydrogenase increased. A serious adverse reaction was aseptic meningitis.

To report SUSPECTED ADVERSE REACTIONS, contact CSL Behring Pharmacovigilance at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

----------------------------------DRUG INTERACTIONS--------------------------------------The passive transfer of antibodies may: D Lead to misinterpretation of the results of serological testing.

D Interfere with the response to live virus vaccines.

----------------------------USE IN SPECIFIC POPULATIONS--------------------------------D Pregnancy: No human or animal data. Use only if clearly needed.

D Geriatric: In patients over age 65 or in any patient at risk of developing renal insufficiency, do not exceed the recommended dose, and infuse Privigen at the minimum rate practicable.

Based on November 2013 revision.

“Leadership in Action” is authored by Ernest R. Anderson Jr., MS, RPh, of Brockton, Mass.

Mr. Anderson welcomes your input on leadership issues, at ernestanderson1130 @gmail.com

Ernest R. Anderson Jr., MS, RPh

sense of what is in their control and then let them run with it. According to Dr. Henry Cloud in his book “Boundaries for Leaders” (HarperCollins 2013), neuroscience has shown that the more experiences we have of being in control, the better our higher brain functions. The converse is also true. When we feel out of control by the circumstances around us and cannot regain control, our brains slow down and creativity is lost.

Thus, our role as a leader of others is to give them control within set boundaries for them to thrive. Too often leaders stifle their employees’ creativity and resourcefulness by their top–down approach of telling people what to do and how to think. Great leaders want to give away control to their employees to drive the appropriate outcomes. This becomes an upward spiral.

Let’s take the example of an accountable care organization (ACO) that is focused on population-based patient care in the “right” location, delivered at the highest quality and at the lowest cost. Let’s assume that the ACO is seeing inpatient census reduced as patients are shifted to other locations for care within the system. There also are quality metrics to incentivize reduced readmissions and emergency visits and to drive positive patient satisfaction scores. Inpatient pharmacists could be defeated or threatened by this new focus on ambulatory care, which is somewhat outside their sphere of influence and control. On top of that, administration may even be talking about reducing staff. As the leader, you must frame the issues differently, asking what you still have control over. What changes can be made to address the new needs of the ACO framework? The first

Operations & Management 7

Pharmacy Practice News • January 2014

Leadership in Action step is to make sure your staff understands the shift that is occurring, from a fee-for-service world, where more is better, to a mentality of high-quality patient care delivered in a low-cost environment.

Once staff understands that new focus, they can take control and address these issues in the new paradigm.

So, what are they likely to come up with in this scenario? With some initial guidance from you, perhaps they might suggest moving some of the inpatient pharmacists to the ambulatory setting in clinics or doctors’ offices to do direct patient care. Or they might propose performing medication reconciliation in patients’ homes or medication follow-up phone calls to patients post-discharge.

Perhaps it is the implementation of a new software that collects all the patients’ prescription data to determine those who are at the highest risk for adverse events, and who thus need to be contacted by the pharmacist or primary care physician. Developing the programs and the metrics to show the value of pharmacists in this new delivery system will enhance the care of patients and advance the practice of pharmacy.

This is by no means an exhaustive prescriptive solution, but a simple example of understanding that giving your staffers a sense of what is in their control breeds problem-solving; by giving them license to develop solutions, you can harness their creativity and the department will benefit accordingly.

Victims or Conqueror With all the pessimism in health care, it is easy to feel the victim and play the martyr. In “Boundaries for Leaders,” Dr. Cloud suggests actions that can be taken to move your department from the victim to the conqueror, no matter the issues, through a programmed approach.

Create connections. Relational support is critical to changing brain chemistry and moving into the higher cortical levels of thinking. This step allows people to acknowledge their struggles, find comfort in others with similar experiences and feel safe, but agree to move beyond the current state to solutions.

Regain control through “control divide.” First make a list of the items that you have no control over and that are making your business difficult. Next, take some time to think about the issues and worry about them for 10 minutes.

Set the list aside. On day 2 as a group do the same process. This allows the brain to comprehend “how bad it is.”

Next, circle the list and put a boundary around it, so that you can think about it no more. Now make a list of everything you do have control over. Focus on this list every day, making it a priority. This builds your working memory to allow you to behave in a positive, action-oriented way both as an individual and as

part of a group. First on the list may be something like, “show up to work with energy and optimism.” This is a choice we all can make. Empower people to take controll of the things they can controll that drive results.

Take control of your thinking patterns. Encourage people to be aware of their own thinking patterns through self-observation, logging these thoughts in a journal or even just cognitively, and then refuting each negative thought with a counter argument and taking action. These steps reverse

the sense of helplessness.

Add structure and accountability.

Social psychology research shows that when people assign a specific timeline to complete tasks and goals, their chances of success increase 300%. Our brains function at their highest levels when we have structure, stability, security, routine and predictability.

Take the right kind of action. Take actions that drive high performance and create results. Watch for behaviors in yourself and your staff that encourage positive outcomes.

Be Agents of Change Health care is all about change. Leaders have to assume the role of change agent, which requires a positive approach to be successful. Leaders must set their own strong boundaries against negativity and helplessness. Getting people to look at what they can control to produce results, while inhibiting activities and thinking that they have no control over, can move a department from stagnation to one with positive energy and creative results to advance patient care and the pharmacy profession.

■

For the Management of Postsurgical Pain

EXPAREL® (bupivacaine liposome injectable suspension)

Patient-Focused Pain Control That Lasts For Up To 72 Hours The only single-dose local analgesic to UÊ Reduce or eliminate opioids with pain control for up to 3 days UÊ Without the need for catheters or pumps

Pivotal studies have demonstrated the safety and efficacy of EXPAREL in patients undergoing bunionectomy and hemorrhoidectomy procedures.

The clinical benefit of the attendant decrease in opioid consumption was not demonstrated.

EXPAREL is a liposome formulation of bupivacaine indicated for administration into the surgical site to produce postsurgical analgesia.

Important Safety Information: EXPAREL is contraindicated in obstetrical paracervical block anesthesia. EXPAREL has not been studied for use in patients younger than 18 years of age. Non-bupivacaine-based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more. Other formulations of bupivacaine should not be administered within 96 hours following administration of EXPAREL. Monitoring of cardiovascular and neurological status, as well as vital signs should be performed during and after injection of EXPAREL as with other local anesthetic products. Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations. In clinical trials, the most common adverse reactions (incidence ≥10%) following EXPAREL administration were nausea, constipation, and vomiting.

Reference: Gorfine SR, et al. Dis Colon Rectum. Dec 2011;54(12):1552-1559.

Please see brief summary of Prescribing Information on reverse side.

For more information, visit www.EXPAREL.com ©2013 Pacira Pharmaceuticals, Inc., Parsippany, NJ 07054

EXP-AP-0039-201302

8 Operations & Management

Pharmacy Practice News • January 2014

Finance

STRATEGIES continued from page 4

and expensive staff,” she said. “Think about the activities being performed, qualifications needed to perform them and whether those activities really require a pharmacist.”

Significant Savings With Dedicated Clinical Staff Like JCH, the USC Norris Cancer Hospital (NCH), part of the University of Southern California’s Keck Medical Cen-

ter (KMC), in Los Angeles, clearly knows the value of a multipronged approach to cost management. One of the facility’s most successful efforts has been the creation of a clinically staffed department that focuses solely on obtaining thirdparty payor authorizations and interfacing with patient assistance programs—a strategy that yielded savings of $500,000 in its first year and $1.4 million within 2.5 years. The process, created by a pharmacist at the USC School of Pharmacy, also has reduced disputed claims from thirdparty payors ((Am J Health-Syst Pharm

2011;68:828-834). The program has since been expanded to the entire medical center, said Caroline Chellamy, PharmD, KMC’s director of ambulatory pharmacy services. According to Dr. Chellamy, the allocation of dedicated nursing staff to handle these complex and time-consuming tasks has freed pharmacists to focus more on patient care and to spend more of their time working at their level of training. “We don’t expect our pharmacists to become insurance experts.

We prefer that they stay focused on the patients,” she said.

The pharmacy works proactively to identify medication shortages as quickly as possible, keeps all clinical staff abreast of developments with a monthly newsletter, “Pharmacy Capsule,” and sends department heads frequent updates via email, Dr. Chellamy added.

“We’ve built in our own process improvements and checks to help reduce costs, but everything we do is centered on the patients,” Dr. Chellamy stressed. “We collaborate with the physicians and nurses so we get the right drug, regardless of payment structure.”

—Susan Birk Ms. Griffith disclosed that she has received consulting fees from Amgen, Celgene, Dendreon and Lilly. Dr. Chellamy reported no relevant financial conflicts of interest.

Industry News

A Letter from Bedford Labs Bedford Laboratories recently issued an “open letter” to the pharmacy industry, following the announcement that Ben Venue Laboratories, a manufacturer for the company, ceased production at the end of 2013. The full text of the letter follows.

S

ince opening our doors more than 20 years ago, everyone at Bedford Laboratories has shared a singular goal of meeting the needs of our customers and their patients as a leader in generic sterile injectables. Founded in 1993, Bedford Laboratories has grown to become a leading provider of generic sterile injectable medicines with a focus on acute-care hospitals, Group Purchasing Organizations (GPOs), oncology treatment centers and drug wholesalers. While we were disappointed to learn that Ben Venue Laboratories, one of our longest-standing manufacturers, will cease production by the end of 2013, Bedford will continue to provide products manufactured by Ben Venue and will distribute these products until that inventory is depleted. We will also continue to supply products manufactured by our other third-party manufacturing partners today and going forward. That will not change. A full and up-to-date list of products currently available can be accessed at www.bedfordlabs.com.

Bedford’s parent company, Boehringer Ingelheim, recognizes the importance of our portfolio of products, including some currently listed on the U.S. Food and Drug Administration’s Current Drug Shortages Index. As a result, we are actively exploring strategic options for Bedford and its product portfolio to help ensure that these critical medicines continue to EXP-AP-0020-201301

•

see BEDFORD LABS, page 29

Operations & Management 9

Pharmacy Practice News • January 2014

Safe Handling Nurse buy-in helps ease adoption of closed system transfer devices

Collaboration Is a Key to Success in CSTD Transitions N

urses need as much say and control as pharmacists over the selection and implementation of a closed drug transfer system if it is to be effective, several experts asserted. Ron Ozuna, PharmD, BCPS, clinical coordinator of Pharmacy Services at Doctors Hospital at Renaissance in Edinburg, Texas, led a team that recently transitioned to a preparation strategy that employed closed system transfer devices (CSTDs).

He said that, “ultimately, you need buyin from the end-users of CSTDs.” Similarly, Dr. Ozuna’s colleague, Gavino Garza, RPh, the director of pharmacy at Doctors Hospital at Renaissance, said that he believes pharmacists considering a closed system should solicit as much feedback from nursing staff as possible and address any of their concerns. “We found out our nurses were worried about the practicability and impact of CSTDs on their workflow,” Mr. Garza said. “For example, it was important for them to have the same systems in place in both the adult and pediatric oncology units while allowing them to continue using secondary infusion sets in adults but primary sets in pediatric patients.”

A six-month pilot and evaluation period of the product they ultimately chose provided nurses with an opportunity to familiarize themselves with the new system and to make workflow process modifications, according to Dr. Ozuna. “After an initial learning curve, nurse and pharmacy staff have become efficient despite the added

The trial period also provided a chance to observe the reduced potential for drug exposure with CSTDs, he said.

Adaptability a Concern For Nurses

‘You can’t just tell nursing to use the [CSTD] system and expect they won’t need further education.

This is why a collaborative relationship is so crucial to success.’

—Ryan Forrey, PharmD, MS steps with a closed system and they feel safer and comfortable,” he told Pharmacy Practice News.

The evaluation period also provided a chance for nurses to see the benefits of a CSTD for themselves. For example, they

noticed that there was much less residual medication in drug vials using a CSTD, and that this could potentially have positive effects on patient care by providing a fuller, and therefore more effective, dose of the drug, Dr. Ozuna explained.

If the concerns of nurses are not taken seriously, the entire project of implementing a closed system risks failing, according to Ryan Forrey, PharmD, MS, the associate director of Pharmacy and Infusion Services at the James Cancer Hospital at The Ohio State University (OSU), in Columbus, “CSTDs are only as good as the actual compliance with them,” said Dr. Forrey, an expert on CSTDs. “Pharmacists tend to think about the pharmacy side” but neglect the nurses’ perspective, he noted. A better approach, he said, is to adopt a shared governance model that includes nurses as equal partners in the transition to a closed system.

The multi-stakeholder team responsible for the transition to a closed system at the National Institutes of Health Clinical Center (NIHCC), in Bethesda, Md., provides a successful case study in the shared governance model that Dr. Forrey recommended. Daniel Zlott, PharmD, an oncology pharmacy clinical specialist for the National Cancer Institute Surgery & Immunotherapy programs at the NIHCC, and the pharmacy lead on the CSTD transition team, said the sheer size of the nursing contingent at the NIHCC—numbering more than 400 staff—left no question that nursing needed to be as involved in

•

see COLLABORATION, page 10

Tips for Picking a CSTD Vendor

N

ursing concerns about the integration of closed system transfer devices (CSTDs) into their workflow may have been the foremost consideration at Doctors Hospital at Renaissance when they decided on a CSTD vendor, but the implementation team evaluated other factors as well, according to Ron Ozuna, PharmD, BCPS. “The company rep was key in helping make the switch,” said Dr. Ozuna, the clinical coordinator of Pharmacy Services at the Hospital, in Edinburg, Texas. His team ultimately chose the Texium closed male lure and SmartSite needle-free valve products (CareFusion). “We had reps from several companies come in, but the CareFusion rep was most effective in educating and assisting staff with the closed system.”

Dr. Ozuna said the CareFusion representative helped obtain nursing buy-in to the very idea of a closed system, emphasizing the added safety of CSTDs and promptly addressing staff questions, with the goal of minimizing workflow disruptions.

Other institutions have documented rigorous CSTD evaluations, including wipe studies to determine how much a CSTD reduces surface contamination (see

Pharmacy Practice News 2009;36:08). However, Dr. Ozuna said his team’s evaluation process was “relatively informal. We did conduct some [ultraviolet] light examinations to identify spills and leaks, and we looked to published literature showing a closed system reduces exposure, But we did not look at product-specific studies; it was mostly a matter of trying out the different products and feeling out how comfortable we were with these products.”

Compatibility was also a consideration that led to choosing CareFusion as their vendor, he noted.

“We already had CareFusion elements in place, including Alaris pumps, so this was a natural fit and staff already felt comfortable with the pharmacy and intravenous line products,” Dr. Ozuna said. Finally—but not least among the evaluation considerations—there was the cost variable, he noted, adding, “CareFusion’s system was the most affordable.”

At the National Institutes of Health Clinical Center (NIHCC), in Bethesda, Maryland, where Amy Callahan, RN, DNP, AOCNS, is a clinical nurse specialist in oncology and critical care, the primary reason they settled on their product—which they would not name—was versatility.

T i Texium closed l d male l luer l and d SmartSite S tSit needle-free dl f valve system.

“This is necessary in the research environment, when you are working with various compounds and different methods of delivery,” Dr. Callahan said.

“Also, ease of use was important. We worked with infection control to review the products and this one had a surface that could be easily scrubbed to help in the prevention of contamination, which could lead to central line bloodstream infections.”

—David Wild

10 Operations & Management

Pharmacy Practice News • January 2014

Safe Handling

COLLABORATION continued from page 9

the selection and implementation of a closed system as pharmacists. Working with a committed nurse representative was a critical factor, he said.

“Finding someone on the nursing end who was willing to learn about all the different line systems we have and to understand why we set them up the way we do really helped me communicate to the nursing staff,” Dr. Zlott told Pharmacy Practice News. “If this

had been only been a pharmacy-driven project, it would have been much more difficult.”

On the nursing end, Amy Callahan, RN, DNP, AOCNS, an oncology and critical care clinical nurse specialist in the Nursing Department at the NIHCC, framed the implementation of a closed system almost identically. Dr. Callahan said it was a “co-led project” and that, “if it was only a nursing-led initiative, it would have been much more challenging.

“I needed to understand all the ins and outs of each preparation and Dan

[Dr. Zlott] was the expert in explaining drug delivery in every protocol,” she said. “Where Dan was, I was.”

Both Drs. Zlott and Callahan noted that a top priority was to ensure the added workload linked with implementation to a closed system was spread across their two disciplines. “We found a nice middle ground where nobody was getting everything they wanted,” Dr. Zlott said.

The nursing team modified their infusion processes and the pharmacy team agreed to spike hazardous drugs and

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attach CSTDs in the pharmacy. “We’ve always spiked and primed certain hazardous drugs, primarily for our pharmacokinetic studies because our investigators want to know precise information,” Dr. Zlott said. “What we agreed to do when the closed system was put in place was to spike, but not prime, all of the remaining hazardous drugs. Not only did it save nursing time, but it was a potential area for drug exposure that we took on in the pharmacy.”

According to Dr. Callahan, there was almost no resistance to a shift to CSTDs, even with the added burden on workflow—a fact she attributed to the strong nursing safety culture at the NIHCC. “We have up-to-date evidence-based safe-handling policies and procedures,” she explained. “We use solid front gowns and we double-glove.

This was just another method of ensuring we were doing the best we could as an institute to protect the nurses while they handle hazardous drugs.

We don’t fully know the complete hazardous profile of some of the research compounds, so safety is a strong concern for us.”

Perhaps it is indicative of the success of a collaborative model that Dr. Zlott played a pivotal role in training nurses, Dr. Callahan added. “A training video that Dan made was instrumental in the implementation phase of the project,” she said, noting the video is now used to train new nurses in the use of CSTDs.

Soon to be flowing in more sizes.

According to OSU’s Dr. Forrey, collaboration should not end when a closed system is implemented. He said there is potential for errors and events that come with the introduction of any new technology and that pharmacists and nurses need to work together to determine whether events are a result of product flaws, systemic issues or human error. “For every event, look for the root causes and address these,” he said. “You can’t just tell nursing to use the system and expect they won’t need further education. This is why a collaborative relationship is so crucial to success.”

If necessary, Dr. Forrey said staff should be re-educated; if there a significant increase in events—as in his own institution after implementation of a closed system—pharmacy and nursing may need to redesign work processes.

“With re-education and nursing collaboration, we’re now down to baseline spill levels,” he said. “However, if you don’t address the causes early, you can actually increase the number of spills.”

—David Wild

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

None of the participants reported any financial conflicts of interest.

Operations & Management 11

Pharmacy Practice News • January 2014

Medication Safety

Storytelling Can Revitalize Drug Error Communication ‘[Making videos] well requires a lot of work.

However, the final product is timeless, and it can be used again and again.’

—Matthew Fricker, RPh, MS Committee, the presentation is posted to the hospital’s intranet site, and hospital leaders are notified that a new

video is available.

According to Dr. Monroe, between October 2012 and June 2013, when the

approach was piloted, hospital leaders accessed the eight once-monthly videos nearly 3,500 times (Figure, page 12). Survey questionnaire responses revealed that 83% showed the videos at committee or staff meetings or during “team huddles.” Most hospital leaders considered the video approach a “very” or “extremely” successful way to share medication event information,

Because Gammaplex has a viscosity similar to that of human plasma1* Mean Corrected Viscosity (cP) of IGIV Products 3.0 2.5 2.0

1.64 cP

1.5 1.0 0.5

1.64

1.60

2.91

3.06

3.09

Plasma

Gammaplex 5%

Gammagard Liquid 10%

Gamunex 10%

Privigen 10%

•

see STORYTELLING, page 12

is indicated for replacement therapy in adults with Primary Humoral Immunodeficiency (PI). Gammaplex is also indicated for the treatment of adults with chronic Immune Thrombocytopenic Purpura (ITP) to raise platelet counts.

3.5

Mean Viscosity (cP)

Atlanta—Patient safety experts at the University of Texas MD Anderson Cancer Center are transcending old ways of highlighting medication-related error details. Instead of simply issuing recommendations stemming from drugrelated events, they are opting to use homegrown videos to “tell stories.”

According to Matthew Fricker, RPh, MS, a program director at the Institute for Safe Medication Practices (ISMP), in Horsham, Pa., who is not involved in the project, narrative-based approaches like this are more effective than “telling people we had an error and here are the changes we are making.” Whether the medium used is “video or another approach, telling stories is an excellent way of conveying the gravity of an event.”

Patrick Sayer Monroe, PhamD, a medication safety consultant at MD Anderson Cancer Center, said his hospital decided to go to the storytelling route after completing the ISMP’s Medication Safety Self-Assessment for Hospitals in 2011 and finding they “were not doing a good job of communicating details of events on an institutional level.”

Dr. Monroe explained that the center’s “process for sharing details of our events before was a unit-based approach. We relied on unit managers to share details of events with their staff and in our Patient Safety Committee meetings, but the lessons learned were not communicated institutionally.”

Short videos during staff and committee meetings reached more people and the videos could be uploaded to the hospital’s secure intranet site, said Dr. Monroe, who presented his team’s approach at the 2013 University HealthSystem Consortium Annual Meeting (abstract T37).

The videos are not intended to replace root-cause analyses, he noted. Rather, they illustrate gaps in everyday drug use processes that can lead to errors, from prescribing to administration.

Errors that fit this criterion are identified each month by a multidisciplinary team that includes a pharmacist, a nurse and a patient safety specialist. Once they select three events or topics that they believe are good examples of these gaps, another larger multidisciplinary group of pharmacists, nurses and mid-level providers chooses one of the topics to be developed into a visual presentation.

“Our communications department helps us create scripts, take photos and record the audio and, if we’re creating a reenactment, they also help create a video component,” Dr. Monroe explained. “All of this is then packaged into a PowerPoint presentation.”

After approval of the video by the hospital’s Institutional Patient Safety

0

* A 5% concentration may reduce the need for hydration compared to a 10% formulation

For more information visit www.gammaplex.com For medical information or reimbursement queries, please call 1-866-398-0825 or email BPLinfo@LashGroup.com To report side effects or adverse events, contact BPL by phone (1-866-398-0825) or email (adr@bpl.co.uk). You are also encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch, or call 1-800-FDA-1088

Infusion rate can be increased every 15 minutes to a maximum rate of 0.08 mL/kg/min2 Low IgA content (<10 μg/mL) 2 Can be pooled into IV infusion bags3 Liquid product / no reconstitution needed2 Bio Products Laboratory Limited (BPL) offers 60 years of plasma product heritage

Please see the Brief Summary of Prescribing Information, including boxed warning, on the reverse.

IMPORTANT SAFETY INFORMATION Gammaplex is indicated for the replacement therapy in adults with primary humoral immunodeficiency (PI). This includes, but is not limited to, the humoral immune defect in common variable immunodeficiency, X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome and severe combined immunodeficiencies.

Gammaplex is also indicated for treatment in adults with chronic immune thrombocytopenic purpura (ITP).

WARNING: Thrombosis may occur with immune globulin products, including Gammaplex. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors.

Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur in predisposed patients who receive immune globulin intravenous (lGIV) products, including Gammaplex.

Patients predisposed to renal dysfunction include those with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs [see Warnings and Precautions (5.1)]. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. Gammaplex does not contain sucrose.

For patients at risk of thrombosis, renal dysfunction or acute renal failure, administer Gammaplex at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration.

Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity [see Dosage and Administration (2.3), Warnings and Precautions (5.1)].

See full prescribing information for complete boxed warning December 2013 US/Gx/1213/0036 Printed in USA

Gammaplex is contraindicated in patients who have had a history of anaphylactic or severe systemic reactions to human immune globulin; an hereditary intolerance to fructose and infants with undiagnosed fructose intolerance; and IgA deficient patients with antibodies to IgA and a history of hypersensitivity.

Thrombotic events may occur following treatment with Gammaplex and other IGIV products. Monitor patients with risk factors for thrombotic events, including a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization and/or known/ suspected hyperviscosity.

In patients at risk of developing renal failure, monitor urine output and renal function including blood urea nitrogen (BUN) and serum creatinine.

Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV therapy.

Aseptic meningitis syndrome (AMS) may occur infrequently with IGIV treatment. AMS usually begins within several hours to 2 days following IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. AMS may occur more frequently in association with high doses (2 g/kg) and/or rapid infusion of IGIV. Hemolysis and hemolytic anemia can develop subsequent to IGIV treatments. Patient risk factors that may be associated with development of hemolysis include high dose (>2 g/kg), non-O blood group, and underlying inflammatory state. Noncardiogenic pulmonary edema may occur in patients following IGIV treatment (i.e. transfusionrelated acute lung injury [TRALI]). Monitor patients for pulmonary adverse reactions (TRALI). If TRALI is suspected, test product and patient’s serum for anti-neutrophil antibodies.

Gammaplex is made from human plasma and may contain infectious agents, e.g. viruses and, theoretically, the Creutzfeldt-Jakob disease agent. Based on effective donor screening and product manufacturing processes, Gammaplex carries an extremely remote risk of transmission

of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) is considered to be extremely remote. No confirmed cases of transmission of viral diseases or CJD have been associated with the use of Gammaplex.

In clinical studies, the most common adverse reactions with Gammaplex were headache, pyrexia, vomiting, fatigue, pain, nausea, hypertension, chills and myalgia.

Please refer to the Gammaplex Prescribing Information for full prescribing details.

REFERENCES 1. Bio Products Laboratory Limited, Data on file, December 2011 2. Gammaplex US Prescribing Information, Revision Date: Sept 24 2013, version VSUS4PI V3 3. Bio Products Laboratory Limited, Pooling Study, Data on File, December 2013

Report adverse reactions to adr@bpl.co.uk The permanent HCPCS “J” code for Gammaplex is J1557, effective January 1, 2012

12 Operations & Management

Pharmacy Practice News • January 2014

Medication Safety 700 606

STORYTELLING

600

continued from page 11

500

Frequency, n

Dr. Monroe said, adding that the video approach has been adopted permanently as a way of sharing non–drugrelated errors as well.

He said front-line pharmacists, physicians and nurses have provided similarly positive questionnaire responses.

Ninety percent of respondents said the videos were “somewhat” or “extremely” effective in helping them prevent similar errors.

499

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Figure. Leadership access of videos.

Gammaplex

®

Immune Globulin Intravenous (Human), 5% Liquid BRIEF SUMMARY CONSULT FULL PRESCRIBING INFORMATION FOR COMPLETE PRODUCT INFORMATION WARNING: ACUTE RENAL DYSFUNCTION THROMBOSIS, RENAL DYSFUNCTION and ACUTE RENAL FAILURE Thrombosis may occur with immune globulin products, including Gammaplex. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur in predisposed patients who receive immune globulin intravenous (lGIV) products, including Gammaplex. Patients predisposed to renal dysfunction include those with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. Gammaplex does not contain sucrose. For patients at risk of thrombosis, renal dysfunction or acute renal failure, administer Gammaplex at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.

INDICATIONS AND USAGE Primary Humoral Immunodeficiency (PI) - Gammaplex is an Immune Globulin Intravenous (Human), 5% Liquid indicated for replacement therapy in adults with primary humoral immunodeficiency (PI).

Chronic Immune Thrombocytopenic Purpura (ITP) - Gammaplex is indicated for the treatment of adults with chronic immune thrombocytopenic purpura (ITP) to raise platelet counts.

CONTRAINDICATIONS Gammaplex is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin. Gammaplex is contraindicated in patients with hereditary intolerance to fructose, also in infants and neonates for whom sucrose or fructose tolerance has not been established.

Gammaplex is contraindicated in IgA-deficient patients with antibodies to IgA and a history of hypersensitivity.

WARNINGS AND PRECAUTIONS Renal Dysfunction / Failure: Acute renal dysfunction/failure, osmotic nephropathy, and death may occur upon use of human IGIV products. Ensure that patients are not volume depleted before administering Gammaplex. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of Gammaplex and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing Gammaplex.

Thrombotic Events: Thrombosis may occur following treatment with immune globulin products, including Gammaplex. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia / markedly high triacylglycerols (triglycerides), or monoclonal gammopathies.

For patients at risk of thrombosis, administer Gammaplex at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.

Hypersensitivity: Severe hypersensitivity reactions may occur. In case of hypersensitivity, discontinue Gammaplex infusion immediately and institute appropriate treatment. Medications such as epinephrine should be available for immediate treatment of acute hypersensitivity reactions. Gammaplex contains trace amounts of IgA (<10 μg/ mL). Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. Gammaplex is contraindicated in patients with antibodies against IgA and a history of hypersensitivity reaction.

Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia: Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV therapy. It is critical to clinically distinguish true hyponatremia from a pseudohyponatremia that is associated with or causally related to hyperproteinemia with concomitant decreased calculated serum osmolality or elevated osmolar gap, because treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and a possible predisposition to thrombotic events.

Aseptic Meningitis Syndrome (AMS): AMS may occur with IGIV treatment. AMS usually begins within several hours to 2 days following IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. AMS is characterized by the following signs and symptoms: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting.

Cerebrospinal fluid (CSF) studies frequently reveal pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dL, but negative culture results. Conduct a thorough neurological examination on patients exhibiting such signs and symptoms, including CSF studies, to rule out other causes of meningitis. AMS may occur more frequently in association with high doses (2 g/kg) and/or rapid infusion of IGIV. Hemolysis: Gammaplex may contain blood group antibodies that can act as hemolysins and induce in vivoo coating of red blood cells (RBCs) with immunoglobulin, causing a positive direct antiglobulin test (DAT) (Coombs’ test) result and hemolysis. Delayed hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration and acute hemolysis, consistent with intravascular hemolysis, has been reported. The following risk factors may be associated with the development of hemolysis following IGIV administration: high doses (e.g., *2 g/kg), given either as a single administration or divided over several days, and non-O blood group. Closely monitor patients for clinical signs and symptoms of hemolysis, particularly patients with risk factors noted above.

If clinical signs and symptoms of hemolysis or a significant drop in hemoglobin or hematocrit have been observed, perform confirmatory laboratory testing. If transfusion is indicated for patients who develop hemolysis with clinically compromising anemia after receiving IGIV, perform adequate cross-matching.

Transfusion-related Acute Lung Injury (TRALI): Noncardiogenic pulmonary edema may occur in patients following IGIV treatment. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function and fever. Symptoms typically appear within 1 to 6 hours following treatment. Monitor patients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and the patient’s serum. TRALI may be managed using oxygen therapy with adequate ventilatory support.

Volume Overload: Carefully consider the relative risks and benefits before prescribing the high dose regimen (for chronic ITP) in patients at increased risk of volume overload.

Transmissible Infectious Agents: Because Gammaplex is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No cases of transmission of viral diseases or CJD have been associated with the use of Gammaplex. All infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare providers to BPL Inc. 1-866398-0825. Before prescribing Gammaplex, the physician should discuss the risks and benefits of its use with the patient.

Laboratory Tests: After infusion of immunoglobulin, the transitory rise of the various passively transferred antibodies in the patient’s blood may yield positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test. Clinically assess patients with known renal dysfunction, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or those receiving nephrotoxic agents, and monitor as appropriate (BUN, serum creatinine, urine output) during therapy with Gammaplex. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with polycythemia, cryoglobulins, fasting chylomicronemia/markedly high triglycerides, or monoclonal gammopathies. Consider measuring hemoglobin or hematocrit at baseline and approximately 36 to 96 hours post infusion in patients at higher risk of hemolysis. If signs and/or symptoms of hemolysis are present after an infusion of Gammaplex, perform appropriate laboratory testing for confirmation. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and patient’s serum.

ADVERSE REACTIONS Serious adverse reactions (ARs) observed in clinical trial subjects with primary humoral immunodeficiency (PI) were thrombosis and chest pain. Serious ARs observed in clinical trial subjects with immune thrombocytopenic purpura (ITP) were headache, vomiting and dehydration. The most common ARs observed in the PI clinical trial were headache (18 subjects, 36%), pyrexia (8 subjects, 16%), fatigue (6 subjects, 12%), nausea (6 subjects, 12%), hypertension (3 subjects, 6%), chills (3 subjects, 6%), myalgia (3 subjects, 6%), pain (4 subjects, 8%), and vomiting (3 subjects, 6%). The most common ARs observed in the chronic ITP clinical trial were headache (12 subjects, 34%), vomiting (8 subjects, 23%), nausea (5 subjects, 14%), pyrexia (5 subjects, 14%), pruritus (2 subjects, 6%) and arthralgia (2 subjects, 6%).

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 clinical practice.

Treatment of Primary Humoral Immunodeficiency: In a multicenter, open-label, non-randomized clinical trial, 50 subjects with PI received doses of Gammaplex ranging from 279 to 799 mg/kg every 21 days (mean dose 465 mg/kg) or 28 days (mean dose 458 mg/kg), for up to 12 months. Twenty-four subjects (48%) had an AR at some time during the clinical trial that was considered product-related. The total number of ARs during infusion or within 72 hours of infusion was 237 (a rate of 0.34 ARs per infusion). The percentage of Gammaplex infusions with one or more ARs within 72 hours of infusion was 21%. The upper bound of the 1-sided 97.5% confidence interval for this percentage was 24%, which was below the pre-specified upper limit of 40% for this safety endpoint. The most common ARs observed in this clinical trial were headache (18 subjects, 36%), fatigue (6 subjects, 12%), nausea (6 subjects, 12%), pyrexia (6 subjects, 12%), pain (4 subjects, 8%), hypertension (3 subjects, 6%), chills (3 subjects, 6%), myalgia (3 subjects, 6%) and vomiting (3 subjects, 6%). Two subjects experienced serious ARs (thrombosis and chest pain).

Forty-seven of the 50 subjects enrolled in this clinical trial had a negative direct antiglobulin test (DAT) at baseline. Of these 47 subjects, 4 (9%) developed a positive DAT at some time during the clinical trial. However, no subjects showed evidence of hemolytic anemia.

Table 1: Adverse Reactions (ARs*) Occurring in >5% of Subjects with PI Adverse Reactions

Subjects (%) PI [n=50]

Infusions (%) PI [n=703]

Headache

18 (36%)

53 (7.5%)

Pyrexia

7 (14%)

10 (1.4%)

Sinusitis

8 (16%)

9 (1.3%)

Fatigue

6 (12%)

9 (1.3%)

Nausea

6 (12%)

7 (1.0%)

Nasal Congestion

5 (10%)

3 (0.4%)

Pain

4 (8%)

5 (0.7%)

Vomiting

3 (6%)

3 (0.4%)

Chills

3 (6%)

5 (0.7%)

Hypertension

3 (6%)

4 (0.6%)

Insomnia

3 (6%)

3 (0.4%)

Muscle spasms

3 (6%)

2 (0.3%)

Myalgia

3 (6%)

3 (0.4%)

Upper respiratory tract infection

3 (6%)

5 (0.7%)

*Adverse Reactions (ARs) are defined as treatment emergent adverse events which met any of the following criteria: (a) adverse events which began during an infusion of Gammaplex or within 72 hours of the end of an infusion, (b) adverse events considered by the investigator or sponsor to have been possibly, probably, or definitely related to administration of Gammaplex, (c) adverse events for which the investigator’s causality assessment was either missing or indeterminate.

Treatment of Chronic Immune Thrombocytopenic Purpura:: In a multicenter, open-label, non-randomized clinical trial, 35 subjects with chronic immune thrombocytopenic purpura were treated with a nominal dose of 1,000 mg/kg on each of two consecutive days (total dose 2,000 mg/kg). Doses of Gammaplex ranged from 482 to 1149 mg/kg on an infusion day. The median total dose per subject was 2035 mg/kg. All 35 subjects received at least one infusion of clinical trial drug, and all but one subject completed the first course of treatment. Twenty-four subjects (69%) reported at least one AR (103 in total); the most commonly reported being headache (12 subjects, 34%), vomiting (8 subjects, 23%), nausea (5 subjects, 14%), pyrexia (5 subjects, 14%), pruritus (2 subjects, 6%), dehydration (2 subjects, 6%) and arthralgia (2 subjects, 6%). Three subjects experienced a total of five serious ARs. Of the five serious ARs, one subject had three concurrently (vomiting, dehydration and headache) and two subjects each had one serious AR (headache). One of these latter two subjects discontinued from the clinical trial because of the severe headache. Table 2 lists the ARs in more than 5% of subjects. Based on a review of clinical and laboratory data, 4/35 subjects (11%) with drops in hemoglobin exceeding 2 g/dL following administration of Gammaplex were considered to have experienced suspected treatment-emergent hemolysis. Milder treatment-emergent hemolysis could not be excluded for an additional 7 subjects, giving a total of 11 of 35 subjects (31%) for whom hemolysis could not be excluded (not including an additional two subjects who lacked follow-up testing for hemolysis, so their hemolysis status was considered unassessable).

Table 2: Adverse Reactions (ARs ) Occurring in >5% of Subjects with ITP Adverse Reactions

KCl, potassium chloride; LA/SA, look-alike/sound-alike

KEY

Subjects (%) ITP [n=35]

Infusions (%) ITP [n=94]

Headache

12 (34%)

15 (16%)

Vomiting

8 (23%)

9 (9.6%)

Nausea

5 (14%)

5 (5.3%)

3. Dec ’12–Jan ’13 – Same day

Pyrexia

5 (14%)

7 (7.4%)

4. Feb ’13 – Concentrated KCl

Pain

2 (6%)

2 (2.1%)

5. March ’13 – Allergy (brand/generic)

Abdominal pain upper

2 (6%)

2 (2.1%)

6. April ’13 – Self-medication

Nausea

6 (12%)

7 (1.0%)

Nasal Congestion

5 (10%)

3 (0.4%)

Gastritis

2 (6%)

2 (2.1%)

Contusion

2 (6%)

2 (2.1%)

Arthralgia

2 (6%)

2 (2.1%)

Cough

2 (6%)

2 (2.1%)

Anemia

2 (6%)

1 (1.1%)

Ecchymosis

2 (6%)

3 (3.2%)

Pruritus

2 (6%)

2 (2.1%)

Dehydration

2 (6%)

2 (2.1%)

Hypertension

2 (6%)

1 (1.1%)

Neck pain

2 (6%)

1 (1.1%)

*Adverse Reactions (ARs) are defined as treatment emergent adverse events which met any of the following criteria: (a) adverse events which began during an infusion of Gammaplex or within 72 hours of the end of an infusion, (b) adverse events considered by the investigator or sponsor to have been possibly, probably, or definitely related to administration of Gammaplex, (c) adverse events for which the investigator’s causality assessment was either missing or indeterminate.

In neither of the above trials was there evidence of transmission of HBV, HCV, HIV and parvovirus B19.

Postmarketing Experience: Because adverse reactions are voluntarily reported post-approval from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure.

In addition to the adverse reactions identified in clinical studies, the following adverse reactions have been identified during postmarketing use of Gammaplex: Infusion reactions:: Dizziness, back pain, flushing; Respiratory:: Pulmonary embolism, dyspnea; Cardiovascular:: Myocardial infarction; Integumentary:: Rash, urticarial. The following adverse reactions have been identified during post-marketing use of intravenous immune globulins: Infusion reactions:: hypersensitivity (e.g., anaphylaxis), headache, diarrhea, tachycardia, fever, fatigue, dizziness, malaise, chills, flushing, urticaria or other skin reactions, wheezing or other chest discomfort, nausea, vomiting, rigors, back pain, myalgia, arthralgia, and changes in blood pressure; Renal:: Acute renal dysfunction/failure, osmotic nephropathy; Respiratory:: Apnea, Acute Respiratory Distress Syndrome (ARDS), TRALI, cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm; Cardiovascular:: Cardiac arrest, thromboembolism, vascular collapse, hypotension; Neurological:: Coma, loss of consciousness, seizures, tremor, aseptic meningitis syndrome; Integumentary: Stevens-Johnson syndrome, epidermolysis, erythema multiforme, dermatitis (e.g., bullous dermatitis); Hematologic:: Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs’) test; Gastrointestinal:: Hepatic dysfunction, abdominal pain; General/ Body as a Whole:: pyrexia, rigors DRUG INTERACTIONS: Transitory rise of the various passively transferred antibodies in the patient’s blood after infusion of immunoglobulin may yield positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test. Passive transfer of antibodies may transiently interfere with the immune response to live virus vaccines such as measles, mumps, rubella and varicella. Inform the immunizing physician of recent therapy with Gammaplex so that appropriate measures may be taken.

Manufactured by: Bio Products Laboratory Limited Dagger Lane Elstree Hertfordshire WD6 3BX United Kingdom.

US License No. 1811 U.S. Distributor: BPL Inc. 8601 Six Forks Road, Suite 400 Raleigh North Carolina 27615 U.S.A.

1. Oct ’12 – Oral chemotherapy 2. Nov ’12 – Heparin event

7. May ’13 – Medication reconciliation 8. June ’13 – High-alert and LA/SA drugs

MD Anderson rolled out another error-prevention initiative around the same time, a pharmacy and nursing shadow program, so the visual reporting program’s effect on outcomes cannot be measured. However, Dr. Monroe noted that “through voluntary reporting, we’ve found that those errors that we’ve highlighted in the videos have rarely occurred again.” This finding is placed against the backdrop of a trend of increased medication event reporting coinciding with the inception of the video program. He acknowledged, however, that “because reporting is voluntary, there is the possibility that some events [described in the presentations] are still occurring but not being reported.”

Both Dr. Monroe and the ISMP’s Mr. Fricker noted that the visual presentation approach is not without its drawbacks. Both experts said there is a risk for the videos finding their way outside of the hospital’s domain. Additionally, each video requires between 18 to 24 hours to produce, according to Dr. Monroe. That amount of time could be prohibitive for some institutions, Mr. Fricker suggested.

“If these resource and security challenges can be overcome, such an approach is highly beneficial,” Mr. Fricker concluded. “I’ve helped develop videos, and to do them well requires a lot of work. However, the final product is timeless, and can be used again and again.”

—David Wild Dr. Monroe and Mr. Fricker reported no relevant financial conflicts of interest.

Operations & Management 13

Pharmacy Practice News • January 2014

Care Transitions

Targeted Efforts Reduce Readmissions, ER Visits Atlanta—Conducting targeted medication reconciliations in patients at highest risk for post-discharge medication-related issues and providing them with short-term pharmacist follow-up can reduce 30-day readmission rates by more than 40%, according to a presentation at the 2013 University HealthSystem Consortium Annual Meeting (abstract T57).

The model, implemented at Hennepin County Medical Center, in Minneapolis, is one of many cropping up across the country as health systems meet the demands of the new shared-risk model of reimbursement.

According to Bruce Thompson, RPh, MS, the director of Health System Pharmacy Services at the medical center, who led the initiative, the project’s success shows that “pharmacists have a great opportunity to improve all aspects of transitional patient care” and, more specifically, that “dedicating pharmacy resources to medication reconciliation at discharge can really help reduce readmissions, emergency room visits and unnecessary physician visits.”

Explaining the medical center’s

approach, Mr. Thompson said that “because it’s a resource-intensive process, we don’t conduct medication reconciliations for all our patients, but we do target the top-tier patients, particularly those receiving 10 or more medications or those who have had significant recent changes to their therapy.” He noted that roughly 50% of all Hennepin patients fall into this top-tier group.

The program uses a two-pronged approach. The first involves a pharmacist conducting medication reconciliation at the time of discharge, targeting those top-tier patients. Three to five days after these high-risk patients are discharged with the correct medications, they meet with a pharmacist either in the clinic or, if necessary, in their home. This second element of the approach allows pharmacists to examine all of the medications, ensuring there are no duplications, and that patients have filled their discharge prescriptions and are using them as prescribed.

According to Mr. Thompson, over the past four years since the twopronged approach was implemented, 30-day readmission rates have dropped

42%, from approximateely 11% to 6%, and emerrgency department visitss among those patients decreased by 36%.

He said word of the project’s success has spread, and other teach-ing and community hosspitals have borrowed the t approach and added staff s and resources to launch h similar initiatives.

The low level of 30-d day readmissions Mr. Thompson and his team achieved was app plauded

by Ernest R. Anderson Jr., J MS, RPh, a pharmacy consu ultant in Brockton, Mass., and a consultant to MCS Carelin nk, a company based in Dan nvers, Mass. that provides solu utions for pharmacy care accross the continuum. “I belieeve a reduction of this magn nitude can be replicated arround the country, although aan 11% baseline readmission rrate is probably already lower than

Elevating Pharmacy Technician’s Role In Transitional Care Pays Off

A

TLANTA—Pharmacy

technicians can help address the increasing need for transitional health-system pharmac cy care, a program at the University of Wisconsin Hospital (UWH), in Madison, has demonstrated. The technician initiative has expedited the hospital’s discharge dispensing process, increased outpatient pharmacy drug capture rates and iimproved patient, nursing and provider satisfaction.

Karen Trenkler, PharmD, MS, BCPS, a clinical coordinator of pharmacy services at Mt. Sinai Hospital in Chica ago, who was not involved in the project, commended the program for demonstrating the significant benefits that can be achieved by expanding pharmacy technician duties. “As long as their tasks are clearly defined and there is a clear chain n of responsibility, they can, for example, potentially free up the pharmacist’s time and enable them to perform the specialized functions they have trained for,” said Dr. Trenkler.

Joseph Cesarz, PharmD, MS, the manager of ambulatory pharmacy services at UWH, said that the hospital’s Pharmacy Department has created five full-time “transitional care pharmacy specialist” (TCPS) positions, staffed by pharmacy technicians.

The TCPS meets with patients upon admission, determine a patient’s ability to pay for their medications and enroll them in prescription assistance programs, if necessary. The TCPS also promotes the hospital’s retail pharmacy services and, if the patient agrees, delivers discharge medications to the patient’s bedside.

“The work done by the TCPS has pulled a lot of the workload off our inpatient pharmacists in terms of ensuring patient access to medications after discharge, and it has removed duplicative inpatient and outpatient pharmacist counseling, which had occurred before,” Dr. Cesarz said at the 2013 University HealthSystem Consortium Annual Meeting (abstract T77).

“From a medication access perspective, the new process is much more proactive, rather than reactive,” Dr. Cesarz noted.

Surveys conducted before and after the program’s 2012 implementation show patients now find it easier to obtain their medications and to receive payment and insurance assistance from the hospital, Dr. Cesarz said.

The Pharmacy Department also has seen financial benefits, he added. Specifically, the outpatient pharmacy’s discharge capture rate increased from 55.8% in 2012 to 65% in 2013, and enrollment in the university’s prescription home delivery service “within targeted areas” has risen by 45%, he added.

Dr. Cesarz said the Pharmacy Department also has created two “ambulatory medication prior authorization coordinator” (AMPAC) positions, again filled by outpatient pharmacy technicians. The AMPACs’ focus is on ensuring that patients from the university’s ambulatory clinics prescribed specialty medications receive them in a timely manner. This entails reviewing patient clinic visit records; verifying drug insurance coverage; enrolling patients in prescription assistance programs, if necessary; and completing prior authorizations (PAs) on behalf of ambulatory clinic staff. AMPACs promote the university’s prescription home delivery programs, schedule those deliveries and arrange for medication administration training. They also coordinate the prescription filling process at the patient’s preferred pharmacy.

“These services are provided regardless of whether their medications are dispensed at a University of Wisconsin Health pharmacy,” said Dr. Cesarz, noting that the AMPACs have saved ambulatory clinic patients more than $295,000 in cumulative outpatient specialty drug copayments during the year they have been in place. “The AMPACs also have reduced the amount of time our registered nurses, medical assistants and physician assistants spend on the PA process,” Dr. Cesarz said. “And it has increased their job satisfaction.”

—David Wild

thee average,” said Mr. Anderso on, who was not involved iin the Hennepin initiative.

Other hospitals might be interested in a third element of the new Hennepin model for transitional pharm macy care: community retail m ph harmacy partnerships.

One area where such partO nersships could have tremendous benefit is anticoagulant monitoriing, Mr. Thompson said.

“There are a over 24 million prescription ns for warfarin dispensed each yeear,” he said, “and almost 100% o of the time the retail pharmacy h has no clue if the patient has h had an INR [international normalized ratio] or if it’s in ran nge, yet they continue to refill the medication!”

To aaddress this problem, Hennepin n County Medical Center has paartnered with several nearby Wa Walgreens pharmacies, and together they have received grant fundingg to support a pharmacy residen nt who will divide his or her tim me between the hospital and rettail settings. “Our plan is to sharre medical record information fo or individuals treated for congesttive heart failure and acute myocard dial infarction, as well as those receeiving high-risk drugs like warfarin, an nd to look at the medical records of th hese high-risk patients and conduct inteerventions at the community retail ph harmacy, if necessary,” Mr. Thompson said. sa Mr. Anderson said this type of collaboration between health systems and community pharmacies “has been somewhat of a missing link. Unfortunately, pharmacies in the past have always been operating in silos,” he noted. “I think it’s a great thing that Hennepin is providing access to patients’ data, and I believe we’ll see more partnerships like this emerge.”

For the moment, health systems and community pharmacies that do not have the luxury of grant funding could face barriers to implementing similar partnerships. “Community pharmacy workflows and business plans don’t have the time built in for pharmacists to look at a medical chart,” Mr. Thompson explained.

However, Mr. Thompson said a financial and clinical case for such a partnership can be made. He will be measuring the partnership’s effect on patient outcomes and health care expenses and will report those findings at a future conference.

—David Wild

14 Operations & Management

Pharmacy Practice News • January 2014

Care Transitions

MED REC continued from page 1

observational investigation, compared medication reconciliation by pharmacists to that done by physicians at Brigham and Women’s Hospital, in Boston. The pharmacist team, which included pharmacy students from Northeastern University, evaluated physicians’ admission notes and identified 1,580 discrepancies among 306 enrolled patients during a three-month period in 2012.

More than one-third of the discrepancies (37%) were rated category F in severity, according to the National Coordinating Council for Medication Reporting and Prevention (NCC-MERP) system, meaning they could have caused patient harm that required initial or extended hospitalization. Thirty-six discrepancies were ranked as category I, indicating that they could have contributed to or caused a patient’s death.

Studies such as this and others have helped fuel an increase in the use of pharmacists to obtain accurate patient medication lists during transitions of care, particularly in emergency departments (EDs), said Darryl Rich, PharmD, MBA, FASHP, a medication safety specialist at the Institute for Safe Medication Practices.

And indeed one of the other two ACCP studies describes the positive results of a pilot pharmacist medication reconciliation intervention initiative in the emergency department at Huntington Hospital, a North Shore-Long Island Jewish Health System affiliate, in Huntington, N.Y. The study sought to determine whether bringing in a clinical pharmacist to help gather patient histories and accurate medication lists during the ED’s peak 2 to 10 p.m. hours would improve patient safety and reduce the burden on admitting hospitalists.

It did both, according to Anna Dushenkov, PharmD, the assistant director of clinical pharmacy services and study co-author. During the sixmonth pilot, Sanu u Koshy-Varghese, PharmD, the clinicaal pharmacist hired for the pilot, carried d out approximately 1,600 interventio ons per month. In the first two monthss, the interventions resulted in 90% few wer medication history inaccuracies and 97% fewer medication administration delays. The researchers estimaated that 73 of the interventions were for discrepancies with w a high potential for patien nt harm; the annualized cost avoidance a of those errors was pegged at more than $860,000.

“We don’t havve data showing improved ED thro oughput,” said Dr.

‘My threshold for questioning a home medication list is much lower than before.’

—Kena J. Lanham, PharmD Dushenkov. “But it’s just intuitive,” she added, that if hospitalists are relieved of some of their history-taking tasks, they can spend more time with difficult patients and seeing additional patients.

“That can improve ED workflow as well as patient satisfaction,” she said. One result of the pilot study, Dr. Dushenkov said, was that the hospital is considering extending the ED hours that are covered by pharmacists dedicated to medication reconciliation at admission.

Another pilot study reported at the ACCP meeting was carried out at St. Vincent Hospital, in Indianapolis. It was based on the premise that if medi-

accuracy of medication histories gathered at the time of admission by nursing staff and prescribers. They compared discrepancies identified both before and after the implementation of an electronic medical records (EMR) system. They found that completion of medication reconciliation increased from 82% before the EMR system to 91% afterward. They also found that the number of discrepancies identified post-EMR increased substantially. For example, the average number of medications identified as incorrect rose from 0.16 to 0.88 per patient after the EMR system went live, and then to 1.74

‘We try to have all of our med recs done within 24 hours of admission because that’s the time when information is typically most useful.’

—Michael M. Gonyeau, PharmD cation reconciliation is done accurately at hospital admission, “the patient is better served throughout the stay and at discharge,” said Kena J. Lanham, PharmD, BCPS, a clinical pharmacist specialist in cardiology at St. Vincent and an assistant professor at Butler University College of Pharmacy and Health Sciences, in Indianapolis.

Dr. Lanham and her colleagues performed a retrospective audit to determine the

following an EMR upgrade.

One outcome of the study, Dr. Lanham said, has been that “my threshold for questioning a home medication list is much lower than before. Patients often just take the medications. Maybe someone is laying it out for them.

Often they’re unsure of the dose. And physicians’ records may not be up to date because the patient may have gone to a different physician

who changed the dose. That is going on with patients in every single hospital throughout the country.”

At Brigham and Women’s Hospital, Michael M. Gonyeau, PharmD, BCPS, FCCP, a clinical professor at Northeastern University School of Pharmacy, in Boston, and a clinical pharmacist at Brigham and Women’s, leads a team of pharmacists and students who interview patients on a general medicine service unit and call outpatient pharmacies and primary care physician offices to verify the accuracy of medication lists compiled at admission. “We identify any discrepancies, talk to the team and make any needed changes while the patient is in the hospital,” Dr. Gonyeau said. “We try to have all of our med recs done within 24 hours of admission because that’s the time when information is typically most useful.”

As an example of the potential severity of some discrepancies, Dr. Gonyeau said they identified several patients who “were supposed to be taking blood pressure medications” but weren’t doing so and “as a result, they had come into the hospital with a hypertension-related issue.”

Dr. Gonyeau said one result of the study is that “physicians have become more cognizant of the need to go deeper into the medication reconciliation process, some making calls to verify patient lists.”

Despite the preponderance of evidence showing the benefit of medication reconciliation, progress in getting hospitals to comply with the 2005 Joint Commission Patient Safety Goal has been slow. “It’s a big issue,” Dr. Rich said. “There are probably about 20 things people have to do to make it work better,” including “dedicating more resources to it and making sure it doesn’t rely on one discipline to do everything.”

—Bruce Buckley Drs. Rich, Dushenkov, Koshy-Varghese, Lanham, and Gonyeau reported no relevant financial fi nancial conflicts conflicts of interest interest.

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16 Operations & Management

Pharmacy Practice News • January 2014

Diabetes

IMPACT continued from page 1

multiple medications for diabetes and other chronic conditions, was able to achieve a significant 0.7-point average reduction in hemoglobin (Hb) A1c (from 9.0% to 8.3%) during the first six months of intensive management by health care teams that included pharmacists as leading players (Table). Other indicators of cardiovascular health also improved significantly, including low-density lipoprotein (LDL) cholesterol (from 99.5 to 92.2 mg/dL), systolic blood pressure (from 131.8 to 129.9 mm Hg) and body mass index (from 35.1 to 34.9 kg/m2).

“Even in this very difficult population, we were able to achieve results that were similar to those that we saw in earlier studies,” Benjamin M. Bluml, RPh, the senior vice president for research and innovation at the APhA Foundation, said in an interview with Pharmacy Practice News.

The 25 organizations that took part in the project represented a wide range of practices, including university pharmacy school programs, community and supermarket pharmacies, employer worksites, federally qualified health centers and physicianrun clinics. Mr. Bluml said they were selected from among nearly 300 organizations that had expressed initial interest because they met stringent criteria, including location in areas with a high burden of diabetes and the resources to carry out the research initiative effectively. They also had to “put a continuous quality improvement program on the ground,” he said, and “use our patient self-management credential. And they had to report a minimum data set to us quarterly.”

Although the foundation set rigorous

standards for participation, it sought to avoid a cookie-cutter approach to care. “We encouraged each community to take an inventory of resources available in their communities and sort out the best way to create a team-based approach to delivering patient-centered care,” Mr. Bluml said.

Mindy Smith, RPh, the executive director of the APhA Foundation, told Pharmacy Practice News that the program’s success could be a lesson for insurers and health care organizations nationally, as they gear up for the huge expansion in care delivery under the Affordable Care Act. “We’ve now shown what pharmacists can do in the underserved and underinsured” populations, she said. “It’s a great story to be able to say, ‘pharmacists can be part of the solution to really help meet the needs of health equity and access to care within those environments.’”

Patients came to know pharmacists and other team members extremely well during clinic visits, and vice versa. That closeness was crucial to the patients’ progress, according to Ms. Smith, who said when patients were later asked to name the factors that had made a difference in their progress, many replied, “My pharmacist cares for me.” It helped that there were no time limits on clinic sessions. Pharmacists could take as much time as needed to engage patients in taking charge of their own health.

That extra time was needed because it could be very difficult to reach some patients, said Joy Waddell, PharmD, the pharmacist in charge of the Mountain State Health Alliance’s Northeast Tennessee Dispensary of Hope, in Johnson City. “For the most part, our patients are underserved, underprivileged and indigent,” she said. “At one time, 50% of our patients were homeless. Even after you bond with them, it’s very difficult to

Courtney Davis, PharmD, of the University of Mississippi, counsels a patient enrolled in the Project IMPACT: Diabetes study.

At The Ohio State University College of Pharmacy, Stuart J. Beatty, PharmD, BCPS, CDE, works as part of a multidisciplinary team that delivers diabetes care to uninsured or underinsured patients.

keep them here.” Tennessee is one of a handful of states where diabetes prevalence exceeds 10%.

Still, Dr. Waddell said she could think of as many as 10 patients, “right off the top of my head, where we really made a difference.” One such patient,

‘This is not a quick fix; it’s a marathon that we have to keep up because it takes years and years, and maybe a generation, to make a difference for these folks.’

—Joy Waddell, PharmD

Table. Project IMPACT: Diabetes Interim Results Clinical Indicators

Patients, n

Mean Initial Value

Mean Interim Value

Mean Change

HbA1C (ADA goal <7.0%)

1,580

9.0%

8.3%

–0.7%a

LDL cholesterol level (NCEP goal <100 mg/dL)

966

99.5 mg/dL

92.2 mg/dL

–7.3 mg/dLa

Systolic blood pressure (JNC VII goal <130 mm Hg)

1,702

131.8 mm Hg

129.9 mm Hg

–1.9 mm Hga

BMI (WHO normal 18.5-24.9 kg/m2)

1,699

35.1 kg/m2

34.9 kg/m2

–0.2 kg/m2a

ADA, American Diabetes Association; BMI, body mass index; HbA1c, glycosylated hemoglobin; JNC VII, The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report; LDL, low-density lipoprotein; NCEP, National Cholesterol Education Program; WHO, World Health Organization a

Statistically significant change.

she said, had lost his job and was living “off a couch” in a relative’s home and trying to go back to school to change careers. “He’ll tell you that we changed his life,” she said. Recent tests showed that his HbA1c, blood pressure and cholesterol levels “had dropped dramatically,” she said. “I got so excited, I did a little happy dance.”

Despite the successes, Dr. Waddell said she is often frustrated because “we can’t change generations of living, education, or eating and exercise habits” easily. “This is not a quick fix; it’s a marathon that we have to keep up because it takes years and years, and maybe a generation, to make a difference for these folks.”

At OSU, More Frequent Visits Spur Results The Project IMPACT rules required enrolled patients to visit clinics at least three times during the study year. But for patients with especially high HbA1c levels, an assortment of other comorbidities and a tendency to not adhere to medication regimens, three visits a year were hardly enough. At The Ohio State University (OSU) College of Pharmacy diabetes clinic, for example, patients

Operations & Management 17

Pharmacy Practice News • January 2014

Diabetes WA MN MT

ND VT

OR

MN

NH

ID

WI SD

NY MI

WY CA

PA

IA

NJ

OH

NE

NV

MA A RI CT

IL

UT

IN

DE DC MD D

WV

C) KS

MO

VA

KY

NC TN

OK AZ

SC

NM AR

AL

GA

MS TX

LA FL

HI

AK

Diabetes prevalence (%) <7 7.1 to 8 8.1 to 8.9 9 to 10.4

Figure. Project IMPACT: Diabetes communities (25) by state were scheduled to come in anywhere from every two weeks to every three months, depending on the severity of their disease and the number of changes needed in treatment regimens.

Stuart Beatty, PharmD, BCPS, CDE, an assistant professor of clinical pharmacy at the OSU College of Pharmacy, in Columbus, said the typical patients referred to the clinic were “very poorly controlled,” with an average baseline HbA1c of nearly 10% and some as high as 15%. “They have multiple chronic illnesses and are taking lots of other medications,” he said. One reason patients are sent to the clinic, he added, is that “there is too much going on for their primary care physicians to take care of in a standard office visit.”

Because of that complexity, “we have a team-based approach that is focused on diabetes,” Dr. Beatty said. “I think the patients appreciate that. We really want them to be part of the process, so there is a lot of education involved, and we do a lot of questioning to let them tell us what their barriers are, so we can help them overcome that.”

With an overall HbA1c reduction of nearly 1.5%, the clinic’s approach has worked for most patients. Moreover, the results are not just an impressive statistic: A 1% reduction in HbA1c is associated with an approximately 40% reduction in the incidence of microvascular

complications, which underscores the clinically meaningful effect of the interventions ((Diabetes 1995;44:968-983).

Continuity of Care Pharmacists also made sure that patients stayed on course between regular clinic appointments by staying in touch via telephone, email or through their primary care providers. At the Diabetes Care Group in Jackson, Miss., which partners with pharmacists from the University of Mississippi School of Pharmacy, patients were asked to record their glucose levels in a paper log and to bring them in or fax them between scheduled visits. Courtney Davis, PharmD, a clinical assistant professor at the University of Mississippi School of Pharmacy, said that with the paper logs she could track patient daily glucose level trends over time and suggest between-visit medication adjustments to the physicians in the group.

Mississippi is another state that has a major diabetes burden, with a prevalence greater than 11%. Dr. Davis said Diabetes Care Group patients enrolled in the Project IMPACT study had an average baseline HbA1c level of 9.2%. “We achieved a 1.2% reduction within a year,” she said. “Quite a number [of patients] met their goal [<7.0%]. The problem is that A1c tends to fluctuate over time. It’s just a constant struggle trying to remo-

>10.5 Project IMPACT

tivate them because diabetes is lifelong and constantly changing.”

But she added, “It’s really rewarding to see those who have come so far.”

Diabetes care teams have tried to stay close with patients’ progress after the study year to make sure, as Dr. Beatty said, “that they don’t fall off the deep end with poorly controlled diabetes.”

Looking at the wide range of prac-

ect has been “much larger” than he ever would have imagined in the early years.

“To my knowledge, there are similar programs now in more than 30 states. In fact, I just got an email from a colleague who is working on implementing an Asheville-type model project in India,” said Dr. Bunting, who is now the vice president of clinical services at American Health Care, a Rocklin, Calif.-based

‘We’re really hopeful that these results can be fundamentally transformative in the health care delivery system.’

—Benjamin M. Bluml, RPh tices involved in the project, Dr. Beatty said it was “clear that it doesn’t matter what setting patients are seen in and it doesn’t matter what the demographics are. If a pharmacist is involved in the health care of a patient with diabetes, they will have better outcomes.”

A Model for Other Programs The success of the Asheville Project and Project IMPACT has helped spawn other similar programs. Barry Bunting, PharmD, who coordinated the Asheville Project in the late 1990s, when he was the clinical manager of community pharmacy practices for Mission St. Joseph’s Health Systems, in Asheville, said the impact of the proj-

provider of pharmacy benefit management services.

As the Project IMPACT: Diabetes sites continue to be successful throughout the country (Figure), the APhA Foundation is looking ahead to other, potentially larger Project IMPACT programs. “We’re really hopeful that these results can be fundamentally transformative in the health care delivery system,” Mr. Bluml said. “And with support from our current sponsor [Bristol-Myers Squibb Foundation] and the potential support from others, we’ll be in a position to really translate that into practices all across the country.”

—Bruce Buckley

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.

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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

22 Operations & Management

Pharmacy Practice News • January 2014

Trends

FORECAST continued from page 1

• Fiscal issues

Forecast was presented and whose Leaders for the Future Fund partly paid for the report’s development.

In his personal communications with pharmacy leaders, Mr. Zilz said he has found some who “have articulated a very clear vision and strategic plan, but … as a group, we’re all over the map in terms of how well pharmacists have positioned their departments to effectively influence optimum patient outcomes in this new environment.”

William Zellmer, BSPharm, MPH, the president of Pharmacy Foresight Consulting, in Baltimore, headed the creation of the Pharmacy Forecast, a project of the ASHP Foundation’s Center for Health-System Pharmacy Leadership. He and the other Forecast creators, all of whom held positions on various ASHP executive committees, developed a 64-item questionnaire that covered eight topic areas, including fiscal issues, quality of care, health care analytics, the pharmaceutical marketplace, pharmacy practice models, ambulatory care, pharmacy department operations and pharmacy leadership. They mailed the questionnaire to a group of 164 geographically representative health system pharmacists who they identified as “recognized experts” with “knowledge of trends and new developments [in health-system pharmacy] and a demonstrated ability to think analytically about the future of pharmacy practice in hospitals and health systems.”

Of those surveyed, 150 (91%) responded, the investigators noted, adding that

• Quality of care • Health care analytics • Pharmaceutical marketplace • Pharmacy practice model • Ambulatory care • Pharmacy department operations • Leadership

31% held some type of health-system practice management position, 22% were clinical health-system pharmacists, 22% were academic faculty members, 11% were informatics and technology specialists and the remainder represented a variety of other pharmacy positions.

Many of the surveyed panelists reported that they anticipate that increasing financial demands on hospitals will, in turn, be passed on to hospital pharmacies, said Lee Vermeulen, BS Pharm, MS, the director of the University of Wisconsin in Madison’s Health Center for Clinical Knowledge Management and a clinical professor of pharmacy at the University’s School of Pharmacy.

Many panelists anticipate more revenues being provided as bundled payments intended to cover the continuum of patient care from short-term acute care to long-term post-acute care in the community. Nearly all of the survey respondents said they believe that more than half of all hospital revenues

will be in some way contingent on how well organizations and pharmacies perform on pre-established, standardized quality indicators.

“Pharmacists will be developing programs that tie fixed reimbursement to high-quality outcomes, particularly outside the acute care environment,” said Mr. Vermeulen, suggesting that cutting 30-day readmission rates will be a significant goal and will force resources to be shifted to manage outpatient care.

Coaching Better Compliance One of the primary goals of outpatient care will be coaching patients to achieve high adherence rates and monitoring drug therapy outcomes, said Joel A. Hennenfent, PharmD, MBA, BCPS, the system director of pharmacy for Truman Medical Centers, a not-forprofit health system based in Kansas City, Mo. “One thing to consider is optimizing the use of emerging pointof-care diagnostics for patient selection in order to improve care and reduce

100

Survey Responses, %

ASHP Foundation Pharmacy Forecast 2013-2017 Topics

80

6

52 39

4

2 7 0

Very likely

3

Some- SomeVery what what unlikely likely unlikely

Figure 1.

At least 50% of hospitals will have at least one pharmacist dedicated to working with patients on drug therapy management (including outcomes monitoring and coaching on adherence) after they are discharged from the hospital.

costs,” Dr. Hennenfent said. Increasing use of such diagnostics, he noted, will allow pharmacists to fine-tune drug dosing and optimize a drug’s efficacy and safety. Of the survey respondents, 60% reported that they expect these types of tests to accompany at least one-fourth of all newly approved molecular entities.

Scrupulous patient monitoring will also be critical because, as 58% of the surveyed pharmacy experts reported, the number of drug shortages is unlikely to diminish any time soon, meaning that agents with potentially less favorable safety profiles than the drugs in short supply will be used as alternatives or substitutes, Dr. Hennenfent said.

According to 91% of those surveyed, more than half of all hospital pharmacies are expected to assign at least one pharmacist to manage the increasing outpatient care load (Figure 1). Addi-

The Case for In-House Management of Outpatient Pharmacy

C

ontracting with a retail chain to manage hospital outpatient pharmacy services “can be the wrong thing to do from a patient care perspective,” according to Mark Eastham, BS, RPh, the senior vice president and general manager of McKesson’s Pharmacy Optimization team, in San Francisco.

“If the health-system pharmacist is in control of outpatient prescriptions in addition to knowing what drugs a patient is taking upon admission, during their hospital stay and upon discharge, [the pharmacist] can provide a degree of medication therapy management that typically can’t be done through a retail contract,” Mr. Eastham said.

Managing medication therapy throughout the continuum of care helps ensure patients are in optimal health and are, therefore, at lower risk for hospital readmission within 30 days, Mr. Eastham said. This is important from a financial perspective, given that more reimbursement is arriving in the form of fixed bundles, and penalties for 30-day readmissions can be imposed, he said.

Like Mr. Eastham, Justin Brock PharmD, who is the manager of the University of Arizona Medical Center’s Outpatient Pharmacy Services in Tucson, said in-house pharmacy management yields some “incredible benefits, both financially and clinically.” He said they have augmented their care by adding an outpatient specialty pharmacy component catering to their transplant and HIV patients and also have taken measures to deepen their pharmacists’ engagement in patient care.

“With the addition of the specialty pharmacy and this deeper patient engagement, we have increased our discharge prescription capture rate by 60% and boosted our revenue by 15%,” Dr. Brock said. “And ensuring our

patients receive the appropriate medications upon discharge has also pushed down our 30-day readmission rates.”

Another advantage of keeping outpatient pharmacy management in-house is that pharmacists can access patient medical records, Dr. Brock said. “Accessing charts ensures that patients receive the appropriate medications and also allows our pharmacists to document new therapies directly in the patients’ charts,” he noted. In contrast, many contract retail pharmacies do not link in to the hospital’s medical record system.

According to Mr. Eastham, the University of Arizona and other outpatient pharmacies in large academic centers are in a unique position to add to their financial case for in-house outpatient pharmacy management. “Some of our large, selfinsured customers, including large academic centers, are now providing their own employees’ drug benefits through their outpatient pharmacies, which has led to 10% to 15% reductions in employee benefit spending while adding to their revenue stream,” Mr. Eastham noted.

Despite all the benefits of in-house outpatient pharmacy management, Dr. Brock said, “fighting for even more resources is always a battle. Thus, while we are certain that at the moment both financial and clinical outcomes would be better served by providing these services in house, our hospital leadership will be open to contracting out our outpatient pharmacy services if, in the future, that proves to be the best option for the bottom line and for patient care.”

—D.W. Dr. Brock reported no relevant financial conflicts of interest.

Operations & Management 23

Pharmacy Practice News • January 2014

Finance Survey Responses, %

100

80

systems, experts note (sidebar).

Pay Contingent on Patient Care Outcomes

6

4

2

0

36

42

12

Very likely

11

Some- SomeVery what what unlikely likely unlikely

Figure 2.

At least 50% of hospitals that have an outpatient (dispensing) pharmacy will contract with a corporate entity (e.g., a chain drugstore company) to operate that pharmacy.

To thrive operationally and financially, hospital pharmacies will need to demonstrate their effect on patient outcomes, Pamela K. Phelps, PharmD, the director of Clinical Pharmacy Services at Fairview Health Services, and an adjunct associate professor at the University of Minnesota College of Pharmacy, in Minneapolis, said. “To build a convincing business case to senior hos-

pital leadership that will garner additional pharmacy resources, you should identify all medication-related qualityof-life measures within the health system and position your department to improve on these measures.”

Pharmacy leaders whose departments are not demonstrably helping to improve hospital outcomes will be held directly accountable for their department’s shortcomings, according to Joyce Tipton, RPh, MBA, the director of pharmacy and respiratory care at Memorial Hermann, in Houston.

“Rather than simply being evaluated on the pharmacy department’s success in routine operations, pharmacy leaders will be financially incentivized primarily on their department’s contribution to the organization’s long-term strategic goals,” Ms. Tipton said, citing survey results.

For more information on the Pharmacy Forecast, visit www.ashpfoundation. org/pharmacyforecast.

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

Committed to Meeting Patient Needs tionally, Dr. Hennenfent said that nearly half the respondents reported that they believed the majority of hospital outpatient pharmacies will ultimately contract with chain retail pharmacies to manage their operations (Figure 2)—a strategy that may not be the best bet for alll health New Product

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he FDA has approved sofosbuvir (Sovaldi, Gilead Sciences), a oncedaily, oral nucleotide analog polymerase inhibitor, for the treatment of patients with chronic hepatitis C virus (HCV) infection.

Sofosbuvir is the first-ever, all-oral treatment regimen for patients with HCV genotypes 2 or 3.

The drug is approved for use in combination with ribavirin (RBV) for adults with HCV genotypes 2 or 3, and in combination with pegylated interferon (PEG-IFN) and RBV for adults with HCV genotypes 1 or 4.

It may be used to treat patients with hepatocellular carcinoma awaiting liver transplantation to prevent HCV recurrence, and also in patients with HCV/HIV coinfection.

Sofosbuvir’s approval primarily was based on data from four Phase III studies. In the studies, patients who received sofosbuvir achieved sustained virologic response (SVR) rates of 50% to 90% at week 12. Sofosbuvir was well tolerated; adverse events were generally mild and resulted in few treatment discontinuations.

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24 Clinical

Pharmacy Practice News • January 2014

Critical Care

Liposomal Bupivacaine Boosts TAP Block

C

linicians may have an effective new anesthetic at their disposal for patients requiring 72 hours or more of postoperative pain relief. Liposomal bupivacaine (Exparel, Pacira) has been found to be effective for pain relief following surgical procedures involving incisions of the mid- and lower abdominal wall, according to the results of a study presented at the New York School of Regional Anesthesia (NYSO-

RA) 2013 annual meeting on regional anesthesia, pain management and perioperative medicine.

The study found that the drug, a recently approved extended-release form of liposomal bupivacaine, provided pain relief for up to 72 hours after surgery when injected by infiltration of the transversus abdominis plane (TAP), along the fascial planes of the abdomen. Previously, using bupivacaine for

TAP infiltration was found to provide pain relief for 12 to 18 hours after surgery involving incisions of the mid- and lower abdominal wall.

The study included 13 patients undergoing open umbilical hernia repair under general anesthesia, with an incision length between 3 and 12 cm. Using ultrasound guidance, a bilateral TAP infiltration was performed at the end of surgery, but before the general anesthesia wore

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

off. The patients were first injected with 5 mL of saline to identify the TAP. That was followed by 20 mL of liposomal bupivacaine that had been diluted with 10 mL of sterile saline, for a total injectate volume of 30 mL, 15 mL of which was injected into each patient on each side of the TAP. The patients, who ranged in age from 28 to 65 years, reported their level of pain on a scale of 0 to 10 before the injection and at regular intervals up to 120 hours after TAP block. “We also made daily phone calls up to four days post-op as part of their follow-up,” noted Eduard Logvinskiy, DO, a pediatric anesthesiologist at Maimonides Medical Center, in New York City, who helped conduct the study.

Although one TAP infiltration failed due to significant pain, the remaining 12 were successful, with mean satisfaction scores of 4.4 at discharge and 4.6 at the follow-up visit. The patients reported an average pain score of 1.6 at 72 hours after the TAP infiltration, with a standard deviation of 1.4. None of the patients reported any serious adverse events or complications as a result of the drug, according to the researchers.

“This study demonstrates the excellent efficacy nonopioid analgesics can provide with minimal to no side effects,” said Christopher Gharibo, MD, the director of chronic pain management at New York University’s Langone Center for Musculoskeletal Care, in New York City. “The benefits here are cleaner, more functionally relevant pain relief that is also more convenient for the patient.”

However, Dr. Gharibo, who was not involved in the study, had reservations about the study, noting that it had few patients and lacked a control group.

Dr. Logvinskiy and his colleagues acknowledged that their study was not a randomized controlled trial. “We basically wanted to see if this would actually work,” he said.

The results further suggest that nerve blocks have the potential to supplant local anesthetics for postsurgical pain

•

see LIPOSOMAL, page 29

Clinical 25

Pharmacy Practice News • January 2014

Pharmacogenomics

Algorithm Aims for Safer, Smarter Codeine Use Albuquerque, N.M.—To avoid administering codeine to ultra-rapid metabolizers—individuals whose livers convert codeine to morphine so quickly the reaction can be fatal—clinicians at St. Jude Children’s Research Hospital, in Memphis, Tenn., have created an algorithm to help determine which pediatric patients can safely receive the analgesic. Before ordering codeine, the hospital’s electronic health records (EHR) system prompts physicians to request CYP2D6 genotyping, which can distinguish ultra-rapid or poor metabolizers from other patients.

In February 2013, the FDA added a black box warning label stating that codeine is contraindicated for adenoidectomy and tonsillectomy, citing deaths and serious adverse events in children who received the drug after these procedures. Despite this label, codeine remains an important analgesic, said Kristine Crews, PharmD, who codirects the pharmacokinetics research center at St. Jude and presented this algorithm at the 2013 annual meeting of the American College of Clinical Pharmacy (abstract 261). “Some children’s hospitals chose to take codeine off their formularies altogether,” she said, “but clinicians at St. Jude feel that codeine is good to have in the armamentarium.” About 10% of patients are poor metabolizers, she said, and another 2% are ultra-rapid metabolizers. But codeine is a valuable option for up to 88% of the remaining patient population, Dr. Crews said.

If hospitals completely replace codeine with other analgesics, they run the risk of relying on drugs that may be less understood, said Howard McLeod, PharmD, the director of the Personalized Medicine Institute at the Moffitt Cancer Center, in Tampa, Fla., who was not involved with this research. Such alternatives, he said, may not have accumulated an equivalently large body of clinical knowledge.

To keep codeine in the armamentarium, however, clinicians at St. Jude have to ensure children who are poor or ultra-rapid metabolizers of CYP2D6 do not receive the drug. The hospital created a therapeutic algorithm for codeine administration, which is implemented via the EHR system. Whenever a physician orders codeine, the EHR checks for the patient’s CYP2D6 genotype—if no genotype is on file, the algorithm reminds physicians to order a test. The system suggests other analgesics, such as morphine, hydromorphone or nonopioid pain relievers, for use in the interim.

When a genotype result is on file, the algorithm will inform physicians whether or not codeine is safe to administer.

In the six months that the algorithm has been operational, “it has collective-

ly fired over 500 times,” Dr. Crews said, adding that there have been no clinician overrides. The advantage of a system like this, Dr. McLeod said, is that it reduces the number of decisions a prescriber has to make. “The prescriber doesn’t have to be a molecular biologist,” he said, and can use the results of the test to help choose appropriate agents for pain management.

Although St. Jude has not developed

algorithms for other drugs, the hospital has implemented three other clinical genotyping tests: TPMT T genotyping for thiopurines; SLC01B1 genotyping for simvastatin; and CYP2C19 genotyping for clopidogrel. But Dr. Crews said that he believes that a system similar to the one used for codeine could be applied to other drugs in the future. “Alerts are meant to be reminders of patients’ statuses,” she said, but they have the added benefit

of providing “a little bit of education” to prescribers. “By wiring the electronic medical records to include decision support tools, such as these,” Dr. McLeod said, algorithms “can eliminate human error and give [clinicians] more time to focus on seeing patients.”

—Ben Guarino Drs. McLeod and Crews reported no relevant financial conflicts of interest.

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26 Clinical

Pharmacy Practice News • January 2014

Practice Pearl

A Centralized Approach to Medication Safety Michael Kanter, MD SCAL Medical Director of Quality & Clinical Analysis

Gail Lindsay, RN, MA SCAL Clinical Operations Director

Jennifer Polzin, PharmD, FCSHP, BCACP, CPHQ SCAL Pharmacy Sr Consultant

Andrea Smith, RN, MSN SCAL Nurse Consultant Kaiser Permanente Southern California Medical Group

I

n 2009, the Southern California Permanente Medical Groups (SCPMG) initiated the Outpatient Medication Safety Net Program to prevent potential harm to high-risk patients. SCPMG has taken several proactive steps in the initiative, including ordering nearly 400,000 overdue lab results to ensure proper drug therapy, changing the drug regimens of nearly 1,000 elderly patients to reduce their risk for fractures and falls, and revamping the regimens of thousands of patients to preserve normal renal function. In this Practice Pearl, the authors detail key reasons why the initiative was undertaken, the steps needed to achieve a successful outcome, and lessons learned for other health-systems facing similar medication safety challenges.

One of the primary drivers of the Safety Net program was the sheer size of SCPMG. It serves more than 3.6 million members and dispenses more than 2 million prescriptions a month. After SCPMG evaluated medication use across such a large scale, it identified significant breakdowns in medication use oversight that affected several different drug classes.

Some of those breakdowns were due to technological challenges. For example, although Kaiser Permanente operates

within an integrated care delivery system with a robust electronic medical record (EMR), potential gaps in the EMR system led to discharged patients being lost to follow-up.

The Safety Net program was designed in part to fill those informatics gaps. As a result, the initiative now can be used to identify and address groups of patients with significant outpatient medication safety risks at the regional level.

Support for Front-Line Care Part of the program’s success is due to the multidisciplinary approach taken to support frontline patient care. The care team consists of a pharmacist, a nurse consultant and two licensed vocational nurse (LVN) case coordinators. Specific projects fall into 3 realms of outpatient medication safety: delayed treatment, medication errors and mismanaged polypharmacy in the elderly. SCPMG implemented the following programs over the past 4 years (Figure 1): monitoring amiodarone dosing; preventing drug-disease interactions in elderly patients; initiating angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ ARB) therapy in diabetic hypertensive patients; reducing acetaminophen overuse; monitoring high-dose digoxin in elderly patients; monitoring lab values annually for ACEI, ARB, diuretics, and anticonvulsants; and converting gemfibrozil to alternative agents when appropriate in patients on statins.

A Centralized Approach SCPMG determined that a centralized development process and applying the initiative to small populations of less than 5,000 patients would be more effective than implementing the program across 14 different medical centers in the hospital network. Prior to implementation, a new initiative is vetted by a panel of subject-matter experts

that includes physicians, pharmacists, and nurses. Using this standardized process, new Safety Net ideas can be approved and implemented within a few months. Processes are maintained with structured protocols, data accuracy, staff accountabilities, and effective communications that ensure that providers are supported and patients are engaged to minimize outpatient medication safety risk. Once an initiative is launched, the lessons learned from the program become part of usual care and the volume of patients needing intervention is reduced.

The daily role of the pharmacist is to develop and lead the clinical interventions of each initiative. LVNs assist the pharmacist with non-clinical interventions involving pending labs, triaging, contacting patients, sending letters, and booking appointments. For the larger initiatives, such as the one that seeks to address overdue annual labs for diuretics and anticonvulsants, where the population is greater than 100,000 affected patients, Kaiser Permanente has the ability to leverage technology to batchorder labs and letters for patients.

Medication Safety Initiatives ACEI/ARB initiation

Studies have shown that ACEI/ARB therapy can slow the rate of progression to diabetic kidney disease and improve blood pressure control.1 If a patient has no exclusionary labs, allergies, or contraindications to use an ACEI/ARB, the pharmacists initiate an order for a formulary ACEI or ARB agent, along with follow-up labs. The LVN contacts patients by phone or letter, alerting them of the new medication order and the reasons for the new medication and the follow-up labs. If the patient never picks up the prescription or is delinquent on any of follow-up labs, he or she is contacted

via a phone call and letter until both compliance issues are resolved. If any follow-up labs are abnormal, indicating that there may be a problem with the drug regimen, charts are triaged to the pharmacist to reassess and discontinue the ACEI/ARB if warranted.

Potentially Harmful Elderly Drug-Disease Interactions

In 2011, the Outpatient Medication Safety Net Program added the potentially harmful drug-disease interactions initiative, which identified patients with a prior history of falls or dementia who are currently on medication that could increase the risk for another fall or affect cognition. The pharmacist’s role is to change the medication to a safer alternative or discontinue the medication if the patient no longer needs it. The LVN is responsible for contacting patients by phone or letter, to alert them of the change and the reasons for the change.

High-Dose Digoxin Conversion

In 2013, the high-dose digoxin initiative was added to the Safety Net program. As part of that effort, a pharmacist reviews the records of patients who qualify and reduces their dosages as needed. As with other components of the program, the LVN contacts patients by phone or letter to alert them of the change and the reasons for the change.

Gemfibrozil + Statins Conversion

In 2012, the FDA made the recommendation to avoid gemfibrozil in combination with most statins due to the risk for rhabdomyolysis.2 The pharmacist identifies different conversions available and changes patients to a safer alternative or discontinues the gemfibrozil. The LVN is responsible for contacting patients by phone or letter to alert them of the change and the reasons for the change.

Amiodarone Monitoring

The Case for Improving Medication Use

W

hy spend so much time and effort to ensure that health systems or hospitals are doing all they can to guarantee the safe use of medications in post-discharge patients?

Part of the reason is the risks of nott taking such measures: Although drug therapy can be lifesaving for many diseases, if the medications are not taken correctly and monitored appropriately, there is significant potential to cause harm.

According to the Institute for Safe Medication Practices (ISMP) executive annual summary (www.ismp.org/QuarterWatch), the FDA received notification of 210,648 serious, disabling, or fatal adverse drug events (ADE) in 2012, many occurring in the outpatient setting. This represents an increase of 16% from the previous year. (Most of the reported events were submitted by the manufacturers.)

A June 2013 report from IMS Health (http://bit.ly/1cjM8Hl) estimated that there are $213 billion in avoidable costs due to the inappropriate use of outpatient medications, leading to increased physician visits, hospitalizations, and emergency

department visits. The report focused on 6 key problem areas: nonadherence, delayed evidence-based treatment, antibiotic misuse, medication errors, suboptimal generic use, and mismanaged polypharmacy in the elderly, all of which can lead to potentially serious ADEs. Furthermore, it is likely that the number of ADEs will continue to increase in the future due to several factors, including the introduction of new and complex medications into the market, the aging population, an increase in the number of medications patients take concomitantly, the expansion of health care insurance, and a higher prevalence of chronic disease.

Clearly, the stakes are high for ensuring that facilities have programs in place to guarantee that medication use in the outpatient setting—and indeed, in all settings—is as safe as possible.

For more tips on how Kaiser Permanente addressed this challenge, email Jennifer Polzin, PharmD, at jennifer.k.polzin@kp.org.

Due to the potential serious adverse effects of amiodarone, patients must be annually or biannually monitored for liver, thyroid, QT or ophthalmic changes, and pulmonary toxicity.3 Prior to 2009, however, when SCPMG first implemented the amiodarone initiative, laboratory and pulmonary monitoring rates in patients taking amiodarone were substantially lower than recommended in guidelines. As a result of the initiative, patients with gaps of care are identified and the pharmacist and LVN work together to order all labs, procedures, and appointments and to clinically intervene when lab results are abnormal, ensuring that patients do not fall through the cracks while taking amiodarone.

Clinical 27

Pharmacy Practice News • January 2014

Practice Pearl Delayed Treatment

Elderly Mismanaged Poly-pharmacy

Medication Error References

Drug-disease Interactions

Gemfibrozil + statin Batch labs to uncover errors

ACEI/ARB in diabetes/hypertension

Amiodarone adverse effects High-dose digoxin Acetaminophen overuse

Acetaminophen (APAP) Overuse

In 2010, patients identified as using more than 4 g of APAP daily were sent to a primary care provider with a recommendation to change to another agent.

This initiative was based on data from FDA’s Adverse Event Reporting System and the Acute Liver Failure Study Group showing that the median daily dose of acetaminophen related to liver injury was 5 to 7.5 g/day, very near the current maximum daily dose of 4 g/day.4 Letters were sent to the patient to educate them on the risks of exceeding 4 g of APAP a day.

Promising Results Kaiser Permanente’s Safety Net Program has shown promising results. More than 370,000 overdue labs, for example, have been ordered in patients taking diuretics or anticonvulsants. Of those lab results, 16% were abnormal and alerted clinicians to the need for intervention.

More than 200 patients who were taking 4 g or more of APAP daily were identified and were no longer exceeding the daily dose after intervention. Eight hundred elderly patients taking anticholinergic medications were changed to safer medications to decrease fall and fracture risk.

Patients with dementia taking anticholinergic medications were also identified and more than 750 medications were discontinued. More than 1,600 individuals with diabetes and hypertension who were not receiving ACEIs or ARBs were initiated on one of the medications to preserve kidney function. More than 5,000 patients on concomitant statin plus gemfibrozil have been converted to a safer combination or another medication or discontinued if not needed. Post followup analysis shows these patients were safely converted to an alternative without any incidence of triglyceride-induced pancreatitis, and annual cases of rhabdomyolysis decreased from an average of 16 cases per year before the initiative to 3 cases in 2012.

nization could take a systemic approach to medication management, preventable ADEs and unnecessary visits to the hos-

pital or provider would be reduced and overall patient outcomes would improve significantly.

2. FDA Drug Safety Communication July 2012. www.fda.gov/drug/drugsafety/ucm293101.htm.

Accessed January 3, 2014.

3. Cordarone (Amiodarone) [package insert].

Philadelphia, PA: Wyeth Pharmaceuticals Inc. 2004.

4. FDA 2009. Acetaminophen overdose and liver injury—background and options for reducing injury. http://tinyurl.com/klzzv2. Accessed January 3, 2014.

PATIENT SAFETY. PharMEDium’s single highest priority.

Conclusion The Outpatient Medication Safety Net Program has been very successful in identifying patients at high risk for adverse medication-related events and intervening before harm. Each year the centralized program has been able to add more initiatives using technology and improved efficiencies, without adding additional costs. If every healthcare orga-

1. National Kidney Foundation. K/DOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am J Kidney Dis 2007;49(suppl 2):s1-180.

PharMEDium.com | 1-800-523-7749 twitter.com/pharmedium © PharMEDium Services, LLC 2014 P10377

28 Policy

Pharmacy Practice News • January 2014

Reimbursement Matters

2014 OPPS Payments Take a Hybrid Approach T

he hospital outpatient prospective payment system (OPPS) covers more than 4,000 hospitals or facilities and 5,000 Medicare-participating ambulatory surgery centers (ASCs).

OPPS includes payment for most hospital outpatient department services, as well as partial services furnished by hospital outpatient departments and community mental health centers.

Toward the end of 2013, all of these practice sites—particularly those with savvy finance departments—had at least one thing in common: a mounting curiosity about how scheduled updates to OPPS would effect reimbursement and billing procedures in 2014.

Unfortunately many facilities lag behind in being able to appropriately distribute funds or to unbundle. Is your facility one of these?

On Dec. 10, that curiosity was partly satisfied when the updates were published in the Federal Register (tinyurl. com/my2mnpl). After reading most of the key provisions in the 1,200-plus page document, I can say that the new rules can best be described as a hybrid of a prospective payment system and a fee schedule. This approach represents a continuing move away from only a fee-based payment strategy. The following three types of payments form the core of this new hybrid model: 1. Some payments that represent costs packaged into a primary service; 2. Other payments that represent cost of a particular item, service or procedure; 3. Payment amounts that vary according to the Ambulatory Payment Classification (APC) group to which a service is assigned.

Packaged Items Packaged payment means that the facility will be paid for the eligible line items that previously were separate as well as the facility visit in one payment rather than as individualized line items.

The unbundling or unpackaging of the payment with subsequent distribution to the appropriate departments is left as an internal finance function at the facility. This expanded concept is not a new one, but unfortunately many facilities lag behind in being able to appropriately distribute funds or to unbundle. Does your facility share this shortcoming? How can you work with your finance team to help expedite the process?

One step you can take is to ensure that you understand the new OPPS payment rules and communicate them effectively to your billing and finance department. A good place to start is to know that the new rules created five new categories of supporting items and services that are to be paid for as

a package or a bundle. These include: 1. Drugs, biologics and radiopharmaceuticals that function as supplies when used in a diagnostic test or procedure 2. Drugs and biologics that function as supplies when used in a surgical procedure, including skin substitutes. Skin substitutes will be classi-

“Reimbursement Matters” is a tool for maintaining your health system’s fiscal health.

Please email the author at bkirschen@aol.com with suggestions on reimbursement issues that you would like to see covered.

Table. Federal Register Table 33: Drugs and Biologicals with Pass-Through Status In CY2014 CY2013 CY 2014 CY 2014 HCPCS HCPCS Long Descriptor Code Code

Final Final CY CY 2014 2014 SI APC

C1204

A9520

Technetium Tc 99m tilmanocept, diagnostic, up to 0.5 millicuries

G

1463

C9130

J1556

Injection, immune globulin (Bivigam), 500 mg

G

9130

C9131

J9354

Injection, ado-trastuzumab emtansine, 1 mg

G

9131

C9132

C9132

Prothrombin complex concentrate (human), Kcentra, per i.u. of Factor IX activity

G

9132

C9290

C9290

Injection, bupivicaine liposome, 1 mg

G

9290

C9292

J9306

Injection, pertuzumab, 1 mg

G

9292

C9293

C9293

Injection, glucarpidase, 10 units

G

9293

C9294

J3060

Injection, taliglucerase alfa, 10 units

G

9294

C9295

J9047

Injection, carfilzomib, 1 mg

G

9295

C9296

J9400

Injection, ziv-aflibercept, 1 mg

G

9296

C9297

J9262

Injection, omacetaxine mepesuccinate, 0.01

G

9297

C9298

J7316

Injection, ocriplasmin, 0.125 mg

G

9298

N/A

C9133 a

Factor ix (antihemophilic factor, G 1467 recombinant), Rixubus, per i.u.

G

1467

N/A

C9441

a

Injection, ferric carboxymaltose, 1 mg

G

9441

N/A

C9497 a

Loxapine, inhalation powder, 10 mg

G

9497

N/A

J7508 a

Tacrolimus, Extended Release, Oral, 0.1 mg

G

1465

N/A

J9371 a

Injection, Vincristine Sulfate Liposome, 1 mg

G

1466

J0178

J0178

Injection, aflibercept, 1 mg vial

G

1420

J0716

J0716

Injection, centruroides (scorpion) immune f(ab)2, up to 120 milligrams

G

1431

J7315

J7315

Mitomycin, ophthalmic, 0.2 mg

G

1448

J9019

J9019

Injection, asparaginase (erwinaze), 1,000 iu

G

9289

Q4122

Q4122

Dermacell, per square centimeter

G

1419

Q4127

Q4127

Talymed, per square centimeter

G

1449

Q4131

Q4131

Epifix, per square centimeter

G

9366

Q4132

Q4132

Grafix core, per square centimeter

G

9368

Q4133

Q4133

Grafix prime, per square centimeter

G

9369

a. HCPCS codes C9133, C9441, C9497, 17508, and J9371 are effective Jan. 1, 2014 APC, Ambulatory Payment Classification; CY, current year; HCPCS, Healthcare Common Procedure Coding Syste ; SI, System; S , st statu tatuss indicator d cato .

Bonnie Kirschenbaum, MS, FASHP

fied as either high- or low-cost and will be packaged into the associated surgical procedures with other skin substitutes of the same class 3. Certain clinical diagnostic laboratory tests 4. Certain procedures described by add-on codes 5. Device removal procedures In certain cases, a separate payment will be made if the item or service is furnished on a different date of service as the primary service. The rule also created 29 comprehensive APCs to replace 29 existing device-dependent APCs, but with a modification to apply a complexity adjustment for the most complex multiple device claims with an implementation delay of these comprehensive APCs until calendar year 2015.

Action Step: Determine which products are going to fall into these new packaged payment categories (e.g., stress testing agents). Be sure to continue to bill for each of these line items although they will not be separately reimbursed

NEXT UP: Specialty Pharmacy The next “Reimbursement Matters” column will focus on specialty pharmacy and its impact on healthsystem finances. Here is an excerpt:

T

he surge in specialty pharmaceutical spending can no longer be ignored. No matter how uncomfortable some health systems may be with brown-bagging and other so-called “hassles” associated with these products, it is time to address this juggernaut. Not convinced?

Consider this: specialty pharmaceuticals are expected to be the biggest driver of branded drug spending in developed markets, with a projected 30% increase in spending over the next five years, according to the latest industry figures.

Are you ready to benefit from this market trend? Or are you going to continue to fight change and defend your culture, simply because “that’s the way we do it here?” Your decision on this important practice challenge will have a major impact—good or bad—on your hospital’s bottom line in coming years.

Policy 29

Pharmacy Practice News • January 2014

Reimbursement Matters by the Centers for Medicare & Medicaid Services (CMS) for Medicare patients.

This step continues to provide data as to the total cost of the procedure, and private payors may still reimburse for these products. Work internally with your finance team to create or enhance the internal fund transfer mechanism to insure credit to the pharmacy budget.

Payments for Cost Of a Particular Item As anticipated from the proposed rule published in fall 2013 and discussed in

LIPOSOMAL continued from page 24

relief for surgeries involving incisions of the abdominal wall between 3 and 12 cm.

“As of now, we apply local anesthetic for postoperative analgesia,” Dr. Logvinskiy said. “With nerve blocks we insert catheters next to the bundle of nerves, connected to continuous infusion pumps, where we insert medication. We have the associated costs of filling the pumps, creating the solution, nursing care—which can potentially be eliminated if you’re using a drug like liposome bupivacaine, with a single injection.”

Pacira funded the study.

—Ajai Raj

our December 2013 article (page 6), both pass-through drugs and separately payable medications costing more than $90 per day will continue to be reimbursed at average sales price (ASP) plus 6%. This, of course, will be reduced by approximately 2% for as long as sequestration remains in effect. (For a schematic description of this rule, see online version at www.pharmacypracticenews.com).

The usual annual reworking of the cache of pass-through drugs has occurred, resulting in 14 drugs and biologics losing their pass-through status

effective Dec. 31, 2013. Interestingly, only nine of these products will be separately paid for in 2014 and five no longer will be separately reimbursed, as noted in Table 32 in the final rule.

Drugs and biologics keeping or newly assigned pass-through status (Table 33 in the final rule; reprinted here) will have their pass-through payment rates reviewed on a quarterly basis with payment adjustment as needed.

Action Step: It is imperative that pharmacy be familiar with the drugs on these two lists. Look carefully at the 2014

Healthcare Common Procedure Coding System (HCPCS) because several have changed, as well as the status indicators that will show whether there is separate payment in 2014. Ensure that these HCPCS code changes have been added to the pharmacy computer system’s drug master files as well as to the charge description master.

The next few columns will continue to examine implications of these changes and offer suggestions and action steps.

As always, we welcome your comments and questions.

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BEDFORD LABS continued from page 8

reach the patients who need them.

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 United States. As we look toward the future, we remain focused on strengthening our relationships with customers and continuing to serve the needs of patients.

Bedford Laboratories is committed to continuing to address drug shortage, one of our industry’s most prevalent concerns.

We have been working closely with regulatory agencies and other third parties, including GPOs, to help ensure important medicines reach the people who need them most. It has been our experience, especially during times where a product is in critical need and considered to be in drug shortage, that GPOs are flexible, often working with multiple manufacturers in order to ensure supply to their members. We appreciate this partnership, and we hope that, together, we can continue to make progress against this industry wide challenge.

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30 Technology

Pharmacy Practice News • January 2014

Medication Safety

BIG DATA continued from page 1

Midyear Clinical Meeting. “This is a great example of how big data analytics can be leveraged to gather information and to generate important clinical insights so that patient safety can be improved,” said Mr. Owad, the senior vice president of Operational Excellence at Cardinal Health, in Dublin, Ohio, who was not involved in the project. In addition to the VA program, there are many commercially available dashboards (Table).

EHR Alerts Part of the Problem Jannet Carmichael, PharmD, the chair of the committee that developed the clinical dashboard (see screen shot, right), said her team was spurred to create the dashboard because many VISN 21 patients were receiving inappropriate medications or improper dosing despite the use of clinical EHR alerts. “This dashboard helped us overcome barriers like time limitations and clinical alert fatigue, while strengthening team efforts to improve ongoing medication safety,” said Dr. Carmichael, who is the VISN 21 pharmacy executive and postgraduate year 2 residency director at VA Sierra Pacific Network, in Reno, Nev. The 19 metrics were chosen based on systematic reviews of the VISN 21’s EHR, recommendations from national quality organizations, reviews of national medication safety warnings databases and published literature, she said. Some had previously been

Table. Companies with Dashboard Systems Armada Health Care Asolva, Inc bioMerieux, Inc Health Care Systems ICNet Systems, Inc McCreadie Group MedAccuracy LLC MedKeeper Oztech Systems PatientSafe Solutions, Inc Pharmaconomics, Inc Pharmacy OneSource Philips Healthcare Siemens Healthcare TheraDoc Truven Health Micromedex Solutions Vigilanz

piloted in a similar dashboard at one of the VISN 21’s six medical centers with success.

For example, one VISN 21 hospital used the dashboard to tighten monitoring of heart failure (HF) patients receiving eplerenone and spironolactone—a move prompted by a study showing that increased spironolactone use can boost the incidence of hyperkalemia ((N Engl J Med 2004;351:543-551). The dashboard flags all HF patients with an active spironolactone or eplerenone prescription whose records either do not include recent potassium or serum creatinine laboratory test results or whose lab results indicate high potassium levels or low serum creatinine levels.

In 2005—five years before the dashboard was implemented—approximately 3,550 VISN 21 patients were receiving spironolactone or eplerenone. As the number of patients on one of the two drugs increased to approximately 4,000 in 2010, just prior to the pilot program, the frequency of hyperkalemia-related hospitalizations and emergency department visits in the group also spiked, thus underscoring the need for improved management of these patients.

By the end of the three-year clinical dashboard pilot period, those improvements were readily apparent. Although the number of patients receiving eplerenone and spironolactone increased to 4,200 by the end of the pilot, hyper-

kalemia-related hospitalizations and emergency room visits remained steady.

Additionally, the 7.5% mortality rate in this patient group at the end of the pilot program was significantly lower than the 9.3% mortality rate Dr. Carmichael’s team found in 2005 (P ( =0.012). These positive outcomes were due in no small part to the 99% rate of provider compliance with pharmacist recommendations, the investigators noted.

A Consistent Approach Regardless of the specific intervention, the overall dashboard strategy at VISN 21 is the same: “We have pharmacists and pharmacist-led teams solely dedicated to looking through the dashboard results, identifying patients with suboptimal medication management, reviewing their records, and choosing from a variety of interventions, depending on the patient-specific situation,” Dr. Carmichael said. Interventions include ordering laboratory tests on behalf of the patient’s primary care provider, mailing lab test reminders directly to the patient, recommending dose or medication changes, or requesting a medication reconciliation, she noted.

As a result of those efforts, several additional outcomes related to the 19 targeted metrics improved during the three-year pilot period, including a 32% drop in the number of hypo-

glycemia cases and deaths in diabetic patients receiving glyburide and a 4% decrease in hospitalizations and emergency department visits due to metformin-related acidosis.

Overall, the dashboard prompted interventions for 113,000 patients over the three-year period, Dr. Carmichael reported. “Any health system with an [EHR] can implement a similar novel pharmacovigilance tool,” she said, “shifting patient care toward a more proactive versus reactive model.”

—David Wild Dr. Carmichael reported no relevant financial conflicts of interest. Dr. Owad is an employee of Cardinal Health, which provides financial funding for the ASHP Foundation’s Award for Excellence in Medication Use Safety.

Pharmacy Practice News TWEETS! Follow us @ PharmPracNews And send your Twitter handle to editor David Bronstein at davidb@mcmahonmed.com so we can follow you.

Best practices in automation, automation informatics and patient safety Don’t miss our debut issue, mailing in the Summer of 2014 Each annual installment of PTR will include: Practice Profiles Innovative health systems share tips on automation, CPOE and other key pharmacy technology rollouts.

The Safety Connection Bar coding, smart IV infusion pumps and other other hi-tech approaches to ensuring safe medication use.

ROI by the Numbers Want to ad technology but can’t convince the c-suite that it’s cost cost-effective? Our return on investment case studies can help.

Informatics Clinical decision support software and other methods for tapping into crucial diagnostic information at the point of care.

These are just a few of the topics and features on tap for our first issue. Interested in contributing?

Send an email with your article ideas to davidb@mcmahonmed.com

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Immune Globulins: Therapeutic, Pharmaceutical, Cost, and Administration Considerations JERRY SIEGEL, PHARMD, FASHP Clinical Associate Professor The Ohio State University College of Pharmacy Columbus, Ohio

F

or the past several years, the availability of immune globulin (Ig) products has been very good, so product shortages have not played a major role in product choice.

This allows clinicians to match the best product to the patient based on clinical condition and comorbidities.

New products have become available, providing more treatment options. For example, Bivigam (Biotest), a 10% liquid product for IV use, was released in early 2013. There now are 4 Ig products indicated for subcutaneous (SQ) use in patients with primary immunodeficiency: Gammagard Liquid (Baxter), Gammaked (Kedrion), and Gamunex-C (Grifols) come in 10% concentrations and can be administered intravenously or subcutaneously; Hizentra (CSL Behring) comes in a 20% concentration and can be administered subcutaneously. It should be noted that dosing adjustments are required for all SQ agents when converting from IV. Two products, Gammaked and Gamunex-C, are approved for use in patients with chronic inflammatory demyelinating polyneuropathy (IV only). Gammagard Liquid is approved to treat multifocal motor neuropathy.

A common question regarding Ig products relates to whether they all are the same. Although clinicians have considered all Ig products to have comparable efficacy, they are not pharmaceutically equivalent. It is imperative that Ig products not be interchanged without full consideration of the pharmaceutical differences.

The reasons for switching products may be clinical in nature and related to tolerability; they may be fiscal and based on contracting issues; or they may be due to product availability. It is best to consider product changes as if the patient is naive to Ig use, with increased monitoring and conservative infusion times.

Whereas Tables 1 to 5 may help facilitate these

I N D E P E N D E N T LY D E V E L O P E D B Y M C M A H O N P U B L I S H I N G

decisions, it is important to understand the clinical impact of changing products. Although all of the products contain primarily IgG, trace amounts of other Igs—IgA and IgM—as well as widely different stabilizing agents, may affect tolerability. The differences in salt, sugar, and overall osmolarity of these products are particularly important when patients have various comorbidities, such as renal dysfunction, diabetes mellitus, vascular disease, or heart failure. Differences between lyophilized and liquid products may result in changes in product concentration and infusion rate, as well as tolerability.

The tables in this review may be helpful for providing optimal care for patients receiving Ig products. They should be used as a general guide to help determine the product that is best suited for a particular patient population. Because there is variation from batch to batch, the exact numbers represent averages of selected batches; any one batch of any Ig product may have ranges outside these average numbers. When comparing administration rates, clinicians need to keep in mind that each patient has a maximum tolerated rate. This rate is based on patient tolerability and may be different for each product. Ig must be administered slowly initially and titrated as tolerated. The rate should be adjusted based on comorbidities as well. The infusion should be slowed or stopped if adverse events (AEs) become evident during the infusion. (See the prescribing information for each agent for more information about AEs.)

P H A R M AC Y P R AC T I C E N E WS • JA N UA RY 2 0 1 4

1

Table 1. Therapeutic Considerations FDAApproved IgA Indications Content

pH (after reconstitution) Plasma Source

Halflife, db

Pathogen Inactivation/Removal

Producta

Manufacturer

Bivigam 10%

Biotest Pharmaceuticals Medical info: (800) 458-4244 www.biotestpharma.com www.bivigam.com

PID

≤200 mcg/mL

4.0-4.6

Plasmapheresis, 30 US donors

Precipitation and removal of fraction III from resuspended fraction II+III, SD, 35 nm filtration

Carimune NF

CSL Behring Customer service: (800) 683-1288 Medical info: (800) 504-5434 www.cslbehring.com

ITP, PID

1,000-2,000 6.4-6.8 mcg/mL (6%)

Plasmapheresis, 23 US donors (>16,000)

pH 4.0/pepsin, nanofiltration, TSE removal

Flebogamma 5% DIF Flebogamma 10% DIF

Instituto Grifols SA Barcelona, Spain Customer service: (888) GRIFOLS www.grifols.com

PID

<3.2 mcg/mLc,d

5.6±0.1 (5%)c,d 5.5±0 (10%)c,d

US source IQPP-certified plasma from FDA-registered sites

4-week dosing: 32±5 (5%) 37±13 (10%)

Pasteurization (60°C, 10 h), SD, 20 nm nanofiltration, fraction I precipitation, fraction II+III incubation, PEG precipitation, acid treatment, TSE removal

Gammagard Liquid 10%

Baxter Healthcare Corp Direct inquiries: (800) 423-2090 www.baxter.com

MMN, PID

37 mcg/mL

4.6-5.1

Plasma from FDA-registered sites

35

SD, low pH, nanofiltration

Gammagard S/D 5%

Baxter Healthcare Corp Direct inquiries: (800) 423-2090 www.baxter.com

CLL, ITP, KD, PID

<1 mcg/mLe

6.4-7.2

Plasmapheresis, 37.7±15 10,000 donors

Gammaked 10%

Manufactured by Grifols Therapeutics Inc for Kedrion Biopharma Customer service/medical info: (855) 353-7466; www.gammaked.com; www.kedrion.com

CIDP, ITP, PIDf

47±13 mcg/mLc,d

4.0-4.5c,d US source IQPP-certified plasma from FDA-registered sites

35

Caprylate precipitation/depth filtration, caprylate incubation, depth filtration, column chromatography, low pH incubation, TSE removal

Gammaplex 5%

Bio Products Laboratory (distributed by FFF Enterprises) Customer service: (800) 843-7477 www.fffenterprises.com

ITP, PID

<10 mcg/mL

4.8-5.1

Plasma from FDA-registered sites

4-week dosing: 41±14

SD, nanofiltration, terminal low pH incubation

Gamunex-C 10%

Grifols Therapeutics Inc Customer service: (800) 243-4153 Medical info: (800) 520-2807 www.gamunex-c.com

CIDP, ITP, PIDf

51±1.4 mcg/mLc,d

4.0-4.5c,d

US source IQPP-certified plasma from FDA-registered sites

35

Caprylate precipitation/depth filtration, caprylate incubation, depth filtration, column chromatography, low pH incubation, TSE removal

Hizentra 20%

CSL Behring Customer service: (800) 683-1288 Medical info: (800) 504-5434 www.cslbehring.com www.hizentra.com

PID

≤50 mcg/mL

4.6-5.2

Plasmapheresis, NA US donors

pH 4.0 incubation, nanofiltration, depth filtration, virus filtration, TSE reduction

Octagam 5%

Octapharma Pharmazeutika Octapharma USA Customer service: (866) 766-4860 www.octapharma.com

PID

<200 mcg/mLg

5.1-6.0

US source and recovered plasma from FDA-registered sites

Cold ethanol, pH 4.0 incubation, SD

Privigen 10%

CSL Behring Customer service: (800) 683-1288 Medical info: (800) 504-5434 www.cslbehring.com; www.privigen.com

ITP, PID

≤25 mcg/mL

4.6-5.0

Plasmapheresis, 36.6 US donors (≥60,000)

Footnotes on page 7; Key on page 8.

2

I N D E P E N D E N T LY D E V E L O P E D B Y M C M A H O N P U B L I S H I N G

40

SD

pH 4.0 incubation, 20 nm virus filtration, depth filtration, TSE removal

IgG Subclass,c %

Type 1

Type 3

Haemophilus influenzae Type Bc

18.2 IU/mL

NA

NA

NA

NA

NA

NA

17 IU/mL

NA

Type 1: 0.99 x Ref (176)

2.8

3.6 IU/mL (NT)

313 (EIA)

180 (EIA)

1:60 (CF)

300 IU/mL (HAI)

1:512 (IFA); 1:2,560 (EIA)

1:348 (RIA)

1:64 (RIA)

1:128 (CF)

1:64 (NT)

2.7 (5%) 3.0 (10%)

2.2 (5%) 2.5 (10%)

7.0±1.0 NA IU/mL (5%); 13.7±1.4 IU/mL (10%)

NA

15±1 mg/L (5%)

NA

30±6 PEI U/mL (5%); 36±7 IU/mL (10%)

21±4 IU/mL (5%)

88.0± 41.8 IU/g Ig (5%); 80.7± 23.0 IU/g Ig (10%)

NA

NA

32.1

5

2.1

4.0 units/mL (NT)

NA

21.2 mcg/mL (EIA)

1:2,320 (EIA)

NA

68 PEI U/mL (EIA)

16.4 IU/mL (RIA)

≥0.20 IU/mL (EIA)

VZV: 32 U/mL (NT)

Type 1: 1:190 mIU/mL (NT)

67

25

5

3

2-5 IU/ mL (NT); J5 lipid A 1:273

17.5 mcgAbN/ mL (EIA)

8.5 mcg/mL (EIA)

11 mcg/mL (EIA)

1,150 IU (HH)

37 PEI mcg/mL (EIA), 1:2,480 (NT)

1:267 (RIA)

820 mIU/mL (RIA)

1:1,000 (EIA)

1:305 (NT)

62.8

29.7

4.8

2.7

7±2 AU/mL

87.4±22.2 mcg/mL

26.1±7.7 mcg/mL

13.0±2.4 mcg/mL

16,846± 13,648 Todd units/mL

57 PEI U/mL

1:139

65±19 IU/g Ig

NA

1:22±0.35

64

30

5

1

2.2 IU/mL

2.3 mcg/mL

NA

791 mcg/mL

185 IU/mL

431 U/mL

20 IU/mL

4.7 IU/mL

5,129 AU/mL

NA

62.8

29.7

4.8

2.7

7±2 AU/mL

87.4±22.2 mcg/mL

26.1±7.7 mcg/mL

13.0±2.4 mcg/mL

16,846± 13,648 Todd units/mL

57 PEI U/mL

1:139

65±19 IU/g Ig

NA

1:22±0.35

68.7

26.6

2.7

2

≥2.5 IU/mL

NA

NA

NA

≥1,000 IU/mL

NA

NA

≥0.4 IU/mL NA

NA

65

30

3

2

5-30 IU/mL

NA

NA

NA

600-800 IU/mL

33-40 IU/mL

21-25 IU/mL

51 IU/g

1:8,192

1:160-1:320 (NT)

67.8

28.7

2.3

1.2

4.9 (3.8-7.3) IU/mL

NA

NA

36.1 1,746 (26.4-45.0) (1,310IU/mL 2,010) IU/mL

76.4 (51.2-116.8) IU/mL

NA

5.3 (3.0-10.1) IU/mL

NA

NA

IgG1

IgG2

IgG3

IgG4

Diphtheria Toxinc

62.5

30.1

6

1.4

60.5

30.2

6.6

66.6

28.5 (5%) 27.9 (10%)

60.9

Streptococcus pneumoniaec

Streptolysin Oc

CMVc

HAVc

HBV Herpes (Surface Simplex Antibody)c Type 1c

Polio Type 2c

I N D E P E N D E N T LY D E V E L O P E D B Y M C M A H O N P U B L I S H I N G

3

Table 2. Pharmaceutical Considerations

Producta

Method of Preparation

Available Dosing Forms

Bivigam 10%

Cohn-Oncley,h cold ethanol fractionation, SD

IV

Liquid

≥96

100 monomer + dimers

Carimune NF

Kistler-Nitschmann,h pH 4.0 + trace pepsin, nanofiltration

IV

Lyophilized

≥96

92

Flebogamma 5% DIF Flebogamma 10% DIF

Cohn-Oncley,h ion-exchange chromatography, acid pH treatment, PEG precipitation, SD, pasteurization, dual nanofiltration (35+20 nm)

IV

Liquid

≥99c,d

>99.95 monomers + dimers (5%)c,d >99.89 monomers + dimers (10%)c,d

Gammagard Liquid 10%

Cohn-Oncley,h anion-exchange chromatography, SD, nanofiltration, ultrafiltration, low pH incubation

IV, SQ (SQ for PID only)

Liquid

≥98

≥95 monomers + dimers

Gammagard S/D 5%

Cohn-Oncley,h ultrafiltration, anion-exchange chromatography, SD

IV

Lyophilized

≥90

96.4

Gammaked 10%

Cold ethanol fractionation, anion-exchange chromatography, caprylate chromatography purified, low pH incubation

IV, SQ (SQ for PID only)

Liquid

100

100 monomers + dimersc,d

Gammaplex 5%

Cold ethanol fractionation, ion-exchange chromatography, SD, nanofiltration (20 nm), ultrafiltration, terminal low pH incubation

IV

Liquid

>99

≥99 monomers + dimers

Gamunex-C 10%

Cold ethanol fractionation, anion-exchange chromatography, caprylate chromatography purified, low pH incubation

IV, SQ (SQ for PID only)

Liquid

100

100 monomers + dimersc,d

Hizentra 20%

Cold ethanol fractionation, anion-exchange chromatography, octanoic acid fractionation, pH 4.0 incubation, depth filtration, nanofiltration (20 nm)

SQ

Liquid

≥98

≥90 monomers + dimers

Octagam 5%

Cold ethanol fractionation, ultrafiltration, anion-exchange chromatography, SD, pH 4.0 incubation

IV

Liquid

≥96

≥90 monomers + dimers

Privigen 10%

Cold ethanol fractionation, octanoic acid fractionation, anion-exchange chromatography, pH 4.0 incubation, depth filtration, nanofiltration (20 nm)

IV

Liquid

≥98

≥98 monomers + dimers

Footnotes on page 7; Key on page 8.

4

I N D E P E N D E N T LY D E V E L O P E D B Y M C M A H O N P U B L I S H I N G

Form

Gamma Globulin, %

Monomers, %

IgM Content

Albumin

PEG

Sodium Content

Stabilizer

Osmolality/Osmolarity

2.3 mcg/mL

<0.5%

NA

100-140 mEq/L

Glycine

≤510 mOsm/kg

Trace

0

0

0% water, 0.9% NS

5% sucrose

In sterile water: 3%, 192 mOsm/kg; 6%, 384 mOsm/kg; 12%, 768 mOsm/kg In NS: 3%, 498 mOsm/kg; 6%, 690 mOsm/kg; 12%, 1,074 mOsm/kg

Trace

<2 mcg/mL (5%)c,d <5 mcg/mL (10%)c,d

Not detectable

Trace (<3.2 mEq/L)c,d

5% sorbitol (polyol)

326±5.1 mOsm/kg (5%)c,d 343±6.1 mOsm/kg (10%)c,d

Trace

NA

Not detectable

No sodium added

Glycine

240-300 mOsm/kg

Trace

<3 mg/mL

<2 mg/mL

0.85%

2% glucose, glycine

636 mOsm/L (5%), 1,250 mOsm/L (10%)i

Trace

<2 mcg/mLc,d

0

Trace (<7 mEq/L)c,d

Glycine

264±3 mOsm/kgc,d

<0.02 mcg/mLj

0j

0j

30-50 mEq/L

Sorbitol, glycine, and polysorbate 80

420-500 mOsm/kg, but not less than 240 mOsm/kg

Trace

<2 mcg/mLc,d

0

Trace (<7 mEq/L)c,d

Glycine

264±3 mOsm/kgc,d

Trace

≤2 mcg/mL

NA

Trace

Proline

380 mOsm/kg

≤0.1 mg/mL

0

0

≤30 mEq/L

10% maltosek

310-380 mOsm/kg

3 mg/L

Trace

0

Trace

Proline

240-440 mOsm/kg

I N D E P E N D E N T LY D E V E L O P E D B Y M C M A H O N P U B L I S H I N G

5

Table 3. Cost Considerations Producta

Supply

Storagel

Distribution

Return Policy Warranty

Packaging or Labeling Enhancements

Bivigam 10%

5, 10 g

2°C-8°C, 24 mo; do not freeze

Wholesaler or direct

Shipping error; defective or damaged product; no out-of-date products

Tamper-evident seal, peel-off label with name, latex-free packaging, lot number, expiration date

Carimune NF

3, 6, 12 g

≤30°C, 24 mo

Wholesaler or direct

Shipping error; defective or damaged product; no out-of-date products

Tamper-evident seal, RSS bar code, peel-off label with lot number, expiration date

Flebogamma 5% DIF Flebogamma 10% DIF

2.5, 5, 10, 20 g (5%); 5, 10, 20 g (10%)

2°C-25°C, 24 mo; do not freeze

Wholesaler or direct

Shipping error; defective or damaged product; no out-of-date products

Tamper-evident seal with hologram, prior handling recognition, integral suspension band, laser-etched vials with UIN, bar code, peel-off label with product lot number

Gammagard Liquid 10%

1, 2.5, 5, 10, 20, 30 g

2°C-8°C, 36 mo; ≤25°C, 24 mo; do not freeze

Wholesaler or direct

No

Latex-free packaging, tamper-evident cap, RSS bar code, peel-off label with lot number, expiration date

Gammagard S/D 5%

2.5, 5, 10 g

≤25°C, 24 mo; do not freeze

Wholesaler or direct

No

Tamper-evident cap, peel-off label with lot number, expiration date

Gammaked 10%

1, 2.5, 5, 10, 20 g

2°C-8°C, 36 mo; ≤25°C, 6 mo; do not freeze

Wholesaler

Shipping error; defective or damaged product; no out-of-date products

Tamper-evident cap, laser-etched vials with UIN, NDC bar code, integral suspension band on larger vial sizes, peel-off label with product lot number, vial stopper not made with natural rubber latex

Gammaplex 5%

5, 10 g

2°C-25°C, 24 mo; do not freeze

Wholesaler

Shipping error; defective or damaged product; no out-of-date products

Latex-free, single-use vial, tamperevident cap, peel-off label with lot number, expiration date

Gamunex-C 10%

1, 2.5, 5, 10, 20 g

2°C-8°C, 36 mo; ≤25°C, 6 mo; do not freeze

Wholesaler or direct

Shipping error; defective or damaged product; no out-of-date products

Tamper-evident cap, laser-etched vials with UIN, NDC bar code, integral suspension band on larger vial sizes, peel-off label with product lot number, vial stopper not made with natural rubber latex

Hizentra 20%

1, 2, 4, 10 g

≤25°C, 30 mo

Wholesaler or direct

Shipping error; defective or damaged product; no out-of-date products

Latex-free packaging, single-use tamper-evident vials, peel-off label with lot number, expiration date

Octagam 5%

1, 2.5, 5, 10, 25 g

2°C-25°C, 24 mo; do not freeze

Wholesaler or direct

Shipping error; defective or damaged product; no out-of-date products

Tamper-evident, latex-free packaging, peel-off label with lot number, expiration date

Privigen 10%

5, 10, 20 g

≤25°C, 36 mo

Wholesaler or direct

Shipping error; defective or damaged product; no out-of-date products

Latex-free, single-use vial, tamperevident seal, RSS bar code, peel-off label with lot number, expiration date

Key on page 8.

6

I N D E P E N D E N T LY D E V E L O P E D B Y M C M A H O N P U B L I S H I N G

Table 4. IVIG Administration Ratesm Initial Infusion Rate

Maintenance Infusion Rate

Maximum Infusion Raten

Bivigam 10%

0.3 mL/kg/h for 10 min

Increase by 0.48 mL/kg/h every 20 min if tolerated up to 3.6 mL/kg/h

3.6 mL/kg/h

No filter required; for patients at risk for renal dysfunction or failure, administer at the minimum dose recommended and the minimum infusion rate practicablep

Carimune NF 3%-12%

0.48 mL/kg/h

1-2 mL/kg/h

3 mL/kg/h

Reconstitution time is several minutes; no filter required; compatible with NaCl, D5W; increased risk for renal and thrombotic adverse effectsp

Flebogamma 5% DIF Flebogamma 10% DIF

0.6 mL/kg/h

Increase gradually as tolerated to: 6 mL/kg/h (5%); 4.8 mL/kg/h (10%)

6 mL/kg/h (5%) 4.8 mL/kg/h (10%)

No filter required; administer at the minimum infusion rate practical to patients >65 and those at risk for renal failure or thrombotic eventsp

Gammagard Liquid 10%

0.5 mL/kg/h for 30 min (PID)

Increase every 30 min if tolerated, up to 5 mL/kg/h (PID)

5 mL/kg/h (PID)

No filter required; patients at risk for renal dysfunction or thrombotic events should be gradually titrated up to a more conservative maximum rate <2 mL/kg/hp

Gammagard S/D 5%

0.5 mL/kg/h for 30 min

Increase gradually as tolerated to: 4 mL/kg/h

4 mL/kg/h (5%)

Reconstitution time is <5 min at RT & >20 min if cold; 15-micron filter required and supplied with administration set; compatible with sterile water

Gammaked 10%

0.6 mL/kg/h 1.2 mL/kg/h (CIDP)

Increase gradually as tolerated to: 4.8 mL/kg/h

4.8 mL/kg/h

No filter required; do not dilute with NaCl, but NaCl flush is fine; incompatible with heparin (refer to full PI for details); administer at minimum infusion rate practical to patients >65 or at risk for renal or thrombotic eventsp

Gammaplex 5%

0.6 mL/kg/h for 15 min

Increase gradually as tolerated every 15 min to: 4.8 mL/kg/h

4.8 mL/kg/h

15- to 20-micron in-line filter recommended; ensure that patients with pre-existing renal insufficiency are not volume depleted; discontinue Gammaplex if renal function deteriorates; administer at minimum infusion rate practical to patients at risk for renal dysfunction or thrombotic eventsp

Gamunex-C 10%

0.6 mL/kg/h 1.2 mL/kg/h (CIDP)

Increase gradually as tolerated to: 4.8 mL/kg/h

4.8 mL/kg/h

No filter required; do not dilute with NaCl, but NaCl flush is fine; incompatible with heparin (refer to full PI for details); administer at minimum infusion rate practical to patients >65 or at risk for renal or thrombotic eventsp

Octagam 5%

0.6 mL/kg/h for 30 min

1.2 mL/kg/h for 30 min, then 2.4 mL/kg/h for 30 min, then as tolerated, up to maximum rate

<4.2 mL/kg/h

No filter required or supplied; if an in-line filter is used, the pore size should be 0.2-200 microns; for patients at risk for renal dysfunction or thrombotic events, administer at the minimum infusion rate practical, not to exceed 0.07 mL/kg/minp

Privigen 10%

0.3 mL/kg/h

As tolerated, up to maximum recommended rate

2.4 mL/kg/h (ITP) 4.8 mL/kg/h (PID)

No filter required; administer at minimum infusion rate practical to patients at risk for renal dysfunction or thrombotic eventsp

IVIGa

Commentso

FOOTNOTES a

All agents are contraindicated for IgA deficiency with antibodies to IgA.

b

Varies with disease state, immune status, and age of the patient.

ethanol fractionation; Kistler-Nitschmann is the specific cold ethanol fractionation method used by the manufacturer (CSL Behring). i

Limit infusion rate to <3.3 mg IgG/kg per minute (2 mL/kg/h) for 10% solutions.

c

Average of sample lots.

d

Data on file at Grifols.

j

Data on file at Bio Products Laboratory.

e

As of Dec. 2012, Baxter has discontinued Gammagard S/D 5%; the low IgA product will remain available for patients with known reactions to IgA or IgA deficiency with antibodies; all Gammagard S/D will be manufactured with IgA <1; special request only.

k

Maltose does not significantly affect serum glucose or insulin levels and can be safely administered to diabetic patients. Certain BGMS falsely interpret maltose, icodextrin, galactose, and xylose as glucose and can provide falsely elevated glucose readings. If insulin is administered as a result of these readings, hypoglycemia can occur. The BGMS that use test strips containing GDH-PQQ and GDO can provide these false readings. See PI for full details.

f

DO NOT USE Gammaked or Gamunex-C subcutaneously for ITP or CIDP.

g

With additional purification steps added in 2010, current release lots contain <100 mcg/mL. Data on file at Octapharma.

l

Under appropriate storage conditions.

h

Cohn-Oncley is the original method of cold

m

Some infusion rates were converted from those

listed in the PI for consistency and reader convenience. n

Certain severe adverse drug reactions may be related to the rate of infusion. Slowing or stopping the infusion usually allows the symptoms to disappear promptly.

o

Unless specific compatibility information is available, do not mix with other drugs or solutions.

p

Patients at high risk for thromboembolic events include patients who are elderly, overweight, or immobilized; patients with a history of hypertension, cardiovascular disease, or thrombotic disorders; and those who are >65 or dehydrated.

q

Log reduction factor values obtained from those listed in the PI; most are available on respective websites.

r

Data on file at Octapharma.

I N D E P E N D E N T LY D E V E L O P E D B Y M C M A H O N P U B L I S H I N G

7

Table 5. Log Reduction Factor Comparisonsq Enveloped Viruses

HIV Producta

Models for HCV

Model for Large DNA

SBV

BVDV

PRV

Nonenveloped Virus

TSE (Prion)

Bivigam 10%

>9.62

>7.11

>11.79

>8.65

5.29 (MEV), 6.18 (BPV), 4.0 (PPV), 7.02 (SV40)

NA

Carimune NF

≥26

≥19

≥9

≥25

≥19 (BEV)

NA

Flebogamma 5% DIF, 10% DIF

≥25.11

≥6.49

≥21.28

≥27.78

≥15.04 (PPV), ≥19.25 (EMCV)

≥11.64

Gammagard Liquid 10%

>14.8

NA

>16.8

>16.9

>5.7 (HAV), >7.7 (EMCV), >5.1 (MMV)

NA

Gammagard S/D 5%

>15 (HIV-1)

NA

>7.5

>9.3

>5.2 (HAV), >5.0 (EMCV), >5.3 (MMV)

NA

Gammaked 10%

≥14

NA

≥16.3

≥12.2

≥5.0 (HAV), 8.2 (PPV)

≥6.6

Gammaplex 5%

>12.9

>20.2

>11.7

NA

>5.9 (HAV), >7.5 (EMCV)

NA

Gamunex-C 10%

≥14

NA

≥16.3

≥12.2

≥5.0 (HAV)

≥6.6

Hizentra 20%

≥16.0

NA

≥11.8

≥17.7

≥9.6 (EMCV), ≥7.8 (MMV)

≥14.8

Octagam 5%

≥14.6

≥16.7

NA

≥16.1

≥9.5 (MEV), ≥7.7 (PPV)

≥6.7r

Privigen 10%

≥16.0

NA

≥11.8

≥17.7

≥9.6 (EMCV), ≥7.8 (MMV)

≥14.8

Footnotes on page 7.

KEY BEV

bovine enterovirus (RNA model)

HCV

hepatitis C virus

NDC

National Drug Code normal saline

BGMS blood glucose monitoring systems

HH

inhibition of hemolysis

NS

BPV

HIV

human immunodeficiency virus

NT

neutralization test

IFA

immunofluorescence assay

PEG

polyethylene glycol

PEI

Paul Ehrlich Institute International Units

bovine papillomavirus

BVDV bovine viral diarrhea virus CF

complement fixation

CIDP

IgA

immune globulin A

chronic inflammatory demyelinating polyneuropathy

IgG

immune globulin G

PI

prescribing information

CLL

chronic lymphocytic leukemia

IgM

immune globulin M

PID

primary immunodeficiency

CMV

cytomegalovirus

IQPP

International Quality Plasma Program

PPV

porcine parvovirus pseudorabies virus

D5W

dextrose 5% in water

ITP

idiopathic thrombocytopenic purpura

PRV

EIA

enzyme immunoassay

IU

international unit

RIA

radioimmunoassay

IVIG

intravenous immune globulin

RSS

reduced space symbology

SBV

Sindbis virus

SD

solvent detergent

SQ

subcutaneous

EMCV encephalomyocarditis virus (RNA model) FDA

Food and Drug Administration

GDH- glucose dehydrogenasePQQ pyrroloquinolone quinone

KD

Kawasaki disease

MEV

mouse encephalomyelitis virus

MMN

multifocal motor neuropathy

SV40 simian virus

MMV

mouse minute virus (model for non-lipid DNA virus)

TSE

transmissible spongiform encephalopathies

GDO

glucose-dye-oxidoreductase

HAI

heterologous anti-immunoglobulin

HAV

hepatitis A virus

NA

information not available

UIN

unique identifier number

HBV

hepatitis p B virus

NaCl

sodium chloride

VZV

varicella zoster virus

8

I N D E P E N D E N T LY D E V E L O P E D B Y M C M A H O N P U B L I S H I N G