The December 2011 Digital Edition of Pharmacy Practice News by McMahon Group

B WI U N Y TE G e in E R se U R rt I D ’S af te E r pa

The Pharmacist’s News Source

pharmacypracticenews.com

Volume 38 • Number 12 • December 2011

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Stories of Success In Cutting Costs Yet Preserving Value

s hospitals continue to pinch pennies, strategies that minimize waste and length of stay, while maximizing reimbursements and a pharmacist’s documented value, are crucial to the future of pharmacy practice. This was the message of several initiatives reported by health systems in 2011, each providing evidence that every dose, day and dollar can make a difference. The fact that hospitals are actively seeking ways to find more cost efficiencies in today’s practice model is not surprising to Robert T. Adamson, PharmD, corporate vice president of clinical pharmacy systems at Saint Barnabas Health Care System, in West Orange, N.J. “More than ever, pharmacy is under scrutiny,” Dr. Adamson said. “Since a hospital pharmacy

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see CUTTING COSTS, page 32

Serotonin Syndrome, Linezolid Alert Poses Challenge in MRSA

he FDA is warning that linezolid use in patients receiving serotoninergic drugs may cause serotonin syndrome. An agency statement dated Oct. 20 noted that linezolid’s often forgotten monoamine oxidase inhibitor (MAOI) properties can raise serotonin levels and lead to the central nervous system complication. The restricted use of linezolid in some methicillin-resistant Staphylococcus aureus (MRSA)infected patients receiving serotoninergic drugs “poses a significant clinical conundrum and a limitation for providers,” said Romy George, PharmD, an infectious diseases clinical pharmacist at Cooper University Medical Center, in Camden, N.J. “While there are oral alternatives to linezolid for the treatment of community-acquired MRSA, alternatives for hospital-acquired MRSA need to be administered intravenously. Given that IV treatment with these agents, such as daptomycin and

•

see LINEZOLID, page 14

in this issue Clinical

Practice Pearl VA strategies for meeting drug shortages head-on.

Critical Care Two new studies of tight glucose control in the surgical ICU a mixed bag.

Hem/Onc Pharmacy Aflibercept touted as breakthrough for colorectal cancer.

Operations & Mgmt

Leadership in Action After 35 years, one constant: Leaders don’t succeed on their own.

Medication Safety Practice-based research network shows its worth in drug-safety monitoring.

Policy

Drug Costs Patient assistance programs for oncology medications.

Drug Abuse Adolescents at high risk for prescription drug abuse.

Continuing Medical Education

Opioid REMS in Practice: How To Measure Success See page 17.

Educational Review

Management of Warfarin Therapy Access at pharmacypracticenews.com

Is QT Prolongation a Valid Reason To Abandon Zofran? Hem/onc pharmacists caution against overreaction

lthough the FDA is conducting a safety review of Zofran (ondansetron) because of its link to cardiac arrhythmias, some pharmacists say the drug is still useful in many patients, provided it is appropriately monitored. Ondansetron, used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy and surgery, is a serotonin type 3-receptor (5-HT3) antagonist. The FDA previously noted that ondansetron could prolong the QT interval of the electrocardiogram, which can lead to the potentially fatal heart rhythm known as torsades de pointes (TdP). In September, the agency announced it added a new warning that ondansetron should not be used in patients with congenital long QT syndrome because these patients are at particular risk for developing TdP. (Previous versions of the labels for ondansetron included a warning about QT interval prolongation.) The FDA also added recommendations for electrocardiogram monitoring in patients with electrolyte abnormalities, congestive heart failure and bradyarrhythmias, or in patients taking other medications that can

•

see QT Prolongation, page 28

Breakpoints to MICs Help Hone Pseudomonas aeruginosa Therapy Pittsburgh—Selecting the most appropriate antibiotic therapy can be a challenge when it comes to empirical treatment for severe, multidrugresistant infections, such as those caused by Pseudomonas aeruginosa. At the University of Pittsburgh Medical Center, clinical pharmacists bolstered the odds of success against likely P. aeruginosa infec-

New Product

tions by devising a combination antibiogram that applied pharmacodynamic (PD) breakpoints to minimum inhibitory concentration (MIC) distributions for a range of commonly used antibiotics. Inclusion of PD breakpoints led to “substantial changes” in antibiotic treatment

•

see BREAKPOINTS, page 14

The Book Page

AHP expands its line of unit-dose medications.

Pharmacotherapy Handbook, Eighth Edition

See page 40.

See page 41.

Barbara Wells, Joseph DiPiro, Terry Schwinghammer, Cecily DiPiro

Sandoz offers Enoxaparin Sodium Injection, USP

WARNING: SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: • Use of indwelling epidural catheters • Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants • A history of traumatic or repeated epidural or spinal punctures • A history of spinal deformity or spinal surgery Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis. Please see brief summary of full prescribing information including boxed warning on following page. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. www.us.sandoz.com © 2011 Sandoz Inc., a Novartis company. All rights reserved. SDZ0132

Available in 7 strengths in pre-filled syringes. ▲ 30 mg/0.3 mL pre-filled syringe; 40 mg/0.4 mL pre-filled syringe; 60 mg/0.6 mL pre-filled syringe; 80 mg/0.8 mL pre-filled syringe; 100 mg/1.0 mL pre-filled syringe; 120 mg/0.8 mL pre-filled syringe; 150 mg/1.0 mL pre-filled syringe ▲ Sandoz is a member of the Novartis family of companies — a name you can trust for quality and reliability Choose the full potential of generics.

Enoxaparin Sodium Injection,USP WARNING: SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: • Use of indwelling epidural catheters • Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants • A history of traumatic or repeated epidural or spinal punctures • A history of spinal deformity or spinal surgery Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

- - - - - - RECENT MAJOR CHANGES - - - - - Administration (04/2011) - - - - - - INDICATIONS AND USAGE - - - - - Enoxaparin sodium injection, USP is a low molecular weight heparin [LMWH] indicated for: • Prophylaxis of deep vein thrombosis (DVT) in abdominal surgery, hip replacement surgery, knee replacement surgery, or medical patients with severely restricted mobility during acute illness • Inpatient treatment of acute DVT with or without pulmonary embolism • Outpatient treatment of acute DVT without pulmonary embolism • Prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction [MI] • Treatment of acute ST-segment elevation myocardial infarction [STEMI] managed medically or with subsequent percutaneous coronary intervention [PCI] - - - - - - DOSAGE AND ADMINISTRATION - - - - - Indication

Dose

DVT prophylaxis in abdominal surgery

40 mg SC once daily

DVT prophylaxis in knee replacement surgery

30 mg SC every 12 hours

DVT prophylaxis in hip replacement surgery

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

DVT prophylaxis in medical patients

40 mg SC once daily

Inpatient treatment of acute DVT with or without pulmonary embolism

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

Outpatient treatment of acute DVT without pulmonary embolism

1 mg/kg SC every 12 hours *

Unstable angina and non-Q-wave MI

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

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

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

Acute STEMI in patients ≥75 years of age

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

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

- - - - - - ADVERSE REACTIONS - - - - - -

Most common adverse reactions (>1%) were bleeding, anemia, thrombocytopenia, elevation of serum aminotransferase, diarrhea and nausea To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. - - - - - - DRUG INTERACTIONS - - - - - Discontinue agents which may enhance hemorrhage risk prior to initiation of enoxaparin sodium injection or conduct close clinical and laboratory monitoring - - - - - - USE IN SPECIFIC POPULATIONS - - - - - Severe renal impairment: Adjust dose for patients with creatinine clearance <30 mL/min Geriatric patients: Monitor for increased risk of bleeding Patients with mechanical heart valves: Not adequately studied Hepatic Impairment: Use with caution Low-weight patients: Observe for signs of bleeding

Manufactured by Baxter Pharmaceutical Solutions LLC for Sandoz Inc., Princeton, NJ 08540 Rev. May 2011

4 Up Front

Pharmacy Practice News • December 2011

Capsules e-HIT Collaborative Advances Pharmacy Practice

surf

DECEMBER 2011

watch

The five most-viewed articles last month on pharmacypracticenews.com: 1. In Emergency Room, Pharmacists Slash Rate of Drug Errors 2. Oncology Drug Shortage Worsens; “Mayhem” Cited 3. Antibiotic Stewardship Made Simple: Pointers for Small Sites 4. The “Second Victims” of Medication Errors Begin To Gain Support 5. Leveraging 340B Savings To Re-Engineer Pharmacy Register for free at pharmacypracticenews.com to read these and other articles on the latest developments in hospital pharmacy.

heard here

‘Our data clearly suggest that complying with SCIP

INF-4 may not improve

first

outcomes, and [that]

the benefits of glucose control in cardiac surgery patients may be overstated.’ —Avery Tung, MD

See article, page 15

year after nine pharmacy organizations banded together to launch the Pharmacy e-HIT (health information technology) Collaborative, the group has gained additional members and continues to work on its goals. The collaborative was formed in September 2010 as a result of the Joint Commission of Pharmacy Practitioners’ strategic plan to ensure that pharmacists had a consistent message for national HIT initiatives. Its goals are to ensure the meaningful use of standardized electronic health records (EHR) that support safe, efficient and effective medication use, continuity of care, and provide access to the patient care services of pharmacists with other members of interdisciplinary patient care teams, and to ensure that the pharmacist’s role of providing patient care services is integrated into the national HIT framework. “Pharmacists have a role to play in HIT, not only for dispensing medications but information exchange, such as the documentation of medication therapy management, making sure that’s part of an electronic health record and exchanging that information with other health care providers,” said Rachelle “Shelly” Spiro, RPh, collaborative director and president of Spiro Consulting, Inc., a consulting firm specializing in long-term and post–acute care pharmacy services and HIT. The collaborative continues to pursue EHR standards that support the delivery and documentation of and billing for patient care services performed by pharmacists in all care settings. The group also has been working to influence HIT policy by submitting comments to the U.S. Department of Health and Human Services, the Office of the National Coordinator of HIT, and the Centers for Medicare & Medicaid Services about pharmacist-provided patient care services. The Pharmacy e-HIT Collaborative was established by the Academy of Managed Care Pharmacy, the Accreditation Council for Pharmacy Education, the American Association of Colleges of Pharmacy, the American College of Clinical Pharmacy, the American Pharmacists Association, the American Society of Consultant Pharmacists, the American Society of Health-System Pharmacists, the National Alliance of State Pharmacy Associations and the National Community Pharmacists Association. The National Council for Prescription Drug Programs, Surescripts, RelayHealth, Medco and Mirixa have since joined as associate members. For more information, go to www.pharmacye-hit.org.

e-HIT Scores in NEJM Study Recent evidence suggests that e-HIT initiatives such as EHR can positively impact patient care. A study in the New England Journal of Medicine (2011;365:825-833) found that the rate of achieving several composite standards for diabetes care was 35.1% higher at EHR practice sites than at paper-based sites (P<0.001). Overall, EHR sites were associated with higher achievement on eight of nine component standards, including receipt of a glycated hemoglobin value, testing for urinary microalbumin, prescribing an angiotensin-converting enzyme inhibitor, and conducting an eye examination to screen for diabetic retinopathy, among others. —Karen Blum

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Administration

Michele McMahon Velle, MAX Graphics/Creative Director

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

Volume 38 • Number 12 • December 2011 • pharmacypracticenews.com

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

Internal Medicine

EDITORIAL STAFF

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

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Biotechnology

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Indu Lew, PharmD, Livingston, NJ

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Cardiology

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McMAHON PUBLISHING Raymond E. McMahon, Publisher and CEO, Managing Partner

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6 Clinical

Pharmacy Practice News • December 2011

Practice Pearl

Practical Approaches for Handling Drug Shortages Ka Yiu Carmen Lam

Vaiyapuri Subramaniam, PharmD, MS

Vincent Calabrese, PharmD

PharmD Candidate University of Maryland School of Pharmacy Baltimore, Maryland

Associate Chief Consultant Pharmacy Benefits Management Services Department of Veterans Affairs, Washington, DC Clinical Affiliate Professor Nova Southeastern University College of Pharmacy Fort Lauderdale, Florida University of Maryland School of Pharmacy Baltimore, Maryland

Associate Chief Consultant Pharmacy Benefits Management Services Department of Veterans Affairs Hines, Illinois

ccording to the FDA, the number of drug shortages has nearly tripled over the last 6 years—jumping from 61 drug products in 2005 to 178 in 2010 and more than 200 in 2011.1,2 Such drug shortages, caused by a variety of factors (Table 1),3,4 adversely affect drug therapy regimens, patient care, and health system finances. The associated labor costs for health systems to address challenges of drug shortages are very high, and more than two-thirds of health-system pharmacists recently surveyed reported that available resources to manage drug shortage problems are insufficient.5 Against this backdrop, this practice pearl provides an update of current legislative efforts to alleviate drug shortages and offers practical strategies that federal agencies such as the US Department of Veterans Affairs (VA) use to address this issue.

interruption, or adjustment of the drug product by the manufacturer that likely would result in a shortage. The bills would be applied to any approved prescription drug, and HR 2245 also includes biologics. Upon receiving the notice from manufacturers, the FDA would be required to publish the information on current and pending shortages. These measures would allow extra time for physicians, pharmacists, and nurses to find potential substitutes and would allow the FDA to work with other manufacturers, both domestic and international, to find new sources of affected drug products. The goals are to prevent interruption in patient care and ensure patients receive optimal care. At press time, these bills were in

the first step of the legislative process and are expected to be debated over the next few months. In the meantime, on October 31, 2011, President Obama “issued an Executive Order directing the FDA and the Department of Justice to take action to help further reduce and prevent drug shortages, protect consumers, and prevent price gouging.”9 This executive order also encourages early notification of potential drug shortages and further requires the FDA to expedite review of new manufacturing sites, drug suppliers, and manufacturing changes to enhance manufacturing capacity.

The VA’s Approach As the largest integrated health

care system in the country, the VA has implemented various strategies for handling drug shortages. The VA’s actions also include borrowing drugs from private hospitals that may have excess stock and sharing supplies among VA hospitals. To increase efficiency and control, the VA also consolidated the dispensing of many products using its VA Consolidated Mail Outpatient Pharmacies (CMOPs), 7 regional pharmacies that provide comprehensive pharmacy services for the entire VA system. Additionally, VA pharmacists directly contact pharmaceutical manufacturers for more information or resolution dates regarding shortages. They also coordinate with their prime vendor contacts for drug products, directly contact manufacturers for available alternative sources of drug supplies, and work with VA pharmacists who have expertise in particular therapeutic areas for guidance on therapeutic alternatives and strategies to conserve supplies. Furthermore, to ensure that health care providers from all disciplines are well informed, the VA publishes a weekly pharmaceutical

Table 1. Supply Chain Factors Contributing to Drug Shortages

Legislative, Policy Initiatives In dealing with drug shortages, lack of advance notice is a primary concern for pharmacists. According to the Institute for Safe Medication Practices, “most pharmacists (40%) and pharmacy technicians (51%) learn about a drug shortage the hard way—when the pharmacy department fails to receive an ordered product from a wholesaler or manufacturer.”6 To address this problem, Senator Amy Klobuchar (D, MN) introduced the Preserving Access to Life-Saving Medications Act (S 296) in the Senate in February 2011.7 A companion bill (HR 2245) was introduced in the House of Representatives by Congresswoman Diana DeGette (D, CO) in June 2011 and referred to the House Committee on Energy and Commerce.8 Both bills aim to amend the Federal Food, Drug, and Cosmetic Act to provide the FDA with improved capacity to prevent drug shortages and to create an early warning detection system. Current federal law requires drug manufacturers to notify the FDA when production of critical drugs is being discontinued only when they are the sole manufacturer of the drugs.9 Under the new bills, manufacturers will be required to notify the US Department of Health and Human Services and health care providers 6 months in advance regarding any discontinuance, planned

Contributing Factors

How Does It Lead to Drug Shortages?

Contributing Percentage

• Production may be halted or delayed in response to FDA enforcement Product quality/significant action if products are noncompliant with USP standards for identity, CGMP issues (eg, particulate, strength, quality, purity, packaging, and/or labeling. contamination, impurities)

54%

Delays/capacity issues

• Change in product’s formulation or manufacturer may delay product availability. • Manufacturers may not have enough manufacturing capacity and may lack redundancy.

21%

Discontinuation

• If the costs associated with making a drug begin to outweigh the profits because of availability of generics or competing treatments, companies may wish to discontinue production of the drug in favor of a newer, more profitable product. • If the number of companies making an older drug decreases and there is a delay or problem in manufacturing, shortages can and do occur.

11%

Raw material issues

• The FDA inspects and approves suppliers of raw materials, which can take weeks or months. If manufacturers cannot obtain needed raw materials, they may be forced to discontinue the product line or wait until a new supplier is approved by the FDA. • Common business practice today dictates a “just-in-time” inventory system, so a small glitch in supply or production can become a major supply problem, resulting in a drug shortage.

Increase in demand/market shifts

• A change in clinical practice can lead to unexpected increases in demand. • Generic drugs becoming available may alter demand.

Loss of manufacturing site

• Manufacturer mergers often result in decisions to narrow the focus of product lines or move a production line to a new facility, resulting in discontinuation or delayed availability.

Others

• Drug shortages also may occur because of component problems or shortages that delay the product line. • Other factors such as natural disasters can influence product availability.

CGMP, current good manufacturing practices; USP, United States Pharmacopeia Based on references 3 and 4.

Pharmacy Practice News • December 2011

Clinical 7

Practice Pearls procurement newsletter, which includes the names of drug products in short supply with National Drug Code numbers, vendor names, comments, and expected dates of availability. To alleviate the effects of shortages of products prescribed to veterans who are outpatients, the VA reduces prescription quantity from 90-day to 30-day supplies. VA pharmacists did just that to deal with a recent shortage of mexiletine. Additionally, they routed all the orders through one CMOP to increase control and minimize waste.

To manage a recent shortage of the anesthesia drug succinylcholine, the VA first looked for therapeutic alternatives for appropriate patients. They then reserved the balance of succinylcholine injection on hand for emergency use and tried to extend its stability and shelf life by drawing up the product in syringes under the pharmacy hoods.

Conclusion Drug product supply issues are becoming more frequent and frustrat-

TEFLARO (ceftaroline fosamil) injection for intravenous (IV) use Rx Only Brief Summary of full Prescribing Information Initial U.S. Approval: 2010 INDICATIONS AND USAGE: Teflaro® (ceftaroline fosamil) is indicated for the treatment of patients with the following infections caused by susceptible isolates of the designated microorganisms. Acute Bacterial Skin and Skin Structure Infections - Teflaro is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca. Community-Acquired Bacterial Pneumonia - Teflaro is indicated for the treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli. Usage - To reduce the development of drug-resistant bacteria and maintain the effectiveness of Teflaro and other antibacterial drugs, Teflaro should be used to treat only ABSSSI or CABP that are proven or strongly suspected to be caused by susceptible bacteria. Appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to ceftaroline. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. CONTRAINDICATIONS: Teflaro is contraindicated in patients with known serious hypersensitivity to ceftaroline or other members of the cephalosporin class. Anaphylaxis and anaphylactoid reactions have been reported with ceftaroline. WARNINGS AND PRECAUTIONS: Hypersensitivity Reactions - Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterials. Before therapy with Teflaro is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. If this product is to be given to a penicillin- or other betalactam-allergic patient, caution should be exercised because cross sensitivity among betalactam antibacterial agents has been clearly established. If an allergic reaction to Teflaro occurs, the drug should be discontinued. Serious acute hypersensitivity (anaphylactic) reactions require emergency treatment with epinephrine and other emergency measures, that may include airway management, oxygen, intravenous fluids, antihistamines, corticosteroids, and vasopressors as clinically indicated. Clostridium difficile-associated Diarrhea - Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents, including Teflaro, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated [see Adverse Reactions]. Direct Coombs’ Test Seroconversion - Seroconversion from a negative to a positive direct Coombs’ test result occurred in 120/1114 (10.8%) of patients receiving Teflaro and 49/1116 (4.4%) of patients receiving comparator drugs in the four pooled Phase 3 trials. In the pooled Phase 3 CABP trials, 51/520 (9.8%) of Teflaro-treated patients compared to 24/534 (4.5%) of ceftriaxonetreated patients seroconverted from a negative to a positive direct Coombs’ test result. No adverse reactions representing hemolytic anemia were reported in any treatment group. If anemia develops during or after treatment with Teflaro, drug-induced hemolytic anemia should be considered. Diagnostic studies including a direct Coombs’ test, should be performed. If druginduced hemolytic anemia is suspected, discontinuation of Teflaro should be considered and supportive care should be administered to the patient (i.e. transfusion) if clinically indicated. Development of Drug-Resistant Bacteria - Prescribing Teflaro in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. ADVERSE REACTIONS: The following serious events are described in greater detail in the Warnings and Precautions section: Hypersensitivity reactions; Clostridium difficile-associated diarrhea; Direct Coombs’ test seroconversion. Adverse Reactions from Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be compared directly to rates from clinical trials of another drug and may not reflect rates observed in practice. Teflaro was evaluated in four controlled comparative Phase 3 clinical trials (two in ABSSSI and two in CABP) which included 1300 adult patients treated with Teflaro (600 mg administered by IV over 1 hour every 12h) and 1297 patients treated with comparator (vancomycin plus aztreonam or ceftriaxone) for a treatment period up to 21 days. The median age of patients treated with Teflaro was 54 years, ranging between 18 and 99 years old. Patients treated with Teflaro were predominantly male (63%) and Caucasian (82%). Serious Adverse Events and Adverse Events Leading to Discontinuation - In the four pooled Phase 3 clinical trials, serious adverse events occurred in 98/1300 (7.5%) of patients receiving Teflaro and 100/1297 (7.7%) of patients receiving comparator drugs. The most common SAEs in both the Teflaro and comparator treatment groups were in the respiratory and infection system organ classes (SOC). Treatment discontinuation due to adverse events occurred in 35/1300 (2.7%) of patients receiving Teflaro and 48/1297 (3.7%) of patients receiving comparator drugs with the most common adverse events leading to discontinuation being hypersensitivity for both treatment groups at a rate of 0.3% in the Teflaro group and 0.5% in comparator group. Most Common Adverse Reactions - No adverse reactions occurred in greater than 5% of patients receiving Teflaro. The most common adverse ®

ing for everyone involved, including pharmacists, physicians, nurses, and patients. Pharmacists should always be informed about the most recent updates from the FDA and American Society of Health-System Pharmacists through their drug shortages Web sites.10,11 They have the opportunity to take a leadership role in developing appropriate strategies and processes to ensure safe and uninterrupted therapies for patients. The VA’s strategies may be useful for health care systems handling drug shortage problems in

reactions occurring in > 2% of patients receiving Teflaro in the pooled phase 3 clinical trials were diarrhea, nausea, and rash. Table 4 in the full prescribing information lists adverse reactions occurring in ≥ 2% of patients receiving Teflaro in the pooled Phase 3 clinical trials (two in ABSSSI and two in CABP). The first value displays the percentage of patients in the pooled Teflaro trials (N=1300) and the second shows the percentage in the Pooled Comparatorsa trials (N=1297). Gastrointestinal disorders: Diarrhea (5%, 3%), Nausea (4%, 4%), Constipation (2%, 2%), Vomiting (2%, 2%); Investigations: Increased transaminases (2%, 3%); Metabolism and nutrition disorders: Hypokalemia (2%, 3%); Skin and subcutaneous tissue disorders: Rash (3%, 2%); Vascular disorders: Phlebitis (2%, 1%) a Comparators included vancomycin 1 gram IV every 12h plus aztreonam 1 gram IV every 12h in the Phase 3 ABSSSI trials, and ceftriaxone 1 gram IV every 24h in the Phase 3 CABP trials. Other Adverse Reactions Observed During Clinical Trials of Teflaro - Following is a list of additional adverse reactions reported by the 1740 patients who received Teflaro in any clinical trial with incidences less than 2%. Events are categorized by System Organ Class. Blood and lymphatic system disorders - Anemia, Eosinophilia, Neutropenia, Thrombocytopenia; Cardiac disorders Bradycardia, Palpitations; Gastrointestinal disorders - Abdominal pain; General disorders and administration site conditions - Pyrexia; Hepatobiliary disorders - Hepatitis; Immune system disorders - Hypersensitivity, Anaphylaxis; Infections and infestations - Clostridium difficile colitis; Metabolism and nutrition disorders - Hyperglycemia, Hyperkalemia; Nervous system disorders - Dizziness, Convulsion; Renal and urinary disorders - Renal failure; Skin and subcutaneous tissue disorders - Urticaria. DRUG INTERACTIONS: No clinical drug-drug interaction studies have been conducted with Teflaro. There is minimal potential for drug-drug interactions between Teflaro and CYP450 substrates, inhibitors, or inducers; drugs known to undergo active renal secretion; and drugs that may alter renal blood flow [see Clinical Pharmacology]. USE IN SPECIFIC POPULATIONS: Pregnancy Category B - Developmental toxicity studies performed with ceftaroline fosamil in rats at IV doses up to 300 mg/kg demonstrated no maternal toxicity and no effects on the fetus. A separate toxicokinetic study showed that ceftaroline exposure in rats (based on AUC) at this dose level was approximately 8 times the exposure in humans given 600 mg every 12 hours. There were no drug-induced malformations in the offspring of rabbits given IV doses of 25, 50, and 100 mg/kg, despite maternal toxicity. Signs of maternal toxicity appeared secondary to the sensitivity of the rabbit gastrointestinal system to broad-spectrum antibacterials and included changes in fecal output in all groups and dose-related reductions in body weight gain and food consumption at ≥ 50 mg/kg; these were associated with an increase in spontaneous abortion at 50 and 100 mg/kg. The highest dose was also associated with maternal moribundity and mortality. An increased incidence of a common rabbit skeletal variation, angulated hyoid alae, was also observed at the maternally toxic doses of 50 and 100 mg/kg. A separate toxicokinetic study showed that ceftaroline exposure in rabbits (based on AUC) was approximately 0.8 times the exposure in humans given 600 mg every 12 hours at 25 mg/kg and 1.5 times the human exposure at 50 mg/kg. Ceftaroline fosamil did not affect the postnatal development or reproductive performance of the offspring of rats given IV doses up to 450 mg/kg/day. Results from a toxicokinetic study conducted in pregnant rats with doses up to 300 mg/kg suggest that exposure was ≥ 8 times the exposure in humans given 600 mg every 12 hours. There are no adequate and well-controlled trials in pregnant women. Teflaro should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers - It is not known whether ceftaroline is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Teflaro is administered to a nursing woman. Pediatric Use - Safety and effectiveness in pediatric patients have not been established. Geriatric Use - Of the 1300 patients treated with Teflaro in the Phase 3 ABSSSI and CABP trials, 397 (30.5%) were ≥ 65 years of age. The clinical cure rates in the Teflaro group (Clinically Evaluable [CE] Population) were similar in patients ≥ 65 years of age compared with patients < 65 years of age in both the ABSSSI and CABP trials. The adverse event profiles in patients ≥ 65 years of age and in patients < 65 years of age were similar. The percentage of patients in the Teflaro group who had at least one adverse event was 52.4% in patients ≥ 65 years of age and 42.8% in patients < 65 years of age for the two indications combined. Ceftaroline is excreted primarily by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in this age group and it may be useful to monitor renal function. Elderly subjects had greater ceftaroline exposure relative to non-elderly subjects when administered the same single dose of Teflaro. However, higher exposure in elderly subjects was mainly attributed to age-related changes in renal function. Dosage adjustment for elderly patients should be based on renal function [see Dosage and Administration and Clinical Pharmacology]. Patients with Renal Impairment Dosage adjustment is required in patients with moderate (CrCl > 30 to ≤ 50 mL/min) or severe (CrCl ≥ 15 to ≤ 30 mL/min) renal impairment and in patients with end-stage renal disease (ESRD – defined as CrCl < 15 mL/min), including patients on hemodialysis (HD) [see Dosage and Administration and Clinical Pharmacology]. OVERDOSAGE: In the event of overdose, Teflaro should be discontinued and general supportive treatment given. Ceftaroline can be removed by hemodialysis. In subjects with ESRD administered 400 mg of Teflaro, the mean total recovery of ceftaroline in the dialysate following a 4-hour hemodialysis session started 4 hours after dosing was 76.5 mg (21.6% of the dose). However, no information is available on the use of hemodialysis to treat overdosage [see Clinical Pharmacology]. Distributed by: Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, Inc. St. Louis, MO 63045, USA Teflaro is a registered trademark of Forest Laboratories, Inc. IF95USCFR04 Revised: April 2011 © 2010 Forest Laboratories, Inc. All rights reserved. 69-1020503-BS-A-APR11 Please also see full Prescribing Information at www.teflaro.com.

both outpatient and inpatient settings. The key to success is proper planning to anticipate and address impending drug shortage Scan for more problems ahead drug shortage of time to minicoverage. mize interruptions of appropriate pharmacotherapeutic treatment.

References 1. US Food and Drug Administration. FDA works to lessen drug shortage impact. US Food and Drug Administration. Published June 9, 2011. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm258152.htm. Accessed October 17, 2011. 2. Shaw G. Oncology drug shortage worsens; mayhem cited. Pharm Pract News. 2001;38(11):1,22,24. 3. Kaakeh R. Sweet BV. Reilly C. Bush C. DeLoach S. Higgins B. Clark AM. Stevenson J. Impact of drug shortages on U.S. health systems. Am J Health Syst Pharm. 2011;68(19):1811-1819. 4. US Food and Drug Administration. FDA Webinar on prescription drug shortages. US Food and Drug Administration. http://www.fda.gov/ downloads/AboutFDA/Transparency/Basics/ UCM273360.pdf. Published September 30, 2011. Accessed November 7, 2011. 5. ASHP guidelines on managing drug product shortages. Am J Health Syst Pharm. 2001;58(15):1445-1450. 6. ISMP. Drug shortages: national survey reveals high level of frustration, low level of safety. ISMP Medication Safety Alert! http:// www.ismp.org/Newsletters/acutecare/ articles/20100923.asp. September 23, 2010. Accessed October 28, 2011. 7. GovTrack.us. Text of S 296: Preserving Access to Life-Saving Medications Act. Civic Impulse, LLC. http://www.govtrack.us/congress/billtext.xpd?bill=s112-296. 8. GovTrack.us. Text of HR 2245: Preserving Access to Life-Saving Medications Act of 2011. Civic Impulse, LLC. http://www.govtrack.us/ congress/billtext.xpd?bill=h112-2245. June 21, 2011. Accessed October 31, 2011. 9. Office of the Press Secretary. Fact sheet: Obama administration takes action to reduce prescription drug shortages in the U.S. The White House. http://www.whitehouse.gov/ the-press-office/2011/10/31/fact-sheet-obamaadministration-takes-action-reduce-prescription-drug-sh. October 31, 2011. Accessed November 7, 2011. 10. Current drug shortages. US Food and Drug Administration (FDA). http://www.fda. gov/Drugs/DrugSafety/DrugShortages/ ucm050792.htm. 11. Drug shortages: current drugs. American Society of Health-System Pharmacists (ASHP). http://www.ashp.org/DrugShortages/ Current/.

This article was written by the authors in their private capacity. No official support or endorsement by the VA is intended or should be inferred. At the time of writing this article, Ka Yiu Carmen Lam was a pharmacy student on training rotation at VA Pharmacy Benefits Management Services, Washington, DC.

8 Clinical

Pharmacy Practice News • December 2011

Journal Scan

Psychiatric Pharmacist Consultation Improves Inpatient Outcomes and approved by a senior psychiatric pharmacist. The consult service was available to practitioners on a referral basis, with the referring physician identifying a primary reason for the referral. Pharmacists in the consultation service also found secondary issues and made recommendations for them. Outcomes were assessed using 2 Clinical Global Impression (CGI) scales, CGI-Severity (CGI-S) and CGIImprovement (CGI-I), which evaluate a patient’s global symptom severity and the extent to which the patient’s symptoms have improved or worsened. The researchers found that 66.9% of pharmacist recommendations were implemented by treating physicians: 72.9% of the pharmacist recommenda-

From Journal of the American Pharmacists Association

mplementing clinical pharmacists’ recommendations for treating psychiatric patients results in better clinical outcomes, according to a study by researchers at the University of Texas at Austin (J Am Pharm Assoc 2011;51:599-604). In the study, researchers conducted a retrospective chart review of patients who received a pharmacy consult while admitted to Austin State Hospital between Sept. 1, 2005 and May 31, 2006, analyzing 105 pharmacy consultations and associated physician progress notes. Consultations were provided by 11 psychiatric pharmacists, psychiatric pharmacy residents or student pharmacist interns, with those completed by residents or interns being reviewed

tions related to the reason for referral and 46% of the secondary recommendations were implemented. To assess outcomes based on whether recommendations were implemented, the researchers divided consultations into 2 groups, high or low level of implementation. If 80% or more of the primary consult recommendations were implemented, a patient was categorized into the highlevel group (53.3% of patients in the study), with the remaining patients in the low-level group. When evaluating the implementation of recommendations in these groups, the researchers found that patients in the highlevel group had more favorable CGI-S scores and a better CGI-I rate than the low-level group.

COMMENTARY Lawrence J. Cohen, PharmD, BCPP, FASHP, FCCP Professor of Pharmacotherapy Washington State University College of Pharmacy President American College of Clinical Pharmacy

Pharmacists have been performing consultations for a long time in primary and ambulatory care, and this paper demonstrates the improvement that these kinds of activities can make in psychiatric inpatient care. I am encouraged by the finding that the recommendations were followed by physicians nearly 73% of the time and that following the recommendations led to better outcomes. That is certainly what we desire to see.

As we go through the economic downturn in this country, we [psychiatric pharmacists] are going to be under increasing scrutiny as mental health professionals to prove that what we do is cost-effective. Part of the puzzle is doing what the Austin team has demonstrated with inpatients in this paper. I am not surprised at the results or that the recommendations were adopted. This is a stationary staff—the

physicians and pharmacists have a history of working together as a health care delivery team and working as colleagues to get patients well. We need to have more of that, especially with what is being proposed with accountable care organizations and the medical home model. By working collectively you can improve outcomes, which is our primary goal, and the Centers for Medicare & Medicaid Services will pay for it, as well.

Medical Residents See Pharmacists as ‘Go-To’ Sources for Supervision From Journal of Hospital Medicine

esidents in critical care medicine depend on interprofessional supervision when making medication-related decisions and often rely on pharmacists for nonjudgmental answers to their questions, according to a multicenter study (J Hosp Med 2011;6:448-456). The findings were based on inter-

views with 17 residents who worked in the intensive care units of 3 hospitals where medication error prevention was particularly important because of the proportion of vulnerable patients or the extensive use of highly hazardous drugs. The research team coded interview transcripts by theme and included the residents’ descriptions of their experiences.

The residents described how they were supervised by other physicians per the traditional medical hierarchy, and by other health professionals, including nurses, staff pharmacists and clinical pharmacists. The residents, who were at different stages of their training, through the fourth year, consistently reported that pharmacists used deferential language by asking ques-

tions instead of directly stating their concerns. The residents also described pharmacists as reliable, extremely useful, helpful and approachable. The researchers also found that residents, mindful that supervising physicians evaluate them, “selectively sought nonjudgmental advice from professionals outside the medical hierarchy,” including pharmacists.

COMMENTARY Amy L. Seybert, PharmD Associate Professor Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy Pittsburgh, Pennsylvania

—Compiled by Terri D’Arrigo

I was grateful to see this study because it highlighted what pharmacy education is trying to do by focusing on interprofessional care. It demonstrated how pharmacists can help improve patient safety through interprofessional education, and showed the willingness of pharmacists to provide that education in a positive way.

This study also reflects pharmacist education in that it provides good examples of nonjudgmental language and how we are trained to communicate. Our own pharmacy residency programs focus on this very well, teaching residents to interact as part of a team. That is something pharmacy residents take into their practice

as they work with other health care professionals. It can only enhance our role as care providers as the emphasis shifts toward a team environment and pharmacy is no longer seen as an independent profession. The study is a small one, but it’s a good start and shows that we are headed in the right direction.

None of the commentators had any relevant disclosures.

Pharmacy Practice News • December 2011

Clinical 9

Journal Scan

Entrepreneurism, Availability of Resources Key to Practice Change From Research in Social & Administrative Pharmacy

new analysis of the 2004 National Pharmacy Workforce Survey of outpatient pharmacies suggests that changes in pharmacy practice are affected not only by the availability of resources but also by several aspects of what study authors call “entrepreneurial orientation” (EO). Researchers at the University of Iowa College of Pharmacy and several other centers analyzed a subset of 400 surveys on dimensions of EO such as proactiveness, risk taking, autonomy and

work ethic. Of these 4 dimensions, proactiveness and employee autonomy had the greatest impacts on practice change (Res Social Adm Pharm 2011 Sep 27. [Epub ahead of print]). The survey contained questions about pharmacy services offered, dimensions of EO, adequacy of resources to provide pharmacy services and how much the pharmacy had changed over the past 2 years. The amount of change was

assessed by 12 categories that provided a snapshot of staffing and workflow. The team also assessed levels of proactiveness, risk taking, autonomy and work ethic by measuring 3 of the items using a 5-point Likert scale, and they evaluated the respondents’ perceived adequacy of resources by measuring 6 items that included both tangible and intangible resources. The researchers found that the most

commonly reported changes were changes in patient information collected, the pharmacy’s documentation system, the skills and knowledge of the pharmacists, and the responsibilities and activities of the pharmacy technicians. The occurrence of practice change was significantly associated with 2 dimensions of EO (proactiveness and autonomy), the availability of adequate resources and pharmacy technician staffing.

COMMENTARY Ernest R. Anderson Jr., MS, FASHP System Vice President of Pharmacy Steward Health Care Boston, Massachusetts

Although this study included hospitals, it is more focused on the retail sector. When considering the results at an outpatient pharmacy in a hospital, you need to look at clinic practices there. What is the EO in that type of setting? If you think about reimbursement and what type of scenarios you can put together to take care of the patient in a cost-effective way, the model would be that pharmacists work with physicians in clinics to get patients to their goals. The survey was conducted in 2004, and a lot has occurred since then. That is not to take away from the design of the study but to consider that in the time since these data were collected, hospitals and health systems have been introduced to ideas such as those put forth in the Pharmacy Practice Model Initiative (PPMI). For example, the increased use of pharmacy technicians was an important change noted in the paper. That is also one of the goals of the PPMI. Increased use of technicians would allow pharmacists more time to work with patients, and someone who had a strong EO might speak with physicians about working together, especially when accountable care organizations are on the horizon as part of the Affordable Care Act. We need to address the basic premise of the study, that of looking at EO and the adequacy of resources, in a way that advances the profession. It would be helpful to redo the survey now, given how things have changed in the marketplace, the adoption of new regulations governing pharmacy practice, and the greater opportunities for pharmacists that have arisen since 2004.

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PREMIXED AMIODARONE. 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. 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: s

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

s 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.

s 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. 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.

s 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.

s Like all antiarrhythmics, NEXTERONE may cause worsening of existing arrhythmias or precipitate a new arrhythmia. s The most common adverse reactions leading to discontinuation (1-2%) of intravenous amiodarone therapy are hypotension, asystole/cardiac arrest/pulseless electrical activity, VT, and cardiogenic shock.

s Other important adverse reactions are torsade de pointes (TdP), congestive heart failure, liver function test abnormalities, pulmonary disorders, and thyroid abnormalities. s 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. 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 ďŹ brillation (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 patientâ&#x20AC;&#x2122;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: s +NOWN HYPERSENSITIVITY TO ANY OF THE COMPONENTS OF .%84%2/.% 0REMIXED )NJECTION 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 (inďŹ&#x201A;ammation around blood vessels). s #ARDIOGENIC SHOCK s -ARKED SINUS BRADYCARDIA s 3ECOND OR THIRD DEGREE ATRIO VENTRICULAR !6 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 beneďŹ ts 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 signiďŹ cant hypotension during infusions was seen most often in the ďŹ rst 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 difďŹ cult because the values may be elevated in patients who have had recent myocardial infarction, congestive heart failure, or multiple electrical deďŹ brillations. Approximately 54% of patients receiving intravenous amiodarone in clinical studies had baseline liver enzyme elevations, and 13% had clinically signiďŹ cant 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 conďŹ&#x201A;uent 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]. )N PATIENTS WITH LIFE THREATENING ARRHYTHMIAS THE POTENTIAL RISK OF HEPATIC INJURY SHOULD BE WEIGHED against the potential beneďŹ t of NEXTERONE therapy. Carefully monitor patients receiving NEXTERONE FOR EVIDENCE OF PROGRESSIVE HEPATIC INJURY )N 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 ďŹ&#x201A;uoroquinolones, 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 4HERE HAVE BEEN POSTMARKETING REPORTS OF ACUTE ONSET DAYS TO WEEKS PULMONARY INJURY IN PATIENTS treated with intravenous amiodarone. Findings have included pulmonary inďŹ ltrates 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 ďŹ brosis. 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.

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

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. 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. 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. 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.

CONTROLLED AND OPEN-LABEL STUDIES (> 2% INCIDENCE) Study Event

Controlled Studies (n=814)

Open-Label Studies (n=1022)

Total (n=1836)

Body as a whole Fever

Body as a whole 24 (2.9%)

Body as a whole 13 (1.2%)

Body as a whole 37 (2.0%)

Cardiovascular System Bradycardia Congestive heart failure Heart arrest Hypotension Ventricular tachycardia

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 Liver function tests normal Nausea

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 Cardiovascular: hypotension (sometimes fatal), sinus arrest Dermatologic: toxic epidermal necrolysis (sometimes fatal), exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, skin cancer, pruritus, angioedema 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: myopathy, muscle weakness, rhabdomyolysis Nervous System: hallucination, confusional state, disorientation, and delirium, pseudotumor cerebri Pancreatic: pancreatitis

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.

Renal: renal impairment, renal insufﬁciency, acute renal failure

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%).

Vascular: vasculitis

Respiratory: 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 Thyroid: thyroid nodules/thyroid cancer

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

Sourced from: 07-19-65-459 Rev. November 2010

14 Clinical

Pharmacy Practice News • December 2011

Infectious Disease

BREAKPOINTS continued from page 1

recommendations, according to the pharmacist-researchers, who presented the results of their investigation at the American College of Clinical Pharmacy annual meeting (abstract 135). The study was based on 376 P. aeruginosa isolates identified from blood or bronchoalveolar lavage cultures at three ICUs from January 2009 to December 2010. “There were some striking findings,” said Brian A. Potoski, PharmD, BCPS (AQ-ID), associate director of the medical center’s Antibiotic Management Program and one of the authors. For example, he said, although cefepime has been used extensively as monotherapy at the medical center, “we found that we should probably not be [using] cefepime in the empiric setting, at least by itself, based on the PD breakpoint.” Drawing on the medical center’s susceptibility and MIC data, the researchers also found that the optimal PDbased combination therapy for P. aeruginosa involved the use of a ß-lactam antibiotic with an aminoglycoside. The top selection reported in their study was piperacillin-tazobactam plus tobramycin, followed closely by meropenem plus tobramycin. “We think that’s important,” Dr. Potoski said, “because there seems to be this reflex to use just a quinolone along with a ß-lactam backbone. That doesn’t give you the best

LINEZOLID continued from page 1

vancomycin, comes with attendant risks of infusion-site infections, this means trading off one possible set of adverse events for another.” Dr. George urged providers to make their decision to use or not to use linezolid on a case-by-case basis, weighing the risks and benefits based on patient presentation, type of infection and organism susceptibility profile. Patients who are administered the two drugs in combination need to be followed to ensure serotonin syndrome does not develop, she said.

chance for appropriate therapy.” Dr. Potoski noted that susceptibility patterns can vary greatly from institution to institution, even between those in the same locality. “It might be worthwhile,” he said, “for other institutions to take a look at using these methods because they might find something very different and yet very appropriate and important for their populations.” The PD breakpoints recommended by the Pittsburgh researchers were at least 50% lower than those published by the Clinical and Laboratory Standards Institute (CLSI). “We know that there are certain MICs for particular antibiotics that are extremely unattractive,” Dr. Potoski explained, adding that outcomes at those MICs “are poorer” than those attained at lower MICs, even if the organism has been shown to be susceptible. PD breakpoints recommended in the Pittsburgh P. aeruginosa antibiogram included cefepime no greater than 4 mcg/mL (vs. the CLSI standard of up to 8 mcg/mL); piperacillin-tazobactam no greater than 16 mcg/mL (vs. up to 64 mcg/mL); meropenem 2 mcg/mL or less (vs. 4 mcg/mL); and tobramycin 2 mcg/ mL or less (vs. up to 4 mcg/mL).

Getting the Complete Picture David P. Nicolau, PharmD, FCCP, FIDSA, director of the Center for AntiInfective Research & Development at Hartford Hospital, Hartford, Conn., said, “Certainly we understand as a collective that there are some inadequacies

Table. SSRIs Implicated in the AERS Cases of Serotonin Syndrome With Linezolid

Many Cases—Some Fatal— Reported The FDA’s warning is based on several reports submitted to its Adverse Event Reporting System (AERS) that described patients receiving drugs with serotoninergic activity who developed serotonin syndrome after being administered linezolid. Some cases resulted in death, the FDA statement said. The FDA staff also conducted a literature

Generic Name

Brand Names

Citalopram

Various

Escitalopram

Lexapro

Fluoxetine

Various

Fluvoxamine

Various

Paroxetine

Various

Sertraline

Various

Vilazodonea

Viibryd

lthough the FDA has not received cases of A serotonin syndrome to date involving vilazodone, the pharmacology of this drug places it in the SSRI category and suggests that it possesses a risk comparable to that of the SSRIs.

AERS, Adverse Event Reporting System; SSRI, selective serotonin reuptake inhibitor

search that yielded several reports of serotonin syndrome, including one related death, in patients receiving this drug combination (Pharmacotherapy 2006;26:269-276).

from simply presenting susceptibility as defined by the laboratory. It works for a great many patients, but it doesn’t give the complete picture. So the [pharmacodynamic] approach is an opportunity to not only try to pick the right drug but also the right dose, dosing interval and infusion technique to optimize exposures. “What these folks basically said was, ‘Hey, at the end of the day we can’t get there with one drug. So we’re going to take a PD-optimized drug A and ... PDoptimized drug B, and if we put them together, do we have a greater probability of success?’ And the answer is yes.” Dr. Nicolau said the same approach could be used for other “drug–bug combinations, and we have done that both nationally and with international databases. We have a global program called Passport, [which] tries to take local resistances in South America, North America, Europe and the Asia-Pacific region and link them with drug exposures and dosing and optimization” (Int J Antimicrob Agents 2011;37:225-229). The Pittsburgh researchers, he said, are taking the same concept and “bringing it home. What [they] have done is take their local Pseudomonas and asked, ‘What’s the best combination for our bugs?’ I think it makes a great deal of sense. It is something that could be done at many institutions if people took a little bit of time.” Debra A. Goff, PharmD, FCCP, clinical associate professor at Ohio State University (OSU) College of Pharmacy and

Even though the FDA’s warning recommended discontinuing serotoninergic drug treatment at least two weeks prior to initiating linezolid therapy, Dr. George suggested that many patients receiving prolonged treatment can have their serotoninergic drugs tapered while receiving an alternative IV agent for the first two weeks and then receive oral linezolid for the duration of therapy. However, “tapering selective serotonin reuptake inhibitors [SSRIs] such as fluoxetine would not be feasible due to their longer half-life,” noted Dr. George, who is also an assistant professor of clinical pharmacy, College of Pharmacy at the University of the Sciences, in Philadelphi. She stressed that despite this, “Treatment for the infection ... cannot wait.” The FDA statement stressed that clinicians should administer linezolid immediately in cases of potentially life-threatening vancomycin-resistant Enterococcus faecium infection, nosocomial pneumonia, complicated skin and skin structure infections, and potentially fatal MRSA. Symptoms of serotonin syndrome

Pseudomonas aeruginosa

infectious disease specialist at the OSU Medical Center in Columbus, said the Pittsburgh Medical Center study was “an excellent example of how important pharmacodynamic modeling is in selecting optimal antibiograms. It also demonstrates how stewardship programs need to go beyond the antibiograms to make drug therapy selections for multidrug-resistant gram-negatives such as P. aeruginosa.” The study, she added, “drives the point home with cefepime. We did a similar analysis at The Ohio State University Medical Center in partnership with Dr. Nicolau’s research lab. We found it necessary to increase the dose of cefepime to 2 g every eight hours infused over three hours to achieve the optimal pharmacodynamic target, despite the antibiogram reporting a 91% susceptibility. We are running out of options so we must learn how to get the most out of the agents we have. If we continue prescribing the same dose and the same drug to treat multidrug-resistant P. aeruginosa, we cannot expect a different response.” —Bruce Buckley

include confusion, hyperactivity, memory problems, muscle twitching, excessive sweating, shivering, shaking, diarrhea, trouble with coordination Scan to access FDA and possibly fever. communication on linezolid. Although most of the cases reported to the FDA’s AERS occurred in patients receiving SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs), the FDA has cautioned that the syndrome may occur in patients receiving drugs with milder degrees of serotoninergic activity. These medications include tricyclic antidepressants, MAOIs and various other psychiatric medications (Table). Treatment with serotoninergic drugs can be resumed 24 hours after the last dose of linezolid, the FDA communication said. The statement can be accessed at www.fda.gov/drugs/drugsafety/ucm 265305.htm or by scanning the QR code above. —David Wild

Pharmacy Practice News • December 2011

Clinical 15

Critical Care

Results for Glucose Control in Cardiac ICU Not All Sweet T ‘Looking at our outcomes,

wo different critical care teams reported mixed success meeting infection prevention goals set forth by the Surgical Care Improvement Project (SCIP). For investigators at The University of Chicago, the problematic goal was SCIP INF-4, which specifies keeping blood glucose levels in cardiac surgery patients to less than 200 mg/dL at 6 a.m. on the first and second days

TEFLARO® (ceftaroline fosamil) injection for intravenous (IV) use Rx Only Brief Summary of full Prescribing Information Initial U.S. Approval: 2010 INDICATIONS AND USAGE: Teflaro® (ceftaroline fosamil) is indicated for the treatment of patients with the following infections caused by susceptible isolates of the designated microorganisms. Acute Bacterial Skin and Skin Structure Infections - Teflaro is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca. Community-Acquired Bacterial Pneumonia - Teflaro is indicated for the treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli. Usage - To reduce the development of drug-resistant bacteria and maintain the effectiveness of Teflaro and other antibacterial drugs, Teflaro should be used to treat only ABSSSI or CABP that are proven or strongly suspected to be caused by susceptible bacteria. Appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to ceftaroline. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. CONTRAINDICATIONS: Teflaro is contraindicated in patients with known serious hypersensitivity to ceftaroline or other members of the cephalosporin class. Anaphylaxis and anaphylactoid reactions have been reported with ceftaroline. WARNINGS AND PRECAUTIONS: Hypersensitivity Reactions - Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterials. Before therapy with Teflaro is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. If this product is to be given to a penicillin- or other betalactam-allergic patient, caution should be exercised because cross sensitivity among betalactam antibacterial agents has been clearly established. If an allergic reaction to Teflaro occurs, the drug should be discontinued. Serious acute hypersensitivity (anaphylactic) reactions require emergency treatment with epinephrine and other emergency measures, that may include airway management, oxygen, intravenous fluids, antihistamines, corticosteroids, and vasopressors as clinically indicated. Clostridium difficile-associated Diarrhea - Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents, including Teflaro, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated [see Adverse Reactions]. Direct Coombs’ Test Seroconversion - Seroconversion from a negative to a positive direct Coombs’ test result occurred in 120/1114 (10.8%) of patients receiving Teflaro and 49/1116 (4.4%) of patients receiving comparator drugs in the four pooled Phase 3 trials. In the pooled Phase 3 CABP trials, 51/520 (9.8%) of Teflaro-treated patients compared to 24/534 (4.5%) of ceftriaxonetreated patients seroconverted from a negative to a positive direct Coombs’ test result. No adverse reactions representing hemolytic anemia were reported in any treatment group. If anemia develops during or after treatment with Teflaro, drug-induced hemolytic anemia should be considered. Diagnostic studies including a direct Coombs’ test, should be performed. If druginduced hemolytic anemia is suspected, discontinuation of Teflaro should be considered and supportive care should be administered to the patient (i.e. transfusion) if clinically indicated. Development of Drug-Resistant Bacteria - Prescribing Teflaro in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. ADVERSE REACTIONS: The following serious events are described in greater detail in the Warnings and Precautions section: Hypersensitivity reactions; Clostridium difficile-associated diarrhea; Direct Coombs’ test seroconversion. Adverse Reactions from Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be compared directly to rates from clinical trials of another drug and may not reflect rates observed in practice. Teflaro was evaluated in four controlled comparative Phase 3 clinical trials (two in ABSSSI and two in CABP) which included 1300 adult patients treated with Teflaro (600 mg administered by IV over 1 hour every 12h) and 1297 patients treated with comparator (vancomycin plus aztreonam or ceftriaxone) for a treatment period up to 21 days. The median age of patients treated with Teflaro was 54 years, ranging between 18 and 99 years old. Patients treated with Teflaro were predominantly male (63%) and Caucasian (82%). Serious Adverse Events and Adverse Events Leading to Discontinuation - In the four pooled Phase 3 clinical trials, serious adverse events occurred in 98/1300 (7.5%) of patients receiving Teflaro and 100/1297 (7.7%) of patients receiving comparator drugs. The most common SAEs in both the Teflaro and comparator treatment groups were in the respiratory and infection system organ classes (SOC). Treatment discontinuation due to adverse events occurred in 35/1300 (2.7%) of patients receiving Teflaro and 48/1297 (3.7%) of patients receiving comparator drugs with the most common adverse events leading to discontinuation being hypersensitivity for both treatment groups at a rate of 0.3% in the Teflaro group and 0.5% in comparator group. Most Common Adverse Reactions - No adverse reactions occurred in greater than 5% of patients receiving Teflaro. The most common adverse

it’s not apparent what the risk factors are for infection. In this case, it may not be just glucose.’

—Avery Tung, MD

after surgery. Clinicians at the university’s medical center often failed to hit the goal, they reported at the American Society of Anesthesiologists (ASA) annual meeting (abstract A1372). However, missing the goal had no demonstrable effect on infection rates or hospital length of stay (LOS). The University of Chicago investigators conducted an eight-month retrospective review of patients who had undergone cardiac surgery. The researchers examined patient charts and ICD-9 codes to determine the type of surgery the patients had and the presence of diabetes, congestive heart failure, hypertension and ischemic heart disease. They also measured intensive care unit (ICU) duration, hospital LOS and infection rates. Of the 188 patients who had undergone cardiac surgery during the study period, 165 passed the blood glucose control measure and 23 did not. Although patients who did not achieve the required level had a significantly higher incidence of diabetes (52% vs. 29%; P<0.03), those who achieved it and those who did not had similar outcomes with regard to ICU duration (median, 60.43 vs. 72.6 hours; P=0.928), hospital LOS (median, 171.83 vs. 211.25 hours; P=0.328) and infection rates (15.15% vs. 13.04%; P=1.00).

Glucose May Not Be The Answer “In our small population, we found no real difference between the two groups,” said Avery Tung, MD, professor and quality chief for anesthesia in the University of Chicago’s Department of Anesthesia and Critical Care. “Looking at our outcomes, it’s not apparent what the risk factors are for infection. In this case, it may not be just glucose.” Whatever the explanation may be for the disconnection resulting in SCIP noncompliance, the implications are clear, Dr. Tung noted. “Our data clearly suggest that complying with SCIP INF-4 may not improve outcomes, and it also raises the possibility that the benefits of glucose control in cardiac surgery patients may be overstated.” Study co-author Katherine D. Mieure, PharmD, a clinical pharmacy resident specializing in cardiothoracic surgery, noted that although there is evidence to support the requirements for people with diabetes, the breadth of the SCIP glucose control module may be problematic. “One study in patients with diabetes showed an association between blood glucose over 200 mg/ dL and deep tissue infections, but we are obligated to follow these measures

•

see GLUCOSE CONTROL, page 42

16 Clinical

Pharmacy Practice News • December 2011

Drug Safety

‘PPI Bashing’ Drives Use of Alternatives Chicago—The growing list of side effects being linked to proton pump inhibitors (PPIs) is driving demand for alternatives to the popular medications, according to Ronnie Fass, MD, who lectured on the topic at this year’s Digestive Disease Week (DDW) meeting. “It will not surprise me very much to open a journal in the next couple of years and find that PPIs have been linked to global warming,” quipped Dr. Fass. “It is not only patients who are looking for alternatives,” he continued. “I am now hearing from physicians who ask me if there is another approach to therapy. Pressure may be not only coming from patients and physicians but also from regulators, particularly about the use of escalating doses of PPIs. “I do not expect that this trend will slow down. Rather, I think we will be hearing more about safety concerns in regard to PPI use,” said Dr. Fass, who is chief of gastroenterology, Southern Arizona VA Health System, Tucson.

Side Effects on the Rise The rise in the number of published articles that have identified a potential for side effects associated with PPIs has been particularly steep during the past five years. The list now includes an increased risk for osteoporosis, vitamin B12 deficiency, respiratory infections, bowel infections—including Clostridium difficile—and PPI withdrawal syndrome, which is purported to keep patients dependent on PPIs. Notably, many of the risks related to PPIs are supported by population studies rather than prospective clinical trials. Additionally, some side effects, such as osteoporosis and respiratory infection, may be relevant only in patients with specific comorbidities or precipitating factors. Reviewing the long list of side effects associated with PPIs, many of which are based on limited data, Dr. Fass expressed skepticism about the validity of some of the claims about adverse effects. He does not question the importance of efforts to identify risks, but he suggested that news reports from the lay press might prevent some patients from appropriately assess-

ing the potential benefits and potential risks associated with the medications. However, he said, “It does not matter if I believe that the risks of a PPI are significant [for a given individual]. The noise is out there, and we need to consider this concern.”

What’s the Alternative? So, are there options for patients with gastroesophageal reflux disease (GERD) who are seeking alternatives to treatment with PPIs? According to Dr. Fass, options exist, albeit limited ones. Some alternative pharmacologic agents, such as tricyclic antidepressants or H2-receptor antagonists, may offer benefit in some subgroups of patients with GERD. However, overall efficacy tends to be lower than that provided by PPIs in patients with conventional symptoms, such as heartburn. The near-term likelihood of the availability of any new pharmacologic agent that would be as effective for GERD as a PPI appears to be low. The recent failure of investigational drugs, including potassium-competitive acid blockers and agents designed to improve lower esophageal sphincter pressure, has left non-medical approaches, such as lifestyle changes, endoscopic procedures and surgery as the most viable alternatives. Based on the limited number of alternative options, Dr. Fass predicted a resurgence of interest in anti-reflux surgery. Surgical intervention is likely to be the most effective alternative to PPI therapy, Dr. Fass said. Long-term efficacy of surgery appears to be similar to that achieved with PPIs. However, there is some divergence of data in studies that have attempted to compare these therapeutic modalities. He stressed that clinicians need to be familiar with surgical procedures and be prepared to talk about them with patients who are seeking alternatives to PPI treatment for GERD. For patients who do not wish to undergo surgery, lifestyle modifications may offer relief. However, data in support of this intervention are limited.

We Want Your Pearls

In fact, only two lifestyle modifications are supported by objective clinical data, according to Dr. Fass. These are weight loss and elevation of the head of the bed. This does not preclude potential benefits from other lifestyle modifications, such as avoidance of foods that can be identified as precipitants of GERD symptoms. But it is appropriate to recognize which modifications are and which are not evidence-based, noted Dr. Fass. Endoscopic interventions for GERD have been largely disappointing. Most of the trademarked procedures— including EndoCinch, Gatekeeper, and Enteryx—are no longer actively marketed or have been withdrawn from the market. The reasons for withdrawals are varied, including insufficient financial return, safety concerns, lack of efficacy or a combination of factors. Some endoscopic procedures for

that patient education about the value of PPI therapy, rather than a review of alternative strategies, is probably the best approach in most situations. “I would agree with Dr. Fass that ‘PPI bashing’ is the new trend by studies that try to link many conditions with PPI use,” Dr. Vaezi said. “However, it is important to remember that this class of acid-suppressive agents has revolutionized what we can offer the patients. They heal erosive esophagitis and peptic ulcer disease without the need for surgical interventions, which were the only options left for patients in the prePPI era,” he said. “In fact, we know that if patients’

‘It does not matter if I believe that the risks of a PPI are significant [for a given individual]. The noise is out there, and we need to consider this concern.’

—Ronnie Fass, MD

GERD remain available, and others may be introduced, but Dr. Fass said there is now substantial skepticism about endoscopic approaches to GERD. New endoscopic procedures will need to demonstrate efficacy in well-conducted controlled trials with sufficient followup to demonstrate a durable effect and long-term safety, Dr. Fass said. Acupuncture and cognitive-behavioral therapy also might be considered for some patients, but these options are backed by even fewer data.

PPIs Still the Best Option Asked to comment on Dr. Fass’ perspective, Michael Vaezi, MD, professor of medicine at Vanderbilt University Medical Center, in Nashville, Tenn., concurred that reports of potential safety risks of PPIs have raised concern among patients. However, he suggested

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symptoms do not respond to PPI therapy, surgical intervention is most likely not helpful,” Dr. Vaezi continued. “Thus, we still employ them as the ‘gold standard’ for not only diagnosing but also for treating reflux disease.” Dr. Vaezi did acknowledge the importance of tapering PPIs to the lowest possible dose in patients being treated with these medications. But he concluded that the importance of these agents should not be underestimated. “They are the key agents for relieving reflux symptoms still.” —Ted Bosworth Dr. Fass has received research support from AstraZeneca, Takeda Pharmaceuticals and Wyeth; he is a speaker for Eisai; and he is a speaker and advisor for Takeda Pharmaceuticals. Dr. Vaezi has received research funding from Takeda Pharmaceuticals.

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PHARMACY PRACTICE NEWS • DECEMBER 2011

Opioid REMS in Practice How to Measure Success RELEASE DATE: December 1, 2011

EXPIRATION DATE: December 1, 2012

ACPE LIVE DATE: May 19, 2011 ESTIMATED TIME TO COMPLETE ACTIVITY: 1 hour Jointly sponsored by The Postgraduate Institute for Medicine and Miller Medical Communications, LLC.

MMC

DISCLOSURE OF CONFLICTS OF INTEREST

Miller Medical Communications, LLC.

This activity is supported by an educational grant from Endo Pharmaceuticals Inc.

TARGET AUDIENCE This activity has been designed to meet the educational needs of physicians and pharmacists working in the area of pain management.

EDUCATIONAL OBJECTIVES Upon completion of this activity, the participant should be better able to: 1. Summarize the key benefits of opioid REMS from a public health perspective. 2. Discuss educational strategies that contribute to changes in prescriber behavior. 3. Review elements of a successful approach to increasing prescription opioid safety. 4. Provide accurate and appropriate counsel as part of the treatment team.

FACULTY Perry G. Fine, MD Professor of Anesthesiology Pain Research Center University of Utah School of Medicine Salt Lake City, Utah Nabarun Dasgupta, MPH Department of Epidemiology Gillings School of Global Public Health University of North Carolina at Chapel Hill Chapel Hill, North Carolina

educational activities and, ultimately, reductions in the incidence of prescription opioid abuse and unintentional death due to opioid overdose. This supplement is based on a live satellite luncheon symposium which took place on Thursday, May 19, 2011, in conjunction with the 30th Annual Scientific Meeting of the American Pain Society, in Austin, Texas. If you have received credit for the live program (UAN 0809-9999-11023-L01-P), you are not eligible to receive credit for this activity.

ACCREDITATION STATEMENTS Physicians: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of The Postgraduate Institute for Medicine and Miller Medical Communications, LLC. The Postgraduate Institute for Medicine is accredited by the ACCME to provide continuing medical education for physicians. Pharmacists: The Postgraduate Institute for Medicine is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

CREDIT DESIGNATIONS

Simon Budman, PhD Founder, President & CEO Inflexxion, Inc. Newton, Massachusetts

Physicians: The Postgraduate Institute for Medicine designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Erin Johnson, MPH Program Manager Prescription Pain Medication Utah Department of Health Salt Lake City, Utah

Pharmacists: The Postgraduate Institute for Medicine designates this continuing education activity for 1.0 contact hour (0.1 CEUs) of the ACPE. (UAN 0809-9999-11-141-H05-P).

PROGRAM OVERVIEW Classwide opioid Risk Evaluation and Mitigation Strategies (REMS) are being developed federally to manage escalating prescription opioid abuse while not hindering the provision of adequate pain control for the growing number of Americans with pain-related disorders. Although a successful, statewide educational initiative in Utah provides a model for REMS, little evidence offers insight into the details of the implementation of this national public health initiative. REMS endeavors to educate patients, prescribers, and pharmacists and to implement opioid-prescribing surveillance, proper medication disposal, and enforcement against any individuals (including health professionals) who engage in diversion or abuse. The success of this initiative will be measured based on the participation of prescribers in

Course” and search by course ID 8648. Upon registering and successfully completing the post-test with a score of 70% or better and the activity evaluation, your certificate will be made available immediately. Processing credit requests online will reduce the amount of paper used by nearly 100,000 sheets per year.

TYPE OF ACTIVITY Knowledge

METHOD OF PARTICIPATION There are no fees for participating and receiving CME credit for this activity. During the period from December 1, 2011 through December 1, 2012, participants must read the learning objectives and faculty disclosures and study the enduring material. The Postgraduate Institute for Medicine supports Green CME by offering your Request for Credit online. If you wish to receive acknowledgment for completing this activity, please complete the post-test and evaluation on www.cmeuniversity.com. On the navigation menu, click on “Find Post-Test/Evaluation by

The Postgraduate Institute for Medicine assesses conflict of interest with its instructors, planners, managers, and other individuals who are in a position to control the content of CME activities. All relevant conflicts of interest that are identified are thoroughly vetted by The Postgraduate Institute for Medicine for fair balance, scientific objectivity of studies utilized in this activity, and patient care recommendations. The Postgraduate Institute for Medicine is committed to providing its learners with high-quality CME activities and related materials that promote improvements or quality in health care and not a specific proprietary business interest of a commercial interest. The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity: Perry G. Fine, MD Consulting fees: Ameritox, Cephalon, Covidien, Meda Pharmaceuticals, PriCara/Ortho-McNeilJanssen Pharmaceuticals/Johnson & Johnson, Purdue Pharma Fees for non-CME/CE services received directly from a commercial interest or their agents: PriCara/ Ortho-McNeil-Janssen Pharmaceuticals/Johnson & Johnson Other/Medical-Legal Expert: Cephalon, Johnson & Johnson Nabarun Dasgupta, MPH Consulting fees: Covidien, King Pharmaceuticals Simon Budman, PhD Consulting fees: Endo Pharmaceuticals Inc., Johnson & Johnson Other/Surveillance and education for FDA reporting: Actavis Group, Endo Pharmaceuticals Inc., Johnson & Johnson, Merck, Pfizer, Purdue, Shire Pharmaceuticals, Teva Pharmaceutical Industries Erin Johnson, MPH No significant financial relationships or relationships to products or devices

The planners and managers reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity: Jan Hixon, RN, BSN, MA Trace Hutchison, PharmD Julia Kimball, RN, BSN Samantha Mattiucci, PharmD Jan Schultz, RN, MSN, CCMEP Patricia Staples, MSN, NP-C, CCRN Lyerka Miller, PhD Rebecca A Bachmann, PhD

None None None None None None None None

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DISCLOSURE OF UNLABELED USE This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The Postgraduate Institute for Medicine, Miller Medical Communications, LLC, and Endo Pharmaceuticals Inc, do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of The Postgraduate Institute for Medicine, Miller Medical Communications, LLC, and Endo Pharmaceuticals Inc. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

DISCLAIMER Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. The content of this activity was provided and factual accuracy confirmed by Miller Medical Communications, LLC. Applied Clinical Education (ACE) is responsible for review of the educational format and design only. Although the information included in this activity is believed to be true and accurate at the time of publication, ACE accepts no legal responsibility for any errors that may have been made. ACE makes no warranty, expressed or implied, with respect to the material contained herein.

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Overview of Policy-Based Strategies To Reduce Prescription Opioid-Related Morbidity and Mortality

isk Evaluation and Mitigation Strategies (REMS) are created to ensure that the benefits of a drug outweigh its risks; the development of REMS for longacting opioids (LAOs) has progressed rapidly, despite the lack of a strong evidence base to support their development or a real understanding of the root causes surrounding the recent rise in prescription opioid abuse. Despite these deficiencies, a statewide initiative in Utah successfully reduced unintentional deaths due to prescription opioid overdose and can function as a model for further development of programs to curb opioid abuse and misuse. The FDA has a legislative obligation, mandated by the September 2007 Food and Drug Administration Amendment Act (FDAAA), to require REMS with New Drug Applications as it deems necessary.1 From a clinician’s standpoint, some of the most important requirements of the REMS program, updated April 19 and 20, 2011, fall under the rubric of Elements To Assure Safe Use (ETASU). These provisions require the sponsor (the maker of an FDA-approved drug with a REMS) to inform prescribers about the existence of a REMS and to provide the associated required training.1 Concurrent with the release of the updated REMS program, a new federal interagency initiative to reduce prescription opioid morbidity and mortality was announced. Called “Epidemic: Responding to America’s Prescription Drug Abuse Crisis,” this nationwide plan involves the collaboration of the White House Office of National Drug Control Policy, FDA, Drug Enforcement Administration (DEA), Department of Health and Human Services, National Institute on Drug Abuse, and Substance Abuse and Mental Health Services Administration.2 This is perhaps the largest public safety initiative ever mounted in the United States; it has a goal of reculturing American society to improve public health outcomes, while not interfering with legitimate medical practice or access to needed pharmaceuticals for individuals with pain-related disorders. This initiative involves 4 distinct but interrelated parts: the education of parents, youth, and health care providers; tracking and monitoring opioid use; proper medication disposal; and enforcement. The tracking element includes funding to implement prescription drug monitoring programs (PDMPs) in every state, enabling prescribers to garner useful information regarding the behaviors of their patients, even across state lines. The enforcement element involves identifying illegitimate prescribers of controlled substances and establishing a Model Pain Clinic Regulation Law for states to use.

Opioid REMS as a Major National Public Health Intervention Opioid REMS have involved an ongoing, collaborative effort by the FDA and industry to identify mechanisms to thwart prescription drug misuse and abuse. Certainly, the program has evolved. There are 6 key differences between previous REMS for other types of medications and the extended-release (ER) opioid and LAO REMS—each resulting in unique measurement challenges. 1 Previous REMS have focused on a single active ingredient in a single formulation, including generic and branded products. By contrast, opioid REMS address 7 active ingredients, representing numerous branded and generic products, more than 20 manufacturers, and 2 dosing mechanisms. 2 Previous REMS were designed to mitigate a single biological risk. With current REMS, the FDA has stated that there should be a decrease in abuse, addiction, misuse, and fatal overdose-related outcomes. Although all of these risks can be caused by opioid exposure, they are complex and have separate

PHARMACY PRACTICE NEWS • DECEMBER 2011

etiologies, with different social, genetic, and individual physiologic influences (most of which lie beyond the control of REMS, especially in the non-patient population). 3 REMS for other types of medications are intended to reduce risks primarily in patients; opioid REMS also focus on patients, but they have important implied beneficial implications for non-patients as well. 4 Other risk management programs affected much smaller patient populations. There were close to 1 million registered prescribers of opioids, and pharmacists filled approximately 28 million prescriptions for 4 million patients taking opioids covered by the classwide REMS in 2008.3 5 Older REMS relied primarily on Medication Guides and Communication Plans, whereas opioid REMS include those elements as well as others to ensure the safe use of opioids.

Table 1. Training Required by FDA’s Elements To Assure Safe Use4 For Prescribers Patient selection, assessment Considerations when prescribing opioids Managing patients on opioid therapy Initiating/modifying dosing for opioids for chronic pain, maintenance therapy Monitoring for abuse, misuse Product-specific information Patient counseling For Patients How to take opioids properly

6 The scope of the current REMS is unprecedented in the history of pharmaceutical medicine and in the history of the FDA. Just as the planning of the REMS has required the cooperative efforts of numerous companies, individuals, and stakeholders, so too the evaluation must be done in a careful manner to account for the unique nature of the program.

Reporting adverse effects

Each of the 6 differences between previous REMS and the proposed opioid REMS gives rise to specific methodologic considerations affecting evaluation. First, because multiple active ingredients and formulations are affected by the opioid REMS, the drugs could be combined into groups for measurements or assessed in parallel. Drugs with the same active ingredients could be grouped for a single evaluation. This raises the question of whether to assess the effect of the REMS on the use of immediaterelease (IR) or rapid-release (RR) opioids. Although several IR and RR formulations will be on the market at the same time as ER formulations, most publicly sponsored data collection systems do not differentiate among formulations. In addition, there may be changes in the use of the most common illicit opioid, heroin, suggesting that heroin use should be monitored as well. Second, it is well recognized that drug abuse and addiction have multiple causal factors, including genetics and social circumstances. Although REMS cannot modify these factors, these factors still play integral roles in the likelihood that an individual will experience the outcomes intended for reduction. The contributions of social factors could be incorporated as confounding variables or effect measure modifiers, for example. Third, previous REMS addressed only a single adverse outcome. The 4 outcomes noted by the FDA have different etiologies, sometimes with conflicting causal pathways. Perhaps the greatest measurement challenges are whether and how to address the effect of REMS in nonpatients. Previous REMS focused on mitigating risks in a defined patient population, and this appears to be the intent of the authority given to the FDA by Congress through the FDAAA. Yet the FDA has suggested strongly that it is interested in the non-patient population as well. Without further clarification, it will be very difficult to know how to assess the impact of REMS implementation on the non-patient population. The extremely large population covered by the proposed REMS—including patients, prescribers, and pharmacists—all but guarantees variation in the ways that REMS elements are carried out. Decades of experience with clinical guidelines and evidence-based treatment standardization strongly suggest that every health care provider will have his or her own interpretation of how specific elements should be applied, despite best efforts for uniformity. Natural logistical hurdles also will cause localized variation.

Proper storage, disposal

Potential problems associated with concomitant use of other central nervous system drugs Discontinuation of opioid medications Risks associated with sharing

Purpose, content of the patient treatment agreement

Furthermore, it is important to differentiate patient knowledge from patient behavior. The current REMS are focused on educating patients, prescribers, and pharmacists, with expected changes in behavior as a result. Still to be determined are the best ways to measure such changes in behavior, as well as whether these measurements could be conducted feasibly on a national level. Finally, it is not clear whether the FDA intends to evaluate REMS elements individually or collectively. Although the FDAAA defines the time frame for evaluation of the REMS from the date of their approval, there may be a delay in implementing certain elements, as they may need to be pilot tested to ensure that they do not overburden the health care system. There also will be changes to REMS over time, as lessons are learned and the programs are optimized.

Assessing the Impact of REMS According to the FDAAA, the FDA is mandated to assess REMS at 3 time points: 18 months, 3 years, and 7 years, but more frequent analyses are likely. By the 18-month time point, surveillance systems should have data available on the amount of opioid dispensed and broad drug abuse indicators; however, lack of a comprehensive data set will preclude inferences on causal relationships on the effect of REMS at that stage. For the 3-year assessment, data from claims databases, electronic medical records, and PDMPs will be available. By the 7-year assessment, large, national, federally sponsored data sources on overdoses and nonmedical use will be available. This timeline portrays a long-term, formal process of assessing the impact of REMS carried out in parallel by FDA and industry. The diversity of data sources and the time lags in their availability are likely to lead individual stakeholders and policy makers to come to their own conclusion about the effectiveness of REMS. The required elements of the formal REMS assessment

CONTINUING MEDICAL EDUCATION

PHARMACY PRACTICE NEWS • DECEMBER 2011

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were detailed in the April 2011 letter from the FDA to industry.4 Seven explicit requirements were specified therein.

Perhaps measuring change in clinical practice might be achieved by assessing counterfactual circumstances; in other words, what happens to individuals who would have received opioids in the absence of REMS. To accomplish this, a baseline of current clinical practice would be generated by assembling a cohort of patients who were diagnosed recently with moderately to severely painful degenerative conditions likely to require opioid medication, and tracking those who were given treatment with opioids before the implementation of REMS. Then, after REMS goes into effect, a new cohort of patients would be enrolled and monitored, and the data evaluated for changes in the number and nature of individuals treated with opioids. These data are critically important in determining whether REMS have a negative effect on patients with legitimate indications for opioid therapy.

1 Prescriber training is an important educational aspect of REMS, and will be evaluated. The number of prescribers of ER opioids who successfully complete a single training must be assessed, although the level of understanding or knowledge attained through this training is not specified. Provided educational material must undergo an accreditation process involving an independent audit of the quality of its content by accredited Continuing Education (CE)/Continuing Medical Education (CME) providers. The audit should evaluate the quality of the content compared with that approved by the FDA as part of the REMS, as well as compared with the standards for CME set by the Accreditation Council for Continuing Medication Education (ACCME). Health care providers’ awareness and understanding of the serious risks associated with opioid products must be evaluated, potentially through surveys.

Patients’ understanding of the serious risks associated with these products also must be evaluated. This is perhaps the most important and telling of all metrics in the process. The FDA requires pharmaceutical companies to assess this, although little information or direction for doing so is provided.

Five categories of data must be monitored in drug use surveillance plans: misuse, abuse, overdose, addiction, and death. Surveillance data should be drug specific and include information on changes in these metrics for different risk groups (eg, teens, chronic abusers) and in different settings (eg, emergency rooms, addiction treatment centers, poison control call centers). These metrics also must be coupled with a plan for intervention should a need for such intervention surface.

Methodology to evaluate drug use patterns must be developed and implemented to measure changes in use and access.

Finally, changes in the prescribing behavior of prescribers must be evaluated. This could include assessing the number of prescriptions for potent opioids given to non–opioid-tolerant patients and the number of excessive prescriptions for early refills.

Educational activities for prescribers are central to the ER opioid REMS; hence useful measures to assess the outcome of such education are important. The ACCME describes 7 levels of outcomes, graded by intensity of educational activity.5 The most basic levels are simple participation in an educational activity and participant satisfaction with the activity. Levels 3 through 7 are characterized by learning the intended material, being able to show competence in the learned material, performance of the learned material in practice, patient health status, and community health.5 The FDA’s REMS guidance focuses on Level 1 (participation) and Level 7 (community health) outcomes in particular. The topics to be covered by the educational materials distributed to patients and clinicians were detailed in the appendix of the final opioid REMS letter (Table 1). The letter from the FDA calls for an assessment of how many prescribers of LAOs and ER opioids have completed training successfully. This is a Level 1 outcome, with the “number of participants” (those exposed to the programs and required content) functioning as the numerator, and the total number of prescribers of LAOs and ER opioids as the denominator. Yet, in order for REMS to be effective and efficient, the specific prescribers who are targeted in this outcome must be carefully considered. The FDA suggests an aggressive approach—reaching a high percentage of prescribers in a short period of time. However, because this program currently is voluntary, it is very important to target the audience who will have the largest impact. It is unclear whether this should include high-volume prescribers of opioids (eg, specialists) or general practitioners, such as primary care physicians and nurse practitioners—who, when taken together, prescribe the most opioids. Furthermore, it also is unclear whether the total prescriber population (the

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Prescriber Education as a Key Component of REMS: Measuring Success

Emergency Medicine

Figure. Opioid prescriptions dispensed in the United States by specialty of medicine and patient age, 2009.6 Unprojected data shown. Prior prescriptions (dispensed within the past month) could be from the same or a different prescriber or specialty. DO, doctor of osteopathic medicine; ENT, ear, nose, throat; FM, family medicine; GP, general practitioner; IM, internal medicine; OB/GYN, obstetrics/gynecology JAMA. 2011;305(13):1299-1301. Copyright © (2011) American Medical Association. All rights reserved.

denominator) should include all DEA-registered prescribers, even if not all of them actually prescribe opioids. Some leaders in the field of pain management contend that focusing on the major prescribers of opioids as the target audience for the training initiation would optimize this element of REMS. A letter to the editor published in the Journal of the American Medical Association examined the amount of prescriptions dispensed in the United States by specialty and patient age using data from the Vector One: National (VONA) database from SDI Health (Figure).6 This analysis found that the major prescribers of opioids for patients older than 20 years are general practitioners, doctors of osteopathic medicine, and family doctors. For younger patients (aged 10-19 years), the major prescribers of opioids are dentists. The data did not differentiate between IR and ER formulations of opioids, which might change the landscape of prescribers significantly, but it did illustrate a high level of opioid use. Fifty percent of the sample had an opioid prescription in the month before the data were gathered. Level 7 outcomes are the primary focus of the FDA’s REMS initiative. The FDA is extremely concerned with reducing abuse, misuse, accidental ingestion, overdose, and death while maintaining pain care and appropriate access to pain medication for those who need it. Measuring Level 7 outcomes should be possible by considering the effect of ER opioid REMS on data from substance abuse treatment centers, which have a high concentration of prescription opioid abusers. The analysis of this small population may provide an early indicator of the potential effect of REMS on the general public. Real-time, product-specific data from more than 400 substance abuse treatment centers across the United States are available now to provide baseline information on addiction populations through the Addiction Severity Index-Multimedia Version (ASI-MV).7 The ASI-MV is an automated, online system that compiles information on a variety of issues surrounding opioids and other drugs used by patients in drug treatment centers.7 According to the National Addictions Vigilance Intervention Prevention Program (NAVIPPRO), 17.1% of people entering substance abuse treatment centers report abusing prescription opioids (based on data from January 2010 through the first quarter of 2011, wherein 13,959 of 81,738 individuals entered drug treatment abusing opioids).8 Among those surveyed in the previous 30 days (N=13,963), 39.8% used both ER and IR prescription opioids, whereas 24.7% used ER opioids only and 35.4% used IR opioids only.8 Successful ER opioid REMS should have a major effect on overall prescription opioid abuse by significantly reducing the number of individuals entering drug treatment centers for opioid abuse. Furthermore, opioid REMS could affect the sources of opioids used recreationally. Among prescription drug abusers in the ASI-MV database (from January 1, 2010 to March 31, 2011), 47.6% identify family and/or friends as their source, 45.3% receive opioids from their own prescriptions, and 31.5% use drug dealers.8 When only IR formulations are considered, the breakdown of sources is similar, with 49.1% receiving abused opioids from family and/or friends, 42.2% from their own prescriptions, and 29.6% from drug dealers.8 However, for ER formulations, 42.2% of abusers obtain their opioids from family and/or friends, 39.3% from drug dealers, and 27% from their own prescriptions.8 When an ER formulation is obtained from a family and/or friend, 58.9% are bought, 56.5% are given, and 12.5% are stolen.8 The relationship between the top sources of abused prescription opioids is consistent over time with small confidence intervals.8 Subsequent to REMS implementation, several outcomes are possible. Family and friends might account for a smaller proportion of drug suppliers, because of education on preventing medication theft through better storage, informed decisions about prescription drug sharing, and greater knowledge of the legal ramifications of selling controlled substances. More effective screening could alert clinicians to patients with elevated risks for drug abuse and enable intensive, ongoing follow-up with those

CONTINUING MEDICAL EDUCATION

Table 2. Promoting Safety: Patient Information for Prescription Pain Medication9,19 • Follow medication instructions exactly, including dosage and frequency • Never adjust your own medication schedule or dosage • Never mix medications with alcohol • Taking sleeping aids or anti-anxiety medications with prescription pain medicine can be dangerous • Contact your health care provider if you have medication side effects • Never take prescription medication that is not prescribed to you • Never give medication to anyone else • Always store prescription pain medication in a concealed, safe place • Discard unused medication safely

individuals. Another 2.6% of opioid drug abusers obtain ER opioid formulations from multiple doctors.8 If opioid REMS lead to the establishment of effective PDMPs throughout the United States, then fewer individuals would be able to access drugs in this manner. Unintended consequences also may result from the institution of ER opioid REMS. With restrictions on ER opioid products, the use of IR formulations could increase dramatically, as could the use of heroin—particularly among those abusing prescription opioids as their drug of choice because of the ease with which they are obtained. Little is known about where or how drug dealers obtain prescription opioids. It is not possible to gauge the effect of opioid REMS on the amount of prescription opioids available through dealers, but this may be affected as well.

Lessons Learned From a Statewide Program: A Model for Success From 2000 to 2007, unintentional deaths in Utah from prescription opioid overdose increased by approximately 500%—escalating from 56 deaths to 301. Although the Utah medical examiner noticed this trend early, several years of lobbying were required before the passage of legislation to fund a program intended to reduce drug overdose deaths.9 In the meantime, overdose death gained several notorious titles in Utah, including the “#1 cause of lives lost due to injury.” Indeed, deaths resulting from prescription opioid overdose have outnumbered those caused by motor vehicle crashes in the state since 2003.10 The legislative mandate to reduce harm and deaths from prescription opioids, House Bill 137, passed in 2007 and appropriated $250,000 for each of 2 years.9 It established 4 objectives for the Utah Department of Health. 1

Educate providers, patients, and the public on recognizing and preventing medication-related harms.

Conduct research to improve the understanding of why deaths related to prescription pain medications occur and the factors that increase the risk for death.

Provide recommendations for using the controlledsubstances database, Utah’s state PDMP, to identify risk factors for prescription pain medication overdose.

Create medical treatment and quality care guidelines on prescribing opioids.

PHARMACY PRACTICE NEWS • DECEMBER 2011

Leaders from related state agencies were invited to provide oversight of the program through participation in a steering committee. The agencies included the Utah Division of Occupational and Professional Licensing; HealthInsight, the Agency for Health Research and Quality designee; the Utah Poison Control Center; the Utah Labor Commission; the Utah Medicaid Program; the Utah Department of Human Services, Division of Substance Abuse and Mental Health; and the Utah Attorney General’s office.9 To supplement the steering committee, an advisory committee was formed to provide a mechanism for collaborating with the many stakeholders interested in the issues surrounding prescription medications. This committee was subdivided into work groups to discuss patient and community education; mechanisms for changing provider behaviors; guideline recommendations; guideline tools; and data, research, and evaluation. The committee included pharmacists, practitioners from a variety of health care fields, government officials, public health professionals, law enforcement officers, pharmaceutical representatives, and other interested members of the community.

Media Campaign

A statewide media campaign using the slogan “Use Only as Directed” initially ran from May 2008 to May 2009.9 Educational materials, including television and radio spots, posters, patient information cards, and bookmarks, were developed and introduced to the community during the campaign. The key messages of the education campaign, as well as other basic messages regarding prescription opioids, are shown in Table 2.9 Surveys were conducted before and after the campaign. In the post-survey, the majority of respondents recalled seeing the television spots (59%), whereas fewer reported seeing messages on the Internet (24%) or hearing them on the radio (30%).9 These latter two elements of the campaign were allocated minimal funds.9 Although no funds were invested into print media, the campaign messages were still disseminated when picked up by print news agencies, and 62% of those surveyed recalled seeing prescription drug safety messages in these media. Nearly one-third (29%) of respondents reported that their understanding of the dangers of prescription pain medication had changed during the past year.9 The legislative funding ended in 2009, as did the initial run of the “Use Only as Directed” campaign. However, the state agencies that had been collaborating with the Utah Department of Health were able to pool funds to relaunch the campaign at the beginning of 2011. Meetings of stakeholders continue in order to maintain a unified voice among state agencies, under the guidance of the DEA, as the Utah Pharmaceutical Drug Crime Project.

Clinical Guidelines

The Utah Clinical Guidelines on Prescribing Opioids for Treatment of Pain were developed by a multidisciplinary consensus panel that reviewed existing evidence-based guidelines and common recommendations on acute and chronic pain. The final guidelines, which are not mandatory, consist of 18 recommendations and 20 tools. They were made available to medical providers in March 2009. Postcards informing all controlled substances licensees in Utah about the existence of the finished guidelines and methods for obtaining them generated nearly 3,000 requests for copies from more than 300 hospitals, clinics, and providers.9 The guidelines were published in the Journal of Pain and Palliative Care Pharmacotherapy,11 and a complete set is available online at www.useonlyasdirected.org. Utah is working with other states that have expressed interest in modifying, merging, or adopting the guidelines.

Provider Education

Another element of the Utah prescription opioid safety campaign focused on provider education. Presentations highlighting 6 recommended prescribing practices were developed and presented to health care workers. Participants were encouraged to utilize the state PDMP and to complete a series of surveys assessing their confidence and behavior change at 0, 1, and 6 months. They could earn up to 20 CME credits for completion of all the requirements: homework prior to the presentation, attendance at the presentation, and completion of 3 surveys. During the course of 46 presentations, 581 physicians and numerous nonphysician health care workers were reached. The combined results for the evaluations showed that 60% to 80% of providers reported no longer prescribing LAOs for patients with acute pain or in combination with sedatives. Fifty percent noted using Utah’s controlled-substances database during patient care and utilizing lower starting doses and slower escalations; and 30% to 50% reported obtaining electrocardiograms and sleep studies on appropriate patients, using patient education tools, and implementing Utah’s prescribing guidelines. Although the provider education initiative received a very positive response from those who participated, the small number of providers educated did not justify the costs of this component. Nonetheless, some communities within the state have modified the presentations based on feedback from the experience and are continuing smallgroup presentations at the county level.

Research

The Utah program also involved a research initiative. To collect data on medication use statewide, 12 questions were added to the state’s Behavioral Risk Factor Surveillance System (BRFSS) survey in 2008.12 (The BRFSS is a health-related survey established by the Centers for Disease Control and Prevention in 1984, which collects data monthly in all 50 states.13) There were 5,330 respondents aged 18 years or older, of whom 20.8% indicated receiving a prescription for an opioid during the previous year. Among them, 72% reported having leftover medication, and of that group, 71% said they did not discard it.12 Approximately 3% reported using their medication more frequently or in higher doses than had been directed by their doctor, and 1.8% reported use of an opioid in the past 12 months that was not prescribed to them.12 Other research was directed at learning more about unintentional nonillicit overdose deaths with one or more opioids. Interviews were conducted with family members of the 432 individuals who died from unintentional overdose of any drug in Utah from 2008 to 2009.14 By working under the medical examiner, a very high response rate was attained. Telephone interviews were completed in 385 cases (89%), 214 of which involved the next of kin of individuals who had at least one opioid and no illicit drugs involved as their cause of death. Of these, 82% were reported to have suffered from chronic pain. In 2008, however, only 15% of Utah residents who received an opioid prescription in the previous year said that the purpose was to treat chronic pain. Half of those who died from a prescription opioid overdose reportedly had a mental illness that had been diagnosed by a health care provider.14 Although directly comparable data are not available, the National Institute of Mental Health estimates that approximately 26% of people in the United States have a diagnosable mental disorder.15 Compared with 24% of the Utah population (>18 years of age) in 2008,16 37% of the decedents were obese. The difference is most striking for employment status: 63% of the decedents were unemployed compared with only 4% of Utah adults (at the beginning of the study).14,17 Forty-nine percent of decedents reportedly had received treatment for substance abuse, and 50% smoked daily at the time of death. This is significantly higher than expected because in Utah, only 9% of individuals report

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smoking daily.18 Compared with 92% of the general population of Utah, 60% of decedents received pain medication only from their health care provider, whereas the other 40% were known to have received pain medication from other sources—usually in addition to receiving it from a health care provider. In the year before their deaths, 61% of decedents showed signs of prescription pain medication misuse and/ or abuse as defined by obtaining prescription pain medications from a source other than a health care provider, taking more than prescribed on a daily basis, using prescription pain medication for reasons other than treating pain, or filling a prescription for opioids from 5 or more providers. Although there is no way to show a causal link between the efforts of the Utah Department of Health and the overall public health, a drop in the number of deaths per year was observed. The goal of the program was to see a 15% decrease in the number of unintentional, opioidrelated drug deaths by 2009 compared with 2007 numbers.9 In fact, there was a 14% reduction in the number of these deaths, from 301 in 2007 to 259 in 2008, then stabilization to 265 in 2009.9 Had the number of deaths continued to increase at the same rate as before the program began, 350 to 400 opioid overdose deaths would have been expected in 2008. Other indications of success include distribution of more than 130,000 items of collateral material and copies of the guidelines. The collaboration among local and state organizations caused the educational materials to be well accepted and dispersed throughout the state. Also, the continued collaboration and strong relationships among stakeholders, as demonstrated by their willingness to continue

the “Use Only as Directed” campaign, illustrates that the efforts initiated by this program will continue into the future.

References

10. Utah Department of Health. Utah health status update: uninsured Utah children on the rise. August 2007. http://health.utah.gov/opha/publications/hsu/07Aug_UninsKids.pdf. Accessed October 17, 2011.

US Department of Health and Human Services, US Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for industry: format and content of proposed risk evaluation and mitigation strategies (REMS), REMS assessments, and proposed REMS modifications. September 2009. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM184128.pdf. Accessed October 17, 2011. Office of National Drug Control Policy. Epidemic: responding to America’s prescription drug abuse crisis. 2011. http://www.whitehouse.gov/ sites/default/files/ondcp/issues-content/prescription-drugs/rx_abuse_ plan.pdf. Accessed October 17, 2011. Schnoll S. Presentation to stakeholders: metrics. United States Food and Drug Administration Risk Evaluation and Mitigation Strategies for Certain Opioid Drugs Public Meeting. December 4, 2009. http:// www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/ UCM193696.pdf. Accessed October 17, 2011.

4. US Department of Health and Human Services, US Food and Drug Administration. Center for Drug Evaluation and Research. Postapproval REMS notification. 2011. http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM251595.pdf. Accessed October 17, 2011. 5.

Moore DE Jr., Green JS, Gallis HA. Achieving desired results and improved outcomes: integrating planning and assessment throughout learning activities. J Contin Educ Health Prof. 2009;29(1):1-15.

Johnson EM, Porucznik CA, Anderson JW, Rolfs RT. State-level strategies for reducing prescription drug overdose deaths: Utah’s prescription safety program. Pain Med. 2011;12(suppl 2):S66-S72.

11. Rolfs RT, Johnson E, Williams NJ, Sundwall DN. Utah clinical guidelines on prescribing opioids for treatment of pain. J Pain Palliat Care Pharmacother. 2011;24(3):219-235. 12. Centers for Disease Control and Prevention. Adult use of prescription opioid pain medications—Utah, 2008. MMWR Morb Mortal Wkly Rep. 2010;59(6):153-157. 13. Centers for Disease Control and Prevention. About the BRFSS: turning information into public health. 2008. http://www.cdc.gov/brfss/about. htm. Accessed October 17, 2011. 14. Utah Department of Health. Utah health status update: characteristics of decedents from unintentional prescription opioid related overdose. April 2010. http://health.utah.gov/opha/publications/hsu/10Apr_Overdose.pdf. Accessed October 17, 2011. 15. National Institute of Mental Health, National Institute of Health. Statistics. 2010. http://www.nimh.nih.gov/statistics/index.shtml. Accessed October 17, 2011. 16. Utah Department of Health. Utah health status update: obesity and associated chronic conditions. May 2010. http://health.utah.gov/opha/ publications/hsu/10May_Obesity.pdf. Accessed October 17, 2011. 17. US Department of Labor, US Bureau of Labor Statistics. Local area unemployment statistics. Databases, Tables & Calculators by Subject. http:// data.bls.gov/timeseries/LASST49000004?data_tool=XGtable. Accessed October 17, 2011.

Volkow ND, McLellan TA, Cotto JH, Karithanom M, Weiss SR. Characteristics of opioid prescriptions in 2009. JAMA. 2011;305(13):1299-1301.

Brownstein JS, Green TC, Cassidy TA, Butler SF. Geographic information systems and pharmacoepidemiology: using spatial cluster detection to monitor local patterns of prescription opioid abuse. Pharmacoepidemiol Drug Saf. 2010;19(6):627-637.

18. Utah Department of Health. Utah tobacco facts. Utah tobacco prevention and control program. 2009. http://www.tobaccofreeutah.org/utahfacts.htm. Accessed October 17, 2011.

Budman SH. Prescriber education as a key component of REMS: measuring success. Presented at: American Pain Society 30th Annual Scientific Meeting; May 18-21, 2011; Austin, TX.

19. Zacharoff KL, Chiauzzi E, Corsini E, Pant P, Venuti SW, Weisman R. Your Guide to Pain Management: A Road Map for PainACTION. Newton, MA: Inflexxion, Inc; 2009.

CME Post-Test If you wish to receive acknowledgment for completing this activity, please complete the post-test online at www.cmeuniversity.com. On the navigation menu, click on “Find Post-tests by Course” and search by project ID 8468. Upon successfully registering/logging in, completing the post-test and evaluation, your certificate will be made available immediately. 1. Which of the following is NOT true regarding Risk Evaluation and Mitigation Strategies (REMS)? a. The law requiring REMS was enacted in 2007. b. They are being developed for long-acting opioids (LAOs). c. They are intended to ensure that the benefits of a drug outweigh its risks. d. They have a strong evidence base supporting their development.

6. Which of the following is the most prevalent source of abused prescription opioids according to prescription drug abusers? a. Prescription written for the person abusing the drugs b. Drug dealers c. Family and/or friends d. The Internet

2. The FDA was given a legislative mandate to require REMS with each new drug application (if deemed necessary) by which law? a. Controlled Substance Act b. Elements To Assure Safe Use Act c. Food and Drug Administration Amendment Act d. Harrison Narcotics Act

7. Since 2003, which of the following became the “#1 cause of death by injury in Utah?” a. Electrocution b. Illegal drug overdose c. Motor vehicle crashes d. Prescription opioid drug overdose

3. The classwide opioid REMS initiative involves 4 distinct but interrelated parts; in which part are prescription drug monitoring programs categorized? a. Education of parents, youth, and health care providers b. Enforcement c. Proper medication disposal d. Tracking and monitoring

8. In a 2008 statewide survey of Utah residents, among those who responded that they had received an opioid prescription in the previous year, approximately ___ had leftover medication, and ___ of these kept it. a. 22%; 51% b. 52%; 41% c. 72%; 51% d. 72%; 71%

4. In 2008, approximately how many patients took opioids now covered by the classwide REMS? a. 500,000 b. 1 million c. 2 million d. 4 million

9. From 2008 to 2009, compared with the general population of Utah, individuals who died from a prescription opioid overdose had a higher incidence of ___. a. obesity b. unemployment c. smoking (at least daily) d. all of the above

5. Who are the major prescribers of opioids for patients aged 20 years or older? a. Anesthesiologists and pain medicine specialists b. Dentists c. General practitioners, doctors of osteopathic medicine, and family doctors d. Oncologists

10. Following the Utah “Use Only as Directed” education initiative, from 2007 to 2008, the number of unintentional, opioid-related drug overdose deaths ___. a. decreased by 2% b. decreased by 8% c. decreased by 14.0% d. continued to increase rapidly

26 Clinical

Pharmacy Practice News • December 2011

Compliance

Patients Abandoning Oral Chemo Because of High Copays Chicago—One-tenth of new oral chemotherapy prescriptions are not filled by patients, according to a study based on national pharmaceutical claims data. Presented at the 2011 annual meeting of the American Society of Clinical Oncology (abstract 6036) and also published in both the Journal of Oncology Practice (2011; 7:46s-51s) and the American Journal of Managed Care (2011;17:SP38-SP44), the results “highlight the importance of iden-

tifying strategies to minimize the impact of high cost-sharing requirements in prescription drug plans so that they do not pose a barrier to access to newer oral therapies,” noted the authors from The West Clinic in Memphis, Tenn., and health care consultancy Avalere Health, in Washington, D.C. Using claims data from the Wolters Kluwer Dynamic Claims Database, the investigators found 10,508 patients who

met inclusion criteria for the study and had at least one pharmacy claim for one of the study drugs between January 2007 and June 2009. The drugs included were the oral chemotherapeutic agents that were widely available at the time of the study—capecitabine (Xeloda, Roche), erlotinib (Tarceva, Genentech), imatinib (Gleevec, Novartis), lapatinib (Tykerb, GlaxoSmithKline), lenalidomide (Revlimid, Celgene), sorafenib (Nexavar,

Bayer), sunitinib (Sutent, Pfizer) and temozolomide (Temodar, Merck). For these patients, 67% of the claims were adjudicated and paid for and 33% were reversed. Although 24% of those who reversed their initial claims did follow up with therapy, there may have been unnecessary delays in treatment. The investigators found several factors associated with medication abandonment. For example, the rate of

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Clinical 27

Compliance prescription abandonment increased with copayment required. Claims for which patients were required to pay $500 or more Scan for tips on had the highest making drugs rate of abandonmore affordable. ment (25%), and those for which patients had copays of $100 or less had a significantly lower rate of abandonment (6%; P<0.05). Another factor associated with an

‘The prices of new drugs are outrageous. We need to move to a system in which buyers (read insurance companies …) negotiate prices with drug companies.’

—Steven Vogl, MD

increased likelihood of an abandoned therapy was multiple concurrent prescriptions. Patients with more than five concurrent prescriptions during the previous month had an abandon-

ment rate of 12%, and those with no claims during the previous month had an abandonment rate of 9% (P<0.05). Lower annual household income also was associated with higher rates of

COMING SOON

Bridging the gap between the hospital and post-discharge care

In This Issue Technology Watch

Patient telemonitoring helps hospitals maintain seamless post-discharge care.

Cindy Kuzendorf, PharmD discusses the rewards of preceptoring the nation’s only ASHPaccredited home infusion residency program.

Business Case Study

TPN Regimens In Hospital Causing Problems at Home

For Aralast, Limiting Distribution Helps Boost Drug Safety

Overfeeding triggers risky electrolyte imbalances post-discharge

Registries, monitoring plan help ensure optimal outcomes

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Q&A

Volume 1 • Number 1 • November 2011

Fight or switch? One health-system’s strategy for becoming a specialty pharmacy contractor.

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•

see TPN REGIMENS, page 3

Clinical Controversies

Continuous vs. intermittent IV antibiotic dosing: why the disconnect between hospital and home?

Educational Review

Compatibility of Commonly Used Intravenous Drugs

see ARALAST, page 1

Coding Consult POLICY WATCH

Joint Commission Eyes Stronger Oversight Of Specialty Pharmacy

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•

see COMMISSION, page 1

Top 10 Coding Mistakes—And How To Fix Them

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medication abandonment, although this association was not statistically significant. Patients with incomes less than $40,000 were 20% more likely than those with incomes greater than $75,000 to abandon their prescription (P=0.058). The authors acknowledged that the study had some limitations. They noted that they did not have full access to IV chemotherapy claims data, so some of the patients who were counted as abandoning therapy altogether may have switched to IV chemotherapy or may have received the originally prescribed oral agent through a manufacturer patient assistance program. Based on the findings, the authors suggested that “as the structure of Medicare Part D and commercial plans are modified and health reform initiatives evolve, policymakers and stakeholders should be aware of the impact of benefit structure on adherence and access to vital oncology therapy.” Steven Vogl, MD, a community oncologist practicing in New York City, shared the authors’ concerns about the problems associated with the cost of some of the oral agents. Calling the price of oral cancer drugs “a huge problem,” he recounted the story of an elderly patient with myeloma for whom he prescribed lenalidomide. The patient was unable to pay the $7,000 yearly out-of-pocket cost for the drug and was not a candidate for alternative agents. The patient ended up dying as a consequence of this treatable myeloma. Dr. Vogl added that “the prices of new drugs are outrageous. We need to move to a system in which buyers (read insurance companies, Medicare and Medicaid) negotiate prices with drug companies. This would be simplest in a single-payer system, which would have many other advantages.” —Sarah Tilyou

Hem/Onc Pharmacy

Pharmacy Practice News • December 2011

In Focus

QT PROLONGATION continued from page 1

lead to QT prolongation. Furthermore, the FDA is requiring drug manufacturer GlaxoSmithKline to conduct a study to determine the extent to which Zofran may cause QT interval prolongation. However, Ali McBride, PharmD, clinical pharmacy specialist at Barnes-Jewish Hospital in St. Louis, cautioned that the results of such a study may not apply to all

ondansetron products because of the bioequivalence range allowed by the FDA.

How Much Concern Warranted? The new alert—although important— is not cause for major concern, in part because the relationship between 5-HT3 antagonists and QT prolongation has been well known for years, according to Rowena Schwartz, PharmD, director of oncology pharmacy at the Johns Hopkins Kimmel Cancer Center, in Balti-

more. Last December, the FDA issued a warning about the use of the intravenous form of Anzemet (dolasetron mesylate) in cancer patients with underlying heart conditions or heart rate abnormalities. The previous October, the agency changed the label for granisetron (Kytril, Roche; Sancuso, ProStrakan) to state that the drug should be used with caution in patients with pre-existing arrhythmias or cardiac conduction disorders. Based on the breadth of 5-HT3 agents

Table. Drugs With a Risk for Torsades de Pointesa Drug Name

Class/Clinical Use

Comments

Amiodarone (Various)

Antiarrhythmic/abnormal heart rhythm

Women>men; TdP risk regarded as low

Arsenic trioxide (Trisenox, Cephalon)

Anticancer/leukemia

Citalopram (Various)

SSRI/antidepressant

Chloroquine (Various)

Antimalarial/malaria infection

Chlorpromazine (Various)

Antipsychotic/antiemetic/schizophrenia/nausea

Clarithromycin (Various)

Antibiotic/bacterial infection

Disopyramide (Various)

Antiarrhythmic/abnormal heart rhythm

Dofetilide (Tikosyn, Pfizer)

Antiarrhythmic/abnormal heart rhythm

Droperidol (Various)

Sedative; antinausea/anesthesia adjunct, nausea

Erythromycin (Various)

Antibiotic; GI stimulant/bacterial infection; increase GI motility

Flecainide (Various)

Antiarrhythmic/abnormal heart rhythm

Haloperidol (Various)

Antipsychotic/schizophrenia, agitation

When given intravenously or at higher than recommended doses, risk for sudden death, QT prolongation and TdP increases.

Ibutilide (Various)

Antiarrhythmic/abnormal heart rhythm

Women>men

Mesoridazine (Various)

Antipsychotic/schizophrenia

Methadone (Various)

Opiate agonist/pain control, narcotic dependence

Moxifloxacin (Avelox, Schering)

Antibiotic/bacterial infection

Pentamidine (Various)

Anti-infective/Pneumocystis pneumonia

Pimozide Antipsychotic/Tourette’s tics (Orap, Gate Pharmaceuticals)

Should no longer be used at doses greater than 40 mg per day due to QT changes

Women>men

Women>men Women>men

Procainamide (Various)

Antiarrhythmic/abnormal heart rhythm

Quinidine (Various)

Antiarrhythmic/abnormal heart rhythm

Women>men

Sotalol (Various)

Antiarrhythmic/abnormal heart rhythm

Women>men

Thioridazine (Various)

Antipsychotic/schizophrenia

SSRI, selective serotonin reuptake inhibitor; TdP, torsades de pointes a Drugs that are generally accepted by the QTdrugs.org advisory board to carry a risk for TdP; some additional agents that carry the risk for TdP are no longer marketed. Table does not include drugs that pose a possible or conditional risk for TdP.

Source: Adapted from a table by the Arizona Center for Education and Research on Therapeutics.

involved in these alerts, some experts have suggested that QT prolongation is a class effect; others still claim it is agentspecific, Dr. Schwartz noted, which further blurs the extent of the risks involved. (Earlier this year, a medical officer at the FDA chimed in by stating in a clinical review that QT prolongation and other electrocardiographic changes are indeed “class effects” of 5-HT3 antagonists.) However, Dr. McBride pointed out that there are data showing that granisetron and palonosetron (Aloxi, Eisai) (Support Care Cancer 2011 July 20 [Epub ahead of print]) do not cause QT prolongation, which disputes the idea of a class effect.

Monitoring Questions Remain Dr. Schwartz pointed to another unresolved question regarding QT prolongation: the impact of the drug dose and duration of effect in specific patients. Yet another challenge “is figuring out if there is any type of pre-treatment evaluation or any ongoing monitoring required,” she said. “There’s often a trend toward relying too much on monitoring versus evaluating.” Despite these unresolved questions, ondansetron is frequently used at her hospital, Dr. Schwartz noted. In fact, “this class of drugs is beneficial—it has revolutionized how we treat chemotherapyinduced nausea and vomiting.” She added that she and her colleagues try to find the lowest effective dose to minimize side effects. Dr. Schwartz also recommended doing a complete evaluation of all medications that the patient is on prior to initiating therapy with a 5-HT3 antagonist. James Kalus, PharmD, senior manager for patient care services in the Department of Pharmacy Services at Henry Ford Hospital in Detroit, said he and others also continue to use ondansetron, although they monitor for heart arrhythmias in specific patient populations, such as those with low potassium and magnesium or those who take other medications that cause QT prolongation. Many antiemetics have similar risks, Dr. Kalus said, and some of the newer ones could be considerably more expensive. “At this point, I don’t have a sense of the magnitude of the QT interval increase,” he noted. “An increase of 30 is worrisome; an increase of 60 is bad; but for a 10-millisecond increase, it may not be a big deal. Should [the FDA warning] be taken seriously? Yes, but I don’t think we should throw [ondansetron] away since we don’t know the magnitude of the problem. About 20% of drugs we use regularly have similar risks.” Cynthia Sanoski, PharmD, chair of the Department of Pharmacy Practice at the Jefferson School of Pharmacy at Thomas Jefferson University, in Philadelphia, said the data on QT prolongation from ondansetron “is not the

•

see QT PROLONGATION, page 30

“NATURE IS

PLEASED WITH SIMPLICITY.” ISAAC NEWTON

Closed-System Drug Transfer Device

Hem/Onc Pharmacy

Pharmacy Practice News • December 2011

In Focus

Aflibercept Improves Survival in Metastatic Colon Cancer Stockholm—Oncologists treating patients with metastatic colorectal cancer (mCRC) may soon have a new weapon in their arsenal, according to results from VELOUR, a multicenter randomized trial. Patients with previously treated mCRC derived a significant survival benefit when treated with the investigational angiogenesis inhibitor aflibercept (Zaltrap, Sanofi/Regeneron) in combination with chemotherapy. “Adding aflibercept to FOLFIRI chemotherapy in metastatic colorectal cancer patients previously treated with an oxaliplatin-based chemotherapy resulted in overall survival [OS] and progressionfree survival [PFS] benefits that are both statistically significant and clinically meaningful,” reported investigator Josep Tabernero, MD, at the European Multidisciplinary Cancer Conference (EMCC; abstract LBA6). The primary results of this trial were presented at the World Congress of Gastrointestinal Cancer and subgroup analyses were reported at the EMCC. Dr. Tabernero, head of the Medical Oncology Department at Vall d’Hebron University Hospital in Barcelona, Spain, noted that previous exposure to bevacizumab did not significantly affect the safety or efficacy of aflibercept. “Preplanned subgroup analyses supported the consistency and robustness of the efficacy results for aflibercept in all the different subgroups of patients,” including those previously

treated with bevacizumab, he said. For the multicenter trial, investigators randomized 1,226 patients with mCRC who had progressed after firstline treatment containing oxaliplatin to FOLFIRI plus aflibercept (4 mg/kg IV, day 1, every two weeks) or to FOLFIRI and a placebo. Patients in both groups continued treatment until progression. The primary end point was OS, and key secondary end points included PFS and overall response rate. After a median follow-up of 22.3 months, there was a statistically significant survival advantage for patients treated with aflibercept and FOLFIRI (hazard ratio [HR], 0.82; P=0.0032). The primary analysis showed a median OS of 13.5 months in the aflibercept arm and 12.1 months in the placebo arm. PFS also favored aflibercept (6.9 vs. 4.7 months; HR, 0.76; 99% confidence interval [CI], 0.58-0.99; P=0.00007), as did response rate (19.8% vs. 11.1%; P=0.0001). The primary objective of the subgroup analysis was to examine the consistency of the aflibercept survival benefit across a variety of patient subgroups, considering Eastern Cooperative Oncology Group (ECOG) performance status (PS), prior bevacizumab treatment, demographics and baseline characteristics. A similar effect of aflibercept on OS was seen in patients with PS 0, 1 or 2. The investigators observed no significant differences between patients treated with prior bevacizumab and those with no

previous exposure to bevacizumab. The HR among the 30% of the study population that had already been treated with bevacizumab was 0.86, while the HR among the 70% of patients without prior bevacizumab exposure was 0.79 (P=0.723). Analysis of survival by demographic characteristics revealed a similar benefit for patients younger than age 65 years or age 65 and older, for men and for women, and for patients from all geographic regions represented in the trial. Tests for interaction again confirmed the consistency of the results. Examination of OS by baseline characteristics showed a similar survival benefit with aflibercept regardless of the location of the primary tumor, as well as whether or not patients had hypertension, liver metastases, or one or more metastatic sites. The analysis showed a slight trend toward improved outcomes with aflibercept in patients with liver metastasis only (HR, 0.65 vs. 0.87; P=0.090). A similar pattern of consistency emerged from the subgroup analysis of PFS. The only exception was patients whose organ involvement was limited to the liver; these patients derived significantly greater benefit from treatment with aflibercept (HR, 0.55 vs. 0.84; P=0.008). Consistent with the results for OS, PFS did not differ significantly by previous bevacizumab exposure. Patients who had not been previously treated

QT PROLONGATION

accordingly. I don’t see this as being any different from other drugs in the class of medications that have gotten the same warnings regarding QT prolongation.”

um. If there’s a big uptick in drug spending, eyebrows will definitely be raised and not everyone will have the patience to wait for downstream savings to accrue.”

Liability Also a Concern

The Literature on QT Effect

Dr. McBride said clinicians may be liable if they don’t monitor patients on 5-HT3 drugs for the arrrhythmia. “The problem is that nobody has determined just how much monitoring is required; how often it should be performed; and by whom,” he said. He also echoed Dr. Kalus’ point that there could be considerable financial fallout if health systems switch from ondansetron to a branded drug such as palonosetron (Aloxi, Eisai) that does not cause heart-rhythm abnormalities. Such a switch “could be a pharmacy budget buster, especially on the inpatient side,” he said. Could such a switch ultimately be a cost saver, because it would likely reduce rehospitalizations and lawsuits triggered by ondansetron-induced arrhythmias? “That argument could be made,” Dr. McBride acknowledged. “But there is still a large ‘silo’ mentality in health systems; drug budgets are often viewed in a vacu-

The FDA’s review was triggered in part by two studies linking QT interval prolongation to ondansetron and droperidol therapy published in the journal Anesthesiology. The first study (2008;109:206212) showed that the drug combination increased the QT interval by 17 to 20 milliseconds in patients with postoperative nausea and vomiting (PONV); the second (2005;102:1094-1100) showed that the combination increased QT prolongation in healthy volunteers by an average of 28 milliseconds. Christian C. Apfel, MD, PhD, associate professor of anesthesia, epidemiology and biostatistics at the University of California, San Francisco, and an expert in PONV, said he has doubts—supported by the literature—that the relatively small degree of QTc prolongation caused by ondansetron or droperidol “can lead to any meaningful cardiac outcomes.” However, Dr. Apfel added, the chal-

continued from page 28

strongest evidence in the world. But if you use it in the wrong type of patient— someone with heart issues or on other drugs causing QT prolongation—it could result in a life-threatening emergency.” Physicians had been “giving out Zofran like water,” she added, but the FDA warning gives a reason to pause and take steps like checking patients’ magnesium and potassium levels before administering the medicine. Dr. Sanoski stressed that other drugs also can cause QT prolongation, including citalopram (Table, page 28). In August, the FDA announced the drug no longer should be given in dosages that exceed 40 mg per day because of the potential for QT prolongation and TdP. But with antidepressants, she pointed out, there are so many options that a different drug can easily be selected. With nausea and vomiting, in contrast, “there are not a lot of great alternatives to the 5-HT3-receptor antagonists such as Zofran. In most cases you are probably still going to give the drug and document

VEGF

Aflibercept

with bevacizumab had a median PFS of 6.9 months with aflibercept versus 5.4 months with placebo. In the subgroup of bevacizumab-treated patients, median PFS was 6.7 months with aflibercept and 3.9 months with placebo. The test for interaction showed no significant differences (P=0.6954). Invited discussant David Kerr, MD, medical oncologist at the University of Oxford in England, said the “beautifully well-designed and well-powered” trial had “changed the landscape” of secondline therapy for mCRC. However, he cautioned that this subgroup analysis, like all such analyses, should be considered hypothesis-generating rather than practice-changing. —Charles Bankhead Dr. Tabernero reported no relevant disclosures. Dr. Kerr disclosed relationships with AstraZeneca, Genomic Health, GlaxoSmithKline, Merck and Roche.

lenge for clinicians is that even young and healthy-looking individuals may have mutations on the HERG receptor—a potassium receptor in the cardiac rhythmogenic circuitry—and thus be at considerably higher risk for severe arrhythmias or cardiac arrest than the average population. “This may be the tip of the iceberg we are seeing and why alternatives like palonosetron, which does not possess the class-specific QTc prolongation effect, may be safer,” he said. “And this might be even more relevant for chemotherapy settings, where higher doses [of 5-HT3 antagonists] are often used.” Dr. McBride agreed that palonosetron and/or granisetron might be better options for some chemotherapy patients—expecially those being seen in outpatient settings, where the reimbursement climate for the antinausea medications is more favorable. For inpatients, in contrast, “I would not give up on ondansetron just yet.” —Karen Blum Drs. Sanoski, McBride and Schwartz reported no relevant disclosures.

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32 Operations & Management

Pharmacy Practice News • December 2011

Finances

CUTTING COSTS department is generally a cost center rather than a revenue maker, their only answer is to cut costs.”

Huntsville Hospital Focuses On Insulin Administration Edward H. Eiland, PharmD, clinical practice and business supervisor in pharmacy at Huntsville Hospital, in Huntsville, Ala., shared one costcutting approach that takes aim at the administration of insulin in the critical care setting. Alabama, like much of the country, has a high incidence of diabetes—meaning a large number of critical care patients also have diabetes and require frequent doses of insulin. Regular human insulin, insulin lispro and NPH insulin typically had been dispensed in 10-mL vials at Huntsville Hospital, even though that full amount is not always administered to a patient. By converting to 3-mL vials of insulin, Dr. Eiland and his team were able to cut nearly 19% of their waste, amounting to $14,720 between March 2010 and March 2011. Compared with the preceding year, they also found a decrease in adverse drug reactions with use of the smaller vials: 127 (11.57%) vs. 115 (10.45%) episodes. The smaller vials are also believed to reduce the risk for infection thanks to fewer plunger entries, although the team has not yet quantified that effect. The transition is timely, given the Joint Commission’s recommendation that hospitals stock the smallest possible drug dosage formulations.

Expensive Garbage Costly waste had also been a problem and a concern for the University Hospital, in Cincinnati, where pharmacists were tossing out valuable IV bags daily. So they decided to look into the potential benefits of using commercial premixed products, as well as altering their preparation schedule. On average, the hospital wasted about 2,318 of a total of about 46,000 (5.04%) dispensed doses of IV admixtures every month, at an average cost of $53,269, noted Alex C. Lin, PhD, assistant professor of pharmacy practice and administrative sciences at James L. Winkle College of Pharmacy at the University of Cincinnati. But after the department’s introduction of a commercial premixed system, ADD-Vantage, in September 2009, monthly averages dropped to 1,069 doses and $25,876. “The premix reduced waste by 50%,” said Dr. Lin. “But we were still not happy.” So, in April 2010, the department made another change, increasing the number of times a day that they prepared their IV batch from three to five. (Before any interventions, batches were

Financial Value Increase, %

continued from page 1

100

15% due to prevention or mitigation of drugrelated problems 85% due to drug therapy cost avoidance

the information is stored and retrievable, so if there is a question weeks later, he noted that they could go back to the archives and pull out relevant information.

Choosing the Right Drug Key to Cost Savings Along with optimizing how drugs are dispensed, identifying the right drug is imperative to reducing costs. And this

Figure. Documenting the value of pharmacy specialists.

nating all inpatient use of long-acting octreotide could have saved the hospital an estimated $83,829 annually. “If you are trying to treat an acute leak, it doesn’t make sense to use something that may not kick in for five days anyway,” added Dr. Brown.

IV Routes Can Be Costly For Exempla Lutheran Medical Center, in Wheat Ridge, Colo., the

‘The premix [IV admixtures] reduced waste by 50%. But we were still not happy.’ —Alex C. Lin, PhD

(Kaiser Permanente, 2010 vs. 2009).

prepared only once daily.) Reducing the time intervals between batches further trimmed waste to 676 doses and $22,458. Stephen L. Speth, RPh, MS, pharmacy manager at Indiana University Health Bloomington Hospital, noticed similar waste and error problems in his pharmacy’s production and verification of IV doses. “Pharmacists were never 100% sure of what actually went into the bag,” said Mr. Speth. In November 2010, he and his colleagues decided to implement the DoseEdge system for the processing of compounded sterile products, premixed piggybacks and large-volume parenteral solutions, parenteral syringes and chemotherapy. The system began processing 335 doses during an average day, resulting in an average of about four errors. These mishaps occurred during bar-code scanning and pharmacist verification and were tied to the wrong premix doses or compounded sterile products. Overall, Mr. Speth and his colleagues were pleased to find that DoseEdge improved safety and workflow in the IV room, preventing nearly 625 compounding and dispensing errors in the first 22 weeks of use. “Now I have some assurance that the right drug and right dose is in the right bag,” he said. Furthermore, because the technician scans the bar code prior to mixing anything with the new system, drug errors are caught before any doses are wasted. “In the old days, a pharmacist might catch this but still have to toss it away,” Mr. Speth said. “There’s a real savings involved.” By eliminating errors, he and his team prevented 190 doses from going to waste during the 22-week period, for a savings of about $5,400. New reporting tools also helped the staff identify opportunities for process improvement and optimal training, staffing and workflow decisions, according to Mr. Speth. Additionally,

choice isn’t always as obvious as it may seem, according to some researchers, because it can go beyond a drug’s price tag and efficacy. Differences in how drugs affect length of stay, for example, can have a tremendous impact on the total hospital bill. Joslyn Brown, PharmD, a clinical pharmacist at Georgetown University Hospital, in Washington, D.C., noticed that the depot formulation of octreotide—usually reserved for outpatients— was being used on the post-surgical floor of her hospital, typically to treat fistulas after pancreatic surgery. The alternative is an immediate-release form that peaks early and diminishes after a few hours, in contrast to the depot formulation’s effectiveness over two to three weeks. “Our physicians were using the sustained-release formulation because they figured they could give patients just one shot and send them home earlier,” explained Dr. Brown. However, because sustained-release octreotide is only indicated for outpatients, reimbursement is not guaranteed in the inpatient setting. Staggering additional costs can result due to the substantially higher price tag for a course of the long-lasting versus immediaterelease versions: $2,196 compared with $200, respectively. “Cost savings is coming up all the time,” Dr. Brown said. “So I thought I would look into this use: Was this use appropriate? And is there an alternative that is less expensive and that is covered, so we can get reimbursed?” Of 419 doses dispensed between January 2010 and January 2011, she and her team found that 59 were given to inpatients. Of these, 88% were prescribed to inpatients in surgical units, and it didn’t appear to be beneficial to these patients. Although the researchers were not certain if length of stay, surgical complications or mortality were impacted, the evidence did not suggest a benefit of the more expensive drug. In fact, elimi-

At Indiana University Health Hospital, the DoseEdge system improved safety and workflow in the IV room, preventing nearly 625 compounding and dispensing errors in the first 22 weeks of use.

financial challenge they chose to tackle involved the administration of N-acetylcysteine, a potentially lifesaving antidote for liver damage from acetaminophen toxicity. An oral formulation costs approximately a dollar per dose. However, this route of administration relies on the gut’s ability to absorb the drug, and due to its unpalatability, it can cause nausea in some patients. An IV version avoids these problems, but it carries a much higher price tag: $750. After conducting a retrospective chart evaluation, Mark R. Bishard, PharmD, a clinical pharmacist at Exempla Lutheran, and his team found that 64 patients received IV N-acetylcysteine between October 2009 and October 2010. The IV treatment was administered to patients who had no contraindications—such as a gastrointestinal bleed or coma—to the less expensive oral therapy in 38% of those cases. “That’s a lot of people that got IV who could have gotten the oral; we could’ve saved a lot of money,” said Dr. Bishard. “This tends to fly under the radar. But it is important. If they can take oral, then they should be getting oral.”

Pharmacy Practice News • December 2011

Operations & Management 33

Finances Valuation of an Intervention It is difficult to put a price tag on some efforts, such as the cognitive work provided by pharmacists. But Sheryl J. Herner, PharmD, BCPS, clinical pharmacy specialist in medication safety, and Lea Price, PharmD, BCPS, clinical specialist in palliative care of Kaiser Permanente, in Denver, attested to how increasingly important it is to attempt this valuation. In response to a request from their management to document the value of clinical pharmacy specialists, Drs. Herner and Price and their colleagues launched an effort to better identify and quantify exactly what they did. The team estimated that their department’s total value in 2010 was $6.7 million, of which $5.7 million resulted from drug cost savings. Counterdetailing to optimize drug prescribing and decreasing the length of stay in both the hospital and skilled nursing facilities contributed the remaining $1 million. Drs. Herner and Price also documented a significant increase in cost savings during the study period, which began in July 2009. By the end of 2010, the team noted, the financial value docu-

‘While the focus is often solely on drug cost savings, in actuality we provide a lot of cognitive skill–based services that don’t get documented. We have to start documenting those efforts to show our value.’

—Lea Price, PharmD, BCPS

mented by clinical pharmacy specialists at Kaiser increased by approximately 60%, with the lion’s share of that value (85%) attributable to drug therapy cost

avoidance (decreased cost of goods), they reported (Figure, page 32). “Although the focus is often solely on drug-cost savings, in actuality we

provide a lot of cognitive skill–based services that don’t get documented; we have to start documenting those efforts to show our value,” Dr. Price said. “We need to capture the whole picture of the pharmacist.” —Lynne Peeples Editor’s note: Some of these cost-cutting initiatives were presented as posters at the ASHP 2011 Summer Meeting.

Drs. Adamson, Eiland, Price, Herner, Bishard, Brown, and Lin, and Mr. Speth, reported no conflicts of interest.

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34 Operations & Management

Pharmacy Practice News • December 2011

Leadership in Action

Comings and Goings F

or the past several months, we have explored some of my favorite leadership “nuggets” from the book Leadership Gold by John Maxwell (Nashville, Tenn.: Thomas Nelson Publishers; 2008). This month’s column is the last in this series. I hope these columns have helped you in your leadership journey.

Team Building As leaders, we are responsible for the

development of our teams. We know that change is difficult for people (including ourselves!). However, few leaders become successful without the support of a large group of people. It is impossible to be a solo leader. As I reflect on my own career, I feel enormous gratitude for the mentoring and support I’ve received from many individuals throughout my 35 years in the profession.

Maxwell identifies several areas where “supporters” can be helpful. Take a moment to reflect on the people in your life who have helped you in the following areas: • Time relievers: people who save you time • Gift complementers: people who do things that you are unable to do • Team players: people who add value to you and your team

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Ernest R. Anderson Jr., MS, RPh

• Creative thinkers: people who solve problems and present options • Door closers: executers who complete assignments with excellence • People developers: people who develop and elevate other leaders • Servant leaders: people who lead with an attitude of humility • Mind stretchers: people who expand your thinking • Relational networkers: people who bring other people into your life • Spiritual mentors: people who encourage your spiritual side • Unconditional lovers: people who know your weaknesses and love you anyway

When the Team Changes It is not unusual for us to build our

An End— And a Beginning

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his month’s column is the last in a series focusing on Leadership Gold by John Maxwell. I hope these columns have helped you in your leadership journey. Next month, we transition to the concept of “servant leadership,” a notion that has been promulgated by many top leadership and management writers such as Ken Blanchard, Stephen Covey and others. Servant-leaders achieve results for their organizations by giving priority attention to the needs of their colleagues and those they serve. Servant-leaders are often seen as humble stewards of their organization’s resources: human, financial and physical. I’ve benefited greatly from these leadership ideals and look forward to bringing them to you.

Pharmacy Practice News • December 2011

Operations & Management 35

Leadership in Action own pharmacy “dream teams.” The reality, however, is that those who start the journey with you seldom will be those you finish with. People come, and people go. Turnover in personnel can be disruptive and hard on the team, but it is the leader’s job not only to restore equilibrium but also to analyze the departures to thoroughly understand what happened and why. As each team member leaves, there are a few questions that I would encourage you to ask yourself: • Is this person moving on to a new opportunity that fits him or her better? Is it a professional advancement? Will it help him or her accomplish a personal goal? • Did you do as much as you could to develop this person, value him or her as a part of the team and support him or her by offering new challenges and opportunities? • Is this departure the best move for both the individual and the department? You should be encouraged when staffers leave to advance their careers. Hopefully, you can take consolation in the fact that you have helped support their journeys. I candidly ask departing employees if there was anything I could have done to have prevented them from leaving the team. However, I have rarely heard that I was to blame. It was usually for reasons beyond my control. You may find, in some circumstances, that you celebrate a departure because you can see how much it will benefit your former team member.

The older I get, the more I think about the type of legacy I am leaving behind. I ask myself the question, “How do I want to be known?” In my opinion, we should consciously take steps to create our own legacies. Maxwell agrees, encouraging us all to articulate the legacies that we want to leave behind in one sentence—almost like a mission statement. I want to be remembered as a person who did his utmost to promote the profession of pharmacy through servant leadership. What’s yours?

Preparation for Team Changes Knowing that changes in our teams are inevitable, it is best to be prepared. Here are several questions to ask yourself: • Do you have people waiting in the wings to join your organization? • Do you know anyone to whom you’d like to offer an opportunity? • Are you developing internal candidates and promoting them as the opportunities arise? • Have you accounted for the fact that there are “seasons” for different skill sets as our profession changes?

When the Leader Leaves As I mentioned, people come, and people go...and that includes team leaders. Sometimes leaving can be difficult and emotional after you have invested your heart, your time and your commitment to developing a team. Those you leave behind need encouragement and reassurance, too. They are your legacy. Like me, you may wish to continue working with or mentoring some of your team members long after you—or they—have moved on to a new opportunity. For me, it represents a commitment to the betterment of our profession.

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36 Operations & Management

Pharmacy Practice News • December 2011

Medication Safety

ACCP Practice Network Sheds Light on Medication Errors Pittsburgh—A practice-based research network can be a powerful tool for yielding high-quality data on medication errors in hospitals, according to a new pilot study presented at the annual meeting of the American College of Clinical Pharmacy (ACCP). The findings, detailed in a poster session, illustrate the collaborative strength of dozens of pharmacists in diverse clinical practice settings nation-

‘It was just a matter of [reporting] what you do on a day-to-day basis, and not necessarily spending a huge amount of time, in order to participate in something that has enormous value and meaning to pharmacists and to our patients.’ —Jill S. Borchert, PharmD, BCPS, FCCP

ally who contributed to the medication error research. The research tool, known as a PracticeBased Research Network, or PBRN, was adopted by the ACCP Research Institute last year as a way to conduct large and timely investigations into issues that have relevance for clinical pharmacy practice without the obstacles that can slow traditional research ventures. The ACCP PBRN now has more than 700 member pharmacists. In the pilot study, the investigators focused on pharmacist medication error documentation and prevention. More than 70 ACCP PBRN pharmacists working in inpatient and outpatient settings participated in the study, known as MEDAP, or Medication Error Detection, Amelioration and Prevention. The team reported 779 medication errors during a 14-day period in 2010. More than 80% of the pharmacists’ recommendations for amelioration and prevention of the errors were accepted by prescribers. The researchers also found that 61% of the reported errors occurred in inpatient settings, whereas 39% occurred in outpatient settings (including homes). The leading therapeutic category involved in the errors was systemic anti-infectives (25% of reported errors), followed by hematologic medications (21%) and cardiovascular medications (19%). Most of the reported errors (95%) did not result in patient harm, according to the researchers, but 33 caused temporary harm and six resulted in permanent harm. One death was reported.

Strength in Numbers The objective of the initial investigation was not only to catalog errors but also to learn “how we as a professional group can help each other and help our health systems, hospitals and clinics prevent medication errors and identify high-risk drugs,” said Grace M. Kuo, PharmD, MPH, PhD, associate professor of clinical pharmacy and associate dean for academic clinical affairs at the University of California, San Diego (UCSD) Skaggs School of Pharmacy and Pharmaceutical Sciences, and the study’s lead author. The ultimate goal was to design effective strategies to prevent medication errors from occurring in the first place, she said. “The advantage in having a practice-based network is that together, we have a large sample size,” Dr. Kuo said. Additionally, “we are able to complete a large study in very quick turnaround time. Imagine this: If I study 100 patients in two months here in San Diego and 10 other pharmacists around the country do the same, then together

Pharmacy Practice News • December 2011

Operations & Management 37

Medication Safety ‘The advantage in having a practice-based network is that together, we have a large sample size [and] we are able to complete a large study in very quick turnaround time.’ —Grace M. Kuo, PharmD, MPH, PhD

She noted another benefit, at least for the MEDAP study. “It was just a matter of [reporting] what you do on a day-today basis, and not necessarily spending a huge amount of time, in order to participate in something that has enormous value and meaning to pharmacists and to our patients.” The PBRN is looking at additional research possibilities. Future projects include a pilot study evaluating the impact of drug shortages on oncology patients and a study evaluating the activities of clinical pharmacists, according

to Daniel R. Touchette, PharmD, MA, FCCP, associate professor of pharmacy practice at the University of Illinois College of Pharmacy, in Chicago, and the director of the ACCP PBRN. Dr. Kuo mentioned another potential study that could be conducted by the ACCP PBRN—one that will focus on how to build a sustainable, reimbursable model for collaborative clinical pharmacy services. She said, “I think that would be very helpful research to conduct in the future.” —Bruce and Joan Buckley

we will have more than a thousand patients.” To carry out the venture, the ACCP PBRN licensed a centralized electronic tool with the ability to capture data from a diverse array of inpatient and outpatient settings, each with a potentially different information technology system. The PBRN concept dates back several decades in the United States, with physician groups, particularly primary care providers, as the main driving force in the movement. PBRNs have won research grants from the National Institutes of Health and the Agency for Healthcare Research and Quality to conduct a variety of studies. The ACCP research network eventually may qualify for public or private funding, but as a start-up it had to rely on a Frontiers Fund grant from the ACCP Research Institute to perform its initial study.

MEDAP Contributor’s Take Jill S. Borchert, PharmD, BCPS, FCCP, professor of pharmacy practice at Midwestern University Chicago College of Pharmacy, was one of 71 clinical pharmacists who contributed to the MEDAP research. Dr. Borchert practices at Mercy Family Health Center, a Federally Qualified Health Center (FQHC) Lookalike, where she and two other pharmacists provide clinical pharmacy services to an underserved patient population on Chicago’s South Side. (An FQHC Lookalike is an organization that meets all of the eligibility requirements of facilities that receive certain federal health grants, but does not actually receive grant funding.) With a limited population of patients to study, Dr. Borchert said she welcomed the opportunity to “pool resources to look at issues that often face pharmacy and have [the findings] apply to multiple and diverse practice settings.”

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38 Policy

Pharmacy Practice News • December 2011

Drug Costs

Patient Assistance Programs: Finding The Right Fit Jeff Klaus, PharmD

Ali McBride, PharmD, MS, BCPS

Clinical Pharmacy Specialist Hematologic Malignancies/Stem Cell Transplant Barnes-Jewish Hospital St. Louis, Missouri

Clinical Pharmacy Specialist Barnes-Jewish Hospital St. Louis, Missouri

n an era of changing economic times and health care uncertainty, patients are increasingly facing the challenge of how to pay for the rising costs of their medications. In 2009, it was estimated that more than 43 million people were living in poverty and 50 million did not have health insurance.1 The high cost of pharmaceutical care, coupled with an uninsured patient population, has created a large group of patients who cannot afford optimal health care; this portends a par-

Brand

ticularly worrisome outlook for patients requiring high-cost drug therapies. Pharmaceutical companies are shifting the focus of new drug research. Historically, these organizations have relied on blockbuster therapies that treat many people for common chronic disease states, such as cardiovascular disease and diabetes mellitus. While research is continuing in these areas, pharmaceutical companies are increasingly shifting their focus to highly sophisticated, targeted

Generic

Total

therapies that serve smaller groups of patients. The field of targeted oncology drugs is growing exponentially compared with other classes of drugs.2,3 Although it is absolutely necessary to develop these new drugs if we are to advance the treatment of cancer, this advancement comes at an enormous price: In 2009, the average cost of brand-name drugs increased by 8% to 9%, with generic drugs showing a smaller increase in price (Figure).3-5 The patient’s share of costs associated with health care and medications has been increasing at a disproportionate rate to most patients’ incomes. This increased cost is being passed on to patients in the form of increased cost or copayments.1 In some cases, these costs can be exorbitant.

CPI-U

Number of brand-name drug products that had extraordinary price increases

9.2

Inflation, %

8.3

7.4

6.9

6.7

6.3 5.2

5.5

5.3

4.9

4.7

5 3 0.5

0.4

0.2

2004

2005

2006

1 -1

0.5

0.3

2007

2008

2009

N/A

Figure. Increasing cost of brand-name and generic drugs. Average sales price of the 219 most widely prescribed brand-name and generic drugs increased on average by 9.3%; this was the fastest growth rate in costs for brand-name drugs since 2002. CPI-U, Consumer Price Index for All Urban Consumers; NA, not available Based on references 3-5.

Correction To the Editor:

he article in the November issue of Pharmacy Practice News, “Oncology Drug Shortage Worsens; Mayhem Cited,” reported that patients are unable to access our product Doxil (doxorubicin HCl liposome injection), a critical therapy for patients with certain types of cancer. We deeply regret the circumstances that have caused this shortage. We are writing to address some points in the article. Although there are a variety of factors causing drug shortages nationwide in many different disease areas, the Doxil shortage is due to the inability of our supplier to consistently produce the medication. Equipment failures have been a significant cause of these manufacturing delays. Such equipment failures require investigation and repair, sometimes resulting in the shutdown of entire production lines, which is the case for Doxil. Importantly, we wanted to clarify that we’ve contracted with Ben Venue Laboratories, Inc.—not Bedford—to manufacture Doxil. Thus, the current challenges faced by Bedford have no relation to or impact on Doxil supply. While we work with our contract manufacturer to resolve these production issues, Doxil will be intermittently available during the next several months. We recognize this is a challenging situation and are committed to continuing to work with our

For example, one course of sipuleucel-T (Provenge, Dendreon) used for metastatic prostate cancer treatment can cost $93,000, with a resulting life extension averaging 4 months. Malignant melanoma treatment employing ipilimumab (Yervoy, Bristol-Myers Squibb) costs as much as $120,000 for an estimated benefit of 3.5 months. Dasatinib (Sprycel, Bristol-Myers Squibb/Otsuka) is an oral chemotherapy medication taken daily for the treatment of chronic myelogenous leukemia; one month of treatment can cost over $10,000, and therapy is usually continued until disease progression or the development of unacceptable toxicity. Depending on the specific insurance plan, patient copayments may be derived from tiered drug levels or percentages of the total drug cost. While some patients have access to affordable insurance coverage, in many cases, the end result of copayments seems to have changed from one that prevents inappropriate medication use to one that prohibits the continuation of optimal patient care.

Patient Assistance Programs To continue the treatment of patients on high-cost medications, including chemotherapy, health care professionals are increasingly turning to the aid of pharmaceutical manufacturer patient assistance programs (PAPs). PAPs provide brand-name medications at no cost or reduced cost to patients who meet specific program criteria, including income, prescription coverage, and residence. Oral, injectable, and infused medications are available through PAPs. For intravenous medications, there are programs that supply medications for use in the outpatient infusion clinic; there also are limited PAPs that replace medications used by uninsured patients during an inpatient admission (Table, page 39).

supplier to ensure that as we receive new and limited supply of Doxil, it is quickly made available through the Doxil Creating Awareness & Reinforcing Education Support (C.A.R.E.S.) Physician Access Program to patients next on the wait list. Since its launch on Aug. 5, Doxil has been received by approximately 2,000 patients through the Doxil C.A.R.E.S. Physician Access Program. The article notes that patients were already on ‘the wait list’ as of Aug. 9. That is not accurate. On that date, we were still validating enrollment forms and lining up physician requests to the modest and limited supplies announced available on Aug. 5, in conjunction with the program. Importantly, we have provided and will continue to provide regular updates to the FDA on the progress of the allocation program and the Doxil supply situation. Program information and regular updates we’ve shared with the health care community are available at www. DOXIL.com. Thank you. Sincerely, Monica Neufang Business Unit Communication Leader, Immunology & Oncology Global Pharmaceuticals Communication & Public Affairs Janssen Global Services, LLC

2011/2012

CATEGORIES Pharmacy Automation Information Systems

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Medication Management Systems Pharmacy Waste Systems IV Devices

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Content for the Buyerâ&#x20AC;&#x2122;s Guide has been provided by advertisers. Pharmacy Practice News is not responsible for the accuracy of the content of this special advertising supplement. To request additional information on any product listed in the Buyerâ&#x20AC;&#x2122;s Guide, please fill out the accompanying Reader Service Card and return the card to Pharmacy Practice News.

Pharmacy Automation

IV Automated Devices

BAXA CORPORATION

Bar-Code Packaging

ExactaMix™ 1200 Compounder

TALYST

Address: 9540 S. Maroon Circle, Suite 400, Englewood, CO 80112 Phone: 800-567-BAXA (2292) Fax: 494-BAXA (2292) Email: marketing@baxa.com Web Site: www.baxa.com

AutoPack Address: 11100 NE 8th St, Suite 600, Bellevue, WA 98004 Phone: 425-289-5400 Fax: 425-289-5401 Email: info@talyst.com Web Site: talyst.com

Product Description: Product Cost: Varies by contract; call for pricing. Product Specifications: Bar-code verification, 12-ingredient ports, closed system with no sterility breaks, accurate delivery with secondary check, easy setup, high-speed delivery, electronic V-site for high-use ingredients and lockout for incompatible ingredients as well as air occlusion detection. Disposables available on group purchasing organization contracts.

Product Description: Offers accessible, fully-automated packaging for oral solid medications, ensuring all oral solid medications are unit dose and bar coded for patients’ bedsides. It is scalable, reliable and includes workflow management features that can help improve the efficiency of pharmacy operations.

Bar-Coding Systems

IV Automated Devices

TALYST

BAXA CORPORATION

AutoLabel

ExactaMix® 2400 Compounder (EM2400) Address: 9540 South Maroon Circle, Suite 400, Englewood, CO 80112 Phone: (800) 567-BAXA (2292) Fax: (800) 494-BAXA (2292) Email: info@baxa.com Web Site: www.baxa.com

Address: 11100 NE 8th St, Suite 600, Bellevue, WA 98004 Phone: 425-289-5400 Fax: 425-289-5401 Email: info@talyst.com Web Site: talyst.com

Product Description: The EM2400 streamlines multisource mixing applications, improving productivity and reducing labor costs. It features bar-code verification, 24-ingredient ports, a closed system with no sterility breaks, accurate delivery with a secondary check, easy setup, high-speed delivery, air occlusion detection as well as an electronic Y-site for high-use ingredients and lockout for incompatible ingredients. Disposables are available on group purchasing organization contracts.

Product Description: Allows bar-code labeling of virtually 100% of your formulary. It uses a special, patent-pending transfer label to ensure your medications have a scanready bar code and a human-readable label.

Decentralized Ward-Based Cabinets MCKESSON AUTOMATION

BAXA CORPORATION

AcuDose-Rx®

IntelliFill® i.v.

Address: 500 Cranberry Woods Drive, Cranberry Township, PA 16066 Phone: 800-594-9145 Fax: 724-741-8350 Email: inquire@mckesson.com Web Site: www.mckesson.com/automationsolutions

Address: 9540 South Maroon Circle, Suite 400, Englewood, CO 80112 Phone: (800) 567-BAXA (2292) Fax: (800) 494-BAXA (2292) Email: info@baxa.com Web Site: www.baxa.com

Product Description: McKesson’s AcuDose-Rx® medication dispensing cabinet gives nurses ready access to the medications they need, but pharmacy maintains oversight. The exclusive RightStockTM system optimizes inventory based on daily usage, virtually putting an end to stock outs. And Acudose-Rx cabinets are designed, built and supported in the USA, with durable, jam-resistant drawers.

IV Automated Devices

Product Description: With IntelliFill® I.V., each dose is individually labeled, bar coded, scanned and matched to order. It captures source images for review and verification. IntelliFill™ I.V. also provides high-speed automation and on-demand reconstitution and filling. It saves significant costs in medication acquisition.

SPECIAL SUPPLEMENT | PHARMACY PRACTICE NEWS DECEMBER 2011

Information Systems

IV Automated Devices

BAXA CORPORATION RapidFill™ Automated Syringe Filler

BAXA CORPORATION

Address: 9540 South Maroon Circle, Suite 400, Englewood, CO 80112 Phone: (800) 567-BAXA (2292) Fax: (800) 494-BAXA (2292) Email: info@baxa.com Web Site: www.baxa.com

DoseEdge® Pharmacy Workflow Manager Address: 9540 South Maroon Circle, Suite 400, Englewood, CO 80112 Phone: (800) 567-BAXA (2292) Fax: (800) 494-BAXA (2292) Email: info@baxa.com Web Site: www.baxa.com

Product Description: The RapidFill™ Automated Syringe Filler reduces costs from premade syringes. RapidFill automates filling, capping, labeling and bar coding of sterile batch syringes—800/hour. It is designed to fit in the hood, and colored labels are available. Disposables are available on group purchasing organization contracts. Visit www.baxa.com/rapidfill for more information.

Other Pharmacy Automation

Dose Management System

Product Description: DoseEdge® Pharmacy Workflow Manager is the first and only completely integrated system for managing IV and oral dose preparation. DoseEdge provides real-time status of incoming and in-process doses, bar-code drug verification, dose tracking and automatic dose calculation. It offers a best-practices approach for pharmacy workflow and remote inspection of pharmacy preparation steps. Also available: DoseEdge® TPN for managing the parenteral nutrition compounding process, including manual additions. Visit www.baxa.com/doseedge for more information.

Productivity Software

TALYST

AutoCarousel / AutoCarousel HD

AutoPharm Enterprise Address: 11100 NE 8th St, Suite 600, Bellevue, WA 98004 Phone: 425-289-5400 Fax: 425-289-5401 Email: info@talyst.com Web Site: talyst.com

Address: 11100 NE 8th St, Suite 600, Bellevue, WA 98004 Phone: 425-289-5400 Fax: 425-289-5401 Email: info@talyst.com Web Site: talyst.com

Product Description: A powerful software platform designed to deliver improved patient safety through better medication inventory control and workflow management. AutoPharm Enterprise has multi-facility capabilities, batch dispensing, managing code (crash) carts and improved order routing. It works throughout health care systems to automate medication ordering, receiving, stocking, picking, bar coding and return processes.

Product Description: Provides maximum medication storage in an organized, accessible and compact footprint. Its vertical design provides secure, automated storage and accurate retrieval. AutoCarousel decreases required storage space by 30% to 50% and enables customers to easily store, track and access medications.

Other Pharmacy Automation

Productivity Software

TALYST

AutoCool

AutoSplit 340B Address: 11100 NE 8th St, Suite 600, Bellevue, WA 98004 Phone: 425-289-5400 Fax: 425-289-5401 E-mail: info@talyst.com Web Site: talyst.com Product Description: Delivers access-controlled refrigerated storage and automated dispensing for valuable refrigerated medications. It’s flexible, scalable and can be installed in remote locations. It provides pharmacy-grade refrigeration with password-protected access and enables perpetual inventory management with par levels and order preparation.

PHARMACY PRACTICE NEWS DECEMBER 2011 | SPECIAL SUPPLEMENT

Address: 11100 NE 8th St, Suite 600, Bellevue, WA 98004 Phone: 425-289-5400 Fax: 425-289-5401 E-mail: info@talyst.com Web Site: talyst.com Product Description: AutoSplit® 340B is the industry leader in 340B purchase order splitting. The automated system provides full audit trails for all eligible 340B dispenses and splits. AutoSplit is easy to implement and maximizes 340B savings while reducing program administration hours. It works with multiple wholesalers and has exportable reports to help maintain regulatory compliance.

Pharmacy Waste Systems

Lab Monitoring Software

VERACITY GROUP INC VersaTrak

CLEAN HARBORS ENVIRONMENTAL SERVICES

Address: 7575 E. Kemper Rd., Cincinnati, OH 45249 Phone: 888-369-3601 Fax: 888-729-0411 Email: ssmall@VeracityGroupInc.Com Web Site: www.VeracityGroupInc.com

Pharmaceutical Waste Disposal Services Address: 42 Longwater Drive, Norwell, MA 02061 Phone: 888-304-7035 Fax: 781-792-5938 Email: healthcareservices@cleanharbors.com Web Site: cleanharbors.com

Product Description: VersaTrak wireless systems lead the industry in flexible, compatible, versatile, powerful technology for all monitoring and compliance needs in health care facilities. VersaTrak is designed with the focus on industry compliance and accuracy. With features like Auto NIST Calibration, Intelligent Messaging, Watch-Dog, lab-grade probes and simulators, and state of the art Wi-Fi, 900 MHz and hardwired sensors, VersaTrak is unmatched!

Product Description: Clean Harbors is the only environmental services provider that has the ability to manage 100% of your pharmaceutical and hazardous waste, spill cleanups, and facility maintenance within a company-owned network of 100+ service centers, 50 hazardous waste disposal facilities and the largest hazardous waste incineration capacity in North America.

Medication Management Systems

IV Devices

Oral & Enteral Devices

Fluid Dispensing Systems

BAXA CORPORATION

ExactaMed® Oral Syringes

Repeater™ Pump

Address: 9540 South Maroon Circle, Suite 400, Englewood, CO 80112 Phone: (800) 567-BAXA (2292) Fax: (800) 494-BAXA (2292) Email: info@baxa.com Web Site: www.baxa.com

Product Description: ExactaMed® includes market-leading syringes and accessories for accurate and safe filling and delivery of oral medication. Unique tip design, gray piston and blue printing provide clear differentiation from IV syringes. They are the only complete range of dispensers—from 0.5 to 60 mL—that ensures precise delivery as low as 0.01 mL. Also available: specialty dispensers for enteral, vaginal and topical medications. Available on group purchasing organization contracts. Visit www.baxa.com for order numbers.

Refrigeration Systems

Product Description: Tired of reconstituting, pooling and then filling syringes, dispensers and elastomeric devices? The Repeater Pump automates fluid transfer needs with high flow rates, variable speeds and delivery accuracy to as low as 0.2 mL. Disposables available on group purchasing organization contracts. Visit www.baxa.com for order numbers.

IV Protective Devices

VERACITY GROUP INC

BAXA CORPORATION

VersaFridge

Tamper-Evident Luer Lock Tip Caps Address: 7575 E. Kemper Rd., Cincinnati, OH 45249 Phone: 888-369-3601 Fax: 888-729-0411 Email: ssmall@VeracityGroupInc.Com Web Site: www.VeracityGroupInc.com

Product Description: VersaFridge set a new standard in “Medical Refrigeration” as the ONLY refrigerator that is fully compliant with TJC MM.03.01.01 (EPs 3 & 6) regarding medication security. The removable refrigeration module means that no access is required to the medication compartment for repairs. Using less than 1 KWH per day, it is the most energy efficient refrigerator in its class. With drawers, glass doors and more, it’s the ultimate refrigerator!

Pharmaceutical Waste Services

Address: 9540 South Maroon Circle, Suite 400, Englewood, CO 80112 Phone: (800) 567-BAXA (2292) Fax: (800) 494-BAXA (2292) Email: info@baxa.com Web Site: www.baxa.com Product Description: Tamper-Evident Luer Lock Tip Caps are latex-free—no natural-rubber latex components—and made of non-DEHP materials. A three-part cap requires the user to break off the outer sleeve to dispense medication. A red ring remains, indicating the outer sleeve has been tampered with. The caps are sold in sterile packs of 10 for convenient use. Available on group purchasing organization contracts. Visit www.baxa.com for order numbers.

SPECIAL SUPPLEMENT | PHARMACY PRACTICE NEWS DECEMBER 2011

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Other IV Devices

BAXA CORPORATION

DiscPac™ Self-Righting Luer Tip Caps

Supor® Syringe Filters

Address: 9540 South Maroon Circle, Suite 400, Englewood, CO 80112 Phone: (800) 567-BAXA (2292) Fax: (800) 494-BAXA (2292) Email: info@baxa.com Web Site: www.baxa.com

Product Description: DiscPac™ Self-Righting Luer Tip Caps secure easily to any size Luer syringe. Available in 12 colors, the caps are packaged individually or in convenient DiscPacs of 25 and 100. They are latex-free—no natural-rubber latex components—and made of nonDEHP material that withstands freezing. DiscPacs may be closed and stored in the hood for later use. Available on group purchasing organization contracts. Visit www.baxa.com for order numbers.

Other IV Devices

Product Description: Supor® sterile syringe filters assure quality control during sterile drug preparation. The filters feature double-Luer design for secure attachment and rapid filtration and high throughput, with low protein binding and broad drug compatibility. They allow for fast and effective filtration. Available on group purchasing organization contracts. Visit www.baxa.com for order numbers.

Other IV Devices

BAXA CORPORATION

ExactaMix® EVA Bag

TwoFer™ Needles

Address: 9540 South Maroon Circle, Suite 400, Englewood, CO 80112 Phone: (800) 567-BAXA (2292) Fax: (800) 494-BAXA (2292) Email: info@baxa.com Web Site: www.baxa.com Product Description: ExactaMix® EVA Bag offers better bag clarity for ease of visual inspection; attached bag clamp for convenient closure and covered addition port to keep the area protected until used. New lay-flat tube material minimizes the risk for particulates in the bag. EVA construction provides cleaner disposal for incineration. Manufacturing in North America reduces shipping time. Available on group purchasing organization contracts. Visit www.baxa.com for order numbers.

Other IV Devices

BAXA CORPORATION RapidFill™ Connectors Address: 9540 South Maroon Circle, Suite 400, Englewood, CO 80112 Phone: (800) 567-BAXA (2292) Fax: (800) 494-BAXA (2292) Email: info@baxa.com Web Site: www.baxa.com

Address: 9540 South Maroon Circle, Suite 400, Englewood, CO 80112 Phone: (800) 567-BAXA (2292) Fax: (800) 494-BAXA (2292) Email: info@baxa.com Web Site: www.baxa.com Product Description: TwoFer™ dual-purpose Luer-lock needles allow for vented and non-vented vial additions and withdrawals. Huber points minimize the risk for coring. Reconstitution and fluid transfer applications can be performed without changing needles. Available on group purchasing organization contracts. Visit www.baxa.com for order numbers.

Scan here to access this Buyer’s Guide online 1. Download a QR Code scanner app via the app store on your smartphone. 2. Open the QR Code scanner app and let it focus on the bar-code image to instantly access related materials and/or Web sites.

Product Description: RapidFill Connectors enable connections of male Luer syringes, tube sets, repeating syringes, bag ports and other containers. They are available with caps, allowing intermittent fills and capped storage. The connectors are latex-free—no natural-rubber latex components—and made of non-DEHP materials. Available 50 per case. Available on group purchasing organization contracts. Visit www.baxa.com for order numbers.

PHARMACY PRACTICE NEWS DECEMBER 2011 | SPECIAL SUPPLEMENT

COMING SOON

Bridging the gap between the hospital and post-discharge care

In This Issue Technology Watch

Patient telemonitoring helps hospitals maintain seamless post-discharge care.

Cindy Kuzendorf, PharmD discusses the rewards of preceptoring the nation’s only ASHPaccredited home infusion residency program.

Business Case Study

TPN Regimens In Hospital Causing Problems at Home

For Aralast, Limiting Distribution Helps Boost Drug Safety

Overfeeding triggers risky electrolyte imbalances post-discharge

Registries, monitoring plan help ensure optimal outcomes

Q&A

Volume 1 • Number 1 • November 2011

Fight or switch? One health-system’s strategy for becoming a specialty pharmacy contractor.

•

see TPN REGIMENS, page 3

Clinical Controversies

Continuous vs. intermittent IV antibiotic dosing: why the disconnect between hospital and home?

Educational Review

Compatibility of Commonly Used Intravenous Drugs

see ARALAST, page 1

Coding Consult POLICY WATCH

Joint Commission Eyes Stronger Oversight Of Specialty Pharmacy

•

see COMMISSION, page 1

Top 10 Coding Mistakes—And How To Fix Them

New Products Ipilimumab (Yervoy, BMS) approved for metastatic or unresectable melanoma. See page 50.

Scriptpro announces new enhancements to its remote telepharmacy system. See page 50.

Pharmacy Practice News • December 2011

Policy 39

Drug Costs Until there is an efficient method for providing complete health care coverage for all patients, it will be important for members of the health care team to be aware of patient access to medications through these programs. The first step to providing uninsured patients with the optimal therapy is to match the PAP with the patient’s current financial and insurance situation. Enrolling patients in these programs can be time-consuming because of wide variations in eligibility require-

ments. Depending on the source of funding for the PAP, eligibility criteria for specific medications are established by either the manufacturer or charitable organizations. The process of enrolling patients may include the completion of application forms, reporting of a patient’s health insurance coverage, assets, salary, liabilities, Social Security benefits, and proof of income such as federal tax returns or W-2 forms. Once the enrollment paperwork is completed and submitted to the

PAPs, the turnaround time will vary. In some cases, it can be as quick as the same day, but most programs take from 5 business days to 6 weeks to process and receive medications. The downside of many of these programs is that the application process can be rather nebulous. Furthermore, as health care costs rise and these programs increase in number, it is likely that navigation of program loopholes will become more difficult, especially because a uniform application process does not exist.

Table. Selected Industry-Sponsored Patient Assistance Programs Patient Assistance Program(s)

Sponsoring Organization

Examples of Covered Drugs

AZ&Me Prescription Savings Program

AstraZeneca www.astrazeneca-us.com/ help-affording-your-medicines

Arimidex, Faslodex, Zoladex

ASAP Program Allos Support for Assisting Patients

Allos www.getasapinfo.com

Folotyn

The Safety Net Foundation

Amgen www.amgenassistonline.com

Aranesp, Epogen, Neulasta, Neupogen, Vectibix, Xgeva

NexCCAP

Bayer http://nexavar-us.com/scripts/pages/en/rcc/ patient-assistance-and-support/nexccap/

Nexavar

Destination Access

Bristol-Myers Squibb http://www.destinationaccess.com/index.aspx

Erbitux, Ixempra, Sprycel, Yervoy

Celgene Patient Support

Celgene www.celgenepatientsupport.com

Abraxane, Istodax, Revlimid, Thalomid, Vidaza

CORE: Cephalon Oncology Reimbursement Expertise

Cephalon www.cephalononcologycore.com

Treanda, Trisenox

The Eisai Reimbursement Resources

Eisai www.eisaireimbursement.com

Aloxi, Dacogen, Fragmin, Gliadel, Halaven, Ontak

Lilly Patient One

Eli Lilly www.lillytruassist.com

Alimta, Gemzar

Genentech Access Solutions

Genentech, Inc. www.genentechaccesssolutions.com

Avastin, Herceptin, Rituxan, Pegasys, Pulmozyme, Tarceva, Xeloda

Genzyme Patient Assistance

Genzyme Corporation www.genzymeoncology.com http://www.genzyme.com/healthcare/ services_reimbursement.asp

Aldurazyme, Cerezyme, Fabrazyme, Hectoral, Renagel/Renvela, Campath, Clolar, Fludara, Leukine, Mozobil, Thyrogen

GlaxoSmithKline http://www.commitmenttoaccess.com/ index.html http://www.caresbygsk.com/hcp.html

Arranon, Arzerra, Bexxar, Hycamtin, Promacta, Tykerb, Votrient

Merck & Co. www.merck.com/merckhelps

Emend, Intron A, Gardasil, Noxafil, Pegintron, Sylatron, Temodar, Zolinza

Commitment to Access, CARES by GSK

The ACT Program

Velcade Reimbursement Assistance Program

Millennium Pharmaceuticals, Inc www.velcade.com/payingfortreatment.aspx

Velcade

Novartis Patient Assistance NOW, EPASS Prescription and Reimbursement

Novartis Pharmaceuticals http://www.patientassistancenow.com/ index.jsp

Affinitor, Exjade, Gleevec, Sandostatin LAR Depot, Tasigna, Zometa

First Resource, Pfizer Pfriends

Pfizer www.pfizerhelpfulanswers.com

Aromasin, Camptosar, Ellence, Emcyt, Idamycin, Neumega, Sutent, Torisel, Xalkori, Zinecard

PACT+Provider Portal

Sanofi Patient Assistance Programs www.pactplusonline.com

Eligard, Elitek, Eloxatin, Taxotere

In some cases, application to a PAP can be initiated by the patient; however, action by the prescribing physician or the health care team is required to complete the application. While oncology practices would undoubtedly jump at the chance to provide the necessary therapy to their patients at a reduced and affordable cost, most have not yet created a systematic, organized approach to identifying the PAP that will provide the most assistance to each patient. Some oncology practices that have taken this step have identified a point person in the pharmacy department or have outsourced this role to a PAP manager to streamline the process. In many community oncology offices, a nurse has been assigned the responsibility of assisting patients with PAPs. In other cases, PAPs may be delegated to companies, such as McKesson and Cardinal, that run the program for a percentage of the reimbursed amount. Whatever the approach, heightened awareness of such programs is crucial for the optimal provision of treatment in the face of ever-rising health costs.

Conclusion As drug development increasingly shifts to targeted therapies, response rates will continue to improve; but at the same time, health care costs will rise. The effect of current health care reform on the individual patient remains to be seen. It seems reasonable to assume that widespread and affordable access to vital drugs will not be secured by government agencies in the near future. It will remain the responsibility of the health care team to ensure that patients have access to the drugs they need for optimal treatment. PAPs can be a valuable tool to facilitate that access.

References 1. Kaiser Family Foundation. Family health premiums rise 3 percent to $13,770 in 2010, but workers’ share jumps 14 percent as firms shift cost burden. http://www.kff.org/ insurance/090210nr.cfm. Accessed November 15, 2011. 2. The costly war on cancer. New cancer drugs are technically impressive. But must they cost so much? The Economist. http://www.economist.com/node/18743951?story_id=18743951. Accessed November 15, 2011. 3. Medco R&D Directions. 2010 Drug Trend Report. http://www.drugtrend.com/art/drug_ trend/pdf/DT_Report_2010.pdf. Accessed November 28, 2011. 4. US Government Accountability Office. Report to Congressional Requesters. Brand-name prescription drug pricing. Lack of therapeutically equivalent drugs and limited competition may contribute to extraordinary price increases. http:// www.gao.gov/new.items/d10201.pdf. Accessed November 28, 2011. 5. US Department of Labor. Bureau of Labor Statistics. Consumer Price Index All Urban Consumers U.S. City Average, All Items 198284=100. ftp://ftp.bls.gov/pub/special.requests/ cpi/cpiai.txt. Accessed November 28, 2011.

40 Policy

Pharmacy Practice News • December 2011

Drug Abuse

Study Highlights Prescription Misuse Among Teens M

ore than one in five adolescents have abused their prescribed controlled medications in the past year, according to results of an epidemiologic study conducted among middle and high school students in Michigan. Although the rates of misuse and abuse in adolescents are roughly equivalent to those seen in young adult and adult populations, the study highlights growing concerns that younger patients are abusing their prescribed medications. This adolescent age group is a particFile Slug Esteularly vulnerable one, said Sean ban McCabe, PhD, 1stresearch associate CMEzone qtrpg Proof LaYout aPProvEd InItIaLs and datE professor at the University of Michigan MaX sign-off Center and Substance Abuse Research Institute for Research on Women and senior Editor Gender in Ann Arbor, and the study’s Copy Editor lead author. “Adolescence represents r2 sales to monitor conan important period trolled medications because individuoctober 28, 2011 8:36 aM Production als often become responsible for their Creative own medication management during Half vertical older adolescence,” CoMMentS: Dr. McCabe stated in an email. “In addition, adolescents 4C serve as the leading diversion source for their adolescent peers and many [teenagers] report using their own left-

over medication nonmedically.”

Study Results

In this study, published in the Archives of Pediatric Medicine (2011;165:729735), Dr. McCabe used a Web-based survey offered to the entire grade 7 to 12 population (N=4,209) of two school

measure alcohol and other drug dependence. Overall, 18% of the students said they were prescribed at least one of the medications and of these, 22% reported misusing a prescribed controlled medication within the past year. Close to 10% of students said they used their

‘We are getting a lot more information about teens ... and the relationships between prescription drug misuse and all sorts of StatuS andillicit HiStory drug use.’ other problems, such as binge drinking and fInaL oK InItIaLs and datE

Proof 1 12/10 rEv 1 12/17 rEv 2 rEv 3 rEv 4 districts in the DetroitrEv 5area; 61.7% (n=2,597) of the students rEv 6 responded. The survey covered four classes of conrEv 7 rEv 8 stimulant, trolled medications—pain, rEv 9 sleeping and anti-anxiety—and asked

specific questions regarding medication use, misuse, abuse and diversion. The survey also included the Drug Abuse Screening Test-Short Form (DAST-10) and the six-item, self-report CRAFFT mnemonic, both of which

PICKEd uP froM: aPPLIEd to:

—James Zacny, PhD

prescribed medications to intentionally get high or to increase the effect of alcohol or other drugs. The breakdown among specific classes of drugs provided interesting results. Overall, students abused pain drugs more than any other class of drugs, but compared with the other medication classes, pain drugs were the least popular for getting high intentionally or simultaneously with alcohol or other

drugs. For example, 9.2% of students who admitted misusing pain pills said they intentionally used them to get high or augment other drugs, whereas 17.1% of those misusing sleeping pills, 15.8% of anti-anxiety drug misusers and 11% of stimulant misusers did so to get high. And although girls were prescribed controlled medications more

•

see TEENS, page 42

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42 Policy

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Drug Abuse

TEENS continued from page 40

often than boys, there were no gender differences in the misuse of controlled medications. Dr. McCabe also found that those who misused prescription medications were much more likely to divert their prescription drugs and to abuse other substances. For example, prescription drug misusers were 7.4 times more likely to have used another illicit drug in the past year (95% confidence interval [CI], 3.3-17) and 4.4 times more likely to have engaged in binge drinking in the past two weeks (95% CI, 2.1-9.1). “These odds ratios are high. These are strong associations,” said James Zacny, PhD, professor of anesthesia and critical care at the University of Chicago in Illinois.

A Byproduct of Increased Prescribing? Because the study is the first to look at how adolescents use their prescribed controlled medications, it is difficult to draw any conclusions about their behaviors. However, it is likely that increases in pediatricians prescribing these medications have led to an increase in their misuse. “Since the mid-1990s, these drugs are being prescribed more for this age group, both stimulant kinds of drugs and prescription opioids,” said Silvia Martins, MD, PhD, associate scientist

in the Department of Mental Health at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “We don’t have that many studies looking at whether the increase in prescriptions is also related to an increase in misuse, but if you look at prescription opioids, there are papers showing a direct relationship between the increase in the prescribing of prescription opioids and the increase in nonmedical use. And that’s something that appears in the general population and we also see it among adolescents.” This increase in prescribing may be an outcome of the growing concern that pain, and to a lesser degree psychiatric disorders, have previously been undertreated. “What is currently being discussed and debated by key opinion leaders in this area, particularly with prescription opioids, is whether doctors are overprescribing,” Dr. Zacny said. “This is the exact opposite from about two to three decades ago when many doctors were underprescribing opioid analgesics because they were afraid of getting their patients addicted.”

Better Screening Needed According to Dr. Martins, the message for clinicians is “to do a better job screening before they prescribe these drugs,” perhaps as little as asking about alcohol abuse within the past weeks or months. However, according to Dr. Zacny, busy physicians may not have the time to screen patients thoroughly and those

adolescents who wish to abuse their medications will try to thwart them nonetheless. “I don’t know that kids are going to volunteer that [information] to the doctor—‘I’m using more than prescribed,’” said Dr. Zacny. “I also don’t know if [more thorough screening is] practical [because] doctors are so busy now and there are not as many pediatricians as we need in this country.” Regardless of how to curb misuse among adolescents, Dr. Zacny said that this group’s work—the latest in a series of studies on misuse and abuse among young and underrepresented populations—has been particularly important to the field. “When this research started coming out in 2005, it really opened my eyes [and] it’s really made a major contribution to the field,” said Dr. Zacny. “We are getting a lot more information about teens and young adults and the relationships between prescription drug misuse and all sorts of other problems, such as binge drinking and illicit drug use.”

Another topic under debate is whether drugs exist that have less potential for abuse, which can be prescribed to teens and young adults, especially if the teens show signs of prescription drug misuse. With moderately severe to severe acute pain, there are no other options besides potent opioid analgesics; however, “if a kid has their impacted wisdom teeth removed, I don’t know what the alternative is,” Dr. Zacny said. “There are weak opioids, but if they are in a lot of pain, the question is should a doctor prescribe that over a more appropriate medication for severe pain?” Dr. McCabe believes that “the answer may not be to withhold controlled medications but to be more careful when prescribing and monitoring.” Dr. McCabe added that better screening and patient and parent education, frequent checkups, prescription drug monitoring programs and evidence-based prescribing practices could all contribute to better compliance. “A combination of these approaches is likely to provide the greatest probability of reducing medication misuse and abuse,” he said. —Gabriel Miller

Drs. McCabe, Zacny and Martins reported no relevant financial relationships with any manufacturer or provider of commercial products or services. This study was supported by grants from the National Institute on Drug Abuse at the National Institutes of Health.

CLINICAL

Critical Care

GLUCOSE CONTROL continued from page 15

for all patients, not only those with diabetes,” she said. “The [ideal blood glucose goal] may differ depending on pre-op risk, including whether patients have diabetes.” In other words, she noted, patients who don’t have diabetes may have more leeway, and higher blood glucose levels may not present as much risk for them as for their diabetic counterparts. Dr. Mieure added that variables affecting blood glucose also should be considered. “A protocol would help as would finding a systematic way to affect patient outcomes, but as all pharmacists and physicians know, the variables for blood glucose control are many. There may not be just one standard that will work.”

At Maimonides, a Bit More Success In the second study (abstract A1706), by researchers at Maimonides Medi-

cal Center, in New York City, compliance with some of the SCIP modules increased significantly over the study period and they documented improved hospital LOS, as well as decreased mortality. However, the team was unable to show a significant reduction in rates of infection as a result of the SCIP compliance efforts, they reported at the ASA annual meeting. The researchers tracked outcomes related to several SCIP infection prevention measures, including prophylactic antibiotic administration, perioperative glucose control and intraoperative insulin use. Mortality and hospital LOS also were assessed. The retrospective study was based on a review of all cardiac surgeries performed at the hospital in 2006 and 2009 (the SCIP national campaign began in 2005). Of the 460 patients, 227 had cardiac surgery performed in 2006 and 233 had the surgery in 2009. Overall, 179 patients had diabetes and 284 were using insulin.

The intraoperative use of insulin was significantly higher in 2006 than in 2009 (66.7% vs. 57.3%; P=0.043), indicating a growing awareness of the SCIP INF-4 quality measure, the team reported. However, despite increased use of insulin, compliance with intraoperative blood glucose goals—a precursor to meeting the 200 mg/dL postsurgical blood glucose target set forth by SCIP INF-4—was not significantly different (22.3% of patients in 2006 vs. 15.6% in 2009; P=0.17). Possible contributing factors included higher body mass index of patients in 2009 than in 2006 (30.75 vs. 29.12 kg/m2; P=0.024) and inadequate efforts to optimize serum glucose preoperatively, the investigators reported. As far as other SCIP quality control measures, the study showed that compliance with antibiotic prophylaxis was significantly increased in 2009 compared with 2006 (93.2% vs. 88.75%, respectively; P<0.001). Altogether, the infection control measures had some impact: Patients in 2009

had a significantly shorter hospital LOS (7.71 vs. 8.4 days; P<0.001) and slightly lower mortality (3.16% vs. 5.6%; P<0.1) than patients in 2006, the team reported. However, rates of sternal wound infection did not differ significantly between the two groups (0.63% in 2009 vs. 1.53% in 2006; P<0.2).

More Questions Than Answers? For Dr. Tung, these types of studies may raise more questions than answers, especially in the assessment of the impact of blood glucose on postoperative infection. “It comes down to the risk-and-gain argument,” he said. “What are you risking by tighter control, and what do you have to gain by meeting these requirements? And is there any way we can predict risks associated with not meeting the requirements? A larger study might help us get a better grip on that. But right now, the answers are not clear.” —Terri D’Arrigo

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