The August 2012 Digital Edition of Pharmacy Practice News by McMahon Group

The Pharmacist’s News Source

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in this issue UP FRONT

Drug shortage bill passes; a victory for pharmacy advocacy.

TECHNOLOGY

10 16

High-tech tools for enhancing safety of sterile IV compounding. Off-the-shelf clinical decision software is nott a prescription for success.

OPERATIONS & MGM MGMT G T

MEETING HIGHLIGHTS

27 28 34

Tips for boosting HCAHPS scores. Revamping IV workflow eases drug shortages.

Fast-tracked nuclide therapy for prostate cancer ‘exceptionally exciting.’

EDUCATIONAL REVIEW

Antimicrobial Stewardship Management of Infections: Beyond the Costs of Antimicrobials See insert after page 44.

Co io

Volum me 39 • Number 8 • August 2012

Pr rp

of ag

40th ANNIVERSARY YEAR 1972–2012

Building a Better CPOE System Via MEDMARX Data

Smart Pumps Get Better Grades After QI Initiatives

Revamping drug libraries at heart of the quality improvement efforts

physician–pharmacist research team at Brigham and Women’s Hospital, in Boston, has data-mined a decade’s worth of computerized prescriber order entry (CPOE) system error reports. Their findings—reported at an informatics meeting last year and now bolstered by more recent data—have shed new light on the types of errors that sometimes plague this medication safety technology. Pull-down menu mishaps, interoperability snafus and incorrect dosing instructions are just a few of the common errors the researchers uncovered, according to Gordon Schiff, MD, the associate director of the Center for Patient Safety Research and Practice at Brigham and Women’s Hospital, and the study’s principal investigator. The results offer current CPOE users a roadmap for improving their own systems, with an important added benefit: “We’ve gained the ability to create and test a new taxonomy for understanding CPOE-related errors,”

Baltimore—A five-year quality improvement effort at a California children’s hospital aimed at revamping the facility’s “smart” programmable infusion pump drug libraries has significantly bolstered the technology’s impact on patient safety. A 40% reduction in potentially severe adverse drug events, a nearly 50% reduction in nonclinically significant alerts and a doubling of drug library usage are among the improved outcomes documented, according to Katie Tu, PharmD, a pharmacy educator at Children’s Hospital of Orange County (CHOC), in Calif. The efforts have resulted in millions of dollars in avoided costs annually, Dr. Tu noted during a poster presentation at the American Society of Health-System Pharmacists (ASHP) 2012 Summer Meeting.

see CPOE, page 9

see SMART PUMPS, page 12

•

‘Good Results’ program slashes HIV adverse drug events.

HEM/ONC PHARMACY

Carfilzomib Gets Approved for MM: Practice Changer?

n late July, the FDA approved carfilzomib as a monotherapy for patients with relapsed and refractory multiple myeloma. Interviews with several hematology/oncology experts suggest that the drug will have a significant impact on the treatment of this challenging malignancy. Onyx Pharmaceuticals, which will market the drug as Kyprolis, had asked that carfilzomib be approved for patients with multiple myeloma

•

see CARFILZOMIB, page 40

•

Milk-thistle Extract Takes the Sting Out of Amanita Mushroom Toxicity San Diego—Silibinin, a constituent of milk thistle ((Silybum marianum), can help reverse the effects of severre mushroom poisoning, accord-ing to a case series present-ed at Digestive Disease Weeek (abstract Su1606). In the case series, four patients ate mushrooms of the genu us Amanita, which the researchers said is responsible for more than 9 90% of fatal mushroom poisonings in n the United States. All four patieents recovered, further bolstering evi-

dence of the efficacy of the investigational agent, which has been used successfully in more tthan 40 patients to date. Thee four patients presented over a two-week period at Medstar Georgetown University Hospital, in Washington, D.C., with acute hepatitis caused by acute mushroom poisoning. One patient had concurrent pancreatitis. The patients received aggrressive hydration, IV silibinin infussion (Legalon SIL, Madaus),

The Book Page Best Practices for Hospital and Health-System Pharmacy 2011-2012 American Society of Health-System Pharmacists See page 43.

•

see POISONING, page 37

New Product Cooper Atkins introduces new temperature data loggers. See page 42.

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4 Up Front

Pharmacy Practice News • August 2012

Capsules

Senate Passes Bill To Address Drug Shortages

n June 26, in a 92-4 vote, the Senate approved reauthorizing the Prescription Drug User Fee Act, in a bill that includes provisions addressing the nation’s rampant drug shortages. Known as the Food and Drug Administration Safety and Innovation Act (s.3187), the bill already had been passed by the House and now goes to President Obama for signature. Joseph M. Hill, the director of federal legislative affairs at the American Society of Health-System Pharmacists (ASHP), said that the president is expected to sign the bill. To address drug shortages, the legislation requires drug manufacturers to notify the FDA at least six months in advance of a product discontinuation or interruption, or as soon as possible. In

heard here

the event of noncompliance, the FDA will send a letter to the manufacturer and require a response within 30 days that explains the noncompliance. In addition, the bill calls for a task force to establish a strategic plan to deal with shortages, and permits health systems to repackage drugs and transfer them to other hospitals within the system. The FDA and Drug Enforcement Administration are required to collaborate and, if necessary, adjust quotas related to shortages of controlled substances. The bill’s establishment of user fees for generic drugs and biosimilars “will help FDA to approve generic products faster; this will speed up approval times and get products to market quicker,” Mr. Hill told Pharmacy Practice News.

‘We realized a

$2 million ROI in drug costs savings,

first

mostly because we were able to get away from outsourcing IV

preparations.’ —Bill Churchill, MS, RPh

See article, page 10

A coalition of organizations was active in the effort to produce the legislation. The Institute for Safe Medication Practices (ISMP) is part of that coalition; other core members include the ASHP, the American Hospital Association, the American Society of Clinical Oncology and the American Society of Anesthesiologists, according to Allen J. Vaida, PharmD, FASHP, executive vice president of ISMP, in Horsham, Pa. “We’re pleased the legislation finally came through, although it’s taken a long time,” said Dr. Vaida, who noted that the coalition has been working on the issue since 2010. “A lot of our suggestions have gotten incorporated into the legislation.” Speaking of ASHP’s position on the bill, Mr. Hill said, “We are very much in support of it.” Commenting on the legislation, Erin R. Fox, PharmD, FASHP, the director of the Drug Information Service at the University of Utah Hospitals & Clinics, in Salt Lake City, said, “It’s a great start and I think it will help.” Referring to the FDA’s record of success with voluntary early notification, Dr. Fox said, “If notified early enough, [the] FDA can try to prevent shortages. Once a shortage starts, there’s not always much FDA can do.” Dr. Fox noted that the number of new shortages beginning in 2012 is about half the number that occurred during the same time period in 2011. Calling this an “encouraging” sign, she said, “I believe we are seeing the

results of [the FDA’s] efforts in the rate of new shortages.” Drs. Fox and Vaida both stressed that other changes besides this legislation would be needed to improve the shortage problem. Dr. Fox said manufacturing is a major issue: “Manufacturers need to step up quality and adhere to good manufacturing practices.” Dr. Vaida said redundancy in the supply chain is needed, such as requiring that several different manufacturing facilities be approved to produce a drug if a company is the sole supplier. In the meantime, Dr. Fox said her hospital faces continuing shortages of drugs such as leucovorin, naloxone, lorazepam, fentanyl, sufentanil, etomidate and midazolam. To deal with shortages, she said, “We rotate the stock frequently, try to centralize stock and draw up doses in the clean room.” She also uses alternative agents, such as levoleucovorin (Fusilev, Spectrum) instead of leucovorin. “We’re getting by with time and effort and lots of concern for potential errors.” —George Ochoa Drs. Fox and Vaida reported no relevant financial conflicts of interest.

EDITORIAL BOARD

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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 39 • Number 8 • August 2012 • pharmacypracticenews.com

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

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EDITORIAL STAFF

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NUCLEAR PHARMACY

BIOTECHNOLOGY Jeffrey Norenberg, PharmD, Albuquerque, NM

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CARDIOLOGY

ONCOLOGY

C. Michael White, PharmD, Storrs, s CT

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Kevin Horty, Don Pizzi, Adam Marcus, Cynthia Gordon, Contributing Editors

CNS/PSYCHIATRY

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TECHNOLOGY

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Important Safety Information Levetiracetam in Sodium Chloride Injection is an antiepileptic drug indicated when oral administration is temporarily not feasible in adults (16 years and older) with: partial onset seizures; myoclonic seizures in patients with juvenile myoclonic epilepsy; primary generalized tonic-clonic seizures. Levetiracetam should be gradually withdrawn to minimize the potential of increased seizure frequency. Antiepileptic drugs (AEDs) increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Levetiracetam in Sodium Chloride Injection causes neuropsychiatric reactions including somnolence and fatigue, muscle coordination difﬁculties and behavioral abnormalities as well as hematological abnormalities. The most common adverse reactions observed with Levetiracetam were somnolence, weakness, infection and dizziness. Important behavioral adverse reactions include hallucinations, delusions, and non-psychotic mood disorders including suicide ideation, aggression, anger, apathy, conduct disorder, irritability, depression, nervousness, anxiety and emotional lability. Dosing must be individualized according to seizure type, patient’s renal function status and therapy objective. Based on animal data, Levetiracetam may cause fetal harm and therefore should be used during pregnancy after consideration of the potential beneﬁt-risk ratio. Levetiracetam should be gradually withdrawn to minimize the potential of increased seizure frequency.

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Brief Summary of Risk Information for LEVETIRACETAM IN SODIUM CHLORIDE INJECTION, for intravenous use WARNINGS AND PRECAUTIONS Neuropsychiatric Adverse Reactions Partial Onset Seizures: Levetiracetam can cause central nervous system adverse reactions: 1) somnolence and fatigue: levetiracetam 14.8%, placebo 8.4%. In a study without titration, 45% reported somnolence from 4000 mg/ day; considered “serious” by 0.3% levetiracetam, versus 0% of placebo patients; discontinuation: 3% levetiracetam, versus 0.7% of placebo patients; dose reduction: 1.4% levetiracetam versus 0.9% placebo; 0.3 % levetiracetam patients were hospitalized for somnolence. Asthenia: levetiracetam 14.7%, versus 9.1% placebo; treatment discontinuation: 0.8% versus 0.5% placebo; dose reduction: 0.5% versus 0.2% of placebo; 2) coordination difficulties (ataxia, abnormal gait, or incoordination): 3.4% levetiracetam versus 1.6% placebo; discontinuation from ataxia: 0.4% levetiracetam versus 0% placebo; dose reduction: 0.7% levetiracetam versus 0.2% placebo; one patient hospitalized from worsening of pre-existing ataxia. Somnolence, asthenia and coordination difficulties occurred most frequently within the first 4 weeks of treatment. 3) behavioral abnormalities (psychotic symptoms and other behavioral and mood symptoms): Psychotic symptoms: 5 (0.7%) levetiracetam versus 1 (0.2%) placebo. Two (0.3%) levetiracetam patients hospitalized and treatment discontinued. Both developed in the first treatment week, resolved in 1 to 2 weeks following discontinuation. Two events of hallucinations, occurred after 1-5 months and resolved within 2-7 days while remaining on treatment. One psychotic depression occurring within a month, resolved within 45 days while treatment continued. Other behavioral symptoms (aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.): 13.3% levetiracetam versus 6.2% placebo; approximately half reported within the first 4 weeks; treatment discontinued in 1.7% levetiracetam versus 0.2% placebo; dose reduction in 0.8% levetiracetam versus 0.5% placebo. Serious behavioral event causing hospitalization in 0.8% levetiracetam versus 0.2% placebo. Attempted suicide after 4-6 months treatment (one completed suicide) in 4 (0.5%) levetiracetam versus 0% placebo. Myoclonic Seizures: Somnolence and behavioral abnormalities: It is expected that the events seen in partial seizure patients would occur in patients with juvenile myoclonic epilepsy (JME). In JME patients JME experiencing myoclonic seizures: somnolence occurred in 11.7% of levetiracetam versus 1.7% of placebo patients (no treatment discontinuations); dose reduction in 1.7% levetiracetam versus 0% of placebo. Non-psychotic behavioral disorders (aggression and irritability): 5% levetiracetam versus 0% placebo. Non-psychotic mood disorders (depressed mood, depression, and mood swings) 6.7% levetiracetam versus 3.3% placebo. Dose reduction or discontinuation: 5.0% of levetiracetam versus 1.7% placebo. Primary Generalized Tonic-Clonic Seizures: Behavioral symptoms appeared to be associated with levetiracetam. Gait disorders and somnolence were described in patients with primary generalized seizures, but no difference between placebo and levetiracetam groups and no appreciable discontinuations. In some patients levetiracetam causes behavioral abnormalities: irritability 6.3% levetiracetam versus 2.4% placebo. In patients with idiopathic generalized epilepsy, non-psychotic behavioral disorders (abnormal behavior, aggression, conduct disorder, and irritability): 11.4% levetiracetam (one discontinued due to aggression) versus 3.6% placebo; non-psychotic mood disorders (anger, apathy, depression, mood altered, mood swings, negativism, suicidal ideation, and tearfulness): 12.7% levetiracetam versus 8.3 placebo. Suicidal ideation in one levetiracetam patient. Delusional behavior in one patient requiring lowering of the levetiracetam dose. In a long-term open label study of various forms of primary generalized epilepsy, along with the non-psychotic behavioral disorders, 2 of 192 patients studied exhibited psychotic-like behavior, one characterized by auditory hallucinations and suicidal thoughts (led to drug discontinuation), the other as worsening of pre-existent schizophrenia (did not lead to discontinuation). Withdrawal Seizures: Antiepileptic drugs, including levetiracetam, should be withdrawn gradually to minimize the potential of increased seizure frequency. Hematologic Abnormalities: Minor, but statistically significant, decreases in total mean RBC count (0.03 x 106/mm3), mean hemoglobin (0.09 g/dL), and mean hematocrit (0.38%), were seen in levetiracetam patients. A total of 3.2% of treated and 1.8% of placebo patients had at least one possibly significant (≤2.8 x 109/L) decreased WBC, and 2.4% of treated and 1.4% of placebo patients had at least one possibly significant (≤1.0 x 109/L) decreased neutrophil count. Of the treated patients with a low neutrophil count, all but one rose towards or to baseline with continued treatment. No patient was discontinued secondary to low neutrophil counts. Hepatic Abnormalities: No meaningful changes in mean liver function tests

(LFT) in controlled trials in adult patients; lesser LFT abnormalities were similar in drug and placebo patients in controlled trials (1.4%). No patients were discontinued from controlled trials for LFT abnormalities except for 1 (0.07%) adult epilepsy patient receiving open treatment. Laboratory Tests: Relatively infrequent abnormalities seen in hematologic parameters and liver function tests. ADVERSE REACTIONS: Most common (≥ 5%) versus placebo include: somnolence, asthenia, infection, and dizziness; important behavioral (< 5%) include depression, nervousness, anxiety, and emotional lability. See full prescribing information for adverse reactions in specific types of seizures and incidence when levetiracetam was added to concurrent AED therapy. Postmarketing Experience: Additional adverse events reported worldwide (alphabetically): abnormal liver function test, hepatic failure, hepatitis, leukopenia, neutropenia, pancreatitis, pancytopenia (with bone marrow suppression identified in some), thrombocytopenia and weight loss. Alopecia was reported; recovery was observed in majority of cases where levetiracetam was discontinued. Reports of suicidal behavior (completed suicide, suicide attempt and suicidal ideation) with marketed levetiracetam. See Patient Counseling Information. USE IN SPECIFIC POPULATIONS. Pregnancy Category C: No adequate and well-controlled studies in pregnant women. Animal studies: evidence of developmental toxicity, including teratogenic effects, at doses similar to or greater than human therapeutic doses. Levetiracetam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. As with other antiepileptic drugs, physiological changes during pregnancy may affect levetiracetam concentration. There have been reports of decreased levetiracetam concentration during pregnancy. Discontinuation of antiepileptic treatments may result in disease worsening, which can be harmful to the mother and the fetus. North American Antiepileptic Drug Pregnancy Registry: Physicians are advised to recommend that pregnant levetiracetam patients enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry, toll free number 1-888-233-2334 (must be done by the patients themselves), website http://www.aedpregnancyregistry.org. Effect on Labor and Delivery: unknown. Nursing Mothers: Levetiracetam is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from levetiracetam, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Safety in Pediatric Use: Safety and effectiveness below age 16 years have not been established. Geriatric Use: No overall differences in safety were observed compared to younger subjects. Numbers of clinical trial subjects were insufficient to assess effectiveness in the elderly. A study in 16 elderly subjects (age 61-88 years) with oral administration of single dose and multiple twicedaily doses for 10 days showed no pharmacokinetic differences related to age alone. Levetiracetam is substantially excreted by the kidney, with concomitant risk of adverse reactions in patients with impaired renal function. Accordingly, care should be taken in dose selection for the elderly, and it may be useful to monitor renal function. Use in Patients with Impaired Renal Function: Clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance. Caution should be taken in dosing patients with moderate and severe renal impairment and in patients undergoing hemodialysis. The dosage should be reduced in patients with impaired renal function receiving levetiracetam and supplemental doses should be given to patients after dialysis. OVERDOSAGE: Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans: The highest known dose of oral levetiracetam received in the clinical development program was 6000 mg/day. Only drowsiness was observed in the few known cases of overdose in clinical trials. Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma observed in overdoses in postmarketing use. Treatment or Management of Overdose: No specific overdose antidote. If indicated, elimination of unabsorbed drug should be attempted by emesis or gastric lavage; usual precautions to maintain airway. General supportive care is indicated including monitoring of vital signs and observation of clinical status. A Certified Poison Control Center should be contacted for up to date information. Hemodialysis: Standard hemodialysis procedures result in significant clearance of levetiracetam (approximately 50% in 4 hours) and should be considered in cases of overdose. Although hemodialysis has not been performed in the few known cases of overdose, it may be indicated by the patient’s clinical state or in patients with significant renal impairment. Patient Counseling: Patients should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician as suicide, suicide attempt and suicidal ideation have been reported in patients treated with levetiracetam. To report SUSPECTED ADVERSE REACTIONS, contact Mylan Institutional LLC at 1-877-4RX INFO or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. g /

Technology 9

Pharmacy Practice News • August 2012

Automation

CPOE

particularly struck by the problems of interoperability,” the classic one being ordering systems trying to communicate with different types of pharmacy systems “and somehow things go wrong in those handshakes.” “One thing we observed was the possibility of putting in too many zeros and having a 10-fold overdose,” Dr. Schiff said. Some systems have decision-support functions that include dosagerange checking, but “it’s inconsistent and varies from drug to drug,” he said.

continued from page 1

Dr. Schiff told Pharmacy Practice News.

USP MEDMARX Tapped As a Rich Research Vein The investigators embarked on their research two years ago, to gain a deeper insight into why the use of CPOE systems—designed to avoid medication errors inherent in handwritten and verbal orders—was creating a whole new category of alarming mistakes. Their investigation began with a search of the rich database of medication errors reported to the United States Pharmacopeia (USP) MEDMARX program in the decade leading up to 2010. The aim was to mine the collection of more than a million voluntary reports, looking for patterns in CPOE-linked errors that could be distilled into a coded classification system, and one that might provide a new tool for preventing costly errors. “With the rise in computerized prescribing, we’re hearing more and more about unintended consequences and frustrations related to CPOE,” Dr. Schiff said. “We thought that understanding the errors increasingly being reported—particularly med errors related to CPOE—was very important.” The first results of their investigation were unveiled in a poster at the 2011 annual meeting of the American Medical Informatics Association, in Washington, D.C. They have since been refined. Of the approximately 1.04 million errors reported to MEDMARX from 2004 to 2010, just over 63,000 listed CPOE as the source. Of those, the team reviewed more than 10,000, according to Andrew Seger, PharmD, RPh, a senior research pharmacist at Brigham and Women’s, and a co-investigator for the study. The team was aided by USP’s decision, in 2003, to add a new field in the MEDMARX reporting form allowing users to check CPOE as the error source. The presence in some reports of free-text narratives describing what had gone wrong and why gave them the basic research material needed to explore the language that researchers and clinicians can use to describe CPOE-related errors. Funded by a grant from the National Patient Safety Foundation, the team of three pharmacists and a physician spent a year sorting and analyzing the narratives into logical categories. The result was the creation of 262 codes classifying what had happened and why and what might have been done to prevent the errors. Among the leading “what” codes were missing or incorrect directions for taking medications; missing number/quantity or wrong number ordered; wrong dose or strength; and duplicate drug

Benefits to Stakeholders

‘We were particularly struck by the problems of interoperability,’ the classic one being ordering systems trying to communicate with different types of pharmacy systems ‘and somehow things go wrong in those handshakes.’ —Gordon Schiff, MD

ordered. The top “why” codes included multiple system (two or more electronic systems); use of system or sigma abbreviations; profiling issues (failure to do or perform correctly); and inexperienced

end users. (See Table for more details.) “Certain ‘whys’ are unique to computers,” Dr. Schiff said, such as pulldown menu errors where the wrong line is selected. But he added, “We were

Table. Common “What” and “Why” Codes For CPOE-Related Errors Top “What” Codes

Top “Why” Codes

Subcode

Missing or incorrect SIG/patient instructions

1,763

Unknown

4,542

Missing number/quantity or wrong number ordered

766

Multiple systems (two or more electronic systems)

1,072

Ordered wrong dose or strength

751

Use of system or SIG abbreviation

416

Unknown

611

Profiling issues: failure to do or perform correctly

377

Wrong schedule entered

497

Failure to follow established protocol or procedures

366

Duplicate order—same exact drug

422

Inexperienced end user

362

Overdose or potential overdose

316

Lack of computer training/ system knowledge

276

Ordered wrong formulation/ dosage form

309

Hybrid system (electronic and paper)

182

Order not processed or delayed

304

Typing error

182

Patient potential for extra dose

289

Medication reconciliation issue

170

Ordered wrong drug

266

Lack of clinical knowledge

162

Routing issue

248

Routing/mapping issue

155

Order was confusing: comment field has conflicting information

232

Communication issues

147

Wrong time selected

218

Dr. Seger said a key goal of the team’s work was to a create a classification system that vendors could use to “develop systems that are more clinically feasible, not only for physicians but also for pharmacists and patients in the ambulatory care setting and pharmacists and nurses on the inpatient side.” He also saw a potential “for assisting information technology developers, for people implementing and using these systems, and for those in the safety world to make sure the systems they have installed are in fact working properly within the design parameters of prescribing systems.” He continued, “Obviously there are a lot of very smart clinicians out there, but the complexity of our medical system makes it very difficult for any single person to try to maintain a knowledge base for every possible iteration of what may go on with a medication.” Dr. Seger added, “We want to use computers in a way that assists us in our care of patients, but we also want to make sure that we’re not introducing new errors; or at least if we are, then we’re taking steps to reduce them.” The second phase of the project involved what Dr. Schiff described as “kicking the tires, where we went out and tried to replicate these errors in real-life systems.” What they found, he said, was that in many cases, medication orders in which errors had deliberately been introduced “sailed right through with no warnings.” According to Dr. Schiff, “the most shocking example was a system in which all of the errors went through. It turned out that several months earlier the system had been upgraded, but when it went live again everyone forgot to turn the alerts back on. “I don’t want to claim we’re going to save anyone’s life by this study or change the way computerized prescribing is done,” Dr. Schiff said, “but who knows, in this one hospital, we may have actually saved a life or two.”

ISMP’s Take Nursing administration issues

136

CPOE, computerized prescriber order entry; SIG, drug label dosage instructions (short for signatura).

Michael R. Cohen, ScD, MS, RPh, FASHP, president of the Institute for Safe Medication Practices (ISMP), said that

•

see CPOE, page 11

10 Technology

Pharmacy Practice News • August 2012

Automation

Adding Technology to IV Rooms Boosts Patient Safety T

he Medical University of South Carolina Medical Center (MUSC), in Charleston, a 700-bed academic hospital, and the 800-bed Harvard-affiliated Brigham and Women’s Hospital, in Boston, have reaped safety and financial benefits from adding robotics, barcode verification and other medication safety technologies to their sterile products areas. Speaking in a webinar sponsored by the UnSummit, Christopher R. Fortier, PharmD, the manager of pharmacy support and operating room services at MUSC, and Matt Maughan, PharmD, currently the director of pharmacy at Rainbow Babies & Children’s Hospital, in Cleveland, but until recently the manager of the pharmacy at MUSC’s Children’s Hospital, described what they called the “dramatic” improvements that MUSC has experienced since the implementation of a bar-code medication preparation (BCMP) system at the children’s hospital last fall. Within the first month of implementation, 85% of all IV drugs in the children’s hospital IV room were covered by the BCMP system, which does the following: “prints” labels to a touchscreen computer from which a technician can pick which dose he or she wants to prepare; verifies via bar-code technology that the correct medication and diluent were chosen, provides instructions to technicians about how make the preparation, allows technicians to take pictures of the preparation process and automatically time stamps each step in that process for future record keeping and management reporting.

Standardizing Processes Improves Reliability The unique bar code that is assigned to each product then can be used to track the medication to the nursing unit, or whatever end location has been provided, with a location bar code. Since the implementation of the BCMP IV system, which both Drs. Fortier and Maughan describe as a “best practice for the near future,” MUSC staff have seen “eight to 10 medications a day that could have been an error [with] the old system,” according to Dr. Maughan. “That represents 1.3% to 3% of the total number of doses dispensed.” Such improvements occurred because the BCMP system gave MUSC the ability “to standardize our workflow processes in the IV room in a way that has been vetted and validated,” according to Dr. Maughan. By controlling and improving variability, he added, the system “automatically improves reliability.” Dr. Fortier noted that although it is “difficult” to quantify the percentage of

dose. In contrast, “with some of these automated systems, they know exactly how much product was placed in the IV; they can weigh the bag as another safety check.” The system that MUSC implemented can guarantee that the correct medication was in the dose, but it doesn’t have gravimetrics, so it can’t guarantee that the correct amount of the medication was put into the dose. However, he noted that they take photographs to document each step. Dr. Maughan said he agreed that gravimetrics would be the next step “if you can apply it to 100% of the doses that the pharmacy prepares.”

A Cytocare robot at Brigham and Women’s Hospital draws up an IV drug dose and places it into an IV bag or syringe (right). Below, the sterile compounded product can be weighed with a gravimetric scale to ensure accuracy.

Gravimetric Checking in Action

medication preparation errors in an IV room, partly because “there is so much variability across hospitals by training and processes, the occurrence of medication errors is obviously a big issue.” Hospital IV rooms, he noted, are constantly dealing with high-risk patients, high-risk medications, high-expense medications, drug shortages, different sizes, different concentrations and different processes for preparing dosages. “The traditional IV process,” he noted, “is very manual and the systems being used are 30 to 40 years old.”

Ron Schneider, RPh, MHA, formerly a pharmacist consultant with the VA’s Barcode Resource Office, and now the president and founder of Schneider Consulting in Olney, Md., pointed out that in the manual IV system, “the techs make up the IVs and the pharmacists check them. If it is not a premanufactured IV, the technician will leave the solution and the vial for the pharmacist to check, but that doesn’t mean, for example, that the technician actually put 5 ccs into the bottle and drew out the 2 ccs required for the patient

Brigham and Women’s Hospital certainly sees the value of gravimetric checking—so much so that it is using the technology to test 50% of prepared doses. The assay is built into its BCMP IV workflow software “to accurately and precisely weigh the medications during the compounding process,” said Bill Churchill, MS, RPh, the chief of service in the Department of Pharmacy at Brigham and Women’s. “This ensures that the compounded sterile product has been made accurately.” In addition to the gravimetric work flow software, Brigham and Women’s Hospital also has four IV robots preparing upward of 50% of its IV admixture volume. For example, this past June, the robots, integrated with the bar-code verification software and the gravimetric checking functionality, prepared 41,000 IVs out of 82,000 for that month. Mr. Churchill told Pharmacy Practice News that with the integration of all

How Bar-code Medication Preparation Works at MUSC

USC uses its BCMP IV system to improve the accuracy, efficiency and safety of IV drug preparation and delivery. Among other things, the system can “organize drug selection to ensure we are using the correct product when preparing a dose and tying that product back to the patient order for that drug,” noted Dr. Fortier. In every step of the preparation process, the BCMP system takes a picture of exactly what is happening, from the initial selection of a drug and a dosage through injection into a storage bag, labeling and scanning. “That really helps a pharmacist approve the medication,” noted Dr. Fortier. “There is no more need for a pharmacist to hold an IV bag. Using the pictures, the pharmacist has everything in front of him or her. They can magnify the image or any of its parts.” Once a medication is checked and sorted by the pharmacist, a label is printed that indicates that the drug has been checked and is ready to be administered through MUSC’s bar-code administration system. After items leave the pharmacy, they are scanned again when they are delivered, making it possible for pharmacist to know where each dose is at any given time and to share that information with nurses waiting for the drug. And that tracking can be done off premises at other sites that are receiving medications from a centralized pharmacy. In the past, “it could take up to an hour to find out where a missing dose went. Now it takes two to three minutes, and that results in serious cost savings,” said Dr. Maughan. Tracking also gives hospitals the ability to centralize the preparation of hazardous medications and time-sensitive preps, said Dr. Maughan. “We now have a level of accuracy that was unheard of before. There are a lot of advantages to that in helping to prevent missing doses,” said Dr. Fortier. Additionally, he said, “because of the tracking, there will be less calls to the pharmacy from nurses about missing drugs.” The system also saves time on the back end, he noted, “because you don’t necessarily need the pharmacist to actually be in the IV room to check the drugs. You will also decrease medication waste because you will be making the medications on demand, according to the order in which they are needed.” —L.P.

Technology 11

Pharmacy Practice News • August 2012

Automation three technologies—IV bar-code verification, gravimetric checking and IV robotics—“we were able to show that the degree of precision for making our batch-compounded sterile products was in the range of plus or minus 1% to 3% for product accuracy. The United States Pharmacopeia standard for accuracy is plus or minus 1% to 10%. This increase in accuracy means less compounding errors, which will lead to decreases in adverse drug events for our patients as we strive to get to zero medication errors.”

Systems Are Cost Effective In researching the cost effectiveness of implementing a BCMP system, MUSC looked at a number of factors that could be measured, including medication waste, which has a significant effect on costs. MUSC collected information about waste for the three months prior to the implementation. After implementation, MUSC discovered that waste, which had ranged between 10% and 11% a month, declined to approximately 4%. Calling that “a dramatic decline,” Dr. Maughan said that it “met the ROI [return on investment] we were hoping for.” Such a sharp decrease in waste, he said, created “a potential for a $10,000 gain over capital investment costs per month. The capital investment costs for the system we chose were actually quite low. That created a strong case for moving forward on the fiscal side.” At Brigham and Women’s Hospital, an ROI was realized “immediately” after implementation of a BCMP system, according to Mr. Churchill. “We realized a $2 million ROI in drug costs savings,” he said, “mostly because we were able to get away from outsourcing IV preparations. Those outsourced IVs have a premium price tag attached to them. When we did a line-by-line analysis, by using the robots over outsourcing, we were able to take $2 million out of [the pharmacy] budget, and, at the same time, improve the quality of our compounded sterile products, and improve the pharmacy technician’s job function-

CPOE continued from page 9

while the use of CPOE systems has led to “a vast improvement over handwritten prescriptions, we certainly get error reports” associated with CPOE use. Lately, he said, ISMP has been dealing with CPOE systems employing standard schedules that limit practitioners’ dosing flexibility. For example, he said, if a drug is supposed to be given every 12 hours—say, 8 p.m. and 8 a.m.—and a starting dose is ordered

How MUSC Approached BCMP Implementation

efore implementing their BCMP, MUSC management determined that “very little [information technology] resources were needed. Essentially a lot of the information that has to be gathered for these systems can be done within the pharmacy department itself,” said Matt Maughan, PharmD. However, Dr. Maughan added, it is important to get the person in charge of managing the server involved early. “All of the BCMP systems we looked at ‘live’ on the hospital server and will be accepting patient information from other systems that ‘live’ on the server.” MUSC also engaged its physician leaders and members of the Risk Management Department early in the development and implementation process, because these groups “were very focused on having safety gaps in our health care processes solved and solved well,” said Dr. Maughan. “There is a potential to have a pretty big windfall for the organization if we can close the safety gaps and not have the organization at risk from a very serious adverse event.” MUSC initially wanted to include 100% of the medications in IV when they implemented the BCMP process, Dr. Maughan said. But, that turned out to be impossible in the initial implementation at the children’s hospital because pediatric chemotherapy often required a wide range of diluent volumes. There were, for example, 12,000 possible diluents for pediatric chemotherapy. MUSC made those numbers more manageable by working with the vendor of their automated compounding device to create special compound diluents with volumes within three increments of each other. When these specific volumes of diluents were selected, a bar code would appear that was readable by their BCMP system. They applied the same principle to other high-risk IV medications, such as heparin intended for patients in the neonatal intensive care unit. So although they could not cover all medications with the BCMP process, currently more than 95% of all IV drugs in the children’s hospital are covered by the system. Dr. Maughan stressed that to make the BCMP IV system highly reliable and flexible requires “an enormous amount of background work,” including all the work cited above. From a fiscal and ROI perspective, Dr. Maughan noted that if hospitals can’t decrease their waste and expenses in their IV rooms, it becomes very difficult for an organization to justify investments in technology. “So, we really looked at how much waste we reduced and how much expenses decreased.” An additional major payback, he said, was how the BCMP IV system enhanced the morale of IV room staff, creating a sense of comfort and relief that they had a system that could and did reduce medication errors. —L.P.

ality without laying anyone off.” BCMP systems also give pharmacists the ability to review past doses to search for potential errors. For example, in only three hours, MUSC’s BCMP system could review all dopamine doses made over a two-month period, said Dr. Maughan. “In the old way, which was to save the bag and send it for analysis, it would cost $300 each time and we wouldn’t have an answer for at least a week.” Through the productivity metrics provided by the system, MUSC also can find out such things as which technicians are overriding dosages, how long it takes to prepare certain dosages, the fluctuations in preparations by time of day, how to adjust their labor and so forth. In June, MUSC expanded the BCMP IV system to two additional 24-hour adult pharmacies and a clinic pharmacy. Also on the horizon is implementing the system for compounding and investigational drug services. Although BCMP is still in the ear-

ly phase of adoption, current trends are pointing to a rising increase in implementations, said Dr. Fortier. “I’ve heard a lot of great comments from people wanting to implement this process because obviously it makes a lot of good sense.” Additionally, he said, The Institute for Safe Medication Practices has endorsed these systems and it is a recommendation that came out of the Pharmacy Practice Model Initiative summit. Mr. Schneider called the BCMP process “a safety feature that has long been missing in the manual IV manufacturing process.” He and Mr. Churchill both predicted that the use of bar-code verification software with workflow management and gravimetrics workflow in hospital IV rooms eventually will become standard practice and that it would become more widely adopted over the next three to five years. “I can’t see anyone not having the ability to justify the investment in these BCMP IV workflow systems to ensure that you are making the IVs correctly,”

said Mr. Churchill. “It costs between about $6,000 and $10,000 a year, so even the smallest rural hospitals should be able to invest some money to ensure that their IVs are being prepared accurately. This is a no-brainer.” —Liz Parks

for 6 p.m., the system automatically schedules the next dose for 8 p.m., “so it’s almost a duplication of a single dose. We’ve been hearing a lot of things like that lately.” Wrong-patient errors also are cropping up more frequently, Dr. Cohen said. These can happen, he said, when doctors have two or more patient screens open and don’t realize that the patient they are typing in an order for is not the one they had in mind. In some CPOE systems, he said, a warning message asks if the order being

entered is for the right patient. But that feature doesn’t exist in all systems, he said, adding, “in too many cases, it’s up to the vendor to decide whether to do something or not.”

of experts representing both practitioner and vendor interests and task them with coming up with standard solutions for all systems. For now, Dr. Cohen wants to encourage more reporting from CPOE users about the kinds of problems they’re encountering and errors that are occurring. “We need more and more feedback,” he said, “so that when things go wrong, we can get vendors to really focus on improvement efforts.”

A Role for Federal Oversight? To ensure greater standardization among systems, he suggested some form of government oversight might be required, either by the FDA or the Office of National Coordinator for Health Information Technology. These agencies, he said, could bring together panels

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12 Technology

Pharmacy Practice News • August 2012

Automation

SMART PUMPS

‘You spend a lot of money

Table. “Good Catches” of Potentially Serious Medication Errors

continued from page 1

Rita Jew, PharmD, the executive director of pharmacy and clinical nutrition services at CHOC, and a co-author of the poster, said that hospitals that don’t make similar efforts to maximize the effectiveness of their smart pumps are missing out on the benefits of the medication safety technology. “You spend a lot of money on these smart pumps and if you’re using it as just a regular pump, you’re wasting your money,” Dr. Jew said. “The pump is only smart when you’re using it the smart way. Buying the pump is just the beginning of the investment.” CHOC made its initial investment in smart pumps in 2004. But a year later, when Dr. Jew joined the hospital as its pharmacy director, she soon noticed that the staff wasn’t analyzing data that were being collected. When they started to look at the data on a quarterly basis, the numbers pointed to a problem: people were ignoring a lot of pump alerts. “We saw that nurses were not compliant with using the guardrails and were not using the pump appropriately. That’s when we started doing a lot of data mining and [instituted] nursing compliance rounds,” Dr. Jew said, adding that efforts also were made to make the data from the pumps more user-friendly. A smart pump oversight committee of pharmacists, nurse educators and representatives from the hospital’s biomedical, information technology, and quality and safety groups was the prime mover in the quality improvement effort. Pharmacists prioritized about 250 drugs in their standardized smart pump software library and set the system so alerts would be generated when an IV medication was programmed outside the institution-defined drug limits, or

on these smart pumps

Medication

Programmed

Re-Programmed

and if you’re using it

Dopamine drip

596 mcg/kg/min

5.96 mcg/kg/min

as just a regular pump,

Midazolam drip

0.5 mg/kg/h

0.05 mg/kg/h

Propofol drip

100 mL/h (1,022 mcg/kg/min)

100 mcg/kg/min

Total parenteral nutrition

32 mL/h (for 2.6-kg neonate)

8.5 mL/h

money.’ —Rita K. Jew, PharmD

‘Creating central drug libraries has become a huge push among larger health systems. If they didn’t already do it, they’re regretting it and trying to figure out how they can do it now.’ —Lee Fiebert, PharmD guardrails. They monitored to ensure appropriate use of smart pumps and modified programmed limits for several drugs to reduce the number of nonclinically significant alerts and prevent alert fatigue. Nursing educators were actively involved in ongoing compliance surveys. The team found that drug library use increased from 41% to 91% during the last three years (Figure 1); modifications to eliminate nonclinically significant alerts led to a 38% reduction in guardrail-related alerts; and alert overrides were reduced by nearly 26% over five years (Figure 2). As a result of the system improvements in CHOC, alerts overridden in less than two seconds decreased from an initial 40% in 2008 to consistently less than 20% in following years. Generally, nurses who see an alert and override it in less than two seconds are not evaluating the alert properly, Dr. Tu noted. “Now, our nurses actually pay

attention to the alerts,” she said. “I know that because I hear from them if they see an alert that doesn’t make sense, through an email or through their nurse manager.” The CHOC initiative also has succeeded in averting approximately 70 potential adverse drug events each year, at a resulting cumulative cost avoidance estimate of more than $3 million, the team reported. The system has detected and prevented numerous potentially serious medication errors, such as a dopamine infusion programmed for 596 mcg/kg per minute that was then reprogrammed to the correct rate of 5.96 mcg/kg per minute. Documenting these “good catches” helps the team reeducate the nurses about why guardrails are in place, Dr. Jew noted. (For more catches, see Table.) “I know it’s not always about the money—our ultimate goal is to improve patient safety,” Dr. Jew said. “But at the end of the day, we also have to be good stewards of our investment

100 90 80 70 60

1st major data set change based on continuous quality improvement analysis

Partnering with vendor for nursing education

50 40 30 20 10

Compliance rounds

Wireless implementation and complete rebuild of data set

▲

Guardrails usage

Better

0 Jan-June 2005

Jul-Dec l 2006

Jan-May 2007

Dec 2008

Apr A 2009

Jan-Mar 2010

A Apr-June 2010

Jul-Sep l S 2010

O Oct-Dec 2010

Jan-Mar 2011

Figure 1. Guardrailsa usage and nursing compliance rounds (%). a.

Includes drug library and other medication safety software.

you’re wasting your

A Apr-June 2011

Jul-Sep l S 2011

in medication safety technology. And if you’re not doing everything in your power to data-mine these systems and make sure they are operating at peak efficiency, with spot-on alerts and high staff compliance, then you’re really doing a disservice to your patients and to your hospital’s bottom line.”

Another Tack—Central Drug Libraries Larger health systems with multiple hospitals are taking a slightly different approach to getting the most out of their smart pumps: Several of them are moving toward consolidating drug libraries to one standard to be used system-wide, so that every hospital can benefit equally from software updates and other key enhancements. North Shore-Long Island Jewish Health System, which has facilities on Long Island, N.Y., and New York City, implemented a master library for its 15 hospitals and infusion and dialysis centers last year. Health-system leaders had been considering this initiative for some time, according to Lee Fiebert, PharmD, a medication safety specialist at the health system’s Long Island Jewish Medical Center (LIJ), in New Hyde Park, N.Y., who spoke about his system’s consolidation efforts at a session of the ASHP Summer Meeting. But it was an FDA recall of one of the infusion pumps used at North Shore that launched the health system into action. In just 41 business days last spring, a team of more than 600 pharmacists, physicians, nurses and others devised a master library of more than 550 drugs, now listed as more than 2,400 unique line items. The smart pumps were rolled out to LIJ on June 28, and other sites shortly after. Only one community hospital that had purchased new pumps just before the launch is not using the master library. The single library makes sense in a large system such as North Shore, Dr. Fiebert said, because when medical residents, nurses and in-house emergency medical technicians move from site to site within the system, there’s uniformity in pump programming and function. As additional perks, the strategy enables leaders to enforce compliance, have a set

•

see SMART PUMPS, page 14

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14 Technology

Pharmacy Practice News • August 2012

Automation

SMART PUMPS

A Primer on Smart Pumps

continued from page 12

point-person overseeing the system and leverages buying power with vendors. “Creating central drug libraries has become a huge push among larger health systems,” Dr. Fiebert told Pharmacy Practice News. “If they didn’t already do it, they’re regretting it and trying to figure out how they can do it now.” North Shore just hired a full-time employee to mine data for outcomes, Dr. Fiebert said, although “there’s no doubt there have been some radical catches on both the pediatrics and adult sides.” The Cleveland Clinic also has created a master drug library. Thomas Stanek Jr., a pharmacy student at Northeast Ohio Medical University who interns at the Cleveland Clinic’s main campus, helped with the initiative last summer by consolidating drug information from three of Cleveland Clinic’s 10 hospitals. Although each hospital used the same pumps, each had its own practice, formulary and standard concentration for IV medications. Developing one library for their flagship hospital and two others provided a starting point in working toward a single library for the entire system, Mr. Stanek noted. He and his colleagues obtained IV drug file library reports from the three

early 68% of U.S. hospitals use smart pumps, according to a 2011 ASHP survey. The devices include software allowing hospitals to create a library of medications providing dosing guidelines by establishing drug concentrations and hospital-defined upper and lower dosing limits. Alerts and clinical advisories can be built into the software to prevent errors like overdosing. Users may easily override a “soft” limit, and infuse the medication without changing the pump settings. But a “hard” limit won’t allow the user to administer the infusion unless the pump is reprogrammed within the acceptable range. —K.B.

‘The use of a single medication list for smart pumps only allows for one deployment or push of a medication, resulting in better consistency of care for the patient across the entire health system.’ —Thomas Stanek Jr. hospitals to create a rough-draft master drug library. The team re-organized the drugs by general medication class into a new database. They then compared each hospital’s IV formulary with the others and the master, noting discrepancies and discussing them with management and clinical pharmacists. This resulted in the smart pump team having an overall master library for all three hospitals.

“The biggest challenge was the amount of data,” Mr. Stanek said. “Even though it was only three hospitals, it was quite a bit of [information] to go through to get the draft.” But the results should be worth it, he said, when it comes to improving the quality of patient care. “Not only will it allow for optimal decisions regarding the health system’s formulary, but more importantly, it will improve medication

100 9 % 97%

95 90 88

84 80 82

▲

74 4

Better 70 0 July l 2006 May 2007

2008 2006

2009 2007

Jan-Mar 2010

Apr-June A 2010

Figure 2. Change in alert overrides (%).

Jul-Sep l S 2010

Oct-Dec O 2010

Jan-Mar 2011

Apr-Jun A 2011

Jul-Sep l S 2011

safety. The use of a single medication list for smart pumps only allows for one deployment or push of a medication, resulting in better consistency of care for the patient across the entire health system. At the local level, it accounts for consistent care despite possible staffing changes due to floating.”

Smart Pump Guidelines In Works ASHP is working with the Association for the Advancement of Medical Instrumentation (AAMI) and the FDA to help develop guidelines and recommendations for the management of programmable pumps. The AAMI Foundation’s Healthcare Technology Safety Institute is now investigating assorted smart pump issues, including why workarounds happen with drug libraries, who owns drug libraries and how to manage updates, according to Karl Gumpper, RPh, a member of AAMI’s Infusion Systems Steering Committee and the director of ASHP’s Section of Pharmacy Informatics & Technology. He said the committee also is looking at error reporting, noting that it’s sometimes tough to determine if an error resulted from a problem with a drug itself or with a malfunction of the smart pump using that drug. Mr. Gumpper and Bona Benjamin, RPh, the ASHP’s director of medicationuse quality improvement, are compiling a resource of standard concentrations and standard drug libraries that could be used as a starter library for hospitals to adopt and build into their use of the technology, or offered through a vendor. In addition, Mr. Gumpper said, “We’re all interested in the wireless integration between electronic health records and smart pumps.” To maximize the use of technology, he said, a physician could enter a prescription through computerized provider order entry, which a pharmacist then could verify and transmit to the device. A nurse then could use barcode technology to scan the drug and the patient and program the pump. So far, only about 10 hospitals are using this integrated technology, he noted. “It could save a lot of time for the nurses, but we have to make sure everything is working appropriately.” —Karen Blum

If you missed any recent issues of Pharmacy Practice News, visit www.pharmacypracticenews.com.

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16 Technology

Pharmacy Practice News • August 2012

Decision Support

Customizing Urged To Reap Benefits of CDS Software Baltimore—An ongoing, pharmacistled process of clinical decision support (CDS) customization is the only way for hospitals and health systems to establish an electronic medication safety management system that is truly meaningful, according to John R. Horn, PharmD, FCCP, a professor of pharmacy and the associate director of pharmacy at the University of Washington, Seattle. This customization, based on the organization’s unique practice patterns, protocols and range of clinical services, takes time and is not easy, but it is the best method currently available for preventing “alert fatigue” among physicians due to excessive, unfiltered warnings about drug–drug interactions (DDIs) and drug allergies, said Dr. Horn, during a presentation at the American Society of HealthSystem Pharmacists (ASHP) 2012 Summer Meeting. Virtually all of the electronic health record (EHR) systems on the market come with extensive databases of DDIs and allergies designed to alert physicians to potential medication safety problems, said Dr. Horn. These CDS tools can help hospitals meet the Centers for Medicare & Medicaid Services’ EHR meaningfuluse requirements for medication safety. But they also can frustrate the physicians who have been forced, with the advent of computerized prescriber order entry, to spend their time overriding countless alerts that are clinically irrelevant to their practice and their patients. “The problem is getting that clinical decision support software to interact with the prescribers in a manner that provides the expected benefit without producing unintended or unexpected adverse consequences,” Dr. Horn said in an interview. Those consequences can include desensitization to all alerts, even clinically important ones. Turning off the alerts—a common response by hospitals—is a bad idea that can hinder medication safety efforts, he said (Table). So is attempting to turn off selected warnings for selected prescribers, or modifying the system to send alerts to pharmacists and not to physicians. This latter option, which requires pharmacists to call physicians to discuss drug alerts, “creates an adversarial rela-

Table. Selected Interactions That Will Be Missed If Alerts Are Used for Only Most Severe DDIs Drug Combination

Resulting Potential Interaction

Amiodarone and haloperidol

Arrhythmia

Bepridil and clarithromycin

Arrhythmia

Colchicine and clarithromycin

Colchicine toxicity

Conivaptan and ergot alkaloids

Ergot toxicity

Cyclosporine and ketoconazole

Renal toxicity

Cyclosporine and rifampin

Organ rejection

Simvastatin and clarithromycin, erythromycin, cyclosporine

Myopathy

DDI, drug-drug interaction.

tionship that is a very ineffective way to mitigate the risk for drug interactions,” he said. “At our institution, we do not want our pharmacists dealing with physicians at this level.” The customization process should be based on a careful evaluation of the risks and benefits of clinically relevant drugpair interactions, with the goal of creating a system that requires further action by the physician only for DDIs that the institution classifies as serious, said Dr. Horn. That action could involve selecting an alternative for one of the two drugs, prescribing the two drugs and monitoring the patient or documenting the rationale for overriding the alert. “Every institution has a top tier of drug interactions that they consider to be most problematic,” he said. “That’s where we focus most of our attention [at the University of Washington]. We go through every single interaction pair in the list and reassess its severity ranking.” The customized system retains the complete DDI and allergy database but places less clinically relevant information in the background and allows physicians to sidestep it without disrupting their normal workflow. Physicians see and are required to take action regarding DDIs deemed “major” by the institution, whereas those classified as “moderate” or “modest” still appear but do not require physicians to stop and document a substitution or other course of action. “That then avoids the problem of alert

fatigue, which is why people turn the alerts off. They’re not turning things off because they think they’re bad; they’re turning them off because they’re irritating,” said Dr. Horn. “We’re trying to prevent patients from being harmed … and that’s why I think the risk–benefit approach is a reasonable way to think about [these interactions],” he added. “It’s really the way physicians think about any drug they prescribe. The solution is not to turn the less important ones off; the solution is to the fix the ones that you want to actually produce an alert.” Dr. Horn stressed the importance of establishing a set of rules for the severity rankings, applying them consistently, communicating them to the clinical staff and asking for input from clinicians about specific drug pairs that they feel merit special attention. He recommended assigning ongoing responsibility for customization to a small committee that can stay abreast of the literature and monitor decisions regarding system changes that reflect the new information. At the University of Washington, for example, a subcommittee of the Pharmacy Patient Safety Committee meets monthly to review new information about interactions and internal reports and concerns from physicians. “We’ve set up a formal process so that everything comes to one place,” said Dr. Horn. The subcommittee then reports changes to the clinicians who will be affected.

The customization process also should look at existing clinical safeguards and eliminate electronic drug interaction alerts related to protocols that are in place already, Dr. Horn advised. For example, a hospital that already has a rule for mitigating the side effects of administering antacids and antibiotics to a patient could turn off these electronic alerts because the institution already addresses the problem in another way. Marianne Ivey, PharmD, MPH, FASHP, an associate professor in the Division of Pharmacy Practice and Administrative Sciences at the University of Cincinnati, questioned the need for every hospital to create its own customized CDS system. She acknowledged that some customization of CDS is important in every health care environment but suggested that a significant portion of the laborious stratification of drug interactions into serious, moderate and rarely occurring classifications possibly could be done centrally and more cost effectively by an organization such as ASHP and then made available to the profession as a whole. A system of pharmacist-filtered drug alerts also could offer an effective alternative strategy for some institutions, she noted. “Pharmacists don’t mind seeing those alerts because they believe that’s their job, while physicians only want to be bothered by those that have been filtered by the pharmacist,” she said. Maren Everton, RPh, a managing partner of HealthCare Sage Consulting, LLC, and the vice chair of the ASHP Section Advisory Group on Clinical Information Systems, noted that ASHP is developing guidelines to help healthsystem pharmacists customize CDS systems for drug interactions and allergies, and is exploring the development of an “in-between” database that would offer institutions more strength and stratification than the prepackaged databases available through EHR vendors. —Susan Birk Dr. Horn disclosed that he is a partner with H&H Publications. Dr. Ivey reported no relevant financial conflicts of interest. Dr. Everton is a third-party consultant for Allscripts and an employee of Dell.

An App for Every Pharmacist Toronto—Pharmacists do not need to be extremely tech-savvy to use mobile devices in their work to improve patient care—getting comfortable with several applications or “apps” in their professional life will be of assistance to them. “Get familiar with a few apps, and know them well, so information will be

at your fingertips when you need to access it,” said Sean Spina, BScPh hm, ACPR, PharmD, a clinical coordinatorr at Royal Jubilee Hospital, in Victoria, and a clinical assistant professor at the University of British Columbia, in Canada. Speaking at the annual professional practice conference of the Canadian

Society of Hospital Pharmacists, Dr. Spina discussed integrating smartphone technology into daily professional practice as a means to enhance patient care.

“Smartphones can improve your life and make you more efficient,” he said. “Look at them as an opportunity, and become an early adopter.”

•

see APPS, page 18

Find us at the Intersection of Patient Safety and Pharmacy Efficiency Hospital pharmacies juggle many critical tasks. The top priority is patient safety. Operational efficiency is important too; institutions seek to provide bar-coded medications while minimizing packaging tasks to enable BCMA. American Health Packaging can support you at this â&#x20AC;&#x153;key intersectionâ&#x20AC;? of patient safety and operational efficiency. The AHP unit dose line is the fastest growing in the industry. And we offer many exclusive items to eliminate pharmacy packaging on lower-volume items. Easy-to-read bar codes ensure both accurate and easy scanning. In addition, our cartons feature color-coded labels to more easily distinguish between similar items on the pharmacy shelf.

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18 Technology

Pharmacy Practice News • August 2012

Informatics

‘With cloud computing and programs like Dropbox [a Web-based file hosting service using cloud storage],

APPS

it is a fine line for IT departments to maintain a

continued from page 16

Concerns about privacy and patient confidentiality can be addressed through information technology (IT) architecture, according to Dr. Spina. At his institution, a portal exists that pharmacists visit through their mobile devices to access information in real time. Patient information does not reside on mobile devices, but lies on a secure server. “I can access patient information

balance of open access versus security.” —John Poikonen, PharmD when I’m I m down the street from the hospital or across the country,” said Dr. Spina. “If I lose my phone, there is no security breach.” Decision support tools that would aid clinicians in making treatment choices are in their infancy, said Dr. Spina, giv-

ing the example of using software to determine the optimal dose of warfarin for a patient. “The information is now mobile, but the challenge is to have the technology use this information to help me make a good decision at the bedside,” Dr. Spi-

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na said. “I want to be able to confirm my clinical judgment with a device, the way another colleague would [confirm my judgment]. We should be able to find out about possible drug interactions [with the technology] at the bedside.” Dr. Spina cautioned that if smartphones are locked down because of privacy and security concerns, pharmacists are then unable to add apps to their devices that are relevant to their area of expertise. “If I need a special app because I work in HIV, I should be able to add that app to my device,” said Dr. Spina. “I should be able to tailor it.” Dr. Spina recommended that pharmacists use apps developed by larger, established companies or by established medical journals. “Anyone can develop an app,” he said. “I suggest that people use apps that have been developed by companies that have a good track record, so we can trust the information.”

Pharmacy Blogger’s Take

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John Poikonen, PharmD, the clinical informatics director at University of Massachusetts Memorial Healthcare, in Worcester and a frequent blogger on pharmacy-related technology trends (www.rxdoc.org), said restricting access to a proliferation of Internet content for health professionals to address security concerns is a challenge. “With cloud computing and programs like Dropbox [a Web-based file hosting service using cloud storage], it is a fine line for IT departments to maintain a balance of open access versus security,” Dr. Poikonen said. The movement of BYOD, or bring your own device, factors into this delicate balance. “There is virtualization, where you dial in on an external device, and there is a virtualized PC on the server side,” he said. “You are on the intranet of your facility, but it gives you flexibility of going anywhere else you want.” According to Dr. Poikonen, the FDA has published guidelines on decision support software and it disclosed that it intends to review the safety of health apps. “It is a complicated discussion whether regulation will stifle innovation or support safety,” he said. “The jury is out on that at the moment.” The FDA did take action when reports surfaced about a dosing application that produced inaccurate results. —Louise Gagnon

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American Health Packaging

Grifols

PharMEDium Services

CutisPharma, Inc.

ICU Medical, Inc.

Pharmacy Practice News

Medi-Dose, Inc./EPS, Inc.

The profiles in this section were submitted by the advertisers.

American Health Packaging Prepackaged Unit Dose Provides Many Benefits for Health Systems

AT A GLANCE Address American Health Packaging 2550-A John Glenn Ave. Columbus, OH 43217 Phone: (800) 707-4621 Fax: ( 614) 492-0448 Web site: www.americanhealthpackaging.com

Products Bar-coded unit dose generics, unit-of-use bottles, bar-coded pouches, compliance prompting packaging

Vice President/ General Manager Rick Knight

Vice President, Sales and Marketing Brian McMillan

Patient safety is a critical issue for health systems. As a result, many health systems seek bar-coded product to dispense to patients. Bar-coded products used in conjunction with bar code medication administration (BCMA) systems, automate the “five rights.” American Health Packaging supports this health systems’ priority with its growing line of prepackaged unit-dose products. There are many benefits to American Health Packaging prepackaged unit-dose products: Safety. Companies that specialize in pharmaceutical packaging are highly regulated and scrutinized by the FDA. Good Manufacturing Practices (cGMP) compliance ensures that products are packaged in a regulated and safe environment. Packaging professionals are adept at ensuring the product’s lot number, National Drug Code and expiration date are recorded correctly and legibly. Pharmacy efficiency. Pharmacies are concerned with the timely processing of orders to supply the proper medications to patients quickly as possible. Adding a multitude of steps to package and check commercially available products in-house not only slows down this process, it also takes those clinicians away from their core competency—patient care. Liability management. Packaging products within health system pharmacies can be met with various distractions in terms of quality systems and process controls. Errors that arise can place the liability on the hospital, as well as the caregivers themselves. Mitigation of risk is key. Purchasing medications from a highly regulated, cGMP compliant company such as AHP shifts some of the burden of responsibility from the health system. Cost savings. In addition to shifting the potential costs of errors, health systems that choose to package on-site must consider other direct costs such as establishing the Find Us at the

packaging infrastructure as well as paying the highly trained professional staff to perform, manage and support non-core work.

Safety in Every Dose Bar-coded to the dose level, our unit dose line has grown substantially in the last couple of years. The line now contains over 350 SKUs. And, nearly a third are industry exclusives— only available from American Health Packaging in a unit dose bar coded package format. American Health Packaging’s products support many therapeutic classes. Recent product Our bar-coded unit dose products support introductions include health systems’ patient safety efforts. Atorvastatin Calcium tablets, Clopidogrel tablets, Quetiapine Fumarate tablets, Olanzapine and Ziprasidone HCl tablets.

About American Health Packaging American Health Packaging is a subsidiary of AmerisourceBergen. Our manufacturing facility is registered with the FDA and fully adheres to current cGMP. Industry veterans with nearly 100 years of collective experience lead the quality and manufacturing departments. American Health Packaging is licensed by the Drug Enforcement Administration to package Schedule II to V controlled substances.

Intersection of Patient Safety and Pharmacy Efficiency! Many of our UD products are industry exclusives—only available from AHP.

Corporate Profile 2012

Special Advertising Section Pharmacy Practice News

CutisPharma, Inc. CutisPharma, Inc., brings innovation and value to the prescription-compounding sector of hospital and healthsystem pharmacies. Unit-of-Use kits simplify the entire process—they quicken preparation, enhance patient safety, and facilitate reimbursements. What typically takes compounders up to fifteen minutes to do now takes just one minute or less. All kits are bar-coded and facilitate pharmacists’ conformance to USP Chapter <795> standards.

wash BLM 4 oz and FIRST® - Mouthwash BLM 6 oz compounding kits. These products expand the FIRST® Magic Mouthwash line for CutisPharma. The product line already includes FIRST® - MouthAddress wash BLM 8 oz, Duke’s Mouthwash, Mary’s Mouth68 Cummings Park wash and BXN Mouthwash. The active ingredients Woburn, MA 01801 in FIRST® - Mouthwash BLM are comparable to Contact: Jim Nagle, Vice those found in the most routinely prepared formuPresident–Business Development lation of Magic Mouthwash containing Benadryl®, Phone: (781) 935-8141 ext. 120 lidocaine and Maalox®. The kits are made for one E-mail: JNagle@cutispharma.com patient and include pre-weighed Web site: www.cutispharma.com powders and a pre-measured sus® pension. With FIRST - Mouthwash Products Kits, the pharmacist needs only to add the powders to the liquid susFIRST® - Omeprazole Suspension 3, 5, 10 oz sizes pension, shake, and then dispense FIRST® - Lansoprazole Suspension to the patient. 3, 5, 10 oz sizes “Pharmacies have told CutisFIRST® - Mouthwash BLM 4, 6, Pharma, and our research has 8 oz sizes indicated that there are just as ® The FIRST® Magic Mouthwash line FIRST - BXN Mouthwash many 4 oz and 6 oz prescriptions ® contains FIRST® _ Mouthwash BLM 4, FIRST - Dukes Mouthwash for ‘Magic Mouthwash’ containing 6 and 8 oz sizes, BXN, Duke’s and ® FIRST - Mary’s Mouthwash ® ® Benadryl , lidocaine and Maalox Mary’s versions. FIRST® 10% Hydrocortisone in as there are for 8 oz prescriptions. Ultrasound Gel Compounding Kit By launching FIRST® - Mouthwash BLM 4 oz and 6 oz, pharmacists now have greater flexibility in filling FIRST® ‘Magic Mouthwash’ prescriptions,” said Dr. Muni. “The Company now has a wide range of FIRST® ‘Magic Mouthwash’ formulations to choose from, particularly for the most commonly prescribed and used.” FIRST® products save dispensing time, and can be compounded by the pharmacist while the patient Now available: FIRST® – Omeprazole waits, increasing customer satisfaction. Using FIRST® and FIRST® – Lansoprazole Suspension Unit-of-Use CompoundMouthwash kits, the pharmacist can compound a ing Kits in 3, 5 and 10 oz sizes. prescription faster than those prepared in the conventional way.

Greater efficiencies in the compounding process bring multiple financial and clinical gains to hospital and health-system pharmacies. By using premeasured, pre-weighed unit-of-use prescription compounding kits, pharmacies and nurses save significant staff time in preparation, help lower the total costs of compounding, facilitate reimbursements, and refine their just-in-time inventories to ensure ingredients are on hand when needed and ready to use over longer periods of shelf life. Clinically, the packaged reagents help deliver consistent accuracy of the compound admixtures and quicken medication delivery to patients, if compounded according to instructions, because they’re easier and quicker to use than the typical laborious processes. These benefits in turn may lead to better patient health outcomes. Industry-wide savings can be vast. FDA estimates 30 million hospital-outpatient and retail compounding prescriptions are filled per year. Inpatient figures are also significant, yet harder to pinpoint because they lack a single NDC number, says Jim Nagle, Vice President-Business Development, CutisPharma, Woburn, MA. Every FIRST® Unit-of-Use kit end-use container has a bar code. The NDC number imprinted on each end-use container in every CutisPharma FIRST® Unit-ofUse kit facilitates third-party reimbursement for hospitals and health systems. The single NDC number for the entire kit may also improve patient safety, because of minimized dispensing errors, suiting the growing number of inpatient and outpatient pharmacies that barcode prescriptions from point of dispensing to point of care.

CutisPharma Expands Product Line with new Oral Suspension Prescription Compounding Kits CutisPharma, Inc., introduced in January 2012, FIRST® - Omeprazole and FIRST® - Lansoprazole Unit-of-Use oral suspension compounding kits. These new kits will help pharmacists dispense these compounded prescriptions containing widely used proton pump inhibitors (PPIs). Traditionally, compounded omeprazole and lansoprazole oral suspensions can take up to several hours to prepare and are quite unpleasant to the taste. With FIRST® - Omeprazole and FIRST® - Lansoprazole, pharmacists need only add the liquid suspension to the powder, shake, and then within minutes can dispense to the patient with improved flavoring. “We invested a lot of time to develop these new suspension kits. The results are a pleasant-tasting strawberry-flavored medication with adequate stability once compounded,” said Dr. Indu Muni, founder, chairman, and CEO of CutisPharma, Inc. “These products offer another advantage for hospital use; since the suspensions are made using powders, and not pellets, our new compounded suspensions should flow more easily through nasogastric (NG) tubes, with minimal clogging compared to current practice. Also, our three different sizes of packaging, 3 oz, 5 oz and 10 oz, provide considerable prescribing flexibility.”

AT A GLANCE

10% Hydrocortisone in Ultrasound Gel Compounding Kit Primarily prescribed for physical therapy patients, the FIRST® 10% Hydrocortisone in Ultrasound Gel Compounding Kit made for a single patient, contains 6 grams of micronized hydrocortisone USP in a 24-gram suspension with propylene glycol USP and simethicone USP. It also includes 36 grams of ultrasound gel for topical use. The kit has a two-year shelf life prior to compounding. There are approximately 350,000 10% Hydrocortisone in Ultrasound Gel prescriptions written annually. CutisPharma cost comparison shows that FIRST® 10% Hydrocortisone unit-of-use kit can yield a profit of over $9 for a compounding pharmacy vs. a loss of over $16 when the admixture is compounded conventionally. Also, preparation time is cut to two minutes from well over fifteen minutes.

Growing Portfolio Serves Compounding Needs The CutisPharma portfolio is growing to meet pharmacy’s increasing reliance on compounding—and its need for efficiencies, safety and convenience. CutisPharma now has twenty proprietary prescription compounding kits on the market: five progesterone suppository compounding kits, two testosterone kits, one hydrocortisone kit, six Magic Mouthwash kits, three omeprazole suspension kits and three lansoprazole suspension kits. Several more compounding kits are in the planning stages. The use of FIRST® Unit-of-Use Prescription Compounding Kits facilitates compliance with United States Pharmacopeia (USP) Chapter <795>.

CutisPharma Launches New Prescription Mouthwash Kits, Expanding Product Line CutisPharma, Inc., announced the introduction of FIRST® - Mouth-

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Corporate Profile 2012

Grifols AT A GLANCE Address 2410 Lillyvale Ave. Los Angeles, CA 90032 Phone: (888) GRIFOLS (474-3657) Web site: www.grifols.com

Divisions Bioscience: Specializes in the research, development, production and commercialization of high-quality plasma therapies. Hospital: Specializes in operational solutions for compounding areas in pharmacy. Diagnostic: Specializes in diagnostic instrumentation, reagents, software and related products for the clinical laboratory.

Grifols is a global healthcare company headquartered in Barcelona, Spain. The company produces and markets plasmaderived medicines as well as hospital pharmacy products, compounded IV solutions, and in vitro diagnostic products for clinical laboratories. Grifols employs more than 8,000 people in the U.S. and 11,200 people worldwide, and its products are sold in more than 90 countries. A Legacy of Innovation At Grifols, a history of innovation defines our modern-day approach to medicine. More than 70 years ago, a Spanish hematologist named Dr. Jose Antonio Grifols Roig pursued a line of research

Products Albumin (Human), marketed as Albutein® 5%, Albutein® 25% and Plasbumin® _ 5 and Plasbumin® _ 25 Alpha1-Proteinase Inhibitor (Human), marketed as Prolastin®-C Antihemophilic Factor/von Willebrand Factor Complex (Human), marketed as Alphanate® Antithrombin III (Human), marketed as Thrombate III ® Coagulation Factor IX (Human), marketed as AlphaNine® SD

Edwin J. Cohn & Jose Antonio Grifols at the 4th International Congress of Blood Transfusion, Lisbon 1951.

Factor IX Complex, marketed as Profilnine® SD Hyperimmune Globulin Therapy Products, marketed as Hypermunes™: • Rabies Immune Globulin (Human) marketed as HyperRAB® S/D

that would set the stage for contemporary use of human plasma to treat disease. Together with his sons, he founded Laboratorios Grifols in 1940. Among their pioneering achievements, they

obtained a patent in Spain for the process of plasma lyophilization, or freeze-drying of human plasma, along with the devices needed to inject plasma into patients who required its therapeutic properties. Shortly thereafter, in 1951, Dr. Jose Antonio Grifols Lucas published the first large-scale clinical data describing the plasmapheresis technique of extracting plasma from donors while returning their red blood cells. Combined with the work of Edwin Cohn, Grifols paved the way for the birth of the plasma fractionation industry as we know it today.

Expanding to Meet the Demand From these auspicious beginnings, Grifols has evolved into an industry leader in the collection, manufacture and marketing of plasma-derived therapies. Through recent acquisitions, Grifols is now the third largest global producer of plasma-derived medicines. Grifols operates the world’s largest plasma collection platform, with 150 source plasma donation centers across the U.S. Grifols currently has the world’s highest plasma protein fractionation capacity of more than 8 million liters of plasma per year. To accommodate the growing global demand for plasmaderived medicines, Grifols is significantly expanding its three manufacturing sites in Clayton, NC, Los Angeles, CA, and Barcelona, Spain – the company’s global headquarters. The expansions include a new, 185,000-square-foot fractionation facility in Clayton and a new facility in Los Angeles dedicated to the production of immune globulin therapies. The new manufacturing facilities will increase the company’s capacity to fractionate plasma to 12 million liters by 2015. In addition, this year, Grifols opened a new, state-of-the-art plasma testing laboratory in San Marcos, TX, where every plasma donation undergoes rigorous scientific analysis prior to being approved for use in manufacturing. The 72,000-square-foot-facility houses the latest technology for conducting sophisticated viral testing, including transcription mediated amplification to rapidly detect minute levels of viral material within plasma samples. The San Marcos laboratory, together with an existing plasma testing laboratory in Austin, will analyze millions of plasma samples annually. Grifols is firmly committed to giving patients and healthcare providers broad access to our products. As Grifols grows, it continues to pursue its mission of improving the health and well-being of people around the world.

• Tetanus Immune Globulin (Human) marketed as HyperTET® S/D • Rho (D) Immune Globulin (Human) marketed as HyperRHO® S/D • Hepatitis B Immune Globulin (Human) marketed as HyperHEP B® S/D Immune Globulin Intravenous (Human) or IVIG Immune Globulin Injection (Human) Gri-fill® System 3.0 for compounding sterile preparations Misterium®: modular clean room solution Grifols-SencorpWhite inventory management system solutions Phocus® Rx: remote pharmacist validation system for compounding IV preparations Grifols Triturus® Fully Automated EIA Analyzer Interlab G26 Clinical Agarose Gel Electrophoresis Systems

Flebogamma® DIF manufacturing plant in Barcelona, Spain, designed by Grifols Engineering.

Diesse Ves-Matic ESR (Sed Rate) Systems A full line of Diagnostic Reagents and Complete Solutions for the Clinical Laboratory

CO23-0612

Corporate Profile 2012

Special Advertising Section Pharmacy Practice News

ICU Medical, Inc. ICU Medical connects patients and caregivers through safe, life-saving, life-enhancing medical devices, providing clinicians around the world with innovative and cost-effective patient care solutions for unmet clinical needs. Since the 1970s, the unsafe handling of hazardous drugs used to treat many forms of cancer has been recognized as a significant health hazard to healthcare workers, including oncology pharmacists. In response to these well-documented risks, ICU Medical has developed the ChemoClaveTM system, the world’s only needlefree closed system transfer device (CSTD) for the safe handling of hazardous drugs. The ChemoClave System ICU Medical’s ChemoClave system is designed to keep clinicians safe from dangerous exposure to hazardous drugs and features a variety of needlefree vial access devices, bag spikes, as well as primary and administration sets that can be configured to meet individual clinical needs. These devices work together to create and maintain

tem with automatic self-sealing technology that requires no cumbersome component assembly. This intuitive system meets NIOSH and ASHP guidelines, and can help ensure safe handling compliance throughout the entire hazardous drug handling process.

Less Waste, Lower Cost

AT A GLANCE Address ICU Medical, Inc. 951 Calle Amanecer San Clemente, CA 92673 Phone: (866) 829-9025 Fax: (949) 366-2183 Web site: www.icumed.com

As economic pressures increase for healthcare facilities, the need to drive clinical and economic efficiencies is more critical than ever. The ChemoClave system can help facilities sigChairman of the Board, nificantly reduce biohazardous waste and lower President and Chief their implementation costs compared to other Executive Officer commercially available CSTDs. Reducing biohazardous waste helps lower the chance of George A. Lopez, MD environmental exposure to hazardous drugs and decreases hazardous waste removal costs. A recent study looked at the costs associated with implementing various CSTD systems throughout the clinical delivery continuum, including the preparation, transportation, administration, and disposal of hazardous drugs. Real cost savings was estimated to be as much as $307,000 a year with the ChemoClave System for a single high-volume cancer facility as compared to other CSTD systems. Another study that analyzed costs of available CSTDs estimated that using the ChemoClave System could save a facility between $57.50 and $112.50 for every 100 chemotherapy bags administered.

Commitment to the Safety of Oncology Pharmacists Treating cancer patients takes compassion. It shouldn’t take your life. With limited federal regulation for devices that reduce exposure to hazardous drugs, ICU Medical has taken responsibility to increase clinical awareness of the dangers of exposure to these chemicals and improve safety throughout the oncology drug handling process. ICU Medical is committed to providing easy-to-use needlefree solutions that generate less biohazardous waste and lower costs, while helping keep clinicians and patients safe. Only ICU Medical gives you a simple, safe and secure needlefree closed system transfer device to help enhance healthcare worker safety and comply with OSHA, NIOSH, ASHP, ISOPP, ONS, APHON and USP <797>. For more information on how to keep you and your patients safe, visit us at www.icumed.com or call 1-866-829-9025. a mechanically and microbiologically closed system throughout the preparation, transportation, administration, and disposal of hazardous drugs. At no point in the process are clinicians, patients, or the environment exposed to hazardous chemicals.

Needlefree ICU Medical is committed to helping facilities adhere to needlefree policies. The needlefree ChemoClave system eliminates the risk of hazardous needlestick injuries during the oncology drug safe handling process. ChemoClave system features a passive, self-sealing technology that automatically returns each device to the closed position when disconnected, whether intentionally or by accident. As a closed system, ChemoClave features permanently bonded connections that eliminate add-on components and the potential for unsafe disconnect points.

Easy to Use Because ChemoClave is so easy to use, it reduces opportunities for misuse or malfunction while increasing compliance with safe handling best practices. ICU Medical developed the ChemoClave sys-

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Corporate Profile 2012

Medi-Dose, Inc./EPS, Inc. AT A GLANCE

Pioneers of unit-dose packaging, The Medi-Dose® Group constantly responds to pharmacy needs with innovative solid and liquid, oral unit-dose packaging products and a wide range of flexible, cost-effective IV, filtration, pharmacy and nursing accessories.

EPS, Inc.: A Focus on IV Medications

EPS® (Extemporaneous Packaging Systems), Inc., a companion company to Medi-Dose, Inc., was founded in 1977. Today, EPS manufactures and markets liquid unit-dose packaging supplies and IV addiAddress tive disposables for the preparation and dispensing of IV medications. 70 Industrial Drive Other EPS products include male/female Luer-lock closures, injection Ivyland, PA 18974 ports, trays and totes, tapes and labels, UV inhibitant bags and resealPhone: (800) 523-8966 able bags, IV software and high-alert medication identification bands. Fax: (800) 323-8966 Like Medi-Dose, the EPS TampAlerT® system for liquids offers E-mail: info@medi-dose.com The Medi-Dose Group has always had deep tamper evidence. “The premier advantage of TampAlerT is its Web site: www.medi-dose.com roots—family roots. Medi-Dose began as a small tamper-evident seal,” Robert Braverman said. “Ten minutes after family business in 1971, when Milton Braverman, you dispense your liquid and screw Products a former pharmaceutical company territory manthe TampAlerT cap on the vial, the ager, formed his own company. He was acutely seal is in place. Heat tunnels and Medi-Dose® (Solid) and TampAlerT® (Liquid) Oral aware of the requirements of hospital pharmacy. accessory sealing equipment are not Unit-Dose Packaging His sons, Robert and Mark, continue the tradition necessary. TampAlerT is tamper evi® for The Medi-Dose Group. dence with a twist of the wrist!” Medi-Cup PLUS packaging for The Bravermans carved a niche for the comThe company’s IV accessories also extended beyond-use dating pany—initially with solid oral unit-dose packagare highly successful. “We see them ® MILT by Medi-Dose unit-dose and ing. Although the concept of unit dose is familiar as natural advancements of the inibar-coding software today, launching the idea was one of the biggest tial Medi-Dose system. In essence, LiquiDose® labeling, IV additive and Milt 3.0 software. problems the new company faced. “We were IV dispensing is a highly specialized filtration products one of the pioneers, the innovators promoting form of unit dose,” he added. “It’s the Nultraviolet® ultraviolet light inhibiunit dose in hospitals,” Robsame idea—preparing and admintant bags ert Braverman recalled. “Due istering predetermined amounts of Steri-Dropper sterile ophthalmic in part to Medi-Dose’s educamedication for one regular dose or dropper bottles tional efforts, pharmacists and application.” nurses accepted the validity of Although all of the products conHigh Alert and I.V. Line Tracing Labels unit dose.” tinue to meet with gratifying, wideMedi-Dose is constantly spread acceptance, both Medi-Dose Resealable bags, bottles and other responding to pharmacy packand EPS remain highly motivatpharmacy supplies and disposables aging needs. Providing stability, ed. “We’re always looking for new ultraviolet (UV) light inhibition, products and developing innovaPharmacists’ input has made Medi-Dose the ideal easy opening and tamper evitive, cost-effective ways to help manual, solid oral unit-dose packaging system. dence have always been parapharmacists, always with an eye mount concerns regarding prepackaging. Using toward reducing the potential for Medi-Dose, a pharmacist can medication error,” noted Mr. Braverpackage a medication and store man. “One of our newest products it for up to one year without loss meeting these criteria is our line of potency due to UV light transof IV and High Alert Line Tracing mission or moisture permeation. Labels which makes it easy to label Hospitals can install the Mediand trace IV lines for any medicaDose solid oral unit-dose system tion in any setting (hospital, home for about $700; this includes all or clinic). Pharmacy simply places the supplies for 5,000 doses of the entire label on an IV infusion medication, as well as software container. When the medication is EPS’s innovative Line Tracing Label with a unique three-part piggyback for complete medication and administered at the bedside, nursdesign provides safe and economical protection for IV lines. bar-coding identification. Total ing applies one line label to each solid and liquid oral systems can be set up for less than $1,000. end of the tubing. This facilitates easy line traces, improves accuracy and helps minimize IV line confusion.” He added that 10 preMILT® by Medi-Dose Software printed labels as well as customizable Line Tracing Labels (when With bar coding increasingly important to pharmacy practice, used with the MILT 3.0 software) are immediately available. Medi-Dose designed its widely used MILT® by Medi-Dose software “All our IV High Alert and Line Tracing Labels reduce the potential (Medi-Dose Information Labeling Technology, named for the comfor error, minimize liability exposure and save lives—all for an extremepany’s founder). “My father wanted bar coding on medication packagly affordable price,” Mr. Braverman said. ing early on, to minimize the potential for medication error,” Robert Mark D. Braverman, director of operations, is responsible for Braverman said. “So, we’ve been constantly improving our programs the company’s extensive computer network. He coordinates all to meet this vital pharmacy challenge and need.” purchasing activities, both domestic and international. Mark and MILT 3.0 by Medi-Dose not only has sophisticated one- and twoRobert are aggressively bringing an expanded line of economically dimensional bar-coding technology to include lot numbers, beyondpriced, generic alternatives to expensive brands of plastic products use dates and National Drug Codes (NDC) on one bar code; it also to the company’s customers. includes an upgradable NDC database, directly from the FDA. PharRobert Braverman noted, “We’ve come a long way from being macists can simply type or scan in the NDC number, and MILT by a small family business; we still have remained as attentive and Medi-Dose will supply the pertinent information. The pharmacist can responsive to pharmacy needs as we were more than 30 years ago. map this information to designated fields, reducing the risk for error. Now we have the ability and the products to respond to pharmaMILT by Medi-Dose also contains field-locking capability for extra cists’ needs all over the security; enhanced formatting for quick medication identification; world—and we do.” support for syringe, ampule and IV Line Tracing labeling; customized work flow and comprehensive logs and reports; as well as laser, inkjet and thermal printer capabilities.

Corporate Profile 2012

Special Advertising Section Pharmacy Practice News

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Special Advertising Section Pharmacy Practice News

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Corporate Profile 2012

Pharmacy Practice News AT A GLANCE Address 545 W. 45th Street, 8th Floor New York, NY 10036 Phone: (212) 957-5300 Fax: (212) 957-7230 Web sites: www.mcmahonmed.com www.pharmacypracticenews.com www.cmezone.com

Launched more than 30 years ago, Pharmacy Practice Newss has become the best-read newspaper in its field, according to a syndicated, independent readership survey by Kantar Media. According to the survey, Pharmacy Practice Newss achieved a No. 1 ranking in at least five major readership categories* among staff pharmacists, pharmacy directors and other key health-system personnel.

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combating cardiac drug poisonings.

Educational Reviews One of the core editorial features of Pharmacy Practice News is our monthly educational reviews. Written by authorities in a given treatment area, the reviews are comprehensive summaries of state-of-theart thinking on specific disease states and practice areas. Topics this year included hazardous drug handling, medication safety systems in the ICU, emerging therapies in the treatment of metastatic melanoma, and management of anemia in patients with chronic kidney disease. Many of these educational reviews are featured in Pharmacy Practice News Special Edition, our annual print compendium that mails in October.

Web Site Initiatives

Medical newsmagazines, custom medical publications, educational reviews, educational and instructional pocket guides, special editions.

Our Mission

Each month, all of our print articles are posted to pharmacyThe mission of Pharmacy Practice Newss is twopracticenews.com and can be shared via easy-to-access links to fold: to provide health-system pharmacists with Facebook, Twitter and other social and business networking sites. the information they need to provide high-quality Web-exclusive content, such as breaking news and expanded coverpatient care, and to help them age of stories that appear in the magazine, also demonstrate the value of that care are featured. Employees to colleagues and administrators. Our monthly opt-in e-newsletter, previewing 69 To achieve these goals, our edicover stories and other featured content, contors follow developments in both tinues to grow and is sent about a week before Publisher, CEO and research and hospital practice. the print issue mails. We also are continuing to pharmacypracticenews.com Managing Partner Most of our coverage comes from post podcast interviews with our advisory board Raymond E. McMahon attending meetings convened by members, who comment on articles and issues the major pharmacy groups, such as the American of interest to health-system pharmacists. President, Partner Society of Health-System Pharmacists. But we also Van Velle Parent Company attend smaller, more focused conferences to keep our readers abreast of specialty care. For example, Pharmacy Practice News’’ leading position in readership did not Pharmacy Practice News the magazine continues to step up its coverage occur in a vacuum: The magazine is part of the McMahon PublishPublication Director of the Hematology/Oncology Pharmacy Associaing family of specialty newspapers, many of which are the No. 1 read tion’s annual meeting. We also cover the annual publications in their fields. Anesthesiology News, General Surgery Dave Kaplan meeting of the Society of Critical Care Medicine News and Gastroenterology and Endoscopy News, for example, are (SCCM) and the UnSummit for Bedside Barcoding. perennial favorites. Additional titles launched within the past five Editorial Director years, such as Clinical Oncology News and Pain Medicine News, conDavid Bronstein Peer-to-Peer Content tinue their impressive growth in market share and readership. The magazine also welcomes contributions Senior Editor Supplements and Projects from readers in an effort to facilitate a peer-toSarah Tilyou peer exchange of best practices in health-system All of our publications include educational supplements such as Special pharmacy. Contributions can be in the form of Reports and Literature Reviews—custom-written monographs bound Production Manager Practice Pearls, such as the one submitted by inside the newspapers. These supplements, produced by the Special Marty Barbieri the AIDS Healthcare Foundation, on preventing Projects division of McMahon Publishing, can be based on symposium adverse drug events in patients with HIV/AIDS coverage, interviews with experts, recently published research and Art Director (p. 34). We also so forth, and often are CME/CE accredited. Other Frank Tagarello feature regular offerings from the company’s Special Projects division contributions from include wall charts and pocket guides—often based thought leaders in on our educational reviews—that serve as on-the-spot pharmacy, includinstructional tools for health care providers. ing Ernie Anderson Jr., MS, RPh, who Taken together, all of these educational initiatives authors the monthly “Leadership in underscore our company’s mission: to be a full-service Action” column (p. 31), and Bonnie publishing company for a full-service profession. Kirschenbaum, MS, FASHP, who pens the bimonthly “Reimbursement Mat* No. 1 ranking in: average ters” column (p. 33). issue readers, directors This year, we also continue to fea(Table 115); average page ture our special “Spotlight” sections exposures, directors (Table focusing on important clinical and 115); high readers, total operational areas of pharmacy prachealth-system pharmacy tice. Our latest Spotlight theme, on (Table 217); average page Medication Safety, appeared in the exposures, total healthApril 2012 issue and featured articles system pharmacy (Table on the ISMP’s new International Medi117); high readers, staff cation Safety Self-Assessment Tool (Table 216). 2010 Pharmacy for Oncology; ISMP’s “Year in Review” Readership Study, Kantar educational review on medication Media. safety; and the latest strategies for

Corporate Profile 2012

Special Advertising Section Pharmacy Practice News

Operations & Management 27

Pharmacy Practice News • August 2012

Patient Satisfaction

Tales of Success in Boosting HCAHPS Scores Baltimore—How much impact can pharmacists have on the survey scores for satisfaction that patients give to hospitals following discharge? A big one, according to some pharmacy directors, but mainly on survey questions that zero in on how well patients are taught about the uses and side effects of their medications. Interdisciplinary collaboration also is vital to improving scores, they say. But perhaps the most important way pharmacists can affect the results of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is by interacting with patients. “The more pharmacists talk to patients while they’re in inpatients, the more impact they can have on HCAHPS scores,” said Ernest R. Anderson Jr., MS, FASHP, system vice president of pharmacy at Steward Health Care, a 10-hospital health system in Massachusetts. Mr. Anderson listed three prime areas covered by the HCAHPS questionnaire where pharmacists can have a “dramatic impact on patient care and patients’ perception of that care: pain management, discharge information and medication information.” Ideally, “you would like to have a pharmacist see every patient at discharge, but that’s probably not possible,” he said, adding that the solution is to focus on patients with most complicated disease states and the ones most likely to be nonadherent to their medications. “The more work pharmacists can do on the back end with medication reconciliation and patient education, the more they’ll improve the care of patients and provide a greater satisfaction level for those patients,” he said. “The result will be a positive financial as well as quality impact by keeping people healthy and on their medications and out of the hospital.”

Cleveland Clinic: a Dual Focus On HCAHPS and HF Readmits At a time when hospitals nationwide are facing increasingly difficult financial challenges, HCAHPS scores—which can bolster or batter incentive payments under the Centers for Medicare & Medicaid Services’ Hospital Value-Based Purchasing program—have taken on crucial importance, and hospitals are searching for more ways to win a bigger share of patient “likes.” At Cleveland Clinic, the focus has been on improving both HCAHPS scores and reducing heart failure readmissions, said Scott Knoer, MS, PharmD, FASHP, chief pharmacy officer. Pharmacists have played a role in both, he said. “We have a system-wide initiative [dubbed “Ask 3, Teach 3”] that encourages patients to ask questions about

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Figure. Cleveland Clinic HCAHPS scores. HCAHPs, Hospital Consumer Assessment of Healthcare Providers and Systems.

‘We have a system-wide initiative that encourages patients to ask questions about the purpose and possible side effects of their medications.’ —Scott Knoer, MS, PharmD the purpose and possible side effects of their medications,” said Dr. Knoer, who presented the initiative during a session at the 2012 Summer Meeting of the American Society of Health-System Pharmacists. Pharmacists, nurses and physicians are trained to reinforce those descriptions for every new drug ordered, he noted. The program is designed to educate patients on two specific survey questions, centering on the number of times hospital staff described in understandable terms the reasons for taking a new drug as well as its potential side effects. Dr. Knoer said pharmacists and other providers have been trained to use the specific term “side effects” in describing a new drug. “If you tell a patient it might cause nausea, but don’t use the words side effects, they might not put two and two together” when filling out

the HCAHPS survey, he said. “Basically,” he said, “it’s ‘training for the test,’ but it’s also the right thing to do for patients.” Since the program’s launch in 2011, Cleveland Clinic’s medication-related HCAHPS scores have risen significantly, according to Dr. Knoer, from a baseline of between 50% and 60% to around 64% recently. Part of that increase, he noted, can be attributed to another part of the hospital’s initiative to boost patient satisfaction—the delivery of discharge medications to the patients’ bedside (sidebar). “This service has been extremely wellreceived,” Dr. Knoer said. “I first saw it in action when my father was hospitalized [at another facility], and we both benefitted from the added convenience. It’s just one less thing you have to worry about when you’re about to leave the hospital for home.” In addition, Cleveland Clinic makes

sure that every patient with a primary diagnosis of heart failure (HF) gets discharge medication counseling from a pharmacist. That represents a significant number of patients for a hospital system with an average census of around 1,050 and that specializes in heart disease. “We’re on a 140-acre campus, so getting pharmacists to patients’ bedsides can be a challenge,” he said. The solution is to use support staff to extend pharmacists’ efforts. Before discharge, a technician will go to patients’ rooms and do a literacy survey. Based on the assessment, pharmacists then tailor their approach, deciding just how broad and in-depth their educational efforts should be. Although readmission rates fluctuate from quarter to quarter, “HF readmissions decreased by 12% after the program’s launch,” Dr. Knoer said. “While I would love to claim it was all pharmacy, like everything else in the hospital it was multidisciplinary. At the same time pharmacists started educating patients, caseworkers got more involved in making sure patients had follow-up visits, and nurses were educating patients in other ways.”

University of Utah Targets Pain Management At the University of Utah Hospitals and Clinics, the first priority has been improving pain scores. Shantel Mullin, PharmD, BCPS, the manager of inpatient clinical services, said the emphasis has been on moving away from the 0-to-10 pain score scale “and focusing on questions that allow us to assess patients’ pain tolerability overall,” including how pain interferes with sleep, adequacy of pain control measures and the ability to carry out daily activities. Nurses have the primary role in evaluating pain with the new tool, she said, which is being piloted in four units, but pharmacy also has played a part in help-

•

see HCAHPS, page 30

Bedside Offers Another HCAHPS Scoring Opportunity

elivering medications to home-bound patients’ bedsides can be an effective way for pharmacy not only to ensure greater post-discharge adherence but also to raise the likelihood that patients will remember the encounter when it comes to marking their HCAHPS surveys. Cleveland Clinic, for example, launched a bedside medication delivery service for insured patients who choose that option. Pharmacy technicians use hand-held devices to swipe credit cards and capture co-pays, but they also carry iPads that can securely connect with centrally located pharmacists. Pharmacists thus are able to “video-educate” patients just prior to discharge, said Scott Knoer, MS, PharmD, FASHP, the Cleveland Clinic’s chief pharmacy officer. “So it’s convenient for the patient and also it helps to ensure compliance because we know the prescription got filled if the patient got it filled here,” he said. “It also helps keep revenue within our system. Why would I want that margin siphoned off when it can help us with our mission of taking care of patients here?” The University of Utah Hospitals and Clinics has a similar program. “If the patient has insurance and consents to bedside delivery, we absolutely do that,” said Shantel Mullin, PharmD, BCPS, clinical pharmacy manager. “We also provide a discharge summary that has all of the medications that they need to continue, which ones have changed and which ones they should stop using.” “Having someone bring the medications to the room,” she said, and having a pharmacist to talk to face-to-face “has been really positive over the last two to three years as we developed this first as a pilot and now as standard practice.” —B.B.

28 Operations & Management

Pharmacy Practice News • August 2012

Sterile Injectables

Tweaking Compounding Workflow Eases Drug Shortages Baltimore—Health-system pharmacists can reduce drug wastage and minimize the effects of shortages of sterile injectables by modifying their compounded sterile products workflow, experts told attendees of the 2012 American Society of Health-System Pharmacists’ Summer Meeting. “There are steps you can take to actively mitigate sterile drug shortages,” said Matthew Eberts, PharmD, MBA, the director of pharmacy at West Penn Allegheny Health System, in Pittsburgh, and president of the Pennsylvania Society of Health-System Pharmacists, who moderated a session on the topic. “If you eliminate compounding errors and create a just-in-time distribution process, you can reduce waste to almost zero, which is a tremendous help in coping with shortages.” Computerized prescriber order entry (CPOE) systems are central to ensuring that sterile products are used only when absolutely necessary, explained Terri Albarano, PharmD, MS, the manager of pharmacy operations at West Penn Allegheny Health System. “In case of shortages, we flag drugs in short supply through our CPOE system so that physicians are aware of the

‘If you’re not confident that you can produce a safe product, perhaps [in-house compounding is] not the best option.’ —Garrett Eggers, PharmD

problem and the specific criteria for use, and we provide them [with] suggested alternatives,” Dr. Albarano said. For example, she said that using this approach, they have reduced overuse of the warfarin reversal agent IV phytonadione, “limiting its use to only lifethreatening bleeds, conserving [their] supply of this lifesaving medication.” Modifying their pharmacy workflow management system for sterile products, West Penn Allegheny also has shifted to just-in-time product formulation—another crucial method of reducing waste, Dr. Albarano said. “Backordered on-hand medications are now prepared and delivered only once the nurse has called down to the pharmacy and confirmed the drug is still required,” she explained. “This minimizes wastage that occurs when, for example, an intravenous medication is admixed and delivered but then is left unused because the patient died or lost IV access between the time of order and the time of delivery.” Dr. Albarano said her team also has started bar coding products as a way of eliminating “wrong drug” errors. They now also provide automatic dose calculations. “This technology helps us avoid wasting our supply of backordered drugs because of dilution errors,” she said. Providing up-to-date lists of backordered drugs and sharing them in real time also has helped the West Penn team preserve precious stock, according to David Cecere, PharmD, MBA, the system director of the pharmaceutical supply chain at West Penn Allegheny. “Given our limited storage space, when a drug shortage does occur, it’s more of an immediate problem for us than it is with larger competitors, so we need to react and communicate quickly,” Dr. Cecere told Pharmacy Practice News. He leads weekly backorder meetings that include operations managers, clinical and pharmacy specialists, safety managers, pharmacy information systems specialists and administrators. At these meetings, he presents updated charts of backordered products that include information on the quantity on hand, historical monthly usage, the anticipated product release date and suggested alternatives. The chart also is emailed to medical and nursing staff weekly and made available online, where it is modified as shortages occur. “As a result of this process, one person’s burden has become our entire organization’s focus,” Dr. Cecere said.

Extending Shelf Life of Drugs Sterile drug shelf life also can be extended if sterility tests are properly

Cleveland Clinic pharmacists can compound high-risk sterile products in this United States Pharmacopeia regulation <797>–compliant clean room.

‘Backordered on-hand medications are now prepared and delivered only once the nurse has called down to the pharmacy and confirmed the drug is still required.’

—Terri Albarano, PharmD, MS

conducted, according to Garrett Eggers, PharmD, MS, a manager of sterile products at the Cleveland Clinic in Ohio. There are two testing methods: direct inoculation or membrane filtration. Although the former is simpler, it generates more wasted product, said Dr. Eggers. Conversely, membrane filtration is more complex but less of the end product is wasted. Dr. Eggers told Pharmacy Practice News that, as the shortage crisis has worn on, more pharmacies have been weighing the potential costs and benefits of in-house high-risk sterile compounding compared with outsourcing. “Compounding outsource vendors are not manufacturers and, therefore, are not held to the same Food and Drug Administration standards as manufacturers,” he noted. “So there are varying levels of product quality and it’s difficult to know whether—even if a product has been prepared under sterile conditions—it was contaminated at some point in the process.” As an alternative to outsourcing, in-house compounding of high-risk sterile compounds increases the likelihood a product will be sterile. However, there is still risk involved in this process even when it is completed

in the hospital pharmacy, Dr. Eggers said. “If you’re not confident that you can produce a safe product, perhaps it’s not the best option,” he cautioned. Stringent criteria laid out in the U.S. Pharmacopeia’s (USP) regulation <797> also may be prohibitive for some, he added. Compounders of high-risk products are required to purchase costly equipment and create a USP-compliant “clean room.” Training in specialized high-risk compounding and sterility testing is another potentially costly investment. “If you’re deciding whether in-sourcing is right for you, you need to consider not only the costs of facilities, major equipment and labor, but also the ongoing costs of materials like sterilization filters, testing supplies, raw materials, syringes and needles and the cost of managing waste generated by sterility tests,” Dr. Eggers cautioned. “You also need to consider that your return on investment may change dramatically in the event that the shortage environment changes.” —David Wild Drs. Eberts, Albarano, Cecere and Eggers reported no relevant financial conflicts of interest.

30 Operations & Management

Pharmacy Practice News • August 2012

Patient Satisfaction

HCAHPS continued from page 27

ing to design the comprehensive pain program and in evaluating patients’ pain medications at admission. “Our pharmacists do medication reconciliation for all newly admitted patients, and a big part of that is assessing how we can restart their home medication for pain. Do we need to look at somatic and neuropathic pain issues and address them from a multimodal approach?” she said. As for the impact of the pilot on

HCAHPS scores, “results are not available yet,” Dr. Mullin said. “But we do have early results from Press Ganey patient satisfaction surveys, which contain pain questions similar to those on the HCAHPS survey, and the results are very impressive.” She noted, for example, that in answer to the patient question, “How well was your pain controlled?” the university went from the bottom to the top quartile compared with other university hospitals in the past year. “Our customer service director told me that she has never seen improvements like this in the past

seven years [during which time] we have been below the national average on pain scores,” Dr. Mullin said. “So we’re excited about the whole integrated process of staff education and patient information, and we’re confident that these gains will translate to improved HCAHPS scores.”

A Rural Hospital’s Approach Even a small hospital with limited resources can move the HCAHPS needle into positive territory by collaborating with other departments. At Sheridan Memorial Hospital, in northern WyoA pharmacy technician at Cleveland Clinic delivers discharge medications at the bedside.

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ming, HCAHPS survey results are distributed quarterly. Then, said pharmacy manager Kirsi Ludwig, PharmD, “I get together with nursing and dietary to discuss what’s working and what’s not. Then we come up with a plan of attack.” After it became apparent that the hospital wasn’t faring well on the medication-related HCAHPS questions, Dr. Ludwig said pharmacy created a simple, trifold medication guide that nurses could use to strengthen patient education efforts at bedside. The guide listed the hospital’s top 30 medications, drawn from drug utilization review data in the pharmacy information system, with indications and side effects for each. The pamphlet is designed in an easy-to-read tabular format, and it is used regularly by nurses, she said. Furthermore, pharmacy and dietary got together to design a similar pamphlet listing drug, food and herbal interactions. It’s distributed as part of every incoming patient’s information packet. However, Dr. Ludwig said, “we felt that was not enough, and we needed something additional to clarify the message.” So now, as part of the discharge process, a clinical pharmacist also goes through the pamphlet, pointing out food and herbal interactions for every drug the patient is on. Still, Dr. Ludwig said she remains doubtful that the HCAHPS scores “truly reflect the quality of care that any hospital provides, but rather how well the institution has adapted its practices to get the desired result—that is, a high HCAHPS score.” She continued, “At our hospital HCAHPS review is just another tool to identify areas to concentrate our efforts on. But at the same time, we understand that our competitors use these scores to compare themselves to us, so we have to play the game. As long as the outcome of scripting or teaching to the test [also] will help improve patient care and educate our patients, we will continue trying to do our best to improve our scores.” —Bruce Buckley

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Operations & Management 31

Pharmacy Practice News • August 2012

Leadership in Action

Building a Sense of Internal Peace I

n our last segment, we begaan exploring the ideal approaches to resolving conflict, both personally and in our roles as leaders on the job, based on the work of Ken Sande in his 2004 book, “The Peace Maker.” Resolving conflict is about creating peace, whether it is peace between you and another person or within a department. Peace is one of those mindsets that everyone can sense in him or herself and in thosee around them. A sensing leader knows if there is a lack of peace by listening and watching the body language of others. Leaders then need to take the initiative to ask why. When there is a lack of peace, relationships are strained, trust is eroded and productivity is hindered. First and foremost, the leader must have an internal sense of peace about him or herself before peace can be effectively created in a department. When individuals know that they have done their best and are true to their own core ideals, then they can have inner peace. But the effort does not stop there. Obtaining inner peace also may require that one forgives others and forgives him or herself. Sometimes people are too hard on themselves and set unreasonable expectations. Then, when these expectations are not met, individuals tend to beat themselves up. This is very self-defeating and not purposeful. Achieving inner peace yields multiple benefits. Perhaps most notably, peace within allows each of us to have peace with others. Peace with others breeds unity, which is a necessary dynamic within any department. I like to think of it as unity in diversity. This means that there is a complementary unity achieved by each person bringing his or her unique skills to the table. In such a scenario, the leader can take advantage of the diversity of each person, recognizing each person’s unique skills, talents and abilities.

Trusting Through the Difficulties I’m sure we all have spoken with someone who has gone through a difficult situation only to hear the person say, “Things worked out for the best in the end.” I have found this to be true many times in my own life. When an individual is going through the difficulty, it’s not unusual for him or her to feel quite dejected. Still, it is incumbent on us to help resolve the situation. I learned a long time ago to “just do the next thing,” whatever that may be. In many cases, doing “the next thing” may be calling that person who is in some type of crisis, sending an email or writing a letter. If we have a positive attitude about difficulties and can look for

the potential long-term benefits—even if we don’t see them in the present situation—then we can seek the positive in the seemingly negative. This is especially helpful when the person you are helping has difficulties that are overwhelming and immobilizing. It’s good to have a comrade to turn to in times of such need; someone who can be confided in and from whom wisdom can be sought. In fact,

“Leadership in Action” is authored by Ernest R. Anderson Jr., MS, RPh, System Vice President of Pharmacy, Steward Health Care System, Boston, Mass. Mr. Anderson welcomes your input on leadership issues, at ernest.anderson@ steward.org.

Ernest R. Anderson Jr., MS, RPh

seeking that individual at the first signs of the difficult situation arising may be

•

see PEACE, page 32

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IMPORTANT SAFETY INFORMATION FOR INTRAMUSCUL CULAR AR USE ON ONLY. LY. Proge gesterone injection in sesame oil is contraindicated in patients with current or past history of thrombophlebitis, thrombo boemb emboli olicc diso disorde rders, rs, orr ce cerebral apoplexy; liver dysfunction or disease; known or suspected malignancy of breast or genita tall organs; undiagnose osed d vagi vaginal nal bleed bleeding ing;; missed m abortion; and known sensitivity to progesterone injection in sesame oil. Since progestero one metabolites are seecre creted ted mainl i ly by b the kidneys, progesterone should be administered with caution and careful monitoring in patients with renal insufficiency. The physician should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, cerebrovascular disorders, pulm monary embolism, and retinal thrombosis). Should any of these occur or be suspected, the drug should be discontinued immediately. Meedication should be discontinued pending examination if there is a sudden partial or complete loss of vision, or if there is a sudden onset of proptosis, diplopia or migraine. If examination reveals papilledema or retinal vascular lesions, medication should be withdrawn. Because progestational drugs may cause some degree of fluid retention, conditions which might be influenced by this co condition, such as epilepsy, migraine, asthma, cardiac, or renal dysfunction, require careful observation. Patients who have a history of psychi hicc depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree. There are possible risks wh which may be associated with the use of progestin treatment, including adverse effects on carbohydrate and lipid metabolism. A decrease in glucose gl tolerance has been observed in a small percentage of patients on estrogen-progestin combination treatment. For this reason, diabetic ic patients should be carefully observed while receiving such therapy. Progesterone at high doses is an antifertility drug and high doses woul uld d be expected to impair fertility until the cessation of treatment. A statistically significant association has been demonstrated between use of estrogen-progestin combination on drugs and pulmonary embolism and cerebral thrombosis and embolism. For this reason patients on progestin therapy should be carefullllyy observed. There is also evidence suggestive of an association with neuro-ocular lesions, e.g., retinal thrombosis and optic neuritis. Adverse events associated with use of Progesterone injection in sesame oil include breakthrough bleedi ding; ng; sp spott otting; change in menstrual flow; amenorrhea; edema; change in weight (increase or decrease); changes in cervical erosion and ce cervi rvical secretions; cholestatic jaundice; breast tenderness and galactorrhea; pain, irritation, and/or redness at the injection area; ski sk n sens ensitivity reactions consisting of urticaria, pruritus, edema and generalized rash; acne, alopecia and hirsutism; rash (allergic) with and d without w pruritus; anaphylactoid reactions; mental depression; pyrexia; insomnia; nausea; and somnolence. Because laboratory results may be altered by the use of estrogenprogestin combination drugs, pathologists should be advised of progestin therapy when spec pe imenss are submitted. One Luitpold Drive | PO Box 9001 | Shirley, NY 11967 | Phone 800-645-1706 | Fax 631-924-1731

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32 Operations & Management

Pharmacy Practice News • August 2012

Leadership in Action

PEACE continued from page 31

the best option, when possible. By taking these various steps—whether proactive or reactive—conflicts and crises can become an opportunity.

Am I the Problem? Here is a difficult question that leaders need to ask themselves when a conflict arises: Am I the problem? We are all quick to point out the faults in others. We may even think we can change the

other person. For those of us who have been married to someone for any significant amount of time, we have probably learned that we cannot easily change the other person. In reality, we only have control over ourselves. Often, as we change ourselves and the way we relate to others, the other person changes of his or her own will. It is one of those paradoxes of human relations. The more we try to change someone else, the more that person might resist; however, the more we change ourselves, the more we get positive responses from the other person.

PROGESTERONE INJECTION, USP IN SESAME OIL FOR INTRAMUSCULAR USE ONLY

Rx Only

DESCRIPTION Progesterone injection, USP, a progestin, is a sterile solution of progesterone in a suitable vegetable oil available for intramuscular use. INDICATIONS AND USAGE This drug is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer. CONTRAINDICATIONS 1. Current or past history of thrombophlebitis, thromboembolic disorders, or cerebral apoplexy. 2. Liver dysfunction or disease. 3. Known or suspected malignancy of breast or genital organs. 4. Undiagnosed vaginal bleeding. 5. Missed abortion. 6. Known sensitivity to progesterone injection, USP. WARNINGS The physician should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, cerebrovascular disorders, pulmonary embolism, and retinal thrombosis). Should any of these occur or be suspected, the drug should be discontinued immediately. Medication should be discontinued pending examination if there is a sudden partial or complete loss of vision, or if there is a sudden onset of proptosis, diplopia or migraine. If examination reveals papilledema or retinal vascular lesions, medication should be withdrawn. PRECAUTIONS General The pretreatment physical examination should include special reference to breast and pelvic organs, as well as a Papanicolaou smear. Because progestational drugs may cause some degree of fluid retention, conditions which might be influenced by this condition, such as epilepsy, migraine, asthma, cardiac, or renal dysfunction, require careful observation. In cases of breakthrough bleeding, as in all cases of irregular bleeding per vaginum, nonfunctional causes should be borne in mind, and adequate diagnostic measures undertaken. Patients who have a history of psychic depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree. The age of the patient constitutes no absolute limiting factor although treatment with progestin may mask the onset of the climacteric. The pathologist should be advised of progestin therapy when relevant specimens are submitted. There are possible risks which may be associated with the use of progestin treatment, including adverse effects on carbohydrate and lipid metabolism. The dosage used may be important in minimizing these adverse effects. A decrease in glucose tolerance has been observed in a small percentage of patients on estrogen-progestin combination treatment. The mechanism of this decrease is obscure. For this reason, diabetic patients should be carefully observed while receiving such therapy. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term intramuscular administration of Medroxyprogesterone acetate (MPA) has been shown to produce mammary tumors in beagle dogs. There is no evidence of a carcinogenic effect associated with the oral administration of MPA to rats and mice. Medroxyprogesterone acetate was not mutagenic in a battery of in vitroo or in vivoo genetic toxicity assays. Progesterone at high doses is an antifertility drug and high doses would be expected to impair fertility until the cessation of treatment. Geriatric Use: The safety and effectiveness in geriatric patients (over age 65) have not been established. Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Sometimes the change we need to make in our relationships and within ourselves requires an apology to someone whom we have offended. Giving an apology breaks down walls and begins the healing process between people. Often, if we apologize first, the other person will take responsibility for their actions as well and apologize for their contribution to the conflict. Conflict after all, always involves at least two people.

Defining the Issues Sande separates the conflict issues into

Hepatic Insufficiency: The safety and effectiveness in patients with hepatic insufficiency have not been established. Since progesterone is metabolized by the liver, use in patients with liver dysfunction or disease is contraindicated. Drug Interactions: The metabolism of progesterone by human liver microsomes was inhibited by ketoconazole (IC50 < 01 μM). Ketoconazole is a known inhibitor of cytochrome P450 3A4 and these data suggest that ketoconazole or other known inhibitors of this enzyme may increase the bioavailability of progesterone. The clinical relevance of the in vitroo findings is unknown. ADVERSE REACTIONS Breakthrough bleeding; spotting; change in menstrual flow; amenorrhea; edema; change in weight (increase or decrease); changes in cervical erosion and cervical secretions; cholestatic jaundice; breast tenderness and galactorrhea; pain, irritation, and/or redness at the injection area; skin sensitivity reactions consisting of urticaria, pruritus, edema and generalized rash; acne, alopecia and hirsutism; rash (allergic) with and without pruritus; anaphylactoid reactions; mental depression; pyrexia; insomnia; nausea; and somnolence. A statistically significant association has been demonstrated between use of estrogenprogestin combination drugs and pulmonary embolism and cerebral thrombosis and embolism. For this reason patients on progestin therapy should be carefully observed. There is also evidence suggestive of an association with neuro-ocular lesions, e.g., retinal thrombosis and optic neuritis. The following adverse reactions have been observed in patients receiving estrogen-progestin combination drugs: Rise in blood pressure in susceptible individual, premenstrual syndrome, changes in libido, changes in appetite, cystitis-like syndrome, headache, nervousness, fatigue, backache, hirsutism, loss of scalp hair, erythema multiforme, erythema nodosum, hemorrhagic eruption, itching, and dizziness. The following laboratory results may be altered by the use of estrogen-progestin combination drugs: increased sulfobromophthalein retention and other hepatic function tests; coagulation tests: increase in prothrombin factors VII, VIII, IX, and X; metyrapone test; pregnanediol determinations; thyroid function: increase in PBI, and butanol extractable protein bound iodine and decrease in T3 uptake values. DOSAGE AND ADMINISTRATION Progesterone injection, USP is administered by intramuscular injection. It differs from other commonly used steroids in that it is irritating at the place of injection. Amenorrhea: Five to 10 mg are given for six to eight consecutive days. If there has been sufficient ovarian activity to produce a proliferative endometrium, one can expect withdrawal bleeding forty-eight to seventy-two hours after the last injection. This may be followed by spontaneous normal cycles. Functional Uterine Bleeding: Five to 10 mg are given daily for six doses. Bleeding may be expected to cease within six days. When estrogen is given as well, the administration of progesterone is begun after two weeks of estrogen therapy. If menstrual flow begins during the course of injections of progesterone, they are discontinued. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. HOW SUPPLIED Progesterone Injection USP, 50 mg/mL is available in 10 mL multiple dose vials, individually boxed. Store at 20° C to 25° C (68° F to 77° F) [See USP Controlled Room Temperature]. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Do not use Progesterone Injection after the expiration date which is printed on the vial label.

Nursing Mothers: Detectable amounts of drug have been identified in the milk of mothers receiving progestational drugs. The effect of this on the nursing infant has not been determined. Special Populations: Renal Insufficiency: The safety and effectiveness in patients with renal insufficiency have not been established. Since progesterone metabolites are excreted mainly by the kidneys, progesterone should be administered with caution and careful monitoring in this patient population.

AR154 Iss. Date 6/2012

the two camps of material and personal. Material conflicts arise over property, money, rights and responsibilities. This could include the “right” of a manager to fire another on the job. Personal issues are more prevalent in the workplace on a day-to-day basis and include how we treat one another. We have all heard, and probably used the phrase, “throwing someone under the bus.” We have all been victims of this from time to time and understand how it feels, justified or unjustified. The first decision when this occurs is how to respond. If one responds in the attack mode, the conflict might escalate the conflict. If one runs away and avoids the other person, the conflict is left it to fester. Sometimes material issues and personal issues get all tangled up. The two first must be separated. Often the personal issues are surrounded by strong emotions that can cloud an appropriate response. The material components are the facts. As leaders, we are called on frequently to learn the facts and to come to an appropriate decision. This often may lead to confronting the issue directly. I recommend that the two parties try to work out the differences on their own. If that is unsuccessful, then the manager may need to step in. From a practical standpoint, having appropriate structure in an organization by which to make decisions is very helpful. Often conflicts arise on the job because an individual, or a group, disagrees with a particular decision. If there is a structure and process in place, then each person has the opportunity to express his or her “concerns” and should be encouraged to do so through that structure. Once the decision has been made through the appropriate structure, then the issue is holding people accountable. These can be difficult management situations that require difficult conversations. Sometimes personal offenses are best overlooked; they are not worth the conflict. I often overlook some of these minor issues based on my work with an individual, knowing that I can work on many issues in the overall mentoring of the individual. This requires that leaders not have an overly sensitive attitude and not be easily offended. When leaders exhibit an attitude of gentleness and compassion and subsume their own egos, they can develop and encourage colleagues. If one comes across aggressively, he or she might incite a similar aggressive response and will likely escalate the conflict. This may require that leaders take a deep breath and respond and not react. A response is thoughtful and calculated; a reaction is not. Next time we will look further at the origins of conflict and the process of resolution.

Operations & Management 33

Pharmacy Practice News • August 2012

Reimbursement Matters

Pathways and Decision Support O

ne of the things that facilities have discovered in their quest for computerized prescriber order entry (CPOE) and electronic health records is that it’s necessary to create a clinical pathway or decision support tree for each and every possible situation for which orders are being written. The goal is to guide the practitioner in making a decision that is in the best interest of the patient and at the same time meets safety and efficacy criteria established by the facility. That process—if done correctly—has some useful parallels when it comes to developing and maintaining an effective reimbursement strategy. Health systems rarely, if ever, adopt the clinical pathways or decision support trees established by other facilities; rather, they insist on creating their own. And even within a facility, there’s dissension among the practitioners as to whose practice habits or standards should be used. Despite all the grumbling and hand wringing, eventually a consensus is reached and CPOE moves forward. A mechanism for dealing with special circumstances usually is created so that an unusual situation can be resolved and patient care can proceed. In much the same way, the payers have created decision pathways that are designed to prevent unnecessary medical use. These programs are one of a number of efforts that payers are taking to help reduce unwarranted variations in the delivery of health care and to help manage rising health care costs. As such, they tend to focus on high-priority areas in the top tiers of paid services for their members. This is the case for both the Centers for Medicare & Medicaid Services (CMS) and for private payers. CMS uses the concept of Local Coverage Determinations (LCDs) and National Coverage Determinations (NCDs), whereas private payers require prior authorization for certain therapy services and pharmaceuticals. Each state creates its own rules for prior authorization within its Medicaid program. Some of these decisions apply just to inpatients, some just to outpatients and some to any practice setting. Although the goal of appropriate use and appropriate drug spending is the common theme, there is a very big difference between the actions that pharmacy needs to take if LCDs and NCDs apply and those that they need to take if prior authorization is required.

Prior Authorization Prior authorization means exactly that. Assuming that the facility or pharmacy intends to be paid for the medication or therapy, before they proceed with dispensing the medication, authorization for doing so must be granted by the payer.

Although this sounds like a simple concept, pharmacy must have taken several steps to ensure that this is not an insurmountable roadblock. Does the facility’s computer system support its needs? From a patient perspective, at a minimum, pharmacy needs to know who the payer is. Has this data been included in the admission criteria that the facility routinely receives? If not, what steps can be taken to resolve this?

Next comes the pharmacy drug master (or whatever one chooses to call the listing of drugs in the computer system) supporting both the inpatient and outpatient systems. Is it robust enough to support a mechanism that will identify whether or not third-party payers require prior authorization? Does it support a link to those payers so that their criteria are readily retrievable? Once the criteria for use have been

“Reimbursement Matters” is a tool for maintaining your health system’s fiscal health. Please email the author at bkirschen@aol.com with suggestions on reimbursement issues that you would like to see covered.

Bonnie Kirschenbaum, MS, FASHP

retrieved, the process of methodically determining whether or not the patient meets them and gathering the documentation required to support the use of the

•

see PATHWAYS, page 36

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34 Operations & Management

Pharmacy Practice News • August 2012

Practice Pearl ‘Good Results’ program:

Preventing Adverse Drug Events in Patients with HIV/AIDS ADE Other No problems

Sarah Butler O’Rourke, PharmD Staff Pharmacist AHF Pharmacy AIDS Healthcare Foundation Tampa Bay, Florida

Laura Middleton Fields PharmD Candidate University of Florida, College of Pharmacy St. Petersburg, Florida

IDS Healthcare Foundation (AHF) Pharmacy implemented the Good Results Program as a medication safety initiative to provide and document safe medication use and prevent adverse drug events (ADEs) in a complex HIV/ AIDS patient population with adherence issues, multiple chronic conditions, and complex medication regimens. The AHF Pharmacy-Tampa Bay is a specialty community pharmacy practice site attached to the AHF Tampa Bay Healthcare Center. In addition to pharmacists specialty-trained in the care of patients with HIV/AIDS, the Tampa site employs pharmacy interns and is an Advanced Pharmacy Practice Experience rotation site for third- and fourth-year pharmacy students. AHF’s American Academy of HIV Medicine–certified physician provides primary and specialty care for the clinic patients. The foundation’s patients are prescribed complex highly active antiretroviral therapy with multiple drug interactions, as well as medications for chronic medical conditions and adjunctive therapy. Patients frequently feel overwhelmed with the vast amount of new medical or prescription information given during an office visit, and some may not comprehend or remember what was communicated to them by the medical provider and the clinical pharmacist. It also is common that patients do not initiate communication with their health care providers because they feel they are intruding on time that could be used for a more difficult patient. Thus, AHF pharmacists play an especially important role in ensuring that patients understand the dosing, indication, and side effects associated with their antiretroviral regimens and other chronic medications. The Good Results Program began when the community-based clinical pharmacists identified 2 points as being

11%

64%

21% 4%

Figure 1. Medicationrelated issues identified during follow-up calls. ADE, adverse drug event

critical “new transitions of care”: when new medications were prescribed and when medications were changed. The program was designed to track initial and follow-up consultations for patients prescribed new medications or those with changes to their current regimens. During the initial consultation, patients are counseled regarding proper medication dosing and instructions, auxiliary warnings or directions (food), potential ADEs, how to prevent ADEs, and when to contact the medical provider. Pharmacists or pharmacy students provide follow-up telephone consultation to these patients to address their concerns and ensure safe and appropriate medication use. By contacting patients in the comfort of their homes, AHF is better able to reinforce important dosing information and address their questions or concerns about their medications. Because most patients do not visit their medical provider for 3 to 6 months after a new medication is prescribed, pharmacists play a crucial role by reinforcing the proper use, answering questions about the medication, and preventing ADEs related to the new medication. Data collection is completed by using the pharmacy computer system to print the “New Prescription” tracking report that identifies new prescriptions or dosage changes. Data are collected only for patients prescribed new medications for chronic conditions; short-term or one-time prescriptions are excluded. Relevant information—including patient name, date of

Number of ADEs

Potential ADE

Assistant Director of Clinical Services AHF Pharmacy AIDS Healthcare Foundation Tampa Bay, Florida

birth, medication, and date written— is entered on the Good Results Data Collection Form (a Microsoft Excel spreadsheet). Additionally, patient comments or reported ADEs are documented on the form. The data collection form automatically populates callback dates for 7 and 30 days after the initial date written. A pharmacist or a pharmacy student contacts patients within 7 to 14 days of the start date of the medication, and again at 30 days if indicated by comments and feedback entered on the data collection form (after the initial or follow-up contact). Potential or reported ADEs are documented and classified on the “Medication Therapy Intervention and Safety Documentation Program” form.¹ (This form, developed by Steven Chen, PharmD, an associate professor of clinical pharmacy at USC School of Pharmacy in Los Angeles, was shared with pharmacy teams participating in the Health Resource and Service Administration’s Patient Safety and Clinical Pharmacy Services Collaborative.) The AHF Pharmacy-Tampa Bay team collected data over a 6-month period. The team counseled 138 patients

12 10

regarding the safe and appropriate use of their medications. Of these patients, 29 (21%) experienced an ADE in one of the following categories: no harm because medication was ineffective, patient self-managed the ADE, the ADE was temporary and was modified by pharmacist intervention, and the ADE resulted in temporary harm (Figures 1 and 2). Additionally, 15 (11%) patients experienced a potential ADE categorized by dose and administration discrepancy, treatment not optimal based on current evidence/guidelines, medication underuse or misuse, concerns about an ADE, and perceived ineffectiveness of medication therapy (Figure 3). Other documented interventions and issues reported during the follow-up calls involved an additional 4% of patients. Most patients were highly responsive to the follow-up consultation regarding the safe and proper use of their medication. Pharmacist counseling rectified problems in the early stage of this “new” transition of care and treatment by correcting/clarifying dosing instructions, identifying medication under-

•

see GOOD RESULTS, page 37

No harm, medication ineffective Patient self-management Temporary, requiring intervention Event occurred, temporary harm

8 6 4 2 0

Types of ADEs

Figure 2. Types and occurrences of ADEs. ADE, adverse drug event

Number of ADEs

Cheryl Graziose, RPh

Dose discrepancy

5 4 3

Treatment not optimal Underuse or misuse ADE concerns Perceived ineffectiveness

2 1 0

Types of ADEs

Figure 3. Types and occurrences of potential ADEs. ADE, adverse drug event

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36 Operations & Management

Pharmacy Practice News • August 2012

Reimbursement Matters

PATHWAYS

What’s Your Strategy?

continued from page 33

medication can begin. Documentation on the prescriber’s part is key and the electronic health record must be flexible enough to support this. It might need to be determined whether it’s the documentation that’s missing or whether another step has to be taken to support the use of the chosen medication. There may not be a match between what the payer has established as appropriate use and what the prescriber has

are to weigh in on how your facility handles these issues? Post your comments at the end of this article, which will appear in mid-August at www.pharmacypracticenews.com.

ordered. Which of the two divergent paths will be taken? Support the prescriber’s decision and challenge the payer’s prior authorization criteria requesting an exception? Or, work with the prescriber to find an alternative treatment? In any case, if the prior authorization is granted, the facility knows that it will be paid for

the use of the medication or therapy and if it isn’t and the facility chooses to go ahead anyway, it is doing so knowing that there will be no payment.

LCDs and NCDs Set by CMS CMS also has adopted the concept of needing to meet clinical criteria to

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ensure payment. And like the other third-party payers, there is variability in the requirements for LCDs depending on who the Medicare Administrative Contractor (MAC) is for specific geography. The clinical criteria are readily available on each of the MAC Web sites and any changes to them are routinely and widely announced. Who receives this information in the facility and how is it disseminated? It’s easy to put oneself on the distribution list for e-correspondence from the MAC or from CMS if one prefers getting this information directly. Once again, it’s important to have established a mechanism for identifying which drugs are affected by LCDs and NCDs and for having established a link to determine the details. Because these change frequently, a link to the most current data is vastly superior to hard coding this into a computer system and then trying to keep it current. However, the action steps with LCDs and NCDs differ from those with prior authorization. CMS has put the responsibility for understanding the requirements of the LCD or NCD and meeting them with thorough documentation before ordering the drug or therapy squarely on the shoulders of the prescriber and the health care team. Once the request for payment has been submitted to CMS, the MAC determines whether or not the patient met the requirements. If so, payment is granted; if not, it’s denied. But the medication already has been given and short of an appeal, there’s little that can be done at this point. Bad surprise if the drug is preposterously expensive and the facility is left holding the bag. Naivete is not an acceptable excuse. If the drug is carried at the facility, it is pharmacy’s responsibility to understand the payment mechanism set by CMS and to shepherd this in the facility. Because pharmacy is purchasing the product, it behooves the department to ensure that its actions or lack of them aren’t contributing to loss of payment. Recognizing the frustration in dealing with multiple policies from multiple payers, at their recent annual meeting, the American Society of Health-System Pharmacists House of Delegates approved the following language: Payment Authorization and Verification Processes. To advocate that public and private payers work together and in collaboration with providers to create standardized and efficient strategies for payment authorization and verification processes, such as local and national coverage determinations, that facilitate communication between patients, providers, and payers prior to therapy; result in timely coverage decisions; and do not disrupt patient care. Pharmacy might say, “Not my problem” and leave it up to someone else in the facility to handle. I hope not!

Clinical 37

Pharmacy Practice News • August 2012

Toxicology

POISONING

always clear to the patients or even to the initial treating physician that they have amatoxin mushroom poisoning. Symptoms Scan for more don’t develop until information on a minimum of six the Legalon SIL Mushroom hours or more post-ingestion.” As Poisoning Clinical Study. a result, Dr. Mitchell noted that “in many cases, patients have made a second meal of the mush-

continued from page 1

and in the two more severe cases, nasobiliary drainage via endoscopic retrograde cholangiopancreatography. No patient progressed to fulminant hepatic failure. “What we experienced in caring for these four patients is that clinicians will need to promptly recognize if their patient has ingested toxic mushrooms and to initiate care immediately, which includes aggressive IV hydration, and potentially the study drug, IV silibinin,” said lead author Maiyen Tran Hawkins, DO, a gastroenterology fellow in the Division of Gastroenterology and Hepatology at Medstar Georgetown University Hospital.

Not Approved in U.S., But Access Still Possible Silibinin is not approved in the United States, although it is used in Europe

‘We’re … very close to the point of approaching the FDA for full orphan drug The Amanita genus of mushrooms (above) is among the most poisonous and psychoactive fungi known. Silibinin, an extract of milk thistle (right), has been shown to be an effective antidote.

The silibinin protocol ‘is the best available

approval.’ —Todd Mitchell, MD, MPH

an emergent basis and it takes a skilled person to

biliary drainage is added only after a large ingestion of amatoxin-containing mushrooms or in situations where silibinin is unavailable.

facilitate the biliary drainage.’

‘The Best Available Approach’

approach... [but] it is not available universally on

—Edward P. Krenzelok, PharmD for poisoning due to amatoxin, the deadly toxin found in Amanita and certain other mushroom genera, and it is being studied in a prospective U.S. trial. The Prevention and Treatment of Amatoxin Induced Hepatic Failure With Intravenous Silibinin (Legalon® SIL): An Open Multicenter Clinical Trial (NCT00915681) is “the first prospective clinical trial ever conducted with regard to amatoxin poisoning,” according to principal investiagor Todd Mitchell, MD, MPH, from Dominican Hospital, in Santa Cruz, Calif. Begun in 2009, the trial has now treated more than 40 patients. “An

GOOD RESULTS continued from page 34

use or misuse, and educating patients regarding the effectiveness of therapy. Many patient concerns were alleviated regarding optimal treatment for their conditions, and potential ADEs were prevented with pharmacist intervention. The patients who did not have any issues to report were appreciative of the additional attention and relationship with their pharmacist that the program fostered. Pharmacist involvement in the safe and proper use of medication is impor-

open-label clinical trial like ours follows a time-honored model used by the FDA to approve new antidotes for the most deadly of poisons,” Dr. Mitchell told Pharmacy Practice News. He added, “We’re … very close to the point of approaching the FDA for full orphan drug approval.” Dr. Mitchell added a few details regarding the protocol that his team has developed and that was used in Dr. Hawkin’s patients to treat amatoxin poisoning. The aggressive hydration, he noted, is included to prevent renal failure; the IV silibinin blocks reentry of amatoxin into hepatocytes; and the

Edward P. Krenzelok, PharmD, FAACT, DABAT, the director of the Pittsburgh Poison Center & Drug Information Center at the University of Pittsburgh Medical Center, who was not associated with the case series, commented that the series is valuable because it underscores the efficacy of the treatment strategy. As pioneered by Dr. Mitchell, he said, it is “the best available approach.” The limitation “is that silibinin is not available universally on an emergent basis and it takes a skilled person to facilitate the biliary drainage.” Dr. Mitchell acknowledged that amatoxin poisoning is uncommon in the United States. However, “when it occurs, it’s deadly,” he said. Moreover, “It’s not

tant because “an estimated one-third to one-half of all patients in the United States do not take their medications as prescribed.”² The AHF Good Results Program provides a format to document pharmacist counseling and follow-up communication when new medications are initiated or therapy changes. Additionally, AHF interventions allowed patients to voice other concerns about their health and helped foster important pharmacist–patient relationships. This program supports AHF’s safe medication use initiative and provides another tool to improve medication adherence in a complex disease state population.

rooms before becoming symptomatic with severe vomiting and ‘cholera-like’ diarrhea. Many patients are initially discharged from the ER emergency room] with a diagnosis of garden-variety gastroenteritis.” Once clinicians have diagnosed mushroom toxicity, said Dr. Hawkins, “they should immediately contact poison control, who should get them in contact with Todd Mitchell to be able to obtain the IV silibinin.” Other therapies, said Dr. Krenzelok, such as highdose penicillin and multiple-dose activated charcoal, are “rarely successful.” He added, “Liver transplants are used if a donor liver is available.” —George Ochoa Drs. Hawkins and Krenzelok reported no relevant financial conflicts of interest. Dr. Mitchell reported that he is a consultant for Rottapharm-Madaus. Clinicians in need of IV silibinin can contact Dr. Mitchell via email: tmitchmd@yahoo.com.

References 1. Chen S. Medication Therapy Intervention and Safety Documentation Form. http://www. acumentra.org/downloads/medicare/ADE/ USC-ADE-pADE-tool-manual-4-6-2012.pdf. Accessed July 17, 2012. 2.

Wettergreen S. Pharmacy Times. October 10, 2011. http://www.pharmacytimes.com/ news/A-Script-for-Change-Improving-Medication-Adherence/. Accessed July 17, 2012.

Presented as a poster (29-T) at the 2012 ASHP Summer Meeting.

Hem/Onc Pharmacy

Pharmacy Practice News • August 2012

In Focus

Alpha-emitting Nuclide Targets Bone Metastases Treatment is fast-tracked by FDA for difficult-to-treat metastatic prostate cancer San Francisco–Clinical oncologists soon may have a new treatment for patients with metastatic castrationresistant prostate cancer (CRPC), based on results of a randomized, Phase III multinational study. The novel radiation-emitting agent, radium-223 chloride (Ra-223; Alpharadin, Algeta), targets bone metastases

with high-energy α-particles. In interim results presented at the 2012 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium and updated results presented at the 2012 ASCO annual meeting, Ra-223 improved survival and delayed cancer-related bone problems in men with CRPC. The study agent is the first α-particle–

emitting drug that been shown to improve survival in metastatic CRPC. In August 2011, the FDA granted the agent Fast Track review status; in June, following updated results presented at ASCO, the company announced that it plans to seek marketing approval in the United States in the second half of this year.

‘The fact that Dr. Sartor and colleagues observed survival improvement in men with castrateresistant prostate cancer is exceptionally exciting.’

Presents

The Summer issue of

Bridging the gap between the hospital and alternate-site care

In This Issue Ask the Expert

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

Volume 1 • Number 2 • Spring 2012

Reports from the PBMI conference

Cost Containment In Specialty Pharmacy

Q&A

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

Practice Proﬁle

The Apothecary Shops applies a personal touch to disease management.

Operations & Mgmt

New study underscores savings potential of alternate-site infusions.

Clinical

Anti-EGFRs linked to increased risk for thromboembolic events.

Disease State Spotlight

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

Excelera Eyes Market Growth For Hospitals

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

•

see EXCELERA, page 8

Breadth of problem is ‘scary’

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

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

see CONTAINMENT, T page 10

see INTERACTIONS, page 17

•

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

Do MTX Drug Interactions Fall Below Radar?

•

Our quarterly publication from the editors and publisher of Pharmacy Practice News. Each issue will provide essential clinical and business information for stakeholders in specialty pharmacies, home infusion providers, insurers and managed care organizations. Our goal: to help foster high-quality, cost-effective treatment across the entire patient-care continuum. To subscribe, visit www.specialty pharmacycontinuum. com/subscription

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

Bridging the gap between the hospital and alternate-site care

—William D. Figg Sr., PharmD “As recently as two years ago, we had very few options for patients with this particularly difficult form of advanced prostate cancer,” said lead author of the study, A. Oliver Sartor, MD, a professor of cancer research at Tulane University School of Medicine, in New Orleans. “Now we have a handful. But Radium-223 is the first treatment to both reduce adverse skeletal-related events (SREs) and improve survival, making this a particularly promising therapeutic option.” Prostate cancer is considered castration-resistant when growth continues despite extremely low levels of testosterone. In the ALSYMPCA (Alpharadin in Symptomatic Prostate Cancer Patients) trial, 922 patients with progressive CRPC with bone metastases were randomized in a 2:1 ratio to receive Ra-223 plus best supportive care (BSC) or placebo and BSC. BSC included antibiotics, analgesics, radiation therapy for pain from bone metastases and corticosteroids. In an interim analysis of 805 patients presented at ASCO Genitourinary Cancers Symposium (abstract 8), Ra-223 significantly improved median overall survival compared with placebo (14 vs. 11.2 months; hazard ratio [HR], 0.695; 95% confidence interval [CI], 0.5520.875; two-sided P=0.00185). As a result, the trial was discontinued early. Additionally, the time to the first SRE— bone fracture, spinal cord compression, external beam radiation to bone or bone surgery—was significantly delayed

Hem/Onc Pharmacy 39

Pharmacy Practice News • August 2012

In Focus Bone marrow

Tumor cells

NCI Pharmacist’s Take Asked to comment on the study, William D. Figg Sr., PharmD, the head of the Molecular Pharmacology Section and a senior scientist at the National Cancer Institute, in Bethesda, Md., said, “We are just now starting to reap the rewards of considerable investment over the past 20 years into understanding the biology of prostate cancer and developing treatments for this disease that kills approximately 30,000 men in the U.S. each year. Ra-223 is just one more new exciting agent that will be available to us.” Perhaps most importantly, Dr. Figg added, “this agent works through a different mechanism of action (not simply another taxane or hormonal agent) than the other agents that have shown activity in prostate cancer (as an alpha-emitting nuclide that targets bone metastases). Most experts

Newly formed bone

Osteoblast

in the field, including myself, would have predicted symptomatic control and delay in events (delay in new bone lesions or decreased fractures) with this agent, but the fact that Dr. Sartor and colleagues observed survival improvement in men with castrate-resistant prostate cancer is exceptionally exciting.”

Radium-223 deposition

—John Schieszer Dr. Sartor serves as a consultant for Algeta. Dr. Figg reported no relevant financial conflicts of interest.

MEROPENEM.

(median time to SRE 13.6 vs. 8.4 months, respectively; HR, 0.610; 95% CI, 0.4610.807; P=0.00046). In the follow-up data presented at the 2012 ASCO meeting (abstract 4551), the proportion of patients whose Eastern Cooperative Oncology Group (ECOG) performance status (PS) deteriorated two or more points was lower among patients given Ra-223 than among those given placebo at both weeks 12 and 24 (4% vs. 9% and 7% vs. 12%, respectively). The time for patients’ ECOG PS to deteriorate two or more points also was significantly extended in the Ra-223 group compared with the placebo group (HR, 0.62; 95% CI, 0.46-0.85; P=0.003). “These findings will help us to increasingly individualize advanced prostate cancer treatment, with a novel agent that can extend our patients’ lives,” said Dr. Sartor. Further research is planned to examine the effectiveness of combining Ra-223 with other drugs. Dr. Sartor said studies are needed to determine whether Ra-223 is effective in combination with newly available immunotherapies, hormonal therapies and chemotherapy. Additionally, other investigators already have begun testing Ra-223 in patients with breast cancer who have bone metastases. Plans also are under way for clinical studies of Ra-223 in other cancers. “The majority of patients were postdocetaxel. This group of people has not often been included in previous trials,” said Dr. Sartor. “All in all, it is an extremely well-tolerated therapy. We believe this novel α-pharmaceutical may provide a new standard of care for prostate cancer.”

Osteoblast

IMIPENEM.

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Reference: 1. As of March 2012.

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Hem/Onc Pharmacy

Pharmacy Practice News • August 2012

In Focus

CARFILZOMIB

Pharmaceuticals is required to provide additional clinical data about the drug. According to the manufacturer, such studies are now underway.

continued from page 1

(MM) who are refractory to their most recent treatment and who had received at least two prior lines of therapy that included the proteasome inhibitor bortezomib (Velcade, Millennium) and an immunomodulatory agent—either thalidomide or lenalidomide (Revlimid, Celgene). The FDA granted that indication—a decision that followed an 11-0 recommendation for approval by the agency’s Oncologic Drugs Advisory Committee (ODAC). A single-arm, Phase II study (003A1) in 266 patients with relapsed and refractory multiple myeloma was the central trial in carfilzomib’s new drug application. The overall response rate (ORR) was 22.9%, with a median response duration of 7.8 months. Additionally, 62% of responding patients maintained response for at least six months and 27% for at least 12 months. Response did not differ by baseline demographics, disease-related or treatment-related characteristics, including whether patients were refractory to both bortezomib and lenalidomide. These results compare favorably to reports of single-agent therapies in patients with relapsed and refractory MM. The drug was well tolerated. Prior to the ODAC meeting, the FDA distributed a briefing document suggesting the drug’s benefit might not outweigh the risks, especially cardiac risks. In the 0031A1 study, according to the briefing document, seven deaths that occurred in the carfilzomib arm most likely were caused by cardiac toxicities. At the ODAC meeting, however, a non-voting participant from the FDA downplayed this data, saying the life-threatening heart- lungand liver-related adverse events (AEs) documented in the clinical trial were seen in only 4% of patients. The FDA participant pointed out that the singlearm design of the carfilzomib study made it difficult to correlate the deaths directly to the drug therapy, adding that it was not clear what the disease, previous therapy or the study drug itself might have played in the AEs documented in the study. Moreover, Onyx presented data that cardiac toxicities were common in patients with heavily pretreated MM. “It was really unclear whether there was any cause and effect between the carfilzomib [study arm] and cardiac toxicity,” said Wyndham Wilson, MD, PhD, ODAC chairman and chief of Lymphoma Therapeutics at the National Cancer Institute. He said he had no hesitation voting yes.

Option for Refractory Patients Shaji Kumar, MD, an MM expert at Mayo Clinic, in Rochester, Minn., said that carfilzomib “adds one more option for patients who have exhausted cur-

Strength in Numbers

‘It was really unclear whether there was any cause and effect between the carfilzomib [study arm] and cardiac toxicity.’

—Wyndham Wilson, MD, PhD

Table. Discontinuations in Multiple Myeloma Patients Due to Adverse Events Adverse Event

Incidence (N=526) (%)a,b,c

Dyspnea

10 (2)

Pneumonia

10 (2)

Cardiac failure (congestive)

9 (2)

Renal failure (acute)

9 (2)

Blood creatinine increased

7 (1)

Pyrexia

6 (1)

Cardiac arrest

5 (1)

Thrombocytopenia

5 (1)

Excludes adverse events attributed to progressive multiple myeloma disease (e.g., disease progression, hypercalcemia, spinal cord compression).

Patients may be counted in more than one adverse event category

Data culled from several Phase II studies; not limited to the 003A1 trial.

rently available therapies” and carries an added benefit: “It causes very little neuropathy,” he stressed. This AE can range from tingling and numbness in the fingers and toes, to painful neuropathy and to autonomic neuropathy. The condition is a common dose-limiting toxicity of several MM therapies, including bortezomib, thalidomide and vincristine. In the case of IV bortezomib, the drug is associated with a 53% rate of peripheral neuropathy, 16% of which is grade 3/4, according to the drug’s Prescribing Information. In the carfilzomib study, 12.4% of patients had treatment-emergent peripheral neuropathy, with only 1.1% being grade 3, and grade 4 neuropathy was nonexistent. No patients discontinued treatment because of neuropathy. (See Table for other AEs linked to discontinued treatment.) “Neuropathy is a problem that, although not life-threatening, is very vexing,” said Ravi Vij, MD, an associate professor of medicine in the Division

of Oncology at Washington University School of Medicine, in St. Louis, who was heavily involved with the carfilzomib trials. Lenalidomide, in contrast, is rarely associated with mild neuropathy, he added. If neuropathy does set in, Dr. Vij said, it often takes weeks or months to resolve and good supportive-care treatments do not exist. Dr. Vij added that pharmacists also should keep an eye out for dyspnea as a possible side effect associated with carfilzomib therapy. He said that 33.8% of patients in the 003A1 study experienced dyspnea of any grade; 3% experienced grade 3 and 0.04% experienced grade 4. “When people use carfilzomib in the community, they will need to be a little vigilant about dyspnea,” he stressed. Prior to the drug’s approval, some analysts speculated that the FDA might impose a postmarketing program to help ensure the safe and effective use of carfilzomib. Something of the sort did occur; as a condition of carfilzomib’s accelerated FDA approval, Onyx

Both Drs. Kumar and Vij said that carfilzomib is likely to be used in combination with at least dexamethasone or even with lenalidomide and dexamethasone. Two- and three-drug combinations are common in MM, they noted. Their views, stated just prior to the drug’s approval, proved to be partly prescient; the FDA-approved drug label recommends that patients should be premedicated with dexamethasone before each infusion to lower the risk for infusion reactions. Dr. Kumar added that he also sees a role for carfilzomib in up-front therapy, “but obviously there are no Phase III trials that have been done, so there is not going to be an approval in that setting,” he said. “It is something that needs to be studied.” A recent Phase I/II study suggested that up-front combination therapy might indeed be a viable option. The study evaluated carfilzomib in tandem with low-dose dexamethasone and lenalidomide. Of 36 patients newly diagnosed with MM completing eight or more cycles of therapy, 42% reached stringent complete responses. The 24-month progression-free survival estimate was 92%, the investigators reported (Blood ( 2012 June 4 [Epub ahead of print]. The results were first presented at the 2011 annual meeting of the American Society of Hematology, in San Diego; abstract 631.) How the drug will be used also will depend on whether insurers will pay for it, which is dependent on the FDA label and compendia listing, Dr. Kumar noted. The cost of the drug and schedule also will influence use. Convenience also may play into treatment decisions. “With carfilzomib you have to come back two days every week, whereas Velcade, depending on what schedule you are using, can be two days per week or one day per week,” Dr. Kumar said. “I don’t think there is going to be one answer that fits all in how this drug will be used.”

Oncology Pharmacist’s View Ali McBride, PharmD, MS, a clinical pharmacy specialist at the Arthur G. James Hospital, The Ohio State University, in Columbus, said he agreed that several questions remain as to how the drug will be used in clinical practice, including whether the drug has potential for up-front therapy. The proper sequencing of carfilzomib also remains to be determined, he noted. “If you give bortezomib first, can you then use

•

see CARFILZOMIB, page 42

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Hem/Onc Pharmacy

Pharmacy Practice News • August 2012

In Focus

Pharmacists Applaud Chemo Guidelines for Obese Patients

he American Society of Clinical Oncology (ASCO) has released guidelines recommending that physicians and pharmacists use an obese patient’s actual body weight, rather than ideal body weight, to calculate the appropriate dose of nearly all chemotherapy drugs. Although many pharmacists were already following this practice, the guidelines provide clarity and support. “We were already dosing based on actual body weight prior to their release, but I think guidelines like this needed to be published and I am so glad we have them,” said Leigh Boehmer, PharmD, BCOP, a clinical pharmacist in medical oncology at Barnes-Jewish Hospital in St. Louis. “Having these guidelines in place has allowed us to consolidate the literature and, with evidence, go forth to make recommendations for … practices that weren’t using an actual body weight to dose obese or morbidly obese patients.” Sara Kim, PharmD, BCOP, an oncology pharmacy clinical coordinator at the Mount Sinai Medical Center, in New York City, agreed. In 2009, oncologists and hematologists at her institution asked her for input on chemotherapy dosing in obese patients; after an exten-

CARFILZOMIB continued from page 40

carfilzomib if the patient fails to respond? Or do you use carfilzomib as initial therapy followed by bortezomib?” All of these various clinical scenarios “may be in the mix in terms of potential

‘Practitioners tend to seek a second opinion that they are not doing any harm by giving chemotherapy based on actual weight in obese patients. The ASCO guidelines provide a clear guidance’ to support the practice. sive literature review, she recommended using actual body weight, especially in the curative setting. However, she said that even after she presented the data to the prescribers, she would still get calls about the dosing weight. “Physicians are hesitant to use the actual weight for chemotherapy in obese patients,” said Dr. Kim. “Practitioners tend to seek a second opinion that they are not doing any harm by giving chemotherapy based on actual weight in obese patients. The ASCO guidelines provide a clear guidance” to support the practice.

Toxicity Deemed Manageable The ASCO guidelines are based on a systematic review of studies published between 1996 and 2010. The majority of studies involve breast, ovarian, colon

ways to maximize patient response,” he noted. Dr. McBride pointed to a recent study ( (Blood d 2012;119:5661-5670) as evidence that using carfilzomib first may be the preferred strategy. In the multicenter, open-label Phase II trial, 129 bortezomib-naive patients with relapsed/

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—Sara Kim, PharmD and lung cancers. The guidelines committee found there was no evidence that short- or long-term toxicity is increased among obese patients receiving full weight-based doses. In fact, the guidelines concluded, “most data indicate that myelosuppression is the same or less pronounced among the obese than the nonobese who are administered full weightbased doses.” Dr. Boehmer said there are a few exceptions to dosing on actual body weight, and these are highlighted in the guidelines. “Because of the risk for cumulative nerve damage, there is an established maximum dose for vincristine. A capped dose of 2 mg per cycle is used for patients,” she said. Bleomycin, a drug commonly used for testicular cancer, is a fixed dose in the BEP (bleomycin, etoposide, cisplatin) regimen. Carboplatin is dosed based on

refractory MM were treated with IV carfilzomib in two cohorts. Patients in cohort 1 were given 20 mg/m2 of the drug for all treatment cycles; cohort 2 received 20 mg/m2 for cycle 1 and then 27 mg/m2 for all subsequent cycles. The clinical benefit response (overall response rate plus minimal response) was 59.3% in cohort 1 (95% CI, 45.771.9) and 64.2% in cohort 2 (95% CI, 51.5-75.5), according to the study, which included Dr. Vij as a co-investigator. Consistent with the FDA trial data, carfilzomib elicited a relatively low incidence of peripheral neuropathy (17.1% overall, with one grade 3 and no grade 4), the investigators reported. The lower rate of peripheral neuropathy seen in clinical trials of carfilzomib is significant, Dr. McBride stressed. “It may prove to be one of the guiding points in choosing this drug over bortezomib,” he said. He noted, however, that there are now data to suggest that a subcutaneous (SQ) formulation of bortezomib causes very low rates of peripheral neuropathy. In one study ((Lancet Oncol 2011;12:431-440), peripheral neuropathy of any grade occurred in 38% of patients given SQ bortezomib vs. 53% treated with an IV formulation (P ( =0.044). “It will be interesting to see what the head-to-head numbers on peripheral neuropathy are in these patients,” Dr. McBride said.

kidney function rather than weight. Drs. Kim and Boehmer pointed out that the guidelines do not suggest that pharmacogenomics, pharmacokinetics and other variables related to drug clearance are not important. “It is not only weight that is going to make an impact on treatment outcomes or observed toxicities,” said Dr. Boehmer. “For example, there are known homozygous carriers of a UGT1A1*28 mutation. Patients with this mutation have a decreased ability to clear the active metabolite of irinotecan. So, in addition to the data that would suggest we should be dosing irinotecan based on actual body weight, we would empirically start with a lower dose of the drug.” Although the guidelines clear up confusion over doses of chemotherapeutic agents for obese patients, there are other areas of oncology therapy that remain muddy. “In the future,” Dr. Kim said, “I hope to see a dosing guideline developed on the targeted agents and monoclonal antibodies in obese cancer patients as well.” —Kate O’Rourke Drs. Kim and Boehmer reported no relevant financial conflicts of interest.

As far as reimbursement—always a key consideration with newly approved agents—Dr. McBride said it is a bit too soon to speculate on any issues that may arise. “As usual it will be a payer-driven decision,” he said. “The big issue, at least initially, is to remember that you will only be able to use the drug in the relapsed/refractory setting. Payers will most likely be very firm in paying only for that indication.” Dr. McBride added a final note of caution based on the data from the 266-patient carfilzomib study: the trial did not establish whether the drug prolongs patients’ lives or increases progression-free survival, both of which are considered to be important markers of clinical response. Still, carfilzomib’s approval “is an important addition to our armamentarium for multiple myeloma—especially given its role in patients who are running out of other treatment options.” —Kate O’Rourke, with additional reporting by David Bronstein

Dr. Vij is on the advisory board of Onyx and Celgene and has received grant funding from the companies. Dr. Kumar is the principal investigator on clinical trials supported by Celgene, Cephalon, Genzyme, Millennium and Novartis. Drs. Wyndham and McBride reported no relevant financial conflicts of interest.

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Best Practices for Hospital and Health-System Pharmacy 2011-2012

American Society of Health-System Pharmacists September 30, 2011 ASHP position statements and more than 70 guidance documents of varying scope provide ongoing advice to managers and practitioners to help improve the medication-use process, patient care and safety and patient outcomes and quality of life.

Drug Discovery & Development: Technology in Transition: Second Edition

Raymond G. Hill September 26, 2012 The modern pharmacopeia has enormous power to alleviate disease, and owes its existence almost entirely to the work of the pharmaceutical industry. This book provides an introduction to the way the industry goes about the discovery and development of new drugs.

Foye’s Principles of Medicinal Chemistry

David A. Williams March 8, 2012 Now in its seventh edition, this book features updated chapters plus new material that meets the needs of today’s medicinal chemistry courses. It offers an unparalleled presentation of drug discovery and pharmacodynamic agents, integrating principles of medicinal chemistry with pharmacology, pharmacokinetics and clinical pharmacy.

Fundamentals of Pharmacognosy and Phytotherapy, Second Edition

Michael Heinrich April 11, 2012 Drawing on their wealth of experience and knowledge in this field, the authors, who are without doubt among the finest minds in pharmacognosy, provide useful and fascinating insights into the history, botany, chemistry, phytotherapy and importance of medicinal plants in some of today’s y health care systems. y

Get the Residency: ASHP’s Guide to Residency Interviews and Preparation

Joshua Caballero; Kevin Clauson; Sandra Benavides; American Society of Health-System Pharmacists Staff September 1, 2012 You need to get the residency—but the odds are tougher and the field more competitive than ever. How can you stand out in the field of thousands competing for critical residency positions? ASHP’s new guide can help you. Based on a course that has gotten acceptance rates of 83%— versus the national average of about 60%.

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Antimicrobial Stewardship Management of Infections: Beyond the Costs of Antimicrobials DEBRA A. GOFF, PHARMD, FCCP CP Specialty Practice Pharmacist, Infectious Diseases Department of Pharmacy Clinical Associate Professor College of Pharmacy

KARRI A. BAUER, PHARMD, BCPS PS Specialty Practice Pharmacist, Infectious Diseases Department of Pharmacy

JULIE E. MANGINO, MD Medical Director of Clinical Epidemiology y Professor of Internal Medicine Division of Infectious Diseases The Ohio State University Wexner Medicall Center Columbus, Ohio

ntimicrobial resistance nce is a global problem, problem 1

and antimicrobial stewardship programs (ASPs) are

the global solution. Both national and international

organizations are recognizing the growing importance of ASPs and are fostering their development through symposia, workshops, and/or certification programs dedicated to ASP (Table 1).

During the past decade, the prevalence of ASPs at US hospitals has greatly increased, and the state of California now mandates that general acute care hospitals develop a program to evaluate the judicious use of antibiotics.2 Additionally, the Infectious Diseases Society of America (IDSA) has made recommendations to the Centers for Medicare & Medicaid Services (CMS) to require stewardship in all acute care hospitals in the United States as part of infection control.3 To spur stewardship efforts, the Joint Commissionâ&#x20AC;&#x2122;s 2012 National Patient Safety Goals include 2 goals relevant to ASP: Get important test

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results to the right staff person on time and foster hand hygiene compliance to prevent infections.4 The goal of antimicrobial stewardship is to optimize antimicrobial therapy for improved patient outcomes, with maximal effect on subsequent development of resistance.5 The changing landscape of health care reform places increasing pressure on ASPs to use the most cost-effective antimicrobial to decrease expenses. Cost usually plays a major role in the formulary decision process when ASPs examine targeted antimicrobial agents that have similar efficacy and safety. ASPs face

P H A R M AC Y P R AC T I C E N E WS â&#x20AC;˘ AU G U ST 2 0 1 2

Table 1. US and International Organizations With Programs Fostering ASPs National Organizations

International Organizations

Making a Difference Infectious Diseases

European Congress of Clinical Microbiology and Infectious Diseases

Society of Infectious Diseases Pharmacists Infectious Diseases Association of California

International Congress Antimicrobial Agents and Chemotherapy

Infectious Diseases Society of America

Federation of Infectious Diseases Societies of South Africa

Society of Healthcare Epidemiology

ASPs, antibiotic stewardship programs

additional pressures due to the lack of new therapeutic choices. New antibiotic development is at a standstill, in part because antibiotics are not as profitable as other drugs.6 Moreover, once a new antibiotic makes it to the market, ASPs commonly hold it “in reserve” due to fear of drug resistance, as well as fear of the economic effect on the ASP budget. ASPs also face the challenge of being considered “cost centers” and not “revenue generators” by health-system administrators.7 However, there is increasing realization that one of the highest expenses in infection management is the cost of failure or relapse; this is compounded by the added intangible negative effect of patient dissatisfaction and hospital readmission. Reducing readmissions is considered by many in the policy world to be “low-hanging fruit.”8,9 In an attempt to capitalize on this, the Affordable Care Act has provisions to improve performance on 30-day Medicare readmission rates for pneumonia and other diseases.10 Hospitals will be assessed a payment penalty for higher than expected readmission rates effective Oct. 1, 2012. Thus, reducing readmissions likely will become an additional focus of stewardship programs. The Ohio State University Wexner Medical Center (OSUWMC) ASP is based on the concept that appropriate antimicrobial selection should result in the most rapid resolution of the infection, shorten hospital length of stay (LOS), reduce the risk for developing resistant pathogens, and improve morbidity and mortality but that it may increase pharmacy charges.11 Recognizing that a business model emphasizing improved efficiency of care may be the optimal way to support ASP, this paper describes a disease-based approach to stewardship rather than a drug-based approach. The management of 4 types of infection—multidrug-resistant gram-negative infections, staphylococcal bacteremia, candidemia, and Clostridium difficile infection (CDI)— are discussed from a stewardship perspective.

Stewardship Checklist If one of the goals of an ASP is to improve patient outcomes while being fiscally responsible, a coordinated effort by all ASP team members (physicians, pharmacists, microbiologists, epidemiologists, infection preventionists, and data managers) is necessary. The figure shows OSUWMC’s ASP model. Table 2 is a

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checklist of ASP initiatives. It incorporates key stewardship concepts and specific roles for all team members and can be used by both fully staffed programs as well as those with limited resources.

Infection-Prevention Strategies Infection prevention uses scientifically proven concepts—such as tracking resistance trends, applying infection control practices and, importantly, sharing information with staff—to achieve its goals (Table 3). Communicating and collaborating with infection preventionists is critical to the success of an ASP. The best antibiotic for a patient is of little value, if health care workers do not clean their hands and risk cross-transmission to other patients. Lack of compliance with hand hygiene, contact isolation, and meticulous environmental cleaning contributes to the spread of multidrugresistant organisms from one patient to the next.

Microbiology Another strategy ASPs can use is rapid diagnostic tests to identify antimicrobial-resistant bacteria. Infectious Diseases Society of America past president John Bartlett, MD, called the advent of these tests a “game changer” in infectious disease.12 One of the first stewardship papers to apply such tests with infectious disease pharmacist stewardship interventions demonstrated a shorter time to initiation of pathogenspecific therapy when the tests were used to differentiate methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and coagulase-negative staphylococci (CoNS).13 There are now several rapid diagnostic tests using different methods to detect S. aureus and CoNS. These include peptide nucleic acid fluorescence in situ hybridization (PNA-FISH), polymerase chain reaction (PCR) assays, bacteriophage amplification-based assays, and nucleic acid tests to detect genes specific to S. aureus and S. epidermidis. Additional tests with PNA-FISH technology are available to detect Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Candida species from positive blood cultures. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF) is another rapid diagnostic that is just starting to be used in the United States. As more

Table 2. ASP Infection Management Initiatives Ideal ASP Team

Limited-Resource ASP Team

Hand hygiene

✓

Contact isolation

✓

Environmental cleaning • High-touch surfaces

✓

Computer decision support and alerts • Identification of high-risk patients • Microbial results to infection preventionist • Track and trend transmissible pathogens

✓

Infection Preventionist

Microbiologist Antibiogram (hospital-wide) • Unit specific • Combination

✓ ✓ ✓

Rapid diagnostic tests • rPCR, Quick-FISH, nucleic acid test, bacteriophage amplification, MALDI-TOF • Communicate results to pharmacist

✓

Dose optimization • Extended- or continuous-infusion β-lactams • Renal dose adjustments • Drug level monitoring

✓ ✓ ✓ ✓

“Antibiotic hang time”

✓

Core measures • CAP • SCIP

✓ ✓

Computer decision support • Bug–drug mismatch • Duplicate therapy • Results to ASP

✓ ✓ ✓ ✓

Education • One on one • Patient care rounds • Grand rounds • Hospital ASP Web site • Medical apps (eg, iPhone or iPad)

✓ ✓ ✓ ✓ ✓ ✓

✓ ✓ ✓ ✓

Clinical outcomes • LOS • Infection-related LOS • Mortality • 30-day readmissions for MRSA bacteremia, C. difficile, CAP, and SSIs

✓ ✓ ✓ ✓

✓

Pharmacist/Physician

✓ ✓

ASP, antimicrobial stewardship program; CAP, community-acquired pneumonia; FISH, fluorescence in situ hybridization; LOS, length of stay; MALDI-TOF, matrix-assisted laser desorption/ionization–time of flight; MRSA, methicillin-resistant Staphyloccocus aureus; rPCR, rapid polymerase chain reaction; SCIP, surgical care improvement project; SSI, surgical site infection

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Table 3. Infection-Prevention Strategies • Identify occurrences and trends of MDROs such as MRSA, Acinetobacter baumannii, ESBL-producing organisms, and Pseudomonas aeruginosa • Apply practices to prevent transmission of MDROs to other patients: -Use reminders, accountability, and corrective action, if necessary to stress the importance of hand hygiene before and after each patient contact -Isolate patients in private rooms, as feasible, with health care workers wearing a gown and gloves; and re-isolate patients with epidemiologically significant organisms to your organization -Ensure surfaces and equipment are appropriately disinfected to reduce potential spread -Bathe patients with antiseptic soap -Decolonize patients of S. aureus if they are to undergo high-risk surgical procedures -Provide education to patients and family members about the MDRO -Communicate the infection to all health care providers (ie, other health care institutions, ambulatory sites) • Implement care bundles: universal protocol, checklists, and internal practice guidelines that when consistently used, reduce the risk for surgical site- and device-related infections • Share trends about hand hygiene and MDRO-related infections with clinical staff, ASP members, and administrative leadership to improve and share opportunities for control ESBL, extended-spectrum β-lactamase; MDRO, multidrug-resistant organism; MRSA, methicillin-resistant Staphylococcus aureus

ASPs incorporate rapid diagnostics, the clinical effect of implementation of such tests on patient care, specifically reduced time to effective therapy, can be realized.

Clinical Outcomes ASPs have the opportunity to affect several clinical outcomes of infected patients, including the time to effective therapy, optimized dosing, and duration of therapy.

TIME

EFFECTIVE THERAPY

Tools to shorten the time to delivery of appropriate initial therapy are key components of ASPs. Kumar et al found that initiation of effective antimicrobial therapy within the first hour after the onset of hypotension in patients with septic shock was associated with improved survival.14 For every additional hour to effective antimicrobial initiation during the first 6 hours after hypotension onset, survival dropped an average of 7.6%. ASPs should evaluate antimicrobial “hang time”— defined as the time from physician order entry to the time the nurse actually hangs the IV antimicrobial. If excess hang time is not addressed, the opportunity to improve patient outcomes may not be realized. As Dr. Kumar’s study demonstrates, every hour counts.

OPTIMIZED DOSING Vancomycin has been considered the drug of choice for MRSA bacteremia. Pharmacists have traditionally provided vancomycin therapeutic drug monitoring as the standard of care. In addition to monitoring of drug levels, ASPs also should evaulate whether vancomycin is the most appropriate anti-staphylococcal agent for patients with MRSA bacteremia. High rates

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of vancomycin failure in MRSA infections increasingly are being reported.15 Kullar et al identified several independent predictors of vancomycin failure, including 2 that can be addressed by ASPs—an initial vancomycin trough less than 15 mg/L and a vancomycin minimum inhibitory concentration (MIC) greater than 1 mg/L by Etest. Consensus guidelines recommend considering use of alternative agents for infections involving a higher vancomycin MIC.16 A recent study compared vancomycin with daptomycin (Cubicin, Cubist) for the treatment of patients with MRSA bacteremia with a high vancomycin MIC (>1 mg/L) and found a higher probability of survival among those in the daptomycintreated group (P=0.022).17 Treatment of gram-negative infections often includes the use of β-lactam antimicrobials. In vitro and animal studies have demonstrated that the best predictor of bacterial killing is the time during which the free-drug concentration exceeds the MIC of the organism.18 ASPs may be able to optimize the pharmacodynamics of first-line anti-pseudomonal β-lactam antibiotics by implementing extended infusions of β-lactam antibiotics such as piperacillin/tazobactam, cefepime, meropenem, and doripenem (Doribax, Janssen). Improved outcomes have been documented by administering extended-infusion β-lactam therapy to critically ill patients with P. aeruginosa infections.19 An initial assessment of the hospital’s MIC for P. aeruginosa should be done to determine if extended infusion β-lactams provide value; this may not be necessary if P. aeruginosa isolates have low MICs.

REDUCE DURATION OF ANTIMICROBIALS Reducing the length of antibiotic courses is the strategy most likely to be effective in reducing antibiotic

resistance.20 Hayashi et al reviewed several strategies and results from clinical trials that used short-course therapy for reduction in duration of antimicrobials.21 Use of biomarkers such as procalcitonin in conjunction with clinical signs of resolution of infection can assist ASPs in efforts to de-escalate or discontinue antimicrobials. Hospital LOS and antibiotic-related LOS are important parameters for ASPs to monitor. Bauer et al documented that when ID pharmacist interventions resulted in shorter time to optimal antibiotic therapy for patients with bacteremia, LOS also was decreased.13 Considering that LOS is the most expensive component of hospitalization, ASPs should monitor the relationship of interventions to LOS in addition to the antimicrobial budget to remain fiscally responsible over the long term.

Targeted Management of Resistant Organisms The following sections focus on prevalent resistant organisms and strategies to best manage patients infected with these organisms while reducing resistance.

EXTENDED-SPECTRUM β-LACTAMASE–PRODUCING ENTEROBACTERIACEAE Epidemiology Infections caused by resistant bacteria expressing extended-spectrum β-lactamase (ESBL) pose serious challenges to clinicians. These organisms are increasingly identified, having become endemic in many hospital settings and also are reported as causes of communityacquired infections. E. coli and K. pneumoniae are the most frequently identified ESBL-producing organisms. Clinical and Economic Outcomes The presence of ESBL-producing organisms has demonstrated an association with unfavorable patient outcomes. Studies comparing outcomes between ESBL-associated versus non–ESBL-associated Enterobacteriaceae bacteremia show that ESBL production is an independent predictor of delay in initiation of appropriate therapy, LOS, mortality, and cost.22 An important reason associated with poor outcomes is the presence/ acquisition of multiple resistance mechanisms, which decreases therapeutic options. A report from the IDSA emphasized the lack of available antimicrobials for drug-resistant organisms.23 In the treatment of ESBL-producing organisms, carbapenems are associated with a high rate of clinical and microbiologic success. In one study, 96% of patients who received a carbapenem-containing regimen had a favorable response or were cured.24 In a retrospective study of consecutive patients, those treated with imipenem for an ESBL-producing bacteremia were significantly more likely to survive than were patients treated with a cephalosporin.25 Antimicrobial Stewardship ASPs should track the rates of ESBL-producing organisms annually. OSUWMC’s ASP recently joined SMART (Study for Monitoring Antimicrobial Resistance

Trends), a global surveillance program designed to longitudinally monitor the epidemiologic trends and in vitro antimicrobial activity of 12 antimicrobials against a variety of aerobic and facultative gram-negative bacilli isolated from patients. This allows a stewardship program to benchmark resistance rates to other US hospitals in addition to hospitals worldwide. Microbiology laboratories should use the recently lowered Clinical Laboratory Standards Institute (CLSI) breakpoints or confirm the presence of ESBL activity. If an isolate is confirmed as an ESBL producer, the microbiology laboratory should report all penicillins, cephalosporins, and aztreonam as resistant. Consideration should be given to reporting only carbapenems as options for treatment of blood isolates. At the time of ESBL identification, the microbiology laboratory also should prompt the clinician to place a contact isolation order because appropriate infection control can decrease the potential risk of ESBL cross transmission. Additionally, stewardship programs should consider limiting the use of thirdgeneration cephalosporins through prior authorization or prospective feedback and education.

ACINETOBACTER

BAUMANNII

Epidemiology Over the past 3 decades, A. baumannii has emerged from being an organism of questionable pathogenicity to an infectious agent of great importance in hospitals worldwide.26,27 Multidrug-resistant A. baumannii is recognized as being among the most difficult organisms to control and treat. Risk factors for infection include an ICU stay, recent surgery, central vascular catheterization, mechanical ventilation, and treatment with third-generation cephalosporins, fluoroquinolones, or carbapenems.28,29 Clinical and Economic Outcomes A. baumannii is associated with both outbreaks and health care–associated infections (HCAIs) and demonstrates high morbidity, mortality, and costs.30-32 A retrospective, matched cohort study found that patients with A. baumannii infection had a 5-day excess length of mechanical ventilator dependence and ICU stay compared with other critically ill patients without this infection. Additionally, A. baumannii infections are associated with an overall mortality rate between 26% and 68%.30 Antimicrobial Stewardship Infection control for A. baumannnii is paramount to prevent cross transmission and additional development of resistance. Because of the prevalence of resistant organisms, including A. baumannii, in long-term care facilities, institutions should consider placing patients transferred from high-risk locations into contact plus/minus droplet isolation until the presence of A. baumannnii is ruled out. Surveillance cultures may be obtained if patients were previously colonized or infected. Early recognition is important to avoid inadvertent cross transmission and aggressively control potential spread. Additionally, meticulous daily cleaning

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of frequently used surfaces is an important intervention. ASPs must ensure that staff optimize hand hygiene, comply with contact isolation for colonized or infected patients, and use dedicated medical equipment. For hospitals with limited resources for surveillance of hand-hygiene adherence, a free medical application (iScrub) is available to download from the Apple App store to an iPhone or iPad.33 This allows any health care worker to record observations and electronically transmit the data to a hospital epidemiologist. A. baumannii also represents many challenges from a microbiology perspective because the organism can be difficult to identify using conventional microbiology methods. Novel technology, including MALDI-TOF has been used extensively in Europe and is being applied in the United States. This technology allows for the rapid identification of organisms from cultures (respiratory, blood, or wound) within minutes versus conventional methods that take at least 24 hours. With rapid organism identification, patients may receive earlier, targeted therapy, which is of great importance for A. baumannii, because it is becoming increasingly resistant. A. baumannii is intrinsically resistant to commonly used antibiotics, including aminopenicillins and firstand second-generation cephalosporins. A. baumannii has remarkable capacity to acquire mechanisms conferring resistance.34 Antimicrobials with activity against A. baumannii include ampicillin/sulbactam, colistin, carbapenems (doripenem, imipenem, and meropenem), minocycline, and tigecycline (Tygacil, Wyeth). In many hospitals, only colistin provides reliable activity. The microbiology laboratory must confirm susceptibility testing by completing Etests for colistin, minocycline, and tigecycline. OSUWMC’s ASP reviewed minocycline for the treatment of infections due to A. baumannii. The microbiology laboratory performed susceptibility testing and determined that minocycline was an option in the treatment of multidrug-resistant A. baumannii. Among the isolates resistant to imipenem and ampicillin/sulbactam, 18 of 47 isolates (38%) were susceptible to minocycline; the ASP recommended minocycline for formulary addition. OSUWMC’s early experience treating 5 A. baumannii–infected patients showed that all 5 had microbiologic eradication from blood and respiratory sites and all but 1 patient were successfully treated.35

PSEUDOMONAS

AERUGINOSA

Epidemiology P. aeruginosa infections constitute a tremendous burden on hospitals in terms of morbidity, mortality, and health care costs. Studies have demonstrated that P. aeruginosa infections are associated with a mortality rate of 18% to 60% and that the cost of treatment is substantial, ranging from $20,000 to $80,000.36-41 P. aeruginosa infections continue to present unique challenges to ASPs because P. aeruginosa is associated with multiple resistance mechanisms and poor patient outcomes.

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Clinical and Economic Outcomes Carmeli et al examined the clinical and economic outcomes of patients with P. aeruginosa. The emergence of resistance was associated with severe adverse outcomes, including a 3-fold increase in mortality and a 2.1-fold increase in hospital LOS.42 The most important reason for the substantial mortality was the delay in starting effective antimicrobial therapy and inadequate empiric choices based on resistance. The marked escalation in the prevalence of resistance in P. aeruginosa has made the selection of empiric antimicrobial therapy increasingly complex.43 Antimicrobial Stewardship P. aeruginosa is one of the most important organisms for ASP to address because most empiric antimicrobial prescribing is directed toward patients with risk factors for or confirmed infections with P. aeruginosa. Combination therapy may be prescribed until the infecting organism and susceptibilities are available; this time frame often leads to prolonged, unnecessary antimicrobial use. Rapid techniques are now available for identification of P. aeruginosa. One of these technologies, GramNegative Rod (GNR) Traffic Light® PNA Fish® (AdvanDx) provides identification of E. coli, K. pneumoniae, and P. aeruginosa directly from GNR-positive blood cultures in 90 minutes.44 A second technology, MALDI-TOF, also can provide rapid identification from a variety of culture sites, not just blood cultures. These technologies that allow more rapid identification result in patients receiving earlier, targeted therapy, which can lead to more rapid deescalation of additional antimicrobials. The selection of empiric therapy is based in large part on the susceptibility rates compiled from an institution’s antibiogram. Unfortunately, institution-wide antibiograms may fail to reveal important differences in susceptibility data across specific patient-care units, particularly in ICUs within an institution.45 These unit-specific differences are critical to the selection of the optimal regimen and the tracking of emerging patterns of resistance because certain patient types (ie, trauma patients, sepsis patients) and those with mixed disease states are admitted to distinctly different types of units. At OSUWMC, Clinical Epidemiology and Microbiology create ICU-specific antibiograms annually. The data in these antibiograms were invaluable to help identify a then-unknown ESBL outbreak in 2000 and to assess the utility of using fluoroquinolones in specific ICUs in 2011. Hospital-wide and unit-specific antibiograms help ASPs select the optimal regimen for patients at risk for infections with P. aeruginosa and track unit-specific resistance rates. Combination antibiograms to assess any potential advantage for combination empiric treatment of P. aeruginosa also are now completed annually. P. aeruginosa’s multiple resistance mechanisms result in higher MICs and, combined with a lack of newer antibiotics in the pipeline, leave ASPs in search of optimal doses to potentially overcome resistance.46 ASPs must recommend the available agents to achieve optimal outcomes, minimize collateral damage, and prevent

IAL B O

ID Pharmacist

STEWARDSHIP

PR O

AM GR

ANT IMI CR

ID Physician

Microbiologist

Epidemiologist

TH Infection Preventionist

HIO S

S TATE UNIVER

ITY

Data Manager

Figure. OSUWMC ASP model. ASP, antimicrobial stewardship program; ID, infectious diseases; OSUWMC, Ohio State University Wexner Medical Center

inappropriate therapy (ie, continuing anti-pseudomonal therapy when the organism is not identified). Historically, β-lactams are administered via intermittent infusion; this results in high peak concentrations that do not enhance bactericidal activity, but during the dosing interval, concentrations may fall below the MIC.18,47,48 The approved dosing regimens for β-lactams worked reasonably well in the past, but with escalating resistance, these regimens may fail to optimize pharmacodynamics, resulting in suboptimal patient outcomes. Lodise et al evaluated extended-infusion piperacillin/tazobactam in patients with P. aerguinosa infections. Among patients with an APACHE II score of 17 or higher, 14-day mortality was significantly lower among those who received extended-infusions (12.2% vs 31.6%; P=0.04).19 Extended-infusion cefepime also has been evaluated in the treatment of P. aeruginosa infections. In a prospective, observational evaluation of adult patients with ventilator-associated pneumonia (VAP), Nicasio et al demonstrated that cefepime 2 g every 8 hours infused over 3 hours provided the highest probability of target attainment using pharmacodynamic modeling. The study demonstrated a significant decrease in infection-related

LOS (11.7±8.1 vs 26.1±18.5 days; P<0.001).49 OSUWMC infuses all broad-spectrum β-lactams (ie, piperacillin/tazobactam, cefepime, and doripenem) over 4 hours, after the first dose is ordered “stat” and infused over 30 minutes. Compliance with extended infusion is documented to be approximately 95%. OSUWMC’s ASP recently completed a study evaluating the clinical and economic outcomes associated with extended-infusion cefepime. Overall mortality was significantly lower in the patients receiving an extended infusion compared with those receiving an intermittent infusion.50 Institutions should consider obtaining exact MICs on all gram-negative isolates to determine the optimal antimicrobial agent, regimen, and infusion time.

MRSA BACTEREMIA Epidemiology MRSA infections are a significant concern due to their high propensity to increase morbidity, mortality, and health care costs. MRSA has become an increasingly important pathogen in both community and nosocomial infections over the past 2 decades, particularly in ICUs. Approximately 60% of S. aureus nosocomial

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infections occurring among patients in the ICU are caused by MRSA.51 Clinical and Economic Outcomes Bacteremia with MRSA has been reported to be associated with mortality rates between 15% and 60%. Treatment for MRSA bacteremia is substantial, with costs ranging from $20,000 to $70,000 per episode.52,53 The problem of MRSA bacteremia has escalated to the point that US Department of Health and Human Services made MRSA infections 1 of the 6 categories of HCAIs in its 5-year National Prevention Targets.10 In 2013, the management of MRSA bacteremia will be a national hospital quality measure and part of the value-based purchasing program. Antimicrobial Stewardship OSUWMC’s ASP has taken considerable action in optimizing the diagnosis and management of S. aureus bacteremia. Recently, rapid polymerase chain reaction (rPCR) assays have been shown to improve clinical outcomes by decreasing the time to identification of S. aureus. The medical center’s ASP evaluated the clinical effect of rPCR assays on clinical and economic outcomes. The microbiology laboratory contacted an ID pharmacist with results of the rPCR and the pharmacist recommended effective antibiotics and an ID physician consult. Mean time to switch from empiric vancomycin to cefazolin or nafcillin in patients with MSSA was 1.7 days shorter with the rPCR plus the ID pharmacist intervention versus without intervention (P=0.02). For MRSA bacteremia, vancomycin was considered to be effective unless the patient met the stewardship criteria for vancomycin failure, at which time daptomycin was recommended. In the post-rPCR group, daptomycin was recommended 5.5 days sooner in patients who met criteria for vancomycin failure. In this intervention group, the mean hospital LOS was 6.2 days shorter and the mean hospital costs were $21,387 less. Use of a rapid identification test and a stewardship pharmacist resulted in significantly improved clinical and economic outcomes.13 The optimal treatment of MRSA bacteremia continues to evolve. Vancomycin has been the mainstay of therapy for years. Recent reports have linked vancomycin-treatment failure with MRSA and susceptible vancomycin MICs of 1 to 2 mg/L.54,55 As mentioned previously, recent consensus guidelines recommend that clinicians consider using alternative agents when the vancomycin MIC is greater than 1 mg/L.16 Daptomycin is considered a reasonable alternative to vancomycin and is FDAapproved for the treatment of MRSA bacteremia, even in patients with right-sided endocarditis. A recent study evaluated the effectiveness and safety of vancomycin compared with those of daptomycin, in the treatment of patients with MRSA bloodstream infections (BSIs) with a high vancomycin MIC (>1 mg/L). Clinical failure, defined as mortality, microbiologic failure, and/or recurrence of infection, was lower in the daptomycin-treated group

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(31% vs 17%; P=0.084) and was mainly driven by a lower incidence of mortality in the daptomycin group (20% vs 9%; P=0.046). Factors independently associated with clinical failure included acute renal failure and vancomycin treatment.17 This study supports recent guidelines recommending a switch to alternative therapy when the isolate has a high but susceptible MIC to vancomycin. In addition to daptomycin, ceftaroline (Teflaro, Forest) represents another therapeutic alternative. Ceftaroline is FDA-approved for the treatment of community-acquired pneumonia and acute bacterial skin and skin structure infections. In a recent study of ceftaroline as off-label salvage therapy for the treatment of MRSA bacteremia or endocarditis, 6 patients were successfully treated, experiencing rapid clearance after starting ceftaroline.56 Additional studies are necessary to establish the role of ceftaroline in the management of MRSA bacteremia. ASPs should consider completing Etests on MRSA bloodstream isolates to help determine the optimal antibiotic for the treatment of MRSA bacteremia. This methodology has demonstrated increased reliability for predicting treatment response.57,58 Alternative therapy should be strongly considered for isolates with a vancomycin MIC of 1 to 2 mg/L. Stewardship programs should consider prospective auditing and feedback of daptomycin or ceftaroline or an ID physician consultation for all patients with MRSA bacteremia.

CANDIDEMIA

AND INVASIVE

CANDIDIASIS

Epidemiology Hospitalizations complicated by candidemia have increased since 2000.59 Candidemia represents the fourth most common cause of nosocomial bloodstream infections (BSIs) in the United States and results in significant morbidity, mortality, and hospital cost. Studies estimate attributable mortality rates as high as 50%.60,61 Over the past decade, the epidemiology of BSI with Candida species has changed. There has been a global shift toward non-albicans Candida species, particularly C. glabrata.62 This change in epidemiology is particularly concerning because C. glabrata displays dose-dependent fluconazole susceptibility, with resistance reported in as many as 23% of isolates.63 Clinical and Economic Outcomes A recent review of 1,915 patients from 7 randomized trials for treatment of invasive candidiasis assessed the effect of host, organism, and treatment-related factors on clinical cure and mortality.64 After evaluating numerous factors associated with outcomes, the investigators identified only 2 modifiable strategies to improve patient outcomes. Treatment with an echinocandin antifungal and removal of a central venous catheter (CVC) were associated with decreased mortality and greater clinical success. Patients who received an echinocandin—caspofungin (Cancidas, Merck), micafungin (Mycamine, Astellas), or anidulafungin (Eraxis, Pfizer)—had significantly better survival rates than patients who received either a polyene—amphotericin B, liposomal amphotericin B—or

a triazole—fluconazole, voriconazole (mortality, 27% for echinocandins vs 36% for other regimens; P<0.0001). Arnold et al evaluated the effect of inadequate antifungal dosing or administration of an antifungal to which the isolate was resistant, on postculture hospital LOS and costs. Postculture LOS was shorter in the appropriate therapy group (7 vs 10.4 days; P=0.037) and correlated with total hospital costs that were lower in the appropriate therapy group ($15,832 vs $33,021; P<0.001).65 Other studies have found the additional cost of each invasive candidiasis episode to be nearly $40,000.60,61 Antimicrobial Stewardship The IDSA Clinical Practice Guidelines for the Management of Candidiasis published in 2009 suggest that early initiation of antifungal therapy should be considered in critically ill patients with risk factors for invasive candidiasis and no other known cause of fever. In cases of confirmed candidemia, the guideline focuses on CVC removal and rapid initiation of fluconazole or an echinocandin in non-neutropenic patients.66 Echinocandins are recommended as a first-line choice for invasive candidiasis for the critically ill, those with prior triazole exposure, and those infected with less-susceptible Candida species, such as C. glabrata and C. krusei. Clinical application of these guidelines can be inconsistent which may result in suboptimal patient outcomes.67,68 Many ASPs may prefer to position fluconazole, rather than the echinocandins, as the first-line agent for empiric antifungal therapy due to its lower cost. However, in a recent study, Andes et al found the echinocandin class to be superior for both C. albicans and non-albicans groups and suggested that ASPs should re-evaluate the role of fluconazole as first-line therapy for patients with invasive candidiasis.64 The OSUWMC practice guideline lists an echinocandin (caspofungin) as the preferred agent for empiric antifungal therapy in patients with suspected invasive candidiasis. This approach minimizes delay to effective therapy for potential fluconazole-resistant C. glabrata and C. krusei, which have been identified at OSUWMC. A recommendation to de-escalate to fluconazole is made once the species and/or susceptibilities are known. OSUWMC’s microbiology laboratory uses rapid molecular-based diagnostic methods to shorten the time to positive identification of yeast from blood cultures. The Yeast Traffic Light® PNA-FISH test was implemented by the center’s ASP to assist in the management of candidemia.44 The microbiology technician pages the ASP pharmacist with the PNA-FISH test results. This is crucial because others have shown that a delay in therapy (even as little as a few hours) is associated with increased mortality.68,69 For this difficult group of patients, ASP pharmacists recommend removal of the CVC and consultation by ID physicians.

CLOSTRIDIUM

DIFFICILE

Epidemiology CDI is a common cause of health care–associated diarrhea. Symptoms range from mild diarrhea to

pseudomembranous colitis to death. CDIs nearly always are associated with prior antibiotic exposure; ampicillin, clindamycin, third-generation cephalosporins and, more recently, quinolones are the most commonly identified drugs. Recurrences occur in 25% of patients.70 Minimizing the frequency, number, and duration of antimicrobial therapy prescribed will reduce the risk for CDI, and ASPs are recommended.71 Clinical and Economic Outcomes CDI has increased almost 4-fold over the past decade. An epidemic strain termed the North American Pulse Field Type 1 (NAP-1) with increased virulence and toxin production was reported from multiple outbreaks.72 In 2009, 336,600 US hospitalizations involved CDI, representing nearly 1% of all hospital stays; nearly one-third had CDI as the principal diagnosis. Unfortunately, patients with CDI hospital stays were more severely ill than hospitalized patients in general, with 9.1% of CDI stays ending in death versus less than 2% for all other inpatients. Life-threatening conditions such as dehydration, septicemia, septic shock, renal failure, and hypoalbuminemia have been identified as potential complications of CDI by administrative data. The mean hospital LOS for a patient with CDI in US hospitals was 13 days, with a mean cost of $24,400 for all listed diagnoses ($8.2 billion overall).73 Antimicrobial Stewardship and Infection Prevention CDI poses an inherent challenge to infection-prevention programs/ASPs, in that it exists in 2 forms: the vegetative form, which is found primarily within the GI tract, where it is inhibited by GI acid. However, once outside the GI tract the environment induces formation of spores, creating a form that is resistant to gastric acid, routine disinfectants, and hand sanitizers.71 Proton pump inhibitors (PPIs) may result in an increased risk for CDI due to their inhibition of stomach acid.74-76 Epidemiology and infection-prevention departments are responsible for performing CDI surveillance; in many US states, health care facility–onset disease (ie, a positive CDI test specimen collected >3 days after admission or on/after hospital day 4) is publicly reportable. CMS also has determined that this will be a national reporting requirement as of January 2013. Health care facility–onset disease represents the minimum surveillance category for health care organizations to collate, but it often represents less than 50% of the total CDI burden within hospitals.77 All CDI surveillance categories are tabulated at OSUWMC, and cases of health care facility–onset CDI and cases of other potentially preventable events (ie, central line–associated BSIs, VAPs, and selected surgical site infections) also are shared with administrative leadership as a metric on the OSUWMC quality scorecard each month. With the recognition of increasing incidence and severity of CDI, obtaining testing results as rapidly as possible is helpful. Numerous rPCR tests have become available to shorten the time to diagnosis from 2 to 3 days (ie, cytotoxin assay) to hours.78,79 Earlier CDI test

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results lead to earlier treatment and more timely isolation to lessen potential cross transmission. Unfortunately, with implementation of the more sensitive, yet timely test, health care facility–onset cases have increased by approximately 40%, which also has been noted in other organizations.80 When the rPCR (Cepheid Xpert C. difficile®) testing was implemented, OSUWMC’s microbiology lab continued calling clinicians with positive results. In a cohort of its first 68 patients, metronidazole was consistently used as first-line therapy versus vancomycin, regardless of severity of CDI illness.81 ID pharmacists now make follow-up calls to optimize antiCDI therapy based on disease severity82; this study is ongoing to assess a larger number of patients. Recently, a small community hospital reported results from its program’s approach to improving the management of patients with C. difficile.83 Their Pharmacy and Therapeutics Committee approved a policy authorizing pharmacists to switch metronidazole to vancomycin if the patient had severe CDI. Additional ASP initiatives at OSUWMC include a review of order sets with a PPI. Physician stakeholders were asked to re-evaluate the order set and remove PPIs unless they were absolutely necessary. Patients receiving more than 3 antimicrobials per day are being reviewed to assess for de-escalation or discontinuation, based on data by Stevens et al assessing the cumulative risk for antibiotic exposure over time.84 Infection-prevention goals for CDI mitigation include the following: early identification, contact isolation via barrier methods (ie, gown and gloves) for patients with symptoms of diarrhea (ie, 3 stools within 24 hours), and antibiotic exposure.85 Dedicated equipment and patientcare items also are recommended for contact with patients and their environment, and private rooms are preferred. Meticulous compliance with hand-hygiene procedures before and after patient contact must occur. Use of soap and water for at least 15 seconds and decontamination of the environment with bleach in a 1:10 dilution is recommended in hyperendemic settings and outbreaks. Frequent re-education to stress these evidence-based guidelines is important to foster a culture of awareness of the epidemiology surrounding CDI and served as the basis in Ohio for a statewide collaborative in 2009-2010.86 At OSUWMC, ID pharmacists, infection preventionists, hospital epidemiologists, and environmental services receive daily email reports from the Microbiology Department about every new case of CDI. Each day, messaging subsequently goes to the unit nurse manager and attending of record to reinforce isolation processes and educational material for staff and family. Environmental services supervisors validate housekeeper cleaning with a fluorescent marker (Dazo, Ecolab Healthcare) following room cleaning to assure all “high-touch surfaces” are appropriately disinfected. OSUWMC plans to implement multiple ultraviolet emitters in each patient room to augment its current disinfection program. Curtailing cross transmission of CDIs is OSUWMC’s intent, but avoiding the diagnosis in the first place is the

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overarching global aim. CDI is inherently linked to antibiotics, the “lifesavers” that have been handed out at times “like candy” over the past few decades. Reversing cavalier use of antimicrobials represents the next laudable goal.

Conclusion Opportunities for contributions by all members of the ASP to improve patient care are numerous, as outlined above. ASPs, however, should not justify their existence solely by curtailing antimicrobial costs. They should focus on appropriate empirical therapy based on local data, timely identification of pathogens to guide de-escalation, and avoidance of unnecessary antimicrobials. Collaboration of ASPs with clinicians will optimize patient management and should lead to favorable outcomes with a reduced risk for readmission.

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