August 2010 digital edition of Pharmacy Practice News by McMahon Group

Co P P Pr rpo N Se o f rat e pa ile s e ge 23

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pharmacypracticenews.com

Volumee 37 • Number 8 • August 2010

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this issue $17 billion at stake PCI Antiplatelet Therapy in Up Front ‘Meaningful Use’ IT Provision Gets More Complicated In Brief ACC/AHA panel offers tips in wake of clopidogrel warning Tampa, Fla.—Genetics, comorbidities and other patient-specific factors can impact efficacy and need to be considered when patients with acute coronary syndromes (ACS) are being evaluated for antiplatelet medications, according to a session on thrombosis therapy at the American Society of Health-System Pharmacists (ASHP) 2010 Summer Meeting. Speakers at the session paid particular attention to how these factors could impair response to clopidogrel (Plavix, Sanofi-Aventis). That topic choice proved prescient when, several weeks after the ASHP meeting, a task force warned clinicians to heed the potential causes of impaired response to the commonly used antiplatelet agent.

•

see WARNING, page 21

Making Smart-Pump Drug Libraries Smarter Atlanta—It took a multidisciplinary team at Women & Children’s Hospital of Buffalo in New York more than two years to develop and implement a wireless smart pump and customized drug library tailored to the diverse dosing needs of the hospital’s pediatric and high-risk obstetric patient population. When the system went live in 2008 after “no less than four attempted implementations,” according to Kelly A. Michienzi, PharmD, clinical pharmacy coordinator at the 214-bed hospital, it quickly began to pay safety dividends. Within a week, Dr. Michienzi said, the hard-limit safeguards embedded in the pump’s software prevented medication errors such as the administration of an IV immunoglobulin dose at 10 times the safe rate. Other “critical catches” soon followed, she said, including the prevention of insulin, heparin and epinephrine overdoses. In the ensuing months, the system continued to demonstrate safety benefits. “We have had a reduction in preventable errors of 46%—calculated in errors per patient day. We went from 10.4 [errors per patient-day]

•

see DRUG LIBRARIES, page 46

Deemed a Game-Changer

New REMS approved to reduce quinine-associated hematologic reactions.

FDA and NIH launch Web site for reporting safety data.

Operations & Mgmt

Leadership in Action Ernie Anderson describes the importance of selfconfidence in a leader.

Reimbursement Part 2 of a series on how a dedicated pharmacist can help resolve payment issues.

Clinical

IVIG FAQ Exploring the role of immunoglobulins in treatment of complex regional pain syndrome.

Hem/Onc Pharmacy Second-generation TKIs poised to supplant imatinib for CML.

Tampa, Fla.— professionals will .— Hospitals and health care p rro ofe fessionals w ill have far greater il flexibility in “meaningful use” elecn meeting the “me ean anin ingf g ul u gf se” requirements ffor se orr ccertified ertifi fied ed eele lectronic health (EHR) technology h record (EH HR) R) technol loggy under a finall rule issue issued byy ed last month b the Centers for Medi Medicare Medicicare & Medic caid Services (CMS). Reacting to more than th haan 2,000 2 00 2, 000 public comments, many ments, m any of an of them criticizing the proposed he p pr roposed rregueeggulations released ased ed in Januaryy ed as being too o rrigid, igid, CMS reduced to 15 th the he number of “core” meane” me eaan ningful use objectives that have to o be satisfied to qualify alify for Medicare and nd Medicaid incentive tive payments in 2011. 11. In addition on to the core measures, thee ag aagency ency tacked on on a “menu set” of 10 otherr objectives from which hospit hospitals and itaalls an it ital nd clinicians ccllin inicians will have to select att least five to fulfill meaningful usee requirements. Others deemed too difficult to achieve by 2011 can be postponed for a year, according to the rule. In announcing the flexible, two-track approach, CMS abandoned its “allor-nothing” test requiring hospitals to meet 23 objectives and physicians to meet 25 in order to be deemed meaningful users.

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Technology

Automation Industry responds to issues surrounding pump recalls.

Bar Coding Tips on how to select a BCMA system.

Educational Review

Antimicrobial Efficacy See www.pharmacypracticenews.com

see MEANINGFUL USE, page 48

Clinic Travel a Winning Strategy For Onc Pharmacist/Nurse Team Chicago—A program that brings a pharmacist/nurse team directly to oncology clinic patients for supportive care has achieved major reductions in symptoms such as pain and nausea, according to a study presented at the 2010 annual meeting of the American Society of Clinical Oncology. The Supportive Care Consult Service at the University of North Carolina at Chapel Hill (UNC-CH) consists

of a full-time pharmacist and a nurse. Requests are called in from adult oncology clinics—hematology/oncology, gynecologic oncology, surgical oncology or radiation oncology. The team then goes to the individual clinic where the pharmacist and nurse often conduct the consult together. Once they develop a plan of action, they run their recommendation by

•

see ROVING, page 36

New Product APP Pharmaceuticals announces approval and launch of first generic Aztreonam for Injection. See page

Pharmacy’s Most Dispensed Name… now appearing on our tablets and capsules

We know you trust our products. On average, pharmacists fill 1 out of every 6 prescriptions with a Teva product*. We want patients to share your trust and confidence in Teva. That’s why, over the next few months, you’ll begin to see tablets and capsules imprinted with the Teva name. In some cases, this new Teva imprint will replace the company identifier code. Ultimately, all our capsules and most of our tablets will proudly bear the Teva name. Patients will come to know us better, making your job a little easier every time you confidently dispense quality Teva products.

*data on file, Teva Pharmaceuticals

888 TEVA USA • www.tevausa.com

8618

Up Front 3

Pharmacy Practice News • August 2010

Capsules

surf

Collaboration Expands Safe Prescription Medicine Initiative

AUGUST 2010

watch

The five most-viewed articles last month on pharmacypracticenews.com: 1. 2. 3. 4. 5.

Pharmacists Association Launches “Dispose My Meds” Campaign First FDA/ISMP Fellowship Targets Medication Safety Our Role in Expanding Residency Programs QI Project Shows a Less-Is-More Strategy Works in ICU Sedation Investigational Agent Stops Potentially Fatal 5-FU Toxicity

Register for free at pharmacypracticenews.com to read these and other articles on the latest developments in hospital pharmacy.

heard here first

‘The fact that [we achieved a 41% reduction in sepsis mortality in] a community hospital shows that cuttingedge clinical pharmacy is not limited to academic centers.’

See article, page 16

—Gita Wasan Patel, PharmD (first author)

MCMAHONMEDICALBOOKS.COM

The Book Page

Pharmacy Case Studies Soraya Dhillon; Rebekah Raymond See page

ephalon has joined with the American Chronic Pain Association (ACPA) and the American Pharmacists Association (APhA) to broaden the company’s program, When Good Medicines Become Bad Drugs. This national education campaign provides patients, caregivers and the public with information about the abuse of prescription medications, which affects as many as 6 million Americans and now surpasses the national use of most illegal street drugs. The expanded program provides educational tools in select pharmacies across the country and online at the program’s Web site (www. GoodMedicinesBadDrugs.com). The new site features practical tips and information, including videos with leading experts in the pain and addiction communities. As part of the program’s expansion, Cephalon partnered with ACPA and APhA to develop educational materials for use in the pharmacy, providing patients, caregivers and the public with information on how to safely and appropriately use prescription pain medicines. These materials include a countertop display and a patient card that shows how to use, store and dispose of prescription medicines. Through the When Good Medicines Become Bad Drugs program, Cephalon and its partners plan to educate nearly 3 million people and help remind patients to keep their medications safe in the home. “People with pain deserve appropriate treatment for their condition, including prescription pain medicines, but one of our goals as an organization is to help people learn how to use them safely and correctly,” said Penney Cowan, founder and executive director of the ACPA. “We are proud to be a part of this valuable program and to be able to provide people with easy-to-understand information on prescription medicines, including how they should be taken and what things should be avoided, as well as safe storage and disposal.” To learn more about the ACPA, please visit www.theacpa.org, or call the National Office at (800) 533-3231. —Staff

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Volume 37 • Number 8 • August 2010 • pharmacypracticenews.com

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4 Up Front

Pharmacy Practice News • August 2010

In Brief

FDA Approves REMS For Qualaquin Heme Reactions

he FDA has approved a new Risk Evaluation and Mitigation Strategy (REMS) to reduce the number of adverse events that occur when patients use quinine sulfate (Qualaquin, AR Scientific) “off-label” to treat nighttime leg cramps. The plan, announced in an FDA MedWatch alert, requires that health care providers give patients a medication guide outlining both approved and unapproved uses for quinine. The guide is to be issued before the patient starts using the medication and with every refill, according to the MedWatch alert. The REMS also calls for the drug

Pain Foundation Unveils New Back Pain Resource

n response to the high prevalence and burden of back pain, the American Pain Foundation (APF) has launched a new online guide as part of its Spotlight on Back Pain program. The guide contains information and resources to educate people about back pain, and provides tips for prevention, pain management and self-advocacy. According to the National Center for Health Statistics, part of the Centers for Disease Control and Prevention, approximately 26 million Americans with acute back pain will develop chronic back pain. It is estimated that as many as 83 million days of work are missed each year due to back pain. The Spotlight on Back Pain guide contains articles, worksheets and tips about preventing and managing back pain, including: • “Oh, My Aching Back! The ABCs of Chronic Back Pain”; • “Common Causes and Knowing When to Seek Care to Avoid Problems”; • “Who’s Who in Treating Back Pain”; • “Finding Relief: 10 Ways to Manage Back Pain”; • “Lifestyle Tips: Preventing Back Pain from the Start”; • “Back Pain & the Workplace”; • “Back Truths: Debunking Common Myths about Back Pain”; and • “In Your Words: Profiles of People Living with Back Pain.” The guide also contains “Terms You Need to Know: Questions to Ask Your Health Care Provider,” a list of helpful resources and checklists, and handouts that explain exercises that help strengthen the back and self-care at home. To view the APF’s Spotlight on Back

manufacturer to issue a “Dear Health Care Provider Letter” warning clinicians of the risk for hematologic reactions that can accompany misuse of the medication. Health care providers are advised to discuss with patients some of the signs of thrombocytopenia, which include easy bruising, severe nosebleeds and the appearance of unusual purple, brown or red spots on the skin, the FDA noted in the alert. Quinine is approved only for the treatment of uncomplicated malaria, typically in travelers returning from malaria-endemic locations. In the

Pain guide, visit www.spotlightonbackpain.org. The project is supported by Purdue Pharma LP. —Staff

FDA Approves Butrans Transdermal System CIII

he FDA has approved Purdue Pharma’s Butrans (buprenorphine) Transdermal System CIII for the management of moderate to severe chronic pain in patients requiring a continuous, around-the-clock opioid analgesic for an extended period of time. The Butrans Transdermal System is an analgesic product that delivers continuous release of medication for seven days. Buprenorphine is a partial agonist at µ-opioid receptors and an antagonist at κ-opioid receptors. A Schedule III product, Butrans can be abused in a manner similar to other opioid agonists. Working with the FDA, Purdue has developed a Risk Evaluation and Mitigation Strategy (REMS) for Butrans that includes a patient medication guide, elements to ensure safe use (such as health care provider training) and a timetable for submitting assessments of the REMS. Butrans is contraindicated in patients: • who have significant respiratory depression or severe bronchial asthma; • who have or are suspected of having paralytic ileus or known hypersensitivity to any of the product’s components or the active ingredient; or • who require opioid analgesia for a short period of time, for postoperative pain (including use after outpatient or day surgeries), for mild pain or for intermittent pain. Butrans is available in 5, 10 and 20 mcg strengths per hour; each single patch is intended to be worn for seven days. Patients should not exceed a dose of one 20-mcg per hour Butrans Transdermal

United States, however, quinine is most often used to treat or prevent nighttime leg cramps, according to the MedWatch alert. Such misuse can result in life-threatening hematologic reactions, including heavy bleeding due to thrombocytopenia and hemolyticuremic syndrome/thrombotic thrombocytopenic purpura, which can cause permanent kidney damage, the alert stated. Quinine labels warn patients about these risks, which outweigh any possible benefits that might be derived from using the drug to treat nocturnal leg cramps, according to the FDA. Health care professionals and patients can report any adverse reactions related to the use of quinine to the FDA’s MedWatch online at www. fda.gov/MedWatch/report.htm. —Kate Lu

Covidien Launches New Dose-Alert Timer for EXALGO

ovidien recently announced the release of a new dose-alert timer to be used in conjunction with EXALGO, an extended-release hydromorphone tablet marketed by the drug manufacturer. The timer reminds patients when to take their once-daily dose of EXALGO, according to Covidien. The device can be attached to the top of a pill bottle and will sound when the patient needs to take the next dose of the opioid agonist. Patients can then reset the timer in preparation for the following dose. The timer is meant to help ensure the safe use of the extended-release pain medication, reminding patients when to take their daily dose, the company noted.

System because of the risk for QTc interval prolongation. Exposing the Butrans application site and surrounding area to direct external heat sources should be avoided; temperature-dependent increases in buprenorphine release from the system may result in overdose and death. —Staff

Xenical, Alli Weight-Loss Drugs Tied To Liver Injury

he FDA has issued a warning about rare reports of severe vere liver injury in patients taking ng the weight-loss medi-cation orlistat, marketed as Xenical and Alli. The FDA has approved a revised label for the prescription drug Xenical (Roche) to include new safety information about cases of severe liver injury that have been reported rarely. The agency also is working with the manufacturer of Alli (GlaxoSmithKline) on label revisions to reflect the rare occurrences. Xenical, available only by prescription, contains 120 mg of orlistat. Alli, sold over the counter, contains 60 mg of orlistat. An estimated 40 million people worldwide have taken either Xenical or Alli, according to Roche. The FDA’s safety information and labeling changes are based on a review of cases of severe liver injury reported in individuals taking orlistat. The agency reported that it has identified 13 cases of severe liver injury, 12 of which were reports from outside of the United States. The only U.S. report of severe liver injury involved Alli. At this time, a cause-andeffect relationship of severe liver injury with orlistat use has not been established. To report any problems with either of the drugs, physicians are encouraged to visit www.fda.gov/safety/medwatch. —Staff

The dose-alert timer is part of a “New Beginning Kit” that includes an informational brochure, safety information, a diary for recording pain levels and an introductory video. The kit is meant to improve patient knowledge about safe use of the pain medication, according to Covidien. The kit is being distributed to physicians through sales representatives. Patients who are prescribed EXALGO will need to ask their physician for a kit if they are interested in reviewing the materials and using the timer. Approximately 21 million extendedrelease opioid prescriptions were written for 2.7 million patients in 2007, according to FDA data cited by Covidien. The company claims that although the once-daily medications are more convenient, their increased use highlights a need for better and more comprehensive patient education. EXALGO is indicated for once-daily administration in opioid-tolerant patients with moderate to severe pain who require continuous, aroundthe-clock opioid analgesia for an extended period of time, according to the drug’s prescribing information. The drug was approved by the FDA in March 2010. —Kate Lu

TYGACIL is in the 2009 IDSA/SIS guidelines for cIAI and the 2009 SIS guidelines for cSSSI.1,2

Expanded broad-spectrum coverage3* is on your side

*TYGACIL does not cover Pseudomonas aeruginosa.

TYGACIL is indicated for the treatment of adults with: Complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis Complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros Community-acquired bacterial pneumonia caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus inﬂuenzae (beta-lactamase negative isolates), and Legionella pneumophila

Important Safety Information TYGACIL is contraindicated in patients with known hypersensitivity to tigecycline Anaphylaxis/anaphylactoid reactions have been reported with nearly all antibacterial agents, including tigecycline, and may be life-threatening. TYGACIL should be administered with caution in patients with known hypersensitivity to tetracycline-class antibiotics Isolated cases of significant hepatic dysfunction and hepatic failure have been reported in patients being treated with tigecycline. Some of these patients were receiving multiple concomitant medications. Patients who develop abnormal liver function tests during tigecycline therapy should be monitored for evidence of worsening hepatic function. Adverse events may occur after the drug has been discontinued The safety and efficacy of TYGACIL in patients with hospital-acquired pneumonia have not been established An increase in all-cause mortality has been observed across phase 3 and 4 clinical studies in TYGACIL treated patients versus comparator. The cause of this increase has not been established. This increase should be considered when selecting among treatment options TYGACIL may cause fetal harm when administered to a pregnant woman The use of TYGACIL during tooth development may cause permanent discoloration of the teeth. TYGACIL should not be used during tooth development unless other drugs are not likely to be effective or are contraindicated Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including TYGACIL, and may range in severity from mild diarrhea to fatal colitis Monotherapy should be used with caution in patients with clinically apparent intestinal perforation TYGACIL is structurally similar to tetracycline-class antibiotics and may have similar adverse effects. Such effects may include: photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia). As with tetracyclines, pancreatitis has been reported with the use of TYGACIL To reduce the development of drug-resistant bacteria and maintain the effectiveness of TYGACIL and other antibacterial drugs, TYGACIL should be used only to treat infections proven or strongly suspected to be caused by susceptible bacteria. As with other antibacterial drugs, use of TYGACIL may result in overgrowth of non-susceptible organisms, including fungi The most common adverse reactions (incidence >5%) are nausea, vomiting, diarrhea, abdominal pain, headache, and increased SGPT Prothrombin time or other suitable anticoagulant test should be monitored if TYGACIL is administered with warfarin Concurrent use of antibacterial drugs with oral contraceptives may render oral contraceptives less effective The safety and effectiveness of TYGACIL in patients below age 18 and lactating women have not been established Please see brief summary of Prescribing Information on adjacent page. References: 1. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:133-164. 2. May AK, Stafford RE, Bulger EM, et al. Treatment of complicated skin and soft tissue infections. Surg Infect. 2009;10:467-499. 3. TYGACIL® (tigecycline) Prescribing Information, Wyeth Pharmaceuticals Inc.

Expanded broad-spectrum coverage

6 Operations & Mgmt

Leadership in Action Self-Confidence: TYGACIL® (tigecycline) Brief Summary See package insert for full Prescribing Information. For further product information and current package insert, please visit www.wyeth.com or call our medical communications department toll-free at 1-800-934-5556. INDICATIONS AND USAGE TYGACIL is indicated for the treatment of adults with complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillinsusceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis. TYGACIL is indicated for the treatment of adults with complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros. TYGACIL is indicated for the treatment of adults with community-acquired pneumonia infections caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates), and Legionella pneumophila. CONTRAINDICATIONS TYGACIL is contraindicated for use in patients who have known hypersensitivity to tigecycline. WARNINGS AND PRECAUTIONS Anaphylaxis/Anaphylactoid Reactions Anaphylaxis/anaphylactoid reactions have been reported with nearly all antibacterial agents, including TYGACIL, and may be life-threatening. TYGACIL is structurally similar to tetracycline-class antibiotics and should be administered with caution in patients with known hypersensitivity to tetracycline-class antibiotics. Hepatic Effects Increases in total bilirubin concentration, prothrombin time and transaminases have been seen in patients treated with tigecycline. Isolated cases of significant hepatic dysfunction and hepatic failure have been reported in patients being treated with tigecycline. Some of these patients were receiving multiple concomitant medications. Patients who develop abnormal liver function tests during tigecycline therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing tigecycline therapy. Adverse events may occur after the drug has been discontinued. Mortality Imbalance and Lower Cure Rates in Ventilator-Associated Pneumonia A study of patients with hospital acquired pneumonia failed to demonstrate the efficacy of TYGACIL. In this study, patients were randomized to receive TYGACIL (100 mg initially, then 50 mg every 12 hours) or a comparator. In addition, patients were allowed to receive specified adjunctive therapies. The sub-group of patients with ventilator-associated pneumonia who received TYGACIL had lower cure rates (47.9% versus 70.1% for the clinically evaluable population) and greater mortality (25/131 [19.1%] versus 14/122 [11.5%]) than the comparator. Use During Pregnancy TYGACIL may cause fetal harm when administered to a pregnant woman. If the patient becomes pregnant while taking tigecycline, the patient should be apprised of the potential hazard to the fetus. Results of animal studies indicate that tigecycline crosses the placenta and is found in fetal tissues. Decreased fetal weights in rats and rabbits (with associated delays in ossification) and fetal loss in rabbits have been observed with tigecycline [see USE IN SPECIFIC POPULATIONS]. Tooth Development The use of TYGACIL during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). Results of studies in rats with TYGACIL have shown bone discoloration. TYGACIL should not be used during tooth development unless other drugs are not likely to be effective or are contraindicated. Clostridium difficile-Associated Diarrhea Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including TYGACIL, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. Patients With Intestinal Perforation Caution should be exercised when considering TYGACIL monotherapy in patients with complicated intra-abdominal infections (cIAI) secondary to clinically apparent intestinal perforation. In cIAI studies (n=1642), 6 patients treated with TYGACIL and 2 patients treated with imipenem/cilastatin presented with intestinal perforations and developed sepsis/ septic shock. The 6 patients treated with TYGACIL had higher APACHE II scores (median = 13) versus the 2 patients treated with imipenem/cilastatin (APACHE II scores = 4 and 6). Due to differences in baseline APACHE II scores between treatment groups and small overall numbers, the relationship of this outcome to treatment cannot be established. Tetracycline-Class Effects TYGACIL is structurally similar to tetracycline-class antibiotics and may have similar adverse effects. Such effects may include: photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia). As with tetracyclines, pancreatitis has been reported with the use of TYGACIL. Superinfection As with other antibacterial drugs, use of TYGACIL may result in overgrowth of non-susceptible organisms, including fungi. Patients should be carefully monitored during therapy. If superinfection occurs, appropriate measures should be taken. Development of Drug-Resistant Bacteria Prescribing TYGACIL in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, 2514 patients were treated with TYGACIL. TYGACIL was discontinued due to adverse reactions in 7% of patients compared to 6% for all comparators. Table 1 shows the incidence of treatment-emergent adverse reactions through test of cure reported in 2% of patients in these trials. Table 1. Incidence (%) of Adverse Reactions Through Test of Cure Reported in 2% of Patients Treated in Clinical Studies Body System Adverse Reactions Body as a Whole Abdominal pain Abscess Asthenia Headache Infection Cardiovascular System Phlebitis Digestive System Diarrhea Dyspepsia Nausea Vomiting Hemic and Lymphatic System Anemia Metabolic and Nutritional Alkaline Phosphatase Increased Amylase Increased Bilirubinemia BUN Increased Healing Abnormal Hypoproteinemia SGOT Increasedb SGPT Increasedb Nervous System Dizziness Skin and Appendages Rash

TYGACIL (N=2514)

Comparatorsa (N=2307)

6 3 3 6 8

4 3 2 7 5

12 2 26 18

11 2 13 9

4 3 2 3 4 5 4 5

3 2 1 1 3 3 5 5

Vancomycin/Aztreonam, Imipenem/Cilastatin, Levoﬂoxacin, Linezolid. LFT abnormalities in TYGACIL-treated patients were reported more frequently in the post therapy period than those in comparator-treated patients, which occurred more often on therapy. In all Phase 3 and 4 studies that included a comparator, death occurred in 3.9% (147/3788) of patients receiving TYGACIL and 2.9% (105/3646) of patients receiving comparator drugs. An increase in all-cause mortality has been observed across phase 3 and 4 clinical studies in TYGACIL treated patients versus comparator. The cause of this increase has not been established. This increase should be considered when selecting among treatment options. (See Table 2.) Table 2. Patients with Adverse Events with Outcome of Death by Infection Type b

TYGACIL Infection Type

n/N

Approved Indications cSSSI 12/834 cIAI 40/1382 CAP 12/424 Combined 64/2640 Unapproved Indications HAP 65/467 Non-VAPa 40/336 25/131 VAPa RP 11/128 DFI 7/553 Combined 84/1148

n/N

Comparator %

Risk Difference* % (95% CI)

1.4 2.9 2.8 2.4

6/813 27/1393 11/422 44/2628

0.7 1.9 2.6 1.7

0.7 (-0.5, 1.9) 1.0 (-0.3, 2.2) 0.2 (-2.3, 2.7) 0.7 (-0.0, 1.6)

13.9 11.9 19.1 8.6 1.3 7.2

56/467 42/345 14/122 2/43 3/508 61/1018

12.0 12.2 11.5 4.7 0.6 6.0

1.9 (-2.6, 6.4) -0.3 (-5.4, 4.9) 7.6 (-2.0, 16.9) 3.9 (-9.1, 11.6) 0.7 (-0.8, 2.2) 1.2 (-1.0, 3.4)

CAP = Community-acquired pneumonia; cIAI = Complicated intra-abdominal infections; cSSSI = Complicated skin and skin structure infections; HAP = Hospital-acquired pneumonia; VAP = Ventilator-associated pneumonia; RP = Resistant pathogens; DFI = Diabetic foot infections. * The difference between the percentage of patients who died in TYGACIL and comparator treatment groups. a These are subgroups of the HAP population. Note: The studies include 300, 305, 900 (cSSSI), 301, 306, 315, 316, 400 (cIAI), 308 and 313 (CAP), 311 (HAP), 307 [Resistant gram-positive pathogen study in patients with MRSA or Vancomycin-Resistant Enterococcus (VRE)], and 319 (DFI with and without osteomyelitis). In comparative clinical studies, infection-related serious adverse events were more frequently reported for subjects treated with TYGACIL (7%) versus comparators (6%). Serious adverse events of sepsis/septic shock were more frequently reported for subjects treated with TYGACIL (2%) versus comparators (1%). Due to baseline differences between treatment groups in this subset of patients, the relationship of this outcome to treatment cannot be established [see WARNINGS AND PRECAUTIONS]. The most common treatment-emergent adverse reactions were nausea and vomiting which generally occurred during the first 1 – 2 days of therapy. The majority of cases of nausea and vomiting associated with TYGACIL and comparators were either mild or moderate in severity. In patients treated with TYGACIL, nausea incidence was 26% (17% mild, 8% moderate, 1% severe) and vomiting incidence was 18% (11% mild, 6% moderate, 1% severe). In patients treated for complicated skin and skin structure infections (cSSSI), nausea incidence was 35% for TYGACIL and 9% for vancomycin/aztreonam; vomiting incidence was 20% for TYGACIL and 4% for vancomycin/aztreonam. In patients treated for complicated intra-abdominal infections (cIAI), nausea incidence was 25% for TYGACIL and 21% for imipenem/cilastatin; vomiting incidence was 20% for TYGACIL and 15% for imipenem/cilastatin. In patients treated for community-acquired bacterial pneumonia (CABP), nausea incidence was 24% for TYGACIL and 8% for levofloxacin; vomiting incidence was 16% for TYGACIL and 6% for levofloxacin. Discontinuation from tigecycline was most frequently associated with nausea (1%) and vomiting (1%). For comparators, discontinuation was most frequently associated with nausea (<1%). The following adverse reactions were reported infrequently (<2%) in patients receiving TYGACIL in clinical studies: Body as a Whole: injection site inflammation, injection site pain, injection site reaction, septic shock, allergic reaction, chills, injection site edema, injection site phlebitis Cardiovascular System: thrombophlebitis Digestive System: anorexia, jaundice, abnormal stools Metabolic/Nutritional System: increased creatinine, hypocalcemia, hypoglycemia, hyponatremia Special Senses: taste perversion Hemic and Lymphatic System: partial thromboplastin time (aPTT), prolonged prothrombin time (PT), eosinophilia, increased international normalized ratio (INR), thrombocytopenia Skin and Appendages: pruritus Urogenital System: vaginal moniliasis, vaginitis, leukorrhea Post-Marketing Experience The following adverse reactions have been identified during postapproval use of TYGACIL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. Anaphylaxis/anaphylactoid reactions, acute pancreatitis, hepatic cholestasis, and jaundice. DRUG INTERACTIONS Warfarin Prothrombin time or other suitable anticoagulation test should be monitored if tigecycline is administered with warfarin [see CLINICAL PHARMACOLOGY (12.3) in full Prescribing Information]. Oral Contraceptives Concurrent use of antibacterial drugs with oral contraceptives may render oral contraceptives less effective. USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects—Pregnancy Category D [see WARNINGS AND PRECAUTIONS] Tigecycline was not teratogenic in the rat or rabbit. In preclinical safety studies, 14C-labeled tigecycline crossed the placenta and was found in fetal tissues, including fetal bony structures. The administration of tigecycline was associated with slight reductions in fetal weights and an increased incidence of minor skeletal anomalies (delays in bone ossification) at exposures of 5 times and 1 times the human daily dose based on AUC in rats and rabbits, respectively (28 mcg·hr/mL and 6 mcg·hr/mL at 12 and 4 mg/kg/day). An increased incidence of fetal loss was observed at maternotoxic doses in the rabbits with exposure equivalent to human dose. There are no adequate and well-controlled studies of tigecycline in pregnant women. TYGACIL should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers Results from animal studies using 14C-labeled tigecycline indicate that tigecycline is excreted readily via the milk of lactating rats. Consistent with the limited oral bioavailability of tigecycline, there is little or no systemic exposure to tigecycline in nursing pups as a result of exposure via maternal milk. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TYGACIL is administered to a nursing woman [see WARNINGS AND PRECAUTIONS]. Pediatric Use Safety and effectiveness in pediatric patients below the age of 18 years have not been established. Because of effects on tooth development, use in patients under 8 years of age is not recommended [see WARNINGS AND PRECAUTIONS]. Geriatric Use Of the total number of subjects who received TYGACIL in Phase 3 clinical studies (n=2514), 664 were 65 and over, while 288 were 75 and over. No unexpected overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity to adverse events of some older individuals cannot be ruled out. No significant difference in tigecycline exposure was observed between healthy elderly subjects and younger subjects following a single 100 mg dose of tigecycline [see CLINICAL PHARMACOLOGY (12.3) in full Prescribing Information]. Hepatic Impairment No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh A and Child Pugh B). In patients with severe hepatic impairment (Child Pugh C), the initial dose of tigecycline should be 100 mg followed by a reduced maintenance dose of 25 mg every 12 hours. Patients with severe hepatic impairment (Child Pugh C) should be treated with caution and monitored for treatment response [see CLINICAL PHARMACOLOGY (12.3) and DOSAGE AND ADMINISTRATION (2.2) in full Prescribing Information]. OVERDOSAGE No specific information is available on the treatment of overdosage with tigecycline. Intravenous administration of TYGACIL at a single dose of 300 mg over 60 minutes in healthy volunteers resulted in an increased incidence of nausea and vomiting. In single-dose intravenous toxicity studies conducted with tigecycline in mice, the estimated median lethal dose (LD50) was 124 mg/kg in males and 98 mg/kg in females. In rats, the estimated LD50 was 106 mg/kg for both sexes. Tigecycline is not removed in significant quantities by hemodialysis. This Brief Summary is based on TYGACIL direction circular W10521C015 ET01, revised 05/10.

The Mark of an Emotionally Intelligent Leader “Self-confidence” can be defined as understanding your abilities and having the intuition to make decisions with certainty. A self-confident leader portrays a sense of assurance, but without arrogance. These leaders have strong presence, are easy to follow and take on new challenges with enthusiasm. A high degree of self-confidence sets a strong leader apart from an average leader. It is also the third element of a concept I have been exploring in several recent articles—emotional intelligence. So how is this self-confidence developed? Is it something that is innate or can it be learned? What does is take to find a balance of confidence and humility? In his book “Leaders’ Playbook,” Reldan Nadler, PsyD, examines the behaviors of star performers, with regard to self-confidence.1 He finds that the star performers: • Present themselves in an assured, forceful, impressive and unhesitating manner. They willingly seek out challenges. • Take time for thinking and reflection. This private time is an opportunity to think through issues and to mentally rehearse how to handle specific situations. For me, my private time of thinking and reflection occurs while I drive (about two hours a day) and when I run. I review various scenarios in my mind, seek solutions to various issues and think about how to involve people in the solution process. • Know what they think, but seek opinions from others in an effort to acquire multiple perspectives. I have found it always helpful to surround myself with people of a variety of different strengths in order to synergize my management team. I advise you to know your individual team members and their best qualities. This will allow you to best utilize their capabilities, empowering them to be successful. When people sense your trust in them, they are more likely to work hard to demonstrate that this trust is well deserved. They can also fill gaps by helping in those areas where you may have weaknesses. • Go with their gut. Self-confidence is reinforced by the realization of successful outcomes as a result of following intuition. • Are honest with themselves and others by admitting when they are

Operations & Management 7

Pharmacy Practice News • August 2010

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

•

Ernest R. Anderson Jr., MS, RPh

wrong. Learning by evaluating your errors reinforces the building of confidence for future decisions. Are not afraid to say no and to state the reasons. I can think of occasions when people have wanted to make a process more complicated than it needed to be. I try to remind them to keep it simple and continue to move forward. Are sensitive to those around them and are cautious not to come across so strongly that they might stifle others’ contributions. Do not beat themselves up. There is a balance between continuous selfimprovement and being overly selfcritical. Ask yourself what percentage of the time you are too hard on yourself. As Nadler says, “Changing our self-evaluation greatly improves how confident we feel and allows us greater awareness of how we evaluate others.” Use visualization techniques. Before I give a talk to a large audience, I visualize how I want to come across to the audience—with confidence regarding the topic, yet with the humility that I am still a learner and that I don’t know everything. I even visualize what I would do if

something doesn’t go perfectly, such as an audiovisual snafu. We need to be realistic in our expectations of ourselves and realize that we may not hit a home run every time, but that we will never even have the opportunity to do so if we are not at the plate swinging. One exercise that may be helpful for those times when you suffer “performance anxiety” is to keep a success log, or to merely think back to your successes. Reviewing these successes helps build confidence. You can further examine the actions surrounding these

successes that helped to make them so. For instance, how much preparation went into this particular success? Can you replicate these actions surrounding a new project? What was the level of interaction with others and the acceptance of their suggestions? • Are good consensus builders. These leaders are careful not to express their thoughts too soon, but instead first draw out the thoughts of team members. By doing so, they encourage strong, regular participation and develop a team that is not afraid to express itself. Having a strong sense

of self-confidence means communicating the willingness to listen to other points of view and even to change your mind when that is warranted. The leader needs to be a coach, a facilitator and a cheerleader. In our next segment, we will explore strategies of emotional intelligence in relating to others under the umbrella of relationship management.

Reference 1. Nadler R. Leaders’ Playbook: How to Apply Emotional Intelligence—Keys to Great Leadership. Santa Barbara, CA: Psyccess Press; 2006.

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8 Operations & Management

Pharmacy Practice News • August 2010

Reimbursement

Pharmacist Hire Helps Boost Reimbursement Dollars In the second installment of a two-part series on using a pharmacist to manage claims denials, we discuss selling the program to health care administrators and offer suggestions for conducting specific reimbursement projects to demonstrate a healthy return on the investment.

ith widespread approval of highcost pharmaceuticals over the past decade, accurate medication billing and appropriate reimbursement has been at the forefront of hospital budget meetings. In an effort to capture more reimbursement dollars by reducing unnecessary denials, the Saint Barnabas Health Care System (SBHCS) implemented a pharmacy claims denial management program that specifically focuses on medications. Although this program is flexible in that it may be tailored to the needs of a single-entity or a multifacility system such as SBHCS, it must be well planned and structured. And although laborious

and time-consuming at the onset, this pharmacistrun program appears to be worth its weight in gold when it comes to th e retur n on investment (ROI). S BHC S ’s j our ney began when hospital executives sought solutions to optimize reimbursement in the face of diminishing marginal returns and efficiencies. During this process, it quickly became apparent that capturing the true incidence and prevalence of drug denial claims is no simple task from both a clinical and financial perspec-

Table. Successful Pharmacy Revenue Recovery Strategies Discovery Phase Create spreadsheets to track types of drug denials seen in system Identify denial trends by drug dollars, CPT/HCPCS codes and revenue code Identify new drug-related changes through CMS transmittals, quarterly CPT coding changes, state Medicaid or Medicare contractor updates

tive. At that time, SBHCS realized that hiring a pharmacy clinical financial analyst would help navigate and streamline this process. The steps to transform this idea into reality began with what has been termed “engaging the C-Suites” (chief executive officers, chief financial officers, chief operating officers)—a practice that customarily falls on the shoulders of pharmacy directors and other upper pharmacy management personnel as part of their fiscal responsibilities. But prior to presentation of proposals for full-time equivalent (FTE) staff additions to any C-level executive, hospital administrators and pharmacy directors should be well equipped with sufficient research and analysis. In preparation, SBHCS’s pharmacy management conducted a “needs assessment,” examining pharmacy dollars spent for inpatient versus outpatient drug utilization, since the two are reimbursed by different payment methodologies. The management team then quantified potential cost-savings by reviewing denied drug claims by payer mix and by providing specific examples of revenue recruitment opportunities. Once core pharmacy revenue recruit-

Medicare Hemophilia 11%

Ellen Fan, RPh Pharmacy Clinical Financial Analyst Clinical Pharmacist - Revenue Integrity Corporate Pharmacy Services

Robert T. Adamson, PharmD Corporate Vice President Clinical Pharmacy

Indu Lew, PharmD Corporate Vice President Education and Research

Manal Rassam, PharmD Pharmacy Resident

Drew Misuro, RPh, MBA Corporate Vice President Corporate Pharmacy – Operations Saint Barnabas Health Care System West Orange, New Jersey

ment categories were established, the case for adding an FTE was made, using the argument of lost dollars for each unavailable day of personnel dedicated to reviewing denied drug claims. Upon approval and fulfillment of the pharmacy clinical financial analyst position by Ellen Fan, RPh, a host of reimbursement opportunities were identified.

•

see PAY OFF, page 10

Daptomycin Charge Code 5%

Leuprolide Depot 1%

Infliximab ADR 1% MC Drug Denials 4%

Development Phase Schedule meetings with all affected parties to explain issues uncovered during discovery phase; may consist of corporate departments as well as specific individual hospital departments (billing, charge integrity, corporate compliance, corporate reimbursement, corporate pharmacy, pharmacy directors, site-specific billing managers, IT). Develop project plan to include 1. update of current CDM with proper drug billing codes; 2. creation of programming edits within billing system (which can later flag specific accounts for review); and/or 3. update of hospital-specific procedures Testing Phase Test out select number of claims to determine if expected information drops on bill (i.e., drug codes, billing units, NDC information etc.). Make appropriate changes if necessary

MC Contract Amendment 78%

Implementation Phase Inform relevant parties of new procedure roll-out date Educate individual sites on procedure and specific information required on bill. Follow-up Phase Review submitted claims to ensure reimbursement Continuously monitor for new denials Quantify dollars saved or revenue recovered CDM, Charge Description Master; CMS, Centers for Medicare & Medicaid Services; CPT, Current Procedural Terminology; HCPCS, Healthcare Common Procedure Coding System; IT, information technology; NDC, National Drug Code

Figure. Pharmacy revenue capture May–December 2009. Note: Additional recovered pharmacy revenue involved Highmark Medicare Services’ Additional Development Request for infliximab and Medicare coverage on hemophilia clotting-factor drugs. ADR, Additional Development Request; MC, managed care

10 Operations & Management

Pharmacy Practice News • August 2010

Reimbursement

PAY OFF continued from page 8

Identifying Reimbursement And Revenue Opportunities Almost a decade has passed since the traditional Centers for Medicare & Medicaid Services (CMS) percentageof-charge payment method for hospital outpatients converted to a prospective payment system using the Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS). And yet, even with increasing use of health information technology systems, mistakes leading to CMS denials continue to be rampant. One of the greatest sources of error for outpatient claims stems from the difference between how drugs are dispensed from pharmacies or medication dispensing units and how that quantity is ultimately transferred to the patient bill. The majority of injectable drugs are assigned a HCPCS code (in the form of J, C, Q or S codes), which is based on the lowest billable unit but often is vastly different from how drug dosages generally are administered. These billing codes and billing units are not static; CMS continuously makes changes over time after introduction of drugs to market. As an example of how a pharmacist can evaluate and intervene on potential denials within this landscape, Ms. Fan identified up to a 500-fold discrepancy for daptomycin injection, which was mismapped to an incorrect charge code within the pharmacy’s clinical system (Figure, page 8). Ms. Fan reprocessed the identified claims and implemented procedural changes that resulted in notifications of all future additions or changes to pharmacy-related charge codes. In identifying further reimbursement opportunities, a pharmacy clinical financial analyst should be continuously informed of all changes to pharmacy-related Medicare/Medicaid requirements, as well as contractual changes with commercial insurers. For SBHCS, signing up with the multitude of publicly available “listservs” from CMS and local Medicare/Medicaid contractors, as well as timely communication with managed care and billing departments ultimately resulted in recovery of additional pharmacy revenue relating to high-cost pharmaceuticals, particularly inflixi m a b (Re m i c ad e, C ent o co r Ortho Biotech Inc.) and clotting factors for hemophilia. Ms. Fan discovered that Highmark Medicare Services was requesting submission of Additional Development Request (ADR) information for system-wide reimbursement on infliximab; however, the specific criteria were not relayed to the individuals

Even organizations with sophisticate reimbursement management programs are not immune to denials, so knowing when to appeal is vital.

responding to the request. In addressing this problem, Ms. Fan sent out communications (outlining specific criteria requested in the ADR) to all affected departments, especially outpatient infusion centers. Many of the denied claims were then successfully appealed with the appropriate information. Best practices for ensuring receipt and availability of necessary documentation from referring physicians prior to scheduled infusions also were developed. With regard to clotting factors, certain Medicare inpatient claims qualify for separate reimbursement in addition to the diagnosis-related group. Ms. Fan implemented a retrospective process, where she was able to review and identify accounts with specific clottingfactor drugs, recalculate the units and charges and provide billing departments with a spreadsheet listing all pertinent information. Billing departments then were able to reprocess the claims with all the correctly identified information and bill Medicare accordingly.

Carving Out More Payments Other revenue opportunities involve maximizing drug contracts by working with managed care departments to review “carved out” contracts, develop a targeted list of high-cost drugs potentially warranting additional negotiations and identify new drugs that are not carved out for reimbursement. Early in her position, Ms. Fan encountered a national insurer whose contract required manually matching

up invoices to each drug billed. Ms. Fan developed a process to obtain invoices from the wholesaler, created a worksheet that calculated the appropriate reimbursement based on National Drug Code (NDC) package sizes and submitted more than 300 billing packets to the insurer. The process was time and labor intensive, often requiring submission of hundreds of pages per packet. As such, the managed care department renegotiated the contract with the insurer to make the reimbursement process less resource intensive. Ms. Fan also reviewed drug claims that were denied by another insurer for “experimental use” reasons. After researching the insurer’s clinical policy guidelines for reimbursement, Ms. Fan found that the actual reason for the denial was a diagnosis section on the claim that was either missing or required additional clarification from the prescribing physician. Additionally, she was instrumental in helping SBHCS satisfy the recently implemented New Jersey Medicaid NDC requirements for hospital outpatient drugs, using strategies that made this otherwise daunting task more manageable (Table).

Knowing When To Appeal Even organizations with sophisticated reimbursement management programs are not immune to denials, so knowing when to appeal is vital. The appeals process may recapture lost reimbursement dollars, and also may help hospitals identify whether billing, coding or documentation issues need to be addressed. For example, Ms. Fan was asked by a hospital within the Saint

Barnabas system to review a surge in denied claims for leuprolide depot that were unsuccessfully being appealed. She found that, because two different HCPCS codes and payment rates exist for leuprolide depot, differentiation of drug codes by diagnosis was required. This task was accomplished by modifying ordering screens and clarifying charge tickets and order sheets so that prescribing physicians were able to select the correct leuprolide depot charge. Once this corrected billing process was in place, the hospital was able to resubmit documentation illustrating the appropriate leuprolide depot J code to recoup lost revenue and prevent future denials.

Return on Investment Once a hospital has established a robust pharmacy revenue recovery program, it may be necessary to hire additional or ancillary personnel. Methods of justifying expansion include, foremost, developing a business plan to illustrate the expense of expansion and the potential ROI. The next step involves detailing potential contributions of additional personnel on ongoing and new projects. It is important to identify new opportunities associated with dollar figures and timelines. At the very minimum, projects should recover two to five times the cost of the expansion; therefore, hospital executives can realize an almost immediate ROI. By employing a pharmacy clinical financial analyst to manage drug and drug-related claims denials and other reimbursement challenges, SBHCS has achieved an unprecedented revenue recovery of more than $1.2 million over a one-year period (Figure). This very positive ROI was the culmination of various aforementioned activities such as contract amendments, root-cause analyses of drug denials and effective collaboration with multidisciplinary departments to resolve coding, billing or clinical policy issues. Future plans include development of more automated processes to track drug denials and streamlining communication processes to produce more timely notification of drug denials. Ideally, these improvements would result in quicker identification of reimbursement issues, increasing captured pharmacy revenue. Ultimately, the decision by SBHCS to hire an individual dedicated to reviewing pharmacy denials allowed the system to capture otherwise lost reimbursement dollars and, essentially, caused a paramount change to the traditional view of pharmacy as solely an expense line item.

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12 Clinical

Pharmacy Practice News â&#x20AC;˘ August 2010

Critical Care

Pharmacists Help Boost Surgical ICU Quality Measures at least one order for VTE prophylaxis during their hospital stays (J Hosp Med 2009;8:E15-E21).

icaid Services (CMS) to evaluate hospital performance. Other organizations, including the National Quality Forum

The Hines VA Hospital study was â&#x20AC;&#x2DC;another piece of [data] showing that a pharmacist engaged prospectively as a member of a multidisciplinary team can make a difference and impact the quality of patient care.â&#x20AC;&#x2122; â&#x20AC;&#x201D;William E. Dager, PharmD

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Tampa, Fla.â&#x20AC;&#x201D;The timing was perfect: In March 2008, just one month before the pharmacy department at Edward Hines Jr. VA Hospital in Hines, Ill., began decentralizing pharmacists to patient care floors, the hospitalâ&#x20AC;&#x2122;s surgical intensive care unit (SICU) launched a multidisciplinary rounding program. One of the decentralized pharmacists was assigned to the SICU, joining a team that also included an intensivist, surgical residents, nurses, dietitians and respiratory therapists. Within a year, the teamâ&#x20AC;&#x2122;s impact on patient safety became evident. A retrospective review of electronic medical records found that rates of adherence to two core quality measures relating to surgical care had increased significantly during the July 2008 to February 2009 study period compared with the same eight-month period one year earlier, before multidisciplinary rounds were initiated. Data from electronic medical records of 320 patients were evaluated for each period. â&#x20AC;&#x153;The timing worked really well to get one of those decentralized inpatient pharmacists not only up in the SICU working with other professionals but also attending multidisciplinary rounds every day,â&#x20AC;? said Beth Diehl, PharmD, the inpatient pharmacist who led the study reporting on the results of the multidisciplinary initiative. The study, presented at the American Society of Health-System Pharmacists 2010 Summer Meeting, found that one of the core measuresâ&#x20AC;&#x201D;the rate of appropriate venous thromboembolism (VTE) prophylaxis provided from 24 hours before surgery to 24 hours afterâ&#x20AC;&#x201D; had increased from 70.9% to 86.9%. In comparison, an unrelated study, focusing on 188,800 discharged surgical patients, found that 77.7% had received

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In the Hines VA study, the VTE analysis was based on whether or not patients received heparin, a heparin analogue, factor Xa inhibitor or warfarin. However, the use of mechanical VTE prophylaxis also was considered an appropriate alternative for certain patients for whom pharmacologic prophylaxis was contraindicated. Adherence to the second quality measureâ&#x20AC;&#x201D;the proportion of SICU patients whose antibiotic prophylaxis was discontinued within 24 hours after surgeryâ&#x20AC;&#x201D;improved from 91.3% to 99.1%. That percentage contrasted with a national average rate of 72% reported in a separate BlueCross BlueShield Association study (http://www.bcbs.com/ issues/uninsured/highmark-blue-crossblue-shiel.html). Exceptions to the 24-hour rule included patients who had undergone cardiac surgery. In those cases, 48 hours was considered an appropriate time limit for prophylactic antibiotic discontinuation. Both VTE prophylaxis and discontinuation of prophylactic antibiotics are among the Surgical Care Improvement Project (SCIP) National Quality Measures used by the Joint Commission and the Centers for Medicare & Med-

and professional medical and surgical groups, employ the same or similar quality performance benchmarks.

Program Expanding So far, the pharmacy decentralization initiative has resulted in the appointment of four pharmacists to patient care units. â&#x20AC;&#x153;We started initially with just one pharmacist assigned to a general medicine floor,â&#x20AC;? said Dr. Diehl. â&#x20AC;&#x153;As we built up our staff, we decentralized to the ICU floor as well as other units.â&#x20AC;? Dr. Diehl said she was currently rounding with the cardiovascular ICU team, and three other pharmacists were rounding with different general medicine teams throughout the 483-bed hospital. The next step, Dr. Diehl added, will be getting pharmacists into the emergency department and spinal cord injury wards. â&#x20AC;&#x153;Weâ&#x20AC;&#x2122;ve come a long way in a couple of years,â&#x20AC;? she said. William E. Dager, PharmD, pharmacist specialist at the University of California, Davis Medical Center, in Sacramento, said the Hines VA study was â&#x20AC;&#x153;another piece of [data] showing that a pharmacist engaged prospectively as a member of a multidisciplinary team can make a difference and impact the quality of patient care.â&#x20AC;?

Figure. SICU patients whose prophylactic antibiotics were discontinued within 24 hours of surgery. SICU, surgical intensive care unit

â&#x20AC;&#x153;These were surgical ICU patients,â&#x20AC;? Dr. Dager said. â&#x20AC;&#x153;Obviously, VTE and antibiotic stewardship are big concerns.â&#x20AC;? He noted, however, that there were â&#x20AC;&#x153;sometimes other clinical problems in the ICUâ&#x20AC;? that occurred, such as the presence of an epidural catheter, a history of heparin-induced thrombocytopenia or certain antibiotic allergies, that â&#x20AC;&#x153;can come into play as far as making decisions not only to provide prophylaxis and how long to provide it, but also how to do it to optimize the care of the patient.â&#x20AC;? In these situations, Dr. Dager said, the pharmacistâ&#x20AC;&#x2122;s â&#x20AC;&#x153;personal, intuitive inputâ&#x20AC;? can help to achieve optimal therapeutic outcomes with treatment targeted to the individual needs of the patient. â&#x20AC;&#x201D;Bruce and Joan Buckley

Slower Is Better for Antibiotic Infusions in ICU Las Vegasâ&#x20AC;&#x201D;Switching from the standard 30-minute dosing to a four-hour infusion of combination antibiotic piperacillin-tazobactam is associated with shorter stays in the intensive care unit (ICU) and reduced annual drug costs for critically ill patients, a new study shows. At the 2010 Annual Meeting of the Surgical Infection Society, a team of pharmacists and surgeons from New Jerseyâ&#x20AC;&#x2122;s Saint Barnabas Medical Center reported results from a retrospective study comparing standard dosing and extended infusion dosing of piperacillin-tazobactam. The antibiotic is frequently used to treat Pseudomonas

aeruginosa infections in critically ill patients, the authors noted. The study showed that critically ill patients who received the extended dosing spent significantly fewer days in the ICU compared with patients who were given standard dosing. And the more critically ill the patient was, the greater the benefit, the results suggested. Patients who had worse APACHE II scores showed the greatest reduction in ICU stay when the dosing was extended. â&#x20AC;&#x153;There have been a number of small studies looking at targeted patients or specific bugs. What makes this study unique is that itâ&#x20AC;&#x2122;s the first dataset

in an ICU setting to look at various levels of severity for any critically ill patient regardless of the reason they were there,â&#x20AC;? said lead author Daryl S. Schiller, PharmD, assistant director of clinical pharmacy services at Saint Barnabas Medical Center in Livingston. Extended dosing of piperacillintazobactam and similar antibiotics might be â&#x20AC;&#x153;extremely helpful in futureâ&#x20AC;? for keeping infection rates down, said Alicia Mohr, MD, associate professor

of surgery, University of Medicine and Dentistry of New Jersey in Newark. â&#x20AC;&#x153;We do it for some selected patients now,â&#x20AC;? she said. â&#x20AC;&#x153;Iâ&#x20AC;&#x2122;m happy to see someone looking at studying extended dosing, although what Iâ&#x20AC;&#x2122;d really like to see is a prospective, multicenter trial.â&#x20AC;? Resistance to the drug could decrease if extended dosing became standard, she said. â&#x20AC;&#x153;It might be best to use extended dosage in specific groups of patients

â&#x20AC;˘

see DOSING SWITCH, page 14

14 Clinical

Pharmacy Practice News â&#x20AC;˘ August 2010

Critical Care 6[aR_ZVaaR[a 1\`V[T 2eaR[QRQ 1\`V[T

DOSING SWITCH

continued from page 12

# !

Figure 1. Length of stay in the ICU.

Premixed Injection in either 4.8% Dextrose or 0.86% Sodium Chloride 5% Dextrose or 0.83% Sodium Chloride Brief Summary of Prescribing Information Cardene I.V. Premixed Injection in 4.8% Dextrose 20 mg in 200 mL (0.1 mg/mL) Each mL contains 0.1 mg nicardipine hydrochloride, 48 mg dextrose hydrous, USP, 0.0192 mg citric acid, anhydrous, USP, and 1.92 mg sorbitol, NF. Hydrochloric acid and/or sodium hydroxide may have been added to adjust pH to 3.7 to 4.7. Cardene I.V. Premixed Injection in 0.86% Sodium Chloride 20 mg in 200 mL (0.1 mg/mL)

Each mL contains 0.2 mg nicardipine hydrochloride, 50 mg dextrose hydrous, USP, and 0.0384 mg citric acid, anhydrous, USP. Hydrochloric acid and/or sodium hydroxide may have been added to adjust pH to 3.7 to 4.7. CardeneÂŽ I.V. Premixed Injection in 0.83% Sodium Chloride 40 mg in 200 mL (0.2 mg/mL) Each mL contains 0.2 mg nicardipine hydrochloride, 8.3 mg sodium chloride, USP, 0.0384 mg citric acid, anhydrous, USP, and 3.84 mg sorbitol, NF. Hydrochloric acid and/or sodium hydroxide may have been added to adjust pH to 3.7 to 4.7. INDICATION AND USAGE: For the short-term treatment of hypertension when oral therapy is not feasible or desirable. For prolonged control of blood pressure, patients should be transferred to oral medication as soon as their clinical condition permits. CONTRAINDICATIONS: CardeneÂŽ I.V. is contraindicated in patients with known hypersensitivity. CardeneÂŽ I.V. is also contraindicated in patients with advanced aortic stenosis because part of the effect of CardeneÂŽ I.V. is secondary to reduced afterload. Reduction of diastolic pressure in these patients may worsen rather than improve myocardial oxygen balance. WARNINGS: BETA-BLOCKER WITHDRAWAL: Nicardipine is not a beta-blocker and provides no protection against the dangers of abrupt beta-blocker withdrawal; any such withdrawal should be by gradual reduction of dose of beta-blocker. RAPID DECREASES IN BLOOD PRESSURE: No clinical events have been reported suggestive of a too rapid decrease in blood pressure with CardeneÂŽ I.V. However, as with any antihypertensive agent, blood pressure lowering should be accomplished over as long a time as is compatible with patientâ&#x20AC;&#x2122;s clinical status. USE IN PATIENTS WITH ANGINA: Induction or exacerbation of angina has been seen in less than 1% of coronary artery disease patients treated with CardeneÂŽ I.V. Increased frequency, duration, or severity of angina has been seen with chronic oral CardeneÂŽ therapy. USE IN PATIENTS WITH CONGESTIVE HEART FAILURE: CardeneÂŽ I.V. reduced afterload without impairing myocardial contractility in preliminary hemodynamic studies of CHF patients. However, in vitro and in some patients, a negative inotropic effect has been observed. Exercise caution when using CardeneÂŽ I.V., particularly in combination with a beta-blocker, in patients with CHF or signiďŹ cant left ventricular dysfunction. USE IN PATIENTS WITH PHEOCHROMOCYTOMA: Limited clinical experience exists in these patients; therefore, exercise caution when administering CardeneÂŽ I.V. PERIPHERAL VEIN INFUSION SITE: To minimize the risk of peripheral venous irritation, it is recommended that the site of infusion of CardeneÂŽ I.V. be changed every 12 hours. PRECAUTIONS: GENERAL: Blood Pressure: CardeneÂŽ I.V. decreases peripheral resistance; monitoring of blood pressure during administration is required. CardeneÂŽ I.V., like other calcium channel blockers, may occasionally produce symptomatic hypotension. Caution is advised to avoid systemic hypotension when administering the drug to patients who have sustained an acute cerebral infarction or hemorrhage. Use in Patients with Impaired Hepatic Function: Nicardipine is metabolized in the liver; exercise caution in patients with impaired liver function or reduced hepatic blood ďŹ&#x201A;ow; consider use of lower dosages. Nicardipine administered intravenously has been reported to increase hepatic venous pressure gradient by 4 mmHg in cirrhotic patients at high doses (5 mg/20 min). Use CardeneÂŽ I.V. with caution in patients with portal hypertension. Use in Patients with Impaired Renal Function: When CardeneÂŽ I.V. was given to mild to moderate hypertensive patients with moderate renal impairment, a signiďŹ cantly lower systemic clearance and higher AUC was observed. These results are consistent with those seen after oral administration of nicardipine. Careful dose titration is advised when treating renally impaired patients. DRUG INTERACTIONS: Since CardeneÂŽ I.V. may be administered to patients already being treated with other medications, including other antihypertensive agents, careful monitoring of these patients is necessary to detect and promptly treat any undesired effects from concomitant administration. Beta-Blockers: In most patients, CardeneÂŽ I.V. can safely be used with beta-blockers. However, exercise caution when using this combination in CHF patients (see WARNINGS). Cimetidine: Cimetidine has been shown to increase nicardipine plasma concentrations following CardeneÂŽ capsule administration; carefully monitor concomitant use. Data with other histamine-2 antagonists are not available. Digoxin: Studies have shown that CardeneÂŽ capsules usually do not alter digoxin plasma concentrations; however, as a precaution, evaluate digoxin levels when initiating concomitant CardeneÂŽ I.V. therapy. Fentanyl anesthesia: Hypotension has been reported during fentanyl anesthesia with concomitant use of a betablocker and a calcium channel blocker. Even though such interactions were not seen during clinical studies with CardeneÂŽ I.V. (nicardipine hydrochloride), an increased volume of circulating ďŹ&#x201A;uids might be required if such an interaction were to occur. Cyclosporine: Concomitant use of CardeneÂŽ capsules and cyclosporine results in elevated plasma cyclosporine levels. Monitor cyclosporine plasma levels closely and reduce its dose accordingly. In vitro interaction: The plasma protein binding of nicardipine was not altered when therapeutic concentrations of furosemide, propranolol, dipyridamole, warfarin, quinidine, or naproxen were added to human plasma in vitro. CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: Rats treated with nicardipine in the diet (at doses of 5, 15, or 45 mg/kg/day) for two years showed a dose-dependent increase in thyroid hyperplasia and neoplasia (follicular adenoma/carcinoma). One- and three-month rat studies have suggested that these results are linked to a nicardipine-induced reduction in plasma thyroxine (T4) levels, with resultant increase in plasma levels of thyroid stimulating hormone (TSH). Chronic elevation of TSH is known to cause hyperstimulation of the thyroid. In rats on an iodine deďŹ cient diet, nicardipine administration for one month was associated with thyroid hyperplasia that was prevented by T4 supplementation. Mice treated with nicardipine in the diet (at concentrations calculated to provide daily dosage levels of up to 100 mg/kg/day) for up to 18 months showed no evidence of neoplasia of any tissue and no evidence of thyroid changes. There was no evidence of thyroid pathology in dogs treated with up to 25 mg nicardipine/kg/day for one year and no evidence of effects of nicardipine on thyroid function (plasma T4 and TSH) in man. There was no evidence of a mutagenic potential in genotoxicity tests conducted in microbes, mice and hamsters. No fertility impairment was seen in male or female rats administered oral nicardipine doses as high as 100 mg/kg/day (50 times the 40 mg TID maximum recommended human dose [MRHD] in man, assuming a patient weight of 60 kg). PREGNANCY CATEGORY C: CardeneÂŽ I.V. administered at doses up to 5 mg/kg/day and up to 0.5 mg/kg/day to pregnant rats and rabbits, respectively, produced no embryotoxicity or teratogenicity. Embryotoxicity, but not teratogenicity, was seen at 10 mg/kg/day in rats and at 1 mg/kg/day in rabbits. Nicardipine was embryocidal at oral doses of 150 mg/kg/day, given during organogenesis, to pregnant white rabbits but not at 50 mg/kg/day (25 times MRHD). No adverse effects on the fetus were observed when albino rabbits were treated, during organogenesis, with up to 100 mg/kg/day of nicardipine. Pregnant rats receiving oral doses up to 100 mg/kg/day (50 times MRHD) showed no evidence of embryolethality or teratogenicity. However, dystocia and reductions in

Figure 2. Piperacillintazobactam use.

birth weights, neonatal survival, and neonatal weight gain were noted. There are no adequate and well-controlled studies in pregnant women. CardeneÂŽ I.V. should be used in pregnancy only if the potential beneďŹ t justiďŹ es the potential risk to the fetus. NURSING MOTHERS: Studies in rats have shown signiďŹ cant concentrations of nicardipine in maternal milk. Therefore, use in nursing mothers is not recommended. PEDIATRIC USE: Safety and efďŹ cacy in patients under the age of 18 have not been established. USE IN THE ELDERLY: In clinical studies, no signiďŹ cant difference was observed in the antihypertensive effect of CardeneÂŽ I.V. in patients â&#x2030;Ľ65 years compared to other adult patients. Clinical studies of nicardipine did not include sufďŹ cient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identiďŹ ed differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reďŹ&#x201A;ecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. ADVERSE EXPERIENCES: 244 patients participated in two multicenter double-blind, placebo-controlled trials of CardeneÂŽ I.V. Adverse effects were generally not serious and most were expected effects of vasodilation. Some adverse effects required dosage adjustments. Therapy was discontinued in approximately 12% of patients due mainly to hypotension, headache, and tachycardia. The following numbers represent percentage of patients with adverse experiences during the double-blind portion of controlled trials with CardeneÂŽ I.V. (n=144) versus Placebo (n=100), respectively.

Each mL contains 0.1 mg nicardipine hydrochloride, 8.6 mg sodium chloride, USP, 0.0192 mg citric acid, anhydrous, USP, and 1.92 mg sorbitol, NF. Hydrochloric acid and/or sodium hydroxide may have been added to adjust pH to 3.7 to 4.7. CardeneÂŽ I.V. Premixed Injection in 5% Dextrose 40 mg in 200 mL (0.2 mg/mL)

4_NZ`

1Nf`

who would benefit the most.â&#x20AC;? Piperacillin-tazobactam, a Ă&#x;-lactam antibiotic typically given in 30-minute infusions, has a short half-life of two hours. As a result, it must be redosed every six hours in critically ill patients. Some studies have suggested that an extended dosing infusion will improve the effectiveness of the antibiotic by providing a longer duration of active antibiotic concentrations. An earlier study from a hospital in

Percent of Patients with Adverse Experiences During the Double-Blind Portion of Controlled Trials CardeneÂŽ (n=144)

Placebo (n=100)

14.6 0.7 0.7 0.7

2.0 0.0 0.0 0.0

Cardiovascular Hypotension Tachycardia ECG abnormality Postural hypotension Ventricular extrasystoles Extrasystoles Hemopericardium Hypertension Supraventricular tachycardia Syncope Vasodilation Ventricular tachycardia

5.6 3.5 1.4 1.4 1.4 0.7 0.7 0.7 0.7 0.7 0.7 0.7

1.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0

Digestive Nausea/vomiting

4.9

1.0

Injection Site Injection site reaction Injection site pain

1.4 0.7

0.0 0.0

Metabolic and Nutritional Hypokalemia

0.7

0.0

Nervous Dizziness Hypesthesia Intracranial hemorrhage Paresthesia

1.4 0.7 0.7 0.7

0.0 0.0 0.0 0.0

Respiratory Dyspnea

0.7

0.0

Skin and Appendages Sweating

1.4

0.0

Urogenital Polyuria Hematuria

1.4 0.7

0.0 0.0

Adverse Experience Body as a Whole Headache Asthenia Abdominal pain Chest pain

RARE EVENTS: The following events have been reported in clinical trials or in the literature with intravenous use of nicardipine. Body as a Whole: fever, neck pain. Cardiovascular: angina pectoris, atrioventricular block, ST segment depression, inverted T wave, deep vein thrombophlebitis. Digestive: dyspepsia. Hemic and Lymphatic: thrombocytopenia. Metabolic and Nutritional: hypophosphatemia, peripheral edema. Nervous: confusion, hypertonia. Respiratory: respiratory disorder. Special Senses: conjunctivitis, ear disorder, tinnitus. Urogenital: urinary frequency. Sinus node dysfunction and myocardial infarction, possibly due to disease progression, have been seen in patients on chronic oral nicardipine therapy. OVERDOSAGE: Several overdosages with orally administered nicardipine have been reported. One adult patient allegedly ingested 600 mg of nicardipine (standard [immediate release] capsules), and another patient, 2160 mg of the sustained release formulation of nicardipine. Symptoms included marked hypotension, bradycardia, palpitations, ďŹ&#x201A;ushing, drowsiness, confusion and slurred speech. All symptoms resolved without sequelae. An overdosage occurred in a one-year-old child who ingested half of the powder in a 30 mg nicardipine standard capsule. The child remained asymptomatic. Based on results obtained in laboratory animals, lethal overdose may cause systemic hypotension, bradycardia (following initial tachycardia) and progressive atrioventricular conduction block. Reversible hepatic function abnormalities and sporadic focal hepatic necrosis were noted in some animal species receiving very large doses of nicardipine. For treatment of overdosage, standard measures including monitoring of cardiac and respiratory functions should be implemented. The patient should be positioned so as to avoid cerebral anoxia. Frequent blood pressure determinations are essential. Vasopressors are clinically indicated for patients exhibiting profound hypotension. Intravenous calcium gluconate may help reverse the effects of calcium entry blockade. DOSAGE AND ADMINISTRATION: DOSAGE MUST BE INDIVIDUALIZED depending on severity of hypertension and patient response. Monitor blood pressure during and after the infusion; avoid too rapid or excessive reductions in systolic or diastolic blood pressure. Cardene I.V. Premixed Injection is supplied as a single-use, ready-to-use, iso-osmotic solution for intravenous administration in a 200 mL GALAXY container with 20 mg (0.1 mg/mL) nicardipine hydrochloride in either dextrose or sodium chloride, or with 40 mg (0.2 mg/mL) nicardipine hydrochloride in either dextrose or sodium chloride. Cardene I.V. Premixed Injection should not be combined with any product in the same intravenous line or premixed container. Protect from light; store in carton until ready to use. Protect from freezing. Avoid excessive heat.

See package insert for full prescribing information. For questions of a medical nature, or to report an adverse event, please call 1-877-207-5802. CardeneÂŽ I.V. is a registered trademark of EKR Therapeutics, Inc. Manufactured by: Baxter Healthcare Corporation DeerďŹ eld, IL 60015 USA Marketed by: EKR Therapeutics, Inc. Bedminster, NJ 07921 USA Issued July 2009 CAR09-240

Albany, N.Y. showed that critically ill patients infected with P. aeruginosa had significantly lower 14-day mortality and shorter hospital stays when they received extended-infusion therapy (3.375 g IV for 30 minutes every four or six hours) compared with intermittent-infusion piperacillin-tazobactam therapy (Clin Infect Dis 2007;44:357363). Mortality was 12.2% versus 31.6% in the extended- and intermittenttherapy groups, respectively (P=0.04). Median length of hospital stay was 21 versus 38 days (P=0.02), according to the investigators. Based on the earlier reports, Dr. Schiller and his colleagues switched to an extended-dosing strategy in March 2009 for all ICU patients. They compared the outcomes for patients treated in the three months before the switch (n=60) and the four months that followed (n=87). Patients who died in the ICU were excluded from the analysis. The study showed that severely critically ill patients with APACHE II scores of 17 or greater who received extended dosing had markedly shorter ICU stays at a mean of 3.4 days compared with 7.3 days for patients with the intermittent infusion (P=0.06). Patients with APACHE II scores of less than 17 also had shorter stays with extended dosing, but the difference was not significant (8.3 vs. 6.8 days; P=0.8). The investigators said they did not know why sicker patients responded better to the extended dosing. â&#x20AC;&#x153;The drug may not distribute as well in a sicker patient so maybe by prolonging the infusion, they are getting a better exposure to the drug,â&#x20AC;? said Dr. Schiller. A number of factors likely influenced patientsâ&#x20AC;&#x2122; length of stay in the ICU. â&#x20AC;&#x153;From an antibiotic point of view, if they were in the ICU for an infectious reason, they probably had a more efficient treatment with the extended dosing,â&#x20AC;? he said. â&#x20AC;&#x153;By keeping the serum level above the threshold for a longer amount of time, you are forcing the antibiotic to work at its maximum potential.â&#x20AC;? The extended dosing program was associated with reduced overall use of piperacillin-tazobactam. The average daily dose declined from 9.01 to 8.02 g (P=0.77) after initiation of the program. The average duration of therapy was 6.2 (Âą4.76) days. The savings in drug use alone amount to about $8,700 per year for the ICU, Dr. Schiller said. The overall savings are expected to be much higher once length of stay is taken into account, he added. The researchers did not receive financial or personal support from any commercial entity with a direct or indirect interest in the study. â&#x20AC;&#x201D;Christina Frangou

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16 Clinical

Pharmacy Practice News • August 2010

Critical Care

A Sepsis Success Story Gita Wasan Patel, PharmD

Nicki Roderman, MSN, RN, CCRN, CNRN

Clinical Pharmacy Coordinator

Critical Care Clinical Specialist

Department of Pharmacy Services, Medical Center of Plano, Plano, Texas

ccording to the Centers for Disease Control and Prevention, in 2006 septicemia was the 10th leading cause of death in the United States, claiming 34,234 lives annually and more than 500 lives daily.1 In 2005, according to the Society of Critical Care Medicine (SCCM), mortality among patients with severe sepsis ranged between 30% and 50%, and was as high as 60% among those with septic shock.2 These sobering statistics prompted us to investigate the mortality rate in sepsis patients at the Medical Center of Plano. We found that in 2006, the center’s sepsis mortality rate was 62.2%. SCCM’S Surviving Sepsis Campaign (SSC) launched with the stated goal of reducing mortality from severe sepsis by 25% by 2009.2 Because of the excessive mortality rate and the publication of the SCCM Surviving Sepsis Campaign Guidelines (SSCG),3 we decided to pursue the implementation of a sepsis program at our institution. A multidisciplinary team was created that would focus on the development, implementation and monitoring of the sepsis program. The team included the medical directors of our intensive care unit (ICU), emergency department (ED) and hospitalist services, as well as a critical care clinical nurse specialist, the nursing director of critical care, the clinical pharmacy coordinator and the ED nurse clinician. With the SSCG serving as a guide, this multidisciplinary team developed a sepsis screening tool and initial lab, drug and diagnostic orders for two patient groups: those with suspected sepsis in the ED and those with diagnosed severe sepsis in the ICU. We used the Institute for Healthcare Improvement’s Sepsis Individual Chart Measurement Data Collection Toolkit to guide us in this process, which took approximately six months. The sepsis orders were subsequently approved by the Special Care, Pharmacy and Therapeutics and Medical Executive Committees. Education was provided for the medical, nursing and pharmacy staffs over a two-month period.

Collaboration a Challenge Some of the biggest obstacles involved collaboration between the ED, ICU and pharmacy. First, part of the program required sepsis patients to have central lines. Therefore, there was an issue as to who would insert the line. The ED took the responsibility of placing lines.

Lactic acid levels are an integral part of the diagnosis and management of sepsis patients, but this lab test was not being done in-house. (Although the pathophysiology is not well understood, severe sepsis and septic shock patients tend to have hyperlactemia or lactic acidosis. Therefore, lactic acid levels play an important diagnostic role in these patients.) The sepsis multidisciplinary team asked the laboratory department to begin obtaining lactic acid levels in-house. From the pharmacy perspective, it was essential to improve the turnaround time for antibiotics and vasopressor drips. There are data that suggest that the earlier sepsis patients receive the first dose of an appropriate antibiotic, the better the outcome.4 Education was conducted for the pharmacy staff to emphasize the importance of

Both the suspected and diagnosed severe sepsis order sets, or “bundles,” called for the monitoring of ScvO2 (tissue oxygenation) via the Pre-Sep oximetry catheter (Edwards Lifesciences). The ED and ICU staffs needed to be trained on the acquisition of these catheters and compatible monitors, and how to calibrate the catheter and read or interpret the results. The staffing of nurses in both the ICU and the ED needed to be evaluated to ensure that critically ill patients received the nursing attention they required. In an effort to provide additional support, the ICU began dispatching a nurse to the ED when a sepsis patient was identified to aid in patient monitoring, care and line placement, and to expedite the transfer of the patient from the ED to the ICU.

Table 1. Patient Demographics And Clinical Characteristics

Characteristic

2006 (Non-Bundle) (N=53)

2007 (Bundle) (N=59)

Age, y, mean

68.4+13.8

63.2+18.3

Male, %

55.6

Blood glucose, mg/dL, median (range)

145 (64-501)

136.5 (70-313)

APACHE II score, mean

28.4+9.4

28.5+10.1

Initiation of drotrecogin alfa, %

11.1

18.3

Initiation of steroids, %

38.9

48.3

Patients on ventilator, %

46.7

Ventilator use, d, median (range)

7.5 (1-74)

7 (1-22)

Hospital length of stay, d, median (range)

9.5 (1-74)

9 (1-39)

ICU length of stay, d, median (range)

6 (1-74)

5 (1-36)

d, days; ICU, intensive care unit; y, years P=NS for all comparisons

Table 2. Fluids and Vasopressors 2006 (Non-Bundle) (N=53)

2007 (Bundle) (N=59)

P Value

Median days of vasopressor use (range)

3 (1-24)

2 (1-16)

0.024

Median milliliters of fluid administered within first 24 h (range)

2,200 (100-13,996)

7,143 (1,000-19,104)

<0.0001

Outcome

early, goal-directed therapy for sepsis patients. Finally, because our institution does not have an intensivist program, there were discussions as to which practitioner would be responsible for initiating the diagnosed severe sepsis program once the patient was transferred to the ICU from the ED. After much discussion and education, a group was organized, including hospitalists, internists, surgeons and pulmonologists, to ensure compliance with the sepsis bundle.

Drug Order Sets Developed Diagnostic and drug order sets for sepsis were activated and training was completed by the end of 2006. We went live with the sepsis bundle program on Jan. 1, 2007. In January 2008, we decided to do a retrospective review comparing all sepsis patients in 2006 with all sepsis patients treated with the sepsis bundle in 2007. Data collected included demographics, APACHE II score, initiation of vasopressors, days on vasopressors, blood glucose levels, initiation of drotrecogin alfa (Xigris, Eli Lilly), initiation of steroids, initiation of ventilator use, ventilator days, times to cultures, time to first dose of antibiotics, time to transfer from the ED to the ICU, fluid resuscitation in the first 24 hours, percentage of patients started on dialysis, ICU and hospital lengths of stay and mortality. These were the end points of the study to ensure the sepsis bundle was efficacious. Demographics, basic patient baseline parameters, initiation of drotrecogin alfa, steroids, ventilator use, ventilator days, and ICU and hospital lengths of stay were similar for the two groups (Table 1). Sepsis bundle patients were on vasopressors for a significantly shorter time and significantly more fluids were given to these patients (Table 2). Significant differences were seen for median time to culture, median time to the first dose of antibiotic and the mean time to transfer from the ED to ICU (Figure 1). Fewer sepsis bundle patients were on vasopressors or initiated on dialysis (Figure 2). The fact that no bundle patients were initiated on dialysis was particularly interesting, considering the fact that these patients received significantly more IV fluids. Most impressive was a 41.1% decrease in mortality in the sepsis bundle patients in 2007 compared with non-bundle patients in 2006 (Figure 3).

Significant Savings From an economic perspective, we

Clinical 17

Pharmacy Practice News â&#x20AC;˘ August 2010

Mortality Reductions Persist There are many innovative aspects of the sepsis program we have implemented at our institution. Foremost

is the exceptional 41.1% reduction in mortality, which exceeds the goal set by SCCM. This decrease in mortality is unparalleled in the literature. We have continued analysis of mortality in our septic patients and have sustained these impressive outcomes. From January 2007 through December 2008, there were 118 sepsis patients treated with the bundle, with a mortality rate of 22%. The second end point that is impressive is that no patients on the sepsis bundle were initiated on dialysis. There was much hesitation about administering large amounts of fluid to these patients for fear of renal or respiratory failure. The fact that renal failure did not become a problem was exemplary. Similarly, there were no significant differences in the number of patients on the ventilator or ventilator days despite the large amount of fluid the sepsis bundle patients received. Additionally, the cost savings to the hospital was impressive because these were hard-dollar savings. Fewer hospital resources were required by the sepsis bundle patients, saving time and money for the hospital and staff. Often, studies on the implementation of a sepsis bundle are performed at large academic institutions. The truly novel aspect of this program was that it was done at a medium-sized community hospital. Our institution does not have any interns or residents; we solely have private practice physicians and a hospitalist group. To get buy-in from all types of physicians and to get everyone working in a collaborative fashion to achieve a common goal is a significant accom-

plishment for any institution, especially for a community hospital. Also, putting together a focused multidisciplinary team to optimize all facets of the program was a novel aspect of our success. Members of the team had diverse specialty areas and all were committed to the success of the program. Pharmacy practice at our institution has flourished with this sepsis program. Because of the autonomy and visibility accorded to the department, the trust and communication between the medical and pharmacy staffs and the nursing and pharmacy staffs have increased exponentially. The medical staff is much more amenable to pharmacy recommendations and automatic pharmacy interchanges. Pharmacists have an increased level of confidence in the service they provide and have augmented their clinical skills set. We are able to implement more advanced clinical pharmacy services, such as more aggressive antibiotic streamlining, because of the success of the sepsis bundle program. Because of the increased visibility of the pharmacy staff in the ICU, communication with the nursing staff also has improved tremendously. There is an improved sense of teamwork with the nursing department that decreases delays in therapy and employee dissatisfaction.

Proud of Accomplishments Overall, our institution is very proud of the impact the sepsis bundle has had on the care of the sepsis patient. Our patients have realized a tremendous clinical benefit and the hospital has enjoyed an

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:RQVN[ aVZR a\ a_N[`SR_ S_\Z 21 a\ 00B ZV[ P

Figure 1. Times to cultures and transfers. P=0.002;

=NaVR[a` \[ cN`\]_R``\_`N

=NaVR[a` V[VaVNaRQ \[ QVNYf`V`O

Figure 2. Patients on vasopressors and dialysis. a

P=0.011; b P=0.02

# $

# #

Figure 3. Mortality. P<0.0001

economic benefit. Pharmacy has matured in its role as a pharmacotherapy specialist. Teamwork and the success of a multidisciplinary approach to any problem have been validated. The fact that all of this was achieved by a community hospital further solidifies the concept that cutting-edge clinical pharmacy is not limited to academic centers. We continue to expand the autonomy of the pharmacist and follow our sepsis patients in an effort to maintain our superior clinical outcomes and achieve further success.

References 1. Centers for Disease Control Fast Stats. Leading causes of death. http://www.cdc.gov/nchs/ fastats/lcod.htm. Accessed May 21, 2009.

3. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858-873.

# $

2. Surviving Sepsis Campaign Web site. http:// www.survivingsepsis.org/Pages/default.aspx. Accessed July 8, 2010.

# $

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The sepsis care team at the Medical Center of Plano, in Texas (L-R): Nicki Roderman, MSN; John Saad, MD; Hollie Gehring, MSN; and Gita Wasan Patel, PharmD.

AVZR ZV[

examined the impact that the following parameters had on cost: ICU length of stay, fluids administered within the first 24 hours of care, vasopressor days, dialysis days, central line/ScvO2, ventilator days and use of drotrecogin alfa. This examination yielded a $9,772 savings per patient who received the bundle versus those not receiving it. Overall, the annual cost savings realized by our institution was $576,548. Many changes in the pharmacy department and pharmacy practice patterns occurred as a result of this sepsis program. First, the increased awareness of the critical nature of the first 24 hours of a septic patientâ&#x20AC;&#x2122;s care contributed to the decrease in the time to the first dose of antibiotics. Second, built into the program was the autonomy for pharmacy to automatically adjust doses for all antibiotics, including vancomycin. In the past, we relied on the physician to write for a vancomycin consult. However, by building these drug orders into the sepsis management algorithm, our pharmacists were able to dose vancomycin from the start of therapy. This is particularly important, considering the new guidelines for vancomycin recently published in the American Journal of Health-System Pharmacists that advocate the use of a loading dose and higher trough levels of the antibiotic for sepsis patients.4 Third, because using the bundle was optional for the medical staff, some sepsis patients were not being treated with the bundle. Therefore, another multidisciplinary team was established, including a pulmonologist, ICU nurse manager, pharmacist, respiratory therapist, dietician and case manager. This team rounds in the ICU twice a weekâ&#x20AC;&#x201D;a process that allows the team to identify sepsis patients who need intervention and formalizes the dialogue between the team and the attending physician. Pharmacy plays a large role by identifying patients with inappropriate antibiotics, lack of deep vein thrombosis prophylaxis and uncontrolled blood sugar, and ensuring appropriate vaccinations. This type of intensive monitoring of this patient population would not have occurred without the implementation of the sepsis bundle program. Because pharmacy identified multiple areas for improvement in non-bundled patients, the medical executive committee at our institution recently recognized the sepsis bundle program to be the standard care for all sepsis patients and made it mandatory that all sepsis patients be initiated on the sepsis bundle.

=R_PR[a \S =NaVR[a`

Critical Care

P=0.001; c P=0.011

ABX, antibiotics; CCU, critical care unit; ED, emergency department; min, minutes

4. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589-1596. 5. Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health-Syst Pharm. 2009;66:82-98.

18 Clinical

Pharmacy Practice News • August 2010

FAQ

The Case for Immunoglobulins in Chronic Pain Q: Can intravenous immunoglobulins (IVIGs) be used to treat complex regional pain syndrome (CRPS)?

A: Although IVIGs have been used for dozens of off-label indications since they first became available more than three decades ago, there are only five FDAapproved indications (primary immunodeficiency, idiopathic thrombocytopenia purpura, chronic lymphocytic leukemia, Kawasaki’s disease and chronic inflammatory demyelinating polyneuropathy) among the seven IVIG products marketed in the United States. There are several reasons why so few indications have been approved. One reason is the difficulty of studying “orphan diseases” and using placebo controls. The total number of patients with some of the off-label indications, such as complex regional pain syndrome (CRPS), is very small, so finding an eligible study population is difficult. Additionally, using a placebo control makes the study population even smaller. A second issue is that crossover studies are necessary, but it may prove to be an ethical dilemma to enroll patients in the placebo arm of a study. The third challenge is that it is difficult to blind patients and caregivers from the knowledge of which product is the study drug. However, a blinded design is especially important when assessment of a primary end point, such as pain, can be considered subjective. In CRPS, the perception of pain, even when translated to a pain scale, is subjective and easily can be biased. Another final challenge to consider when studying the use of IVIG for a particular indication is that the diagnosis of some of these diseases is not always definitive; it often is a diagnosis of exclusion rather than one based on welldefined and objective markers. So what exactly is CRPS and how do we recognize the symptoms (Table)? The other eponyms for this disorder are reflex sympathetic dystrophy, causalgia, Sudeck syndrome and algodystrophy. Type 1 CRPS is classified as a posttraumatic reaction for which there was no illness or injury directly damaging the nerves of the affected limb. Type 2 CRPS is classified as that resulting from

Table. Characteristics of CPRS Symptoms

Complications

Burning pain in an extremity

Muscle wasting due to lack of use

Skin sensitivity

Contracture due to lack of use

Changes in skin temperature or color

Spread of affected area

Changes in hair or nail growth

Spread to opposite limb

Joint stiffness or swelling

Symptoms in distant areas of body

Muscle spasms or atrophy Decreased mobility of affected limb

distinct nerve injury. Injuries resulting in CRPS vary from gunshots and heart attacks to sprained ankles.1 Because CRPS tends to persist and spread, it is important to identify and treat it early before muscle wasting and permanent damage occur. It also is important for the patient to be able to identify when symptoms were first noticed and whether symptoms were related to an accident or illness. Did the symptoms follow surgery and how long or continuously have the symptoms persisted? Also what, if anything, improves or worsens the symptoms? Because there is no single definitive test for CRPS, other tests are necessary to rule out other diagnosis.

Treatment Options Common treatments target symptoms. Nonsteroidal anti-inflammatory agents are used for pain, antidepressants for “phantom pain” and gabapentin for neuropathic pain, for example. When the pain is intractable, opioid pain medications often are prescribed, with caution. Corticosteroids and cyclooxygenase-2 inhibitors are used to relieve inflammation and swelling, and bisphosphonates are used to combat bone loss. Topical treatments to reduce skin sensitivity and cold or warm compresses to provide skin temperature relief have been used. Other treatments from physical therapy to biofeedback and the use of transcutaneous electrical nerve stimulation units also have been used to provide symptomatic relief. The idea that IVIG therapy would be beneficial in CRPS is based on the pre-

sumption that the disorder somehow has an immune component. Data from Kohr et al showed that 39% (13 of 30) of patients with CRPS have surface-binding autoantibodies against an inducible autonomic nervous system autoantigen, suggesting an autoimmune mechanism for the syndrome.2 In a review article, Dalakis suggested that IVIG suppresses proinflammatory cytokines and may be beneficial in patients with chronic pain syndromes.3 In a prospective open-label cohort study, Goebel et al treated 130 patients with 12 different chronic pain syndromes, including CRPS (11 patients), using IVIG.4 During this study, 20% of patients received greater than 70% pain relief. Six patients (4.6%) had an increase in symptoms. Patients with pain of short duration had the highest rate of relief (33.8%). More recently, Goebel explored the use of IVIG in a small study of patients with CRPS.5 Patients with long-standing CRPS (six to 30 years) were entered in a double-blind, controlled crossover study. Patients with a pain rating of greater than 4 on a 10-point scale were given either a total dose of 500 mg/kg of IVIG (250 mg/kg for two consecutive days) or normal saline and crossed over after 28 days. Of the 13 patients enrolled, 12 completed the trial. The pain intensity scale was 1.55 units lower in the IVIG group than in the normal saline group. Additionally, three of the patients reported a 50% decrease in pain with IVIG compared with placebo. Although the sample size was very small, the difference was significant (P<0.001;

95% confidence interval, 1.29-1.82). This study is encouraging for refractory CRPS patients, who might benefit from IVIG Jerry Siegel, PharmD therapy. Overall there is both observational and literature-based evidence, although limited, to suggest that IVIG could be considered for the treatment of CRPS. Many questions remain as to the appropriate dose and at what stage of treatment would IVIG be most beneficial to patients with this syndrome. More studies are needed to validate the autoimmune basis of this disorder and the treatment algorithm for the use of IVIG. Additional education to help in early diagnosis of CRPS also would be beneficial.

References 1. Mayo Clinic. Complex regional pain syndrome. http://www.mayoclinic.com/health/ complex-regional-pain-syndrome/DS00265/ DSECTION=symptoms. Accessed July 13, 2010. 2. Kohr D,Tschernatsch M, Schmitz K, et al. Autoantibodies in complex regional pain syndrome bind to a differentiation-dependent neuronal surface autoantigen. Pain. 2009;143:246-251. 3. Dalakas M. Role of IVIg in autoimmune, neuroinflammatory and neurodegenerative disorders of the central nervous system: present and future prospects. J Neurol. 2006;253(suppl 5):V/25-V/32. 4. Goebel A, Netal S, Schedel R, Sprotte G. Human pooled immunoglobulin in the treatment of chronic pain syndromes. Pain Med. 2002;3:119-127. 5. Goebel A, Baranowski A, Maurer K, Ghiai A, McCabe C, Ambler G. Intravenous immunoglobulin treatment of the complex regional pain syndrome. A randomized trial. Ann Intern Med. 2010;152:152-158.

CORRECTION:

n the January issue of PPN in the IVIG FAQ article on immunoglobulins and obesity, one of the references was incorrectly listed. The correct reference is the following: Provan D, Nokes TJC, Agrawal S, Winer JB, Wood P, IVIg Guideline Development Group of the IVIg Expert Working Group. National Health Service. Clinical guidelines for the use of immunoglobulin. http:// webarchive.nationalarchives.gov.uk/+/ www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_080790.

Study Highlights Risk for Fatalities With Methadone

disproportionate number of opioidrelated overdose deaths involve methadone, new research suggests. “While methadone is an excellent pain medicine, it is trickier to use than other opioids,” said investigator Lynn Webster, MD. “Our results suggest there may remain a knowledge deficit, even among pain experts, about how to use it.”

Between 2001 and 2005, deaths related to opioids increased by 260%, according to data from the Drug Enforcement Administration (Product No. 2009L0487; www.usdoj.gov/ndic). LifeSource, a nonprofit group cofounded by Dr. Webster, medical director of Lifetree Pain Clinic, Salt Lake City, Utah, convened a panel of experts to study the reasons

behind these deaths as part of its Zero Unintentional Deaths campaign, which aims to reduce opioid-related deaths. The panel collected data from several sources: 91 PubMed, state and local reports on opioid-related fatalities; 35 malpractice suits involving opioids; and data from the Utah Department of Health campaign to reduce deaths from opioid use. The

authors presented their findings in poster form (abstract 228) at the American Academy of Pain Medicine’s annual conference in San Antonio. The panel found that methadone played a role in more deaths, proportional to outpatient prescriptions filled, than any other opioid. Although

•

see METHADONE, page 22

Clinical 21

Pharmacy Practice News â&#x20AC;˘ August 2010

Cardiology

continued from page 1

The task force report was prompted, in part, by a March 2010 black box warning that was added to clopidigrel labeling, cautioning that certain populations, particularly poor cytochrome P450 (CYP)-2C19 metabolizers, do not respond well to to the drug. This follows years of clinical trials documenting the problem. Does this variability in clopidogrel response matter? â&#x20AC;&#x153;Oh yes it does,â&#x20AC;? said speaker Robert L. Page II, PharmD, MSPH, associate professor and clinical specialist in the Division of Cardiology/ Heart Transplant at the University of Colorado Denver Schools of Pharmacy and Medicine. â&#x20AC;&#x153;It is a problem â&#x20AC;Ś and this problem may be a little bit greater than we estimated.â&#x20AC;? The task force, convened by the American College of Cardiology (ACC) and the American Heart Association (AHA), was somewhat split on the issue of testing patients for clopidogrel resistance (Circulation doi: 10.1161/ CIR.0b0113e3181ee08ed). Although the task force called the current evidence â&#x20AC;&#x153;insufficientâ&#x20AC;? to support â&#x20AC;&#x153;routine genetic or platelet function testing,â&#x20AC;? it recommended that â&#x20AC;&#x153;genetic testing to determine if a patients is predisposed to poor clopidogrel metabolism â&#x20AC;Ś may be considered â&#x20AC;Ś in patients believed to be at moderate or high risk for poor outcomes.â&#x20AC;?

Patient-specific Considerations Clinicians can review a multitude of patient-specific factors to assess the risk for suboptimal clopidogrel response and poor outcomes, according to Dr. Page. These include genetic defects, such as polymorphisms of CYP, glycoprotein (GP) Ia, P2Y12, and GPIIIa; clinical factors, such as poor drug absorption, drugâ&#x20AC;&#x201C;drug interactions and comorbidities (e.g., dyslipidemia and diabetes); demographic variables, such as race/ethnicity, increased age and body mass index; and cellular processes, such as accelerated platelet turnover, reduced CYP3A metabolic activity, increased ADP exposure, upregulation of the P2Y12 pathway and upregulation of P2Y-independent pathways. For example, clopidogrel response drops in patients with diabetes, said Dr. Page, noting that â&#x20AC;&#x153;diabetics have what we call â&#x20AC;&#x2DC;angry platelets,â&#x20AC;&#x2122; which clot very rapidly to a small stimulus.â&#x20AC;? In addition to diabetes, he said that the other potential causes of impaired clopidogrel responses include gender, obesity and a history of ACS events. However, he stressed that the role of these factors is not entirely clear because lack of drug compliance in many patients muddies the picture. Although patients with these factors

â&#x20AC;&#x153;may want to be tested,â&#x20AC;? Dr. Page said, at this point, â&#x20AC;&#x153;these tests are not standardized and the results are not correlated to outcomes.â&#x20AC;?

Practice Recommendations The task force recommended several options for patients who have exhibited or are at risk for poor response to clopidogrel. One approach is to increase the clopidogrel dose. The task force stated

that â&#x20AC;&#x153;higher [loading doses] (600 vs. 300 mg), double-dose loading (600 mg twice over 2 hours), and higher [maintenance doses] of clopidogrel (150 mg daily) have been found to improve platelet inhibition and might be considered alternatives for high-risk patients,â&#x20AC;? but cautioned that â&#x20AC;&#x153;there is uncertainty [about] the long-term safety and efficacy of this approach.â&#x20AC;? Dr. Page agreed that â&#x20AC;&#x153;using higher

Itâ&#x20AC;&#x2122;s not an option to â&#x20AC;&#x2DC;just put someone on clopidogrel and hope that they are not the 16% to 20% of people who will not respond adequately to the drug. Especially since prasugrel is on the market without CYP2C19 problems and strong evidence of clinical efficacy.â&#x20AC;&#x2122; â&#x20AC;&#x201D;C. Michael White, PharmD

One More Reason To Heed Clopidogrel Resistance C. Michael White, PharmD, a pharmacist specializing in cardiology at the Hartford Hospital, in Connecticut, agreed that it is time for clinicians to pay more attention to clopidogrel resistance. But thatâ&#x20AC;&#x2122;s not based only on the drugâ&#x20AC;&#x2122;s recent black box warning and the AHA/ACC Task Force report, he noted. In the June issue of JACC: Cardiovascular Interventions (2010;3:648-656), a team of French researchers reported that patients who were low clopidogrel responders had a 7.9% rate of cardiac death compared with 2.2% of patients deemed normal respond ers (P=0.004). The finding â&#x20AC;&#x153;certainly makes $ & % sense,â&#x20AC;? Dr. White said. â&#x20AC;&#x153;If you are not inhibiting platelets adequately, then # you have a higher risk for adverse cardiac events, which can include ! death. So clearly, this is a clinically significant problem.â&#x20AC;? Although the trial did not specify the cause of the clopidogrel resis tance seen, â&#x20AC;&#x153;it is likely that the 0Y\]VQ\T_RY 0Y\]VQ\T_RY Y\d [\_ZNY use of CYP2C19 inhibitors, such as _R`]\[QR_` _R`]\[QR_` omeprazole, prevents the conversion to the active form of clopidogrel Figure. Cardiac death. and impedes efficacy, so that could have been a factor,â&#x20AC;? he noted. â&#x20AC;&#x153;However, the biggest risk for suboptimal clopidogrel response is likely the poor metabolizers through CYP2C19, as noted in the new clopidogrel [labeling].â&#x20AC;? In the JACC: Cardiovascular Interventions study, clopidogrel response was assessed by a relatively new assay, the vasodilator-stimulated phosphoprotein (VASP) flow cytometry test. Should this test be used in clinical practice? â&#x20AC;&#x153;I actually prefer genetic tests for assessing clopidogrel response,â&#x20AC;? Dr. White said. â&#x20AC;&#x153;The field is further along and the tests yield more detailed information about the mechanisms of resistance involved. In fact, the results can be used for other medications that have the same route of metabolism [as clopidogrel]. But if your health system doesnâ&#x20AC;&#x2122;t offer genetic tests, then VASP could be a viable option.â&#x20AC;? Whatâ&#x20AC;&#x2122;s not an option, he stressed, â&#x20AC;&#x153;is to simply do nothing at this point, and just put someone on clopidogrel and hope that they are not the 16% to 20% of people who will not respond adequately to the drug. Especially since prasugrel is on the market without CYP2C19 problems and strong evidence of clinical efficacy.â&#x20AC;? â&#x20AC;&#x201D;David Bronstein

=R_PR[a \S ]NaVR[a`

WARNING

Next month: Q&A with Rick Seip, PhD, head of personalized medicine at the Hartford Hospital, who offers tips for genetic testing in patients treated with clopidogrel and other drugs that are prone to patient-specific variations in response.

[loading] doses may help,â&#x20AC;? and he discussed data supporting such a strategy from the CURRENT-OASIS (Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events/Optimal Antiplatelet Strategy for Interventions) trial that were presented at the European Society of Cardiology 2009 Congress. In that trial, patients were randomized to receive standard doses (300 mg, day 1; 75 mg, days 2-30) or high doses (600 mg, day 1; 150 mg, days 2-7; 75 mg, days 8-30) of clopidogrel and then were further randomized to receive high-dose (â&#x2030;Ľ300 mg, day 1; 300-325 mg, days 2-30) or low-dose (â&#x2030;Ľ300 mg, day 1; 75-100 mg, days 2-30) aspirin. Among those who underwent percutaneous coronary interventions (PCI), the risk for the primary outcome of cardiovascular death, myocardial infarction (MI) and stroke were significantly reduced among those who received the double dose of clopidogrel compared with the standard dose (3.9 vs. 4.5, hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.74-0.99). On the other hand, the dose of aspirin did not seem to matter. The risk for the primary outcome did not significantly differ among the low- and high-dose aspirin groups (4.4 vs. 4.2, HR, 0.96; 95% CI, 0.05-1.00). â&#x20AC;&#x153;The individuals who did the best are those who received the double dose of clopidogrel, and then either high- or low-dose aspirin,â&#x20AC;? said Dr. Page. Data from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial also have demonstrated that a 600-mg loading dose of clopidogrel was associated with a reduced rate of ischemic events (HR, 0.72; 95% CI, 0.530.98; P<0.04), without an increase in bleeding, compared with a 300-mg loading dose in patients with ST-segment elevation myocardial infarction undergoing primary PCI (JACC 2009;54:1438-1446).

Beyond Clopidogrel Although using higher doses of clopidogrel is one option, Dr. Page said other options should be considered. Foremost, â&#x20AC;&#x153;we need to be looking at the newer drugs,â&#x20AC;? specifically prasugrel (Effient, Lilly) and ticagrelor (Brilinta, AstraZeneca), he said. He noted that studies have shown that â&#x20AC;&#x153;clopidogrel-resistant patients tend to respond to ticagrelorâ&#x20AC;? and â&#x20AC;&#x153;possiblyâ&#x20AC;? prasugrel. Based on data from the RESPOND (Response to Ticagrelor in Clopidogrel Nonresponders and Responders and Effect of Switching Therapies) study (Circulation 2010;121:1188-1199), Gurbel and colleagues found that patients with stable coronary disease who were nonresponders to clopidogrel (defined by light transmittance aggregometry) and received ticagrelor exhibited platelet reactivity below the cut points asso-

â&#x20AC;˘

see WARNING, page 22

22 Clinical

Pharmacy Practice News • August 2010

Cardiology

WARNING continued from page 21

ciated with ischemic risk. The recent ACC/AHA task force recommendations also included these agents as options for clopidogrel-resistant patients. Discussing data from TRITON TIMI38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel– Thrombolysis in Myocardial Infarction; New Engl J Med 2007;357:2001-2015), Dr. Page said that for the composite end point of death from cardiovascular causes, nonfatal MI and stroke, prasugrel “looked to be better than clopidogrel, but not all patients are appropriate candidates for prasugrel because of increased bleeding.” The primary efficacy end point occurred in 12.1% of patients receiving clopidogrel and 9.9% of patients receiving prasugrel (HR, 0.81; 95% CI, 0.73-0.90; P<0.001). Although the risk for major bleeding was higher with prasugrel (2.4% vs. 1.8%; HR, 1.32; 95% CI, 1.031.68; P=0.03), the TRITON TIMI-38 investigators concluded that there was “a substantially favorable net clinical benefit for the use of prasugrel.” One issue with the study is that the investigators used the standard dose of clopidogrel. Thus, prasugrel has not been compared with the higher dose of clopidogrel, which may be more effective in patients with clopidogrel resistance. Additionally, both Dr. Page and the ACC/AHA task force pointed out that there are certain patients who should not receive prasugrel, including those

over age 75 years, those who weigh less than 60 kg and those who have a history of stroke or transient ischemic attack. For example, in TRITON TIMI-38, patients with a prior stroke were at a higher risk for intracranial hemorrhage if they took prasugrel than if they took clopidogrel (2.3% vs. 0%; P=0.02). Another option “on the brink of being released,” according to Dr. Page, is ticagrelor. Reviewing the results of the PLATO (Platelet Inhibition and Patient Outcomes) trial, comparing ticagrelor (180 mg loading dose, 90 mg twice daily for 6-12 months) with clopidogrel (300 mg loading dose, 75 mg for 6-12 months), he said that ticagrelor reduced the composite of cardiovascular death, MI or stroke from 11.7% to 9.8% compared with clopidogrel (HR, 0.84; 95% CI, 0.77-0.92; P=0.0003), without an increase in major bleeding. However, he pointed out that they did not evaluate the higher dose of clopidogrel in this study either. Ticagrelor has several benefits in this setting. In addition to a faster onset of antiplatelet effect, it also has a faster offset. “When you stop it, the effects can be reversed in a few days,” said Dr. Page. He noted that this would be beneficial if, for example, “a patient warranted a CABG [coronary artery bypass graft], then we could send them to CABG quicker.” He noted that although the twice-daily dosing required for ticagrelor might lead to adherence issues, this is not a factor in the acute setting. Additional therapeutic options pre-

METHADONE

All Antiplatelet Agents Not Created Equal Session speaker Joel C. Marrs, PharmD, assistant professor in the Department of Clinical Pharmacy at the University of Colorado Denver School of Pharmacy, echoed the task force’s citing of multiple treatment options for patients in need of antiplatelet therapy. But all of the drugs are not created equal, he said. Athough all of the major antiplatelet agents (aspirin and the thienopyridines, clopidogrel, ticlopidine, prasugrel and ticagrelor) act on the adenosine diphosphate (ADP) platelet receptor P2Y12, Dr. Marrs stressed that there are pharmacokinetic differences among these products that can affect their efficacy and patient outcomes. For example, prasugrel has the quickest onset, which may make it better for the acute setting, he noted. On the

In more than 80% of malpractice suits involving methadone or other opioids, death occurred within five days of starting a new dose.

continued from page 18

methadone makes up only 5% of opioid prescriptions (but still nearly 50 million in 2008), it accounts for about one-third of patient deaths. Methadone-related calls to poison control centers, admissions to emergency rooms and malpractice suits exceeded those related to either hydrocodone or oxycodone. Adjusted for number of dispensed prescriptions, the panel found that four times as many calls to poison control centers were related to methadone as to oxycodone, and methadone played a role in 10 times as many calls as hydrocodone. Nearly one-third (30%) of emergency room visits for overdose involved methadone, six times as many as for oxycodone and 23 times as many as for hydrocodone. Finally, half of the 20 malpractice suits reviewed concerned fatalities involving methadone. Starting dose and titration are critical to safe use, the panel’s review suggests.

sented by the task force are adding cilostazol to standard doses of aspirin and clopidogrel (J Clin Pharmacol 2010;50:415421) or using cilostazol alone (Stroke 2005;36:782786; Lancet Neurol 2008;7:494499; J Stroke Cerebrovasc Dis 2000;9:147-157). Dr. Page noted that at his institution, cilostazol has been used in place of clopidogrel with aspirin. He had two caveats with regard to cilostazol, however. First, it only has been shown to be efficacious in patients receiving bare metal stents, not those receiving drugeluting stents; and second, it is not recommended in patients with heart failure.

According to Utah data, 70% of decedents with a methadone prescription died within the first week of starting treatment. In more than 80% of malpractice suits involving methadone or other opioids, death occurred within five days of starting a new dose. For pain physicians, these findings suggest the need for much greater caution when prescribing methadone. In particular, Dr. Webster encouraged physicians to be aware of the dangers of conversion tables and sleep apnea. “Never use a conversion table,” he advised, because these tools may be

inaccurate. Instead, “begin with a very low dose and titrate slowly.” Sleep apnea is another serious risk associated with methadone use, according to the researchers. Although obstructive sleep apnea is correlated with body mass index, central sleep apnea—another risk associated with methadone—is not. “All patients on 50 mg or higher of methadone require a sleep study to assess risk,” said Dr. Webster. Further contributing to methadone fatalities may be insurance company practices, he said. Some insurers require that patients try generic methadone or morphine before moving to brand-name drugs, Dr. Webster

other hand, he said, ticagrelor is “active on oral administration,” whereas clopidogrel, ticlopidine (no longer widely used because of severe hematologic side effects) and prasugrel are hepatically metabolized and require multiple CYP-dependent steps to become bioavailable. Dr. Marrs said that might be relevant if a patient has genetic abnormalities or drug interactions related to those metabolic pathways.

Aspirin Resistance One final point Dr. Page stressed during his presentation was the fact that clopidogrel is not the only antiplatelet agent prone to low response: Patients also can develop resistance to other antiplatelet drugs, he noted. For example, aspirin, recommended by the ACC and the AHA in combination with a thienopyridine as part of dual-antiplatelet therapy for PCI patients (Circulation 2009;120;22712306), has been shown to be associated with resistance in a substantial number of patients. Dr. Page cited data showing that close to 20% of ACS patients who were being considered for PCI and were treated with clopidogrel and/or aspirin were found to have aspirin resistance, and were at increased risk for myonecrosis after PCI (JACC 2004;43:1122-1126). The bottom line for PCI patients? “There are a host of patient-specific factors that could blunt response to multiple antiplatelet agents,” Dr. Page said. “Pay insufficient attention to these factors, and your patients’ outcomes can be significantly compromised.” —Sarah Tilyou

explained. When patients switch insurers, however, this policy sometimes requires them to shift from brandname opioids to generic methadone, prompting physicians to use a conversion table and prescribe a dangerously high initial dose. Jane Ballantyne, MD, professor of anesthesiology and critical care at the Hospital of the University of Pennsylvania, in Philadelphia, noted that methadone can be a “useful drug” for pain treatment and opioid rotation, but it is “highly unpredictable and very dangerous” if used incorrectly. Although prescriptions for it have increased over the past several years, education is “very important” to its safe use, she said. Although methadone requires special care, the authors of the study emphasized that it is not the only opioid to present challenges. As noted, their research indicated that two-thirds of opioid deaths resulted from other opioids, and they wrote, “all must be used judiciously.” —Clayton Simmons

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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, complianceprompting packaging

Patient safety is a critical issue for health systems. As a result, many health systems seek bar-coded products 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 pre-packaged unit dose products.

There are many benefits to AHP pre-packaged unit dose products: Safety. Companies that specialize in pharExecutive Vice President/ maceutical packaging are highly regulated and General Manager scrutinized by the FDA. Compliance with current Domenic Ciarico Good Manufacturing Practices (cGMP) ensures that products are packaged in a regulated and Vice President, Sales and safe environment. Packaging professionals are Marketing adept at ensuring that the product’s lot number, NDC and expiration date are recorded correctly Brian McMillan and legibly. Wouldn’t you feel safer knowing that the products you administer to patients have passed such production and regulatory scrutiny? Pharmacy Efficiency. Health systems are experts in the care of patients. Oftentimes however, they’re not as well suited or staffed for packaging tasks. Packaging can become an added burden to a department already at capacity. Packaging in-house requires close supervision and a number of checkpoints to ensure it is done correctly. Why be in the business of packaging when pre-packaged, bar-coded unit dose products are available? Cost Savings. Establishing a packaging area within the hospital pharmacy is costly. And, in addition to the purchase of expensive equipment, staff must be hired and trained to complete the associated packaging tasks. Pre-packaged unit dose products eliminate the need for this capital expense and the associated increase in overhead costs. Liability Management. Packaging in the hospital setting shifts

the legal burden of accuracy in packaging and dispensing to hospital associates and dispensing caregivers. Pre-packaged products, however, maintain a legal burden to be correct as delivered to the hospital. Protect your pharmacy personnel and dispensing nurses from unnecessary legal exposure with pre-packaged unit dose products.

Safety Every Step of the Way Bar-coded to the dose level, our unit dose line has grown substantially in the last couple of years. The line now contains over 280 SKUs. Our products support many therapeutic classes. Particular areas of growth have been items that support psychiatric care, neuromuscular care and pain management. Recent launches include Dronabinol CIII, Valacyclovir HCl, Tamsulosin HCl, Perphenazine, Amantadine and Phenytoin Sodium. A specific niche in unit dose that American Health Packaging targets is exclusive unit dose items—products not offered by other suppliers. About one-fourth of the line is composed of exclusive items. Therefore, providers look to American Health Packaging when seeking niche or “difficult to find” unit dose items. As an additional safety measure, our packages are color-coded to better distinguish them on the pharmacy shelf prior to dispensing. We also use “tall man” lettering to differentiate very similar product names. Stability-tested to ensure a longer shelf life, these items are also attractive to group purchasing organizations as they seek to provide highly sought-after bar-coded products to their members. The line is stocked by the major wholesalers.

About American Health Packaging American Health Packaging’s manufacturing facility is registered with the FDA and fully adheres to cGMP. Industry veterans with more than 50 years of collective experience lead the quality and manufacturing departments. American Health Packaging is licensed by the Drug Enforcement Administration (DEA) to package Schedule II to V controlled substances. Visit our Web site, americanhealthpackaging.com, for new product information. Drop-ships also can be requested via the Web site.

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Corporate Profile 2010

Special Advertising Section Pharmacy Practice News

B. Braun Medical Inc. B. Braun Medical Inc. (B. Braun) is a recognized health care manufacturing leader with an environmentally friendly focus, supporting today’s dynamic pharmacy environment—in hospital and outpatient settings—with advanced products and services that help improve safety and efficiency.

the convenience of the DUPLEX system simply fold and squeeze the container and shake it to mix pharmaceuticals and diluent.

Making Infusion Therapy Easier and Safer

AT A GLANCE

B. Braun’s Outlook® Safety Infusion System Address automates IV pump programming, reducing man824 Twelfth Avenue ual programming errors that could result in mediBethlehem, PA 18018 cation errors and improving safety. It features an Phone: (800) 227-2862 extensive drug library and bar-coding capabiliB. Braun offers drug delivery, total parenteral nutrition (TPN) E-mail: info@bbmus.com ties, enabling clinicians to improve patient safety management and infusion systems that help pharmacy staffs Web site: www.bbraunusa.com while streamlining care. The simple, easy-to-use, protect patients and the environment while improving workflow. flexible Outlook is designed to improve best B. Braun also works closely with clinicians to help them deliver Products practices as it ensures the right patient is receivthe best patient care, comply with industry guidelines and achieve Pinnacle ™ TPN Management ing the right drug and the right dose by an authoSurgical Care Improvement Project (SCIP), Joint Commission and System rized clinician. The system’s open architecture USP Chapter <797> compliance. Guided by the company’s “Shardesign allows it to interface with hospital or pharing Expertise®” philosophy, B. Braun addresses the critical issues of macy information management systems, making medication safety, infection prevention and environmental responit adaptable to various health care environments. sibility by promoting best practices that help pharmacists and cliWhether for large academic institunicians reduce medication errors, prevent tions or smaller community hospitals, healthcare–acquired infections (HAIs) and B. Braun offers a smart pump solution also achieve sustainability objectives. to meet every facility’s need. Making Drug Delivery Greener Along with Outlook, B. Braun’s DoseFor More Than 30 Years Trac™ Infusion Management Software, which allows real-time monitoring of B. Braun works to ensure that patients IV therapies, has the ability to monitor, are safe during every stage of therapy, and trend, report and manage the IV adminthat the environment is protected from istration process. DoseTrac provides unnecessary waste and chemicals. Efforts to reduce and eliminate these chemicals both end users and hospital informaB. Braun’s Outlook® ES Safety Infusion System smart pump technology and data analysis services help institufrom medical products, along with the envition management systems with realtions evaluate the efficiency and efficacy of their infusion ronmental hazards they represent, are an time and retrospective information to processes to improve best practices and patient care. integral part of B. Braun’s commitment to help ensure patient safety. improve patient care. For more than 30 Making TPN Compounding and years, B. Braun has offered a full line of PVCDelivery More Streamlined free and DEHP-free basic IV solution containers. Medical devices containing PVC and DEHP pose B. Braun’s Pinnacle® TPN Management Syspotential health hazards to humans exposed to tem also makes drug delivery safer and more them during medication administration. They also streamlined. Pinnacle streamlines all functional create serious environmental consequences durareas of operation and manages all aspects ing medical waste disposal. B. Braun’s IV solution of the TPN process for improved efficiency, containers are nontoxic to the environment and safety and patient care. The Pinnacle System help protect patients. automates all TPN calculations in a Windows® browser–based format. These include nutriMaking Drug Delivery Safer and Easier tional assessment, aluminum calculations/ warnings, and Trissel’sTM calcium/phosphate B. Braun developed the revolutionary DUPLEX® (Ca/P) Check. A complete system, not solely Drug Delivery System to help minimize the potena device, Pinnacle streamlines the TPN protial for medication errors, eliminate the pharmacy cess by offering computerized physician order labor component of IV cephalosporin delivery entry and pharmacist approval, IV solution and reduce drug waste while aiding compliance compounding and bar-coded TPN containers and advancing patient safety. B. Braun’s DUPLEX that work with B. Braun bar code–compatible is a convenient, ready-to-use, two-compartment, infusion devices. flexible, eco-friendly IV container that stores preDUPLEX® Drug Delivery System can be stored, ready to use wherever and measured drug and diluent doses. It’s easy to stock whenever it is needed, which means fast, because it can be stored ready to use wherever and convenient and accurate administration whenever it is needed, which means fast, convenient to patients. and accurate administration of IV cephalosporins to patients. The DUPLEX system portfolio of products has a 17-month minimum dating and also fits in automated medication dispensing systems. Health care workers using

B. Braun’s award-winning Pinnacle® TPN Management System represents a major advance in compounding technology.

Special Advertising Section Pharmacy Practice News

Corporate Profile 2010

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Baxter International Inc. Medication Delivery Business

AT A GLANCE

Products

Corporate address One Baxter Parkway Deerfield, IL 60015-4625 Phone: 847-948-2000 www.baxter.com

Chairman, President & Chief Executive Officer Baxter Healthcare Corporation Robert L. Parkinson

Corporate Vice President, President, Medication Delivery

Baxter’s Medication Delivery business manufactures products used in the delivery of fluids and drugs to patients. These include intravenous (IV) solutions and administration sets, premixed drugs and drug reconstitution systems, prefilled vials and syringes for injectable drugs, IV nutrition products, infusion pumps and inhalation anesthetics, as well as products and services related to pharmacy compounding, drug formulation and packaging technologies.

Peter Arduini

IV Solutions and Premixed Drugs Baxter is the world’s leading manufacturer of commercially prepared IV solutions as well as frozen and ready-to-use premixed drugs in flexible IV containers. Baxter’s portfolio of IV solutions and premixed drugs is the broadest in the industry. Baxter introduced the world’s first flexible, closed-system IV container systems that do not require any external venting to outside air to empty the solution and have self-sealing injection ports. Unlike open systems, closed infusion systems prevent unfiltered air from entering the infusion system and stop sterile liquid from coming into contact with the environment, thus helping to reduce the risk for contamination. One of Baxter’s latest IV solution containers, AVIVA, is made of non-PVC (non–polyvinyl chloride) film and offers a DEHPfree fluid pathway to patients.

IV Infusion Systems and Administration Sets Baxter is a recognized leader in IV medication delivery, providing a wide range of infusion pumps, IV tubing and access devices to control the delivery of IV fluids and drugs to patients. Baxter provides infusion pumps used in hospitals and other acute care settings, as well as portable devices used in oncology and pain management. This offering includes pumps that enable clinicians to administer multiple IV solutions simultaneously to a patient from a single pump; deliver a wide range of infusion rates to accommodate use throughout the hospital, from the neonatal unit to the emergency room; and offer features that enable caregivers to establish limits for specific drugs to enhance patient safety and help reduce medication programming errors. Most recently, the company announced an exclusive three-year distribution agreement in the United States and international markets with SIGMA International for infusion pumps. The agreement enables Baxter to immediately provide Spectrum™ large-volume infusion pumps to customers and grants Baxter access to SIGMA’s product development pipeline, which will complement Baxter’s current infusion systems portfolio and next-generation technologies.

Parenteral Nutrition Products Nutrition administered intravenously (parenteral nutrition) provides life-sustaining support for patients who cannot receive adequate nutrients through other means. Baxter is a leading provider of products for parenteral nutrition, from the nutritional solutions themselves to the devices and software used for their preparation. Baxter first introduced liquid proteins in the form of amino acids in the 1940s, and has continued to advance the field of IV nutrition through the development of therapeutic formulations and innovative container technologies.

Anesthesia Baxter sells the three most commonly used modern inhaled anesthetics for general anesthesia, including a proprietary anesthetic that offers rapid recovery. Because the three gases have different properties, most anesthetists make use of all three of them depending on the situation. Despite major advances in anesthesia and postoperative care, many patients may still experience postoperative nausea and vomiting. Baxter offers pharmaceutical agents to prevent such outcomes as part of its anesthesia portfolio.

Drug and Drug Formulation Technologies Baxter is a leader in injectable drugs, offering a broad portfolio of critical medications. Baxter now offers distinctive labeling as an extension of its drug safety initiatives intended to assist clinicians in selecting the correct medications and concentrations of its medications.

Spectrum™ is a registered trademark of SIGMA International General Medical Apparatus, LLC.

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Corporate Profile 2010

Special Advertising Section Pharmacy Practice News

Bedford Laboratories One of the largest generic injectable pharmaceutical companies in the country, Bedford Laboratories offers a broad range of multisource injectables across multiple therapeutic classes. In fact, Bedford has become the market share leader for more than one-third of all the products in its current portfolio. The company currently sells over 92 drugs in 288 presentations, including 10 sole-source generic products, and has one of the most comprehensive lines of generic injectable oncology products available in the United States today. In addition to its impressive oncology portfolio, a leadership position the company is committed to growing, Bedford is ranked second in sales for cardiac agents and third for anesthesia products.

Where To Go for Specialty Injectables According to David Gaugh, vice president and general manager of Bedford Laboratories, the company’s success is due in part to its ability to meet specific market needs. “Bedford focuses on specialty injectable products that are not always available from other manufacturers,” he said. To provide hospital pharmacists with the greatest flexibility and efficiency, Bedford supplies its products in the same presentations offered by the innovator, as well as customized options based on requests from pharmacists and other health care professionals.

On-site Support for Every U.S. Hospital Customer service has also been key to Bedford’s success. The company’s field sales force provides hospitals in the United States with personalized on-site support. This has allowed Bedford to develop an in-depth understanding of the differing needs of hospital pharmacists and health care professionals across the country. Bedford responds quickly to changing customer needs by providing innovative solutions that have included new products, new dosage forms and improved packaging. The company’s U.S.-based service operations facilitate easy communication and quick response, s h i p p i n g a v ai l ab l e products within hours of the initial request. For medical information about Bedford’s products, the company also provides a 24-hour professional services center staffed with PharmDs.

Address Bedford Laboratories A Division of Ben Venue Laboratories, Inc. A Boehringer Ingelheim Company 300 Northfield Road Bedford, OH 44146 Phone: (800) 562-4797 Fax: (440) 232-6264 Web site: www.bedfordlabs.com

Products Generic injectable pharmaceuticals

Vice President and General Manager David Gaugh

Putting the Customer First

Rapid Product Availability Bedford’s growth has been supported by its manufacturing and distribution capabilities. Located in Bedford, Ohio, state-of-the-art facilities and advanced manufacturing technologies provide a reliable supply of products at a better market value. Excellent inventory management at the wholesaler level, combined with customer-focused delivery options, help to ensure constant product availability. Together, the company’s comprehensive product line and distribution capabilities make it faster and easier to purchase more from a single source, saving time and money for hospital pharmacists across the United States.

AT A GLANCE

New Fluconazole Injection 100 mg/50 mL is right-sized for smaller doses.

“Our growth is based on successfully meeting our customers’ needs. Because our field sales force focuses on hospitals and their needs, we’ve been able to build an expansive customer base,” Mr. Gaugh said. “Health care professionals come to Bedford Laboratories because we have a comprehensive and growing product line, competitive pricing and excellent customer service.” Bedford Laboratories was established in 1993 as a division of Ben Venue Laboratories to sell and market its own generic injectable drug products. In 1997, Boehringer Ingelheim acquired the company when it purchased Ben Venue Laboratories.

Indomethacin for Injection USP is another example of Bedford Laboratories helping to make medicine more affordable.

Special Advertising Section Pharmacy Practice News

Corporate Profile 2010

PP5

EKR Therapeutics Advanced acute care pharmaceuticals

AT A GLANCE

Corporate Vision

Address 1545 Route 206 South, 3rd Floor Bedminister, NJ 07921 Phone: (877) 435-2524

Therapeutic Focus Acute care pharmaceuticals

EKR Therapeutics is dedicated to serving the needs of the acute care hospital setting. EKR focuses on advancing novel pharmaceuticals, offering the acute care medical professional broader therapeutic options and greater control to improve patient care, speed recovery and achieve optimal outcomes.

Web Sites www.ekrtx.com www.cardeneiv.com www.depodur.com www.retavase.com

Establishing Preeminence in Acute Care Specialty Pharmaceuticals Under the leadership of a highly experienced management team, EKR has become a class leader in commercializing products to address unmet and undersatisfied medical needs or to otherwise enhance the therapeutic value of acute care products. EKR actively pursues opportunities to selectively acquire approved novel but undervalued products that could significantly benefit from the knowledge and commercial strengths its management team has in the acute care hospital space. EKR’s goal is preeminence as a provider of acute care specialty products, backed by a commitment to excellence in customer service and medical education.

Key Products

advanced aortic stenosis. The most common side effects of CARDENE I.V. are headache (14.6%), hypotension (5.6%), nausea/vomiting (4.9%) and tachycardia (3.5%). Less frequent adverse effects, in each case occurring at 1.4%, include electrocardiographic abnormalities, postural hypotension, ventricular extrasystoles, injection-site reaction, dizziness, sweating and polyuria. Please see www.cardeneiv.com for full prescribing information. DepoDur® (morphine sulfate extended-release liposome injection) for the management of postoperative pain. The extended-release formulation of DepoDur provides sustained regional delivery of morphine without an indwelling epidural catheter. For additional information and prescribing details, see www.depodur.com. DepoDur is contraindicated in patients with known hypersensitivity to morphine or the product components; those patients with respiratory depression, acute or severe bronchial asthma or upper airway obstruction; those who have or are suspected of having paralytic ileus, head injury or increased intracranial pressure; and those who are in circulatory shock. Please see www.depodur.com for full prescribing information. Also available: oral CARDENE® SR (nicardipine hydrochloride) and Retavase ® (Reteplase recombinant).

DepoDur® (morphine sulfate extendedrelease liposome injection)

Ready-to-Use CARDENE ® I.V. (nicardipine hydrochloride) premixed injection for short-term treatment of hypertension is available in either dextrose or sodium chloride IV preparations. For additional information and prescribing details, see www. cardeneiv.com. CARDENE I.V. is contraindicated in patients with known hypersensitivity to the drug and in patients with

Ready-to-Use CARDENE® I.V. (nicardipine hydrochloride) Premixed Injection

PP6

Corporate Profile 2010

Special Advertising Section Pharmacy Practice News

Grifols Grifols, with a global presence in over 90 countries, has established itself as a primary provider to health systems in the United States, of plasma products, sterile IV preparations for specialty therapies such as pain management, oncology and pediatrics, and in vitro diagnostic products for the laboratory.

start to finish, Grifols is committed to giving you the tools to create, operate and maintain your clean room.

Unique Solutions for Clinical Laboratories

AT A GLANCE Address 2410 Lillyvale Ave.

Grifols USA Diagnostic DiviLos Angeles, CA 90032 sion focuses on bringing the Phone: (888) GRIFOLS right in vitro diagnostic prod(474-3657) ucts to the US clinical laboraWeb site: www.grifols.com tory. Our solutions in infectious ® New Albumin Sterile Filling Facility The Triturus EIA Analyzer provides serology, autoimmune disease true flexibility by being completely Divisions In Los Angeles testing and immunochemistry open, fully automated, multi-test and Bioscience – Specializes in solve many of the workflow In December 2009, Grifols received approval multi-batch. the research, development, challenges in today’s clinical from the U.S. Food and Drug Administration production and commercialization lab. From routine testing and (FDA) for use of its new sterile filling facility in of high-quality plasma therapies. disease diagnosis to theraLos Angeles, Calif., for the production of lifesaving Hospital – Specializes in py monitoring, our solutions albumin therapy. This approval is the culmination operational solutions for include platforms that fully of a three-year project to transform the entire pharmacy-compounded automate the testing process process of obtaining, purifying and filling albumin IV solutions. from patient serum to final vials at Grifols Biologicals Inc. (GBI), the Grifols Diagnostic – In vitro diagnostic test result. Our platforms in U.S.-based manufacturing division. products for clinical laboratories. immunoassay, immunofluo“With approval of this new method in the [Unitrescence and other immued States], our production facilities in Barcelona Products nology techniques offer a and Los Angeles will adhere to precisely the same complete system approach, manufacturing process,” explained Willie Zuñiga, Albumin (Human), marketed as including operating software President of GBI. According to Mr. Zuñiga, the Albutein® 5% and Albutein® 25% as well as a wide range of new method offers a number of technical and Antihemophilic Factor/ reagents and applications. We process flow advantages over the method previvon Willebrand Factor Complex partner with forward-thinking ously used at the [Los Angeles] facility. “Approval (Human), marketed as companies to offer innovaof our new albumin facility was obtained in record Alphanate® tive choices to challenging time and represents completion of yet another problems, such as specimen major production-related advancement taking Coagulation Factor IX (Human), MisteriumTM modular clean room preparation. Through Grifols’ place in the [United States],” he continued. ® marketed as AlphaNine® SD system and Gri-fill System 3.0, contributions in clinical diagThe total fractionation capacity of the Los automated compounding system. Factor IX Complex, marketed nostics and advancements Angeles facilities is 2,200,000 liters per year. In as Profilnine® SD from our many partners, addition to a number of other projects, Grifols we offer unique solutions tailored to meet the is focused on construction of a new intravenous immune globulin Immune Globulin Intravenous diverse needs of today’s clinical laboratory. (IVIG) purification facility for Flebogamma® 5% DIF that is planned (Human) or IVIG, marketed as for completion in the third quarter of 2010. Once completed, this will Flebogamma® 5% DIF Sustaining an International Legacy represent the full modernization of all of Grifols’ Los Angeles-based Gri-fill® System 3.0 for Of Leadership production facilities. compounding sterile preparations The achievements of Grifols USA extend the Driving Efficiencies in Pharmacy parent company’s legacy of pioneering plasmaMisterium™ pheresis more than half a century ago, which Grifols USA Hospital Division provides simple, cost-effective soluDosi-fuser™ Ambulatory gave rise to today’s lifesaving plasma therapies tions to operational challenges in pharmacy. Its primary focus is on Infusion Pump that have benefited millions. As expressed by sterile IV preparations for specialty therapies such as pain manageVictor Grifols Roura, president and chief execument, oncology and pediatrics. Providing a wide range of hardware, Quickpin tive officer, the company’s “enduring values software and disposable products for hospital pharmacies, Grifols Triturus® EIA Analyzer emphasize service, scientific excellence, techdevelops technology systems designed to increase the safety of nical proficiency and inventiveness, and a full sterile preparations and clean room solutions in pharmacy settings. A full line of immunology awareness of the needs of the people who trust Depending on the application, the Gri-fill® automated compoundinstruments and reagents and depend upon Grifols products.” ing system can improve a pharmacy’s efficiency, help control costs This corporate culture has driven Grifols to and extend beyond-use date of compounded preparations. sustain a full and active research and developGrifols’ Misterium™ is a modular clean room that can be configured ment program. Grifols has already been granted and installed to suit your needs and bring pharmacies into complimore than 400 patents in the United States and other countries, 253 ance with USP Chapter <797> for sterile compounding. All-inclusive, of which were for plasma therapies. The company also has obtained a total of 1,242 official product registrations. R&D initiatives are currently focused on developing methods to obtain, purify and stabilize additional proteins from plasma, and working to help identify new therapeutic uses for them. The company’s unwavering commitment to develop more effective and safer plasma-derived therapies and processing methods builds on an already impressive record of scientific contributions in the related fields of blood transfusion, blood banking and clinical analysis. —Kristen Martin

Special Advertising Section Pharmacy Practice News

Corporate Profile 2010

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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 additive disposables for the preparation and dispensing of IV medications. Address Other EPS products include male/female Luer-lock closures, injection 70 Industrial Drive ports, trays and totes, tapes and labels, UV inhibitant bags and resealIvyland, PA 18974 able bags, IV software and high-alert medication identification bands. Phone: (800) 523-8966 Like Medi-Dose, the EPS TampAlerT® system for liquids offers Fax: (800) 323-8966 tamper evidence. “The premier advantage of TampAlerT is its The Medi-Dose Group has always had deep E-mail: info@medi-dose.com tamper-evident seal,” Robert Braverman said. “Ten minutes after roots—family roots. Medi-Dose began as a small Web site: www.medi-dose.com you dispense your liquid and screw the TampAlerT cap on the vial, family business in 1971, when Milton Braverman, the seal is in place. Heat tunnels and a former pharmaceutical company territory manProducts accessory sealing equipment are not ager, formed his own company. He was acutely Medi-Dose® (Solid) and necessary. TampAlerT is tamper eviaware of the requirements of hospital pharmacy. TampAlerT® (Liquid) Oral dence with a twist of the wrist!” His sons, Robert and Mark, continue the tradition Unit-Dose Packaging The company’s IV accessories also for The Medi-Dose Group. ® are highly successful. “We see them The Bravermans carved a niche for the comMedi-Cup PLUS packaging for as natural advancements of the inipany—initially with solid oral unit-dose packagextended beyond-use dating tial Medi-Dose system. In essence, ing. Although the concept of unit dose is familiar MILT® by Medi-Dose unit-dose IV dispensing is a highly specialized today, launching the idea was one of the biggest and bar-coding software form of unit dose,” he added. “It’s the problems the new company faced. “We were one LiquiDose® labeling, IV additive same idea—preparing and adminof the pioneers, the innovators promoting unit Milt 3.0 software. and filtration products istering predetermined amounts of dose in hospitals,” Robert Braverman recalled. medication for one regular dose or “Due in part to Medi-Dose’s Nultraviolet® ultraviolet light application.” educational efforts, pharmainhibitant bags Although all of the products concists and nurses accepted the Steri-Dropper sterile ophthalmic tinue to meet with gratifying, widevalidity of unit dose.” dropper bottles spread acceptance, both Medi-Dose Medi-Dose is constantly reHigh Alert and I.V. Line Tracing and EPS remain highly motivated. sponding to pharmacy packLabels “We’re always looking for new prodaging needs. Providing Resealable bags, bottles and ucts and developing innovative, coststability, ultraviolet (UV) light other pharmacy supplies and effective ways to help pharmacists, inhibition, easy opening and disposables always with an eye toward reducing tamper evidence have always the potential for medication error,” been paramount concerns noted Mr. Braverman. “One of our regarding prepackaging. Using Pharmacists’ input has made Medi-Dose the ideal manual, solid oral unit-dose packaging system. newest products meeting these criMedi-Dose, a pharmacist can teria is our line of IV and High Alert package a medication and store it for up to one Line Tracing Labels which makes it year without loss of potency easy to label and trace IV lines for due to UV light transmission or any medication in any setting (hospimoisture permeation. tal, home or clinic). Pharmacy simply Hospitals can install the Mediplaces the entire label on an IV infuDose solid oral unit-dose system sion container. When the medication for about $700; this includes all is administered at the bedside, nursthe supplies for 5,000 doses of ing applies one line label to each end medication, as well as software of the tubing. This facilitates easy line for complete medication and traces, improves accuracy and helps bar-coding identification. Total EPS’s innovative Line Tracing Label with a unique three-part piggyback minimize IV line confusion.” He added solid and liquid oral systems can design provides safe and economical protection for IV lines. that 10 preprinted labels as well as be set up for less than $1,000. customizable Line Tracing Labels MILT® by Medi-Dose Software (when used with the MILT 3.0 software) are immediately available. “All our IV High Alert and Line Tracing Labels reduce the potenWith bar coding increasingly important to pharmacy practice, tial for error, minimize liability exposure and save lives—all for an Medi-Dose designed its widely used MILT® by Medi-Dose software extremely affordable price,” Mr. Braverman said. (Medi-Dose Information Labeling Technology, named for the compaMark D. Braverman, director of operations, is responsible for the ny’s founder). “My father wanted bar coding on medication packagcompany’s extensive computer network. He coordinates all purchasing early on, to minimize the potential for medication error,” Robert ing activities, both domestic and international. Mark and Robert Braverman said. “So, we’ve been constantly improving our programs are aggressively bringing an expanded line of economically priced, to meet this vital pharmacy challenge and need.” generic alternatives to expensive brands of plastic products to the MILT 3.0 by Medi-Dose not only has sophisticated one- and company’s customers. two-dimensional bar-coding technology to include lot numbers, Robert Braverman noted, “We’ve come a long way from being a beyond-use dates and National Drug Codes (NDC) on one bar code; small family business; we still have remained as attentive and responit also includes an upgradable NDC database, directly from the FDA. sive to pharmacy needs as we were more than 30 years ago. Now we Pharmacists can simply type or scan in the NDC number, and MILT have the ability and the products to respond to pharmacists’ needs all by Medi-Dose will supply the pertinent information. The pharmacist over the world—and we do.” can map this information to designated fields, reducing the risk for error. MILT by Medi-Dose also contains field-locking capability for extra security; enhanced formatting for quick medication identification; 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.

PP8

Corporate Profile 2010

Special Advertising Section Pharmacy Practice News

Pfizer Injectables In the business of solutions Launched in 2009, Pfizer Injectables, a division of Pfizer Inc, provides a robust portfolio of injectables and hospital products essential to the health and well-being of patients throughout the United States. The core mission of Pfizer Injectables is to ensure delivery of innovative therapies to patients who need them most. The division is dedicated to providing a broad portfolio of specialized products, from cephalosporins and penicillins to: • SOLU-CORTEF® (hydrocortisone sodium succinate, USP) • SOLU-MEDROL® (methylprednisolone sodium succinate) • GELFOAM® (absorbable gelatin powder/sponge, USP) • UNASYN® (ampicillin sodium/sulbactam sodium) Committed to growth, particularly in anti-infective and oncologic products, finding and filling the needs of niche segments—where quality and supply reliability are crucial and specialized technologies are required—is a strategic imperative.

meet their needs through a variety of options to reduce both costs and the time patients spend in the hospital. An inherent advantage of Pfizer Injectables is its ability to leverage the proven resources of Pfizer to execute at a high level of service and quickly respond to the evolving needs of customers across six key therapeutic segments, including: • Anti-infectives • Oncology • Cardiovascular health • CNS • Corticosteroids • Hospital anesthesia

Innovative Technologies

AT A GLANCE Address Pfizer Injectables 100 Route 206 North Peapack, NJ 07977 Phone: (908) 901-8000 Web site: www.pfizerinjectables.com

Products Key therapeutic areas include anti-infectives, oncology, cardiovascular health, CNS, corticosteroids and hospital anesthesia.

Pfizer Injectables has been built by providing medicines in a market where quality and supply reliability matter most. The division also has demonstrated its dedication to efficient delivery solutions, including: • The ACT-O-VIAL® System—a dual-compartment vial system that allows reconstitution of a sterile, injectable drug by simply pressing on the plastic cap. • The ADD-Vantage® System—a diluent container and drug vial that keep drug and diluent separate until activated. • The Galaxy® Premix System—an aseptic manufacturing process that allows the production of ready-to-use (premix) drug products.

Building on its core portfolio of established sterile injectables, Pfizer Injectables has targeted anti-infective and oncologic products as key areas for growth.

In addition, the division provides a wide range of presentations for many molecules introduced during Pfizer’s long history of innovative research and extensive product development. For example, with the recent integration of Wyeth brings even more established products into the portfolio, such as ZOSYN® (piperacillin/tazobactam), which is available in premixed frozen bags, bulk vials and single-dose units. With several significant agreements recently completed—and more in the works—Pfizer Injectables is off to a strong start in its goal to rapidly become a leading source of sterile injectable solutions.

Emphatically “Customer-Centric” Today, patients, families, healthcare providers and government agencies demand excellence in the quality and delivery of sterile injectables. Pfizer Injectables is committed to helping hospitals

Innovative delivery systems from Pfizer Injectables are designed to help improve efficiencies—from inventory management to drug administration.

The Unmatched Resources of a Proven Leader Founded in 1849, Pfizer is the world’s premier biopharmaceutical company, with annual revenues in excess of $50 billion. Dedicated to helping people stay healthier longer, the professionals at Pfizer are working every day to reduce the human and economic burden of disease.

USI00170

Special Advertising Section Pharmacy Practice News

Corporate Profile 2010

PP9

PharMEDium Services AT A GLANCE Address Two Conway Park 150 N Field Drive, Suite 350 Lake Forest, IL 60045 Phone: (800) 523-7749 Web site: www.pharmedium.com

Services Pain management PCAs and epidurals; labor and delivery, nerve block and local anesthetics, OR anesthesia syringe preparations; electrolyte solutions; antibiotics; antiemetics, cardiovascular/cardioplegia; renal replacement solutions; total parenteral nutrition; intrathecal preparations.

PharMEDium is the leading outsourced pharmacy provider, rigorously ensuring the accuracy and sterility of all your customized sterile compounded preparations. The company has grown into a nationwide network of state-licensed and federally registered compounding centers providing trusted solutions to more than 2,000 hospitals throughout the United States. Managed by licensed pharmacists and staffed by certified technicians, PharMEDium complies with all appropriate state laws and federal regulations, including requirements from the United States Pharmacopeia Chapter <797> and the Drug Enforcement Administration. Admixtures for All Areas Of Your Hospital

PharMEDium can help. With proven admixture services for all areas of the hospital, PharMEDium can significantly reduce the time and effort required to produce high-quality compounded preparations. Your pharmacy will run smoothly, your admixtures will stay compliant with current and future regulations, and you’ll have more time to focus on what you do best: taking care of your patients. Supported specialties include: • Pain management PCAs and epidurals; labor and delivery, nerve block and local anesthetics, ICU, OR anesthesia syringe preparations; electrolyte solutions; antibiotics; antiemetics, cardiovascular/cardioplegia; renal replacement solutions; intrathecal preparations. Rigorous sterility controls, accurate custom syringe preparations: PharMEDium anesthesia custom syringe preparations improve drug-name recognition in critical situations, thanks to labels with American Society of Anesthesiologists–endorsed ASTM color-coding by drug class. At PharMEDium, we understand that accuracy must begin long before a compounded preparation enters the operating room. That’s why we developed a process of 200%

PP10

Corporate Profile 2010

inspection along with a highly specialized system that uses automated bar-code verification to ensure that the right drug in the right concentration is present in each syringe and is labeled correctly, every time. Our tamper-evident packaging enhances patient care by reducing the potential for diversion and waste. PharMEDium OR anesthesia syringe preparations, in an array of requested concentrations, include: • Opioids: fentanyl, morphine PF, hydromorphone, • Vasopressors: phenylephrine, ephedrine • Sedatives: midazolam, lorazepam • Blockade agents: succinylcholine, rocuronium, vecuronium • Reversal agents: neostigmine • Anticholinergics: glycopyrrolate, atropine • Induction agents: ketamine • Local anesthetics: bupivacaine, ropivacaine, lidocaine • Antibiotics: cefazolin • β-blockers: labetolol, esmolol

Industry-Leading Label Design The admixtures you receive from PharMEDium feature easy-toread labels designed to help reduce errors and facilitate proper administration: • Easy-to-see “TALL man” lettering allows for instant drug recognition • Drug concentration and total dose are listed, clearly indicating the precise amount of active drug contained in the admixture • Lot number and expiration date are prominent • Bar codes meet UCC.EAN standards and FDA regulations for drug identification • CII nomenclature indicates a scheduled substance • Enhanced safety messaging for correct infusion

e222: The Only Drug Order Form Officially Endorsed by Trees Paperless. Effortless. Costs less. Only from PharMEDium. Enjoy the benefits of PharMEDium even faster. An electronic version of DEA Form 222 for Schedule II Controlled Substances (e222) can now be filled out and submitted electronically at www.pharmedium.com. You can reduce the time you spend filling out orders from minutes to seconds! PharMEDium is the only outsourced compounder to offer this service! To learn more about PharMEDium, please visit our Web site at www. p h ar m ed i u m . co m o r cal l u s at (800) 523-7749.

Special Advertising Section Pharmacy Practice News

TEVA PHARMACEUTICALS The U.S. Market Leader By any measure, Teva Pharmaceuticals is the leading generic drug company in the United States. Teva introduced 19 generic products in 2009 and had 210 abbreviated new drug applications (ANDAs) pending FDA approval as of April 26, 2010. The company markets the broadest product line in the country, with over 400 generic products in nearly 1,400 dosage strengths and packaging sizes covering all major therapeutic categories. Teva now represents 22% of U.S. generic prescriptions, with one out of every six U.S. prescriptions being filled with a Teva product. A Global Leader Teva’s parent company, Teva Pharmaceutical Industries Limited, is the leading generic drug company in the world in terms of both total and new prescriptions. The company’s global presence covers North America, Europe, Latin America, Asia and Israel, with approximately 60% of its sales generated in North America. Teva has over 35,000 employees including more than 6,000 in the United States, and annual net sales that totaled $13.9 billion in 2009. Teva operates in more than 60 countries, including 38 finished dosage pharmaceutical manufacturing sites, 15 generic R&D centers and 21 active pharmaceutical ingredient (API)/raw material sites around the world, with all pharmaceutical production facilities maintaining one uniform quality standard.

can maintain its high standard of quality and efficiency, and also its long-standing commitment to customer satisfaction.

AT A GLANCE

Innovation in Biosimilars

1090 Horsham Road P.O. Box 1090 North Wales, PA 19454-1090 Phone: (800) 545-8800 Web site: www.tevausa.com

Address

One example of Teva’s innovation is its continued strides in the emerging biosimilars market—a major growth driver in the company’s long-term strategy. Teva entered into a joint venture with Lonza Group Ltd., to develop, manufacture and market affordable, efficacious and safe generic equivalents of a selected portfolio of biologic pharmaceuticals. The combination of Teva’s global leadership and expertise in clinical development and marketing of generic pharmaceuticals, with Lonza’s deep knowledge and experience in biopharmaceutical development, large-scale manufacturing and state-ofthe-art manufacturing facilities, generates significant opportunities and benefits for both companies as well as for patients.

Leading the Way to Affordable Healthcare Teva’s mission is to play a leading role in the continuing transformation of U.S. healthcare. The company’s Government Affairs team occupies an office on Capitol Hill and works on behalf of American consumers to advance both innovation and patient access to needed therapies. Last year, Teva launched a nationwide campaign, ‘Year of Affordable Healthcare,’ as a call for increased access to affordable healthcare for American citizens. Teva is the leading provider of affordable generic medicines. Its robust pipeline of future products is a source of continuing value to American consumers.

Diversified and Vertically Integrated In addition to its leadership in the generics market, Teva has a significant and growing branded pharmaceutical portfolio, including COPAXONE® for multiple sclerosis, AZILECT® for Parkinson’s disease, ProAir® for respiratory disorders, and a sizeable women’s health portfolio. The company’s well-established and balanced portfolio is supported by a vertically integrated API business. This vertical integration ensures that as Teva continues to grow, the company

Special Advertising Section Pharmacy Practice News

Teva’s Recent Generic Product Introductions

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Prevacid® Delayed-Release

Corporate Profile 2010

PP11

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 News has become the best-read newspaper in its field, according to a syndicated, independent readership survey by Kantar Media. In the July 2010 survey, Pharmacy Practice News achieved a No. 1 ranking in at least five major readership categories* among staff pharmacists, pharmacy directors and other key health-system personnel. Our Mission

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

Employees 69

Publisher, CEO and Managing Partner Raymond E. McMahon

President, Partner Van Velle

Pharmacy Practice News Publication Directors Dave Kaplan, Phil Redgate

Editorial Director David Bronstein

The mission of Pharmacy Practice News is twofold: to provide health-system pharmacists with the information they need to provide highquality patient care, and to help them demonstrate the value of that care to colleagues and administrators. To achieve these goals, Pharmacy Practice News editors follow developments in both academic and hospital practice settings. Most of our coverage comes from attending meetings convened by the major pharmacy groups, such as the American Society of Health-System Pharmacists. But we also attend smaller, more focused meetings to keep our readers abreast of specialty care. For example, the magazine continues to step up its coverage of the Hematology/ Oncology Pharmacy Association’s annual meeting. We also cover the Society of Critical Care Medicine (SCCM), with 2010 being a special year for the meeting and the magazine—editorial advisory board member Judi Jacobi, PharmD, was installed as the first pharmacist-president of SCCM. In our November 2009 issue, we featured a Q&A with Dr. Jacobi as well as testimonials from several of her colleagues and mentors.

Senior Editor

Peer-to-Peer Content

Sarah Tilyou

The magazine also welcomes contributions from readers in an effort to facilitate a peer-to-peer exchange of best practices in health-system pharmacy. Contributions can be in the form of Practice Pearls, such as the one on bar-code medication administration in this issue (p. 50). We also feature regular contributions from thought leaders in pharmacy, including Ernie Anderson, MS, RPh, who authors the Leadership in Action column (p. 6), Jerry Siegel, PharmD, who answers Frequently Asked Questions on IV immunoglobulin therapy (p. 18), and our newest contributor, Gita Wasan Patel, PharmD. This month, Dr. Patel and her co-author describe how they achieved a 41% reduction in sepsis mortality, thanks to their hospital’s efforts to comply with the Surviving Sepsis national campaign (p. 16). Also new for this year is our special “Spotlight” sections that focus on important clinical and

operational areas of pharmacy practice. Our latest Spotlight theme, technology, appeared in the July issue and featured articles on bar coding, automation, drug repackaging, robotics, remote telepharmacy and more.

Educational Reviews Of course, Pharmacy Practice News also continues to publish triedand-true content that has helped us build our leading readership position. Our monthly educational reviews, for example, continue to be highly regarded. Written by authorities in a given treatment area, the reviews are comprehensive summaries of state-of-the-art thinking on a specific disease state. Topics this year included safe medication practices, hazardous drug handling, parenteral nutrition therapy, and chemotherapy-induced nausea and vomiting, among others. Many of these educational reviews are featured in Pharmacy Practice News Special Edition, our annual print compendium that mails in October.

Web Site Initiatives Each month, all of our print articles are posted to pharmacypracticenews.com and can be shared via easy-to-access links to Facebook, Twitter and other social and business networking sites. Web-exclusive content, such as breaking news and expanded coverage of stories that appear in the magazine, also are featured. This year, we also debuted a monthly opt-in e-newsletter that is sent about a week before the print issue mails, previewing cover stories and other featured content. We also started a pharmacypracticenews.com monthly podcast by our advisory board members, who comment on articles and issue of interest to health-system pharmacists.

Parent Company Pharmacy Practice News’ leading position in readership did not occur in a vacuum: The magazine is part of the McMahon Publishing family of specialty newspapers, many of which are No. 1 read in their fields. Anesthesiology News, General Surgery News, Gastroenterology and Endoscopy News, for example, are perennial favorites. The company also publishes several recently launched titles that are moving rapidly up the list of competing publications, including Clinical Oncology News and Pain Medicine News.

Production Manager

Supplements and Projects

Mark Neufeld

All of our publications include educational supplements such as Special Reports and Literature Reviews—custom-written monographs bound inside the newspapers. These supplements, produced by the Special Projects division of McMahon Publishing, can be based on symposium coverage, interviews with experts, recently published research and so forth, and are often CME/CE accredited. Other offerings from the company’s Special Projects division include wall charts and pocket guides—often based on our educational reviews—that serve as onthe-spot instructional tools for health care providers. Taken together, all of these educational initiatives underscore our company’s mission: to be a full-service publishing company for a full-service profession.

Art Director Frank Tagarello

PP12

Corporate Profile 2010

* No. 1 ranking in: average issue readers, directors (Table 115); average page exposures, directors (Table 115); high readers, total healthsystem pharmacy (Table 217); average page exposures, total health-system pharmacy (Table 117); high readers, staff (Table 216). 2010 Pharmacy Readership Study, Kantar Media.

Special Advertising Section Pharmacy Practice News

Clinical 35

Pharmacy Practice News • August 2010

Guest Editorial

Multiuse and Multidose Drug Vials: Where Is the Liability? I n early May, a Las Vegas jury awarded Henry Chanin and his wife, Lorraine, $500 million in punitive damages stemming from Mr. Chanin’s infection with hepatitis C during a 2008 endoscopy. Health care workers at the clinic where Mr. Chanin was treated gave him propofol during the procedure, using a vial of the drug from which they had already drawn doses for another patient, and a reused syringe, too. The jury ordered two drugmakers, Teva and Baxter Healthcare (which distributed Teva’s products), to pay $356 million and $144 million, respectively, to the Chanins. Earlier, the same jury awarded the couple $5 million in damages from the companies for failing to adequately warn patients of the infection risks associated with spreading vials of propofol across multiple patients and for selling an inherently unsafe drug. The case is the first in what could be a long string of suits stemming from a 2008 outbreak of hepatitis C in Nevada in which at least nine, and possibly as many as 114 patients, contracted the virus. Multiuse vials have been implicated in other recent outbreaks of infection. In 2001, an anesthesiologist at a New York endoscopy clinic allegedly infected 19 patients with hepatitis C virus (HCV) through reused syringes and a contaminated multidose medication vial used for multiple patients. Similar HCV outbreaks in New York occurred in 2002 and 2007, in which 102 patients were allegedly infected. In 2002, nearly 100 cancer patients contracted HCV in Nebraska, when a health care worker at a hematology clinic used the same syringe and needle to obtain a flush solution from an IV bag. So far, the Las Vegas episode is the first in which drug companies have been found guilty. Teva and Baxter are in the process of appealing the judgment. The firms argue that propofol labeling clearly states that it is intended for use in only one patient, and that aseptic procedures—such as the use of sterile syringes—should be followed at all times when administering the drug. Will the appeal succeed; who is ultimately liable; and what are the implications for clinicians, institutions and for other medications that are dispensed in what could be used as multidose vials? No discussion of infection through the use of multiuse vials—even those not intended to be such—would be complete without mentioning that anything that comes into contact with a patient must subsequently be considered to be contaminated and may carry microorganisms. From a practical point of view, a vial represents simply one stage in the potential transmission of infection. In almost every clinical area involving

injection practices, infections have been traced to a tainted medication, needle, syringe or injection port; thus, contamination may occur at any point of the medication administration chain. Many medications, ranging from IV fluids, local anesthetics and vaccines, are sold in vials that may pose multiuse hazards. Even so, these drugs continue to be dispensed in vials that contain more than the amount of medication needed for a single administration for the following reasons: • There is seldom a single dose that suffices for all, or even most, patients. • Repetitive or incremental dosing of certain titratable medications is frequently necessary. • Hospital pharmacy stocking may be simplified. • Excess medications that are sold but not used represent a potential profit margin to manufacturers. • The costs of distribution are less with larger-volume vials. From a legal analysis, a manufacturer has a duty to make a product as safe as possible. Because few things are completely safe, under most circumstances the more realistic obligation for the manufacturer is to provide adequate warnings of known hazards to users. Product liability lawsuits may be built on several legal theories including negligence, breach of warranty, misrepresentation and strict tort liability. In the suit against Teva and Baxter, for example, jurors found the companies guilty of breach of implied warranty and failure to warn. However, the companies were not found guilty of selling a defective product. Traditionally, users of products must be at least as careful as the “reasonably careful person.” That standard is subtly evolving to the “occasionally careless

consumer,” which is a higher standard for manufacturers to attain. Whether the “careless consumer” standard will apply to health care professionals is unclear. The legal system at present appears to favor consumers over manufacturers. Courts now focus on the magnitude of the risk associated with the use of a product and the ease with which injury could have been avoided through an alternative design, marketing or labeling. Government agencies and professional bodies generally have been explicit about the appropriate way to handle multiuse vials of medications. The Association for Professionals in Infection Control and Epidemiology has stated that infectious outbreaks such as the one in Nevada are unacceptable because proper aseptic technique and basic infection prevention practices would have prevented the incidents. The FDA has not issued regulations specific to multiuse vials. However, throughout the ongoing shortage of propofol, the agency has been clear in its communications with anesthesiologists, pharmacists and other health care providers that they should not split larger vials of propofol into multidose units. The federal government also has begun shifting the costs associated with unused medications from the patient, provider or institution to itself, in what appears to be a patient safety initiative. The Centers for Medicare & Medicaid Services (CMS) has developed policies to ensure proper billing for discarded drugs and biologics in both single-use vials and single-use packages. Whether or not private payers will follow CMS’s lead remains to be seen. Meanwhile, states increasingly are mandating continuing medical education directed at minimizing the transmission of health care–acquired infections. In many instances, failure to adhere to prop-

er infection control practices represents professional misconduct that is enforced at the level of state departments of health. In April 2008, after receiving a formal complaint James Szalados, MD, JD from the Southern Nevada Health District, the Nevada Medical Board filed to temporarily suspend the medical licenses of the physicians involved in the hepatitis outbreak. One of them, a prominent member of the state medical board, has since voluntarily surrendered his medical license there. Similarly, many hospitals now attempt to promote proper infection control practices through mandatory education and reporting, in-house epidemiology, rules and regulations, bylaws and codes of conduct that, when breached, may result in employee dismissal or peerreview sanctions. As the latest lawsuit illustrates, despite the extensive education and training of health care workers, overwhelming epidemiologic evidence and common sense, unacceptable clinical practices persist. That physicians and other health care professionals need reminding that they should wash their hands between cases, use protective isolation barriers when indicated and practice sterile techniques for injections is nearly incomprehensible. And yet ... So why, then, were Teva and Baxter targeted and not the clinicians whose actions led to the outbreak? The answer, in a word, is money. From a litigation perspective, the first target usually will be the deepest pocket— hence, the drugmakers were sued in the Nevada case. Given this background, the companies’ appeal has a strong chance of success. Yet whatever the outcome, medication preparations, pharmaceutical costs and injection practices are likely to change rapidly in the near future as a result of this costly litigation. Clinicians who persist in bad habits of infection control should take note: Considering the present state of knowledge regarding infection control and the widespread culture-of-safety mandates, the focus of litigation regarding nosocomial infections may even shift from manufacturers to health care providers and the institutions in which they practice. —James Szalados, MD, JD Dr. Szalados practices anesthesiology and critical care medicine, is a senior-level hospital administrator and practices law in New York. He is the author of several medical and legal books and texts.

Hem/Onc Pharmacy

Pharmacy Practice News • August 2010

In Focus

Battle of Second-Generation TKIs Declared in CML The data so far suggest that “without a tool to select patients destined for optimal response to imatinib, second-generation TKIs should be used as primary therapy in CML,” said Michael Mauro, MD, associate professor of medicine, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, who was not involved with either study. Dr. Mauro suggested that the arguments for withholding these agents, such as the potential for inducing broad drug resistance, do not appear to outweigh the proven advantages. Dr. Mauro made his remarks at the ASCO meeting directly following the presentations of 12-month data on dasa-

ROVING

already have to make a lot of visits to the hospital for their treatments,” said Dr. Bernard, who works with the pharmacist/nurse team. “We wanted to try not to burden them with a lot of additional visits for symptom management, so we decided to go where the patients are.” John Valgus, PharmD, hematology/ oncology clinical pharmacist practitioner, who estimates that his role as a roving pharmacist takes about 60% of his time, said that typically the oncologist manages a patient’s symptoms in addition to treating the cancer. Sandi Jarr, CNS, supportive care nurse consultant, who teams up with Dr. Valgus, said that “there are times when the primary oncologist uses our consultation service to make recommendations on difficult symptoms.” “As far as we know this is the only program of its kind,” added Dr. Valgus. Dr. Bernard noted that such a program would be most effective in states that allow pharmacists to write prescriptions for narcotics because pain management is such a big part of the program.

continued from page 1

the patient’s physician and, if approved, they implement the treatment plan. To assess the effectiveness of the consult service, the researchers reviewed outcomes in 89 patients who were seen within the first 18 months of the program. Overall, there were 292 patient consults with both new and returning patients. Pain was the reason for the consult in 75% of cases; constipation, 11%; nausea/vomiting, 8%; anxiety, 4%; spiritual concerns, 2%. Tumor types included lung, 20%; gynecologic, 20%; head and neck, 15%; genitourinary, 12%; gastrointestinal, 8%, and breast, 7%. Patient’s symptom scores were one of the primary outcomes measured, using a five-point severity scale (5, maximum severity). In a sample of 49 patients, pain scores decreased from 4 to 2.7, nausea from 4 to 1.4, and constipation from 2 to 1.6, all by the second visit. Those clinical improvements persisted beyond the second visit, “but patient numbers were [small], so it is difficult to assess the significance of that [longer-term] finding,” said lead researcher Stephen A. Bernard, MD, professor of medicine in the Division of Hematology/Oncology at UNC-CH. The investigators also tracked the type and frequency of interventions by pharmacists in the consult program. In the first 18 months after inception, the team recommended an increase in medication in 57% of cases; a decrease in 4%; no change in 21%; a switch of medication in 21%; additional medications in 32%; and a discontinuation of medication in 6%. “Many of our patients in North Carolina live more than an hour away, and they

Reimbursement Crucial To Program’s Success Billing the pharmacist’s time separately is another important feature of the program, Dr. Bernard said. “When we designed the program we met with the billing department and developed a separate code for the program so we can track the revenues that come through the pharmacist. This is important because we can demonstrate the financial impact of the program to groups that are supporting us financially.” He noted that salary support for the pharmacist position comes partly from a grant from the University Cancer

tinib (abstract LBA6500) and 18-month data on nilotinib (abstract 6501), each of which was being compared in a head-tohead study with imatinib. The results of the two trials have been remarkably similar and were published simultaneously in the June 17, 2010, edition of The New England Journal of Medicine. Based on the superior results of the two newer TKIs relative to imatinib, each of the lead investigators concluded that the TKI they studied would become a new standard in CML. Dr. Mauro agreed that second-line TKIs are likely to replace imatinib, but declined to speculate about whether one of these newer

TKIs might be a better first choice than the other. Dr. Mauro also pointed out that there are likely predictors that could single out patients who respond equally well or better to imatinib than the newer second-line TKIs. Although use of such markers would be consistent with a general trend toward individualized therapy in oncology, they could become particularly important if secondgeneration agents cost substantially more than imatinib or when generics are developed for imatinib in advance of the second-generation agents. The relative sequence of TKIs also may change for specific individuals as more is learned about susceptibility to resistance.

Trial Details In the dasatinib trial, after 12 months of follow-up, the complete cytogenetic

•

see TKIs, page 38

Severity Scale

Chicago–Second-generation tyrosine kinase inhibitors (TKIs) appear likely to replace imatinib (Gleevec, Novartis) as first-line therapy in patients with previously untreated chronic myelogenous leukemia (CML). New data from separate head-to-head Phase III trials presented at the 2010 annual meeting of the American Society of Clinical Oncology (ASCO) have shown that nilotinib (Tasigna, Novartis) and dasatinib (Sprycel, Bristol-Myers Squibb) are superior to imatinib for major prognostic indicators, particularly complete molecular and cytogenetic responses. Neither TKI has shown a survival benefit compared with imatinib in the relatively brief follow-up that has occurred so far, but a survival benefit is anticipated based on prognostic markers. On June 17, the FDA approved nilotinib in the first-line setting.

(5=maximum severity)

Baselline

Post-Rollout

2.7 2

1.6 1.6

1.4

Pain

Nausea

Constipation

Figure. Impact of pharmacist consults.

‘If the pharmacists could bill their services as consultants and increase the number of patients they see to cost justify it, then this would be a great service to cancer patients.’ —Jane Pruemer, PharmD, BCOP Research Fund of the Lineberger Comprehensive Cancer Center, which is part of the UNC School of Medicine. Dr. Valgus agreed that tracking revenue is crucial. “A major hurdle is proving the pharmacist is as valuable a provider as a physician assistant or nurse practitioner. It’s key in making this model more widely available.”

Another Pharmacist’s Take Jane Pruemer, PharmD, BCOP, professor of clinical pharmacy practice and administrative sciences at the University of Cincinnati, who is not involved

with the North Carolina program but who is a published expert on supportive care, offered kudos to the UNC-CH team. “This is a great system with regard to availability and convenience to patients who are very ill and live far away,” she said. “The main issue I see would be the cost justification of devoting a full-time clinical pharmacist. If the pharmacists could bill their services as consultants and increase the number of patients they see to cost-justify it, then this would be a great service to cancer patients.” —Celia Vimont

www.BioOncology.com

Taking a broader view — charting a unique course in cancer care

At Genentech BioOncology, not only are we leading the fight against cancer with innovative science, but we’re also dedicated to supporting patients and others within the oncology community. A commitment to patients — We created Genentech BioOncology™ Access Solutions™, a single source for all access and reimbursement issues, so healthcare providers can remain focused on patient care. Reducing barriers to treatment — We help make treatment possible for patients in financial need through our BioOncology Co-Pay Card Program and ongoing charitable donations to various independent nonprofit organizations in support of co-pay assistance. A commitment to care — Our first product was approved in 1985, and since then we have donated approximately $1.5 billion in medicine to uninsured patients through the Genentech® Access to Care Foundation and other donation programs. Our goal is to fundamentally change the way that cancer is treated by personalizing solutions to patient care.

Hem/Onc Pharmacy

Pharmacy Practice News • August 2010

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response (CCyR) rate was 77% for 259 patients randomized to the secondgeneration TKI compared with 66% for 260 patients randomized to imatinib (P=0.0067). The major molecular response (MMR) rates on dasatinib and imatinib were 46% and 28%, respectively (P<0.0001; Figure 1), according to Hagop Kantarjian, MD, professor and chair of the Department of Leukemia at the University of Texas M.D. Anderson Cancer Center, in Houston, who presented the

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Dronabinol SGC CIII is a new unit dose product from AHP!

Dronabinol SGC CIII – another New EXCLUSIVE UD Product from AHP! American Health packaging has expanded its line of unit dose products. Dronabinol SGC CIII (compare to Marinol®) is the latest launch to join our Oncology-related line of products. Others are listed below. All of our unit dose items are bar coded to the dose level and are stability tested to support extended shelf life. In addition, our color-coded labels and use of “tall man” lettering aids in selecting the correct product for dispensing. 800.707.4621 americanhealthpackaging.com ABC 6 Digit Cardinal McKesson Item # Health # Item #

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data as a late-breaking abstract. The nilotinib trial evaluated two doses of the drug. In this trial, by 12 months, the CCyR rates were 80% for the 300-mg dose and 78% for the 400-mg dose of nilotinib, and 65% for imatinib (P<0.001 for both nilotinib doses vs. imatinib). The MMR rates at 12 months, initially reported at the 2009 meeting of the American Society of Hematology, were 44% for the 300-mg dose and 43% for the 400-mg dose of nilotinib, and 22% for imatinib (P<0.001 for both comparisons). In updated nilotinib results presented by Richard A. Larson, MD, professor of medicine at the University of Chicago Pritzker School of Medicine, MMR rates remained almost twice as high on the second-generation TKI as imatinib at 18 months. Rates were 69%, 63% and 36% for nilotinib 300 mg, nilotinib 400 mg and imatinib 400 mg, respectively (Figure 2). Polymerase chain reaction analyses were completed at 18 months on 525 of 846 patients randomized. At 24 months, MMR rates in 145 evaluated patients were 86% in the nilotinib 300-mg arm, 88% in the nilotinib 400-mg arm and 48% in the imatinib arm. The best CCyR rates in the follow-up completed so far are 85%, 82% and 74%, respectively. “With longer follow-up, rates of MMR and CCyR remain superior on nilotinib when compared to imatinib,” Dr. Larson said. He said that the molecular responses “are continuing to deepen over time” and this appears to be reflected in overall survival. At 18 months, there were nine deaths in the imatinib arm versus five in the nilotinib 300-mg arm and two in the nilotinib 400-mg arm. The difference between the higher dose of nilotinib and imatinib was statistically significant (P=0.03), with the expectation that the survival differences will widen over time. In the clinical trials so far, each agent has appeared to be at least as well tolerated as imatinib, although the types of predominant side effects have differed. In the nilotinib study, for example, nausea, vomiting, muscle spasms and diarrhea were more common with imatinib, whereas rash, headache, pruritus and alopecia were more common with nilotinib. Richard Stone, MD, director of the Adult Leukemia Program, Dana-Farber Cancer Institute, and professor of medicine, Harvard Medical School, both in Boston, said the results were practice-changing. “While these results are very important and make up-front use of the secondgeneration TKIs a reasonable option, whether every newly diagnosed chronicphase CML patient should receive nilotinib or dasatinib remains unclear,” Dr. Stone said. “Imatinib has a proven track record; over eight years of follow-up have provided reassuring long-term safety and efficacy data.” —Ted Bosworth

40 Clinical

Pharmacy Practice News • August 2010

Internal Medicine

Quick Response to Tocilizumab Seen in Rheumatoid Arthritis Tampa, Fla.—For patients with rheumatoid arthritis (RA), adding tocilizumab (Actemra, Hoffman-LaRoche) to existing disease-modifying anti-rheumatic drug (DMARD) therapy results in significant improvements in pain, disease activity and inflammation as early as one week after treatment begins, according to research presented at the 2010 Summer Meeting of the American Society of Health-System Pharmacists. “Within seven days after the initial

infusion, a lot of the markers and disease activity measures we checked were already improving, which is important because patients always ask what to expect,” said primary author Yusuf Yazici, MD, director of the Seligman Center for Advanced Therapeutics, New York University Hospital for Joint Diseases in New York City. “It’s good news for those whose disease is very active and who need improvement right away.” Tocilizumab, an interleukin (IL)-6

receptor inhibitor, received FDA approval in January 2010 for patients with moderate to severe RA who have not responded adequately to tumor necrosis factor-α inhibitors. The FDA also mandated a Risk Evaluation and Mitigation Strategy (REMS) for the drug, as it has for all RA biologic therapies. The REMS requires the manufacturer to inform health professionals and patients about the increased risk for serious infections and gastrointes-

The commitment to

‘[Tocilizumab is] good news for those whose disease is very active and who need improvement right away.’

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—Yusuf Yazici, MD

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tinal perforations associated with tocilizumab. The investigators collected data for a subgroup of 62 patients already enrolled in a six-month study of tocilizumab plus DMARDs versus placebo plus DMARDs (73% female; mean age 53.1 years; mean disease duration 6.8 years). Forty subjects were randomized to the treatment arm and 22 to the control group. All subjects had inadequate response to one or more DMARD. Mean improvements from baseline to day 7 were significant in tocilizumab patients for pain (P=0.010), patient global assessment of disease activity (P=0.005), C-reative protein level (P<0.001), and erythrocyte sedimentation rate (P< 0.001). Physician global assessments of disease activity, tender and swollen joint counts, and physical function also improved, but the mean changes were not statistically significantly different between groups. Eric Ruderman, MD, associate professor of medicine, Division of Rheumatology at the Northwestern University Fineberg School of Medicine in Chicago, said the results do not surprise him because tocilizumab blocks IL-6, an important inflammatory cytokine responsible for many RA symptoms. But he questioned the importance of rapid symptomatic relief in RA therapy. “We’re talking about a lifelong disease and lifelong therapy,” Dr. Ruderman told Pharmacy Practice News. “None of the treatments we have now or that are in the pipeline are going to cure the disease. The more important issue is finding an effective therapy with a durable response that also will prevent disease-related damage and activity and subsequent disability. I think

•

see RA PATIENTS, page 46

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42 Technology

Pharmacy Practice News • August 2010

Automation

Post-Pump Recall, Industry Responds H

ospitals that will soon be swapping out older infusion pumps plagued with what the FDA calls “deficiencies in device design and engineering” will not find the process easy. On April 30, the FDA ordered Baxter Healthcare Corp. to recall and destroy its Colleague Volumetric Infusion Pumps and to provide refunds or replace pumps at no cost. Approximately 190,000 pumps are affected by the recall. This recall is the latest event in an ongoing saga of infusion pump malfunctions and safety concerns: The FDA has received more than 56,000 reports of adverse events associated with infusion pumps over the past five years, and Baxter’s pumps are not the only ones with problems. Tom Van Hassel, RPh, MPA, director of pharmacy for the Yuma Regional Medical Center in Yuma, Ariz., noted that the FDA’s concern about infusion pumps covers a “broad spectrum” and

Baxter Healthcare Corp. is offering customers a variety of options for dealing with the company’s recalled Colleague infusion pumps (left), including rebates, replacement pumps with later-generation technology such as Sigma Spectrum pumps (right) or lease termination.

is not just linked to one manufacturer. “All the companies involved will have to respond or face the ire of the FDA and probably the hospitals as well,” he said. “Replacing infusion pumps is a big job.” Michael R. Cohen, RPh, MS, ScD,

‘If hospitals do a good job of training and educating users, and if they take the very important step of standardizing their drug libraries, we should wind up with a much safer process.’ —Michael R. Cohen, RPh, MS, ScD

A Closer Look at the FDA’s Initiatives

s part of its April 30 initiative, the FDA has published draft guidance recommending that infusion pump manufacturers provide additional design and engineering information to the agency during premarket review of the devices. The FDA has told manufacturers that they may need to conduct additional risk assessments to support clearance of new or modified pumps, and the agency is offering manufacturers the option of submitting their infusion pump software codes to FDA experts for a diagnostic static analysis prior to premarket review. Such an analysis can help detect software problems early in the device development process. The FDA also is conducting workshops in which participants (end users and manufacturers) will be asked to discuss common safety problems and explore opportunities to improve the design of infusion pumps on the market or in development. In response to the FDA’s draft guidance on design and development, Baxter spokesman John O’Malley said management already has “expanded our infusion pump design and testing requirements to address elements like human factors and current clinical environments. We have a wide range of verification and validation methodologies, including sophisticated simulated use testing.” Mr. O’Malley noted that Baxter will use the FDA’s draft guidance and modify the company’s product development procedures to ensure that the company catches any potential design issues early in development. Tareta Adams, spokeswoman for Hospira, said Hospira, too, will “continue to be an active part of the guidance process during the review and public comment period. We will participate in the FDA workshop and industry discussions on the implications of the guidance, and will continue to dialogue with the agency and provide feedback during the public comment period.” Gale White, vice president of infusion systems marketing at B. Braun, said the company will be participating in groups, working with the FDA to provide input as well as to increase the amount of “clinical and simulation testing we do and using more external clinicians and nurses in test modes rather than internal employees.” —Liz Parks

president of the Institute for Safe Medication Practices (ISMP), noted that ISMP has been receiving complaints about infusion pumps for 20 to 30 years. Most of these complaints are about older generations of pumps, which can’t be updated wirelessly. “That was one of Baxter’s problems in trying to fix the issues it had with Colleague. Wireless costs more but it’s worth it.” In an ISMP Patient Safety Tip of the Week issued on April 27, the group cited the 56,000 infusion pump adverse event reports to the FDA, adding that there have been 87 infusion pump recalls, “many of which have been for serious safety problems.” According to the FDA, the most frequently reported problems are software error messages, user error, broken components, battery failures, alarm failures and over- and under-infusions. There also have been user-interface issues such as ambiguous on-screen instructions that lead to dosing errors; mechanical or electrical failures, including components that break during routine use; premature battery failures; and sparks or pump fires. The FDA is working with Baxter and health care facilities to develop an orderly transition plan that will minimize disruption to patient care. John O’Malley, spokesman for Baxter, said the company already is talking with customers about compliance with the FDA recall order, but added that there is no timeline designating when swapping will begin or end. Baxter will offer customers a variety of options, “including rebates, replacement pumps with later-generation technology such as Sigma Spectrum pumps or lease termination based on the preferences of our customers.”

Manufacturers Respond Tareta Adams, a spokeswoman for Hospira, noted that the company is increasing production of its current generation Plum A+ smart pumps “to meet hospital replacement needs during the Colleague recall.” Gale White, vice president of infusion systems marketing at B. Braun, which produces pumps for the global marketplace, said the company is diverting all production to the U.S. market, which will give the company the ability to produce approximately 10,000 Space pumps each month. B. Braun also is increasing Outlook ES capacity to a yet to be determined monthly amount, Ms. White noted. Gord LaFortune, senior vice president and general manager, Infusion Systems of CareFusion, said “we have reviewed our Alaris infusion system manufacturing and customer support capacity, and we

•

see POST-PUMP, page 44

Syringe Infuser A Simple Solution

ne way that hospitals may be able to save money and time as they transition to newer generations of smart infusion pumps is to invest in a syringe infuser that allows nurses to administer nonrated critical intermittent antibiotics to patients. Baxa Corporation has introduced the InFuse ™T-10 Syringe Infuser, a mechanical infuser for syringes filled manually or through pharmacy infusion dispensing automation such as the Baxa IntelliFill i.v. or RapidFill Automated Syringe Filler. “Since intermittent antibiotics account for more than 40% of all infusions, the InFuse T-10 can both free up the very precise smart pumps needed for critical infusions as well as reduce the time it takes for nurses to program smart pumps for intermittent doses that don’t demand precise rate-controlled infusion,” said Dennis Schneider, Baxa’s senior vice president of marketing and business. “Hospitals never have enough pumps, and smart pumps cost between $3,000 and $5,000,” Mr. Schneider said. He estimated that at a list price of $150 each, the InFuse Infuser should save hospitals $1 to $5 per dose, due to the technology’s lower acquisition costs. Syringe delivery with the InFuse T-10 Infuser reduces the fluid volume administered with ready-to-use or minibag delivery. According to Mr. Schneider, this should contribute “to better patient outcomes through fluid balancing—reducing adverse effects on internal organs from fluid overload. You can reduce the risk for congestive heart failure in a patients from infusing too much fluid.” The InFuse T-10 accommodates intermittent antibiotic dose deliveries from 0.5 to 10 mL and provides silent delivery. There is no need for beeper alarms to alert nurses to the need to cap and disconnect a smart-pump minibag infuser. —Liz Parks

44 Technology

Pharmacy Practice News • August 2010

Automation

POST-PUMP continued from page 42

are prepared to meet any increase in customer demand. We have previously demonstrated our ability to meet high levels of demand, including shipping as many as 5,000 units per day to customers.” That process seems logical to Mr. Van Hassel. “There will not be a single solution to ease the process of replacement, but a number of creative replacement strategies such as swap-outs, financial incentives—whatever each company works out to replace older-generation

pumps without extreme hardships to hospitals,” he said. He added that newer generations of smart pumps, including those from Hospira, CareFusion and B. Braun, have features that weren’t available before, including improved keypads. He also suggested that newer generations of pumps are easier to use overall. “Their interfaces and technology are more intuitive. This should help reduce the problem of workarounds—that is, instances where nurses administering an infusion decide to bypass the pump’s technology and manually type in the dosages and other

data themselves, which contributes to user errors.” According to Dr. Cohen, the software that comes with newer generations of pumps can help hospitals standardize their drug libraries. “Not having standard drug libraries contributes substantially to user error,” he said. “As we go through the transition, it’s a perfect opportunity for hospitals to maximize their use of drug libraries and to standardize and reduce the options that their doctors have for designating concentrations and units prescribed. This would help enormously in mini-

Immune Globulin Intravenous (Human) Flebogamma® 5% DIF For intravenous use only Rx only

BRIEF SUMMARY CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION INDICATIONS AND USAGE Flebogamma® 5% DIF is indicated for replacement therapy in primary (inherited) humoral immunodeficiency disorders. DOSAGE AND ADMINISTRATION The usual dose of Flebogamma® 5% DIF for replacement therapy in primary humoral immunodeficiency diseases is 300 to 600 mg/kg body weight administered every 3 to 4 weeks. An in-line filter with a pore size of 15 to 20 microns is recommended for the infusion. Antibacterial filters (0.2 micron) may also be used. Discard unused contents and administration devices after use. The infusion of Flebogamma® 5% DIF should be initiated at a rate of 0.01 mL/kg body weight/minute (0.5 mg/kg/minute). If, during the first 30 minutes, the patient does not experience any discomfort, the rate may be gradually increased to a maximum of 0.10 mL/kg/minute (5 mg/kg/minute). For patients judged to be at risk for developing renal dysfunction or considered to be at increased risk of thombotic/thromboembolic events, it may be prudent to limit the infusion rate to a maximum rate less than 0.06 mL/kg body weight/minute (3 mg/ kg/minute). Reduction in dose, concentration, and/or rate of infusion in patients at risk of acute renal failure, which includes patients over 65, has been proposed in the literature in order to reduce the risk of acute renal failure. CONTRAINDICATIONS Flebogamma® 5% DIF should not be administered to individuals with a history of severe or anaphylactic reactions to blood or blood-derived products. Patients with severe selective IgA deficiency (IgA < 0.05 g/L) may develop anti-IgA antibodies that can result in a severe anaphylactic reaction. Anaphylaxis can occur using Flebogamma® 5% DIF even though it contains low amounts of IgA (typically < 50 μg/mL). Such patients should only receive intravenous immune globulin with utmost caution and in a setting where supportive care is available for treating life-threatening reactions. If patients are known to be intolerant to any component of Flebogamma® 5% DIF, such as sorbitol (i.e., intolerance to fructose), they should not receive the product. WARNINGS Immune Globulin Intravenous (Human) (IGIV) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number. Flebogamma® 5% DIF does not contain sucrose. See PRECAUTIONS and DOSAGE AND ADMINISTRATION sections for important information intended to reduce the risk of acute renal failure. Flebogamma® 5% DIF is made from human plasma. As with all plasma derived products, the risk of transmission of infectious agents, including viruses and theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated. The risk that such products will transmit an infectious agent has been greatly reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Grifols Biologicals at 888-GRIFOLS (888-474-3657). All patients, but especially individuals receiving Flebogamma® 5% DIF for the first time or being restarted on the product after a treatment hiatus of more than 8 weeks, may be at risk for the development of inflammatory reactions characterized by fever, chills, nausea, and vomiting. Careful monitoring of recipients and adherence to recommendations may reduce the risk of these types of events. Appropriate supportive care, including immediate access to epinephrine injection, should be available for the management of acute anaphylactic reactions.

mizing errors that nurses might make as they program the pumps.”

Task Force Tackles Safety Issues In the meantime, as the transition gets under way, hospitals may want to do what Yuma Regional Medical Center is doing: Form a task force of staff from key departments such as pharmacy, nursing, and bio med, said Mr. Van Hassel. “We will be doing more training with nurses to make sure they are using the pumps correctly. We also will be verifying the settings and reading the displays before

PRECAUTIONS General: Any vial that has been entered should be used promptly. Partially used vials should be discarded and not saved for future use because the solution contains no preservative. Do not use if turbid. Solution that has been frozen should not be used. Ensure that patients are not volume-depleted before the initiation of the infusion of IGIV. Renal Function: Periodic monitoring of renal function and urine output is particularly important in patients judged to have a potential increased risk for developing acute renal failure. Renal function, including measurement of blood urea nitrogen (BUN)/serum creatinine, should be assessed before the initial infusion of Flebogamma® 5% DIF and again at appropriate intervals thereafter. If renal function deteriorates, discontinuation of the product should be considered. For patients judged to be at risk for developing renal dysfunction, it may be prudent to reduce the amount of product infused per unit time by infusing Flebogamma® 5% DIF at a maximum rate less than 0.06 mL/kg (3 mg/kg) body weight/minute. Aseptic Meningitis Syndrome: An aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV treatment. The syndrome usually begins within several hours to 2 days following IGIV treatment. It is characterized by symptoms and signs including severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, and nausea and vomiting. Cerebrospinal fluid (CSF) studies are frequently positive with pleocytosis up to several thousand cells per cubic milliliter, predominantly from the granulocytic series, and with elevated protein levels up to several hundred mg/dL. Patients exhibiting such symptoms and signs should receive a thorough neurological examination, including CSF studies, to rule out other causes of meningitis. AMS may occur more frequently in association with high-dose (e.g., > 1.0 g/kg body weight) and/or rapid-infusion IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. Hemolysis: Immune Globulin Intravenous (Human) (IGIV) products can contain blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis. Hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration [See ADVERSE REACTIONS]. IGIV recipients should be monitored for clinical signs and symptoms of hemolysis [See PRECAUTIONS: Laboratory Tests]. Thrombotic Events: Thrombotic events have been reported in association with IGIV (See ADVERSE REACTIONS). Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity. Baseline assessment of blood viscosity should be considered in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies [See PRECAUTIONS: Laboratory Tests]. Transfusion-Related Acute Lung Injury (TRALI): There have been reports of non-cardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury (TRALI)] in patients administered IGIV. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever and typically occurs within 1 to 6 hours after transfusion. Patients with TRALI may be managed by using oxygen therapy with adequate ventilatory support. IGIV recipients should be monitored for pulmonary adverse reactions. If TRALI is suspected, appropriate tests should be performed for the presence of antineutrophil antibodies in both the product and patient serum [See PRECAUTIONS: Laboratory Tests]. Information For Patients: Patients should be instructed to immediately report symptoms of decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath (which may suggest kidney damage) to their physicians. It is recommended that the lot number of the vials used be recorded when Flebogamma® 5% DIF is administered. Laboratory Tests: Renal function, including measurement of blood urea nitrogen (BUN)/serum creatinine, should be assessed before the initial infusion of Flebogamma® 5% DIF in patients judged to have a potential increased risk for developing acute renal failure and again at appropriate intervals thereafter.

Technology 45

Pharmacy Practice News • August 2010

Automation we actually turn the pumps on,” he said. “Education is always the No. 1 procedure to enhance safety.” The Yuma transition team also will create a list of best practices and procedures for the nurses, pharmacists and others who will use the pumps, and will have a second individual verify the settings. “It’s just as important that people use the pumps correctly as that the pumps themselves are safe,” said Mr. Van Hassel. “They need to be used as intended.” He estimated that approximately

700 nurses at Yuma Medical Center will require training on the Sigma Spectrum pumps that Baxter will be swapping in, but he is optimistic about the outcome. “We should wind up with smarter pumps and with the people using them smarter as well.” Dr. Cohen noted the potential for process improvement. “If hospitals do a good job of training and educating users, and if they take the very important step of standardizing their drug libraries, we should wind up with a much safer process.” —Liz Parks

Following infusion of Flebogamma® 5% DIF, there may be a transitory rise of various antibody titers that may result in misleading positive results in serological testing. Baseline assessment of blood viscosity should be considered in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. If TRALI is suspected, appropriate tests should be performed for the presence of antineutrophil antibodies in both the product and patient serum. Pregnancy Category C: Animal reproduction studies have not been performed with Flebogamma® 5% DIF. It is also not known whether Flebogamma® 5% DIF can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Flebogamma® 5% DIF should be given to a pregnant woman only if clearly needed. Drug Interactions: Antibodies in Flebogamma® 5% DIF may interfere with the response to live viral vaccines, such as measles, mumps, and rubella. Physicians should be informed of recent therapy with Immune Globulin Intravenous (Human) so that administration of live viral vaccines, if indicated, can be appropriately delayed 3 or more months from the time of IGIV administration. Pediatric Use: The above mentioned clinical trial with Flebogamma® 5% DIF enrolled only a very limited number of children (0) and adolescents (3) with primary humoral immune deficiency, a number insufficient to fully characterize and establish the efficacy and safety in pediatric patients. Geriatric Use: Subjects over 65 are at increased risk of renal failure with IGIV treatment. For these subjects, and for any other subjects at risk of renal failure, the infusion rate of Flebogamma® 5% DIF should be limited to < 0.06 mL/kg/min (3 mg/kg/min). Adverse Reactions Increases of creatinine and blood urea nitrogen (BUN) have been observed as soon as 1 to 2 days following infusion of IGIV. Progression to oliguria and anuria requiring dialysis has been observed, although some patients have improved spontaneously following cessation of treatment. Types of severe renal adverse reactions that have been seen following IGIV therapy include: acute renal failure, acute tubular necrosis, proximal tubular nephropathy, and osmotic nephrosis. Certain severe adverse reactions may be related to the rate of infusion. The recommended infusion rate [See DOSAGE AND ADMINISTRATION] must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period. Adverse reactions may occur more frequently when a high infusion rate is used, the treatment is the initial exposure to immunoglobulin, the immunoglobulin product has been changed to that of a different manufacturer, or there has been a long interval (more than 8 weeks) since the previous infusion. Slowing or stopping an infusion usually results in the prompt disappearance of symptoms. Post-Marketing: The following adverse reactions have been identified and reported during the postapproval use of IGIV products. Respiratory

Cardiovascular Neurological Integumentary Hematologic General/Body as a Whole Musculoskeletal Gastrointestinal

Apnea, Acute Respiratory Distress Syndrome (ARDS), Transfusion-Related Acute Lung Injury (TRALI), cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm Cardiac arrest, thromboembolism, vascular collapse, hypotension Coma, loss of consciousness, seizures, tremor Stevens-Johnson Syndrome, epidermolysis, erythema multiformae, bullous dermatitis Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs) test Pyrexia, rigors Back pain Hepatic dysfunction, abdominal pain

Because post-marketing reporting of these reactions is voluntary and the at-risk populations are of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to exposure to the product. Such is also the case with literature reports authored independently. Adverse events were reported in a study of 46 individuals with primary humoral immunodeficiency diseases receiving infusions every 3 to 4 weeks of 300 to 600 mg/kg body weight. Forty-three (94%) subjects experienced at least 1 adverse event

Puzzling Over Drug Libraries A

s hospitals start to physically replace older-generation infusion pumps—at the lowest estimate, more than 190,000 pumps—that challenging task will be further complicated by the simultaneous need to create or update the drug libraries that standardize the concentrations within formularies. There are no standardized formularies. Every hospital creates its own formularies based on what the phar-

irrespective of the relationship with the product, and these subjects reported a total of 595 adverse events. None of the 46 subjects who participated in this study discontinued the study prematurely due to an adverse experience related to the study drug. One subject had treatment-emergent bronchiectasis, mild, ongoing, after infusion #10; and one subject had recurrent moderate leukopenia after the 7th and 12th infusions. No adverse events occurred with an incidence of > 2% on a per infusion basis. Table 1. Adverse Events Occurring with an Incidence of > 15% Adverse Event

Number of AEs

Combined Bronchitis Cough and productive cough Diarrhea NOSa Headache NOS and sinus headache Nasal congestion Injection site reaction NOS Pyrexia Arthralgia Sinusitis NOS Pharyngitis Upper respiratory tract infection Wheezing and asthma aggravated

19 10 14 46 11 13 27 11 38 9 24 24

Number of Subjects with AEs 14 10 9 16 7 7 17 7 20 8 15 10

Percent of Subjects with AEs 30 22 20 35 15 15 37 15 44 17 33 22

a. NOS = not otherwise specified The total number of AEs (regardless of attribution) reported whose onset was within 72 hours after the end of an infusion of Flebogamma® 5% DIF was 216. There were a total of 709 infusions, resulting in a rate of 0.305 (95% confidence interval 0.225 to 0.412) temporally associated AEs per infusion. There were 144 infusions (20.1%, 1-sided 95% upper bound confidence interval = 24.4%) associated with 1 or more AEs that began within 72 hours after the completion of an infusion. Table 2. Summary of Infusions with Mild, Moderate, and Severe TreatmentRelated Adverse Events Severity of AE Mild Moderate Severe

No. Infusions 58 25 1

Adjusted % a with AE 7.9 3.6 0.1

Confidence Intervalb 10.4 4.9 0.3

a. Adjusted % = average of the % of infusions with a treatment-related adverse event for each individual subject. b. The 95% upper bound for the adjusted % of infusions for which at least 1 treatmentrelated adverse event was reported was derived by using the t-statistic. The number and percent of subjects with treatment-emergent rises in AST or ALT are in Table 3. Table 3. Number (%) of Subjects with Treatment-Emergent Rises in AST or ALT (N = 46) Laboratory Test AST ALT

Assessment Criteria Above 3x the ULNa Above 3x the ULN

n 3 1

% 6.5 2.2

a. ULN = upper limit of normal. None of these subjects had a concomitant treatment-emergent rise in total bilirubin. Reported adverse reactions with Flebogamma® 5% DIF and other IGIV products include: headache, chills, fever, shaking, fatigue, malaise, anxiety, back pain, muscle cramps, abdominal cramps, blood pressure changes, chest tightness, palpitations, tachycardia, nausea, vomiting, cutaneous reactions, wheezing, rash, arthralgia, and edema, often beginning within 60 minutes of the start of the infusion. Rarely, Immune Globulin Intravenous (Human) can induce a severe fall in blood pressure with anaphylactic reaction, even in patients who had tolerated previous treatment with IGIV. In the case of shock, the current standard medical treatment for shock should be implemented. Manufactured by INSTITUTO GRIFOLS, S.A. Barcelona - Spain U.S. License No. 1181 Distributed by GRIFOLS BIOLOGICALS INC. Los Angeles - CA 90032 Phone: 888-GRIFOLS (888-474-3657)

macy and nursing staffs consider appropriate. The process of creating or redefining an existing drug library “is extremely laborious and timeconsuming,” noted Gale White, vice president of infusion systems marketing at B. Braun. “That means that hospitals will not just be challenged by the task of physically replacing some 200,000plus pumps, but also challenged by the need to populate the drug libraries that are a key safety component of later-generation pumps,” Ms. White said. Manufacturers of infusion pumps will be able to help by providing consulting services to hospitals as they begin populating their drug libraries. B. Braun, seeing an opportunity to introduce standardization during the upcoming transition, has developed a standardized drug library that will be available with their Space and Outlook ES infusion pumps. The basic drug library is free to hospitals if they swap out older-generation pumps for Space or Outlook ES. Because the FDA has ordered one of the leading infusion pump manufacturers, Baxter, to recall and destroy all of its almost 190,000 Colleague pumps now in use, hospitals have no choice but to replace these pumps. However, there are also many older-generation pumps that have either no or less comprehensive drug libraries. More comprehensive drug library modules are now a standard safety feature in all new-generation pumps and add an element of complexity to the installation process. “Hospitals can have thousands of drugs in their formularies, and each drug must be evaluated for inclusion in their infusion pump drug library,” Ms. White said. “In addition to selecting the drug, hospitals must establish specific parameters for maximum and minimum dosing limits, hard and soft limits, care areas and more. Developing an IV pump drug library is a complex process that requires a multidisciplinary team and can take two to three months to complete. “Even if a hospital has a drug library, it’s not easy to swap data. The data—such as hard limits, soft limits, rates—has to be redefined and manually entered in the new libraries. It’s very laborious. It can take two to three months. And once the data has been entered, it still has to be verified with the hospital’s pharmacists, clinical staff and risk management.” —L.P.

46 Technology

Pharmacy Practice News • August 2010

Smart Pumps

continued from page 1

down to 5.6” (Figure), said Michael A. Cimino, MS, RPh, manager of clinical services at the Kaleida Health specialty hospital. Dr. Michienzi and Mr. Cimino described the “trials and tribulations” of developing the hospital’s smartpump system at the American Society of Health-System Pharmacists (ASHP) 2010 Summer Meeting. Both pharmacists were members of the multidisciplinary team that won the ASHP Research and Education Foundation’s 2009 Award for Excellence in Medication Use Safety, sponsored by the Cardinal Health Foundation.

Keeping an Eye on Compliance From the beginning, the team was determined to achieve a high rate of user compliance with the drug library being developed for the smart pump. Other hospitals had gone live earlier with a different smart-pump system, Dr. Michienzi said, and “we knew that there were compliance issues. This was reported in the literature as well.” However, the problems with compliance never arose at Women & Children’s Hospital, according to Mr. Cimino. Now, well into the second year, the compliance rate for the drug library ranges from 98.3% to 99.6%. How did they achieve nearly total compliance? One key was getting a large, broadly based implementation team on board from the start. In addition to pharmacists, the team included staff nurses, nurse educators and managers along with medical department chairs, anesthesiologists and a physician toxicologist. Biomedical engineers and vendor consultants also took part. “We were fortunate to have a physician pharmacologist, a clinical toxicologist who happens to be one of our pediatric ICU attendings,” Dr. Michienzi said. Because of his background and knowledge, he was able to resolve any

‘The electronic process captured all but the actual med errors related to IV drug administration.’ —Michael A. Cimino, MS, RPh

disagreements about where hard limits should be set, she added. “He would say, ‘Let’s put the hard limit at this. This is the dangerous dose that we need to worry about.’” Another major challenge, Dr. Michienzi said, was how to develop a drug library that would “represent our diverse patient population, not just within our hospital but within the same units. “In our neonatal ICU,” she explained, “we could have a 460-g patient and in our high-risk obstetrics unit we could have a 200-kg patient. We needed to be able to meet the needs of all those patients.” One solution was to develop customized drug names to distinguish among dosing strategies needed for various patients and indications. Heparin, for example, was given two labels in the library: heparin-ECMO for use in patients requiring extracorporeal membrane oxygenation and heparin-anticoagulation for other indications. “In our clinical experience we found we needed higher doses for patients on ECMO, probably because of higher volume distribution, so we had higher hard limits,” Dr. Michienzi said. “But we didn’t want to have those higher limits open to anyone getting a heparin drip, so we had a separate listing, heparinanticoagulation, with tighter limits.” Vasopressin was another example of a drug that wound up with multiple names in the library. These were vasopressin-shock, vasopressin-GI (gastrointestinal) bleed, and vasopressin-DI (diabetes insipidus), each with different dosing requirements. Dr. Michienzi said nurses had found the vasopressin dosing confusing, often not knowing which to use. “We had

a pharmacy critical care resident go through all of the literature,” she said. “Then we sat down with the pediatric ICU attendings and presented all of the information as well as the limits [of the software], and we simplified. Now for every indication there is one way you are allowed to dose. It’s not the same for all three indications, but at least for each indication the prescribers know how they have to write an order.”

Drug Library Remains Flexible The hospital’s smart-pump library continues to evolve as new drugs are approved and dosing practices are changed based on new guidelines and studies, as well as user feedback. The latter is a regular source of adjustments, according to Dr. Michienzi. “I’ve had nurses tell me that we should tighten the limits on [a particular drug]. ‘We don’t want to be able to give that much this quickly. We would never do that.’ And so I’ll tighten those limits up.” All new drugs and dosing changes have to be approved by the Pediatric Pharmacy & Therapeutics Subcommittee before being added, she said, and the library undergoes a quarterly review and update. Although the rate of prevented medication errors has been high, Mr. Cimino acknowledged that the pump could not determine the rate of errors actually reaching patients. For that, he said, they have had to rely on voluntary incident reporting, and voluntary systems are notably unreliable for delivering accurate data. “If we only had the incident reporting system to rely on,” he said, “we would only be seeing the tip of the iceberg.” In summarizing the accomplishments

12 10.4

Errors per Patient-day

DRUG LIBRARIES

10 8 5.6

6 4 2 0 Baseline

Post-Smart Pump Implementation

Figure. Preventable medication errors.

of the smart-pump tracking system, Mr. Cimino noted that there has been a “significant and sustained reduction in potential medication errors and adverse drug events related to IV administration. The electronic process captured all but the actual med errors related to IV drug administration.” But even without a totally reliable count of actual errors, he said, “we were able to identify 94% to 98% of all errors using this pump-tracking system.” Richard D. Paoletti, RPh, MBA, vice president of operations–Radiology, Laboratory, Pharmacy at Lancaster General Hospital, in Pennsylvania, noted that “the emergence of smart-pump systems has served as a catalyst for pharmacist involvement with IV infusion administration. When implemented correctly, standardization and development of comprehensive drug libraries with dose limits should improve patient safety. Increased FDA regulation and the promise of interoperability will be build on this foundation and further improve the safe delivery of IV medications.” —Bruce and Joan Buckley

CLINICAL L

IInternal Medicine

RA PATIENTS continued from page 40

this drug does that, but how w quickly it does that is more off a marketing issue than an imporportant clinical issue.” Jay Jackson, PharmD, vice president of medical services es at Xcenda, a health care consulting lting firm, said that the fast response ponse to tocilizumab may boost morale

for patients patient with RA, “but more important would b be to see if the initial initia improvements are sustained over time.” (Dr. Yazici said Y that six-month data to be presented later this summer demonsumm strates strate that the

early response is indeed sustained.)

REMS Not a Game-Changer Drs. Jackson and Ruderman predict that the impact of the REMS will be minimal. “The REMS for tocilizumab requires a medication guide and a communication plan, which is similar to requirements for other biologic agents prescribed for RA,” said Dr. Jackson. Some REMS demand far more of clinicians, such as training and certifica-

tion to prescribe or dispense a drug. REMS for most rheumatology drugs are not terribly onerous, added Dr. Ruderman. “At a practical level,” he said, “the whole point of the REMS for this drug and for all biologics we’re using is to make certain that clinicians are familiar with the material in the product insert and data about the drug, which we should be anyhow.” —Steve Frandzel

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48 Technology

Pharmacy Practice News • August 2010

Health Care IT

MEANINGFUL USE

Three Stages of Meaningful Use

continued from page 1

Under the revised regulations, core measures that will have to be met include the maintenance of active medication and medication allergy lists for at least 80% of patients, the implementation of drug–drug and drug-allergy checks and the use of computerized prescriber order entry (CPOE) technology for more than 30% of patients. Hospitals also will be required to provide at least 50% of discharged patients with copies of their discharge instructions, if requested. Among the “ala carte” menu choices, one requires that medication reconciliation be performed for more than 50% of transitions of care. Another necessitates the implementation of drug formulary check systems. An article outlining key provisions of the meaningful use regulations was published online July 13 in The New England Journal of Medicine (10.1056/ NEJMp1006114). At the American Society of HealthSystem Pharmacists (ASHP) 2010 Summer Meeting, several sessions focused on the significance of meaningful use of EHR technology to hospitals and pharmacies. “I think it is safe to say that ‘meaningful use’ is an absolute game-changer. [It shifts] attention away from the technology to what one does with the technology … to improve individual and population health, ” said Charles P. Friedman, chief scientific officer of the Office of the National Coordinator for Health Information Technology (ONC). Dr. Friedman was describing a term that underpins what health officials hope

Stage 1: 2011-2012

Stage 2: 2013-2014

Stage 3: 2015 and Beyond

Electronically capture health information in a coded format; begin to track key clinical conditions and electronically communicate for care coordination purposes.

Build on stage 1 to encourage the use of health IT for continuous quality improvement at the point of care and the exchange of information in the most structured format possible.

Promote improvements in quality, safety and efficiency using decision support for national high-priority conditions and patient access to self-management tools.

IT, information technology Source: Anne M. Bobb Slide e Presentation: 2010 ASHP Summer Meeting

will be a revolution in the way health information technology chnology (IT) is used to drive advances dvances in patient outcomes and nd save on the cost of delivering ng care. The anticipated changes hanges grow out of the 2009 09 Health Information Technology for Economic and Clinical Health (HITECH) Act, which gives the he Department of Health ealth and Human Services (HHS) the authority to establish stablish programs to improvee health care through IT, and the 2009 American Recovery and Reinvestment Act (ARRA), which authorizes incentive payments ents to hospitals and eligible professionals nals who demonstrate the meaningful use of their certified EHR systems. The payments, totaling an estimated $17.2 billion, will come from Medicare and Medicaid and are set to begin in 2011. At the same time that CMS was releasing its final rule on meaningful use, the ONC was issuing its final rule for standards and certification of EHR. The

‘[Meaningful use compliance] is going to require us to rethink what we do and how we do it, but in the end it will provide better care by improving our communication with the rest of the health care team.’ —Anne M. Bobb, RPh

The Three Components of Meaningful Use 1. Use of certified EHR technology in a meaningful manner (e.g., CPOE). 2. The certified EHR technology should be connected in a manner that provides for the electronic exchange of health information to improve the quality of care. 3. In using certified EHR technology, the provider submits to the HHS secretary information on clinical quality measures and such other measures selected by the secretary. CPOE, computerized prescriber order entry; EHR, electronic health records; HHS, Health and Human Svces. Source: Anne M. Bobb Slide Presentation: 2010 ASHP Summer Meeting

EHR certification regulations, which will be administered by the ONC, were developed with advice from the Health Information Technology Policy and Standards Federal Advisory Committees, and in close collaboration with other affected HHS divisions including CMS, which is responsible for administering the meaningful use payment incentives provisions of the HITECH Act. More information on the certification program for EHR technology can be accessed via ONC’s Web site at http://healthit.hhs.gov. For its part, CMS has launched a Web site offering a blueprint on how it will administer the meaningful use incentives program (http://www.cms. gov/EHRIncentivePrograms). Last month, ONC was scheduled to begin accepting applications from notfor-profit organizations seeking designation as testers and certifiers of EHR technology. Those that are designated could begin certifying EHRs by late summer, and the first certified products could be on the market by early fall, according to Carol Bean, ONC division director of certification and testing. Until now the only ONC-approved organization eligible to certify EHR systems has been the Certification Commission for Health Information Technology. That organization is expected to be among those applying to ONC for designation as an

EHR tester and certifier. In his ASHP talk on ARRA and health IT, I Dr. Friedman briefly outlined the th three stages of meaningful use that the government u expects expect health IT systems to go through. “In very general th terms,” he said, “meaningful t use would focus [in 2011] on those things that reflect the capability to capture data d and share it; 2013 would focus on more advanced clinical processes processe that would deliver value from the th data; and by 2015 everything would be in place to really w drive im improved outcomes.” In explaining why the more exp advanced sta stages of meaningful use are so important, important Dr. Friedman posed the question, “D “Does anybody really believe that having information in front of you on a computer screen creates any better care than having the same information in front of you on paper?” The answer, he said, is that studies have shown that just moving clinical data functions from paper to electronic form “really didn’t make a difference. It is only when you add clinical decision support and you add enhancements to the way information is presented, so that it is organized [and] can flow from where it is collected to where it is needed that improvements can result. … That is what meaningful use is all about.”

EHR Adoption Underestimated? Dr. Friedman also commented on an article in The New England Journal of Medicine (2009;360:1628-1638) reporting on a survey that showed a hospital EHR adoption rate of approximately 10%. He noted that more than 75% of U.S. hospitals use electronic laboratory and radiology reports, about 50% have computerized drug-allergy interaction alerts, and another 50% have computerized medication lists. “So I think it is fair to say that the situation in hospitals is not exactly as depicted” in the journal report, he noted. A more accurate description of health IT adoption in hospitals, he noted, would be to say that “almost every hospital has some key elements of an

Technology 49

Pharmacy Practice News • August 2010

Health Care IT electronic medical record in place, but the deployment of various functionalities is uneven and very few are comprehensive.” Dr. Friedman also set the record straight on the amount of money available for meaningful use incentives. “There isn’t $17 billion sitting in an account somewhere waiting to be distributed,” he said. “This is an estimate of the net cost, the difference between the amount that the Congressional Budget Office estimated would be paid out in incentives … and the estimated savings to the Medicare and Medicaid funds resulting from the benefits of meaningful use.” He said that no one knows yet how many hospitals and providers will qualify for payments under the meaningful use criteria. “Five or 10 years from now, we’ll know how much was really spent and what the net benefit was.”

I think that the vendors have worked hard. They are upgrading their systems constantly. I can tell you there are probably a thousand things that I would do differently if we were implementing today, but undoing what we’re doing now and turning the ship is our challenge and can be very overwhelming. “I think it is very possible to go at a more ‘big-bang’ style now,” she said, but organizations that can’t accomplish that can also go at a slower pace “with an eye to meeting [meaningful use criteria] in 2014 or 2015. This doesn’t have to be completely overwhelming.”

However, Ms. Bobb also noted that it is important to start the process now. Why the hurry? “Because the goal is to reach Stage 3 [Table] by 2015. The ‘steepness’—that is, the rate at which you must progress to the next step— goes up quicker the later you start.”

Making Pharmacists Part Of the EHR Communication and documentation will be a major part of the meaningful use compliance process, she said. “We need to rethink how we document in medicine. What we’ve done is put

paper on the computer. In the next few years we’re going to see improvement. Pharmacist documentation should be part of the medical record. When the pharmacist comments on aminoglycoside levels, it should be part of the note. It is going to require us to rethink what we do and how we do it, but in the end it will provide better care by improving our communication with the rest of the health care team. “This is not about IT,” she said, “it is about culture.” —Bruce and Joan Buckley

‘The Right Thing To Do’ Dr. Friedman’s talk set the stage for a more detailed afternoon session on meaningful use presented by James Russell, RPh, pharmacist-clinical informatics at Epic Systems Corporation, and Anne M. Bobb, RPh, clinical informatics pharmacist at Northwestern Memorial Hospital in Chicago. Mr. Russell noted that reaching meaningful use goals “can’t be an IT project. It’s got to be a clinical project,” adding that physicians, nurses and pharmacists “all have to be engaged” along with every layer of management. Additionally, he said that although $17 billion “gets a lot of people’s attention when it is for health care IT,” the decision to implement an EHR system that meets meaningful use criteria should not be based on financial considerations. “You should be installing EHR because it’s the right thing to do,” he said. The final component in implementing meaningful use is the decision to go live, Mr. Russell said, adding that an important part of the “go live” process is to start with a detailed plan of all the tasks and who is responsible for carrying them out. Other important factors, he noted, include the need for flexibility in the plan. “Always have a contingency plan,” he advised, “but don’t let anybody know what it is. If you advertise it, everybody is going to want to use it.” In her presentation, “Demonstrating Meaningful Use at Your Institution,” Ms. Bobb described the challenges that Northwestern Memorial Hospital faced in implementing an EHR system a decade ago. “We took quite a bit of time to roll out our system,” she said. “One of the benefits of starting now versus when we did back in early 2000 is that the systems that are available now are significantly improved from when we implemented.

NDC

Name

Strength

Vial Size

Pack Size

For more information about Brevital, please visit www.brevital.com or call JHP Customer Service at 877-JHP-4JHP (877-547-4547).

50 Technology

Pharmacy Practice News • August 2010

Bar Coding

A Roadmap to Selection of a BCMA System Beju Shah, BS, PharmD/ MBA Candidate South Carolina College of Pharmacy-MUSC Campus Charleston, South Carolina

Christopher R. Fortier, PharmD Manager, Pharmacy Support Services, Department of Pharmacy Services, Medical University of South Carolina Clinical Assistant Professor Department of Clinical Pharmacy and Outcomes Sciences South Carolina College of Pharmacy-MUSC Campus

he incidence of preventable adverse errors occurring during the administration phase of the medication use process has been reported to be as high Prescribing Information as of January 2009.

as 34%.1 This statistic is alarming and underscores the need for technology to help reduce the risk for patient harm. Landmark reports and expert consensus

BREVITAL® SODIUM

3003014B 266

METHOHEXITAL SODIUM FOR INJECTION, USP

For Intravenous Use in Adults For Rectal and Intramuscular Use Only in Pediatric Patients WARNING Brevital should be used only in hospital or ambulatory care settings that provide for continuous monitoring of respiratory (e.g. pulse oximetry) and cardiac function. Immediate availability of resuscitative drugs and age- and size-appropriate equipment for bag/valve/mask ventilation and intubation and personnel trained in their use and skilled in airway management should be assured. For deeply sedated patients, a designated individual other than the practitioner performing the procedure should be present to continuously monitor the patient. (See WARNINGS) DESCRIPTION Brevital® Sodium (Methohexital Sodium for Injection, USP) is 2,4,6 (1H, 3H, 5H)-Pyrimidinetrione, 1-methyl-5-(1-methyl-2-pentynyl)-5-(2-propenyl)-, (±)-, monosodium salt and has the empirical formula C14H17N2NaO3. Its molecular weight is 284.29. The structural formula is as follows: Methohexital sodium is a rapid, ultrashort-acting barbiturate anesthetic. Methohexital sodium for injection is a freeze-dried, sterile, nonpyrogenic mixture of methohexital sodium with 6% anhydrous sodium CH 3 carbonate added as a buffer. It contains not less than 90% and not more than 110% of the labeled O N ONa amount of methohexital sodium. It occurs as a white, freeze-dried plug that is freely soluble in water. CH 2 CHCH 2 This product is oxygen sensitive. The pH of the 1% solution is between 10 and 11; the pH of the 0.2% soluN tion in 5% dextrose is between 9.5 and 10.5. CH 3 CH 2C CCH Methohexital sodium may be administered by direct intravenous injection or continuous intravenous drip, intraO CH 3 muscular or rectal routes (see PRECAUTIONS—Pediatric Use). Reconstituting instructions vary depending on the route of administration (see DOSAGE AND ADMINISTRATION). CLINICAL PHARMACOLOGY Compared with thiamylal and thiopental, methohexital is at least twice as potent on a weight basis, and its duration of action is only about half as long. Although the metabolic fate of methohexital in the body is not clear, the drug does not appear to concentrate in fat depots to the extent that other barbiturate anesthetics do. Thus, cumulative effects are fewer and recovery is more rapid with methohexital than with thiobarbiturates. In experimental animals, the drug cannot be detected in the blood 24 hours after administration. Methohexital differs chemically from the established barbiturate anesthetics in that it contains no sulfur. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation. Intravenous administration of methohexital results in rapid uptake by the brain (within 30 seconds) and rapid induction of sleep. Following intramuscular administration to pediatric patients, the onset of sleep occurs in 2 to 10 minutes. A plasma concentration of 3 μg/mL was achieved in pediatric patients 15 minutes after an intramuscular dose (10 mg/kg) of a 5% solution. Following rectal administration to pediatric patients, the onset of sleep occurs in 5 to 15 minutes. Plasma methohexital concentrations achieved following rectal administration tend to increase both with dose and with the use of more dilute solution concentrations when using the same dose. A 25 mg/kg dose of a 1% methohexital solution yielded plasma concentrations of 6.9 to 7.9 μg/mL 15 minutes after dosing. The absolute bioavailability of rectal methohexital sodium is 17%. With single doses, the rate of redistribution determines duration of pharmacologic effect. Metabolism occurs in the liver through demethylation and oxidation. Side-chain oxidation is the most important biotransformation involved in termination of biologic activity. Excretion occurs via the kidneys through glomerular filtration. INDICATIONS AND USAGE Brevital Sodium can be used in adults as follows: 1. For intravenous induction of anesthesia prior to the use of other general anesthetic agents. 2. For intravenous induction of anesthesia and as an adjunct to subpotent inhalational anesthetic agents (such as nitrous oxide in oxygen) for short surgical procedures; Brevital Sodium may be given by infusion or intermittent injection. 3. For use along with other parenteral agents, usually narcotic analgesics, to supplement subpotent inhalational anesthetic agents (such as nitrous oxide in oxygen) for longer surgical procedures. 4. As intravenous anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli (see WARNINGS). 5. As an agent for inducing a hypnotic state. Brevital Sodium can be used in pediatric patients older than 1 month as follows: 1. For rectal or intramuscular induction of anesthesia prior to the use of other general anesthetic agents. 2. For rectal or intramuscular induction of anesthesia and as an adjunct to subpotent inhalational anesthetic agents for short surgical procedures. 3. As rectal or intramuscular anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. CONTRAINDICATIONS Brevital Sodium is contraindicated in patients in whom general anesthesia is contraindicated, in those with latent or manifest porphyria, or in patients with a known hypersensitivity to barbiturates. WARNINGS See boxed Warning. As with all potent anesthetic agents and adjuncts, Brevital should be used only in hospital or ambulatory care settings that provide for continuous monitoring of respiratory (e.g. pulse oximetry) and cardiac function. Immediate availability of resuscitative drugs and age- and size-appropriate equipment for bag/valve/mask ventilation and intubation and personnel trained in their use and skilled in airway management should be assured. For deeply sedated patients, a designated individual other than the practitioner performing the procedure should be present to continuously monitor the patient. Maintenance of a patent airway and adequacy of ventilation must be ensured during induction and maintenance of anesthesia with methohexital sodium solution. Laryngospasm is common during induction with all barbiturates and may be due to a combination of secretions and accentuated reflexes following induction or may result from painful stimuli during light anesthesia. Apnea/hypoventilation may be noted during induction, which may impair pulmonary ventilation; the duration of apnea may be longer than that produced by other barbiturate anesthetics. Cardiorespiratory arrest may occur. This prescribing information describes intravenous use of methohexital sodium in adults. It also discusses intramuscular and rectal administration in pediatric patients older than one month. Although the published literature discusses intravenous administration in pediatric patients, the safety and effectiveness of intravenous administration of methohexital sodium in pediatric patients have not been established in well-controlled, prospective studies. (See PRECAUTIONS—Pediatric Use) Seizures may be elicited in subjects with a previous history of convulsive activity, especially partial seizure disorders. Because the liver is involved in demethylation and oxidation of methohexital and because barbiturates may enhance preexisting circulatory depression, severe hepatic dysfunction, severe cardiovascular instability, or a shock-like condition may be reason for selecting another induction agent. Prolonged administration may result in cumulative effects, including extended somnolence, protracted unconsciousness, and respiratory and cardiovascular depression. Respiratory depression in the presence of an impaired airway may lead to hypoxia, cardiac arrest, and death. The CNS-depressant effect of Brevital Sodium may be additive with that of other CNS depressants, including ethyl alcohol and propylene glycol. DANGER OF INTRA-ARTERIAL INJECTION—Unintended intra-arterial injection of barbiturate solutions may be followed by the production of platelet aggregates and thrombosis, starting in arterioles distal to the site of injection. The resulting necrosis may lead to gangrene, which may require amputation. The first sign in conscious patients may be a complaint of fiery burning that roughly follows the distribution path of the injected artery; if noted, the injection should be stopped immediately and the situation reevaluated. Transient blanching may or may not be noted very early; blotchy cyanosis and dark discoloration may then be the first sign in anesthetized patients. There is no established treatment other than prevention. The following should be considered prior to injection: 1. The extent of injury is related to concentration. Concentrations of 1% methohexital will usually suffice; higher concentrations should ordinarily be avoided. 2. Check the infusion to ensure that the catheter is in the lumen of a vein before injection. Injection through a running intravenous infusion may enhance the possibility of detecting arterial placement; however, it should be remembered that the characteristic bright-red color of arterial blood is often altered by contact with drugs. The possibility of aberrant arteries should always be considered. Postinjury arterial injection of vasodilators and/or arterial infusion of parenteral fluids are generally regarded to be of no value in altering outcome. Animal experiments and published individual case reports concerned with a variety of arteriolar irritants, including barbiturates, suggest that 1 or more of the following may be of benefit in reducing the area of necrosis: 1. Arterial injection of heparin at the site of injury, followed by systemic anticoagulation. 2. Sympathetic blockade (or brachial plexus blockade in the arm). 3. Intra-arterial glucocorticoid injection at the site of injury, followed by systemic steroids. 4. A case report (nonbarbiturate injury) suggests that intra-arterial urokinase may promote fibrinolysis, even if administered late in treatment. If extravasation is noted during injection of methohexital, the injection should be discontinued until the situation is remedied. Local irritation may result from extravasation; subcutaneous swelling may also serve as a sign of arterial or periarterial placement of the catheter. PRECAUTIONS General—All routes of administration of Brevital Sodium are often associated with hiccups, coughing, and/or muscle twitching, which may also impair pulmonary ventilation. Following induction, temporary hypotension and tachycardia may occur. Recovery from methohexital anesthesia is rapid and smooth. The incidence of postoperative nausea and vomiting is low if the drug is administered to fasting patients. Postanesthetic shivering has occurred in a few instances. The usual precautions taken with any barbiturate anesthetic should be observed with Brevital Sodium. The drug should be used with caution in patients with asthma, obstructive pulmonary disease, severe hypertension or hypotension, myocardial disease, congestive heart failure, severe anemia, or extreme obesity. Methohexital sodium should be used with extreme caution in patients in status asthmaticus. Caution should be exercised in debilitated patients or in those with impaired function of respiratory, circulatory, renal, hepatic, or endocrine systems. Information for Patients—When appropriate, patients should be instructed as to the hazards of drowsiness that may follow use of Brevital Sodium. Outpatients should be released in the company of another individual, and no skilled activities, such as operating machinery or driving a motor vehicle, should be engaged in for 8 to 12 hours. Laboratory Tests—BSP and liver function studies may be influenced by administration of a single dose of barbiturates. Drug Interactions—Prior chronic administration of barbiturates or phenytoin (e.g. for seizure disorder) appears to reduce the effectiveness of Brevital Sodium. Barbiturates may influence the metabolism of other concomitantly used drugs, such as phentyoin, halothane, anticoagulants, corticosteroids, ethyl alcohol, and propylene glycol-containing solutions. Carcinogenesis, Mutagenesis, Impairment of Fertility—Studies in animals to evaluate the carcinogenic and mutagenic potential of Brevital Sodium have not been conducted. Reproduction studies in animals have revealed no evidence of impaired fertility. Usage in Pregnancy—Pregnancy Category B—Reproduction studies have been performed in rabbits and rats at doses up to 4 and 7 times the human dose respectively and have revealed no evidence of harm to the fetus due to methohexital sodium. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Labor and Delivery—Brevital Sodium has been used in cesarean section delivery but, because of its solubility and lack of protein binding, it readily and rapidly traverses the placenta. Nursing Mothers—Caution should be exercised when Brevital Sodium is administered to a nursing woman. Pediatric Use—The safety and effectiveness of methohexital sodium in pediatric patients below the age of 1 month have not been established. Seizures may be elicited in subjects with a previous history of convulsive activity, especially partial seizure disorders. Apnea has been reported following dosing with methohexital regardless of the route of administration used. Studies using methohexital sodium intravenously in pediatric patients have been reported in the published literature. This literature is not adequate to establish the safety and effectiveness of intravenous administration of methohexital sodium in pediatric patients. Due to a variety of limitations such as study design, biopharmaceutic issues, and the wide range of effects observed with similar doses of intravenous methohexital, additional studies of intravenous methohexital in pediatric patients are necessary before this route can be recommended in pediatric patients. (See WARNINGS)

indicate that a fully integrated barcode medication administration (BCMA) system has the potential to reduce medication administration errors and improve overall patient safety.2 A survey conducted by the American Society of Health-System Pharmacists (ASHP) in 2009 indicated that 27.9% of hospitals nationwide were using BCMA.3 This is a dramatic increase from the estimated 1.5% of hospitals in 2002 and 9.4% of hospitals in 2005.4,5

Geriatric Use—Clinical studies of Brevital did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Elderly subjects may commonly have conditions in which methohexital should be used cautiously such as obstructive pulmonary disease, severe hypertension or hypotension, preexisting circulatory depression, myocardial disease, congestive heart failure, or severe anemia. Caution should be exercised in debilitated patients or in those with impaired function of respiratory, circulatory, renal, hepatic, or endocrine systems (see WARNINGS, PRECAUTIONS and ADVERSE REACTIONS). Barbiturates may influence the metabolism of other concomitantly used drugs that are commonly taken by the elderly, such as anticoagulants and corticosteroids. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy (see PRECAUTIONS-Drug Interactions). ADVERSE REACTIONS Side effects associated with Brevital Sodium are extensions of pharmacologic effects and include: Cardiovascular—Circulatory depression, thrombophlebitis, hypotension, tachycardia, peripheral vascular collapse, and convulsions in association with cardiorespiratory arrest Respiratory—Respiratory depression (including apnea), cardiorespiratory arrest, laryngospasm, bronchospasm, hiccups, and dyspnea Neurologic—Skeletal muscle hyperactivity (twitching), injury to nerves adjacent to injection site, and seizures Psychiatric—Emergence delirium, restlessness, and anxiety may occur, especially in the presence of postoperative pain Gastrointestinal—Nausea, emesis, abdominal pain, and liver function tests abnormal Allergic—Erythema, pruritus, urticaria, and cases of anaphylaxis have been reported rarely Other—Other adverse reactions include pain at injection site, salivation, headache, and rhinitis For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact JHP at 1-866-923-2547 or MEDWATCH at 1-800-FDA-1088 (1-800-332-1088) or http://www.fda.gov/medwatch/. DRUG ABUSE AND DEPENDENCE Controlled Substance—Brevital Sodium is a Schedule IV drug. Brevital Sodium may be habit-forming. OVERDOSAGE Signs and Symptoms—The onset of toxicity following an overdose of intravenously administered methohexital will be within seconds of the infusion. If methohexital is administered rectally or is ingested, the onset of toxicity may be delayed. The manifestations of an ultrashort-acting barbiturate in overdose include central nervous system depression, respiratory depression, hypotension, loss of peripheral vascular resistance, and muscular hyperactivity ranging from twitching to convulsive-like movements. Other findings may include convulsions and allergic reactions. Following massive exposure to any barbiturate, pulmonary edema, circulatory collapse with loss of peripheral vascular tone, and cardiac arrest may occur. Treatment—To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient. Establish an airway and ensure oxygenation and ventilation. Resuscitative measures should be initiated promptly. For hypotension, intravenous fluids should be administered and the patient’s legs raised. If desirable increase in blood pressure is not obtained, vasopressor and/or inotropic drugs may be used as dictated by the clinical situation. For convulsions, diazepam intravenously and phenytoin may be required. If the seizures are refractory to diazepam and phenytoin, general anesthesia and paralysis with a neuromuscular blocking agent may be necessary. Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient’s vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient’s airway when employing gastric emptying or charcoal. DOSAGE AND ADMINISTRATION Facilities for assisting ventilation and administering oxygen are necessary adjuncts for all routes of administration of anesthesia. Since cardiorespiratory arrest may occur, patients should be observed carefully during and after use of Brevital Sodium. Age- and size-appropriate resuscitative equipment (ie, intubation and cardioversion equipment, oxygen, suction, and a secure intravenous line) and personnel qualified in its use must be immediately available. Preanesthetic medication is generally advisable. Brevital Sodium may be used with any of the recognized preanesthetic medications. Preparation of Solution—FOLLOW DILUTING INSTRUCTIONS EXACTLY. Solutions of Brevital Sodium should be freshly prepared and used promptly. Reconstituted solutions of Brevital Sodium are chemically stable at room temperature for 24 hours. Diluents—DO NOT USE DILUENTS CONTAINING BACTERIOSTATS. Preferred diluent: Sterile Water for Injection Acceptable diluents: 5% Dextrose Injection (for IV or rectal administration only), 0.9% Sodium Chloride Injection Incompatible diluents: Lactated Ringer’s Injection Dilution Instructions—1% solutions (10 mg/mL) should be prepared for intravenous use. Contents of vials should be diluted as follows: FOR INTRAVENOUS ADMINISTRATION Strength

Amount of Diluent to Be Added to the Contents of the Vial

For 1% methohexital solution

500 mg

50 mL

no further dilution needed

2.5 g

15 mL

add to 235 mL for 250 mL total volume

When the first dilution is made with the 2.5 g, the solution in the vial will be yellow. When further diluted to make a 1% solution, it must be clear and colorless or should not be used. For continuous drip anesthesia, prepare a 0.2% solution by adding 500 mg of Brevital Sodium to 250 mL of diluent. For this dilution, either 5% glucose solution or isotonic (0.9%) sodium chloride solution is recommended instead of distilled water in order to avoid extreme hypotonicity. For intramuscular administration, contents of the vials should be diluted as follows: FOR INTRAMUSCULAR ADMINISTRATION Strength

Amount of Diluent* to Be Added to the Contents of the Vial

500 mg vial

10 mL

5% Solution (50 mg/mL)

2.5 g vial

50 mL

5% Solution (50 mg/mL)

Methohexital Concentration after Dilution

*Sterile Water for Injection or 0.9% Sodium Chloride Injection only. For rectal administration, contents of the vials should be diluted as follows: FOR RECTAL ADMINISTRATION Strength

Amount of Diluent to Be Added to the Contents of the Vial

Methohexital Concentration after Dilution

500 mg vial

50 mL

1% Solution (10 mg/mL)

2.5 g vial (larger vial needed)

250 mL

1% Solution (10 mg/mL)

Administration—Dosage is highly individualized; the drug should be administered only by those completely familiar with its quantitative differences from other barbiturate anesthetics. Adults—Brevital Sodium is administered intravenously in a concentration of no higher than 1%. Higher concentrations markedly increase the incidence of muscular movements and irregularities in respiration and blood pressure. Induction of anesthesia—For induction of anesthesia, a 1% solution is administered at a rate of about 1 mL/5 seconds. Gaseous anesthetics and/or skeletal muscle relaxants may be administered concomitantly. The dose required for induction may range from 50 to 120 mg or more but averages about 70 mg. The usual dosage in adults ranges from 1 to 1.5 mg/kg. The induction dose usually provides anesthesia for 5 to 7 minutes. Maintenance of anesthesia—Maintenance of anesthesia may be accomplished by intermittent injections of the 1% solution or, more easily, by continuous intravenous drip of a 0.2% solution. Intermittent injections of about 20 to 40 mg (2 to 4 mL of a 1% solution) may be given as required, usually every 4 to 7 minutes. For continuous drip, the average rate of administration is about 3 mL of a 0.2% solution/minute (1 drop/second). The rate of flow must be individualized for each patient. For longer surgical procedures, gradual reduction in the rate of administration is recommended (see discussion of prolonged administration in WARNINGS). Other parenteral agents, usually narcotic analgesics, are ordinarily employed along with Brevital Sodium during longer procedures. Pediatric Patients—Brevital Sodium is administered intramuscularly in a 5% concentration and administered rectally as a 1% solution. Induction of anesthesia—For the induction of anesthesia by the intramuscular route of administration, the usual dose ranges from 6.6 to 10 mg/kg of the 5% concentration. For rectal administration, the usual dose for induction is 25 mg/kg using the 1% solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. COMPATIBILITY INFORMATION Solutions of Brevital Sodium should not be mixed in the same syringe or administered simultaneously during intravenous infusion through the same needle with acid solutions, such as atropine sulfate, metocurine iodide, and succinylcholine chloride. Alteration of pH may cause free barbituric acid to be precipitated. Solubility of the soluble sodium salts of barbiturates, including Brevital Sodium, is maintained only at a relatively high (basic) pH. Because of numerous requests from anesthesiologists for information regarding the chemical compatibility of these mixtures, the following chart contains information obtained from compatibility studies in which a 1% solution of Brevital Sodium was mixed with therapeutic amounts of agents whose solutions have a low (acid) pH. Active Potency Volume Physical Change Ingredient per mL Used Immediate 15 min 30 min 1h Brevital Sodium 10 mg 10 m L CONTROL Atropine Sulfate 1/150 gr 1 mL None Haze Atropine Sulfate 1/100 gr 1 mL None Ppt Ppt Succinylcholine chloride 0.5 mg 4 mL None None Haze Succinylcholine chloride 1 mg 4 mL None None Haze Metocurine Iodide 0.5 mg 4 mL None None Ppt Metocurine Iodide 1 mg 4 mL None None Ppt Scopolamine hydrobromide 1/120 gr 1 mL None None None Haze Tubocurarine chloride 3 mg 4 mL None Haze HOW SUPPLIED Store at controlled room temperature (20° to 25°C) (68° to 77°F) [see USP]. Brevital® Sodium Vials*: 500 mg (with 30 mg anhydrous sodium carbonate) are available as follows: 50-mL size, multiple dose—1’s (NDC 42023-105-01) The 2.5 g vials (with 150 mg anhydrous sodium carbonate) are available as follows: 50-mL size, multiple dose—1’s (NDC 42023-106-01)

*In crystalline form. Rx only Prescribing Information as of January 2009. Manufactured and Distributed by: JHP Pharmaceuticals, LLC Rochester, MI 48307

Although the initial high upfront cost to implement a BCMA system (estimated to range from $1 to $5 million) can be a deal-breaker for some institutions,6 advocates suggest that the benefits may outweigh the costs, particularly when costs incurred from medication errors, such as secondary complications and increased hospital length of stay, are considered. An analysis at a large tertiary care hospital actually showed a breakeven point at one year and a $3.5 million net benefit five years following implementation.7 Employing any emerging technology such as BCMA within an enterprise-wide system is a complex process, and there are few studies available that provide BCMA implementation pearls.2,8,9 This article provides a systematic approach for the evaluation of BCMA system that uses an organizational assessment, vendor and product evaluation, and selection of a pharmacy repackaging model. Organizations must understand the financial impact and plan, not only for the software purchase but also for devices and staffing resources needed for a successful implementation. Additionally, the vendor’s customer support and training plan must be closely analyzed for support prior, during and after implementation. Pharmacy departments that are implementing a bar-coding system also need to assess repackaging methods and determine the cost–benefit of either an in-house or an outsourced repackaging center.

Organizational Assessment An initial organizational assessment must include a review of three main components—overall organizational readiness, vendor evaluation, and the financial impact of the project (Table 1). The feasibility of the project must be examined from all perspectives by a multidisciplinary team, with core leadership from nursing and pharmacy. The factors used to evaluate different vendors in the marketplace primarily are based on the request for proposals and vendor demonstrations but can be drawn from various other criteria such as10: • Features and functionality of each system • Vendor experience and client case reports • Customer support and on-site visits • Training and implementation support • Initial and ongoing operational costs • Current data information infrastructure • Product evaluation Vendor selection also must include a systematic approach to software and hardware selection. Primarily, the areas of focus should be general features of the bar-code system, types of scanners and bar-code configurations, system

Technology 51

Pharmacy Practice News â&#x20AC;˘ August 2010

Bar Coding Table 1. Organizational Evaluation Checklist platform options, patient/staff identification recognition, customer support and training resources from the vendor. This part of the puzzle often is difficult to piece together without a standardized vendor comparison tool (Table 2). General functional requirements are varied with the many proprietary systems available. Therefore, a broad range of criteria must be taken into account, as well as an exhaustive search into the types of applications, the depth of features, the flexibility of configurations and user-friendliness of the products that are available on the market. Some examples that may add value for end-users are alerts, clinical decision support, task management, documentation, charge capture and error reporting functions. Additionally, decision makers must not forget to ask pertinent questions to determine whether the products are compatible within their own institutions. For example, how does the system interface with oneâ&#x20AC;&#x2122;s pharmacy system? What is the process for barcode mapping? What type of bar-code scanners will be used? Finally, future

For Barcode Medication Administration â&#x153;&#x201D; Develop a uniform benchmarking system to compare vendor systems. â&#x153;&#x201D; Create a multidisciplinary team with nursing and pharmacy being involved as key players in the entire process. â&#x153;&#x201D; Determine if personnel and technological resources assigned to the project are adequate for planning, implementation, maintenance and optimization. â&#x153;&#x201D; Identify leaders who will champion the technology and super-users who will encourage early adoption of the new system. â&#x153;&#x201D; Ensure the proper internal network infrastructure is available. â&#x153;&#x201D; Formulate a downtime strategy and test frequently. â&#x153;&#x201D; Evaluate vendor training and ongoing support capabilities. â&#x153;&#x201D; Eliminate any potential for bar-code scanning failure and use strategies to prevent clinician workarounds. â&#x153;&#x201D; Train nursing and pharmacy in tandem and continuously monitor for additional educational needs. â&#x153;&#x201D; Standardize the formulary and nomenclature to be compatible with the bar-code system. Unit-dose repackaging, dose-specific medications, manufacturer bar-code labels, and other issues should be considered. â&#x153;&#x201D; Ensure all users have adequate training to troubleshoot problems and understand the basic workflow.

functionality and timelines must always be considered as technology lives in a

world of continuous change. Scanner types and bar-code configura-

tions are another critical element in the product-selection process. Several different specifications must be tested vigorously by the nursing end-users to verify usability or lack thereof. Requirements that must be satisfied are compatibility with various medications, patient and employee identification badges, battery life span, wireless communication and infection control considerations. Furthermore, the use of scanners with other applications (i.e., laboratory results) may extend the scope of the device. Indeed, the limiting factor with all hardware is the ability to correctly scan the bar code; selecting the correct symbologies (linear, RSS, data matrix) prior to implementation can alleviate many frustrations down the road. Similarly, the types of system platforms should be reviewed for different user needs within institutions, depending on patient populations and nursing staff. These range from handheld tablet PCs, to computers in patient rooms, to rolling carts with medication drawers. Careful selection of these crucial

â&#x20AC;˘

see ROADMAP, page 54

in Your Inbox

earch under way for Executive Vice President/CEO of The American Society of Health-System Pharmacists (ASHP), a professional assn of hospital and health-system pharmacists located in Bethesda, MD with approximately 35,000 members, a $43 million budget and 186 staff. Seek individual to represent ASHPâ&#x20AC;&#x2122;s mission, interests and activities to the public and key stakeholders, both domestically and internationally; advocate to influence outcomes of healthcare initiatives in both privateand public-sector healthcare organizations; build effective relationships with federal regulators and agencies (e.g., CMS, FDA, JC), national quality organizations ( e.g., NQF, AHRQ), pharmacy-related organizations (e.g., ACPE, APhA, NCPDP) and international pharmacy organizations; and manage the staff and daily operations of ASHP and the ASHP Foundation. Candidates must be a licensed pharmacist; a masterâ&#x20AC;&#x2122;s or other advanced degree is strongly preferred. Candidates also must have a minimum of 10 years of executive/managerial experience in and/or demonstrated knowledge of hospitals or healthcare systems or other non-profit organization; ability to build consensus among diverse constituencies; an understanding of global opportunities to advance an organizationâ&#x20AC;&#x2122;s leadership position; and demonstrated financial acumen and management skills. Search by Pamela Kaul, Association Strategies, Inc. 1111 North Fairfax St., Alexandria, VA 22314 www.assnstrategies.com Resume submission by October 15, 2010. Email: ashp@assnstrategies.com

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Get the latest news delivered directly to your computer and PDA. The new interactive format has embedded Web site links that give you instant access to additional information, unique searching features and printing capabilities. Each installment contains brief summaries of the most important articles from the current monthâ&#x20AC;&#x2122;s issue, as well as breaking news ahead of print.

52 Technology

Pharmacy Practice News • August 2010

In Brief Wii Fit Helps RA Patients Get Back In the Game

ince its launch in 2006, the Nintendo Wii Fit game console not only has been popularized as a way for players to get in shape, but as a growing form of rehabilitation and physical therapy. Now, researchers have found that Wii Fit can be used to deliver physical therapy for patients with rheumatoid arthritis (RA) foot disease. A new study presented at the European League Against Rheumatism (EULAR) 2010 Congress in Rome, Italy

examined “the feasibility and value of the Wii Fit console in the assessment and rehabilitation of RA foot disease,” according to the authors. The Wii Fit guides players through various exercises by simulating sports and other activities, digitalizing player movements and displaying them on a television screen. It also includes a stand-on balance board that converts foot pressure into the on-screen display. Researchers from the Burton Hospital Foundation Trust in Burton-on-Trent in the United Kingdom studied 13 patients (10 women; mean age, 57 years) with inflammatory arthritis and moderate to

severe planovalgus deformity. Over six sessions, the patients were asked to use the Wii Fit and the balance board to steer balls into an on-screen tilt table. The task gained difficulty with the addition of more balls. The researchers measured one-leg standing balance (the mean of five attempts per leg), visual analog scale (VAS) score for pain and the Wii Fit score before and after each session. Activity-specific balance confidence (a measure of confidence to balance) and “timed up and go” (a measure of standing and dynamic balance) were recorded for the first and last sessions. The study found that one-leg stand-

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ing balance improved for all the patients for each leg, while Wii Fit game scores increased in 11 patients. Ten patients had an improved activityspecific balance confidence score. “Timed up and go” scores improved by the last session by a mean of 3.3 seconds, and in nine cases improved by about 10 seconds. The researchers concluded that “Wiihab” is beneficial as a “patient-friendly, effective means of delivering physical therapy for foot disease in RA.” They added that the Wii Fit is valuable for its “continuous feedback on progress,” its creation of “patient engagement and enthusiasm” and its close mimicry of daily life. Further study, however, is needed to understand how patient outcomes are affected by physical and psychological factors. —Staff

FDA and NIH Launch Electronic Safety Reporting Portal

he FDA and the National Institutes of Health (NIH) have launched a new Web site that, when fully developed, will provide a mechanism for reporting pre- and postmarket safety data to the federal government. Currently, the Web site can be used to report safety problems related to foods, including animal feed and animal drugs, as well as adverse events (AEs) occurring in human gene transfer trials. In the future, the system will encompass other types of clinical trials and, eventually, safety problems arising from products regulated by a broad array of federal agencies. This is a first step toward a universal electronic reporting system that will allow an individual to file a single report to multiple agencies that may have an interest in the event. The new site, called the Safety Reporting Portal, includes different features for different types of reporting: • Clinical trials: Biomedical researchers involved in human gene transfer clinical trials can report an AE, indicating whether it might be an unanticipated consequence of the product being tested. Trial sponsors can use the portal to prepare a report, print it and send it to the agency to satisfy reporting requirements for investigational new drugs. • Reportable food registry: This electronic portal collects reports from the food industry and public health officials regarding problems with food products, including animal feed, that present a reasonable probability of causing serious adverse health consequences or death to humans or animals. • Pet food: Pet owners and veterinarians will be able to use the portal to report problems with pet foods and pet treats. • Animal drugs: Manufacturers of drugs for animals can report AEs associated with these products. —Staff

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Kate Arnold-Forster; Nigel Tallis

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ASHP’s Cardiovascular Pharmacotherapy: A Point-of-Care Guide is designed with the busy practitioner, resident and student in mind. The 18 chapters are organized by disease state and each one includes visually scannable elements such as tables and flow figures, pathophysiological reasons for selecting specific pharmacotherapies, selected guideline statements from leading organizations, evidence-based treatment algorithms, recent clinical controversies and frequently asked questions.

For pricing, a more complete Clinical Pharmacy in the United States review and easy ordering Robert M. Elenbaas, PharmD, FCCP; Dennis B. Worthen, PhD with a credit card, go to Clinical Pharmacy in the United States: Transformation of a Profession is a comprehenMcMahonMedicalBooks.com. sive account of the evolution of clinical pharmacy and is an insightful must-read for anyWe can supply any medical book in print, so if you don’t find the book you want, e-mail your request with billing information to RMcMahon@ McMahonMed.com. If you are an author and would like your medical book featured in this book section, contact Ray McMahon, Publisher, at RMcMahon@ McMahonMed.com.

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Concepts in Pharmacogenomics Martin M. Zdanowicz

The new science of pharmacogenomics aims to understand how an individual’s genetic composition affects his or her response to a specific drug or class of drugs. By studying such characteristics as drug-metabolizing enzymes, drug-transporter activity and receptor sensitivity, the pharmacist is better able to prescribe the right drug the first time.

Fundamentals of Geriatric Pharmacotherapy: An Evidence-Based Approach

Lisa C. Hutchison, PharmD, MPH, FCCP, BCPS; Rebecca Sleeper-Irons, PharmD, FASCP, BCPS This new textbook provides thorough coverage of therapeutic and social issues affecting elderly patients. The book is divided into two sections; the first section addresses general concepts about aging and the second section is organized by both organ system and disease states common in the elderly. These chapters contain a short summary of treatment in normal adults, and then focus on an evidence-based review of treatment in elderly patients.

Instant Clinical Pharmacology, Second Edition

Learning from Medical Errors: Clinical Practice

MCQs in Pharmaceutical Calculations

Pharmacy Case Studies

Women’s Health Across the Lifespan: A Pharmacotherapeutic Approach

Evan J. Begg

Instant Clinical Pharmacology differs from other clinical pharmacology books: It presents essential information about the core topics in clinical pharmacology in a concise, accessible dip-in format and aims to bridge the gap between basic pharmacology and the therapeutic use of drugs in humans. Each topic is concisely displayed in a double-page spread to aid learning and revision. This revised second edition covers the accepted core curriculum of clinical pharmacology: clinical pharmacokinetics, factors affecting dosing, altered drug effects, pharmacovigilance and principles of optimal therapeutics. Simple illustrations and tables support the text and assist to provide rapid access to and explanation of key facts.

Anh Vu T. Nguyen, MD, FAAFP; Dung A. Nguyen, MD, FAAFP

The companion book to Learning from Medical Errors: Legal Issues, this book explores the most common medical errors that can lead to malpractice cases. The authors advocate defensive medicine and cite numerous case examples of what to do and what not to do.

Ryan Donnelly; Johanne Barry

This book aims to help pre-registration trainees and pharmacy students with their revision/study enabling them to perform calculations accurately and with confidence.

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Primarily aimed at pharmacy students and pre-registration pharmacists, this book will also be useful for qualified pharmacists as well as medical students, nurses and others with a professional interest in therapeutics.

Laura Borgelt; Mary Beth O'Connell; Judith Smith; Karim Anton Calis

Women’s Health Across the Lifespan: A Pharmacotherapeutic Approach is a groundbreaking publication, a unique primary reference developed to help educate pharmacy students, pharmacists and other health care professionals in an area of deservedly growing interest and importance. This new book contains contributions from more than 150 clinical experts in pharmacy, medicine and nursing. It is edited by nationally recognized educators and researchers. PPN0810

54 Technology

Pharmacy Practice News • August 2010

Bar Coding

Bar-coding Initiatives Can Start With Baby Steps

ROADMAP continued from page 51

components on the front-end helps to maximize efficiency and enable a point-of-care environment. Identifying patients and employees through bar-coded wristbands and staff badges is an important factor in the evaluation process. Ensuring adequate testing on patients and staff members prior to selecting a system will help to balance costs and scanning compliance. Determining the size and spatial arrangement of the bar code, print resources, wristbands or labels and patient populations (i.e., neonates) are all interrelated considerations. On the back-end, enhanced customer support can add value to the organization’s overall commitment to system integration. In fact, both employee training and implementation resources must be analyzed by the organization throughout the process, as these aspects are key to the foundations and continuous improvement of the system. They often are very time consuming and costly. Organizations must assess whether the vendor provides on-site training and what resources are available. Although an appropriate length of training is crucial to successful naviga-

eminding pharmacists that barcoding has been an FDA requirement since 2004 (2006 final implementation), with countless papers on its effectiveness written and presented, health care consultant Bonnie E. Kirschenbaum, MS, FASHP, offers further encouragement to those who are apprehensive about getting started. In addition to the tips suggested by the Medical University of South Carolina authors, she recommends that institutions “consider baby steps if they are not ready or can’t afford to tackle the entire hospital.” She suggested that one way to begin would be to purchase a few scanners and start by scanning every product coming from the wholesaler. The next step could be using scanners to verify drug and strength for every automated dispensing machine filled. “In no time,” according to Ms. Kirschenbaum, “you’ll have solved the dilemmas of an accurate listing of bar codes in your computer system and be ready to move on.” Ms. Kirschenbaum recommended the following resources for pharmacists pursuing bar-coding initiatives: American Society of Health-System Pharmacists. ASHP Statement on Bar-code Verification During Inventory, Preparation, and Dispensing of Medications. http://www.ashp.org/DocLibrary/Policy/HOD/StBarCodeHOD2010.aspx. Accessed July 20, 2010. American Society of Health-System Pharmacists Section of Pharmacy Information and Technology. ASHP Statement on Bar-Code-Enabled Medication Administration Technology. Am J Health-Syst Pharm. 2009;66:588-590.

tion of the initial stage, it also is a necessary consideration after implementation to reinforce model behaviors in nursing, respiratory and pharmacy.

Repackaging Pharmacy leadership must be concerned with the implications of using manufacturer bar codes versus repackaging unit-dose products with custom bar-code labels. Further cost–benefit analysis may be undertaken to determine whether this process should be performed in-house or outsourced to a third party. If using in-house solutions, direct oversight, flexibility and inventory management provide justification for this model. On the other hand, if an

institution decides to use an external company, it may be useful to research return policies, bar-code compatibility, quality assurance, and general ordering processes. Either way, the institution will need to dedicate pharmacy resources to map all bar codes to ensure 100% scanning compliance and maintain pharmacy databases that interface with the BCMA software. Table 3 summarizes the advantages and disadvantages of each of these approaches to bar-code repackaging.

Conclusion

Customer support

Once a vendor is selected, the organization must quickly focus its efforts on system planning, implementation and optimization. Reviewing additional resource toolkits from ASHP, the ASHP Section of Pharmacy Informatics and Technology, and the Health Information and Management Systems Society (HIMSS) is an efficient way to start. Contacting colleagues who have successfully implemented BCMA and reviewing the peer-reviewed literature will provide new perspectives for institutions beginning to implement a BCMA system. There are inherent challenges in the planning and implementation of BCMA technology in hospitals and health systems, but institutions with existing systems have paved the way and can offer tips on how to overcome some of the pitfalls.

Technical support

References

Reports

1. Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events. JAMA. 1995;274:29-34.

Table 2. BCMA Vendor Comparison Chart System Characteristic Hardware features Hardware limitations Software features Software limitations Bar-code configurations End-user training Implementation support

Network infrastructure

Vendor 1

Vendor 2

Vendor 3

Vendor 4

2. Mahoney CD, Berard-Collins CM, Coleman R, et al. Effects of an integrated clinical information system on medication safety in a multihospital setting. Am J Health Syst Pharm. 2007;64:1969-1977. 3. Pedersen CA, Schneider PJ, Scheckelhoff DJ. ASHP national survey of pharmacy practice in hospital settings: monitoring and patient education-2009. Am J Health-Syst Pharm. 2010;67:542-558. 4. Pederson CA, Schneider PJ, Scheckelhoff DJ. ASHP national survey of pharmacy practice in hospital settings: dispensing and administration-2002. Am J Health-Syst Pharm. 2003;60:52-68. 5. Pedersen CA, Schneider PJ, Scheckelhoff DJ. ASHP national survey of pharmacy practice in hospital settings: dispensing and administration-2005. Am J Health-Syst Pharm. 2006;63:327-345. 6. Cummings J, Bush P, Smith D, et al. Bar-coding medication administration overview and consensus recommendations. Am J Health Syst Pharm. 2005;62:2626-2629. 7.

Maviglia SM, Yoo JY, Franz C, et al. Costbenefit analysis of a hospital pharmacy bar code solution. Arch Intern Med. 2007;167:788-794.

8. Morris FH, Abramowitz PW, Nelson SP, et al. Effectiveness of a barcode medication administration system in reducing preventable adverse drug events in a neonatal intensive care unit: a prospective cohort study. J Pediatr. 2008;154:363-368. 9. DeYoung JL, Vanderkooi ME, Barletta JF. Effect of bar-code-assisted medication administration on medication error rates in an adult medical intensive care unit. Am J Health Syst Pharm. 2009;66:1110-1115. 10. ASHP Foundation. Implementing a bar coded medication safety program: a pharmacist’s toolkit. http://www.ashpfoundation.org/BarCode.pdf. Accessed July 8, 2010.

System requirements Interfaces Medication repackaging Scanner compatibility Patient/staff identification System platform capabilities

Table 3. Hospital Advantages and Disadvantages Of In-house and Outsourced Medication Repackaging Advantages

Disadvantages

In-house repackaging

• Provides flexibility and reduces inventory • Promotes faster turnaround times and better expiration dating • Facilitates greater communication among staff

• Cost of repackaging equipment ($20,000-$250,000) • Increases labor/space/ renovation/consumables required • Increases liability

Outsourced repackaging

• Lessens the need to invest in technology and other resources • Reduces liability and quality assurance issues

• Creates less flexibility • Increases inventory on hand • Limited control on the safe storage of medications

Workflow considerations/ limitations Additional staff resources Initial cost Maintenance costs Future functionality

Does your unit dose packaging offer all this?

does. Simple to Use–No Extensive Training Needed 1 and 2-dimensional barcoding–including NDC, Lot Numbers and Expiration Dating Tall Man Lettering and Dynamic Formatting Options Packaging Logs and Error Reporting 6-month and 1-year Beyond-Use Dating UV and Moisture Resistance Tamper-Evidence 4 Sizes of Blisters to accommodate virtually all meds No machinery or Space Requirements Inexpensive

Unit dose packaging the way it should be: Smart. Simple. Reliable.

Since 1971, hospital and community pharmacies around the world have relied on the proven Medi-Dose® system for the quick, simple and inexpensive method to manually package solid oral unit dose. Medi-Dose provides Tamper-Evidence as well as UV & Moisture Resistance for One-Year beyond-use dating. Our MILT® software maintains packaging logs and lets you design and print your Lid-Label® Covers...In Color! With Tall Man Lettering! In Bold! With optional Bar Codes! Directly from your own computer and printer! Medi-Dose works well in any pharmacy operation and can be used with all classifications of drugs (chemo meds, compounded drugs, controlled substances, etc.) And it’s affordably priced for all pharmacy budgets. For the best in manual unit dose packaging, check out Medi-Dose!

EPS®, INC. Extra Personal Service in supplying pharmacy packaging needs around the world

Milton Building, 70 Industrial Drive Ivyland, PA 18974 800-523-8966 Fax: 800-323-8966 215-396-8600 Fax: 215-396-6662 E-mail: info@medidose.com