Pharmacy Practice News - July 2009 - Digital Edition by McMahon Group

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The Pharmacist’s News Source

pharmacypracticenews.com

Volume 36 • Number 7 • July 2009

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Case for genetic screen debated

Is VKORC1 Test Needed In All Warfarin Patients? Miami—Genetic testing to determine an individual patient’s sensitivity to warfarin would make dosing of the agent more efficient and reduce the risk for bleeding or clotting events. But whether such testing should become routine is still a matter for debate. At the 2009 annual conference of the Hematology/Oncology Pharmacy Association (HOPA), Rowena N. Schwartz, PharmD, director of oncology pharmacy at The Johns Hopkins Hospital, Baltimore, argued that pharmacogenomic testing for vitamin K epoxide reductase (VKORC1), the gene that codes for the enzyme that is the site of action where warfarin exerts its effect, should be done in all patients receiving warfarin. Kelly Nystrom, PharmD, assistant professor of pharmacy practice at Creighton University, Omaha, Neb., took the opposite view, telling HOPA delegates that testing for VKORC1 should not be done in all patients because it is still not known whether the

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see WARFARIN DEBATE, page 17

McMahon Publishing

in this issue Operations & Mgmt

Finance Remote camera checks chemotherapy orders, saves time and money.

Leadership in Action Ernie Anderson Jr., MS, RPh leaves the Lahey Clinic after 15 years of service.

Clinical

Oncology HOPA President Phil Johnson, MS, RPh, on the need to tackle drug noncompliance.

Should all HR+ breast cancer patients be tested for CYP2D6 prior to tamoxifen therapy?

Medication reconciliation can help reduce ESA waste, save big dollars.

Technology

Bar Coding BCMA tweaks nearly eliminate nurse overrides, boost patient safety.

Recruiting, Retaining Pharmacists May Hinge on Depth of Offerings Rosemont, Ill.—Flexible work schedules and a willingness to match job responsibilities to the clinical passion of employees are among the strategies that a Montana hospital has used to eliminate staff turnover in its pharmacy department. Given the 22% rate of turnover that plagued the system several years ago, “we’re extremely pleased with the results,” Dominick A. Caselnova III, BS, MHA, director of pharmacy at Benefis Health System, a 516-bed facility based in Great Falls, said during a poster session at the American Society of Health-System Pharmacists (ASHP) Summer meeting.

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see TAMING TURNOVER, page 11

EHRs

Drug Noncompliance Still Driving Health Care Costs Cancer patients pose particular challenge Miami–Oncology patients who are nonadherent with their oral chemotherapy regimens not only have worse outcomes than their adherent counterparts, they are considerably more costly to the health care system. “Nonadherence is associated with increased consumption of health care resources, more physician visits, higher hospitalization rates and longer hospital stays. Up to 69% of medication-related hospital admissions are due to poor medication adherence at a cost of around $1 billion a year,” Christy S. Harris, PharmD, said at the fifth annual conference of the Hematology/Oncology Pharmacy Association (HOPA).

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see NONCOMPLIANCE, page 16

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Electronic smoking cessation reminders help patients quit.

27 Educational Review Contemporary Management Of Clostridium difficile Infection Insert after page

Medication Safety and Quality, Part 4: Measurement and Reporting See pages 8-9

Mississippi Clinic Wins Fight Against Resistant Hypertension Rosemont, Ill.—More than twothirds of patients with resistant hypertension achieved blood pressure (BP) control by following regimens established by pharmacists and other caregivers in a collaborative hypertension clinic, according to a study presented at the American Society of Health-System Pharmacists (ASHP) Summer Meeting. The results—showing an increase from a baseline rate of 12%—are

particularly dramatic because they occurred in Mississippi, a state beset with both the highest prevalence of hypertension and the highest rate of cardiovascular disease mortality in the nation, noted co-investigator Deborah Minor, PharmD, an associate professor of medicine at the University of Mississippi Medical Center Hypertension Clinic, in Jackson.

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see BP CONTROL, page 18

New Product Hospira, Inc. gets FDA approval for Sterile Vancomycin Hydrochloride, USP. See page

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Expanding our portfolio in 2009 All Teva Unit Dose products contain the following on every cell: • Scannable Bar Code • Product Description • NDC #

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Up Front 3

Pharmacy Practice News • July 2009

Capsules In Brief

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β-Lactams Score for SST Infections in Kids

watch

JULY 2009

The five most-viewed articles last month on pharmacypracticenews.com: 1. Real-World Clinical Use of Warfarin Far From Ideal 2. Some Pharmacists Are Losing Sleep Over REMS for Anemia Rx 3. Chemotherapy-Related Cardiac Toxicity Requires More Vigilance 4. Pharmacogenomics: Gearing Up for Primetime 5. The Impact of the Economy on Pharmacy Services Register for free at pharmacypracticenews.com to read these and other articles on the latest developments in health care pharmacy.

heard here first

‘After implementing any

or children with skin and soft tissue infections (SSTIs), β-lactam antibiotics still should be considered first-line therapy, even in areas where community-acquired methicillin-resistant staphylococcus aureus (CA-MRSA) is prevalent, according to a new study. In the retrospective, nested trial, the investigators compared the effectiveness of β-lactams, clindamycin and trimethoprim-sulfamethoxazole (TMP-SMZ) to treat nondrained, noncultured SSTIs from five pediatric practices in Philadelphia, an area endemic to CA-MRSA. Between January 2004 and March 2007, a total of 2,096 patients with nondrained, noncultured SSTIs— all treated with oral monotherapy—were identified from the five centers. Of these patients, 104 (5%) experienced treatment failures, defined as a drainage procedure, hospitalization, change in antibiotic or being prescribed a second antibiotic within 28 days. These patients were matched randomly to 480 control subjects. Compared with β-lactam monotherapy, TMP-SMZ was associated with an increased risk for treatment failure (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.28-4.34). Treatment with clindamycin monotherapy, however, did not increase the risk for treatment failure compared with β-lactam monotherapy (OR, 1.40; 95% CI, 0.76-2.59). The average rate of treatment failure was 5.7% and did not change during the study period. The researchers also found that empiric CA-MRSA coverage with clindamycin and TMP-SMZ increased dramatically during the study period (16.4% in 2004 vs. 62.2% in 2007), citing the uncertainty of clinicians in a time when CA-MRSA is increasingly prevalent. “Contrary to our initial hypothesis, our findings suggest that the increased use of empiric CAMRSA coverage was not associated with improved clinical outcomes,” the authors wrote (Pediatrics 2009;123:e959-e966). “These findings may suggest that CA-MRSA is not a prevalent cause of nondrained, noncultured SSTIs even in a region with endemic CA-MRSA.” According to the findings, other factors associated with increased risk for treatment failure were white race, being seen initially in the emergency department, antibiotic use within the previous six months, documented or reported fever and the presence of induration or abscess. —Kevin Horty

patient safety technology, don’t assume you’ve optimized it. And even if you do take steps to optimize it after launch, don’t assume it stays optimized.’

See article, page 26

NEW PRODUCT

Sterile Vancomycin Hydrochloride, USP

ospira, Inc. announced that it has received FDA approval for a 10-gram vial of Sterile Vancomycin Hydrochloride, USP, an anti-infective medication. The medication is “an effective agent for fighting methicillin-resistant Staphylococcus aureus (MRSA), a common infection that is often resistant to other antibiotics,” the company noted in a press release. “Approval of Hospira’s 10-gram vial of vancomycin closely follows the FDA’s recent approval of our 750-mg vial, and reinforces Hospira’s commitment to meeting patient needs for high-quality, lower-cost alternatives to proprietary medications,” said Joshua Gordon, vice president, Specialty Pharmaceuticals, Hospira. The company announced that it will begin shipping Sterile Vancomycin Hydrochloride, USP immediately.

—Joseph High, PharmD

For more information, visit www.hospira.com.

EDITORIAL BOARD

Dan Radebaugh, Director of Production and Technical Operations

ADMINISTRATION Robert Adamson, PharmD, Livingston, NJ Ernest R. Anderson Jr., MS, RPh, Boston, MA

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ANESTHESIOLOGY/PAIN

Volume 36 • Number 7 • July 2009 • pharmacypracticenews.com

Robert Barkin, PharmD, Chicago, IL Julie A. Golembiewski, PharmD, Chicago, IL Melvin E. Liter, MS, PharmD, FASHP, Lexington, KY BIOTECHNOLOGY Indu Lew, PharmD, Livingston, NJ CARDIOLOGY

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4 Operations & Management

Pharmacy Practice News • July 2009

Finance

Hospitals Step Up to Cost-Savings Challenge Fiscal successes detailed at ASHP Summer Meeting Rosemont, Ill.—In the midst of the worst economic downturn since the Great Depression, hospitals and health systems across the country have intensified cost-cutting efforts to reduce pressure on their critically stretched budgets. Pharmacy department spending has been a big part of the budgetary calculations. At the American Society of HealthSystem Pharmacists’ Summer Meeting, several sessions focused on the economic challenges faced by hospitals and pharmacies, as well as on the potential impact of the government’s stimulus package. Additionally, a number of poster presentations offered a glimpse into how health-system pharmacists are finding ways to improve patient care and safety, while at the same time reducing medication therapy costs. One poster described the efforts of pharmacist-researchers to determine the cost of IV admixture waste at University Hospital in Cincinnati. They found that over a three-month period from Oct. 27, 2008 to Jan. 31, 2009, approximately 6,500 IV doses were wasted at a total cost of $143,931. By extrapolation, they estimated a yearly waste of more than 26,000 doses at a cost exceeding $575,000. Shih-Feng Chiu, a fourth-year student at the University of Cincinnati’s

James L. Winkle College of Pharmacy, led the study. One of the authors, Alex C. Lin, PhD, assistant professor at the pharmacy college, said the research suggested that more work was needed to determine how at least a portion of those costs could be avoided. Another poster described the impact that four full-time faculty members from the Auburn University Harrison School of Pharmacy in Auburn, Ala., have had on improving clinical care and lowering medication costs at Huntsville Hospital in Huntsville, Ala. The report, written by Lea S. Eiland, PharmD, BCPS, associate clinical professor at Auburn, and Edward H. Eiland, PharmD, MBA, BCPS, AQID, CGP, clinical practice and business supervisor at Huntsville Hospital, found that the clinical faculty members and their students had accounted for an average of 125,000 interventions resulting in approximately $250,000 of cost avoidance per year. Dr. Eiland told Pharmacy Practice News that the cost savings had been calculated using Pharmacy OneSource’s Quantifi software program. (See “Software Helps Document Value of Clinical Pharmacy,” http://www.pharmacypracticenews. com/fwd/6576.htm)

Noting that “tough economic times are ahead, and many hospitals are having to downsize,” she said the goal in writing the poster was to “put into hospitals’ minds the idea of trying to work with schools of pharmacy and bring faculty members into their institutions. It can be advantageous for both parties.”

Saving on Insulin Another study carried out at the Advocate Illinois Medical Center in Chicago found that the preparation of patientspecific basal insulin doses by pharmacy not only improved the safety profile for the high-alert medication, it also resulted in a 75% reduction in expenditures for basal insulin. Previously, the study noted, insulin vials had been stored on nursing units. “Despite several initiatives targeting improved storage of the multidose insulins, several vials of one insulin type were often available on a given unit, opened and unsecured on the counters,” the authors reported. Removing the insulin doses from the nursing units and initiating preparation of patient-specific doses in the pharmacy department’s USP-compliant compounding area helped improve safety by introducing multiple checks into the process of preparing and

administering the insulin. William W. Churchill, MS, RPh, executive director of pharmacy at Brigham and Women’s Hospital in Boston, said it wasn’t surprising to him that “that kind of improvement could be made by having pharmacy involved in the process. “Given the nature of how patients are administered insulin, it’s clearly a challenge for pharmacy,” Mr. Churchill said. “It requires being very adaptive and being able to deliver medication in a justin-time fashion.” A study just completed at Brigham and Women’s, he said, showed that IV insulin bags could be prepared under sterile pharmacy conditions and stored for use on nursing units for several days without any appreciable loss in concentration after an initial reduction. “That gave us a lot of confidence that we could premix insulin bags” in the pharmacy instead of having nursing prepare the infusions, he added, “which we believe is a much better and safer process.” Mr. Churchill said the pharmacy was also getting ready to implement robotic IV preparation for several types of IV bags and syringes, including the mixing of insulin bags. —Bruce Buckley

Remote Camera To Check Chemotherapy Orders Saves Time and Money Rosemont, Ill.—Placing a network camera in a chemotherapy compounding area allowed a Denver hospital with a decentralized pharmacy operation to perform required pharmacist double-checks more efficiently and economically, according to a poster presentation at the American Society of Health-System Pharmacists Summer Meeting. “It’s simple, but it really made a huge difference,” said Jennifer Davis, PharmD, MBA, director of Pharmacy Services at Denver’s Exempla Lutheran Medical Center. “The big savings for us was in labor costs and pharmacy salaries,” Dr. Davis said. But using the camera is “quicker too,” which allows the pharmacy to compound more chemotherapy doses. Explaining the history behind the addition of the camera system, Dr. Davis said that the medical center added an oncologist and a pharmacist to the staff when an infusion center was opened. Then, when a second oncologist was added, “we anticipated an increase in chemo volume” that could not be met. Because creating a decentralized chemotherapy compounding pharmacy and adding staff were not options, they looked to a camera system “to make the process more effi-

Table. Impact of Remote Camera on Efficiency Doses/Day

Seconds/Dose

Seconds/Day

Pre-camera

346

1,386

Post-camera

P value

cient,” and allow them to produce more chemotherapy doses. The network camera was installed in the negative pressure compounding area in the main dispensing section of the pharmacy. Using live video footage provided by the camera, a pharmacist in a decentralized location can remotely verify chemotherapy preparations and communicate that double-check to the dispensing pharmacy via telephone. Prior to implementation, decentralized pharmacists had to go to the compounding area in the central pharmacy to verify the accuracy of the order. The new process improves efficiency by eliminating the time it takes for the pharmacists to travel to the central pharmacy. The process of traveling to the central pharmacy, waiting for other personnel and complet-

<0.001

ing the check took an average of 346 seconds before the camera was put in place; that was reduced to six seconds with implementation of the camera (Table). Additionally, after implementing the new system, the Denver pharmacists were able to more than double the number of chemotherapy doses prepared each day, from four to nine. The costs of checking chemotherapy decreased dramatically as well. Before the camera was put in place, the cost of checking each chemotherapy dose was $5.29; after implementation, each check cost 65 cents (P<0.001). Dr. Davis said there have been no glitches with the new system, which has been in place since 2008. “It’s a very simple and inexpensive technology,” she said, adding that the camera can be purchased

at almost any electronics store for about $300. With additional costs for installation and network connections, the total price tag for the system was approximately $1,500. The investigators noted that the camera paid for itself after a few hundred doses in a little over a month’s time. “We estimate that the post-camera process saves our organization over $15,000 annually in operational expenses.” Asked to comment on the poster, Adam Boon, MBA, PharmD, pharmacy manager at Iowa Lutheran Medical Center, in Des Moines, said that his hospital has a 24-hour pharmacy service and that a remote camera system such as that used at Exempla Lutheran “would really be beneficial to us.” Dr. Boon, who has had success supplying telepharmacy services from one location to a rural hospital an hour away, said, “there’s lots of advantages to [the camera] technology.” In addition to providing cost savings and allowing the decentralized pharmacist more time to be on the floors with patients, he said, the remote camera system “saves on entries into your IV room, which helps with 797 compliance.” —Sarah Tilyou

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Midazolam Hydrochloride Injection CIV Brief Summary See package insert for full prescribing information Adult and Pediatric Intravenous midazolam HCl has been associated with respiratory depression and respiratory arrest, especially when used for sedation in noncritical care settings. In some cases, where this was not recognized promptly and treated effectively, death or hypoxic encephalopathy has resulted. Intravenous midazolam HCl should be used only in hospital or ambulatory care settings, including physicians’ and dental offices, that provide for continuous monitoring of respiratory and cardiac function, i.e., pulse oximetry. Immediate availability of resuscitative drugs and age- and sizeappropriate equipment for bag/valve/mask ventilation and intubation, and personnel trained in their use and skilled in airway management should be assured. (See WARNINGS.) For deeply sedated pediatric patients, a dedicated individual, other than the practitioner performing the procedure, should monitor the patient throughout the procedure. The initial intravenous dose for sedation in adult patients may be as little as 1 mg, but should not exceed 2.5 mg in a normal healthy adult. Lower doses are necessary for older (over 60 years) or debilitated patients and in patients receiving concomitant narcotics or other central nervous system (CNS) depressants. The initial dose and all subsequent doses should always be titrated slowly; administer over at least 2 minutes and allow an additional 2 or more minutes to fully evaluate the sedative effect. The use of the 1 mg/mL formulation or dilution of the 1 mg/mL or 5 mg/mL formulation is recommended to facilitate slower injection. Doses of sedative medications in pediatric patients must be calculated on a mg/kg basis, and initial doses and all subsequent doses should always be titrated slowly. The initial pediatric dose of midazolam for sedation/anxiolysis/amnesia is age, procedure and route dependent (see DOSAGE AND ADMINISTRATION in full prescribing information). Neonates Midazolam should not be administered by rapid injection in the neonatal population. Severe hypotension and seizures have been reported following rapid IV administration, particularly with concomitant use of fentanyl (see DOSAGE AND ADMINISTRATION in full prescribing information). INDICATIONS AND USAGE Midazolam HCl Injection is indicated: intramuscularly or intravenously for preoperative sedation/anxiolysis/amnesia; intravenously as an agent for sedation/anxiolysis/amnesia prior to or during diagnostic, therapeutic or endoscopic procedures, such as bronchoscopy, gastroscopy, cystoscopy, coronary angiography, cardiac catheterization, oncology procedures, radiologic procedures, suture of lacerations and other procedures either alone or in combination with other CNS depressants; intravenously for induction of general anesthesia, before administration of other anesthetic agents. With the use of narcotic premedication, induction of anesthesia can be attained within a relatively narrow dose range and in a short period of time. Intravenous midazolam can also be used as a component of intravenous supplementation of nitrous oxide and oxygen (balanced anesthesia); continuous intravenous infusion for sedation of intubated and mechanically ventilated patients as a component of anesthesia or during treatment in a critical care setting. Midazolam is associated with a high incidence of partial or complete impairment of recall for the next several hours (see CLINICAL PHARMACOLOGY in full prescribing information). CONTRAINDICATIONS Injectable midazolam is contraindicated in patients with a known hypersensitivity to the drug. Benzodiazepines are contraindicated in patients with acute narrow-angle glaucoma. Benzodiazepines may be used in patients with openangle glaucoma only if they are receiving appropriate therapy. Measurements of intraocular pressure in patients without eye disease show a moderate lowering following induction with midazolam; patients with glaucoma have not been studied. Midazolam HCl Injection is not intended for intrathecal or epidural administration due to the presence of the preservative benzyl alcohol in the dosage form. WARNINGS Midazolam must never be used without individualization of dosage particularly when used with other medications capable of producing central nervous system depression. Prior to the intravenous administration of midazolam in any dose, the immediate availability of oxygen, resuscitative drugs, age- and size-appropriate equipment for bag/valve/mask ventilation and intubation, and skilled personnel for the maintenance of a patent airway and support of ventilation should be ensured. Patients should be continuously monitored with some means of detection for early signs of hypoventilation, airway obstruction, or apnea, i.e., pulse oximetry. Hypoventilation, airway obstruction and apnea can lead to hypoxia and/or cardiac arrest unless effective countermeasures are taken immediately. The immediate availability of specific reversal agents (flumazenil) is highly recommended. Vital signs should continue to be monitored during the recovery period. Because intravenous midazolam depresses respiration (see CLINICAL PHARMACOLOGY in full prescribing information) and because opioid agonists and other sedatives can add to this depression, midazolam should be administered as an induction agent only by a person trained in general anesthesia and should be used for sedation/anxiolysis/amnesia only in the presence of personnel skilled in early detection of hypoventilation, maintaining a patent airway and supporting ventilation. When used for sedation/anxiolysis/amnesia, midazolam should always be titrated slowly in adult or pediatric patients. Adverse hemodynamic events have been reported in pediatric patients with cardiovascular instability; rapid intravenous administration should also be avoided in this population. See DOSAGE AND ADMINISTRATION in full prescribing information. Serious cardiorespiratory adverse events have occurred after administration of midazolam. These have included respiratory depression, airway obstruction, oxygen desaturation, apnea, respiratory arrest and/or cardiac arrest, sometimes resulting in death or permanent neurologic injury. There have also been rare reports of hypotensive episodes requiring treatment during or after diagnostic or surgical manipulations particularly in adult or pediatric patients with hemodynamic instability. Hypotension occurred more frequently in the sedation studies in patients premedicated with a narcotic. Reactions such as agitation, involuntary movements (including tonic/clonic movements and muscle tremor), hyperactivity and combativeness have been reported in both adult and pediatric patients. These reactions may be due to inadequate or excessive dosing or improper administration of midazolam; however, consideration should be given to the possibility of cerebral hypoxia or true paradoxical reactions. Should such reactions occur, the response to each dose of midazolam and all other drugs, including local anesthetics, should be evaluated before proceeding. Reversal of such responses with flumazenil has been reported in pediatric patients. Concomitant use of barbiturates, alcohol or other central nervous system depressants may increase the risk of hypoventilation, airway obstruction, desaturation or apnea and may contribute to profound and/or prolonged drug effect. Narcotic premedication also depresses the ventilatory response to carbon dioxide stimulation. Higher risk adult and pediatric surgical patients, elderly patients and debilitated adult and pediatric patients require lower dosages, whether or not concomitant sedating medications have been administered. Adult or pediatric patients with COPD are unusually sensitive to the respiratory depressant effect of midazolam. Pediatric and adult patients undergoing procedures involving the upper airway such as upper endoscopy or dental care, are particularly vulnerable to episodes of desaturation and hypoventilation due to partial airway obstruction. Adult and pediatric patients with chronic renal failure and patients with congestive heart failure eliminate midazolam more slowly (see CLINICAL PHARMACOLOGY in full prescribing information). Because elderly patients frequently have inefficient function of one or more organ systems, and because dosage requirements have been shown to decrease with age, reduced initial dosage of midazolam is recommended, and the possibility of profound and/or prolonged effect should be considered. Injectable midazolam should not be administered to adult or pediatric patients in shock or coma, or in acute alcohol intoxication with depression of vital signs. Particular care should be exercised in the use of intravenous midazolam in adult or pediatric patients with uncompensated acute illnesses, such as severe fluid or electrolyte disturbances. There have been limited reports of intra-arterial injection of midazolam hydrochloride. Adverse events have included local reactions, as well as isolated reports of seizure activity in which no clear causal relationship was established. Precautions against unintended intra-arterial injection should be taken. Extravasation should also be avoided. The safety and efficacy of midazolam following nonintravenous and nonintramuscular routes of administration have not been established. Midazolam should only be administered intramuscularly or intravenously. The decision as to when patients who have received injectable midazolam, particularly on an outpatient basis, may again engage in activities requiring complete mental alertness, operate hazardous machinery or drive a motor vehicle must be individualized. Gross tests of recovery from the effects of midazolam (see CLINICAL PHARMACOLOGY in full prescribing information) cannot be relied upon to predict reaction time under stress. It is recommended that no patient operate hazardous machinery or a motor vehicle until the effects of the drug, such as drowsiness, have subsided or until one full day after anesthesia and surgery, whichever is longer. For pediatric patients, particular care should be taken to assure safe ambulation. Usage in Pregnancy An increased risk of congenital malformations associated with the use of benzodiazepine drugs (diazepam and chlordiazepoxide) has been suggested in several studies. If this drug is used during pregnancy, the patient should be apprised of the potential hazard to the fetus. Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE section).

Usage in Preterm Infants and Neonates Rapid injection should be avoided in the neonatal population. Midazolam administered rapidly as an intravenous injection (less than 2 minutes) has been associated with severe hypotension in neonates, particularly when the patient has also received fentanyl. Likewise, severe hypotension has been observed in neonates receiving a continuous infusion of midazolam who then receive a rapid intravenous injection of fentanyl. Seizures have been reported in several neonates following rapid intravenous administration. The neonate also has reduced and/or immature organ function and is also vulnerable to profound and/or prolonged respiratory effects of midazolam. Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol. Administration of high dosages of medications (including midazolam hydrochloride) containing this preservative must take into account the total amount of benzyl alcohol administered. The recommended dosage range of midazolam for preterm and term infants includes amounts of benzyl alcohol well below that associated with toxicity; however, the amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources. PRECAUTIONS General Intravenous doses of midazolam should be decreased for elderly and for debilitated patients (see WARNINGS above and DOSAGE AND ADMINISTRATION in full prescribing information). These patients will also probably take longer to recover completely after midazolam administration for the induction of anesthesia. Midazolam does not protect against the increase in intracranial pressure or against the heart rate rise and/or blood pressure rise associated with endotracheal intubation under light general anesthesia. Use with Other CNS Depressants The efficacy and safety of midazolam in clinical use are functions of the dose administered, the clinical status of the individual patient and the use of concomitant medications capable of depressing the CNS. Anticipated effects range from mild sedation to deep levels of sedation virtually equivalent to a state of general anesthesia where the patient may require external support of vital functions. Care must be taken to individualize and carefully titrate the dose of midazolam to the patient’s underlying medical/surgical conditions, administer to the desired effect being certain to wait an adequate time for peak CNS effects of both midazolam and concomitant medications, and have the personnel and size-appropriate equipment and facilities available for monitoring and intervention (see BOX WARNING, WARNINGS above and DOSAGE AND ADMINISTRATION section in full prescribing information.) Practitioners administering midazolam must have the skills necessary to manage reasonably foreseeable adverse effects, particularly skills in airway management. For information regarding withdrawal, see DRUG ABUSE AND DEPENDENCE section. Drug Interactions The sedative effect of intravenous midazolam is accentuated by any concomitantly administered medication which depresses the central nervous system, particularly narcotics (e.g., morphine, meperidine and fentanyl) and also secobarbital and droperidol. Consequently, the dosage of midazolam should be adjusted according to the type and amount of concomitant medications administered and the desired clinical response (see DOSAGE AND ADMINISTRATION in full prescribing information). Caution is advised when midazolam is administered concomitantly with drugs that are known to inhibit the P450-3A4 enzyme system such as cimetidine (not ranitidine), erythromycin, diltiazem, verapamil, ketoconazole and itraconazole. These drug interactions may result in prolonged sedation due to a decrease in plasma clearance of midazolam. For additional drug interaction information, refer to full prescribing information. Pregnancy Teratogenic Effects – Pregnancy Category D (see WARNINGS) Labor and Delivery In humans, measurable levels of midazolam were found in maternal venous serum, umbilical venous and arterial serum and amniotic fluid, indicating placental transfer of the drug. Following intramuscular administration of 0.05 mg/kg of midazolam, both the venous and the umbilical arterial serum concentrations were lower than maternal concentrations. The use of injectable midazolam in obstetrics has not been evaluated in clinical studies. Because midazolam is transferred transplacentally and because other benzodiazepines given in the last weeks of pregnancy have resulted in neonatal CNS depression, midazolam is not recommended for obstetrical use. Nursing Mothers Midazolam is excreted in human milk. Caution should be exercised when midazolam is administered to a nursing woman. ADVERSE REACTIONS See WARNINGS concerning serious cardiorespiratory events and possible paradoxical reactions. Fluctuations in vital signs were the most frequently seen findings following parenteral administration of midazolam in adults and included decreased tidal volume and/or respiratory rate decrease (23.3% of patients following IV and 10.8% of patients following IM administration) and apnea (15.4% of patients following IV administration), as well as variations in blood pressure and pulse rate. The majority of serious adverse effects, particularly those associated with oxygenation and ventilation, have been reported when midazolam is administered with other medications capable of depressing the central nervous system. The incidence of such events is higher in patients undergoing procedures involving the airway without the protective effect of an endotracheal tube, e.g., upper endoscopy and dental procedures. Adults: The following additional adverse reactions were reported after intramuscular administration: headache (1.3%); Local effects at IM injection site included: pain (3.7%), induration (0.5%), redness (0.5%), muscle stiffness (0.3%). Administration of IM midazolam hydrochloride to elderly and/or higher risk surgical patients has been associated with rare reports of death under circumstances compatible with cardiorespiratory depression. In most of these cases, the patients also received other central nervous system depressants capable of depressing respiration, especially narcotics (see DOSAGE AND ADMINISTRATION in full prescribing information). The following additional adverse reactions were reported subsequent to intravenous administration as a single sedative/anxiolytic/amnestic agent in adult patients: hiccoughs (3.9%), nausea (2.8%), vomiting (2.6%), coughing (1.3%), “oversedation” (1.6%), headache (1.5%), drowsiness (1.2%); Local effects at the IV site included: tenderness (5.6%), pain during injection (5.0%), redness (2.6%), induration (1.7%), phlebitis (0.4%). Pediatric Patients The following adverse events related to the use of IV midazolam in pediatric patients were reported in the medical literature: desaturation 4.6%, apnea 2.8%, hypotension 2.7%, paradoxical reactions 2.0%, hiccough 1.2%, seizure-like activity 1.1% and nystagmus 1.1%. The majority of airway-related events occurred in patients receiving other CNS depressing medications and in patients where midazolam was not used as a single sedating agent. Neonates For information concerning hypotensive episodes and seizures following the administration of midazolam to neonates, see BOX WARNING, CONTRAINDICATIONS, WARNINGS and PRECAUTIONS sections. DRUG ABUSE AND DEPENDENCE Midazolam is subject to Schedule IV control under the Controlled Substances Act of 1970. Midazolam was actively self-administered in primate models used to assess the positive reinforcing effects of psychoactive drugs. Midazolam produced physical dependence of a mild to moderate intensity in cynomolgus monkeys after 5 to 10 weeks of administration. Available data concerning the drug abuse and dependence potential of midazolam suggest that its abuse potential is at least equivalent to that of diazepam. Withdrawal symptoms similar in character to those noted with barbiturates and alcohol (convulsions, hallucinations, tremor, abdominal and muscle cramps, vomiting and sweating), have occurred following abrupt discontinuation of benzodiazepines, including midazolam. Abdominal distention, nausea, vomiting and tachycardia are prominent symptoms of withdrawal in infants. The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. Generally milder withdrawal symptoms (e.g., dysphoria and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Consequently, after extended therapy, abrupt discontinuation should generally be avoided and a gradual dosage tapering schedule followed. There is no consensus in the medical literature regarding tapering schedules; therefore, practitioners are advised to individualize therapy to meet patient’s needs. In some case reports, patients who have had severe withdrawal reactions due to abrupt discontinuation of high-dose long-term midazolam, have been successfully weaned off of midazolam over a period of several days. Baxter Healthcare Corporation Deerfield, IL 60015 USA For Product Inquiry 1 800 ANA DRUG (1-800-262-3784) BAXTER is a trademark of Baxter International Inc. 462-051-06 4/2009

THE SCIENCE BEHIND POSITIVE PATIENT OUTCOMES

Medication Safety and Quality Part 4: Measurement and Reporting Christian Hartman, PharmD, MBA Medication Safety Officer UMass Memorial Medical Center Worcester, Massachusetts

CATEGORY

OUTCOME

Circumstances or events that have the capacity to cause error

An error that did not reach the patient

Lyndsy Pinchevsky, PharmD

An error that reached the patient but did not cause harm

Medication Safety Resident UMass Memorial Medical Center Worcester, Massachusetts

An error that reached the patient and required monitoring or intervention to confirm that it resulted in no harm to the patient

Temporary harm to the patient and required intervention

Temporary harm to the patient and required initial or prolonged hospitalization

Permanent patient harm

Intervention required to sustain life

Patient death

Introduction The 1999 Institute of Medicine (IOM) Report, To Err is Human, was instrumental in exposing the public to the reality of errors occurring in the health care field and highlighted the need to focus on medication and patient safety. One of the ongoing challenges in health care is how to measure the safety of the medicationuse system reliably and implement needed changes.1 Health care organizations are tasked with balancing appropriate internal measurements, internal reporting, regulatory standards measurements, and external reporting. A systematic approach to maintaining the balance provides the framework for organizations to advance medication safety efforts.

Internal Reporting and Measurement Organizations traditionally have measured medication error rates based on staff-reported occurrences in an attempt to gauge the success of medication safety procedures. These error rates have proved to be of little value for a number of reasons, including a lack of consistency in how the term error is defined, disagreement about the most effective manner in which to learn about errors, and error rates that typically consist of a small sample of true events and are not representative of the entire organization. A high error rate may suggest either unsafe medication practices or an organizational culture that promotes

Table 1. NCC MERP Categories

PHARMACY PRACTICE NEWS • JULY 2009

Measures excluded from the IHI GTT as they DO NOT result in patient harm

Measures included in the IHI GTT as they DO result in patient harm

ADE, adverse drug event; GTT, global trigger tool; IHI, Institute for Healthcare Improvement; NCC MERP, National Coordinating Council for Medication Error Reporting and Prevention Adapted from reference 6.

error reporting. Conversely, a low error rate may suggest either successful errorprevention strategies or a punitive culture that inhibits error reporting. Most experts agree that spontaneous error reporting does not capture all errors and that this method is not designed to measure true medication error rates.2 In addition to improving culture, organizations should develop a strategy for error identification with the goal of developing programs that minimize the chance for failure in a process. Such strategies may include a nonpunitive occurrencereporting system, prospective review, electronic clinical decision support surveillance/rules-based adverse drug event (ADE) alerts, retrospective medical chart reviews (including the global trigger tool) and observation. Many health care organizations make use of “trigger” drugs. Orders for these drugs, which include naloxone for narcotic-induced respiratory depression, vitamin K for anticoagulant overdose, and flumazenil (Romazicon,

Roche) for benzodiazepine overdose, alert the pharmacist to further investigate what possibly could be an ADE.3,4 Recent studies have shown the benefit of using this type of trigger alert in identifying possible ADEs.4,5 The recently published IHI Global Trigger Tool for Measuring Adverse Events adapted portions of previous guidelines published by the the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) for the categorization of medication errors.6 The original NCC MERP index contained nine categories, five of which were included in the Institute for Healthcare Improvement’s Global Trigger Tool (IHI GTT). The first four categories were eliminated, as they did not account for the effect of ADEs on patients, but rather tracked errors that occurred prior to reaching the patient or did not result in patient harm. Table 1 lists the NCC MERP categories and indicates those that were adapted by the IHI. The IHI GTT is broken down into six

module triggers: care, surgical, medication, intensive care, perinatal, and emergency department. Table 2 lists the triggers included in the medication module.7 The IHI strongly encourages that these events be tailored to individual institutions. Many experts recommend a combination of multiple methods to identify potential risks.8 Organizations should prioritize the measurement of medication safety for the purpose of learning and improving the medication-use system. Cohen and colleagues suggest a general approach to measuring medication safety that includes the following steps: 1. determine the opportunity to be measured; 2. perform a literature search; 3. establish goals; 4. construct measures relevant to the process; 5. create a data collection plan; 6. perform a test and measure; and 7. communicate the results.9 The IHI suggests tracking outcome, process, and balancing measures when working to improve the safety of medication systems.10 Rate-based indicators are useful for outcome and process measures because they reflect the frequency of an event as a proportion or ratio.11 Outcome measures track specific improvements in the medication-use system, such as reduction of patient harm from ADEs. Examples of outcome measures include number of ADEs per 1,000 doses, percentage of admissions with an ADE, percentage of patients receiving a specific high-risk medication with a related ADE, and number of high-risk ADEs per 1,000 doses. Process measures specifically focus on the medication-use process and can identify whether procedural changes are leading to a safer system. Examples of process measures include percentage of unreconciled medications, number of self-reported medication errors (culture), number of pharmacy interventions per 100 admissions, risk priority number in failure mode and effects analysis, and number of errors from unreconciled medication per 100 admissions. Finally, balancing measures are used

Section Supportedrt by 9

Pharmacy Practice News • July 2009

Section sub rt

Table 2. Medication and Lab Triggers Trigger Drug Category or Situation M1

Clostridium difficilepositive stool

PTT >100 seconds

INR >6

Glucose <50 mg/dL

Rising BUN or serum creatinine greater than 2 times baseline

Vitamin K administration

Diphenhydramine use

Flumanezil use

Naloxone use

M10

Anti-emetic use

M11

Oversedation/ hypotension

M12

Abrupt medication stop

M13

Other

BUN, blood urea nitrogen; INR, international normalized ratio; PTT, partial thromboplastin time Adapted from reference 7.

to identify potential new problems in the medication-use system as a result of the changes made to improve another part of the system.

Benchmarking Although benchmarking may be a popular and convenient way to compare practices, organizations such as the Institute for Safe Medication Practices and NCC MERP have expressed concern about the application of such a process. Because specific differences exist from organization to organization—thus reducing the applicability of error rates—benchmarking as a measure of health care-wide practices should not be relied on for the following reasons:

1. differences in culture among various or preparation errors; misuse of medihealth care organizations can result cal equipment; and errors in prescribin a variation in the number of errors ing, transcribing, dispensing, and monitoring medications. Recommendations actually reported; 2. differences in the definition of a medi- for error prevention are shared with the cation error across organizations can health care community and consumlead to differences in reporting of ers through newsletters, annual reports, errors (ie, some organizations consid- and/or national alerts. Two examples of er errors that reach the patient to be education dissemination are the Joint true events, whereas others also will Commission’s Sentinel Event Alerts and include “near-misses” or those events ISMP’s Medication Safety Alert!® newsletters. Both organizations highlight error that had potential to cause harm); 3. differences in the patient population trends and encourage health care orgaserved by health care organizations nizations to re-evaluate their current can result in differences in the num- safety practices. To Err is Human strongly supported a ber and severity of medication errors mandatory national error-reporting prooccurring; and 4. differences in the types of reporting gram. Although no such national system and detection systems for medication is currently in place, some states have errors can result in differences in the adopted and implemented various mandatory reporting programs. The majority actual number of errors reported.12 The NCC MERP has stated that bench- of state-reporting systems have adoptmarking of medication error rates are of ed the National Quality Forum’s (NQF) no value to health care organizations recommended core list of standardand strongly recommends that senior ized reportable events. In 2002, the NQF management officials reconsider the use published the study, “Serious Reportable of this process. Management should Events in Health Care,” which listed 27 instead focus on actual and potential “never events”—defined as largely meamedication errors occurring within their surable and extremely serious adverse own organizations and identify ways to events that are of such high concern to improve the medication-use system to both consumers and health care proprevent future errors.12 Additionally, after fessionals that they should never occur. changes have been implemented to Organizations such as the Centers for address the root cause of error, out- Medicare & Medicaid Services (CMS) and come measurements may be a more select health care payers support the pertinent means of gauging the effec- identification and elimination of never tiveness of error-prevention efforts. events. In 2008, the CMS announced it will no longer reimburse hospitals for certain never events; other insurance External Reporting groups are beginning to follow suit.13 National organizations (United States Pharmacopeia [USP] MedMARx™, FDA Conclusion MedWatch, USP-ISMP Medication Errors Error reporting is a common practice Reporting Program and the Joint Commission) collect data on errors with among health care institutions, but cauthe intent of educating health profes- tion is recommended when using error sionals and reducing recurrent errors.3 rates to compare safe practices between These organizations encourage the sub- organizations. A multifaceted approach mission of errors, near-misses, or haz- to identifying medication occurrences ardous conditions, such as adminis- such as staff-initiated reporting, the use tration of the wrong drug, strength, or of trigger tools, clinical surveillance, and dose of a medication; confusion regard- retrospective reviews should be impleing look-alike/sound-alike drugs; incor- mented. A balance of internal, standards, rect route of administration; calculation and external measurements provides a

robust structure for improving the medication-use process.

References 1.

Classen DC, Metzer J. Improving medication safety: the measurement conundrum and where to start. Int J Qual Health Care. 2003;15(1):i41-i47.

The Institute for Safe Medication Practices. ISMP Medication Safety Alert: Benchmarking—when is it dangerous? Horsham, PA: Institute for Safe Medication Practices; 2009.http://www.ismp.org/newsletters/acutecare/articles/19980909.asp?ptr=y. Accessed April 30, 2009.

Joint Commission Resources (JCR). Preventing medication errors: strategies for pharmacists. Oakbrook Terrace, IL: JCR; 2001.

Rozich JD, Haraden CR, Resar RK. Adverse drug event trigger tool: a practical methodology for measuring medication related harm. Qual Saf Health Care. 2003;12(3):194-200.

Takata GS, Mason W, Taketomo C, Logsdon T, Sharek PJ. Development, testing, and findings of a pediatric-focused trigger tool to identify medication-related harm in US children’s hospitals. Pediatrics. 2008;121(4):e927-935.

Griffin FA, Resar RK. IHI global trigger tool for measuring adverse events. 2nd ed. IHI Innovation Series white paper. Cambridge, MA: Institute for Healthcare Improvement; 2009. www.IHI.org. Accessed May 6, 2009.

IHI. Trigger tool for measuring adverse drug events. Cambridge, MA: Institute for Healthcare Improvement and Premier; 2004. www.IHI.org. Accessed May 6, 2009.

Cousins D. Safe medication initiatives—sustaining good practice. Hosp Pharm. 2006;(13):215-217.

Cohen MR, ed. Medication Errors. Washington DC: American Pharmacists Association; 2007:646-648.

10. Institute for Healthcare Improvement. Patient safety: medication systems. Cambridge, MA, Institute for Healthcare Improvement; 2009. http://www.ihi. org/IHI/Topics/PatientSafety/MedicationSystems/ Measures/. Accessed April 30, 2009. 11. Joint Commission Resources (JCR). Medication use: a system’s approach to reducing errors. Oakbrook Terrace, IL: JCR; 1998:26-28. 12. Council recommendations. Statement from NCC MERP: use of medication error rates to compare health care organizations is of no value. Rockville, MD: NCC MERP; 1998-2009. 13. Department of Health and Human Services. Centers for Medicare & Medicaid 42 CFR Parts 411, 412, 413 et al. Medicare Program: proposed changes to the hospital inpatient prospective payment systems and fiscal year 2009 rates. Federal Register. 73(84):23528-23938. http://edocket. access.gpo.gov/2008/pdf/08-1135.pdf. Accessed March 27, 2009.

PHARMACY PRACTICE NEWS • JULY 2009

with distinct labeling from Baxter. Coming soonâ&#x20AC;Śdistinctive labeling from Baxter. To learn more, contact your Baxter representative or call 1-800-4-BAXTER (1-800-422-9837).

Baxter, Committed to a Safer Healthcare Environment, and the distinctive product label design are trademarks of Baxter International Inc. Baxter Healthcare Corporation, Route 120 and Wilson Road, Round Lake, IL 60073 www.baxter.com 111085 03/09

Operations & Management 11

Pharmacy Practice News • July 2009

Staffing

TAMING TURNOVER continued from page 1

Lynnae Mahaney, MBA, RPh, current ASHP president and a veteran of a similar effort to boost employee satisfaction, agreed that the results were impressive. “None of the initiatives alone are groundbreaking. But the fact that Benefis has put it all together and done just about everything you could think of to boost recruitment and retention is really noteworthy,” said Ms. Mahaney, chief of pharmacy services at William S. Middleton Memorial Veterans Hospital, Madison, Wis. One of the first steps Benefis took to improve pharmacy retention was to expand its clinical programs. But as those efforts unfolded—for example, adding pharmacists to critical care teams, women’s and children’s services and pain management—“we also had to make sure we were matching those services to the passions of our staff,” Mr. Caselnova said. Hence, a survey was sent to every staff pharmacist, asking them about their practice areas of choice and then re-deploying them to those areas whenever possible. The survey also asked pharmacy staff to identify, if they had a choice, what work schedule would best meet their

personal and professional needs. Based on the replies, several flexible scheduling options were offered, including a seven-dayson, seven-days-off option, where pharmacists would work in 12-hour shifts in the day or evening. The every-other-week scheduling solved two persistent problems at Benefis: filling weekend spots and evening shifts. The flextime alternative also had another benefit: Because the same group of people tended to work a given shift, “the new schedules promoted teamwork and improved communication among our pharmacy staff,” Mr. Caselnova said.

Career Enhancement One of the additional offerings at Benefis is a career advancement program, implemented in 2004, that takes a threetiered approach to encouraging professional growth. In each tier, pharmacists can earn points for several “domains,” such as community service, volunteering in professional organizations, authoring posters and peer-reviewed articles and writing educational materials for staff physicians. “The first level is fairly easy to achieve and earns you 60 points for any one domain,” he explained.

Tips for Success

thus entitled to sign-on bonuses, along with quarterly bonuses for a one-year commitment to work night shifts. All of these initiatives played a role in tackling the average 22% turnover rate that was present at Benefis from 2000 to 2002, Mr. Caselnova said. Turnover fell to an average of 4.7% annually from 2003 to 2005, when several of the initiatives went into effect. “For the past two years,” he added, “it’s been zero,” with comparable gains in staff satisfaction (Figures 1 and 2, page 12). Mr. Caselnova pointed to one additional component of the retention plan of note—eliminating faxed drug orders and replacing them with a system where the physicians’ orders can be scanned and then viewed by pharmacists online. “Several of our pharmacists said that

ffering flexible work hours to your pharmacists may be one of the most effective strategies for boosting employee satisfaction and retention, according to pharmacy managers interviewed for this article. But for the strategy to work optimally, be sure to keep these implementation tips in mind: Be flexible. Lynnae Mahaney, MBA, RPh, said that her VA hospital is not rigidly beholden to only a few flexible work-hour options. “Basically, if one of our pharmacists has a personal scheduling need that does not affect our department’s efficiency or productivity, and it does not adversely affect patient safety, then that scheduling request is approved.” Avoid specialization. Make sure that pharmacists on flextime shifts still have a balance between drug order entry and more clinical responsibilities, such as drug order review, patient care, physician rounding and so on. “If you have pharmacists who can function in a variety of areas, it makes it much easier to pull off a complicated flex schedule,” said Michael Sanborn, MS, FASHP. “It’s not unlike a baseball team, where if one player goes down, you have several utility players who can fill in and cover multiple positions.” Delegate. When pharmacists have an idea for a new flextime schedule, “put it back on them to make the case” for how the proposal can work without disrupting existing policies and procedures, Mr. Sanborn said. Doing so “saves you time as a pharmacy manager and gives staffers more ownership for their new schedule.” Ms. Mahaney takes that approach a step further and has created a scheduling team to assist her in drafting portions of the schedule for areas such as the ambulatory care pharmacy. “Once the group drafts that portion, they give it to me and I fill in the rest; it’s a huge help.” Look to the future. Today’s innovative flextime schedules are only a start— consider telecommuting as the next step in meeting today’s workforce needs. “We’ve got this on our radar because there’s already a precedent set at Baylor—several staffers in our coding and reimbursement department work successfully from home,” Mr. Sanborn said. “It could work here because all the key components to patient care—electronic medical records, lab results, drug orders, etc.—can all be accessed via computer. So there’s no reason why we couldn’t have a shift of pharmacists at home reviewing drug orders during high-peak times.” —David Bronstein

‘Several of our pharmacists said that [eliminating faxed drug orders] was the single most important change for the better in their day-to-day practice. It really lessened their workload and improved their organization and efficiency.’ —Dominick A. Caselnova III, BS, MHA “The second tier carries additional points and requires that you reach goals in two domains. For the third tier, you have to become board-certified in a specialty area of pharmacy.” (Benefis defrays some of the costs of preparing for the certification exam.) Once each tier is reached, the points allotted translate to annual “professional growth” bonuses (range, $2,080$6,240) that are only given if the goals are consistently achieved, Mr. Caselnova added. Educational opportunities also are stressed at Benefis. For example, returning to school to earn a PharmD degree is a laudable goal that the hospital encourages—and funds—in exchange for a work commitment of at least one year. “It’s a win–win: staffers with BSPharm degrees who are interested in ramping up their clinical training get to do so, and we get to lock them in to a four- to six-year work commitment, based on the time they’re taking classes and then the full-time employment afterward,” he said. “We’ve had three pharmacists do this in the past few years.”

Additional Retention Tools Benefis’ retention and recruitment program also includes the opportunity to attend regional and national meetings in a pharmacist’s area of interest or expertise; weekly staff meetings to improve communication between staff and pharmacy management; and recognition that pharmacists are “critical” employees and

this was the single most important change for the better in their day-today practice,” he said. “It really lessened their workload and improved their organization and efficiency.” Ms. Mahaney echoed the importance of using technology such as drug order scanning to maximize pharmacists’ satisfaction with their jobs. “The best use of a pharmacist’s time is in direct patient care and ways that they can affect prescribing,” she said. “So getting rid of manual tasks such as retrieving and viewing hard-toread handwritten drug orders from the fax, and replacing them with more clinically oriented responsibilities, allows pharmacists to utilize their training and education and truly contribute to patient care. That, in turn, leads to enhanced job satisfaction.”

Other Successes Detailed Michael Sanborn, MS, FASHP, corporate vice president, Baylor Health Care System, Dallas, is also a fan of using technology to free up pharmacists to provide more direct patient care. In fact, like Benefis, he also had great success switching from a fax-based drug order review system to one that enabled pharmacists to review electronic scans of the orders virtually anywhere onscreen. “We were able to reduce the time spent processing and verifying medication orders by 35%,” he said in an interview with Pharmacy Practice News.

•

see TAMING TURNOVER, page 12

12 Operations & Management

Pharmacy Practice News • July 2009

Staffing

“That made a huge difference in worker productivity and satisfaction.” The experience also illustrates an important lesson about pharmacy technology. “I tell every pharmacy director I know that if they are contemplating adding one piece of technology, an electronic drug order scanning system is the way to go,” he said. “If they’re still stuck on CPOE, bar coding or dispensing automation, I point out that those technologies primarily serve physicians and nurses far

macist turnover to about 2%, from a high of 8% several years earlier. Ms. Mahaney, a co-author of the 2008 AJHP report on flextime schedules, said that she is still a fan of the recruiting and retention strategy. “It’s been about seven years since we’ve implemented a seven-days-on, seven-days-off, 11-hour-per-day scheduling option. Coupled with other initiatives, such as enhanced clinical pharmacy services, it’s a major reason why our turnover rate is essentially zero.”

Satisfaction Trendline

4.2 4 .1 4.0 3.9

Score

continued from page 11

more than pharmacy.” Mr. Sanborn stressed, however, that electronic drug order scanning is not a magic bullet, even though he published a paper extolling its benefits in 2006 (Am J Health-Syst Pharm 2006;63:1438-1441). Indeed, two years later, he followed up with another report in AJHP on the ability of flexible scheduling to promote worker satisfaction and retention. Baylor’s strategy was to offer, like Benefis, alternating full-week schedules to pharmacists interested in flextime. The strategy, along with other job satisfaction efforts, resulted in reducing phar-

3.8 3.7 3.6 3.5 3.4 3.3

—David Bronstein

3.2 2004

2005

2006

2007

2008

Figure 1. Staff satisfaction score.

Rate Trendline

35 30 25

Turnover (%)

TAMING TURNOVER

20 15 10 5 0 -5 2000

2001 2002 2003 2004 2005 2006 2007 2008 2009

Year

Figure 2. Pharmacist turnover.

ASHP Task Force Supports Flextime, Other Options

he recruitment and retention strategies employed at Benefis don’t just have the force of good outcomes data behind them: the initiatives also were cited by a recent ASHP Task Force as effective ways to promote pharmacist satisfaction and retention. Known officially as the Task Force on Pharmacy’s Changing Demographics, the group stressed that flexible work schedules, job sharing and other strategies that offer staffers a better work–life balance should be encouraged. The efforts are needed, the Task Force noted, because of a shift in the workforce toward employees—women, generation Xers and millennials—who appreciate and seek such balance. For more details on the task force’s recommendations, see its report in the June 15, 2007, issue of AJHP (64:1311-1319).

Operations & Management 13

Pharmacy Practice News • July 2009

Leadership in Action

Life Portfolio—The Work Continues, But at a New Venue “Leadership in Action” is authored by Ernest R. Anderson Jr., MS, RPh, System Vice President of Pharmacy, Caritas Christi, Boston, Mass. Mr. Anderson welcomes your input on leadership issues, at ernieanderson@ verizon.net.

Ernest R. Anderson Jr., MS, RPh

defining themselves in terms of their work. And they learn to pay attention to the issue of balance, to the interplay of parts that make up a whole life.” In essence, the portfolio is meant to probe deeply beneath the surface, revealing the essence of who we are. Oddly, I feel as though I have always held this perspective.

Building a Life Portfolio Legacy

nce again this season, my son, two friends and I installed the ski slalom course at the lake. Sadly, although it is one of my life goals, I have never successfully completed the entire course. Other people I ski with handle it with relative ease. Frankly, I’m a little frustrated that I haven’t been able to do it yet. My son, who is 20 years younger than me, makes it look easy. I just try to incrementally improve without hurting myself. I’m still hopeful. My progress and passion for this slalom course remind me of the five elements of a balanced life, as described by author David Corbett in “Portfolio Life: The New Path to Work, Purpose, and Passion After 50.”1 He names the five “elements”: 1) working in the form you want, 2) learning and developing, 3) making time for personal pursuits and recreation, 4) enjoying family and friends and 5) giving back to society. When balanced, the author contends, these five elements will help us all to live authentic, realized lives. In a previous column, I encouraged you to write your own life plan. How did you do? In my plan, I identified the following five areas of my life that I find to be the most important: my employment/work life, my professional/organizational life, my mentoring of young people, my family and personal life, and my spiritual life. I have been in the process of seriously reviewing all these aspects of my life. How seriously? Well, for starters, I have made a major decision to move on to a new job after 15-plus years as director of pharmacy at the Lahey Clinic. I have identified deficiencies that can best be remedied by pursuing a new opportunity. This is one of the most radical, difficult decisions that I have made in my life—one that I wrestled with over many months. I consulted with many advisers and mentors about this decision. Making this change is a reflection of the broader view of my life that I have adopted over the last several years. This is in line with Corbett’s message that “two things happen as people shift from a career perspective to a portfolio perspective. They begin to take a broader view of their lives, beyond

One of the questions while build-

ing a life portfolio is to consider what kind of legacy you will leave behind. As I mentioned in our last segment, you should use the gifts and talents that come naturally to you. As Dave Corbett says: “Legacies are inextricably linked to our values. Legacies happen when we respond authentically to our callings.” The portfolio is a method to analyze our lives in an effort to serve a larger calling (to be productive, meaningful and fulfilled). This means that we must

be deliberate in our approaches. Too often, people move in their public and private lives, but never look into their inner lives to conduct a reflective evaluation of who they are, complete with an examination of their driving values. As I consider what my legacy might be, I take stock of the energy I have devoted to the five elements of my life plan. I still haven’t completed some of my goals (such as easily skiing the slalom course).

•

see LIFE PORTFOLIO, page 14

VANCOCIN® is the only product indicated for

treatment of C. difficile infection1 Advantageous Pharmacokinetic Profile Oral vancomycin acts locally in the colon – where C. difficile produces toxin and treatment is needed1 Extremely high levels of vancomycin (often 500-1000 μg/mL) in colonic lumen – several hundred-fold more than the highest MIC for C. difficile1,2

vs. Undetectable to extremely low levels are seen in the colonic lumen with metronidazole, which is virtually 100% absorbed in the small bowel1,2

Outstanding Efficacy Significant head-to-head cure rates in severe C. difficile infection vs. metronidazole1,3

97% for vancomycin

vs.

76% for metronidazole

†3

* The product used in this study was vancomycin liquid. † Metronidazole is not approved for use in the treatment of Clostridium difﬁcile-associated diarrhea.

Plus – the advantageous pharmacokinetics of vancomycin may result in a lower probability of complications2

First-Line, First Choice for Severe Clostridium difﬁcile Infection

Please see brief summary of full Prescribing Information for VANCOCIN® HCl Capsules on following page. INDICATIONS AND USAGE VANCOCIN® (vancomycin hydrochloride, USP) Capsules may be administered orally for treatment of enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains) and antibiotic-associated pseudomembranous colitis caused by Clostridium difﬁcile. Parenteral administration of vancomycin is not effective for the above indications; therefore, VANCOCIN HCl Capsules must be given orally for these indications. Orally administered VANCOCIN HCl Capsules are not effective for other types of infection. IMPORTANT SAFETY INFORMATION To reduce the development of drug-resistant bacteria and maintain the effectiveness of VANCOCIN HCl Capsules and other antibacterial drugs, VANCOCIN HCl Capsules should only be used to treat or prevent infections that are proven or strongly suspected to be caused by a susceptible bacterium. When culture and sensitivity are available, they should be considered in selecting or modifying antibacterial therapy.

AA0076

Take control of C. difﬁcile

Adverse events include nephrotoxicity, ototoxicity, reversible neutropenia, thrombocytopenia, and “Red Man’s Syndrome.” In patients with renal dysfunction, or those receiving concomitant therapy with an aminoglycoside, serial renal function testing should be performed. In patients receiving concomitant therapy with another ototoxic agent, serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity. Infrequently, allergic reactions, including anaphylaxis and exfoliative dermatitis, have been reported. Clinically significant serum concentrations of vancomycin have been reported in some patients treated with VANCOCIN HCl Capsules for pseudomembranous colitis caused by Clostridium difficile. It is noteworthy that total systemic and renal clearance of vancomycin are reduced in the elderly. Monitoring of serum concentrations may be appropriate in patients with renal insufficiency and/or colitis. VANCOCIN HCl Capsules are contraindicated in patients with a known hypersensitivity to vancomycin.

REFERENCES: 1. Bartlett JG. The case for VANCOMYCIN as the preferred drug for treatment of Clostridium difficile infection. Clin Infect Dis. 2008;46:1489-1492. 2. Pépin J. Vancomycin for the treatment of Clostridium difficile Infection: for whom is this expensive bullet really magic? Clin Infect Dis. 2008;46:1493-1498. 3. Zar FA, Bakkanagari SR, Moorthi KMLST, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45:302-307. ©2009 ViroPharma Incorporated. VANCOCIN and the VIROPHARMA INCORPORATED plus design logo are registered trademarks of ViroPharma Incorporated. The disintegrating upside-down triangle alone and in combination with VANCOCIN are trademarks of ViroPharma Incorporated.

05/2009

14 Operations & Management

Pharmacy Practice News • July 2009

Leadership in Action

LIFE PORTFOLIO continued from page 13

As I move toward formal retirement, I need to take action.

The Life Plan Evaluation As I was evaluating the first element of my life plan—my work life—I discovered two goals that presented difficulty for me in my current job. The first goal was to “stay in Quadrant II.” Quadrant II is a concept described in Stephen Covey’s “The 7 Habits of Highly Effective People,”2 in which the author encourages

the reader to focus on tasks that may not be the most urgent on your plate, but that are important to your personal and professional well-being, such as relationship building and recognizing new opportunities. What I had been finding in my current job was a constant crisis-management mode driven by those above me—Quadrant I, in Covey’s time management matrix. The second goal was to “operate in confidence.” At work, I found I was having difficulty operating in confidence with those to whom I reported directly— even though I continually received high

VANCOCIN® HCl CAPSULES (vancomycin hydrochloride capsules, USP) INDICATIONS AND USAGE This preparation for the treatment of colitis is for oral use only and is not systemically absorbed. VANCOCIN HCl Capsules must be given orally for treatment of staphylococcal entero-colitis and antibiotic-associated pseudomembranous colitis caused by Clostridium difficile. Orally administered VANCOCIN HCl Capsules are not effective for other types of infection. Parenteral administration of vancomycin is not effective for treatment of staphylococcal enterocolitis and antibiotic-associated pseudomembranous colitis caused by C. difficile. If parenteral vancomycin therapy is desired, use an intravenous preparation of vancomycin and consult the package insert accompanying that preparation. VANCOCIN HCl Capsules may be administered orally for treatment of enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains) and antibiotic-associated pseudomembranous colitis caused by C. difficile. Parenteral administration of vancomycin is not effective for the above indications; therefore, VANCOCIN HCl Capsules must be given orally for these indications. Orally administered VANCOCIN HCl Capsules are not effective for other types of infection. To reduce the development of drug-resistant bacteria and maintain the effectiveness of VANCOCIN HCl Capsules and other antibacterial drugs, VANCOCIN HCl Capsules should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. CONTRAINDICATION VANCOCIN HCl Capsules are contraindicated in patients with known hypersensitivity to vancomycin. PRECAUTIONS General Prescribing VANCOCIN HCl Capsules in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Clinically significant serum concentrations have been reported in some patients who have taken multiple oral doses of vancomycin for active C. difficile-induced pseudomembranous colitis; therefore, monitoring of serum concentrations may be appropriate in some instances, e.g., in patients with renal insufficiency and/or colitis. Some patients with inflammatory disorders of the intestinal mucosa may have significant systemic absorption of vancomycin and, therefore, may be at risk for the development of adverse reactions associated with the parenteral administration of vancomycin (see package insert accompanying the intravenous preparation). The risk is greater if renal impairment is present. It should be noted that the total systemic and renal clearances of vancomycin are reduced in the elderly. Ototoxicity has occurred in patients receiving vancomycin. It may be transient or permanent. It has been reported mostly in patients who have been given excessive intravenous doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent, such as an aminoglycoside. Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity. When patients with underlying renal dysfunction or those receiving concomitant therapy with an aminoglycoside are being treated, serial monitoring of renal function should be performed. Use of vancomycin may result in the overgrowth of nonsusceptible organisms. If superinfection occurs during therapy, appropriate measures should be taken. ADVERSE REACTIONS Nephrotoxicity — Rarely, renal failure, principally manifested by increased serum creatinine or BUN concentrations, especially in patients given large doses of intravenously administered vancomycin HCl has been reported. Rare cases of interstitial nephritis have been reported. Most of these have occurred in patients who were given aminoglycosides concomitantly or who had preexisting kidney dysfunction. When vancomycin HCl was discontinued, azotemia resolved in most patients. Ototoxicity — A few dozen cases of hearing loss associated with intravenously administered vancomycin HCl have been reported. Most of these patients had kidney dysfunction or a preexisting hearing loss or were receiving concomitant treatment with an ototoxic drug. Vertigo, dizziness, and tinnitus have been reported rarely. Hematopoietic — Reversible neutropenia, usually starting 1 week or more after onset of intravenous therapy with vancomycin HCl or after a total dose of more than 25 g, has been reported for several dozen patients. Neutropenia appears to be promptly reversible when vancomycin HCl is discontinued. Thrombocytopenia has rarely been reported. Miscellaneous — Infrequently, patients have been reported to have had anaphylaxis, drug fever, chills, nausea, eosinophilia, rashes (including exfoliative dermatitis), Stevens-Johnson syndrome, toxic epidermal necrolysis, and rare cases of vasculitis in association with the administration of vancomycin HCl. A condition has been reported that is similar to the IV–induced syndrome with symptoms consistent with anaphylactoid reactions, including hypotension, wheezing, dyspnea, urticaria, pruritus, flushing of the upper body (“Red Man Syndrome”), pain and muscle spasm of the chest and back. These reactions usually resolve within 20 minutes but may persist for several hours.

praise from others, both internally in our department and externally. I found goal setting difficult, due to that lack of clarity above me. In the second element—professional/ organizational life—I had one goal that I have lacked support to attain at Lahey Clinic. That was to try to get nominated to run for the board of the American Society of Health-System Pharmacists and get elected. At this point in my career, I decided, if I truly want to achieve this goal, I cannot afford to procrastinate. In the third element—family and per-

USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects — Pregnancy Category B — The highest doses of vancomycin tested were not teratogenic in rats given up to 200 mg/kg/day IV (1180 mg/m2 or 1 times the recommended maximum human dose based on mg/m2) or in rabbits given up to 120 mg/kg/day IV (1320 mg/m2 or 1.1 times the recommended maximum human dose based on mg/m2). No effects on fetal weight or development were seen in rats at the highest dose tested or in rabbits given 80 mg/kg/day (880 mg/m2 or 0.74 times the recommended maximum human dose based on mg/m2). In a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin HCl on infants were evaluated when the drug was administered intravenously to pregnant women for serious staphylococcal infections complicating intravenous drug abuse. Vancomycin was found in cord blood. No sensorineural hearing loss or nephrotoxicity attributable to vancomycin HCl was noted. One infant whose mother received vancomycin HCl in the third trimester experienced conductive hearing loss that was not attributed to the administration of vancomycin HCl. Because the number of patients treated in this study was limited and vancomycin HCl was administered only in the second and third trimesters, it is not known whether vancomycin HCl causes fetal harm. Because animal reproduction studies are not always predictive of human response, VANCOCIN HCl Capsules should be given to a pregnant woman only if clearly needed. Nursing Mothers Vancomycin is excreted in human milk based on information obtained with the intravenous administration of vancomycin HCl. However, systemic absorption of vancomycin is very low following oral administration of VANCOCIN HCl Capsules (see CLINICAL PHARMACOLOGY). It is not known whether oral vancomycin is excreted in human milk, as no studies of vancomycin concentration in human milk after oral administration have been done. Caution should be exercised when VANCOCIN HCl Capsules are administered to a nursing woman. Because of the potential for adverse events, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Clinical studies of vancomycin HCl for oral use 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. 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. Clinically significant serum concentrations have been reported in some patients who have taken multiple oral doses of vancomycin HCl for active C. difficle-induced pseudomembranous colitis; therefore, monitoring of serum concentrations may be appropriate in some instances, e.g., in patients with renal insufficiency and/or colitis. Some patients with inflammatory disorders of the intestinal mucosa may have significant systemic absorption of vancomycin and, therefore, may be at risk for the development of adverse reactions associated with the parenteral administration of vancomycin. The risk is greater if renal impairment is present. It should be noted that the total systemic and renal clearances of vancomycin are reduced in the elderly (see PRECAUTIONS, General). OVERDOSAGE Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis. Hemofiltration and hemoperfusion with polysulfone resin have been reported to result in increased vancomycin clearance. 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. Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term carcinogenesis studies in animals have been conducted.

The Life Plan Execution Changing your life is difficult. The longer you stay in the same place and in the same position, the harder it becomes to leave. Often, change is forced on us— we may have to relocate (reluctantly, even) to obtain a new position. If we leave on our own, it should come out of a desire to achieve goals that are of a high calling in our lives. Leaving Lahey Clinic is bittersweet. However, I do feel as though I have left a legacy I can be proud of. My efforts have always been to promote individuals, helping them achieve their goals and advance the profession of pharmacy in any way that I could. Making a change to a job that is closer to home, working for an organization that values professional affiliations and has values congruent with my own will afford me an opportunity to realize the professional part of my life plan. I realize that this is something that will not happen overnight. However, I still believe I made the right move. As of the end of July, I will assume the role of system vice president of pharmacy at Caritas Christi, a six-hospital system in Massachusetts. I will keep you posted.

References 1. Corbett D and Higgins R. Portfolio Life: The New Path to Work, Purpose, and Passion After 50. New York, N.Y.: John Wiley & Sons; 2006. 2. Covey S. The 7 Habits of Highly Effective People: Powerful Lessons in Personal Change. 15th anniversary ed. New York, N.Y.: Free Press/ Simon & Schuster; 2004.

What’s Your View? =?6;A

At concentrations up to 1000 μg/mL, vancomycin had no mutagenic effect in vitro in the mouse lymphoma forward mutation assay or the primary rat hepatocyte unscheduled DNA synthesis assay. The concentrations tested in vitro were above the peak plasma vancomycin concentrations of 20 to 40 μg/mL usually achieved in humans after slow infusion of the maximum recommended dose of 1 g. Vancomycin had no mutagenic effect in vivo in the Chinese hamster sister chromatid exchange assay (400 mg/kg IP) or the mouse micronucleus assay (800 mg/kg IP). No definitive fertility studies have been conducted. PATIENT COUNSELING INFORMATION Patients should be counseled that antibacterial drugs including VANCOCIN HCl Capsules should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When VANCOCIN HCl Capsules are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by VANCOCIN HCl Capsules or other antibacterial drugs in the future.

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Has Ernie Anderson’s latest series of columns on developing a Life Portfolio had any effect on your personal and/or professional development? If so, we’d like to hear your stories. The first five readers to get their comments published will be sent a free copy of David Corbett’s “Portfolio Life: The New Path to Work, Purpose, and Passion After 50.” Send replies to

Please see full prescribing information for additional information about VANCOCIN HCl Capsules

ppneditor@mcmahonmed.com

Rx Only Date of issue: 04/2008 Manufactured for and distributed by ViroPharma Incorporated, Exton, PA 19341, USA www.viropharma.com www.vancocin.com AA0076

sonal—there were goals that I could not achieve while working 12-hour days, topped off with a two-hour commute. This hampered my time spent with my family (including my grandchildren) and made it difficult for me to get regular physical exercise before 9 p.m. All of these factors led me to consider a new opportunity in my professional career.

05/2009

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16 Clinical

Pharmacy Practice News • July 2009

Oncology

NONCOMPLIANCE

‘If we can work with patients to catch .... adverse effects early, before they stop taking their medications, we can increase their adherence.’ —Christy S. Harris, PharmD

patients, so we are more than quadrupling the costs just by these patients showing an adherence rate change of

about 20% to 30%,” said Dr. Harris. “As you can see, this echoes over and over and over again. In this economic cli-

HOPA President’s View on Compliance

hil Johnson, MS, RPh, founding director of pharmacy at the H. Lee Moffitt Cancer Center in Tampa, Fla., agreed that patient compliance is “a huge issue” and said that it will be on his radar as HOPA president. “I’ve already brought this up with the group and we may apply for a grant to develop better methods for ensuring compliance,” he said. There is certainly no lack of data showing that medication compliance is a problem. “We’ve got about 20 years’ worth of studies showing that 25% of all prescriptions are not filled, and of those that are filled, only half are fully complied with,” Mr. Johnson said. “That is a major cause for disease exacerbation, hospital readmissions and the negative economic impact Dr. Harris outlined.”

CREDIT: HOPA

One study (Halpern R, et al. J Clin Oncol 2007;26: abstract 6618) that examined patient adherence with the tyrosine kinase inhibitor imatinib (Gleevec, Novartis) and medical costs in patients with gastrointestinal stromal tumors and chronic myelogenous leukemia (CML) found that those who had good adherence—defined as an adherence rate of 90%—had mean total health care costs, including medical and pharmacy, of $22,882. Patients with medium adherence—an adherence rate ranging from 70% to 89.9%—had mean total health care costs of $40,366, and patients with poor adherence—an adherence rate of less than 70%—had total mean health care costs of $104,961. In another study (Wu EQ, et al. J Clin Oncol 2007;26: abstract 17614) that also looked at adherence with imatinib and medical costs, high adherence, described as 95%, was associated with significantly lower hospital costs, days in hospital and total health care costs than low adherence. Compared with highly compliant patients, the lowadherent group incurred 1.6 times the average total health care costs, 5.9 times the inpatient costs, 3.8 times the admissions and 7.3 times the inpatient days of low-compliant (<65%) patients (P<0.001 for all). Pharmacy costs also were higher and outweighed the cost of imatinib therapy, Dr. Harris, of the Dana-Farber Cancer Institute and the Massachusetts College of Pharmacy and Health Sciences, Boston, said. Yet another study (Darkow T, et al. Pharmacoeconomics 2007;26;481-496) that used a prescription database to study imatinib adherence and medical costs for 267 patients with CML found an inverse relationship for total medical costs, inpatient hospitalization costs and outpatient costs in the first year of therapy, after 31% of the study population had interruptions of more than 30 days in their treatment. Each 10% point difference in adherence created a 14% difference in health care costs excluding imatinib and a 15% difference in medical costs. “For example, a 75% adherence rate incurred an additional $4,000 compared with someone with an 85% adherence, so you can see how this is really going to add up as we decrease our adherence,” said Dr. Harris. The same study found that more adherent patients had higher pharmacy costs, but these were offset by the medical costs, so that total health care costs were lower. “Darkow found that the low-adherence patients in their study had total health care costs of $131,357 compared with $39,000 for high-adherence

CREDIT: HOPA

continued from page 1

‘We’ve got about 20 years’ worth of studies showing that 25% of all prescriptions are not filled, and of those that are filled, only half are fully complied with.’ —Phil Johnson, MS, RPh

So how do you incentivize patients to take their medications? “One strategy might be to waive their insurance copays if they can prove they adhered 100%,” Mr. Johnson said. But while the economic carrot-and-stick approach may work for patients, the strategy may not be as alluring—at least initially—for payers. “Short-term, if drug compliance increases, the volume of drugs dispensed will rise and insurers will be paying out more money for those medications,” he said. “But there will be longer-term savings from improved disease control. So we have to do a better job convincing insurers to take that longer, more enlightened view.” As far as differences among patients influencing rates of compliance, Mr. Johnson said there is not much variation. “You’d think, at first glance, that cancer patients take their drugs to a greater degree than others—after all, they do have a life-threatening condition,” he said. “But think about it: many people have cancer because they don’t comply with following a healthy lifestyle, like not smoking or eating well and exercising to avoid obesity. So almost by definition, some cancer patients are a very noncompliant group and just as challenging as patients with benign disease.”

The Influence of Health Care Reform As the national debate over health care reform heats up, the spotlight will remain on drug compliance, Mr. Johnson noted. “The reformers are all trying to figure out who is responsible for this,” he said. “In my view, everyone has to play a role, but patients are key—they have to be more responsible for their health.” Pharmacists can do their part, he said, primarily by reaching out to patients postdischarge. At Moffitt, “if we think there is a need, we call patients on extended cycles of chemotherapy and ask them whether they are experiencing any side effects or if there are any other problems, and then we remind them why it is important to take their medications.” Although the phone call reminders may be difficult to do consistently because of staffing pressures, “they can make a big difference,” he said. Mr. Johnson acknowledged that there are several higher-tech methods of reminding patients to take their medications, such as automated phone calls and e-mails, drug vials that beep or “talk” to patients when a drug dose comes due and so on. “But all of these tools have to be tailored to the individual patient,” he said. “If you’re the type that only checks your voicemail once a week, for example, the automated calls really won’t help.” Mr. Johnson said he feels strongly enough about the compliance issue to make it one of the topics he plans to include in a presentation to pharmaceutical manufacturers scheduled soon after the HOPA meeting. “One question I’m asking is, ‘What’s more important in disease management—developing a better new drug or a better tool for getting patients to comply with existing medications?’ “We have effective drugs; unfortunately, they often fail because patients don’t take them. And that has to change.” —David Bronstein

mate, everybody is looking for ways to save money, so this is what I’m hoping to use to justify the resources needed to create specific projects and materials to increase adherence.” Dr. Harris added that a case also has to be made to insurers. “We know that we can decrease the overall cost. This is something you really have to sell but it is something that makes sense. Hopefully, the insurance companies will pick up on this and find that there is utility and really emphasize adherence.”

Predicting Poor Compliers Knowing how to detect which patients are most likely to be nonadherent is crucial to solving high health care costs, Dr. Harris noted. “Not too many of us can talk with every patient, determine what their factors or problems with adherence might be and work with them specifically because we just do not have the time,” she said. “So we need to be able to identify them.” Major predictors of poor adherence to medications include the presence of psychological problems—particularly depression—and the presence of cognitive impairment, inadequate follow-up or discharge planning, side effects of medication, the patient’s lack of belief in benefit of treatment or lack of insight into the illness, complexity of treatment, cost of medication, copayment, or both, and missed appointments. Elderly patients (>65 years) are less compliant, but surprisingly so are younger patients (35-44 years). Also there is evidence that women are less adherent than men, Dr. Harris said. “This is surprising. We tend to think of women as the caregivers, the ones who prod their men into going to the doctor and to take their medicine.” The use of antidepressant agents, the presence of Parkinson’s disease and dementia are also predictors of poor adherence. It is well known that adverse effects also play an important role in nonadherence, she said. However, they are some of the easiest predictors to modify. “If we can work with patients to catch these adverse effects early, before they stop taking their medications, we can increase their adherence.” —Fran Lowry

Clinical 17

Pharmacy Practice News • July 2009

Medication Safety

WARFARIN DEBATE continued from page 1

information from the test will actually affect clinical outcomes.

The Evidence for VKORC1 Testing There is a single-nucleotide polymorphism (SNP) in the VKORC1 gene that influences the pharmacodynamics of warfarin. The pharmacokinetics of warfarin are influenced by an SNP in the cytochrome P450 C29 (CYP2C9) gene. Together, these genetic factors account for 30% to 35% of the variability in warfarin dosing. However, it is very difficult to determine which individuals have these variants, Dr. Schwartz said.

national Warfarin Pharmacogenetics Consortium, which pooled data from 21 research groups from nine different countries (N Engl J Med 2009;360:753-764). The consortium used data from 4,043 patients to create a dose algorithm based on clinical variables alone, or on genetic information plus clinical variables. Consortium researchers concluded that the algorithm that contained the genetic information provided a significantly better prediction of the appropriate

dose of warfarin than the algorithm containing just clinical variables. The pharmacogenetic algorithm was also better than a fixed-dose approach based on 35 mg per week of warfarin. The consortium also found that 1,711 (33.9%) of the total cohort of patients in their review required a low dose—less than 21 mg per week of warfarin, and that the pharmacogenetic algorithm provided better prediction, with fewer overestimations of dose. Similarly, for 625 (12.4%) individuals

requiring high doses (>49 mg/wk of warfarin), the pharmacogenetic algorithm provided better prediction, with fewer underestimations. “The data from the consortium shows that if you use a fixed dose, you are not right often. You can make up for this if you have very close monitoring. But frequent monitoring and patient visits and the time it takes to evaluate those measures is not cheap either,” Dr. Schwartz said. She concluded, “There is clear evidence that there is a difference in

•

see WARFARIN DEBATE, page 21

Gelfoam + Human Thrombin In one kit.

CREDIT: HOPA

‘There is clear evidence that there is a difference in response to warfarin in patients with different genetic variants. If we can know those and make more knowledgeable decisions about what the dosing should be, especially the initiation dosing, I think that we save people time and problems.’ —Rowena N. Schwartz, PharmD

“A study by Limbi [Pharmacotherapy 2008;28:1084-1097] found that the frequency of the VKORC1 allele 1173C/T was 10.6% among African Americans, 36.5% in Euro-Americans and 87% in Hong Kong Chinese. But you can no longer say for certain which patient will have the variation. So even though this data is really helpful, it doesn’t help us make the adjustment in individual patients,” she said. Adding to the case for testing is the abundant evidence that the 1173C/T allele affects the variability of the dose requirement in patients who are receiving warfarin. Carriers of this allele need a longer time to reach a stable international normalized ratio (INR) than individuals with homozygous wild-type alleles, according to a study by Stehle and colleagues (Clin Pharmacokinet 2008;47:565-594). Dr. Schwartz said that to date, the most convincing data for the benefit of VKORC1 testing comes from the Inter-

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www.baxterbiosurgery.com GELFOAM PLUS Hemostasis Kit Indications GELFOAM PLUS is intended as a hemostatic device for surgical procedures when control of capillary, venous, and arteriolar bleeding by pressure, ligature, and other conventional procedures is either ineffective or impractical. Thrombin (Human) used without the Gelfoam Sterile Sponge is not indicated for hemostasis. Important Safety Information GELFOAM PLUS should not be used in closure of skin incisions, because it may interfere with the healing of the skin edges. GELFOAM PLUS should not be placed intravascularly, because of the risk of embolization. GELFOAM PLUS is not recommended for use other than an adjunct for hemostasis. GELFOAM PLUS contains thrombin, which is made from human plasma. It may carry the risk of transmitting infectious agents, e.g., viruses, and theoretically the Creutzfeldt-Jakob disease (CJD) agent. While packing a cavity for hemostasis is sometimes surgically indicated, GELFOAM PLUS should not be used in this manner unless excess product not needed to maintain hemostasis is removed. Whenever possible, GELFOAM PLUS should be removed after use in laminectomy procedures and from foramina in bone, once hemostasis is achieved. This is because GELFOAM Plus may swell to its original size on absorbing ﬂuids, and produce nerve damage by pressure within conﬁned bony spaces. GELFOAM PLUS is not recommended in the presence of infection. There have been reports of fever associated with the use of Gelfoam Sterile Sponge, without demonstrable infection.

FLOSEAL [Hemostatic Matrix] Indications FLOSEAL is indicated in surgical procedures (other than ophthalmic) as an adjunct to hemostasis when control of bleeding by ligature or conventional procedures is ineffective or impractical. Important Safety Information FLOSEAL must not be injected into blood vessels, or allowed to enter blood vessels. Do not apply in the absence of active bleeding. Extensive intravascular clotting and even death may result. Do not use FLOSEAL in the closure of skin incisions because it may interfere with the healing of the skin edges. Do not use FLOSEAL in patients with known allergies to materials of bovine origin. FLOSEAL is made from human plasma. It may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The maximum swell volume of approximately 20% is achieved within about 10 minutes. Excess FLOSEAL (material not incorporated in the hemostatic clot) should be removed from the site of application using gentle irrigation. RX only: For safe and proper use of these devices, please refer to full device Instructions For Use. 1. 2006 IMS Hemostat and Sealant Revenue, Unit, and ASP Sales Data. Baxter, FLOSEAL and ADVANCING SURGERY,ENHANCING LIFE are trademarks of Baxter International Inc. Gelfoam is a registered trademark of Pharmacia & Upjohn Company LLC., used under license. BS1889 4/2008

18 Clinical

Pharmacy Practice News • July 2009

Cardiology

BP CONTROL continued from page 1

The study is an offshoot of earlier work done by Dr. Minor and her research team, detailing the efficacy of the clinic’s approach in women only.1 For the present study, the team included men in the analysis, and they retrospectively evaluated patients who were newly treated for at least six months at the clinic over the past five years. Inclusion criteria were met by 458 patients (51% white, 65% female, mean follow-up of 25±14 months). The investigators assessed initial and final BP, number and classification of medications, comorbid disease states, patient demographics and nonadherence or other issues influencing BP control. Patients had been treated with one or more of the following medications: diuretics, calcium channel blockers, a renin–angiotensin inhibitor (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker) and an aldosterone antagonist. Prior to treatment at the clinic, 12% of the patients had BPs that were controlled, defined as BP less than 140/90 mm Hg (<130/80 mm Hg in patients with diabetes and/or chronic kidney disease). After receiving treatment at the clinic, 316 (69%) of the patients achieved BP control, and 142 remained uncontrolled (mean BP 130/78 mm Hg.) The results were similar in blacks and whites, as well as in males and females. Using multivariable regression, the investigators found that the only significant predictor of BP control in this clinic population was the absence of diabetes and chronic kidney disease (P<0.001; 95% confidence interval [CI], 2.18-7.25).

A Deeper Look Into Resistance The investigators looked deeper to define the characteristics and prevalence of resistant hypertension and better assess the population with uncontrolled hypertension. Resistant hypertension was defined per JNC 7 guidelines2 and the American Heart Association scientific statement3 as uncontrolled BP despite adherence to maximum tolerated doses of at least three medications, including a diuretic, or the need for more than three medications to achieve BP control. A control rate of 73.3% was achieved in the resistant population, requiring greater than three medications. Of the 142 patients who were uncontrolled, 62 did not meet the definition of resistance. Of the remaining 80 patients with uncontrolled BP, 57 were determined to be “pseudoresistant,” as they had one or more documented factors associated with lack of control, including medication nonadherence, high medication costs, multiple medication intolerances, inability to tolerate lower BP and/or white-coat hypertension. That left 23

patients (5%) with uncontrolled hypertension that met the definition of true resistant hypertension. “The reality of it is—very few of our patients, even those with defined resistant hypertension, would truly be clasified as resistant to control. That’s totally different than what I would have expected to find,” said Dr. Minor. Dr. Minor and her colleagues concluded that their overall rates for BP control “rival those reported in recent clinical trials and most practice-based studies [and] exceed national blood pressure goals.” They suggested that “focused attention on patient medication adherence and other related issues particularly in patients with comorbid diseases will further increase BP control rates in this difficult-to-treat population.” Other centers with less-difficult populations could expect to see even better results,

macist, as well as students and residents from these disciplines, staff the clinic. Patients have almost immediate access to someone on the clinic staff, resulting in their questions and concerns being readily addressed. This collaborative and supportive environment contributes to the clinic’s success, according to Dr. Minor.

Echoes of Iowa Pharmacist’s Research Commenting on the study, Barry L. Carter, PharmD, noted that “Dr. Minor has long been involved in hypertension management and research, and her results confirm what other studies have shown regarding team-based care, especially involving pharmacists.” However, Dr. Carter added, “their results show a larger effect than most other published studies that have evaluated hypertension management assisted by pharmacists

‘Successful adoption of these models for hypertension could reduce stroke deaths by 18% to 25% and coronary heart disease deaths by 12% to 20% if BP can be controlled longterm in these patients.’

—Barry L. Carter, PharmD

predicted Dr. Minor. She suggested that difficult-to-manage patients should be referred to a hypertension specialist. To promote compliance with what can be complex drug regimens, Dr. Minor recommended using “whatever is appropriate and easiest for the patient.” She suggested using combination formulations when possible to decrease the cost and the number of pills the patient needs to take, and using synchronized dosing schedules so patients only need to remember to take medications once or twice a day. “Communication with the patient is so important,” she stressed. “Hypertension is a silent disease. Patients often don’t really understand the implications. We have high adherence because we pay such close attention to all these factors— adherence, costs and rational combinations of medication—and we always solicit the patient’s input.” Dr. Minor added that the staff at the clinic pays “such close attention to … all those obstacles, like if someone can’t afford their medicines, we try to make sure that they have medicines that they can afford. We try to have the kind of environment that people feel comfortable telling us, ‘well, I’m not taking that’ because of this reason, be it sexual dysfunction or whatever, so that we can make adjustments to enable them to have a medication that they can take.” Physician hypertension specialists, a nurse practitioner and a clinical phar-

[and] are similar to what we found in a recent randomized controlled clinical trial.” During that trial, Dr. Carter, professor and associate head of research in the Department of Family Medicine and professor in the College of Pharmacy at the University of Iowa in Iowa City, and his colleagues also had success improving BP control using a physician–pharmacist collaborative care model. They conducted a randomized, prospective trial evaluating 179 patients aged 21 to 85 years who had uncontrolled hypertension and were treated at one of five university clinics over a nine-month period (J Clin Hypertens 2008;10:260-271). During this efficacy study (intervention implemented under ideal conditions), which was funded by the National Heart, Lung and Blood Institute at the National Institutes of Health, two of the clinics were randomly designated as intervention clinics (n=101 patients) and the other three were designated as control clinics (n=78 patients). Clinical pharmacists made recommendations to physicians for patients at the intervention clinics but not at the control clinics. The investigators found that BP was controlled in 89% of patients in the intervention group and 53% in the control group (adjusted odds ratio, 8.9; 95% CI, 3.8-20.7; P<0.001). Physician–pharmacist collaboration resulted in significantly better BP control rates, primarily by intensifying medication therapy and

improving patient adherence. The investigators concluded that their findings suggest “that for clinics or health systems that have clinical pharmacists, their reallocation to provide more direct patient management may significantly improve BP control.” Dr. Carter and his colleagues also conducted a six-month intervention in an effectiveness trial (conducted in a more typical community practice setting) in 402 patients from six medical offices. In this study, BP was controlled in 63% in the intervention group compared with 30% in the control group (P<0.01). After adjustment for the covariates, the odds ratio for controlled BP in the intervention group was 3.2 (95% CI, 2.0-5.1).

Further Study on Tap Dr. Carter is heading a study to implement the collaborative model in 27 clinics around the United States as well as a four-year study to evaluate the effect of a pharmacist-based intervention program among 300 veterans at the VA Medical Center in Iowa City, where Dr. Carter is a senior scientist in the Center for Research in Implementation of Innovative Strategies in Practice. “We know that there are many clinical pharmacists working in VA health systems, academic primary care clinics and managed care clinics who could provide the types of services in these studies,” he said. Dr. Carter estimated that in the United States, 2.4 to 2.7 million patients with hypertension could achieve BP control if these health systems used their clinical pharmacists the way they were used in the collaborative care studies. “We are confident that these are reasonable estimates of the potential impact of implementation of physician– pharmacist collaborative models in these settings.” Additionally, he provided further estimates that “successful adoption of these models for hypertension could reduce stroke deaths by 18% to 25% and coronary heart disease deaths by 12% to 20% if BP can be controlled long-term in these patients. The public health implications are critical,” he concluded, because “such programs could help us achieve the goals of Healthy People 2010.” —Sarah Tilyou

References 1. Tilyou S. Pharmacists help improve blood pressure control in refractory clinic patients. Pharmacy Practice News. 2008;35:1,10. 2. Chobanian AV, Bakris GB, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7. JAMA. 2003;289:2560-2572. 3. Calhoun DA, Jones DA, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51:1403-1419.

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20 Q & A

Pharmacy Practice News • July 2009

Enlon® (edrophonium chloride injection, USP) and Enlon-Plus® (edrophonium chloride, USP and atropine sulfate, USP) Injection

fter Baxter announced in February 2008 the discontinuation of Enlon® (edrophonium chloride injection, USP) and Enlon-Plus® (edrophonium chloride, USP and atropine sulfate, USP) Injection, Bioniche Pharma, a leading developer and manufacturer of injectable pharmaceuticals, initiated the process to acquire these important products and bring them back to market and into the hands of health care professionals. On May 15, 2009, Bioniche Pharma announced the launch of Enlon and EnlonPlus Injection.

Q. What are the indications for Enlon®?

dimethyl-tubocurarine. It is not effective against decamethonium bromide and succinylcholine chloride. It may be used adjunctively in the treatment of respiratory depression caused by curare overdosage.

A. Enlon is recommended for the differential diagnosis of myasthenia gravis and as an adjunct in the evaluation of treatment requirements in this disease. It may also be used for evaluating emergency treatment in myasthenic crises. Because of its brief duration of action, it is not recommended for maintenance therapy in myasthenia gravis. Enlon is also useful whenever a curare antagonist is needed to reverse the neuromuscular block produced by curare, tubocurarine, gallamine triethiodide or

Q. Who should not use Enlon? A. The stopper for Enlon contains latex. Anyone with known hypersensitivity to anticholinesterase agents; intestinal and urinary obstructions of mechanical type should not use Enlon. Enlon should be used with caution in patients with bronchial asthma or cardiac dysrhythmias. Enlon

contains sodium sulfite, which may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The myasthenic patient in crisis who is being tested with Enlon should be observed for bradycardia or cardiac standstill and cholinergic reactions if an overdose is given. The safety of Enlon during pregnancy or lactation in humans has not been established. Therefore, use of Enlon in women who may become pregnant requires weighing the drug’s potential benefits against its possible hazards to mother and child. Care should be given when administering this drug to patients with symptoms of myasthenic weakness who are also on anticholinesterase drugs. Q. What are the indications and usage for Enlon-Plus?

N O W A VA I L A B L E F

Enlon

(edrophonium chloride injection, USP)

Enlon-Plus

(edrophonium chloride, USP & atropine sulfate, USP) Injection

NDC Number

Description

AmerisourceBergen

Cardinal

McKesson

67457-190 -15

10 mg/mL, 15 mL Vial

368878

4119566

1853506

67457-191-15

10 mg/mL edrophonium Cl, 0.14 mg/mL atropine sulfate 15 mL Vial

67457-192- 05

10 mg/mL edrophonium Cl, 0.14 mg/mL atropine sulfate 5 mL Ampul

Enlon-Plus

367797

4119582

1878313

A. The stopper for Enlon-Plus contains latex. The appropriateness of the specific fixed ratio of edrophonium and atropine contained in Enlon-Plus has not been evaluated in myasthenia gravis. Therefore, it is not recommended for use in the differential diagnosis of this condition. EnlonPlus is not to be used in patients with known hypersensitivity to either of the components, or in patients with intestinal or urinary obstruction of mechanical type. Atropine sulfate is contraindicated in the presence of acute glaucoma, adhesions (synechiae) between the iris and lens of the eye and pyloric stenosis. Enlon-Plus should be used with caution in patients with bronchial asthma or cardiac arrhythmias. Cardiac arrest has been reported to occur in digitalized patients as well as in jaundiced subjects receiving cholinesterase inhibitors. Enlon-Plus contains sodium sulfite, which may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. There is a potential for tissue irritation by extravascular injection. Enlon-Plus should be administered with caution to patients with symptoms of myasthenic weakness who are also on anticholinesterase drugs. It is not known whether Enlon-Plus can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Enlon-Plus should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The safety of Enlon-Plus during lactation in humans has not been established. Safety and effectiveness in pediatric patients have not been established. There were insufficient numbers of subjects aged 65 or over in the clinical studies of Enlon-Plus to determine whether they respond differently from younger subjects.

A. Bioniche supplies Enlon in 10 mg/mL, 15 mL vials and Enlon-Plus in 15 mL vials and 5 mL ampuls. Q. How do I order Enlon and Enlon-Plus?

A. To order Bioniche Pharma products, contact your wholesaler or distributor, or call Customer Service at (888) 258-4199. Please see full prescribing information for more information.

367342

4119590

1860527

Q. Who shouldn’t use Enlon-Plus?

Q. How does Bioniche supply Enlon and Enlon-Plus?

PL A C E A N OR DE R TODAY. Enlon

A. Enlon-Plus is recommended as a reversal agent or antagonist of nondepolarizing neuromuscular blocking agents. It is not effective against depolarizing neuromuscular blocking agents. It is also useful if used adjunctively in the treatment of respiratory depression caused by curare overdosage.

Clinical 21

Pharmacy Practice News • July 2009

Medication Safety

WARFARIN DEBATE continued from page 17

response to warfarin in patients with different genetic variants. If we can know those and make more knowledgeable decisions about what the dosing should be, especially the initiation dosing, I think that we save people time and problems.”

Jury Still Out Dr. Nystrom disagreed that evidence justifies VKORC1 testing in all patients receiving warfarin. “We know that VKORC1 affects the dosing of warfarin that we are going to use, but what we don’t know is how that affects clinical outcomes. I don’t think that we have adequate information yet to tell us this.” She cited a study by Schwartz et al. (N Engl J Med 2008;358:999-1008) that showed the risk for bleeding complications in 297 patients was the same regardless of VKORC1 genotype. “Their take-home message was that the patients with the VKORC1 *A/*A variant had a higher INR than patients with the VKORC1 *non-A/*non-A variants, even with empiric dose adjustments, but that serious bleeding effects were not significantly affected by the VKORC1 haplotype or CYP2C9 status.” In addition to genetic testing, Dr. Nystrom said other factors to consider when it comes to dosing warfarin include smoking, alcohol use, comorbidities, weight, height, vitamin K intake, age, gender, medications and amount of exercise. Cost-effectiveness is another factor that needs to be examined when recommending universal VKORC1 testing, Dr. Nystrom said. A study by Eckman and colleagues (Ann Intern Med 2009;150:73-83) studied the costeffectiveness of pharmacogeneticguided warfarin dosing and found that, in comparison with standard warfarin dosing, the strategy cost $144,000 per quality-adjusted life year. The researchers concluded that there is a small group of patients who might benefit, and that the cost-effectiveness may improve as the cost of peforming the test decreases. “Still, it is not cheap,” Dr. Nystrom said. Finally, the Centers for Medicare & Medicaid Services (CMS) released a

What’s Your View? =?6;A

@5.?2

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Should VKORC1 testing be done in all patients receiving warfarin therapy? Send replies to

ppneditor@mcmahonmed.com

‘We know that VKORC1 affects the dosing of warfarin that we are going to use, but what we don’t know is how that affects clinical outcomes. I don’t think that we have adequate information yet to tell us this.’ —Kelly Nystrom, PharmD

statement in May announcing that it would not reimburse warfarin genetic testing, noting a lack of evidence that such testing improves health outcomes

in Medicare beneficiaries. The CMS also released statements from major medical groups, including the American College of Chest Physi-

cians, the American College of Medical Genetics, the Association for Molecular Pathology and the American Society of Hematology, calling for more randomized data from clinical trials before they could support routine VKORC1 testing. “Once we have this information, we can make a better judgment on whether this is something that should be offered to all patients, but currently, I don’t think there is enough information available to offer testing to all patients who are receiving warfarin,” Dr. Nystrom concluded. —Fran Lowry

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22 Clinical

Pharmacy Practice News • July 2009

Oncology

Should Tamoxifen Candidates Be Tested for CYP2D6? Miami—The question of whether or not all women with hormone receptor (HR)-positive breast cancer planning to start treatment with tamoxifen should be tested for CYP2D6 polymorphisms was debated at the fifth annual conference of the Hematology/Oncology Pharmacy Association (HOPA). Slugging it out in favor of routine testing was Chad M. Barnett, PharmD, of The University of Texas M.D. Anderson Cancer Center, Houston, who argued that numerous studies have shown shorter times to recurrence and decreased overall survival in women who have specific CYP2D6 polymorphisms and that not testing for these polymorphisms could be putting them at increased risk for bad outcomes. “It is my position that clinical testing for CYP2D6 is indicated for all women with hormone receptor-positive breast cancer who are planning to take tamoxifen,” Dr. Barnett said. Taking the opposing view, Janet L. Espirito, PharmD, of US Oncology, Inc., The Woodlands, Texas, countered that all but one of these studies were retrospective, with small numbers of patients, conflicting results and variable methodology. Dr. Espirito added that without prospectively validated data from large, randomized controlled trials, recommendations for routine testing for CYP2D6 are premature. “I take the con view, that clinical testing for CYP2D6 is not indicated for all patients with HR-positive breast cancer who are planning to take tamoxifen,” she said. Dr. Barnett told HOPA delegates that CYP2D6 testing can categorize patients into one of four phenotypic groups: poor, intermediate, extensive or ultra-rapid metabolizers. The majority of patients fall into the extensive metabolizer category, closely followed by intermediate metabolizers. Poor metabolizers—women with the *4 variant of the CYP2D6 gene—are the ones who have the worst outcomes with tamoxifen therapy. “Polymorphism frequencies vary by race and ethnicity,” Dr. Barnett said. “The most common nonfunctional allele is the *4 allele in the Caucasian population; in the African population, it is the *17 allele; and in the Asian population, it is the *10 allele.” To support his argument, Dr. Barnett detailed several studies that evaluated the importance of the *4 variant and clinical outcome in white and Asian women. “Two studies by Matthew P. Goetz and colleagues at Mayo Clinic in Rochester, Minn., have contributed a great deal of clinical information in this area,” he said.

The first (J Clin Oncol 2005;23:93129318), a retrospective analysis of a prospective clinical trial of 223 estrogen receptor-positive postmenopausal patients receiving five years of adjuvant tamoxifen therapy with or without an aromatase inhibitor, found that poor metabolizers who were homozygous for *4 had reduced relapse-free time (P=0.023) and disease-free survival (P=0.012) compared with extensive metabolizers who were homozygous for the wild-type allele (wt/wt) and intermediate metabolizers who were heterozygous (wt/*4). A second study by Goetz et al (Breast Cancer Res Treat 2007;101:113-121) reanalyzed 180 of these patients, incorporating concomitant use of CYP2D6 inhibitors and found that patients who were poor metabolizers, either as a result of concomitant medication or polymorphism or both, had significantly reduced times to recurrence

been done (Lim HS, et al. J Clin Oncol 2007;25:3837-3845), 21 HR-positive patients with metastatic breast cancer who were poor responders had a time to progression that was five months, versus 22 months for extensive responders (P=0.0032). “I hope I’ve convinced you with these data that there are many trials that have shown and identified patient populations that have poor outcomes due to specific polymorphisms in CYP2D6,” Dr. Barnett concluded. “In my opinion, we should be testing anyone who receives tamoxifen. There are many studies to back up these recommendations.”

Supportive Studies Lack Weight “While the data that were presented are definitely thought-provoking and compelling, the majority of the studies were retrospective and included

“Many trials … have identified patient populations that have poor outcomes due to specific polymorphisms in CYP2D6.’ —Chad M. Barnett, PharmD (P=0.034) and relapse-free survival (P=0.017) compared with patients who were deemed extensive metabolizers. A third trial, a cohort study of 85 tamoxifen users in the Netherlands (Bijl MJ, et al. Breast Cancer Res Treat 2009 Feb 3 [Epub ahead of print]) found that patients who were deemed to be poor metabolizers had significantly worse breast cancer mortality compared with patients who were extensive metabolizers. Several studies have also evaluated the importance of the *10 allele in the Asian population and found similar results in poor metabolizers. Investigators in China (Xu Y, et al. Ann Oncol 2008;19:1423-1429) analyzed the records of 152 patients who received tamoxifen in the adjuvant setting and found that patients who were poor metabolizers due to the CYP2D6 *10 allele had significantly reduced disease-free survival compared with patients who were extensive or intermediate metabolizers (P=0.04). A Japanese study of 67 HR-positive women (Kiyotani K, et al. Cancer Sci 2008;99:995-999) found significantly shorter recurrence-free survival in the poor metabolizers compared with the extensive metabolizers (P=0.036). In the one prospective study that has

small numbers of patients,” Dr. Espirito said in her argument against routine CYP2D6 testing. “The patient population was also varied and included preand postmenopausal women, and we know that age and menopausal status can influence outcomes.” She pointed out that the majority of the studies had been carried out in the adjuvant setting, thus making it difficult to control for the variability of the treatment the patients received. “In some of the trials, patients were randomized to chemotherapy versus no chemotherapy; radiation versus no radiation, tamoxifen versus no tamoxifen, so there was a great deal of variability there.” Two of the trials actually showed improved recurrence-free survival in patients who were poor metabolizers, she said. “And so we all know the challenges of retrospective studies, with small numbers of patients, and the challenge of controlling for confounding variables. Although some of the studies controlled for various factors, not all controlled for variability in patient and tumor characteristics that might place a patient at higher risk. Nor did they control for the diversity of the treatments that were received.” Compliance with drug therapy and

‘Drugs such as SSRIs, if used with tamoxifen for depression or hot flashes, can reduce tamoxifen’s efficacy, and the studies cited by Dr. Barnett did not adequately account for such concurrent therapy.’ —Janet L. Espirito, PharmD

potential drug interactions were not mentioned in these studies—a lapse that makes recommending routine testing problematic, Dr. Espirito said. “Tamoxifen is an oral therapy. It obviously is not going to work in patients who don’t take it. Compliance and drug interactions are two [variables] that are very difficult to assess retrospectively.” She added that the use of concomitant medications also can influence results—especially those that decrease the activity of CYP2D6. “Drugs such as SSRIs, if used with tamoxifen for depression or hot flashes, can reduce tamoxifen’s efficacy, and the studies cited by Dr. Barnett did not adequately account for such concurrent therapy.” Other enzymes are involved in the metabolism of tamoxifen, not just CYP2D6. Additionally, the strength of estrogen or progesterone positivity, and the potential for crosstalk with other receptors make it unlikely that the acquired resistance to tamoxifen that occurs over time is a result of a single polymorphism, she said. There also are practical aspects to consider, Dr. Espirito argued. “Just because a test is available, does that mean we should use it?” It is important to ask whether knowing the results of the test will change treatment decisions. In the case of tamoxifen and HR-positive breast cancer, this is unlikely, she said. “Specifically in the adjuvant setting for premenopausal women, tamoxifen is the standard of care and there is no proven treatment alternative.” As for postmenopausal women, “most people are prescribing aromatase inhibitor therapy. If we are using aromatase inhibitors up front anyway in these patients, we may not need to do testing. Tamoxifen metabolism is not simple. CYP2D6 testing holds a lot of promise, but we need more prospective, validated data before it goes prime time.” —Fran Lowry

Clinical 23

Pharmacy Practice News • July 2009

Oncology

ESA Restrictions May Be Pushing Up Transfusion Rates Rosemont, Ill.—Centers in Maryland and New Jersey have seen increases in the rates of blood transfusions in cancer patients with anemia ever since label changes and reimbursement cutbacks were implemented for erythropoietinstimulating agents (ESAs), according to presentations at the American Society of Health-System Pharmacists Summer Meeting. Investigators at these and other centers fear that the full effect of the 2007 ESA restrictions on transfusion rates has not yet been seen and that centers need to take a closer look at their own rates. In Maryland, John DiBona, PharmD, corporate director of pharmacy at Lifebridge Health, Sinai Hospital of Baltimore, conducted a retrospective study of transfusion rates in cancer patients before and after implementation of the August 2007 Medicare National Coverage Determination (NCD) restricting coverage for ESAs. The study focused on inpatient and outpatient visit and billing data and laboratory results for all cancer patients treated from Aug. 1, 2005 through Aug. 31, 2008, at the hospital. The researchers assessed chemotherapy episodes for two pre-NCD periods as well as one post-NCD period. Outcome measures included ESA use and number of blood transfusions. The results showed that ESA restrictions had a significant effect on the use of the growth factors: In the two time periods studied before the restrictions were put in place, ESAs were given to 75.4% and 80.9% of patients undergoing chemotherapy. After the restrictions took effect, only slightly more than half (50.4%) of patients were prescribed ESAs, the investigators reported (P<0.0001). Additionally, with the decrease in ESA rates came a corresponding increase in the rate of transfusions (21% before the NCD vs. 31% afterward; P<0.05). The increase from 21% to 31% “is not a huge jump, but if you look at it in relative terms, it is almost one-third,” Dr. DiBona said. He acknowledged that the data are limited to his center and he doesn’t know for sure “whether [the results are] externally valid.” But he expressed concern that if the data were in fact generalizable, “and you extrapolated the one-third increase across the country, that is a huge amount of blood use.” Dr. DiBona further speculated that his study may underestimate the impact of the NCD on transfusion rates because, in the wake of the same adverse events related to increased hematocrits that led to the NCD, prescribers may have become “a little bit skittish about bringing hematocrits up.” That hesitation may have persisted even regarding patients undergoing transfusions instead of ESA therapy, he noted. If that is the case, Dr. DiBona said, the one-third increase in the

rate of blood transfusions would be even more significant in light of the downward effect that a possible increased clinical threshold for transfusions would have exerted on the transfusion rate. At the New Jersey center, investigators conducted a study focused on the NCD’s influence on the use of the ESA darbepoetin alfa (Aranesp, Amgen). Robert T. Adamson, PharmD, and his colleagues at Saint Barnabas Health Care System, in South Plainfield, retrospectively evalu-

ated patients who were admitted as inpatients during Nov. 1, 2006 through Jan. 31, 2008, and had received a dose of darbepoetin for chemotherapy-induced anemia as an outpatient four weeks or less before hospitalization. End points for the study included inpatient and outpatient darbepoetin utilization patterns. The investigators evaluated darbepoetin use before and after four darbepoetin-related events occurred between March and July 2007: Darbepoetin labeling was changed

to include a black box warning; a medication reconciliation program was initiated at Saint Barnabas; the FDA’s Oncology Drug Advisory Committee reviewed the drug; and the NCD was implemented. The investigators reviewed the hospital database and found 726 patients who fit the inclusion criteria and were included in the analysis. Whereas there was a decreasing trend for darbepoetin use after restrictions were in place (28% vs 21%;

•

see TRANSFUSIONS, page 24

A D V E R T I S E M E N T

Postoperative complications: The pharmacist’s role in prevention

An under-recognized complication, immune-mediated coagulopathy (IMC) can result in: • Significant utilization of blood and blood products • Costly studies and consultations • Reoperations for actively bleeding patients • Extended hospital stays Learn how to reduce the risk of this type of complication in July’s supplement to Pharmacotherapy, “The Pharmacist’s Role in the Prevention of Immune-mediated Coagulopathy.” • Developed from a 2008 ASHP Midyear Meeting continuing education n symposium, topics include: “Achieving hemostasis in the surgical field” — Bradley Boucher, PharmD, and Oren Traub, MD, PhD “Topical thrombins: benefits and risks” — Christopher Lomax, PharmD, and Oren Traub, MD, PhD “Immune-mediated coagulopathy: a case study” — Joseph Naoum, MD “Thrombin products: economic impact of immune-mediated coagulopathies and practical formulary considerations” — Stacy Voils, PharmD • Available to all concerned professionals in print or online at www.pharmacotherapy.org

24 Clinical

Pharmacy Practice News â&#x20AC;˘ July 2009

Oncology

Managing ESA Therapy To Minimize Waste To determine which dosing schedule a patient was on and if they would need a dose while in the hospital, the investigators either accessed computer records, if the oncologist was on staff, or called the physiciansâ&#x20AC;&#x2122; offices, if they were not. â&#x20AC;&#x153;Itâ&#x20AC;&#x2122;s just a handful of oncology groupsâ&#x20AC;&#x201D;itâ&#x20AC;&#x2122;s not as onerous as people think,â&#x20AC;? said Dr. Adamson. The investigators found that 30% of the patients who were receiving doses every three weeks before hospitalization were able to avoid a darbepoetin alfa dose during hospitalization, because their next scheduled darbepoetin dose was not needed until after they were discharged. This compared to 1% of patients who were receiving weekly dosing. â&#x20AC;&#x153;ESA therapy is not a stat drug,â&#x20AC;? said co-investigator Indu Lew, PharmD, corporate vice president of education and research at Saint Barnabas. â&#x20AC;&#x153;If it is given at 6 p.m. instead of in the morning, then we have the whole day to do the necessary reconciliation to make sure the patient really needs the dose.â&#x20AC;? Dr. Adamson said that since there are only a couple of people receiving ESAs on any given day, the process is â&#x20AC;&#x153;not too labor-intensive.â&#x20AC;? He added, â&#x20AC;&#x153;the way we sold the medication reconciliation pro-

Rosemont, Ill.â&#x20AC;&#x201D;ESAs remain a costly regimen despite restrictions that were put in place in 2007 to limit their use because of safety concerns, so it behooves pharmacists to keep a watchful eye and ensure doses and frequencies are appropriate for these agents, according to a study presented at the ASHP 2009 Summer Meeting. Robert Adamson, PharmD, and his colleagues at Saint Barnabas Health Care System in South Plainfield, N.J., retrospectively evaluated inpatients who had received a dose of darbepoetin alfa (Aranesp, Amgen Inc.) for chemotherapy-induced anemia as outpatients four weeks or less before hospitalization and instituted a medication reconciliation program to promote appropriate in-hospital dosing for these patients. Dr. Adamson, corporate vice president of clinical pharmacy at Saint Barnabas, said he undertook the reconciliation process to ensure that he doesnâ&#x20AC;&#x2122;t â&#x20AC;&#x153;give a dose to a patient who just received it as an outpatient two days ago,â&#x20AC;? as an example. Patients had been receiving one of several darbepoetin alfa dosing schedules before hospitalization, including weekly and every-three-weeks schedules.

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gram was by explaining that avoiding one of these inpatient doses could save $300 to $400.â&#x20AC;? The Saint Barnabas team started with oncology and is working to â&#x20AC;&#x153;get people to buyâ&#x20AC;&#x201C;in to the concept,â&#x20AC;? noted Dr. Adamson. The next steps will be to â&#x20AC;&#x153;document their cost savings, put operational processes into place and then try to expand into nephrology.â&#x20AC;? The investigators stressed that the findings show â&#x20AC;&#x153;the importance of pharmacy management of ESAs to determine when the patient received their last outpatient dose, thus ensuring appropriate dosing and minimization of unnecessary inpatient doses.â&#x20AC;? Dr. Adamson further noted that â&#x20AC;&#x153;management of ESAs within the hospital is about ensuring appropriate dosing, laboratory assessment, avoidance of unnecessary doses, and implementation of operational policies and protocols to ensure ESA continuity of care.â&#x20AC;?

Disconnects Lead to Overuse Commenting on the study in an interview with Pharmacy Practice News, Jerry Siegel, PharmD, assistant dean of medical center affairs at The Ohio State University College of Pharmacy in Columbus,

TRANSFUSIONS continued from page 23

not significantly different), transfusions showed an upward trend. After implementation of the NCD, more patients received transfusions than before implementation (29% vs. 21%; P=NS). Transfusions also increased after each of the other three darbepoetin-related events. Dr. Adamson said that because Saint Barnabas was slow to adopt the NCD restrictions, only two to three months of data were generated after implementation. Thus, he speculated that if they looked further out, the transfusion rate would continue to increase. Philip E. Johnson, MS, RPh, said that although transfusions have not increased at his center, it is not clear whether this is â&#x20AC;&#x153;because thereâ&#x20AC;&#x2122;s not blood available or that thereâ&#x20AC;&#x2122;s no clinical need.â&#x20AC;? The changes in ESA prescribing appear to be â&#x20AC;&#x153;affecting different places differently,â&#x20AC;? said Mr. Johnson, director of pharmacy at H. Lee Moffitt Cancer Center, in Tampa, Fla. â&#x20AC;&#x153;A lot has to do with the physicianâ&#x20AC;&#x2122;s philosophyâ&#x20AC;? and how conservatively they treat anemia. Jerry Siegel, PharmD, senior director of pharmaceutical sciences at The Ohio State University Medical Center in Columbus, said that while â&#x20AC;&#x153;ESA use is way down, itâ&#x20AC;&#x2122;s harder to assess transfusion rates because transfusion tipping points vary by center.â&#x20AC;? Some centers, for example, wait until the hemoglobin

said, â&#x20AC;&#x153;you donâ&#x20AC;&#x2122;t want to give a dose that the patient doesnâ&#x20AC;&#x2122;t need because the outpatient and inpatient departments arenâ&#x20AC;&#x2122;t talking to each other.â&#x20AC;? The extended dosing frequency complicates the reconciliation process for agents such as ESAs, noted Dr. Adamson. â&#x20AC;&#x153;Medication reconciliation is more challenging with ESAs because they are not given daily but rather weekly or every three weeks,â&#x20AC;? he said. Thus, many patients fail to mention their last administered dose of an ESA when they are queried during a medication history. He suggested that pharmacists can address this challenge â&#x20AC;&#x153;through more pointed questions during the medication history process. Once the last date of administration of an outpatient dose of ESA has been identified, a determination of next dose needs to be made by the pharmacist to ensure continuity of ESA therapy.â&#x20AC;? â&#x20AC;&#x201D;Sarah Tilyou Sejal Badre, MS, and Larry Green, PharmD, from Amgen Inc., were co-investigators involved with the study.

is less than 7 g/dL or even lower, while some have higher thresholds; and some consider whether the patient is symptomatic, while others may not, he noted. Dr. Siegel added that because the cost of blood is so high, if transfusions have gone up, the overall costs of therapy for chemotherapy-induced anemia may be higher now than before the restrictions were put in place. â&#x20AC;&#x153;The message here,â&#x20AC;? he said, â&#x20AC;&#x153;is if you havenâ&#x20AC;&#x2122;t already looked at your transfusion rates and cost of treating anemia post-NCD, maybe you should. Are you just transferring costs?â&#x20AC;? While Saint Barnabas has an approach to reduce ESA waste and costs (see related story, above), Dr. Siegel also suggested that centers can try to reduce transfusion rates and costs in ways unrelated to ESA use. A simple example, he said, is to just â&#x20AC;&#x153;draw less blood.â&#x20AC;? When Ohio State University Medical Center implemented a blood conservation program in 2005, â&#x20AC;&#x153;it really had a big impact on decreasing the need for transfusions,â&#x20AC;? Dr. Siegel said. The actions they took were â&#x20AC;&#x153;switching from adult to pediatric tubes for blood samples to reduce the volume of blood taken when blood is drawnâ&#x20AC;? and putting â&#x20AC;&#x153;more clinical input into the decision of when they are going to do a transfusion.â&#x20AC;? They included hemoglobin levels and clinical symptoms into the mix, eliminating a lot of transfusions that were done automatically but were not necessarily clinically appropriate.

Technology 25

Pharmacy Practice News • July 2009

In Brief FDA Clears Needle-free Injection Technology

ioject Medical Technologies Inc. recently announced receipt of market clearance by the FDA for the Zetajet, a new needle-free injection therapy system. Zetajet has the ability to deliver vaccines and medications both subcutaneously and intramuscularly, according to the company. A major advantage of needle-free injection technology is its ability to prevent dangerous needlestick injuries to health care workers, the company noted in a press release. Used needles can transmit a wide variety of blood-borne disease. Patients, such as children who are needle- and pain-averse, also prefer this technology, according to Bioject. The company said it hopes that the Zetajet injection therapy system can be a valuable tool in the fight against disease in developing countries, allowing parents in rural areas to administer medicine to their children and preventing the reuse of potentially contaminated needles. The technology is also less dependent on technique than needle syringes and allows for improved medication delivery and distribution, Bioject noted. The needle-free injection system works by creating a high-speed stream of highpressure fluids that penetrate the skin through an orifice smaller than the diameter of a single human hair. The Zetajet also is equipped with an automatic disabling feature to prevent syringe reuse and a customizable exterior molding for improved ergonomic options. Studies have shown that needle-free injections improve the body’s immune response to DNA vaccines. In a study by Hartikka et al (Vaccine 2001;19:1911-1923), needle-free injection of naked VR4700 plasmid DNA produced a 15-fold increase in anti-nucleoprotein titers over needle administration at six weeks. Antibody response was quantified using the

At this point, Mr. Johnson said, “I don’t think there’s conclusive data. There’s still a blood supply problem in this country. We are still at war.” With the reductions in ESA use, “the call is out to look at whether transfusions are being used appropriately and how does it affect patient outcomes. That’s what we need more data on.” Dr. DiBona agreed that more information is needed. He said that the findings of the studies raise more questions than they answer, including the question of “whether any consideration was given to these issues when the NCD was made.” —Sarah Tilyou Sejal Badre, MS, and Larry Green, PharmD, from Amgen Inc., were co-investigators involved with the Saint Barnabas study, and Dr. Green was also a co-investigator on the Sinai Hospital of Baltimore study, along with Leo Lichtig, PhD, of AON Consulting.

ELISPOT assay. Bioject is currently seeking partnerships to deliver this technology worldwide in proper therapeutic areas. More information on the Zetajet can be found at Bioject’s Web site (www.Bioject.com). —Seth Kandel

Fluconazole Injection in PVC Flexible Containers

edford Laboratories, a division of Ben Venue Laboratories, Inc., announced the addition of fluconazole injection 2 mg/mL in PVC flexible containers to its existing fluconazole injec-

tion line. The product is AP-rated and is equivalent to Diflucan (Pfizer). Fluconazole injection is an antifungal agent indicated for oropharyngeal and esophageal candidiasis, cryptococcal meningitis, and is also indicated for the prophylaxis of candidiasis. The product launch “represents Bedford’s entry into the IV bag market and demonstrates our ongoing commitment to providing a broad-based portfolio of products,” said David Gaugh, vice president of Bedford Laboratories. In addition to the glass vial presentations, Bedford Laboratories will supply fluconazole injection as a sterile isoosmotic solution containing 2 mg/mL

of fluconazole in 0.9% sodium chloride diluent in the following formulations: 200-mg/100 mL in single-dose PVC flexible containers packaged in cartons containing 10 bags; and 400 mg/200 mL in single-dose PVC flexible containers packaged in cartons containing 10 bags. For more information, call (800) 521-5169 or visit www.bedfordlabs.com.

—Based on a company press release

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26 Technology

Pharmacy Practice News • July 2009

Bar Coding

Sweating Out the Causes of BCMA Breakdowns Quality improvement ‘workout teams’ nearly eliminate nurse overrides, boost patient safety the MAK blitzes quickly uncovered several technical glitches that were causing at least some of the alerts to be issued— alerts that did not truly represent “wrong medication” or “wrong patient” errors. One of the major technology bugs uncovered was a lack of cross-linking of bar codes, noted Carolyn Riffee, RPh, who coordinates all of the databases involved in CAMC’s BCMA system. “We weren’t doing a great job of making sure that every product we brought into the pharmacy had a proper, readable bar code,” she said. Problems with printing readable bar codes also were uncovered. The glitch was discovered during a workout on a unit where printed bar codes were primarily used, and it was thought that the wireless scanners needed to be recalibrated. “We recalibrated the system, but when we tested it by scanning the same bar code 10 times, it scanned eight different numbers,” Dr. High said. A sharp-eyed IT specialist noticed that something was wrong with the bar code—white lines were being introduced, creating voids in the image. “It was an easy fix once we determined the problem,” he said. The workout team also found that breakdowns in the BCMA system’s wireless network led to failed scans and nurse overrides. But in many cases, the fault was not the system’s—rather, nurses were not taking the steps needed to get an accurate scan, Ms. Riffee noted. By simply reorienting the position of the scanner or using a pullback technique on compressed or stacked bar codes, the scan would go through, thus eliminating the need for a nurse override, she said.

appropriately cross-referencing barcoded medications in the pharmacy and improving wireless connectivity are just a few examples of the many improvements the workout team made to the BCMA system. Those efforts quickly began to have an effect: Total product overrides in all three CAMC facilities decreased from the 7% rate noted at the outset of their quality improvement project to less than 2% by the end of the study, they reported (Figure). In several nursing units, the rate of overrides fell to 0.5% or lower. The improvements “helped nurses gain more confidence in the BCMA system,” Ms. Baughan said. “Now, when they receive an error message that states ‘wrong medication’ or ‘wrong patient,’ they believe the system and request assistance from the pharmacy to ensure that they indeed have the right drug that will scan.” That’s no small accomplishment: the 7% rate of overrides documented at baseline equated to more than 300,000 doses given annually, each of which represented a potentially unsafe medication administration. Ms. Baughan attributed the program’s success to the multidisciplinary makeup of the workout teams. “To really determine if the bar-coding and scanning equipment is working properly, you have to have IT and clinical engineering people on board,” she said. “But you also need pharmacists to work on the cross-linking problem, and nurse managers who can help nurses buy-in to the quality-improvement process.” Once all of those different disciplines were involved, she added, “We all stopped blaming each other and instead worked together to fix the system and improve patient safety.”

Measuring the Results Helping nurses refine their scanning technique, fixing printer problems,

Through April 2009 n=375,000 doses per month

Phase 1, Implementation; Phase 2, Education; Phase 3, PI Formulation; Phase 4, Final and Full Optimization

Figure. CAMC hospitals barcode medication administration overrides.

Jan-09 —

Sep-08 —

May-08 —

Jan-08 —

Sep-07 —

May-07 —

Jan-07 —

Sept-06 —

May-06 —

10.00 — 9.00 — 8.00 — 7.00 — 6.00 — 5.00 — 4.00 — 3.00 — 2.00 — 1.00 — Jan-06 —

Individual Value (%)

Rosemont, Ill.—It’s a common time-saver for online shoppers: asked for demographic information, you select the first alphabetized item in a pull-down menu not because it’s the accurate choice, but because it’s the easiest one to access. The shortcut is no big deal if you claim to be the millionth aerospace engineer to buy a pair of espadrilles at Amazon.com. But what if you’re a nurse who uses that pulldown workaround to explain why you just administered a drug to a patient despite getting an error alert from your hospital’s bedside bar-code scanning system? The result may well be that the drug given violates the “five rights of medication administration”: the right patient, right time, right dose, right route and right drug. When that occurs, patients are at risk for potentially serious adverse drug events. “Unfortunately, that’s what was happening in our hospitals about a year after launching our bar-code medication administration [BCMA] system,” said Joseph High, PharmD, corporate pharmacy director at Charleston Area Medical Center (CAMC) in Charleston, W.Va. “We had a 7% rate of overrides, where staff nurses were administering medications despite having been given a message by the system that a problem existed.” The fact that many of the nurses were not picking the true cause of their override in the computer’s drop down menu compounded the problem, noted Jamie Baughan, BS, MHA, lead author of a study on CAMC’s efforts to improve their bedside bar-coding system. The short cut “really made it difficult to troubleshoot the barriers to successful scanning,” Ms. Baughan said during a poster session at the American Society of Health-System Pharmacists Summer Meeting. To gain more insight into why the nurses were overriding the bedside scanning system, Ms. Baughan and her CAMC colleagues took a page out of their six-sigma quality-improvement handbook and implemented a strategy called “workouts.” During a workout, a multidisciplinary team of representatives from pharmacy, nursing, information technology (IT) and clinical engineering were on the floors observing nurses who were having difficulty scanning medications. The team would troubleshoot each scanning issue and fix them on-site in order to determine the root cause of the problem. Visits from the workout teams were dubbed “MAK blitzes,” Dr. High noted— a name reflecting the Siemens Medication Administration Checking system used by the hospital for BCMA. He said

“Jamie did a great job getting champions among all the stakeholders in this— she really instilled a culture of safety,” Dr. High said. “And that’s the human factor in all of this: You can’t just focus on the technology fixes.” He added another lesson learned: “After implementing any patient safety technology, don’t assume you’ve optimized it. And even if you do take steps to optimize it after launch, don’t assume it stays optimized.” The research team on the ASHP poster included Wade Lanham, an employee at Siemens, and Daniel Burgess, an employee of CAMC.

First Step Is the Most Important Ernest R. Anderson Jr., MS, RPh, system vice president of pharmacy, Caritas Christi in Boston, said he was not surprised that many of CAMC’s bar-coding troubles were traced back to the early phases of product stocking and preparation. “If you don’t get that initial bar code verified and compatible with your own scanning equipment, it’s very difficult to have a highly functioning system,” Mr. Anderson said when asked to comment on the poster during the ASHP meeting. One of the first problems he encountered during his own BCMA rollout was the fast pace at which a drug order can change due to something as simple as a revised administration time. “Once that time changes, the drug order changes and the system gives it a new order number,” Mr. Anderson said. “The problem is that the medication has already been sent up to the floor with the ‘old’ bar code from the first order. If your nurse tries to administer that drug to a patient, the system will issue a ‘wrong drug’ alert, because it’s looking for the new order. So what do you do—run up to the nursing unit and relabel the medication? That can really slow things up.” Mr. Anderson said he’s working with his vendors on a fairly straightforward fix that would maintain the old order number while ensuring safe administration. “The point is that it’s hard to anticipate these things, so ongoing efforts to optimize your bedside scanning system are crucial, as the CAMC study shows.” Mr. Anderson also stressed not to get discouraged by hiccups. “BCMA is not an easy technology, but we have to continue to push more widespread adoption,” he said. Without such systems in place, “nurses are at the sharp end of the stick—they’re at the point of administration where errors will occur if you don’t have some type of bedside medication checks in place.” —David Bronstein

Technology 27

Pharmacy Practice News • July 2009

Electronic Health Records

High-Tech Help for Smoking Cessation A

n enhanced electronic health record that prompts physicians to ask patients about their smoking status and suggest treatment when appropriate significantly improved referral of smokers to a cessation counselor, a new study suggests. The percent gains in the study were significant: 3.9% of patients evaluated by primary care physicians using the enhanced electronic health record (EHR) made contact with a smoking cessation counselor, versus only 0.3% of patients in control practices (P<0.001). However, “the absolute rates of our outcomes … were modest,” reported lead researcher Jeffrey A. Linder, MD, MPH, of Brigham and Women’s Hospital in Boston (Arch Intern Med 2009;169:781-787). Indeed, the majority of smokers in both groups never sought counseling, and of those who did, very few actually quit. Given those results, why consider the EHR-based strategy? “[Because] even small differences in counseling and quit rates could have a large influence on premature death,” the investigators noted. They also stressed that the two basic components of the enhanced EHR—a smoking status reminder icon and an e-mail-based referral form—are “easily generalizable to [specialty] practice(s) and EHRs.” A total of 207 clinicians in the study (the intervention group) used the enhanced EHR, while 314 physicians in control practices used an EHR with only limited fields for recording smoking status and no ability to issue referral reminders. The researchers said they were encouraged by the nearly 15-fold increase in contact with smoking cessation counselors documented in the intervention group. Such contact was the primary outcome tracked because it has been shown in earlier studies “to roughly double a patient’s odds of quitting,” Dr. Linder noted. Even so, estimated quit rates in the Boston study were modest. Among the nearly 10,000 patients who were documented smokers at the start of the investigation, 5.3% of those in the intervention group were recorded as nonsmokers by the end of the study versus 1.9% in control practices. The difference, although significant (P<0.001), “may be simply attributable to improved documentation,” Dr. Linder and his colleagues wrote. The authors attributed the mixed-bag nature of their results, in part, to a “lowintensity” system launch that included only one site visit and some follow-up e-mails to the participating practices. But even their limited success, they

stressed, shows that an EHR with builtin history taking and referral reminders can help clinicians “provide more efficient, effective tobacco treatment.”

An Informatic Specialist’s Perspective “It’s clear from this type of research that the simple act of talking with a physician and/or counselor can have an impact on the patient’s behavior,” said Brent Fox, PharmD, PhD, assistant

professor of pharmacy care systems, Auburn University Harrison School of Pharmacy, in Alabama. However, without electronic prompts such as the ones examined in the EHR study, “those discussions don’t always happen.” Dr. Fox added that he could envision a role for pharmacy in such a system. “I could see clinical queries being built in that searched an EHR to identify patients meeting certain criteria, such as a history of smoking, that a pharmacist

BRIEF SUMMARY OF PRESCRIBING INFORMATION TM

RiaSTAP , Fibrinogen Concentrate (Human) For Intravenous Use, Lyophilized Powder for Reconstitution Before prescribing, please consult full prescribing information, a summary of which follows. Some text refers to full prescribing information. 1 INDICATIONS AND USAGE RiaSTAP™, Fibrinogen Concentrate (Human) is indicated for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. RiaSTAP is not indicated for dysfibrinogenemia. 4 CONTRAINDICATIONS RiaSTAP is contraindicated in individuals who have manifested severe immediate hypersensitivity reactions, including anaphylaxis to RiaSTAP or its components. 5 WARNINGS AND PRECAUTIONS 5.1 Allergic Reactions Allergic reactions may occur. If symptoms of allergic or early signs of hypersensitivity reactions (including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis) occur, immediately discontinue administration (see Patient Counseling Information [17.1]). The treatment required depends on the nature and severity of the reaction. 5.2 Thrombosis Thrombosis may occur spontaneously in patients with congenital fibrinogen deficiency with or without the use of fibrinogen replacement therapy.1 Thromboembolic events have been reported in patients treated with RiaSTAP. Weigh the benefits of RiaSTAP administration versus the risk of thrombosis. Patients receiving RiaSTAP should be monitored for signs and symptoms of thrombosis. (see Patient Counseling Information [17.2]) 5.3 Transmissible Infectious Agents RiaSTAP is made from human plasma. Products made from human plasma may contain infectious agents (e.g., viruses and theoretically the Creutzfeldt-Jakob disease agent [CJD]) that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by a process demonstrated to inactivate and/or remove certain viruses during manufacturing. (see Description [11]). Despite these measures, such products may still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products (see Patient Counseling Information [17.3]). 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 CSL Behring at 1-866-915-6958. 6 ADVERSE REACTIONS The most serious adverse reactions that have been reported in clinical studies or through postmarketing surveillance following RiaSTAP treatment are allergic-anaphylactic reactions and thromboembolic episodes, including myocardial infarction, pulmonary embolism, deep vein thrombosis, and arterial thrombosis. The most common adverse reactions that have been reported in clinical studies or through postmarketing surveillance following RiaSTAP treatment are allergic reactions and generalized reactions such as chills, fever, nausea, and vomiting.

could then follow up for the appropriate clinical reasons. This is very similar to what Sentri7, Vigilanz, etc., do.” [Both companies have software that helps identify at-risk patients based on laboratory, patient history and other data sources.] —David Bronstein

6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to rates in other clinical studies and may not reflect the rates observed in practice. The most common adverse reactions observed in more than one subject in clinical studies (frequency >1%) were fever and headache. 6.2 Postmarketing Experience Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure. Adverse reactions reported in patients receiving RiaSTAP for treatment of fibrinogen deficiency include allergic-anaphylactic reactions (including rash, dyspnea, etc.), general reactions such as chills, fever, nausea, vomiting and thromboembolic complications such as myocardial infarction, pulmonary embolism, and deep vein thrombosis. The following adverse reactions, identified by system organ class, have shown a possible causal relationship with RiaSTAP.

(see Warnings and Precautions, Thrombosis [5.2]) 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with RiaSTAP. It is not known whether RiaSTAP can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. RiaSTAP should be used during pregnancy only if clearly needed. 8.2 Labor and Delivery RiaSTAP has not been studied for use during labor and delivery. 8.3 Nursing Mothers RiaSTAP has not been studied in nursing mothers with congenital fibrinogen deficiency. 8.4 Pediatric Use RiaSTAP studies have included subjects below the age of 16 years. In the pharmacokinetic study (see Pharmacokinetics [12.3]), 2 children (8 and 11 years), 3 adolescents (12, 14 and 16 years), were studied. Subjects less than 16 years of age (n = 4) had shorter half-life this study limits statistical interpretation. 8.5 Geriatric Use The safety and efficacy of RiaSTAP in the geriatric population has not been studied. There were an insufficient number of subjects in this age group to determine whether they respond differently from younger subjects. Reference: 1.Peyvandi F, Haertal S, Knaub S, et al. Incidence of bleeding symptoms in 100 patients with inherited afibrinogenemia or hypofibrinogenemia. J Thromb Haemost CSL Behring GmbH US License No. 1765

CSL Behring LLC Kankakee, IL 60901 USA Based on January 2009 version

THE FIRST AND ONLY FIBRINOGEN CONCENTRATE NOW WITHIN YOUR REACH

Important Safety Information RiaSTAP™, Fibrinogen Concentrate (Human), is indicated for the treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. RiaSTAP™ is not indicated for dysfibrinogenemia. RiaSTAP™ was approved using maximum clot firmness (MCF) as a surrogate marker likely to predict clinical benefit. Thus, the hemostatic efficacy of RiaSTAP™ in acute bleeding episodes has not been established. A post-marketing study is being conducted to verify clinical endpoints.

FINALLY—the access and convenience you’ve been waiting for Concentrated lyophilized protein that is easily reconstituted in minutes Labeled ﬁbrinogen content to assist with coagulation management

RiaSTAP™ is contraindicated in individuals who have manifested severe immediate hypersensitivity reactions, including anaphylaxis, to RiaSTAP™ or its components.

Demonstrated ability to effectively raise ﬁbrinogen levels to within target levels

Monitor patients for early signs of allergic or hypersensitivity reactions and if necessary, discontinue administration and institute appropriate treatment. Thrombotic events have been reported in patients receiving RiaSTAP™; weigh the beneﬁts of administration versus the risks of thrombosis.

Concentrated ﬁbrinogen allows for low infusion volume1 and quick administration

RiaSTAP™ is made from pooled human plasma. Products made from human plasma may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The most serious adverse reactions that have been reported in subjects in clinical studies who received RiaSTAP™ are thromboembolic episodes, including myocardial infarction and pulmonary embolism, and allergic-anaphylactic reactions. The most common adverse reactions observed are allergic reactions, including chills, fever, nausea, and vomiting. Monitor patients for early signs of allergic or hypersensitivity reactions and if necessary, discontinue administration. Please see brief summary of prescribing information on next page.

Virus inactivation/removal reduces risk of exposure to infectious agents Easily stored and accessed when needed, due to room temperature storage and 30-month shelf life

For more information, visit www.riastap.com. New

Reference: 1. Mannucci PM, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood. 2004;104:1243–1252. RiaSTAP is a trademark of CSL Behring GmbH. © 2009 CSL Behring LLC, 1020 First Avenue, PO Box 61501 King of Prussia, PA 19406-0901 www.CSLBehring-US.com Printed in USA IO#RIA-007T 3/2009

Strengthens clots. Supports hemostasis.